bluuebunny/crossref_metadata_2025 huggingface dataset:
Aminoacids and Fatty Acids Levels in Patients with Thalassemia Major
Authors: Canatan Duran , Baykal Asli , Duman Handan , Balta Nihal
Published: April 2020

Introduction: The red blood cell(RBC) membrane is a complex of lipids an proteins. When thalassemic RBCs are challenged with oxidant stress, incorporation of fatty acids in RBC phospholipids is affected. We investigated the aminoacids, carnitine and fatty acid levels of thalassemic patients.

Material-Method: A total number of 40 thalassemia major patient aged between 7–30 years, who has been taken regular transfusion and deferasirox therapy are included. Serum lipid profil (trigliserit, cholesterol, HDL and LDL) and ferritin levels were measured. Serum levels of aminoacids (valine, leucine/isoluecine, methionine, phenylalanine, tyrosine, aspartat, glutamat, glysine, alanine, ornitine, sitrulline, carnitine and fatty acids (C2 asetil, C3 propionil, C4 butiril, C5:1 tigilil, C5 izovaleril, C4OH3Ohbutiril, C6 hekzanol, C5OH-3 hidroksiizovaleril, C8oktanol, C10 dekanol, C5DC glutaril, C12 dodekenoil, C14.1 metilglutaril, C1 miristoil, C14OH 3 hidoksimiristoil, C16 1-palmitoleil, C16 OH 3 hidroksipalmitoleil, C18 1 oleil, C18 stearoil, C18.1OH 3 hidrosioil) were measured by using tanden-mass spectrometry.

Results: There was found high level of phenylalanine in 7 (17.5%) and fatty acid: c18 oleil 1 patients (2.5%) and low level of glisin in 4 (10%), metionin 1 patients(2.5%), carnitin 1 patients (2.5%) and as fatty acids; C16 palmitol in 11 (27.5%), C3 propiponil in 8 (20%) and C2 asetil 2 patients. (5%). Other amino acids and fatty acids were normal levels. There was significant relationship between fatty acids such as C16 palmitol, C3 propiponil and lipid profil.

Conclusion: Normal lipid profil and fatty acids is changed in thalassemic cells which in turn leads to altered interactions.
Vascular Heme Oxygenase-1 Induction Suppresses Tissue Factor and Plasminogen Activator Inhibitor-1 Expressions
Authors: Morishita Eriko , Maruyama Keiko , Sekiya Akiko , Ohtake Shigeki , Nakao Shinji , Yachie Akihiro
Published: April 2020

Objective - Heme oxygenase-1(HO-1), the rate-limiting enzyme of heme degradation, has recently been considered to have protective roles against various pathological conditions. 10 years have passed since we lost the first and the only patient of HO-1 deficiency. Since the patient of HO-1 deficiency showed endothelial cell injury and extremely enhanced coagulation and fibrinolytic parameters, we examined the effect of HO-1 modulation on tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) expression on endothelial cells.

Methods and Results -

Human umbilical vein endothelial cell (HUVEC) was stimulated with hemin (100mM), HO-1 inducer, and mRNA and protein levels for HO-1, TF and PAI-1 were examined. Total RNA was extracted from HUVEC, and was analyzed by real time RT-PCR. Protein expression levels of HO-1, TF and PAI-1 were measured by ELISA. Hemin stimulation increased HO-1 mRNA levels by 20 times. On the other hand, TF mRNA and antigen levels were minimum even after 8 hours of stimulation. Importantly, hemin stimulation reduced PAI-1 mRNA more than half after 4 hours. After HO-1 induction by hemin (100 mM) for 6 hours, HUVEC cultures were exposed to 10 ng/ml tumor necrosis factor (TNF).

Prior exposure to hemin significantly increased HO-1 mRNA by 60 times in 30 minutes after stimulation with TNF. However, TNF alone could not induce HO-1 mRNA and protein levels in HUVEC. Although stimulation with TNF enhanced expressions of both TF and PAI-1 mRNA, they were significantly inhibited more than half by prior treatment with hemin. TF antigen levels were similarly decreased (5.0 to 0.7 pg/ml). PAI-1 antigen levels were also inhibited by prior treatment with hemin (1.8 to 0.1 ng/ml)(3) To see if hemin effect on HUVEC is due to HO-1 production, HO-1 inhibitor tin-protoporphyrin IX (SnPP-IX) was added to the cultures. The inhibitor effect of hemin on TF and PAI-1 productions was cancelled when HUVEC was cocultured with SnPP-IX.

Conclusions - These results indicate that hemin exert inhibitory effect on TF and PAI-1 expressions through HO-1 production. Induction of HO-1 may be beneficial in the prevention of thrombosis associated with inflammation.
Vasohibin Inhibits Large Blood Vessel Formation and Supports Development of Microvessels
Authors: Kern Johann , Steurer Michael , Gastl Gunther , Gunsilius Eberhard , Untergasser Gerold
Published: April 2020

Aims: The murine homolog of human vasohibin (mVASH1), a putative antiangiogenic protein, was investigated for its inhibitory effects on in vitro and in vivo angiogenesis. Cell growth and migration was analyzed in murine embryonic fibroblasts, smooth muscle cells and brain endothelial cells (bEND.3). Moreover, angiogenic sprouting was studied on human umbilical vein endothelial cells (HUVEC) in the spheroid sprouting assay. In vivo effects on blood vessel formation were investigated in the chorioallontoic membrane assay and in the murine B16F10 melanoma model.

