bluuebunny/crossref_metadata_2025 huggingface dataset:
Is there a critical gestational age in neutrophil superoxide production activity?
Authors: Ishida K , Tsukimori K , Nagata H , Koyanagi T , Akazawa K , Nakano H
Published: October 2019

We studied superoxide (O2-) production in neutrophils from 78 normal pregnant women at 7 to 39 weeks' gestation to determine whether there is a critical gestational age in O2- production activity of maternal neutrophils. The O2- production was measured by determining the rate of superoxide dismutase-inhibitable reduction of ferricytochrome c at 550 to 540 nm. A scattergram of neutrophil O2- production value versus gestational age was analyzed using the least median of squares regression, leading to a statistical stratification in which the median values of O2- production for outlying and nonoutlying points were 6.60 nmol/10(6) cells and 2.72 nmol/10(6) cells, respectively. All of the outlying points were concentrated at 19 to 22 gestational weeks. There was the significant difference in FMLP-induced O2- production in neutrophils of nonpregnant subjects when incubated with the sera from 10 cases (selected among 60 cases with nonoutlying points) (3.86 +/- 0.77 nmol/10(6) cells) compared with 5 cases with outlying points (5.62 +/- 1.19 nmol/10(6) cells) (P < .05) These results suggest that during the normal course of pregnancy, the production of O2- from the function of circulating neutrophils can be dissociated from such neutrophil functions as adherence, chemotaxis, and phagocytosis.
Mobilization of CD34+ progenitor cells by granulocyte colony- stimulating factor in human immunodeficiency virus type 1-infected adults
Authors: Slobod KS , Bennett TA , Freiden PJ , Kechli AM , Howlett N , Flynn PM , Head DR , Srivastava DK , Boyett JM , Brenner MK , Garcia JV
Published: October 2019

We conducted a clinical trial to determine the feasibility of growth factor mobilization of CD34+ progenitor cells in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Eight asymptomatic, HIV-1-infected adults (median CD4+ T-cell count, 415 cells/microL), received 480 micrograms/d of granulocyte colony-stimulating factor (G-CSF) for 6 days without evidence of viral activation. Despite concerns that HIV-1 might inhibit hematopoiesis, CD34+ cells were successfully mobilized to the periphery of all donors, independent of the baseline CD4+ T-cell count, and the status of antiretroviral therapy. Leukapheresis was performed on day 6, and yielded a median of 194 x 10(6) CD34+ cells per leukapheresis (n = 7). CD34-enriched cells from the leukapheresis were predominantly myeloid-committed, but between 0.2% and 1.7% were primitive CD34+/CD38- progenitors. A median of 21.7% of the mobilized CD34+ cells were dimly positive for CD4. Consequently, CD34(+)-enriched cells were purified on the cell sorter (mean purity, 97.7% +/- 2.4%; n = 7), and examined for HIV-1 DNA. Purified CD34+ cells from two of seven donors were polymerase chain reaction (PCR)-positive for HIV-1, but only from one of three samples from each donor. We conclude that G-CSF can safely mobilize CD34+ progenitor cells in HIV-1-infected subjects, and that these cells are suitable for consideration in gene-transfer strategies.
Biochemical and genetic characterization of multiple splice variants of the Flt3 ligand
Authors: McClanahan T , Culpepper J , Campbell D , Wagner J , Franz-Bacon K , Mattson J , Tsai S , Luh J , Guimaraes MJ , Mattei MG , Rosnet O , Birnbaum D , Hannum CH
Published: October 2019

We have performed a comprehensive analysis of cell lines and tissues to compare and contrast the expression patterns of Flt3 ligand (FL), c-Kit ligand (KL), and macrophage colony-stimulating factor as well as their receptors, Flt3, c-Kit, and c-Fms. The message for FL is unusually ubiquitous, whereas that of its receptor is quite restricted, apparently limiting the function of the ligand to fetal development and early hematopoiesis. We have also sequenced a mouse FL genomic clone, revealing how the three splice variant FL mRNAs that we have isolated arise. The chromosomal location of the FL gene has been mapped, by in situ hybridization, to chromosome 7 in mouse and chromosome 19 in human. Natural FL protein has been purified from a stromal cell line and shown to be a 65 kD nondisulfide-linked homodimeric glycoprotein comprised of 30 kD subunits, each containing 12 kD of N- and O-linked sugars. Pulse-chase experiments show that one of the splice variants (T110) is responsible for producing the bulk of soluble FL, but only after it has first been expressed at the cell surface as a membrane-bound form. The other splice-variant forms produce molecules that are either obligatorily soluble (T169) or membrane-bound but released only very slowly (T118). Finally, even though most cell lines express some amount of FL mRNA, we found that very little FL protein is actually made, with T cells and stromal cells being the major producers. The data suggests that FL plays its roles over very short distances, perhaps requiring cell-cell contact.
Recognition of BCR-ABL positive leukemic blasts by human CD4+ T cells elicited by primary in vitro immunization with a BCR-ABL breakpoint peptide
Authors: Bosch GJ , Joosten AM , Kessler JH , Melief CJ , Leeksma OC
Published: October 2019

