bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Education after an Emergency Department Visit Increases Hydroxyurea Initiation in Children with Sickle Cell Anemia
Authors: Kappa Sarah , Pecker Lydia , Darbari Deepika S. , Nickel Robert 
Published: April 2021

Abstract
Introduction: Hydroxyurea decreases many complications of sickle cell anemia (SCA) but is underused in treatment-eligible patients. Barriers to hydroxyurea initiation occur on the health care system, provider, and patient level. Novel strategies to increase hydroxyurea use in patients with SCA are needed. To address this challenge at our center, we implemented the Quick Start Hydroxyurea Initiation Project (Q-SHIP).
Methods: Patients with SCA were eligible to participate in Q-SHIP if they presented to the Children's National Health System (CNHS) emergency department (ED) for pain or acute chest syndrome and were not taking hydroxyurea. Patients &lt;9 months old, on chronic transfusions, pregnant, or not followed by CNHS hematology were excluded. Eligible patients were referred to a weekly Q-SHIP clinic visit focused on hydroxyurea education and were offered initiating treatment at the visit's conclusion. Participants completed a pre-session questionnaire, discussed hydroxyurea with a hematologist using a handbook developed by CNHS, and watched videos featuring patients and parents of children with SCA sharing their experience with hydroxyurea. Subjects were classified as starting hydroxyurea if they had a clinic visit for hydroxyurea monitoring within 3 months of participation in a Q-SHIP session.
Results: Over 13 months (2/1/2016 - 3/31/2017) 65 eligible patients participated in Q-SHIP a median of 5 days (IQR 2, 20 days) after ED or hospital discharge. Although 44% (28/64) of participants reported no previous hydroxyurea offer, provider clinic documentation indicated that 61% (17/28) of these families had declined a previous hydroxyurea offer. After Q-SHIP, 55% (36/65) of participants started hydroxyurea. Subjects who started hydroxyurea after Q-SHIP were similar to those who did not, except subjects who started were more likely have a history of an intensive care unit admission (Table 1). After a median follow-up of 11 months, 81% (29/36) of participants who started hydroxyurea after Q-SHIP continued on therapy. Among Q-SHIP participants continuing treatment, mean corpuscular volume increased by a median of 8.6 fL (IQR +5.4, +17.7, p&lt;0.0001) and hemoglobin F increased by a median of 5.8% (IQR +3.0, +11.3, p&lt;0.001). One year after implementation of Q-SHIP, the proportion of treatment-eligible patients with SCA who presented to the ED with pain or ACS who were receiving hydroxyurea increased; February 2016: 56% (32/57) vs. February 2017: 73% (43/59), p=0.059.
Conclusion: Addressing indications for hydroxyurea therapy in a clinic encounter exclusively for this purpose soon after a SCA complication is a meaningful time to meet with families of children with SCA to initiate treatment.

Disclosures
No relevant conflicts of interest to declare.
Magnetically Powered Microbots: A Novel Approach to Thrombolysis?
Authors: Neeves Keith B. , Tasci Tonguc , Disharoon Dante , Rana Kuldeepsinh , Schoeman Rogier , Herson Paco , Marr David 
Published: April 2021

Abstract
Fibrinolytic drugs such as recombinant tissue plasminogen activator (tPA) have been successfully used to reestablish blood flow in thrombotic strokes. However, they can also lead to intracranial hemorrhaging, must be used within hours of the onset of symptoms, and have limited efficacy in small vessel occlusions distal to major cerebral arteries. Alternatively, catheter-based thrombectomy devices can restore blood flow quickly but are invasive, limited to larger arteries, and can leave residual prothrombotic material on vessel walls. An approach that overcomes these limitations is the injection of individual superparamagnetic particles coated with fibrinolytic drugs that, upon application of a rotating magnetic field, self-assemble into microbots we call microwheels capable of translating to and directly attacking thrombi. We describe an approach that uses the vessel wall to propel in situ assembled microwheels via rolling.1 Driven by low-strength external magnetic fields (~10 mT), microwheel movement occurs with greatly improved speeds (&gt;100 µm/sec) and directional control compared to approaches that use magnetic field gradients to direct similar types of microdevices. Using this approach, tPA-functionalized particles are introduced at a subtherapeutic concentration, which accumulate to therapeutic levels at the periphery of a thrombus. Fibrinolytic microwheels bore into fibrin-rich and platelet-rich thrombi by mechanical action and accomplish reperfusion faster than soluble tPA at comparable concentrations.2 For example, fibrinolysis of plasma-derived fibrin gels is five-fold faster using tPA-microwheels compared to 1 µg/mL tPA. Using a microfluidic model of vascular injury, ~100 µm sized platelet-rich thrombi were formed on collagen-tissue factor surfaces and then ablated with tPA-microwheels in less than five minutes. Combining mechanical and biochemical methods, this approach could reduce the risk of bleeding associated with fibrinolytics and broaden their indications.
1. Tasci TO, Herson PS, Neeves KB, Marr DWM. Surface-enabled propulsion and control of colloidal microwheels. Nature Communication, 2016;7:10225.
2. Tasci TO, Disharoon D, Schoeman RM, Rana K, Herson PS, Marr DWM, Neeves KB. Enhanced fibrinolysis with magnetically powered colloidal microwheels. Small;in press