Results: Purified mVASH1 protein inhibited cell growth and migration of murine endothelial cell and fibroblasts, but not of vascular aortic smooth muscle cells (AoSMC). Adenovial overexpression did not inhibit proliferation or VEGF/bFGF induced capillary sprouting of HUVEC in the spheroid assay. Murine VASH1 inhibited growth of large vessels in the chorioallantoic membrane assay and induced the formation of a dense, fine capillary network. Subcutaneous growth of VASH1 overexpressing B16F10 melanomas in C57BL/6 mice was not affected within the observed time frame, but there was a significant increase of microvessels and coverage of blood vessels with alpha-smooth muscle cell actin positive mural cells.

Conclusions: Our data implicate that the murine VASH1 causes angiogenic remodelling by inhibiting the growth of large vessels in vivo and by supporting the formation of microvessels and their coverage with smooth muscle cells. EG and GU contributed equally to this work.
Circulating Endothelial Progenitor Cells Is Increasing in Human T Cell Lymphotropic Virus Type 1 (HTLV1) Asymptomatic Carriers
Authors: Meireles Ana Luisa Langanke Pedroso , Chamone Dalton , Godoy Carla Rosa Teixeira , Pereira Juliana
Published: April 2020

The role of angiogenesis in metastasis of solid tumors is well established, but not in hematologic malignancies. Marwan et al demonstrated that Human T Cell Lymphotropic Virus Type 1 (HTLV1) transformed T cells secrete vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and induce angiogenesis in vitro. Adult T-cell leukemia-lymphoma (ATL) leukemic cells produce VEGF and bFGF proteins. Therefore, the role of angiogenesis in ATL development is under investigation. We interested whether endothelial progenitor cells (EPCs) and mature endothelial cells (ECs) contribute to tumor angiogenesis in ATL Thought, this cross-sectional study aimed at quantifying circulating endothelial cells in the blood of HTLV1 asymptomatic carriers in comparison to healthy individuals by flow cytometry. A sample of 30 HTLV1 carrier age and sex matched has been compared to the control group. We demonstrated that the EPCs values were greater in the asymptomatic HTLV1 carrier (median 0.8288 cells/mm3) rather than to the control group (median 0.4905 cells/mm3) (p = 0.035). We identified other pathway of the angiogenesis in HTLV1 carriers. However, others studies are necessary to confirm the role of EPCs in the ATL pathogenesis.
Bone Marrow Adipocytes Prevent Hematopoietic Expansion in Homeostasis and in Bone Marrow Transplantation
Authors: Naveiras Olaia , Nardi Valentina , Daley George Q.
Published: April 2020

In mammalian bone marrow (BM), osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC). Adult BM also contains numerous adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. As described by Neumann’s law in 1882, distal skeletal regions are adipocytic and thus non-hematopoietic in the adult. Fatty infiltration of the hematopoietic red marrow also occurs following irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia. However, whether adipocytes participate in hematopoietic regulation or simply expand to fill marrow space is unclear. We have found that murine hematopoiesis is reduced in adipocyte-rich marrow during homeostasis, and that adipocytes antagonize marrow recovery post-irradiation. By flow cytometry, colony forming assay, and competitive repopulation, we found a reduced frequency of HSCs and short-term hematopoietic progenitors in the adipocyte-rich vertebrae of the tail compared to the adipocyte-free vertebrae of the thorax. In A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes, post-irradiation marrow engraftment is accelerated relative to wild type mice. Likewise, pharmacologic inhibition of adipocyte formation with the PPARg inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE) enhances hematopoietic recovery after BM transplant. Moreover, we have found that mice deficient in the adipocyte-specific protein adiponectin, which has been described to inhibit hematopoietic progenitor expansion in vitro, have increased progenitors in fatty marrow both during homeostasis and after BM transplant. Our data implicate adipocytes as negative regulators of the bone marrow microenvironment, and demonstrate that antagonizing adipogenesis is advantageous for enhancing hematopoietic recovery in the setting of bone marrow transplantation.
Minor Histocompatibility Antigen Mismatches and Graft Versus Host and Relapse in High-Resolution HLA-Matched Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Cliquennois Manuel , Cracco Pascale , Becuwe Dominique , Salleron Julia , Dufossé Françoise , Duhamel Alain , Jouet Jean-Pierre , Dessaint Jean-Paul , Labalette Myriam , Yakoub-Agha Ibrahim
Published: April 2020