In chronic myeloid leukemia (CML) the classical 9;22 translocation results in a BCR-ABL fusion gene, which encodes chimeric BCR-ABL fusion 210 kD oncoproteins (p210BCR-ABL). The two main p210BCR-ABL fusion variants in CML, b2a2 and b3a2 are examples of well characterized antigens expressed by malignant cells. The possibility of an immunotherapeutic approach involving the fusion part of p210BCR-ABL in CML has previously been illustrated by observed peptide binding to major histocompatibility complex (MHC) class I alleles and by demonstrating the immunogenicity of p210BCR-ABL breakpoint peptides. In this report we show that in vitro immunization of human T cells with a 17 amino acid (aa) peptide representing the p210BCR-ABL fusion region resulted in peptide specific CD4+ T-cell lines designated P4, P6, and P7. HLA DR4 (DRB1*0401) restricted T-cell line P4 and several subsequently derived clones recognized HLA-DRB1*0401 and p210b3a2-mRNA expressing blasts from an allogeneic patient with CML in blast crisis. Recognition appeared DR expression-dependent. No responses were observed with DR4 positive p210BCR-ABL negative cells or with p210b3a2 leukemic cells with absent or insufficient expression of DR4. These observations indicate that oncoprotein p210b3a2 can be degraded and processed for presentation by MHC class II molecules at the surface of leukemic cells. The BCR-ABL fusion region is in all likelihood presented as peptides by HLA DR and thus capable to act as a distinctive tumor antigen to peptide specific CD4+ T cells.
Prognostic Significance of Bcl-2 Protein Expression and Bcl-2 Gene Rearrangement in Diffuse Aggressive Non-Hodgkin's Lymphoma
Authors: Gascoyne Randy D. , Adomat Sheryle A. , Krajewski Stanislaw , Krajewska Maryla , Horsman Douglas E. , Tolcher Anthony W. , O'Reilly Susan E. , Hoskins Paul , Coldman Andrew J. , Reed John C. , Connors Joseph M.
Published: October 2019

The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P < .01), DFS (32% v 66%, P < .001), and RFS (25% v 59%, P < .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P < .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs.
Genetic association with B-cell acute lymphoblastic leukemia in allogeneic transplant patients differs by age and sex
Authors: Clay-Gilmour Alyssa I. , Hahn Theresa , Preus Leah M. , Onel Kenan , Skol Andrew , Hungate Eric , Zhu Qianqian , Haiman Christopher A. , Stram Daniel O. , Pooler Loreall , Sheng Xin , Yan Li , Liu Qian , Hu Qiang , Liu Song , Battaglia Sebastiano , Zhu Xiaochun , Block AnneMarie W. , Sait Sheila N. J. , Karaesmen Ezgi , Rizvi Abbas , Weisdorf Daniel J. , Ambrosone Christine B. , Tritchler David , Ellinghaus Eva , Ellinghaus David , Stanulla Martin , Clavel Jacqueline , Orsi Laurent , Spellman Stephen , Pasquini Marcelo C. , McCarthy Philip L. , Sucheston-Campbell Lara E.
Published: October 2019

Key Points

IKZF1 associations with high-risk B-ALL may differ by age and sex. A novel variant on chromosome 14, rs189434316, is associated with over a 3.5-fold risk of normal cytogenetic B-ALL.
Single umbilical cord blood with or without CD34+ cells from a third-party donor in adults with leukemia
Authors: Sanz Jaime , Kwon Mi , Bautista Guiomar , Sanz Miguel A. , Balsalobre Pascual , Piñana José Luis , Solano Carlos , Duarte Rafael , Ferrá Christelle , Lorenzo Ignacio , Martín Carmen , Barba Pere , Pascual María Jesús , Martino Rodrigo , Gayoso Jorge , Buño Ismael , Regidor Carmen , de la Iglesia Almudena , Montoro Juan , Díez-Martín José Luis , Sanz Guillermo F. , Cabrera Rafael
Published: October 2019

Key Points

Haplo-Cord is an effective strategy to quicken neutrophil and platelet recovery. In specific treatment platforms, sUCBT and Haplo-Cord offer similar long-term outcomes.
Loss of mDia1 causes neutropenia via attenuated CD11b endocytosis and increased neutrophil adhesion to the endothelium
Authors: Mei Yang , Feng Gong , Rahimi Nina , Zhao Baobing , Zhang Jingxin , Cao Lan , Yang Jing , Gao Juehua , Chen Yihua , Sumagin Ronen , Muller William A. , Zhang Ling , Ji Peng
Published: October 2019

Key Points

Loss of mDia1 induces neutropenia through increased adhesion of neutrophils to blood vessels and transendothelial migration. mDia1-deficient neutrophils show upregulation of CD11b that is caused by attenuated CD11b endocytosis.
Multiplexed targeted proteomic assay to assess coagulation factor concentrations and thrombosis-associated cancer
Authors: Mohammed Yassene , van Vlijmen Bart J. , Yang Juncong , Percy Andrew J. , Palmblad Magnus , Borchers Christoph H. , Rosendaal Frits R.
Published: October 2019