Disclosures
Neeves: Colorado School of Mines: Patents & Royalties.
Impact of the Coagulation System on the Pathogenesis of Alzheimer's Disease
Authors: Strickland Sidney 
Published: April 2021

Abstract
Alzheimer's disease (AD) leads to cognitive impairment and is eventually fatal. The cognitive decline is associated with extensive neuronal degeneration. The most well-known pathological features of AD are extracellular Aβ plaques, intracellular tau tangles, neuroinflammation, and neuronal loss. Less discussed is that AD is often associated with cerebrovascular abnormalities. The symptoms of AD and cerebrovascular pathology could be independent co-morbidities, with both being increased in aging populations. However, it is also possible that there is a mechanistic link between AD and vascular pathology. The interaction of Aβ with fibrin(ogen) can lead to increased fibrin deposition in cerebral blood vessels, and these accumulated fibrin deposits may disrupt cerebral blood flow and induce microinfarcts, inflammation, and BBB damage, all of which are aspects of cerebrovascular dysfunction observed in AD. At the same time, Ab's ability to activate FXII may contribute to increased fibrin generation through the intrinsic coagulation pathway as well as to increased inflammation and vascular permeability through bradykinin release from HK. These possible roles of Aβ in thrombosis, fibrinolysis, and inflammation via its interaction with fibrinogen and FXII, summarized in Figure 1, will be discussed.

Disclosures
No relevant conflicts of interest to declare.
In Vitro Hematopoietic Reprogramming and Generation of Hematopoietic Stem Cells
Authors: Moore Kateri A. 
Published: April 2021

Hematopoietic stem cell (HSC) transplantation is widely used to treat a variety of disorders. Despite advances in the use of umbilical cord blood and mobilized stem cells, donor material remains limited. This is due to insufficient numbers of stem cells in cord blood, poor mobilization, and the lack of ethnic diversity to provide sufficient genetically matched material. Despite intensive efforts there has been limited success in generating transplantable HSCs from pluripotent stem cells (PSCs). Clearly, alternative approaches are necessary. Directly programmed hematopoietic stem/progenitor cells would provide an unlimited patient-specific source for cell replacement and genetic correction therapies as well as a platform for the future generation of patient specific therapeutics and blood products. In 2013 we demonstrated direct reprogramming of mouse fibroblasts into clonogenic hematopoietic progenitors with just four transcription factors (TFs), Gata2, Gfi1b, cFos and Etv6 (Pereira et al 2013). These four TFs induce a dynamic, multi-stage hemogenic process that progresses through an endothelial-like intermediate. As such, it appears to recapitulate definitive developmental hematopoiesis in vitro. We now have strong evidence that a similar hemogenic process can be optimally induced in human fibroblasts with Gata2, Gfi1b, and cFos. These reprogrammed cells are able to multi-lineage repopulate NSG mice. Therefore we maintain that in vitro reprogramming provides a tractable system to address the underlying molecular mechanisms of hemogenesis not possible in primary cells. We have now studied how the TFs bind DNA and initiate a molecular program that changes the epigenetic landscape to allow a change in cell fate. The studies to date have revealed cooperative binding of two of the factors to the binding motif of the other causing simultaneous silencing of fibroblast genes and activation of endothelial and hematopoietic genes.
Pereira CF, Chang B, Qiu J, Niu X, Papatsenko D, Hendry CE, Clark NR, Nomura-Kitabayashi A, Kovacic JC, Ma'ayan A, Schaniel C, Lemischka IR, Moore K. Induction of a Hemogenic Program in Mouse Fibroblasts. Cell Stem Cell. 2013;13:205-218.