In a fully molecular HLA-matched setting, the outcome of allogeneic stem-cell transplantation (allo-SCT) can be affected by mismatches in minor histocompatibility antigens (mHAs) that might impact on the risk of graft-versus-host (GvH) and graft-versus-leukemia (GvL) effects. The association between mHA disparities and outcome was investigated in 96 consecutive patients who underwent myeloablative HLA-matched allo-SCT (from 69 HLA-identical siblings and 27 HLA-matched unrelated donors, all typed and matched at both allelic levels for HLA-A, -B, -Cw, -DRB1, and -DQB1 loci) for standard-risk hematological malignancy (AML n = 41; ALL n = 29; MDS n = 12; CML n = 8; others n = 6). All patients but 9 received bone marrow graft. Allelic mHAg typing was performed by PCR with sequence-specific primers for 9 autosomally encoded mHA and H-Y (PCR-SSP; Spierings et al. PLoS ONE. 2006 Dec 20; 1:e42). The distribution of autosomal mHAs among donor and recipients conformed to the expected frequencies for this population. As expected, the prevalence of mHAg mismatches was higher in unrelated compared to related recipient/donor pairs (p < .003). In univariate analysis, patients who received a graft with more than 2 mHAg mismatches developed more often grade II-IV acute GvH disease (p = .01; HR=2.92 [1.28–6.64]). In multivariate analysis, HA2 mismatch emerged as an independent determinant of acute GvH disease (p = .05; HR = .42). When only mismatches in the GvL/GvH direction were considered, mismatch for HA-1, that is expressed mainly by the hematopoietic system, tended to influence the incidence of both acute and chronic GvH disease (p = .06; HR=1.47 [0.97–2.21] and p = .049; HR = 1.45 [1.00–2.10], respectively) but also to confer a reduced risk of relapse (p = .07; HR = .58 [0.32–1.05]). Mismatch for HA-8, that has a broad tissue distribution, emerged as an independent risk factor of grade II-IV acute GvH disease (p = .02; HR = 1.77 [1.08–2.89]). This study confirms the impact of mHAg mismatches on patients’ outcome after fully HLA-matched allo-SCT and highlights both the cumulative effect of mHAg disparities on outcome and the distinctive contribution of individual mHAs on GvH versus GvL effects of allo-SCT.
Acute Myeloid Leukemia in the Elderly: Assessment of Multidrug Resistance (MDR1) and Cytogenetics Distinguishes Biologic Subgroups With Remarkably Distinct Responses to Standard Chemotherapy. A Southwest Oncology Group Study
Authors: Leith Catherine P. , Kopecky Kenneth J. , Godwin John , McConnell Thomas , Slovak Marilyn L. , Chen I-Ming , Head David R. , Appelbaum Frederick R. , Willman Cheryl L.
Published: April 2020

Compared with younger patients, elderly patients with acute myeloid leukemia (AML) respond poorly to conventional chemotherapy. To determine if this poor response is due to differences in the biologic characteristics of AML in the elderly, we studied 211 patients (161 de novo, 50 secondary AML) over 55 years of age (median, 68 years) registered to a single clinical trial for previously untreated AML (SWOG 9031, Phase III randomized trial of standard dose cytosine arabinoside and daunomycin ± rhG-CSF ). Pretreatment leukemic blasts were karyotyped and were also analyzed for intrinsic drug resistance by quantitating expression of the multidrug resistance glycoprotein MDR1 and functional drug efflux using sensitive flow cytometric techniques. Results were correlated with clinical variables and outcome. These elderly AML patients had a high frequency of unfavorable cytogenetics (32%), MDR1 protein expression (71%), and functional drug efflux (58%); each of these factors occurred at high frequencies in both de novo and secondary AML patients and was associated with a significantly poorer complete remission (CR) rate. In multivariate analysis, secondary AML (P = .0035), unfavorable cytogenetics (P = .0031), and MDR1 (P = .0041) were each significantly and independently associated with lower CR rates. Resistant disease was associated with unfavorable cytogenetics (P = .017) and MDR1 expression (P = .0007). Strikingly, elderly MDR1(−) de novo AML patients with favorable/intermediate cytogenetics had a CR rate of 81%; with increasing MDR1 expression, CR rate decreased in this cytogenetic group. MDR1(+) secondary AML patients with unfavorable cytogenetics had a CR rate of only 12%. Thus, AML in the elderly is associated with an increased frequency of unfavorable cytogenetics and MDR1 expression, both of which independently contribute to poor outcomes. The high frequencies of these features in both de novo and secondary elderly AML patients suggest a common biologic mechanism for these leukemias distinct from that in younger patients. Investigation of biologic parameters at diagnosis in AML in the elderly may help identify patients with a high likelihood of achieving CR with conventional regimens, as well as those who may require alternate regimens designed to overcome therapy resistance.
Glycoprotein VI Is a Major Collagen Receptor for Platelet Activation: It Recognizes the Platelet-Activating Quaternary Structure of Collagen, Whereas CD36, Glycoprotein IIb/IIIa, and von Willebrand Factor Do Not
Authors: Kehrel Beate , Wierwille Sonja , Clemetson Kenneth J. , Anders Olaf , Steiner Michael , Graham Knight C. , Farndale Richard W. , Okuma Minoru , Barnes Michael J.
Published: April 2020

Simple collagen-related peptides (CRPs) containing a repeat Gly-Pro-Hyp sequence are highly potent platelet agonists. Like collagen, they must exhibit tertiary (triple-helical) and quaternary (polymeric) structure to activate platelets. Platelet signaling events induced by the peptides are the same as most of those induced by collagen. The peptides do not recognize the α2β1 integrin. To identify the signaling receptor involved, we have evaluated the response to the CRP, Gly-Lys-Hyp(Gly-Pro-Hyp)10-Gly-Lys-Hyp-Gly of platelets with defined functional deficiencies. These studies exclude a primary recognition role for CD36, von Willebrand factor (vWF), or glycoprotein (GP) IIb/IIIa. Thus, both CD36 and vWF-deficient platelets exhibited normal aggregation, normal fibrinogen binding, and normal expression of CD62 and CD63, measured by flow cytometry, in response to the peptide, and there was normal expression of CD62 and CD63 on thrombasthenic platelets. In contrast, GPVI-deficient platelets were totally unresponsive to the peptide, indicating that this receptor recognizes the Gly-Pro-Hyp sequence in collagen. GPVI-deficient platelets showed some fibrinogen binding in response to collagen but failed to aggregate and to express CD62 and CD63. Collagen, but not CRP-XL, contains binding sites for α2β1. Therefore, it is possible that collagen still induces some signaling via α2β1, leading to activation of GPIIb/IIIa. Our findings are consistent with a two-site, two-step model of collagen interaction with platelets involving recognition of specific sequences in collagen by an adhesive receptor such as α2β1 to arrest platelets under flow and subsequent recognition of another specific collagen sequence by an activatory receptor, namely GPVI.
Human Monocytes Constitutively Express Membrane-Bound, Biologically Active, and Interferon-γ–Upregulated Interleukin-15
Authors: Musso Tiziana , Calosso Liliana , Zucca Mario , Millesimo Maura , Ravarino Daniela , Giovarelli Mirella , Malavasi Fabio , Ponzi Alessandro Negro , Paus Ralf , Bulfone-Paus Silvia
Published: April 2020