Key Points

The goal was to compare targeted MRM proteomics with conventional assays to assess concentration levels of coagulation- and fibrinolysis-related proteins. MRM offers higher sensitivity and multiplicity and good ability to leverage measurements to discriminate groups using unsupervised clustering.
Erythrocyte β spectrin can be genetically targeted to protect mice from malaria
Authors: Lelliott Patrick M. , Huang Hong Ming , Dixon Matthew W. , Namvar Arman , Blanch Adam J. , Rajagopal Vijay , Tilley Leann , Coban Cevayir , McMorran Brendan J. , Foote Simon J. , Burgio Gaetan
Published: October 2019

Key Points

Mutations in β spectrin cause microcytosis, resulting in increased clearance of erythrocytes and enhanced resistance to malaria in mice. A homozygous CRISPR/Cas9-induced mutation in the binding site between β spectrin and ankyrin-1 increases mouse survival during malaria.
Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation
Authors: Brüggemann Monika , Kotrova Michaela
Published: October 2019

Nowadays, minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by molecular methods that use leukemia-specific or patient-specific molecular markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene rearrangements), and by multi-parametric flow cytometry. The sensitivity and specificity of these methods can vary across treatment time points and therapeutic settings. Thus, knowledge of the principles and limitations of each technology is of the utmost importance for correct interpretation of MRD results. Time will tell whether new molecular and flow cytometric high-throughput technologies can overcome the limitations of current standard methods and eventually bring additional benefits. MRD during standard ALL chemotherapy is the strongest overall prognostic indicator and has therefore been used for refining initial treatment stratification. Moreover, MRD positivity after the maintenance phase of treatment may point to an impending relapse and thus enable salvage treatment to be initiated earlier, which could possibly improve treatment results. The prognostic relevance of pretransplantation MRD was shown by several studies, and MRD high-risk patients were shown to benefit from stem cell transplantation (SCT). Also, MRD positivity after SCT correlates with worse outcomes. In addition, MRD information is very instructive in current clinical trials that test novel agents to evaluate their treatment efficacy. Although conventional clinical risk factors lose their independent prognostic significance when combined with MRD information, recently identified genetic markers may further improve the treatment stratification in ALL.
Developing T-cell therapies for lymphoma without receptor engineering
Authors: Grant Melanie , Bollard Catherine M.
Published: October 2019

T-cell therapy has emerged from the bench for the treatment of patients with lymphoma. Responses to T-cell therapeutics are regulated by multiple factors, including the patient’s immune system status and disease stage. Outside of engineering of chimeric antigen receptors and artificial T-cell receptors, T-cell therapy can be mediated by ex vivo expansion of antigen-specific T cells targeting viral and/or nonviral tumor-associated antigens. These approaches are contributing to enhanced clinical responses and overall survival. In this review, we summarize the available T-cell therapeutics beyond receptor engineering for the treatment of patients with lymphoma.
Prognostic impact of kinase-activating fusions and IKZF1 deletions in pediatric high-risk B-lineage acute lymphoblastic leukemia
Authors: Tran Thai Hoa , Harris Marian H. , Nguyen Jonathan V. , Blonquist Traci M. , Stevenson Kristen E. , Stonerock Eileen , Asselin Barbara L. , Athale Uma H. , Clavell Luis A. , Cole Peter D. , Kelly Kara M. , Laverdiere Caroline , Leclerc Jean-Marie , Michon Bruno , Schorin Marshall A. , Welch Jennifer J. G. , Reshmi Shalini C. , Neuberg Donna S. , Sallan Stephen E. , Loh Mignon L. , Silverman Lewis B.
Published: October 2019

Key Points

Fifteen percent of NCI high-risk, Ph-negative, B-ALL patients harbored a kinase-activating fusion, and often associated with IKZF1 deletion. IKZF1 deletion represents an independent prognostic factor of poor outcomes, regardless of fusion-positivity.
Differential antibacterial control by neutrophil subsets
Authors: Leliefeld Pieter H. C. , Pillay Janesh , Vrisekoop Nienke , Heeres Marjolein , Tak Tamar , Kox Matthijs , Rooijakkers Suzan H. M. , Kuijpers Taco W. , Pickkers Peter , Leenen Luke P. H. , Koenderman Leo
Published: October 2019

Key Points

Neutrophil subsets circulating during acute inflammation are characterized by differential bacterial containment capacity. Adequate antimicrobial containment is associated with profound phagosomal acidification yet independent of reactive oxygen species.
Positron emission tomography–computed tomography predictors of progression after DA-R-EPOCH for PMBCL
Authors: Pinnix Chelsea C. , Ng Andrea K. , Dabaja Bouthaina S. , Milgrom Sarah A. , Gunther Jillian R. , Fuller C. David , Smith Grace L. , Abou Yehia Zeinab , Qiao Wei , Wogan Christine F. , Akhtari Mani , Mawlawi Osama , Medeiros L. Jeffrey , Chuang Hubert H. , Martin-Doyle William , Armand Philippe , LaCasce Ann S. , Oki Yasuhiro , Fanale Michelle , Westin Jason , Neelapu Sattva , Nastoupil Loretta
Published: October 2019

Key Points

Biomarkers are needed to identify patients with PMBCL who will not be cured after single-modality therapy with R-EPOCH. Volume-based and metabolic variables on pre- and postchemotherapy PET-CT seem to identify patients who progress after R-EPOCH alone.
Coagulation parameters during the course of severe postpartum hemorrhage: a nationwide retrospective cohort study
Authors: Gillissen Ada , van den Akker Thomas , Caram-Deelder Camila , Henriquez Dacia D. C. A. , Bloemenkamp Kitty W. M. , de Maat Moniek P. M. , van Roosmalen Jos J. M. , Zwart Joost J. , Eikenboom Jeroen , van der Bom Johanna G.
Published: October 2019

