bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Extended Platelet Storage on Platelet Metabolism and Clot Retraction
Authors: Nair Prajeeda M , Meledeo Michael Adam , Wu Xiaowu , Peltier Grantham , Liu Bin , Reddoch-Cardenas Kristin M , Bynum James , Cap Andrew P. 
Published: November 2019

Background: Platelet (PLT) hemostatic responses are heavily dependent on PLT bioenergetics which drives the generation of PLT contractile forces and contribute to mechanical hemostasis. Although effective clot retraction (CR) requires PLT adhesion, aggregation and formation of strong clots, CR remains an understudied PLT function. In this work, we hypothesize that well-conserved PLT bioenergetics during storage is crucial for highly energy-dependent PLT functions including CR. To further investigate this correlation, we characterized the effect of extended PLT storage for up to 15 days on PLT bioenergetics and CR at room temperature (22°C, RT) and refrigeration (4°C, 4C).
Methods: Apheresis PLT concentrates in plasma were collected from 5 healthy donors and stored for 21 days at RT with agitation, or stored stationary in the cold (4C). Fresh PLTs were treated with metabolic inhibitors for 1 hour at 37°C, recalcified with 20mM calcium chloride, and incubated at 37°C to initiate CR. The clot weights were measured post retraction, and the clots were prepared for immunohistochemistry to assess clot structure. Similarly, extent of retraction and mitochondrial respiration levels were estimated in PLTs stored for 5, 10 and 15 days. Additionally, Platelet additive solution (PAS) stored PLTs were tested as a viable alternative to plasma storage to improve metabolic exhaustion during storage.
Results: 4C-stored PLTs in plasma retracted similar to fresh PLTs for up to 15 days. In comparison, RT-stored PLTs in plasma did not retract after 10 days, whereas PLTs stored in PAS at RT or 4C seemed to retain their contractile function for up to 15 days (Fig 1A). 4C-stored and fresh PLTs yielded heavier clots with a highly organized structure compared to the disorganized structure of clots from RT-stored PLTs. Mitochondrial respiration was significantly reduced over 10 days in RT- plasma stored PLTs, which was mitigated by PAS storage. Similarly, 4C storage in PAS mitigated the reduction in respiration seen in 15 days 4C- stored PLTs in plasma (Fig 1B).
Conclusion: Retraction properties of 4C-stored PLTs were similar to those of fresh PLTs, together with superior clot structure and function compared to RT- stored PLTs. This suggests that 4C storage could be a suitable alternative for extended storage. In RT-stored PLTs, reduction in mitochondrial respiration did not show any correlation with the reduced ability of PLTs to retract, suggesting that preserved glycolysis in PAS- stored RT-stored PLTs enabled CR. Thus, storing PLTs in PAS at RT or 4C could potentially mitigate mitochondrial dysfunction during extended storage.

Disclosures
No relevant conflicts of interest to declare.
Molecular Background of Double Protein Expressor B-Cell Lymphomas
Authors: Meriranta Leo , Alkodsi Amjad , Pasanen Annika , Haukka Jari , Karjalainen-Lindsberg Marja-Liisa , Leppa Sirpa 
Published: November 2019

Introduction: Concomitant deregulation of MYC and BCL2, whether at the genomic or protein level, comprises clinically a significant biological high-risk feature in aggressive B-cell lymphomas. Yet, the molecular background of these lymphomas is not fully understood. We sought to comprehensively characterize BCL2 and MYC aberrations and to identify clinically feasible determinants of the recent genomic subtypes and clinical outcome in diffuse large B-cell lymphoma (DLBCL).
Patients and Methods: We analyzed BCL2, BCL6 and MYC rearrangements and corresponding protein expression in the context of somatic exome-wide driver gene alterations, copy number annotations, transcriptome and clinical data in 181 patients with primary DLBCL.
Results: We found that germinal center B-cell (GCB) and activated B-cell (ABC)-like DLBCLs utilized different mechanisms to deregulate MYC and BCL2 expression. While the structural variations of BCL2 were subtype-specific and specifically increased antiapoptotic BCL2 expression, MYC deregulation was associated with gene expression signatures including biosynthetic pathways and telomerase activity and depletion of JAK-STAT, cytokine and immune cell signatures. Genomic dissection of MYC translocations and protein overexpression revealed associations with other lymphoma drivers, of which we highlight a novel interplay between MYC deregulation and TP53 alterations.
Double protein expression (DPE) arose from different molecular backgrounds in a subtype-dependent manner. In GCB-DLBCL, concurrent alterations of MYC and BCL2 loci gave rise to the majority of DPE DLBCLs. Importantly, we recognized more GCB lymphomas with double hit -like clinical behavior when BCL2 copy number alterations were considered. In the non-GCB DLBCLs in turn, concurrent alterations were rare and clinical behavior of DPE was dependent on the molecular context. Interestingly, BN2/C1 -like non-GCB lymphomas with BCL6 translocations had excellent outcomes regardless of the DPE status. Overall, DPE DLBCL defined a prognostic entity, which was independent of International Prognostic Index (IPI) and cell-of-origin, and together with TP53 alterations had synergistic dismal impact on survival.
Conclusion: Our findings elucidate the pathogenesis and modern biological determinants of high-risk DLBCL and reveal subtype-specific and clinically feasible improvements to risk-stratification and predictors of outcome.