Interleukin-15 (IL-15) is a potent regulator of T-, B-, and natural killer cell proliferation and displays unusually tight controls of secretion. Even though IL-15 mRNA is constitutively expressed in monocytes/macrophages and is upregulated by a variety of stimuli, evidence for IL-15 cytokine secretion is only found exceptionally, eg, conditions of pathological, chronic inflammation. This raises the possibility that monocytes express membrane-bound IL-15 rather than secrete it. The current study explores this hypothesis. We demonstrate here that biologically active IL-15 is indeed detectable in a constitutively expressed, membrane-bound form on normal human monocytes, as well as on monocytic cell lines (MONO-MAC-6, THP-1, and U937), but not on human T or B cells (MT4, M9, C5966, JURKAT, DAUDI, RAJI, and Epstein-Barr virus-immortalized B-cell clones). Furthermore, cell surface-bound IL-15 is upregulated upon interferon-γ stimulation. Interestingly, monocyte/macrophage inhibitory cytokines such as IL-4 and IL-13 fail to downregulate both constitutive and induced cell-surface expression of IL-15. Membrane-bound IL-15 does not elute with acetate buffer or trypsin treatment, suggesting that it is an integral membrane protein and that it is not associated with the IL-15 receptor complex. Finally, membrane-bound IL-15 stimulates T lymphocytes to proliferate in vitro, indicating that it is biologically active. These findings enlist IL-15 in the fairly small family of cytokines for which the presence of a biologically active membrane-bound form has been demonstrated (eg, IL-1, tumor necrosis factor-, and IL-10) and invites the speculation that most of the biological effects of IL-15 under physiological conditions are exerted by the cell surface-bound form.
Molecular Analysis of the ERGIC-53 Gene in 35 Families With Combined Factor V-Factor VIII Deficiency
Authors: Neerman-Arbez M. , Johnson K.M. , Morris M.A. , McVey J.H. , Peyvandi F. , Nichols W.C. , Ginsburg D. , Rossier C. , Antonarakis S.E. , Tuddenham E.G.D.
Published: April 2020

Combined factor V-factor VIII deficiency (F5F8D) is a rare, autosomal recessive coagulation disorder in which the levels of both coagulation factors V and VIII are diminished. The F5F8D locus was previously mapped to a 1-cM interval on chromosome 18q21. Mutations in a candidate gene in this region, ERGIC-53, were recently found to be associated with the coagulation defect in nine Jewish families. We performed single-strand conformation and sequence analysis of the ERGIC-53 gene in 35 F5F8D families of different ethnic origins. We identified 13 distinct mutations accounting for 52 of 70 mutant alleles. These were 3 splice site mutations, 6 insertions and deletions resulting in translational frameshifts, 3 nonsense codons, and elimination of the translation initiation codon. These mutations are predicted to result in synthesis of either a truncated protein product or no protein at all. This study revealed that F5F8D shows extensive allelic heterogeneity and all ERGIC-53 mutations resulting in F5F8D are “null.” Approximately 26% of the mutations have not been identified, suggesting that lesions in regulatory elements or severe abnormalities within the introns may be responsible for the disease in these individuals. In two such families, ERGIC-53 protein was detectable at normal levels in patients’ lymphocytes, raising the further possibility of defects at other genetic loci.
Diazoxide affects mitochondrial bioenergetics by the opening of mKATP channel on submicromolar scale
Authors: Akopova Olga , Kolchinskaya Liudmila , Nosar Valentina , Mankovska Iryna , Sagach Vadim
Published: April 2020

Background

Cytoprotection afforded by mitochondrial ATP-sensitive K+-channel (mKATP-channel) opener diazoxide (DZ) largely depends on the activation of potassium cycle with eventual modulation of mitochondrial functions and ROS production. However, generally these effects were studied in the presence of Mg∙ATP known to block K+ transport. Thus, the purpose of our work was the estimation of DZ effects on K+ transport, K+ cycle and ROS production in rat liver mitochondria in the absence of Mg∙ATP.

Results

Without Mg·ATP, full activation of native mKATP-channel, accompanied by the increase in ATP-insensitive K+ uptake, activation of K+-cycle and respiratory uncoupling, was reached at ≤0.5 μM of DZ,. Higher diazoxide concentrations augmented ATP-insensitive K+ uptake, but not mKATP-channel activity. mKATP-channel was blocked by Mg·ATP, reactivated by DZ, and repeatedly blocked by mKATP-channel blockers glibenclamide and 5-hydroxydecanoate, whereas ATP-insensitive potassium transport was blocked by Mg2+ and was not restored by DZ. High sensitivity of potassium transport to DZ in native mitochondria resulted in suppression of mitochondrial ROS production caused by the activation of K+-cycle on sub-micromolar scale. Based on the oxygen consumption study, the share of mKATP-channel in respiratory uncoupling by DZ was found.