We describe the pattern of change in coagulation parameters during the course of severe postpartum hemorrhage in a retrospective cohort study among 1312 women experiencing severe postpartum hemorrhage necessitating blood transfusion. Levels of hemoglobin, hematocrit, platelet count, fibrinogen, activated partial thromboplastin time (aPTT) and prothrombin time (PT) per categorized volume of blood loss during severe postpartum hemorrhage were described and compared between women with and without the composite adverse outcome. Need for surgical intervention, severe acute maternal morbidity, and maternal mortality were jointly considered the composite adverse outcome. Of the 1312 women, 463 (35%) developed the composite adverse outcome. The incidence of a fibrinogen level <2 g/L was 26% (342 per 1312). Low fibrinogen and prolonged aPTT during the first 2 L of hemorrhage were associated with a subsequent composite adverse outcome; median fibrinogen and aPTT among women with and without the composite end point after 1.5 to 2 L of hemorrhage were 1.5 g/L (interquartile range [IQR], 1.0-1.9) vs 2.7 g/L (IQR, 1.9-3.4) and 39 s (IQR, 30-47) vs 32 s (IQR, 28-36), respectively. PT and platelet count as assessed during the first 2 L of hemorrhage were not associated with morbidity or mortality. Our results suggest that detection of low levels of fibrinogen and elevated aPTT levels during early postpartum hemorrhage can contribute to the identification of women that may benefit from targeted hemostatic treatment. Essential in this identification process is the moment of reaching a level of fibrinogen of <2 g/L during the course of postpartum hemorrhage.
RUNX1 mutations enhance self-renewal and block granulocytic differentiation in human in vitro models and primary AMLs
Authors: Gerritsen Mylène , Yi Guoqiang , Tijchon Esther , Kuster Jorren , Schuringa Jan Jacob , Martens Joost H. A. , Vellenga Edo
Published: October 2019

To unravel molecular mechanisms by which Runt-related transcription factor 1 (RUNX1) mutations contribute to leukemic transformation, we introduced the RUNX1-S291fs300X mutation in human CD34+ stem/progenitor cells and in human induced pluripotent stem cells (iPSCs). In both models, RUNX1mut overexpression strongly impaired myeloid commitment. Instead, self-renewal was enhanced, as shown, by increased long-term culture-initiating cell frequencies and enhanced colony-forming cell replating capacity. Long-term suspension cultures with RUNX1mut-transduced cord blood (CB) CD34+ cells continued for more than 100 days, during which the cells displayed an immature granulocyte-macrophage progenitor-like CD34+/CD123+/CD45RA+ phenotype. The CD34+/CD38− hematopoietic stem cell (HSC) population most likely acted as cell of origin, as HSCs provided the best long-term proliferative potential on overexpression of RUNX1mut. CEBPA expression was reduced in RUNX1mut cells, and reexpression of CEBPA partly restored differentiation. RNA-seq analysis on CB/iPSC systems and on primary patient samples confirmed that RUNX1 mutations induce a myeloid differentiation block, and that a common set of RUNX1mut-upregulated target genes was strongly enriched for gene ontology terms associated with nucleosome assembly and chromatin structure. Interestingly, in comparison with AML1-ETO binding in acute myeloid leukemias (AMLs), we found significantly distinct genomic distribution and differential expression for RUNX1mut of genes such as TCF4, MEIS1, and HMGA2 that may potentially contribute to the underlying difference in clinical outcomes between RUNX1mut and AML1-ETO patients. In conclusion, RUNX1mut appears to induce a specific transcriptional program that contributes to leukemic transformation.
Impact of donor, recipient and matching on survival after high emergency lung transplantation in France
Authors: Roussel Arnaud , Sage Edouard , Massard Gilbert , Thomas Pascal-Alexandre , Castier Yves , Fadel Elie , Le Pimpec-Barthes Françoise , Maury Jean-Michel , Jougon Jacques , Lacoste Philippe , Claustre Johanna , Dahan Marcel , Pirvu Augustin , Tissot Adrien , Thumerel Matthieu , Drevet Gabrielle , Pricopi Ciprian , Le Pavec Jérôme , Mal Hervé , D'Journo Xavier-Benoit , Kessler Romain , Roux Antoine , Dorent Richard , Thabut Gabriel , Mordant Pierre
Published: October 2019

Introduction

Since July 2007, the French high emergency lung transplantation (HELT) allocation procedure prioritises available lung grafts to waiting patients with imminent risk of death. The relative impacts of donor, recipient and matching on the outcome following HELT remain unknown. We aimed at deciphering the relative impacts of donor, recipient and matching on the outcome following HELT in an exhaustive administrative database.

Methods

All lung transplantations performed in France were prospectively registered in an administrative database. We retrospectively reviewed the procedures performed between July 2007 and December 2015, and analysed the impact of donor, recipient and matching on overall survival after the HELT procedure by fitting marginal Cox models.