Disclosures
No relevant conflicts of interest to declare.
Integrative microRNAome analysis of skeletal muscle of Colossoma macropomum (tambaqui), Piaractus mesopotamicus (pacu), and the hybrid tambacu, based on next-generation sequencing data
Authors: Fantinatti Bruno E. A. , Perez Erika S. , Zanella Bruna T. T. , Valente Jéssica S. , de Paula Tassiana G. , Mareco Edson A. , Carvalho Robson F. , Piazza Silvano , Denti Michela A. , Dal-Pai-Silva Maeli 
Published: April 2021

Abstract
Background
Colossoma macropomum (tambaqui) and Piaractus mesopotamicus (pacu) are good fish species for aquaculture. The tambacu, individuals originating from the induced hybridization of the female tambaqui with the male pacu, present rapid growth and robustness, characteristics which have made the tambacu a good choice for Brazilian fish farms. Here, we used small RNA sequencing to examine global miRNA expression in the genotypes pacu (PC), tambaqui (TQ), and hybrid tambacu (TC), (Juveniles, n = 5 per genotype), to better understand the relationship between tambacu and its parental species, and also to clarify the mechanisms involved in tambacu muscle growth and maintenance based on miRNAs expression.

Results
Regarding differentially expressed (DE) miRNAs between the three genotypes, we observed 8 upregulated and 7 downregulated miRNAs considering TC vs. PC; 14 miRNAs were upregulated and 10 were downregulated considering TC vs. TQ, and 15 miRNAs upregulated and 9 were downregulated considering PC vs. TQ. The majority of the miRNAs showed specific regulation for each genotype pair, and no miRNA were shared between the 3 genotype pairs, in both up- and down-regulated miRNAs. Considering only the miRNAs with validated target genes, we observed the miRNAs miR-144-3p, miR-138-5p, miR-206-3p, and miR-499-5p. GO enrichment analysis showed that the main target genes for these miRNAs were grouped in pathways related to oxygen homeostasis, blood vessel modulation, and oxidative metabolism.

Conclusions
Our global miRNA analysis provided interesting DE miRNAs in the skeletal muscle of pacu, tambaqui, and the hybrid tambacu. In addition, in the hybrid tambacu, we identified some miRNAs controlling important molecular muscle markers that could be relevant for the farming maximization.
The transcriptional landscape of a hepatoma cell line grown on scaffolds of extracellular matrix proteins
Authors: Ghosh Souvik , Börsch Anastasiya , Ghosh Shreemoyee , Zavolan Mihaela 
Published: April 2021

AbstractBackgroundThe behavior of cells in vivo is complex and highly dynamic, as it results from an interplay between intercellular matrix proteins with surface receptors and other microenvironmental cues. Although the effects of the cellular niche have been investigated for a number of cell types using different molecular approaches, comprehensive assessments of how the global transcriptome responds to 3D scaffolds composed of various extracellular matrix (ECM) constituents at different concentrations are still lacking.ResultsIn this study, we explored the effects of two diverse extracellular matrix (ECM) components, Collagen I and Matrigel, on the transcriptional profile of cells in a cell culture system. Culturing Huh-7 cells on traditional cell culture plates (Control) or on the ECM components at different concentrations to modulate microenvironment properties, we have generated transcriptomics data that may be further explored to understand the differentiation and growth potential of this cell type for the development of 3D cultures. Our analysis infers transcription factors that are most responsible for the transcriptome response to the extracellular cues.ConclusionOur data indicates that the Collagen I substrate induces a robust transcriptional response in the Huh-7 cells, distinct from that induced by Matrigel. Enhanced hepatocyte markers (ALB and miR-122) reveal a potentially robust remodelling towards primary hepatocytes. Our results aid in defining the appropriate culture and transcription pathways while using hepatoma cell lines. As systems mimicking the in vivo structure and function of liver cells are still being developed, our study could potentially circumvent bottlenecks of limited availability of primary hepatocytes for preclinical studies of drug targets.
Auxin regulated metabolic changes underlying sepal retention and development after pollination in spinach
Authors: Fatima Mahpara , Ma Xiaokai , Zhou Ping , Zaynab Madiha , Ming Ray 
Published: April 2021

Abstract
Background
Pollination accelerate sepal development that enhances plant fitness by protecting seeds in female spinach. This response requires pollination signals that result in the remodeling within the sepal cells for retention and development, but the regulatory mechanism for this response is still unclear. To investigate the early pollination-induced metabolic changes in sepal, we utilize the high-throughput RNA-seq approach.