Disclosures
Leppa: Celgene: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Bayer: Research Funding.
Infection Rates in Autologous Hsct with Prbc Transfusion
Authors: Woodard Christopher Ryan , Locantore-Ford Patricia 
Published: November 2019

Introduction: Infection remains a dominant source of morbidity/mortality for patients undergoing myeloablative chemotherapy and autologous stem cell transplant (ASCT). We sought to determine the relative risk of infection with the use of packed red blood cell (pRBC) transfusion to treat chemotherapy associated anemia.
Methods: Patients who underwent ASCT at Pennsylvania Hospital between 1995 and 2019 were identified. Data on transfusion status and infection were obtained from patient discharge and transplant summary forms including: Participation in bloodless medicine program, number of units of pRBCs transfused, and documented post-transplant infection. Standard 2 variable relative risk analysis and odds ratio were calculated to assess association between transfusion use and post-transplant infection rate.
Results: 306 patients were identified to have undergone ASCT with 176 (57.7%) participating in the bloodless medicine program, 46 (15.1%) having no need of pRBC, and 83 (27.1%) receiving at least 1 unit of pRBC. Median number of pRBC in transfused patients was 2 units. Rate of infection among those who did not receive pRBC was 33.3% while it was significantly higher in those who did at 49.4%. Patients who received pRBC were at higher risk of developing infection (Relative risk (RR) 1.48, odds ratio (OR) 1.95, 95% confidence interval (CI) 1.17-3.26, p=0.01) than those who did not. Further analysis showed that higher quantity of pRBC units further increased infection risk in patients who got 4 or more units of pRBC (RR=1.97, OR=4.14, CI=1.814-9.450, P=.0007).
Conclusion: Infection after ASCT was more common with the use of pRBC transfusion to treat anemia while number of pRBC units was positively correlated with rates of infection. This area needs further study to better plot timelines of events as well multiple regression analysis to control for confounding variables such as relative levels of neutropenia before onset of infection.

Disclosures
No relevant conflicts of interest to declare.
Trends and Outcomes of Venous Thromboembolism in Hospitalized Patients with Pancreatic Cancer: Results from National Inpatient Sample Database 1998-2016
Authors: Alhasson Hussam , Cai Peng , Gong Zimu , Saad Anas , Al-Husseini Muneer , Yang Pei , Alhasson Bassam , Tirumanisetty Pratyusha , Syed Tausif , Zhao Yu 
Published: November 2019