Results

During the study period, 2335 patients underwent lung transplantation in 11 French centres. After exclusion of patients with chronic obstructive pulmonary disease/emphysema, 1544 patients were included: 503 HELT and 1041 standard lung transplantation allocations. HELT was associated with a hazard ratio for death of 1.41 (95% CI 1.22–1.64; p<0.0001) in univariate analysis, decreasing to 1.32 (95% CI 1.10–1.60) after inclusion of recipient characteristics in a multivariate model. A donor score computed to predict long-term survival was significantly different between the HELT and standard lung transplantation groups (p=0.014). However, the addition of donor characteristics to recipient characteristics in the multivariate model did not change the hazard ratio associated with HELT.

Conclusions

This exhaustive French national study suggests that HELT is associated with an adverse outcome compared with regular allocation. This adverse outcome is mainly related to the severity status of the recipients rather than donor or matching characteristics.
A spatially restricted fibrotic niche in pulmonary fibrosis is sustained by M-CSF/M-CSFR signalling in monocyte-derived alveolar macrophages
Authors: Joshi Nikita , Watanabe Satoshi , Verma Rohan , Jablonski Renea P. , Chen Ching-I , Cheresh Paul , Markov Nikolay S. , Reyfman Paul A. , McQuattie-Pimentel Alexandra C. , Sichizya Lango , Lu Ziyan , Piseaux-Aillon Raul , Kirchenbuechler David , Flozak Annette S. , Gottardi Cara J. , Cuda Carla M. , Perlman Harris , Jain Manu , Kamp David W. , Budinger G.R. Scott , Misharin Alexander V.
Published: October 2019

Ontologically distinct populations of macrophages differentially contribute to organ fibrosis through unknown mechanisms.

We applied lineage tracing, single-cell RNA sequencing and single-molecule fluorescencein situhybridisation to a spatially restricted model of asbestos-induced pulmonary fibrosis.

We demonstrate that tissue-resident alveolar macrophages, tissue-resident peribronchial and perivascular interstitial macrophages, and monocyte-derived alveolar macrophages are present in the fibrotic niche. Deletion of monocyte-derived alveolar macrophages but not tissue-resident alveolar macrophages ameliorated asbestos-induced lung fibrosis. Monocyte-derived alveolar macrophages were specifically localised to fibrotic regions in the proximity of fibroblasts where they expressed molecules known to drive fibroblast proliferation, including platelet-derived growth factor subunit A. Using single-cell RNA sequencing and spatial transcriptomics in both humans and mice, we identified macrophage colony-stimulating factor receptor (M-CSFR) signalling as one of the novel druggable targets controlling self-maintenance and persistence of these pathogenic monocyte-derived alveolar macrophages. Pharmacological blockade of M-CSFR signalling led to the disappearance of monocyte-derived alveolar macrophages and ameliorated fibrosis.

Our findings suggest that inhibition of M-CSFR signalling during fibrosis disrupts an essential fibrotic niche that includes monocyte-derived alveolar macrophages and fibroblasts during asbestos-induced fibrosis.
Does adherence to inhaled corticosteroids predict asthma-related outcomes over time? A cohort study
Authors: Dima Alexandra L. , van Ganse Eric , Stadler Gertraud , de Bruin Marijn
Published: October 2019

Inhaled corticosteroids (ICS) adherence is important for asthma management. Current evidence on the impact of ICS adherence on outcomes is mostly based on correlational analyses of between-person data. Although it is widely acknowledged that asthma outcomes fluctuate over time, evidence on predictors of within-person change is scarce. We aimed to quantify these fluctuations and the longitudinal relationships between ICS adherence and outcomes at both between- and within-person levels.

A prospective cohort of persistent asthma patients in France and the UK (n=847, age 6−40 years) provided 3756 reports over up to 2 yearsviacomputer-assisted telephone interviews and text messages on ICS adherence, asthma control, reliever medication use and exacerbations. We examined adherence−outcome relationshipsvialongitudinal models, controlling for confounders, including severity.

Considerable within-person variability was found for exacerbations (91%), asthma control (59%) and reliever use (52%); 431 (11.5%) reports signalled exacerbations and 2046 (54.5%) poor control. At between-person level, patients with higher average adherence were more likely to report asthma control (OR 1.25, 95% CI 1.06−1.47), but not asthma exacerbations (OR 0.99, 95% CI 0.87−1.12) or lower reliever use (b −0.0004, 95% CI −0.089−0.088). At within-person level, higher-than-usual adherence was associated with higher concomitant reliever use (b 0.092, 95% CI 0.053−0.131) and lower subsequent reliever use (b −0.047, 95% CI −0.005− −0.088); it was unrelated to asthma control (OR 0.93, 95% CI 0.84−1.02) or exacerbations (OR 1.04, 95% CI 0.94−1.16).

