bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 PointsLoss 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

Abstract
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

AbstractT-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 PointsNeutrophil 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

Abstract
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 &lt;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 &lt;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

Abstract
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

IntroductionSince 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.MethodsAll 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.ResultsDuring 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.ConclusionsThis 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

Abstract

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

Abstract

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

Abstract

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.