Conclusions

The study of mKATP-channel activation by diazoxide in the absence of MgATP discloses novel, not described earlier, aspects of mKATP-channel interaction with this drug. High sensitivity of mKATP-channel to DZ results in the modulation of mitochondrial functions and ROS production by DZ on sub-micromolar concentration scale. Our experiments led us to the hypothesis that under the conditions marked by ATP deficiency affinity of mKATP-channel to DZ can increase, which might contribute to the high effectiveness of this drug in cardio- and neuroprotection.
Campylobacter jejuni and Campylobacter coli autotransporter genes exhibit lineage-associated distribution and decay
Authors: Mehat Jai W. , La Ragione Roberto M. , van Vliet Arnoud H. M.
Published: April 2020

Background

Campylobacter jejuni and Campylobacter coli are major global causes of bacterial gastroenteritis. Whilst several individual colonisation and virulence factors have been identified, our understanding of their role in the transmission, pathogenesis and ecology of Campylobacter has been hampered by the genotypic and phenotypic diversity within C. jejuni and C. coli. Autotransporter proteins are a family of outer membrane or secreted proteins in Gram-negative bacteria such as Campylobacter, which are associated with virulence functions. In this study we have examined the distribution and predicted functionality of the previously described capC and the newly identified, related capD autotransporter gene families in Campylobacter.

Results

Two capC-like autotransporter families, designated capC and capD, were identified by homology searches of genomes of the genus Campylobacter. Each family contained four distinct orthologs of CapC and CapD. The distribution of these autotransporter genes was determined in 5829 C. jejuni and 1347 C. coli genomes. Autotransporter genes were found as intact, complete copies and inactive formats due to premature stop codons and frameshift mutations. Presence of inactive and intact autotransporter genes was associated with C. jejuni and C. coli multi-locus sequence types, but for capC, inactivation was independent from the length of homopolymeric tracts in the region upstream of the capC gene. Inactivation of capC or capD genes appears to represent lineage-specific gene decay of autotransporter genes. Intact capC genes were predominantly associated with the C. jejuni ST-45 and C. coli ST-828 generalist lineages. The capD3 gene was only found in the environmental C. coli Clade 3 lineage. These combined data support a scenario of inter-lineage and interspecies exchange of capC and subsets of capD autotransporters.

Conclusions

In this study we have identified two novel, related autotransporter gene families in the genus Campylobacter, which are not uniformly present and exhibit lineage-specific associations and gene decay. The distribution and decay of the capC and capD genes exemplifies the erosion of species barriers between certain lineages of C. jejuni and C. coli, probably arising through co-habitation. This may have implications for the phenotypic variability of these two pathogens and provide opportunity for new, hybrid genotypes to emerge.
DolphinNext: a distributed data processing platform for high throughput genomics
Authors: Yukselen Onur , Turkyilmaz Osman , Ozturk Ahmet Rasit , Garber Manuel , Kucukural Alper
Published: April 2020

Background

The emergence of high throughput technologies that produce vast amounts of genomic data, such as next-generation sequencing (NGS) is transforming biological research. The dramatic increase in the volume of data, the variety and continuous change of data processing tools, algorithms and databases make analysis the main bottleneck for scientific discovery. The processing of high throughput datasets typically involves many different computational programs, each of which performs a specific step in a pipeline. Given the wide range of applications and organizational infrastructures, there is a great need for highly parallel, flexible, portable, and reproducible data processing frameworks.

Several platforms currently exist for the design and execution of complex pipelines. Unfortunately, current platforms lack the necessary combination of parallelism, portability, flexibility and/or reproducibility that are required by the current research environment. To address these shortcomings, workflow frameworks that provide a platform to develop and share portable pipelines have recently arisen. We complement these new platforms by providing a graphical user interface to create, maintain, and execute complex pipelines. Such a platform will simplify robust and reproducible workflow creation for non-technical users as well as provide a robust platform to maintain pipelines for large organizations.

Results

To simplify development, maintenance, and execution of complex pipelines we created DolphinNext. DolphinNext facilitates building and deployment of complex pipelines using a modular approach implemented in a graphical interface that relies on the powerful Nextflow workflow framework by providing 1. A drag and drop user interface that visualizes pipelines and allows users to create pipelines without familiarity in underlying programming languages. 2. Modules to execute and monitor pipelines in distributed computing environments such as high-performance clusters and/or cloud 3. Reproducible pipelines with version tracking and stand-alone versions that can be run independently. 4. Modular process design with process revisioning support to increase reusability and pipeline development efficiency. 5. Pipeline sharing with GitHub and automated testing 6. Extensive reports with R-markdown and shiny support for interactive data visualization and analysis.

Conclusion

DolphinNext is a flexible, intuitive, web-based data processing and analysis platform that enables creating, deploying, sharing, and executing complex Nextflow pipelines with extensive revisioning and interactive reporting to enhance reproducible results.
Incidence of heart failure among diabetic patients with ischemic heart disease: a cohort study
Authors: Abdissa Senbeta Guteta , Deressa Wakgari , Shah Amit J.
Published: April 2020

Background

In population studies of heart failure (HF), diabetes has been shown to be an independent risk factor. However, the evidence evaluating diabetes mellitus (DM) as an independent risk factor in incident HF in patients with ischemic heart disease (IHD) is scarce. Our study aimed to assess the incidence of HF in diabetic IHD patients compared to non-diabetic IHD patients in Ethiopia.

