bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-brain magnetic resonance imaging of plaque burden and lenticulostriate arteries in patients with different types of stroke
Authors: Wu Fang , Zhang Qian , Dong Kai , Duan Jiangang , Yang Xiaoxu , Wu Ye , Zhang Ling , Li Debiao , Fan Zhaoyang , Yang Qi 
Published: February 2019

Background: Large-vessel atherosclerotic disease is an important pathogenesis of deep-perforator infarction (DPI). However, altered vessel walls of intracranial large arteries and distribution of small arteries in DPI are unclear because of the limited resolution of current imaging techniques. In this study the intracranial plaque burden and lenticulostriate artery (LSA) distribution in patients with recent DPI and non-DPI using whole-brain vessel-wall imaging (WB-VWI) were investigated. Methods: A total of 44 patients with recent DPI (23 patients) or non-DPI (21 patients) due to intracranial atherosclerotic disease were prospectively enrolled. WB-VWI was performed in all the patients using a three-dimensional T1-weighted vessel-wall magnetic resonance technique. Hemispheres with DPI and non-DPI were considered as the DPI group and non-DPI group, respectively. Hemispheres without a history of stroke were the control group. The intracranial plaque burden was compared between the DPI and non-DPI groups. The number and length of visualized LSA branches among DPI, non-DPI, and control groups were also evaluated. Results: A total of 77 hemispheres were analyzed (23 in the DPI group, 21 in the non-DPI group, and 33 in the control group). Plaque burden was lower ( p = 0.047) in the DPI group (82.0 ± 45.9 mm3) compared with the non-DPI group (130.9 ± 90.3 mm3). There was a significant reduction ( p = 0.002) in length of visualized LSA branches in the DPI group (74.1 ± 21.7 mm) compared with the control group (104.6 ± 33.3 mm). Conclusions: WB-VWI enables the combination of vessel-wall and LSA imaging in one image setting, which can provide information about plaque burden and LSA distribution.
Tissue and Exosomal Serine Protease Inhibitors Are Significantly Overexpressed in Chronic Rhinosinusitis With Nasal Polyps
Authors: Mueller S. K. , Nocera A. L. , Dillon S. T. , Libermann T. A. , Wendler O. , Bleier B. S. 
Published: February 2019

Background The fibrinolysis pathway has been previously implicated in the etiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Objective The purpose of this study was (1) to explore protein derangements of selected protease inhibitors of the serpin superfamily in CRSwNP and (2) to correlate the protease inhibitor derangements of the fibrinolysis pathway in tissue with exosomal samples to evaluate the potential of an exosomal noninvasive “liquid biopsy” for CRSwNP. Methods Institutional review board approved study in which matched tissue and mucus exosomal proteins (SerpinB2, SerpinF2, SerpinG1, and SerpinE1) were compared between control and CRSwNP patients using Western Blot analysis (n = 6/group) and immunohistochemistry (IHC). Transcriptome analysis (n = 10/group) on the same proteins was performed using whole transcriptome sequencing. Semiquantitative analysis of the Western Blots was performed using the Whitney–Mann U test. Results The transcriptomic data set showed multiple differentially expressed genes including SerpinB2 (fold changes [FC] 7.38), SerpinE1 (FC 1.42), SerpinF2 (FC 2.03), and SerpinG1 (FC 0.72). Western Blot and IHC analysis showed an overexpression of the Serpin protease inhibitors in tissue (SerpinB2, P < .01; SerpinE1, P < .01; SerpinF2, P < .01; and SerpinG1, P < .01) indicating a downregulation of the fibrinolysis cascade. The mucus exosomal serpin proteins exhibited similar findings. Conclusion Our analysis supported that protease inhibitors of the fibrinolysis pathway, especially SerpinB2, SerpinF2, and SerpinG1, are highly deranged in patients with CRSwNP. These findings suggest a downregulation of the fibrinolysis pathway via proteolytic cascade imbalance leading to excessive polyp fibrin deposition. Our data further supported our hypothesis that exosomal proteomic analyses may be used as noninvasive “liquid biopsy” for CRSwNP and a novel method to study chronic sinonasal inflammation.
High Altitude Is an Independent Risk Factor for Developing a Pulmonary Embolism, but Not a Deep Vein Thrombosis Following a 1- to 2-Level Lumbar Fusion
Authors: Donnally Chester J. , Vakharia Ajit M. , Sheu Jonathan I. , Vakharia Rushabh M. , Damodar Dhanur , Shenoy Kartik , Gjolaj Joseph P. 
Published: February 2019