Patients maintaining high ICS adherence over time have better asthma control. Temporarily increasing ICS adherence tends to be simultaneous to higher reliever use and reduces reliever use later on. Causes of within-person variation in outcomes require more investigation.
Chromosomal phylogeny and comparative chromosome painting among Neacomys species (Rodentia, Sigmodontinae) from eastern Amazonia
Authors: Oliveira da Silva Willam , Pieczarka Julio Cesar , Rodrigues da Costa Marlyson Jeremias , Ferguson-Smith Malcolm Andrew , O’Brien Patricia Caroline Mary , Mendes-Oliveira Ana Cristina , Rossi Rogério Vieira , Nagamachi Cleusa Yoshiko
Published: October 2019

Background

The Neacomys genus is predominantly found in the Amazon region, and belongs to the most diverse tribe of the Sigmodontinae subfamily (Rodentia, Cricetidae, Oryzomyini). The systematics of this genus and questions about its diversity and range have been investigated by morphological, molecular (Cytb and COI sequences) and karyotype analysis (classic cytogenetics and chromosome painting), which have revealed candidate species and new distribution areas. Here we analyzed four species of Neacomys by chromosome painting with Hylaeamys megacephalus (HME) whole-chromosome probes, and compared the results with two previously studied Neacomys species and with other taxa from Oryzomyini and Akodontini tribes that have been hybridized with HME probes. Maximum Parsimony (MP) analyses were performed with the PAUP and T.N.T. software packages, using a non-additive (unordered) multi-state character matrix, based on chromosomal morphology, number and syntenic blocks. We also compared the chromosomal phylogeny obtained in this study with molecular topologies (Cytb and COI) that included eastern Amazonian species of Neacomys, to define the phylogenetic relationships of these taxa.

Results

The comparative chromosome painting analysis of the seven karyotypes of the six species of Neacomys shows that their diversity is due to 17 fusion/fission events and one translocation, pericentric inversions in four syntenic blocks, and constitutive heterochromatin (CH) amplification/deletion of six syntenic autosomal blocks plus the X chromosome. The chromosomal phylogeny is consistent with the molecular relationships of species of Neacomys. We describe new karyotypes and expand the distribution area for species from eastern Amazonia and detect complex rearrangements by chromosome painting among the karyotypes.

Conclusions

Our phylogeny reflects the molecular relationships of the Akodontini and Oryzomyini taxa and supports the monophyly of Neacomys. This work presents new insights about the chromosomal evolution of this group, and we conclude that the karyotypic divergence is in accord with phylogenetic relationships.
A qualitative cross-cultural analysis of NICU care culture and infant feeding in Finland and the U.S.
Authors: Holdren Sarah , Fair Cynthia , Lehtonen Liisa
Published: October 2019

Background

The benefits of family-centered care for the health and well-being of preterm infants and their families include increased parent-infant closeness, improved lactation, and positive mental health outcomes; however, it is known that the extent to which family-centered care is adopted varies by unit. This study aimed to understand how differences in neonatal care culture in two units in Finland and the U.S. were translated to parents’ infant feeding experiences in the hope of improving relationally focused feeding practices in both locations.

Methods

This qualitative, cross-sectional study utilized narrative methodologies to understand the lived experiences of 15 families hospitalized in a tertiary neonatal intensive care unit in Finland (n = 8) and the U. S (n = 7).

Results

A global theme of lactation as a means or an end showed that lactation and infant feeding were framed differently in each location. The three supporting themes that explain families’ perceptions of their transition to parenthood, support as a family unit, and experience with lactation include: universal early postnatal challenges; culture and space-dependent nursing support; and controlled or empowering breastfeeding experiences.

Conclusions

Care culture plays a large role in framing all infant caring activities, including lactation and infant feeding. This study found that in the unit in Finland, breastfeeding was one method to achieve closeness with an infant, while in the unit in the U.S., pumping was only an end to promote infant nutritional health. Therefore, breastfeeding coupled with closeness was found to be supportive of a salutogenic, or health-promoting, care approach for the whole family.
Arterial resection and reconstruction in pancreatectomy: surgical technique and outcomes
Authors: Zhang Qiyi , Wu Jingjin , Tian Yang , Duan Jixuan , Shao Yi , Yan Sheng , Wang Weilin
Published: October 2019

Background

The outcomes in patients with pancreatic or ampulla tumors remain unsatisfactory, especially with invasion into the hepatic artery (HA) or the superior mesenteric artery (SMA). In this setting, pancreatectomy combined with arterial resection and reconstruction may offer the possibility of an en-block resection with negative margins and acceptable morbidity and mortality.

Methods

A six year retrospective review of pancreatectomies performed at our institution, included 21 patients that underwent a pancreatectomy combined with arterial resection and reconstruction. Arterial reconstruction was performed under an operating microscope. The types of arterial reconstruction included direct anastomosis, arterial transposition, and arterial bypass with a vascular graft.

Results

The surgical procedures consisted of 19 pancreaticoduodenectomies and 2 total pancreatectomies. The tumors were located at the pancreatic head (n = 10), whole pancreas (n = 2), distal common bile duct (n = 5), ampulla (n = 2) and retroperitoneum with pancreatic head involvement (n = 2). All operations achieved R0 resection successfully, with no intraoperative complication. Eighteen patients recovered without complications while three patients died from intra-abdominal hemorrhage due to a pancreatic fistula, though notably the bleeding was not at the arterial anastomosis site. All reconstructed arteries showed adequate patency at follow-up. The median postoperative survival was 11.6 months in all the 11 patients with pancreatic adenocarcinoma.