Results
Spinach variety ‘Cornel 9’ was used for differentially expressed gene analysis followed by experiments of auxin analog and auxin inhibitor treatments. We first compared the candidate transcripts expressed differentially at different time points (12H, 48H, and 96H) after pollination and detected significant difference in Trp-dependent auxin biosynthesis and auxin modulation and transduction process. Furthermore, several auxin regulatory pathways i.e. cell division, cell wall expansion, and biogenesis were activated from pollination to early developmental symptoms in sepals following pollination. To further confirm the role auxin genes play in the sepal development, auxin analog (2, 4-D; IAA) and auxin transport inhibitor (NPA) with different concentrations gradient were sprayed to the spinach unpollinated and pollinated flowers, respectively. NPA treatment resulted in auxin transport weakening that led to inhibition of sepal development at concentration 0.1 and 1 mM after pollination. 2, 4-D and IAA treatment to unpollinated flowers resulted in sepal development at lower concentration but wilting at higher concentration.

Conclusion
We hypothesized that sepal retention and development might have associated with auxin homeostasis that regulates the sepal size by modulating associated pathways. These findings advanced the understanding of this unusual phenomenon of sepal growth instead of abscission after pollination in spinach.
FISH landmarks reflecting meiotic recombination and structural alterations of chromosomes in wheat (Triticum aestivum L.)
Authors: Zou Yang , Wan Linrong , Luo Jie , Tang Zongxiang , Fu Shulan 
Published: April 2021

Abstract
Background
DNA sequence composition affects meiotic recombination. However, the correlation between tandem repeat composition and meiotic recombination in common wheat (Triticum aestivum L.) is unclear.

Results
Non-denaturing fluorescent in situ hybridization (ND-FISH) with oligonucleotide (oligo) probes derived from tandem repeats and single-copy FISH were used to investigate recombination in three kinds of the long arm of wheat 5A chromosome (5AL). 5AL535–18/275 arm carries the tandem repeats pTa-535, Oligo-18, and pTa-275, 5AL119.2–18/275 arm carries the tandem repeats pSc119.2, Oligo-18 and pTa-275, and 5AL119.2 arm carries the tandem repeats pSc119.2. In the progeny of 5AL535–18/275 × 5AL119.2, double recombination occurred between pSc119.2 and pTa-535 clusters (119–535 interval), and between pTa-535 and Oligo-18/pTa-275 clusters (535–18 interval). The recombination rate in the 119–535 interval in the progeny of 5AL535–18/275 × 5AL119.2–18/275 was higher than that in the progeny of 5AL535–18/275 × 5AL119.2. Recombination in the 119–535 interval produced 5AL119 + 535 segments with pTa-535 and pSc119.2 tandem repeats and 5ALNo segments without these repeats. The 5AL119 + 535 and 5ALNo segments were localized between the signal sites of the single-copy probes SC5A-479 and SC5A-527. The segment between SC5A-479 and SC5A-527 in the metaphase 5ALNo was significantly longer than that in the metaphase 5AL119 + 535.

Conclusion
The structural variations caused by tandem repeats might be one of the factors affecting meiotic recombination in wheat. Meiotic recombination aggregated two kinds of tandemly repeated clusters into the same chromosome, making the metaphase chromosome more condensed. To conclude, our study provides a robust tool to measure meiotic recombination and select parents for wheat breeding programs.
Effect of low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy: a prospective randomized trial
Authors: Wang Shun , Gao Peng-fei , Guo Xiao , Xu Qi , Zhang Yun-feng , Wang Guo-qiang , Lin Jing-yan 
Published: April 2021

AbstractBackroundAt present, low-concentration carbohydrate is rarely used in minor trauma surgery, and its clinical efficacy is unknown. The aim of the study was to evaluate the effect of preoperative oral low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy using Quality of Recovery − 15 (QoR-15) questionnaire.MethodsOne hundred twenty patients were randomized to oral intake of 300 ml carbohydrate solution (CH group) or 300 ml pure water (PW group) 2 h before surgery or fasting for 8 h before surgery (F group). The QoR-15 questionnaire was administered to compare the quality of recovery at 1d before surgery (T0), 24 h, 48 h, 72 h after surgery (T1, T2, T3), and perioperative blood glucose was recorded.ResultsCompared to the F group, the QoR-15 scores were statistically higher in the CH and PW group at T1 (P < 0.05), and the enhancement of recovery quality reached the clinical significance at T1 in the CH group compared with the F group. Among the five dimensions of the QoR-15 questionnaire, physical comfort, physiological support and emotional dimension in the CH group were significantly better than the F group (P < 0.05) at T1. Besides, blood glucose of CH group was significantly lower than the PW group and F group at each time point after surgery.ConclusionsLow-concentration carbohydrate could decrease the incidence of postoperative hyperglycemia and improve the patient-centered quality of recovery on patients undergoing open thyroidectomy at the early stage postoperatively.Trial registrationChiCTR1900024731. Date of registration: 25/07/2019.
Dexmedetomidine attenuates myocardial ischemia-reperfusion injury in vitro by inhibiting NLRP3 Inflammasome activation
Authors: Huang Yaru , Sun Xiaotong , Juan Zhaodong , Zhang Rui , Wang Ruoguo , Meng Shuqi , Zhou Jiajia , Li Yan , Xu Keyou , Xie Keliang 
Published: April 2021