Study Design: Retrospective study. Objective: To identify if a 1- to 2-level posterior lumbar fusion at higher altitude is an independent risk factor for postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE). Methods: A national Medicare database was queried for all patients undergoing 1- to 2-level lumbar fusions from 2005 to 2014. Those with a prior history of DVT, PE, coagulopathy, or peripheral vascular complications were excluded to better isolate altitude as the dependent variable. The groups were matched 1:1 based on age, gender, and comorbidities to limit potential cofounders. Using ZIP codes of the hospitals where the procedure occurred, we separated our patients into high (>4000 feet) and low (<100 feet) altitudes to investigate postoperative rates of DVTs and PEs at 90 days. Results: Compared with lumbar fusions performed at low-altitude centers, patients undergoing the same procedure at high altitude had significantly higher PE rates ( P = .010) at 90 days postoperatively, and similar rates of 90-day postoperative DVTs ( P = .078). There were no significant differences in age or comorbidities between these cohorts due to our strict matching process ( P = 1.00). Conclusion: Spinal fusions performed at altitudes >4000 feet incurred higher PE rates in the first 90 days compared with patients receiving the same surgery at <100 feet but did not incur higher rates of postoperative DVTs.
Efficacy and Tolerability of Progen, a Nutritional Supplement Based on Innovative Plasma Proteins, in ACL Reconstruction: A Multicenter Randomized Controlled Trial
Authors: López-Vidriero Emilio , Olivé-Vilas Ramón , López-Capapé David , Varela-Sende Luisa , López-Vidriero Rosa , Til-Pérez Luís 
Published: February 2019

Background: New biologic strategies are arising to enhance healing and improve the clinical outcome of anterior cruciate ligament (ACL) reconstruction. Purpose: To evaluate the efficacy of a new oral nutritional supplement (Progen) that contains hydrolyzed collagen peptides and plasma proteins, a hyaluronic acid–chondroitin sulfate complex, and vitamin C. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: The study included patients who underwent ACL reconstruction with hamstring autografts using the same fixation method. All patients received the same analgesia and physical therapy (PT) protocol and were randomized to receive either the nutritional supplement (supplemented group) or no additional therapy (control group). Patients were followed up at days 7, 30, 60, and 90. Pain was assessed by use of a visual analog scale (VAS) and by analgesic consumption. Clinical outcome was assessed via International Knee Documentation Committee (IKDC) score and the number of PT sessions. Perceived efficacy and tolerability were rated on a 5-point Likert scale. Graft maturation was assessed by a blinded musculoskeletal radiologist using magnetic resonance imaging. The number of adverse events (AEs) was recorded. Results: The intention-to-treat analysis included 72 patients, 36 allocated to the supplemented group and 36 to the control group, with no significant differences regarding demographic and preoperative characteristics. Both groups showed significant improvement in pain and function (measured by VAS and IKDC scores) during the 90-day follow-up period ( P < .001 for both), without significant differences between groups. The supplemented group had fewer patients that needed analgesics (8.5% vs 50.0%; P < .05) and attended fewer PT sessions (38.0 vs 48.4 sessions; P < .001) at 90 days and had a higher IKDC score at 60 days (62.5 vs 55.5; P = .029) compared with the control group. Patient- and physician-perceived efficacy was considered significantly higher in the supplemented group at 60 and 90 days ( P < .05). Perceived tolerability of the overall intervention was better in the supplemented group at 30, 60, and 90 days ( P < .05). Graft maturation showed more advanced degrees (grades 3 and 4) in the supplemented group at 90 days (61.8% vs 38.2%; P < .01). No intolerance or AEs associated with the nutritional supplement treatment were reported. Conclusion: The combination of the nutritional supplement and PT after ACL reconstruction improved pain, clinical outcome, and graft maturation. Nutritional supplementation showed higher efficacy during the second month of recovery, without causing AEs. Registration: NCT03355651 ( ClinicalTrials.gov identifier).
Noninfectious transfusion-associated adverse events and their mitigation strategies
Authors: Goel Ruchika , Tobian Aaron A. R. , Shaz Beth H. 
Published: February 2019