Methods

A retrospective cohort study was conducted among 306 patients with IHD followed-up at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia. The IHD patients who did not have HF at baseline were followed for 24 months beginning from November 30, 2015. We assessed the incidence of HF in patients with diabetic IHD versus the non-diabetic IHD. Cox proportional hazards models were used to assess the association between diabetic IHD and HF after controlling for important covariates. Hypertension was examined as a possible effect modifier as well.

Results

The mean age was 56.8 years, 69% were male, and 31% were diabetic. During the 24 months follow-up period, 196 (64.1%) had incident HF. On multivariate Cox regression, DM was significantly associated with incident HF [Hazard Ratio = 2.04, 95% confidence interval (CI): 1.32–3.14, p = 0.001]. Furthermore, when the patients were stratified by hypertension (HTN), DM was associated with worse prognosis, the strongest association being in those with co-existing DM and HTN [HR = 2.57,95% CI =1.66–3.98, p <  0.0001] followed by the presence of DM without HTN [HR 2.27, 95% CI = 1.38–3.71, p = 0.001] (compared to those with neither).

Conclusion

DM is the strongest predictor of incident HF, compared to other traditional risk factors, in Ethiopian patients with IHD. Those with both DM and HTN are at the highest risk.
Patients without colonoscopic follow-up after abnormal fecal immunochemical tests are often unaware of the abnormal result and report several barriers to colonoscopy
Authors: Cusumano Vivy T. , Corona Edgar , Partida Diana , Yang Liu , Yu Christine , May Folasade P.
Published: April 2020

Background

The fecal immunochemical test (FIT) is the second most commonly used colorectal cancer (CRC) screening modality in the United States; yet, follow-up of abnormal FIT results with diagnostic colonoscopy is underutilized. Our objective was to determine patient-reported barriers to diagnostic colonoscopy following abnormal FIT in an academic healthcare setting.

Methods

We included patients age 50–75 with an abnormal FIT result between 1/1/2015 and 10/31/2017 and no documented follow-up diagnostic colonoscopy. We abstracted demographic data from the electronic health record (EHR). Study personnel conducted telephone surveys with patients to confirm colonoscopy completion and elicit data on notification of FIT results and barriers to colonoscopy. We also provided brief verbal education about diagnostic colonoscopy. We calculated frequencies of demographic data and survey responses and compared survey responses by interest in colonoscopy after education.

Results

We surveyed 67 patients. Fifty-one were aware of the abnormal FIT result, and a majority learned of the abnormal FIT result by direct communication with providers (19, 37.3%) or EHR messaging (11, 21.6%). Overall, fifty-three patients (79.1%) confirmed lack of colonoscopy, citing provider-related (19, 35.8%), patient-related (16, 30.2%), system-related (1, 1.9%), or multifactorial (17, 32.1%) reasons. Lack of knowledge of FIT result (14, 26.4%) was most common. After brief education, 20 (37.7%) patients requested colonoscopy.

Conclusion

Patients with an abnormal FIT reported various multi-level barriers to diagnostic colonoscopy after abnormal FIT, including knowledge of FIT results. When provided with brief education, participants expressed interest in diagnostic colonoscopy. Future efforts will evaluate interventions to improve colonoscopy follow-up.
Performance of TGSE BLADE DWI compared with RESOLVE DWI in the diagnosis of cholesteatoma
Authors: Sheng Yaru , Hong Rujian , Sha Yan , Zhang Zhongshuai , Zhou Kun , Fu Caixia
Published: April 2020

Background

Based on its high resolution in soft tissue, MRI, especially diffusion-weighted imaging (DWI), is increasingly important in the evaluation of cholesteatoma. The purpose of this study was to evaluate the role of the 2D turbo gradient- and spin-echo (TGSE) diffusion-weighted (DW) pulse sequence with the BLADE trajectory technique in the diagnosis of cholesteatoma at 3 T and to qualitatively and quantitatively compare image quality between the TGSE BLADE and RESOLVE methods.

Method

A total of 42 patients (23 males, 19 females; age range, 7–65 years; mean, 40.1 years) with surgically confirmed cholesteatoma in the middle ear were enrolled in this study. All patients underwent DWI (both a prototype TGSE BLADE DWI sequence and the RESOLVE DWI sequence) using a 3-T scanner with a 64-channel brain coil.

Qualitative imaging parameters (imaging sharpness, geometric distortion, ghosting artifacts, and overall imaging quality) and quantitative imaging parameters (apparent diffusion coefficient [ADC], signal-to-noise ratio [SNR], contrast, and contrast-to-noise ratio [CNR]) were assessed for the two diffusion acquisition techniques by two independent radiologists.

Result

A comparison of qualitative scores indicated that TGSE BLADE DWI produced less geometric distortion, fewer ghosting artifacts (P < 0.001) and higher image quality (P < 0.001) than were observed for RESOLVE DWI. A comparison of the evaluated quantitative image parameters between TGSE and RESOLVE showed that TGSE BLADE DWI produced a significantly lower SNR (P < 0.001) and higher parameter values (both contrast and CNR (P < 0.001)) than were found for RESOLVE DWI.

The ADC (P < 0.001) was significantly lower for TGSE BLADE DWI (0.763 × 10− 3 mm2/s) than RESOLVE DWI (0.928 × 10− 3 mm2/s).