Abstract
Background
Myocardial ischemia-reperfusion injury (MIRI) is the most common cause of death worldwide. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome plays an important role in the inflammatory response to MIRI. Dexmedetomidine (DEX), a specific agonist of α2-adrenergic receptor, is commonly used for sedation and analgesia in anesthesia and critically ill patients. Several studies have shown that dexmedetomidine has a strong anti-inflammatory effect in many diseases. Here, we investigated whether dexmedetomidine protects against MIRI by inhibiting the activation of the NLRP3 inflammasome in vitro.

Methods
We established an MIRI model in cardiomyocytes (CMs) alone and in coculture with cardiac fibroblasts (CFs) by hypoxia/reoxygenation (H/R) in vitro. The cells were treated with dexmedetomidine with or without MCC950 (a potent selective NLRP3 inhibitor). The beating rate and cell viability of cardiomyocytes, NLRP3 localization, the expression of inflammatory cytokines and NLRP3 inflammasome-related proteins, and the expression of apoptosis-related proteins, including Bcl2 and BAX, were determined.

Results
Dexmedetomidine treatment increased the beating rates and viability of cardiomyocytes cocultured with cardiac fibroblasts. The expression of the NLRP3 protein was significantly upregulated in cardiac fibroblasts but not in cardiomyocytes after H/R and was significantly attenuated by dexmedetomidine treatment. Expression of the inflammatory cytokines IL-1β, IL-18 and TNF-α was significantly increased in cardiac fibroblasts after H/R and was attenuated by dexmedetomidine treatment. NLRP3 inflammasome activation induced the increased expression of cleaved caspase1, mature IL-1β and IL-18, while dexmedetomidine suppressed H/R-induced NLRP3 inflammasome activation in cardiac fibroblasts. In addition, dexmedetomidine reduced the expression of Bcl2 and BAX in cocultured cardiomyocytes by suppressing H/R-induced NLRP3 inflammasome activation in cardiac fibroblasts.

Conclusion
Dexmedetomidine treatment can suppress H/R-induced NLRP3 inflammasome activation in cardiac fibroblasts, thereby alleviating MIRI by inhibiting the inflammatory response.
The inverse association between unhealthy eating habit and mucosal healing among patients with ulcerative colitis
Authors: Furukawa Shinya , Yagi Sen , Shiraishi Kana , Hashimoto Yu , Kitahata Shogo , Hanayama Masakazu , Tange Kazuhiro , Mori Kenichiro , Ninomiya Tomoyuki , Suzuki Seiyuu , Shibata Naozumi , Murakami Hidehiro , Ohashi Katsuhisa , Hasebe Aki , Tomida Hideomi , Yamamoto Yasunori , Takeshita Eiji , Ikeda Yoshio , Hiasa Yoichi 
Published: April 2021

AbstractBackgroundAlthough the association between eating habits which can be modified and digestive diseases has been reported, to date, no research has evaluated the association between eating habits and ulcerative colitis (UC). Thus, we investigate the association between eating behavior and clinical outcome in Japanese patients with UC.MethodsEating quickly, eating until full, and skipping breakfast data was obtained from a self-administered questionnaire. Information on clinical outcome was collected from medical records. Mucosal healing (MH) and partial MH was defined as a Mayo endoscopic subscore of 0 or 0–1, respectively. Age, sex, BMI, current smoking, current drinking, prednisolone use, and anti-TNFα monoclonal antibody use were selected a priori as potential confounding factors.ResultsStudy subjects consisted of 294 Japanese patients with UC. Eating at speed moderate and eating quickly were independently inversely associated with MH: the adjusted odds ratios (ORs) were 0.38 (95% confidence interval [CI] 0.16–0.85) and 0.38 (95% CI 0.17–0.81) (pfor trend = 0.033). Eating until full was independently inversely associated with MH: the adjusted OR was 0.38 (95% CI 0.27–0.86). MH in patients who skipped breakfast was marginally lower than that in patients who did not skip breakfast. No association between eating habits and clinical remission or partial MH was found.ConclusionAmong patients with UC, eating rate and eating until full may be independently inversely associated with MH but not clinical remission.