Introduction:
Pancreatic cancer (PC) has a known association with venous thromboembolism (VTE), with incidence of approximately 17%. There is limited published data about trends and outcomes of PC patients with VTE. The purpose of this study was to describe the prevalence and mortality trends in PC with VTE and analyze VTE impact on hospitalized PC patients from 1998 to 2016.
Methods:
We analyzed data from the National Inpatient Sample (NIS) database of the Agency of Healthcare Research and Quality (AHRQ). Adults≥18 years with PC as well as presence of VTE were identified by using ICD-9 or ICD-10 codes. Cost of hospitalization was adjusted for inflation in reference to 2016. Comorbidities were classified using the Elixhauser comorbidity index. Demographic characteristics, trends and in-hospital outcomes between PC with and without VTE were compared. Multiple logistic regression was used to obtain risk-adjusted odds ratio (OR) to compare inpatient mortality, length of stay (LOS), total charges, and disability at discharge between PC patients with and without VTE. The regression model was adjusted for age, sex, primary expected payer, teaching status of the hospital, hospital location, and presence of comorbid conditions.
Results:
96,777 (6.5%) of a total of 1,488,543 hospitalized PC patients had an accompanying diagnosis of VTE. Mean age of the study population was 67 years. African Americans, younger age, and metastatic disease are associated with higher VTE prevalence rate. After adjusting for potential confounders, compared with those without VTE, PC patients with VTE had significantly higher inpatient mortality (12.6% vs 9.7%; OR, 1.41 [confidence interval (CI), 1.34-1.49]; P<0.001), longer LOS (8.04 vs 7.98 days; OR, 1.27 [CI, 1.23-1.32]; P<0.001), higher average cost of hospitalization (US $71,332 vs US $57,117; OR, 1.4 [CI, 1.34-1.46]; P<0.001), and greater likelihood of moderate to severe disability (defined as any beyond routine home discharge; ranging from short-term stay to skilled nursing facility to death upon discharge) (62.2% vs 50.6%, OR, 1.71 [CI, 1.65-1.78]; P<0.001). Although the annual prevalence of VTE among PC increased from 2.1% to 8.8%, in-hospital mortality declined from 23.3% in 1998 to 12.9% in 2016 (P<0.001).
Conclusion:
In the NIS cohort of hospitalized patients with PC and VTE from 1998-2016, annual prevalence increased while mortality overall decreased. When compared to patients without VTE, PC patients with VTE had higher inpatient mortality, longer length of stay, higher hospital cost and higher degree of disability upon discharge. Consideration for anticoagulation and interventions to limit VTE in PC patients may improve in-hospital outcomes.
Figure

Disclosures
No relevant conflicts of interest to declare.
The pan-PIM inhibitor INCB053914 displays potent synergy in combination with ruxolitinib in models of MPN
Authors: Mazzacurati Lucia , Collins Robert J. , Pandey Garima , Lambert-Showers Que T. , Amin Narmin E. , Zhang Ling , Stubbs Matthew C. , Epling-Burnette Pearlie K. , Koblish Holly K. , Reuther Gary W. 
Published: November 2019

Key Points
INCB053914 and ruxolitinib synergize to induce apoptosis of JAK2V617F-driven cells and to inhibit neoplastic growth of primary MPN cells. INCB053914 antagonizes ruxolitinib persistence in an in vivo MPN model.
Larotrectinib in TRK fusion–positive pediatric B-cell acute lymphoblastic leukemia
Authors: Schewe Denis M. , Lenk Lennart , Vogiatzi Fotini , Winterberg Dorothee , Rademacher Annika V. , Buchmann Swantje , Henry Dahlia , Bergmann Anke K. , Cario Gunnar , Cox Michael C. 
Published: November 2019

Key Points
Larotrectinib can be effective in patients with ETV6-NTRK3–positive B-cell lymphoblastic leukemia, inducing prolonged molecular remission. Single-agent tyrosine kinase inhibitor treatment could be a valuable treatment option in subgroups of kinase fusion–positive ALL patients.
Association of radiation risk in the second and third generations with polymorphisms in the genes CYP1A1, CYP2E1, GSTP1 and changes in the thyroid
Authors: Massabayeva Meruyert , Chaizhunusova Nailya , Aukenov Nurlan , Bulegenov Tolkyn , Apsalikov Bakytbek , Shapihanova Aigerim , Zhunussov Yersin 
Published: November 2019

Abstract
Background
To study the association of radiation risk in the 2nd –3rd generations with polymorphisms in the genes CYP1A1, CYP2E1, GSTP1 and changes in the thyroid.

Methods
5 polymorphic gene variants (rs1048943, rs4646421, rs2070676, rs3813867, rs1695) were studied in 399 people living in the East Kazakhstan region in this research. 248 people of the 2nd - 3rd generation lived in the territory with radiation exposure in Abai, Borodulikha areas, and 151 people the comparison group lived in Kurchum district without radiation exposure comparable in sex and age with control group.

Results
The results show that there is a significant association of rs1048943 in exposed and unexposed groups (p < 0.003), and the absence of association of rs4646421, rs2070676, rs3813867, rs1695 in the studied groups. The mean value of thyroxine in carriers of the AG + GG genotype of rs4646421 is significantly lower than in AA genotype carriers (p = 0.04); no significant changes were found in genotypes’ distribution with thyroid-stimulating hormone and anti-thyroid peroxidase indicators. Significant changes were in levels of anti-thyroid peroxidase between exposed and unexposed groups (p = 0.007). The thyroxine - thyroid-stimulating hormone levels were not significantly different in exposed and unexposed groups (p > 0.3).