Conclusion

Compared with RESOLVE DWI, TGSE BLADE DWI significantly improved the image quality of cholesteatoma by reducing magnetic sensitive artifacts, distortion, and blurring. TGSE BLADE DWI is more valuable than RESOLVE DWI for the diagnosis of small-sized (2 mm) cholesteatoma lesions. However, TGSE BLADE DWI also has some disadvantages: the whole image intensity is slightly low, so that the anatomical details of the air-bone interface are not shown well, and this shortcoming should be improved in the future.
Correlation between gene polymorphism in angiotensin II type 1 receptor and type 2 diabetes mellitus complicated by hypertension in a population of Inner Mongolia
Authors: Hou Lina , Quan Xiaohong , Li Xian , Su Xiulan
Published: April 2020

Background

The role of angiotensin II type 1 receptor (AT1R) as a key player in type 2 diabetes mellitus (T2DM) complicated with hypertension remains controversial. The present case-control study systematically investigated the association between gene the correct variation type in the angiotensin II type 1 receptor (AT1R) gene and type 2 diabetes mellitus complicated with hypertension in the Han population from the Inner Mongolia region, China.

Method

Here, state which variants were analysis, including age, occupation, triglyceride, systolic, diastolic, sex, culture, marital status, smoking, alcohol, BMI (body mass index), SBP (systolic blood pressure), DBP (diastolic blood pressure), TG (triglyceride), TC (total cholesterol), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol), FPG (fasting plasma glucose). Genomic DNA was extracted from samples from 202 type 2 diabetic patients with hypertension and 216 type 2 diabetic patients without hypertension.

Results

Non-conditional regression analysis showed that in comparison with the TT genotype, the presence of the CC genotype for the T573 site of the AT1R gene increased the risk for diabetes mellitus complicated with hypertension by 3.219-fold (OR = 3.219, 95% CI: 1.042–9.941, P = 0.042). The results from multivariate linear regression analysis suggested the rs5182 polymorphism in the AT1R gene to be associated with diastolic blood pressure (P = 0.032). No other associations were found between the incidence of disease and the correct variation type at other sites of the AT1R gene.

Conclusions

Our results suggest that the rs5182 polymorphism in the AT1R gene is associated with diabetes complicated by hypertension in the Han population of Inner Mongolia.
GRP78 expression in peripheral blood mononuclear cells is a new predictive marker for the benefit of taxanes in breast cancer neoadjuvant treatment
Authors: Raiter Annat , Lipovetzki Julia , Lubin Ido , Yerushalmi Rinat
Published: April 2020

Background

Breast cancer treatment is tailored to the specific cancer subtype. Often, systemic treatment is given prior to surgery. Chemotherapy induces significant endoplasmic reticulum (ER) stress-mediated cell death and upregulation of 78-kDa glucose-regulated protein (GRP78). We hypothesized that chemotherapy induces ER stress not only in the tumor tissue but also in immune cells, which may affect the response to anti-cancer treatment.

Methods

We determined the surface expression of GRP78 on 15 different peripheral blood mononuclear cell (PBMC) subpopulations in 20 breast cancer patients at three time points of the neoadjuvant treatment, i.e., at baseline, after anthracycline treatment, and after taxanes treatment. For this purpose, we performed flow cytometric analyses and analyzed the data using ANOVA and the Tukey test. Serum cytokine levels were also evaluated, and their levels were correlated with response to treatment using the t-test after log transformation and Mann-Whitney U Wilcoxon W test.

Results

A significant increase in GRP78 expression in PBMCs was documented during the taxane phase, only in patients who achieved pathological complete response (pCR). GRP78-positive clones correlated with increased serum levels of interferon gamma (IFNγ).

Conclusions

The presence of GRP78-positive clones in certain PBMC subpopulations in pCR patients suggests a dynamic interaction between ER stress and immune responsiveness. The correlation of GRP78-positive clones with increased levels of IFNγ supports the idea that GRP78 expression in PBMCs might serve as a new predictive marker to identify the possible benefits of taxanes in the neoadjuvant setting.
Evaluation of microvascular network with optical coherence tomography angiography (OCTA) in branch retinal vein occlusion (BRVO)
Authors: Chen Lulu , Yuan Mingzhen , Sun Lu , Wang Yuelin , Chen Youxin
Published: April 2020

Background

To evaluate changes of microvascular network of macular and peripapillary regions and to provide a quantitative measurement of foveal avascular zone (FAZ) in unilateral BRVO patients.

Methods

Forty-seven unilateral BRVO patients and forty-seven normal controls were enrolled. A 3*3 mm scan centered on fovea followed by a 4.5*4.5 mm scan centered on optic nerve head (ONH) were obtained in BRVO eyes, fellow eyes and control eyes of each individual using OCTA (Optovue Inc., Fremont, CA, USA). Vessel density (VD) in superficial (SVC) and deep vascular complex (DVC) of macula and radial peripapillary capillary (RPC) were automatically calculated. Parameters of FAZ region including size, perimeter, acircularity index (AI) and foveal vessel density 300 (FD-300) were measured.

Results

VDs of SCV and DVC were significantly lower, especially in affected regions, in BRVO eyes compared with fellow eyes (P < 0.05). BRVO affected eyes has larger FAZ size, FAZ perimeter, AI and lower FD-300 compared with fellow eyes (all P < 0.05). VD of SVC and FD-300 were lower in fellow eyes compared with normal control eyes (P < 0.05). The average vessel density in whole area and peripapillary area in BRVO eyes were significantly lower compared with fellow eyes (P < 0.05). VD of inside disc in fellow eyes was lower than normal eyes (P < 0.05).