Conclusion

Pancreatectomy combined with arterial resection and reconstruction is a feasible treatment option. The microsurgical technique is critically important to achieving a successful and patent arterial anastomosis.
A case of eccrine porocarcinoma characterized by a progressive increase in the level of Ki-67 index: case report and review of literature
Authors: Shen Jie , Pan Xinfa , Lu Yongfu , Pan Desheng , Ma Yuehui , Zhan Renya
Published: October 2019

Background

Eccrine porocarcinoma is an extremely rare skin adnexal malignant neoplasia with highly invasive and metastatic potential. We report an additional case of eccrine porocarcinoma with intracranial metastases. This case is characterized by a complete record of the progress of eccrine porocarcinoma, its immunohistochemistry after three operations showed a progressive increase in the level of Ki-67 index.

Case presentation

We herein report a case of a 37-year-old-male with eccrine carcinoma occurring on the left posterior occipital scalp which invaded the skull and dura, presenting with progressive headache. This patient has performed three surgeries in total. During the last hospitalization, he underwent an extended surgical resection, lymphadenectomy, myocutaneous flap transplantation and vascular anastomosis in our institution. After surgery, he was treating with radiotherapy at 200 Gray in 12 fractions. But one year after the operation, he developed chest tightness, imaging examination and biopsy puncture revealed pulmonary metastasis.

Conclusion

Intracranial metastasis of eccrine porocarcinoma is a late event with poor prognosis. This case emphases on that progressively increased level of Ki-67 index may predict more chance to occur the intracranial metastasis of scalp eccrine porocarcinoma, long-term follow-up and appropriately dense follow-up interval is necessary.
Using a marine microalga as a chassis for polyethylene terephthalate (PET) degradation
Authors: Moog Daniel , Schmitt Johanna , Senger Jana , Zarzycki Jan , Rexer Karl-Heinz , Linne Uwe , Erb Tobias , Maier Uwe G.
Published: October 2019

Background

The biological degradation of plastics is a promising method to counter the increasing pollution of our planet with artificial polymers and to develop eco-friendly recycling strategies. Polyethylene terephthalate (PET) is a thermoplast industrially produced from fossil feedstocks since the 1940s, nowadays prevalently used in bottle packaging and textiles. Although established industrial processes for PET recycling exist, large amounts of PET still end up in the environment—a significant portion thereof in the world’s oceans. In 2016, Ideonella sakaiensis, a bacterium possessing the ability to degrade PET and use the degradation products as a sole carbon source for growth, was isolated. I. sakaiensis expresses a key enzyme responsible for the breakdown of PET into monomers: PETase. This hydrolase might possess huge potential for the development of biological PET degradation and recycling processes as well as bioremediation approaches of environmental plastic waste.

Results

Using the photosynthetic microalga Phaeodactylum tricornutum as a chassis we generated a microbial cell factory capable of producing and secreting an engineered version of PETase into the surrounding culture medium. Initial degradation experiments using culture supernatant at 30 °C showed that PETase possessed activity against PET and the copolymer polyethylene terephthalate glycol (PETG) with an approximately 80-fold higher turnover of low crystallinity PETG compared to bottle PET. Moreover, we show that diatom produced PETase was active against industrially shredded PET in a saltwater-based environment even at mesophilic temperatures (21 °C). The products resulting from the degradation of the PET substrate were mainly terephthalic acid (TPA) and mono(2-hydroxyethyl) terephthalic acid (MHET) estimated to be formed in the micromolar range under the selected reaction conditions.

Conclusion

We provide a promising and eco-friendly solution for biological decomposition of PET waste in a saltwater-based environment by using a eukaryotic microalga instead of a bacterium as a model system. Our results show that via synthetic biology the diatom P. tricornutum indeed could be converted into a valuable chassis for biological PET degradation. Overall, this proof of principle study demonstrates the potential of the diatom system for future biotechnological applications in biological PET degradation especially for bioremediation approaches of PET polluted seawater.
Fish consumption during menarche, menstruation, pregnancy and postpartum in Sikuani women from Meta, Colombia
Authors: Cubillos-Cuadrado Luisa Fernanda , Muñoz-Hernández Daniela Stephany , Vásquez-Londoño Carlos Alberto
Published: October 2019

Background

Societies have selected their food for health, cultural, religious, political, economical, and environmental reasons. Most of the food included in Sikuani traditional diet still comes from wild natural resources and involves numerous species of fish, mammals, birds, reptiles, amphibians, insects, and plants. During certain periods of the Sikuani women’s reproductive cycle, fish intake is avoided. The objective of this research is to study the conceptions underlying fish consumption regulations among Sikuani women at the Wacoyo Reservation, in Meta, Colombia.

Methods

We conducted a field study through interviews and participant observation with Sikuani Indigenous from the Wacoyo Reservation (Colombia). We inquired about the conceptions of fish consumption regulation by Sikuani women during the stages of the reproductive cycle. PCA (principal component analysis) was used to identify the most important characteristics of fish that are related to the avoidance of fish intake by Sikuani women during pregnancy. This study combines qualitative and quantitative analysis.

Results

It was found that during menarche and postpartum fish consumption is avoided by Sikuani women only before the ritual known as the prayer of the fish is performed. The menstruation does not imply significant regulations for fish intake, while during pregnancy there are multiple and specific avoidances for the consumption of fish. According to our results, there are some features of fish associated with their regulation on the diet of pregnant Sikuani women. The consumption of some fish is avoided during pregnancy because it is related to the appearance of disease caused by ainawi, protector spirits of aquatic animals.