Conclusions
This study demonstrated the association of rs1048943 polymorphism with living in the radiation zone in the 2nd and 3rd generations for the first time. Thyroxine levels decrease was identified in the 2nd and 3rd generation residents of the exposed area, as well as a significant increase of anti-thyroid peroxidase occurs in individuals of the 2nd and 3rd generation living in areas with radiation exposure.
Association of diet and headache
Authors:   On behalf of the School of Advanced Studies of the European Headache Federation (EHF-SAS), Razeghi Jahromi Soodeh , Ghorbani Zeinab , Martelletti Paolo , Lampl Christian , Togha Mansoureh 
Published: November 2019

AbstractThe global prevalence of migraine as a primary headache has been estimated as 14.4% in both sexes. Migraine headache has been ranked as the highest contributor to disability in under 50 years old population in the world. Extensive research has been conducted in order to clarify the pathological mechanisms of migraine. Although uncertainties remains, it has been indicated that vascular dysfunction, cortical spreading depression (CSD), activation of the trigeminovascular pathway, pro-inflammatory and oxidative state may play a putative role in migraine pain generation. Knowledge about pathophysiological mechanisms of migraine should be integrated into a multimodal treatment approach to increase quality of life in patients. With respect to this, within the integrative health studies growing interest pertains to dietary interventions. Although the number of studies concerning effects of diet on headache/migraine is not yet very large, the current article will review the available evidence in this area. All publications on headache/migraine and dietary interventions up to May 2019 were included in the present review through a PubMed/MEDLINE and ScienceDirect database search. According to the current findings, Ketogenic diet and modified Atkins diet are thought to play a role in neuroprotection, improving mitochondrial function and energy metabolism, compensating serotoninergic dysfunction, decreasing calcitonin gene-related peptide (CGRP) level and suppressing neuro-inflammation. It can also be speculated that prescription of low glycemic diet may be promising in headache/migraine control through attenuating the inflammatory state. Moreover, obesity and headaches including migraine could be attributed to each other through mechanisms like inflammation, and irregular hypothalamic function. Thereby, applying dietary strategies for weight loss may also ameliorate headache/migraine. Another important dietary intervention that might be effective in headache/migraine improvement is related to balance between the intake of essential fatty acids, omega-6 and omega-3 which also affect inflammatory responses, platelet function and regulation of vascular tone. Regarding elimination diets, it appears that targeted these diets in migraine patients with food sensitivities could be effective in headache/migraine prevention. Taken together, dietary approaches that could be considered as effective strategies in headache/migraine prophylaxis include weight loss diets in obese headache patients, ketogenic and low-calorie diets, reducing omega-6 and increasing omega-3 fatty acid intakes.
Single-molecule real-time transcript sequencing identified flowering regulatory genes in Crocus sativus
Authors: Qian Xiaodong , Sun Youping , Zhou Guifen , Yuan Yumei , Li Jing , Huang Huilian , Xu Limin , Li Liqin 
Published: November 2019

Abstract
Background
Saffron crocus (Crocus sativus) is a valuable spice with medicinal uses in gynaecopathia and nervous system diseases. Identify flowering regulatory genes plays a vital role in increasing flower numbers, thereby resulting in high saffron yield.

Results
Two full length transcriptome gene sets of flowering and non-flowering saffron crocus were established separately using the single-molecule real-time (SMRT) sequencing method. A total of sixteen SMRT cells generated 22.85 GB data and 75,351 full-length saffron crocus unigenes on the PacBio RS II panel and further obtained 79,028 SSRs, 72,603 lncRNAs and 25,400 alternative splicing (AS) events. Using an Illumina RNA-seq platform, an additional fifteen corms with different flower numbers were sequenced. Many differential expression unigenes (DEGs) were screened separately between flowering and matched non-flowering top buds with cold treatment (1677), flowering top buds of 20 g corms and non-flowering top buds of 6 g corms (1086), and flowering and matched non-flowering lateral buds (267). A total of 62 putative flower-related genes that played important roles in vernalization (VRNs), gibberellins (G3OX, G2OX), photoperiod (PHYB, TEM1, PIF4), autonomous (FCA) and age (SPLs) pathways were identified and a schematic representation of the flowering gene regulatory network in saffron crocus was reported for the first time. After validation by real-time qPCR in 30 samples, two novel genes, PB.20221.2 (p = 0.004, r = 0.52) and PB.38952.1 (p = 0.023, r = 0.41), showed significantly higher expression levels in flowering plants. Tissue distribution showed specifically high expression in flower organs and time course expression analysis suggested that the transcripts increasingly accumulated during the flower development period.