Conclusions

OCTA provided quantitative information of vascular changes in BRVO. FAZ in BRVO eyes showed significant morphological alterations and decreases of VD in surrounding area. Decreases of VD existed not only in SVC and DVC in macular region but also in RPCs in BRVO eyes. Unaffected eyes of unilateral BRVO showed vascular abnormalities in superficial retinal layer, peri-FAZ area and also peripapillary regions.
Acute retinal detachment after Nd:YAG treatment for vitreous floaters and postertior capsule opacification: a case report
Authors: Liu Xiuduo , Wang Qian , Zhao Jie
Published: April 2020

Background

Modern laser surgery uses Nd:YAG laser capsulotomy for posterior capsule opacification (PCO) and Nd:YAG laser vitreolysis for symptomatic vitreous floaters (VF). We report a case of acute retinal detachment seven days after Nd:YAG laser capsulotomy combined with Nd:YAG laser vitreolysis and analyze the cause of this complication.

Case presentation

A 58-year-old myopic woman complained of decreased visual acuity and symptomatic floaters with her left eye for 3 months. We found she had significant PCO and VF in the posterior vitreous. She underwent neodymium-doped yttrium aluminum (Nd:YAG) laser vitreolysis immediately after Nd:YAG capsulotomy. After 7 days, she complained of rapid vision decline and dark shadows in her treated eye. We found she had a acute severe rhegmentogenous retinal detachment (RD) involving the macula. Then she underwent vitrectomy, retinal reattchment and silicone oil tamponade surgery immediately. Six months later, silicone oil was removed and the best corrected visual acuity (BCVA) of her left eye gradually improved to 10/20 and maintained during a 1-year follow-up period.

Conclusion

As myopic patients are at risk of developing retinal detachment, Nd:YAG vitreolysis and capsulotomy should be performed with caution. The laser energy should be as low as possible and careful focus is necessary to reduce interference to the retina.
The NHS visitor and migrant cost recovery programme – a threat to health?
Authors: Potter J. L. , Burman M. , Tweed C. D. , Vaghela D. , Kunst H. , Swinglehurst D. , Griffiths C. J.
Published: April 2020

Background

In April 2014 the UK government launched the ‘NHS Visitor and Migrant Cost Recovery Programme Implementation Plan’ which set out a series of policy changes to recoup costs from ‘chargeable’ (largely non-UK born) patients. In England, approximately 75% of tuberculosis (TB) cases occur in people born abroad. Delays in TB treatment increase risk of morbidity, mortality and transmission in the community. We investigated whether diagnostic delay has increased since the Cost Recovery Programme (CRP) was introduced.

Methods

There were 3342 adult TB cases notified on the London TB Register across Barts Health NHS Trust between 1st January 2011 and 31st December 2016. Cases with missing relevant information were excluded. The median time between symptom onset and treatment initiation before and after the CRP was calculated according to birthplace and compared using the Mann Whitney test. Delayed diagnosis was considered greater or equal to median time to treatment for all patients (79 days). Univariable logistic regression was used to manually select exposure variables for inclusion in a multivariable model to test the association between diagnostic delay and the implementation of the CRP.

Results

We included 2237 TB cases. Among non-UK born patients, median time-to-treatment increased from 69 days to 89 days following introduction of CRP (p < 0.001). Median time-to-treatment also increased for the UK-born population from 75.5 days to 89.5 days (p = 0.307). The multivariable logistic regression model showed non-UK born patients were more likely to have a delay in diagnosis after the CRP (adjOR 1.37, 95% CI 1.13–1.66, p value 0.001).

Conclusion

Since the introduction of the CRP there has been a significant delay for TB treatment among non-UK born patients. Further research exploring the effect of policies restricting access to healthcare for migrants is urgently needed if we wish to eliminate TB nationally.
Informal workplaces and their comparative effects on the health of street vendors and home-based garment workers in Yangon, Myanmar: a qualitative study
Authors: Ko Ko Thant , Dickson-Gomez Julia , Yasmeen Gisèle , Han Wai Wai , Quinn Katherine , Beyer Kirsten , Glasman Laura
Published: April 2020

Background

Globally, two billion workers are employed informally but there is limited research on the relationship between informal work and health. Existing studies have focused on informality as an employment condition, with little emphasis on the diversity of physical and social contexts in which informal work takes place. The study considers the diversity of informal workplaces and explores the ways in which this diversity might influence health and well-being of two informal occupational groups in Yangon, the former capital of Myanmar.

Methods

We conducted 21 field observations and 47 semi-structured interviews with street vendors and home-based garment workers based in Yangon, Myanmar. A constant comparative method was used to identify and compare how the physical characteristics of their informal workplaces affect their health for these two informal subgroups.

Results

Although both street vendors and home-based garment workers work informally, their exposure to occupational health and income risks are specific to the physical features of their informal workplaces. Street vendors, who work in public spaces with minimal coverage, are more likely to experience the direct effects of outdoor pollution, inclement weather and ergonomic risks from lifting, carrying and transporting heavy merchandise while home-based garment workers, many of whom live and work in unsanitary housing and deprived neighborhoods, are more likely to experience pollution in or near their homes, and ergonomic risks from poor posture. Similarly, although both groups face safety challenges, street vendors face urban violence and abuse during their commute and at vending points whereas home-based garment workers felt unsafe in their home-based workplaces due to the presence of crime and violence in their neighborhoods.

Conclusion

While informal employment is universally characterized by lack of social protection, exposure to occupational health and income risks for subpopulations of informal workers is determined by the specific physical and social environments of their workplaces. Efforts to improve the health of informal workers should consider the contexts in which informal work takes place to develop tailored interventions for subpopulations of informal workers.