Conclusions

The traditional diet of Sikuani women includes numerous fish species and an important proportion of them are avoided during menarche, menstruation, gestation, and postpartum. According to our results, there are some features of fish associated with their regulation on the diet of pregnant Sikuani women. The main reasons underlying the avoidance of fish consumption by Sikuani women are the prevention of human disease as well as the strengthening of communities and ecosystems resilience.
Effect of probiotic supplementation in nonalcoholic steatohepatitis patients: PROBILIVER TRIAL protocol
Authors: Silva-Sperb Amanda Souza , Moraes Helena Abadie , de Moura Bruna Concheski , Alves Bruna Cherubini , Bruch-Bertani Juliana Paula , Azevedo Vittoria Zambon , Dall’Alba Valesca
Published: October 2019

Background

Recently factors in the relationship between gut microbiota, obesity, diabetes and the metabolic syndrome have been suggested in the development and progression of nonalcoholic steatohepatitis (NASH). In this sense, this work aims to evaluate the effects of probiotic supplementation on intestinal microbiota modulation, degree of hepatic steatosis and fibrosis, inflammation, gut permeability, and body composition.

Methods

This double-blind, randomized clinical trial will include adult outpatients with a diagnosis of NASH confirmed by biopsy with or without transient elastography. All patients will undergo a complete anamnesis to investigate their alcohol consumption, previous history, medications, nutritional assessment (dietary intake and body composition), sarcopenia, physical activity level and physical and functional capacity, cardiovascular risk, biochemical parameters for assessment of inflammatory status, lipid profile, hepatic function, gut permeability, and assessment of microbiota. These procedures will be performed at baseline and repeated after 24 weeks (at the end of the study). Through the process of randomization, patients will be allocated to receive treatment A or treatment B. Both patients and researchers involved will be blinded (double-blind study). The intervention consists of treatment with a probiotic mix (Lactobacillus acidophillus + Bifidobacterium lactis + Lactobacillus rhamnosus + Lactobacillus paracasei, 1 x 109 CFU for each) and the placebo which is identical in all its characteristics and packaging. Patients will be instructed to consume two sachets/day during 24 weeks and to report any symptoms or side effects related to the use of the sachets. Adherence control will be carried out through the patient’s notes on a form provided, and also by checking the number of sachets used.

Discussion

The final results of study will be analyzed and disseminated in 2020.

Trial registration

ClinicalTrials.gov, ID: NCT03467282. Registered on 15 March 2018.
The Transposon Registry
Authors: Tansirichaiya Supathep , Rahman Md. Ajijur , Roberts Adam P.
Published: October 2019

Transposable elements in prokaryotes are found in many forms and therefore a robust nomenclature system is needed in order to allow researchers to describe and search for them in publications and databases. Here we provide an update on The Transposon Registry which allocates numbers to any prokaryotic transposable element. Additionally, we present the completion of registry records for all transposons assigned Tn numbers from Tn1 onwards where sequence data or publications exist.
Knowledge of neonatal danger signs and associated factors among mothers who gave birth during the last 4 months while attending immunization services in Harar town public health facilities, Ethiopia, 2017
Authors: Welay Fissaha Tekulu , Kassa Nega Assefa , Gebremeskel Gebrekiros Aregawi , Assefa Natnael Etsay , Mengesha Meresa Berwo , Weldemariam Mulu Gebretsadik , Gebremeskel Senait Gebreslasie
Published: October 2019

Objective

The purpose of this study was to assess knowledge about neonatal danger signs and associated factors among mothers who gave birth in the last 4 months attending immunization services.

Result

The study recruited 432 mothers to participate. A knowledge score of neonatal danger signs was found [32.9% (95% CI 28.9%, 37%)]. Mothers educated to secondary level were 4.9 times more likely to know about neonatal danger signs [(AOR = 4.9, 95% CI (1.15, 21). Similarly, mothers whose husband educated to college and above [AOR = 4.95, 95% CI (1.15, 21)], and being multipara mother [(AOR = 2.59, 95% CI (1.05, 6.6)], were factors significantly associated with good knowledge of mothers about neonatal danger signs.
Recent advances in delivery of veterinary DNA vaccines against avian pathogens
Authors: Jazayeri Seyed Davoud , Poh Chit Laa
Published: October 2019

Veterinary vaccines need to have desired characteristics, such as being effective, inexpensive, easy to administer, suitable for mass vaccination and stable under field conditions. DNA vaccines have been proposed as potential solutions for poultry diseases since they are subunit vaccines with no risk of infection or reversion to virulence. DNA vaccines can be utilized for simultaneous immunizations against multiple pathogens and are relatively easy to design and inexpensive to manufacture and store. Administration of DNA vaccines has been shown to stimulate immune responses and provide protection from challenges in different animal models. Although DNA vaccines offer advantages, setbacks including the inability to induce strong immunity, and the fact that they are not currently applicable for mass vaccination impede the use of DNA vaccines in the poultry industry. The use of either biological or physical carriers has been proposed as a solution to overcome the current delivery limitations of DNA vaccines for veterinary applications. This review presents an overview of the recent development of carriers for delivery of veterinary DNA vaccines against avian pathogens.