Conclusions
Full-length transcriptomes of flowering and non-flowering saffron crocus were obtained using a combined NGS short-read and SMRT long-read sequencing approach. This report is the first to describe the flowering gene regulatory network of saffron crocus and establishes a reference full-length transcriptome for future studies on saffron crocus and other Iridaceae plants.
Comparative transcriptomics in Syllidae (Annelida) indicates that posterior regeneration and regular growth are comparable, while anterior regeneration is a distinct process
Authors: Ribeiro Rannyele Passos , Ponz-Segrelles Guillermo , Bleidorn Christoph , Aguado Maria Teresa 
Published: November 2019

AbstractBackgroundAnnelids exhibit remarkable postembryonic developmental abilities. Most annelids grow during their whole life by adding segments through the action of a segment addition zone (SAZ) located in front of the pygidium. In addition, they show an outstanding ability to regenerate their bodies. Experimental evidence and field observations show that many annelids are able to regenerate their posterior bodies, while anterior regeneration is often limited or absent. Syllidae, for instance, usually show high abilities of posterior regeneration, although anterior regeneration varies across species. Some syllids are able to partially restore the anterior end, while others regenerate all lost anterior body after bisection. Here, we used comparative transcriptomics to detect changes in the gene expression profiles during anterior regeneration, posterior regeneration and regular growth of two syllid species:Sphaerosyllis hystrixandSyllis gracilis; which exhibit limited and complete anterior regeneration, respectively.ResultsWe detected a high number of genes with differential expression: 4771 genes inS. hystrix(limited anterior regeneration) and 1997 genes inS. gracilis(complete anterior regeneration). For both species, the comparative transcriptomic analysis showed that gene expression during posterior regeneration and regular growth was very similar, whereas anterior regeneration was characterized by up-regulation of several genes. Among the up-regulated genes, we identified putative homologs of regeneration-related genes associated to cellular proliferation, nervous system development, establishment of body axis, and stem-cellness; such asrupandJNK(inS. hystrix); andglutamine synthetase,elav,slit, Hoxgenes, β-cateninandPL10(inS. gracilis).ConclusionsPosterior regeneration and regular growth show no significant differences in gene expression in the herein investigated syllids. However, anterior regeneration is associated with a clear change in terms of gene expression in both species. Our comparative transcriptomic analysis was able to detect differential expression of some regeneration-related genes, suggesting that syllids share some features of the regenerative mechanisms already known for other annelids and invertebrates.
Transcriptomic analyses suggest a dominant role of insulin in the coordinated control of energy metabolism and ureagenesis in goat liver
Authors: Lu Zhongyan , Xu Zhihui , Shen Zanming , Shen Hong , Aschenbach Jörg R. 
Published: November 2019

AbstractBackgroundThe ureagenesis plays a central role in the homeostatic control of nitrogen metabolism. This process occurs in the liver, the key metabolic organ in the maintenance of energy homeostasis in the body. To date, the understanding of the influencing factors and regulators of ureagenesis in ruminants is still poor. The aim of this study was to investigate the relationship between energy metabolism and ureagenesis and detect the direct regulators of ureagenesis in the liver by using RNA-seq technology.ResultsEighteen four-month-old male goats were divided into two groups randomly and received a diet containing 10% (LNFC group,n = 9) or 30% non-fiber carbohydrate (MNFC group,n = 9), respectively, for four weeks. The global gene expression analysis of liver samples showed that, compared with a LNFC diet, the MNFC diet promoted the expression of genes required for synthesis of fatty acid and glycerol, whereas it suppressed those related to fatty acid oxidation, gluconeogenesis from amino acids and ureagenesis. Additionally, gene expression for rate-limiting enzymes of ureagenesis were highly correlated to the gene expression of key enzymes of both fatty acid synthesis and glycerol synthesis (Spearman correlation coefficient > 0.8 andp < 0.05). In the differentially expressed signaling pathways related to the endocrine system, the MNFC diet activated the insulin and PPAR signaling pathway, whereas it suppressed the leptin-JAK/STAT signaling pathway, compared with the LNFC diet. Reverse transcription quantitative PCR analyses of 40 differentially expressed genes confirmed the RNA-seq results (R2 = 0.78).ConclusionOur study indicated that a dietary NFC-induced increase of energy supply promoted lipid anabolism and decreased ureagenesis in the caprine liver. By combining our results with previously published reports, insulin signaling can be suggested to play the dominant role in the coordinated control of hepatic energy metabolism and ureagenesis.