AbstractBlood transfusions are life-saving therapies; however, they can result in adverse events that can be infectious or, more commonly, noninfectious. The most common noninfectious reactions include febrile nonhemolytic transfusion reactions, allergic transfusion reactions, transfusion-associated circulatory overload, transfusion-related acute lung injury, and acute and delayed hemolytic transfusion reactions. These reactions can be asymptomatic, mild, or potentially fatal. There are several new methodologies to diagnose, treat, and prevent these reactions. Hemovigilance systems for monitoring transfusion events have been developed and demonstrated decreases in some adverse events, such as hemolytic transfusion reactions. Now vein-to-vein databases are being created to study the interactions of the donor, product, and patient factors in the role of adverse outcomes. This article reviews the definition, pathophysiology, management, and mitigation strategies, including the role of the donor, product, and patient, of the most common noninfectious transfusion-associated adverse events. Prevention strategies, such as leukoreduction, plasma reduction, additive solutions, and patient blood management programs, are actively being used to enhance transfusion safety. Understanding the incidence, pathophysiology, and current management strategies will help to create innovative products and continually hone in on best transfusion practices that suit individualized patient needs.
NCAM1 (CD56) promotes leukemogenesis and confers drug resistance in AML
Authors: Sasca Daniel , Szybinski Jakub , Schüler Andrea , Shah Viral , Heidelberger Jan , Haehnel Patricia S. , Dolnik Anna , Kriege Oliver , Fehr Eva-Marie , Gebhardt Wolf H. , Reid George , Scholl Claudia , Theobald Matthias , Bullinger Lars , Beli Petra , Kindler Thomas 
Published: February 2019

Abstract
Neural cell adhesion molecule 1 (NCAM1; CD56) is expressed in up to 20% of acute myeloid leukemia (AML) patients. NCAM1 is widely used as a marker of minimal residual disease; however, the biological function of NCAM1 in AML remains elusive. In this study, we investigated the impact of NCAM1 expression on leukemogenesis, drug resistance, and its role as a biomarker to guide therapy. Beside t(8;21) leukemia, NCAM1 expression was found in most molecular AML subgroups at highly heterogeneous expression levels. Using complementary genetic strategies, we demonstrated an essential role of NCAM1 in the regulation of cell survival and stress resistance. Perturbation of NCAM1 induced cell death or differentiation and sensitized leukemic blasts toward genotoxic agents in vitro and in vivo. Furthermore, Ncam1 was highly expressed in leukemic progenitor cells in a murine leukemia model, and genetic depletion of Ncam1 prolonged disease latency and significantly reduced leukemia-initiating cells upon serial transplantation. To further analyze the mechanism of the NCAM1-associated phenotype, we performed phosphoproteomics and transcriptomics in different AML cell lines. NCAM1 expression strongly associated with constitutive activation of the MAPK-signaling pathway, regulation of apoptosis, or glycolysis. Pharmacological inhibition of MEK1/2 specifically inhibited proliferation and sensitized NCAM1+ AML cells to chemotherapy. In summary, our data demonstrate that aberrant expression of NCAM1 is involved in the maintenance of leukemic stem cells and confers stress resistance, likely due to activation of the MAPK pathway. Targeting MEK1/2 sensitizes AML blasts to genotoxic agents, indicating a role for NCAM1 as a biomarker to guide AML treatment.
Systemic inflammation induces release of cell-free DNA from hematopoietic and parenchymal cells in mice and humans
Authors: van der Meer Anne Jan , Kroeze Anna , Hoogendijk Arie J. , Soussan Aicha Ait , Ellen van der Schoot C. , Wuillemin Walter A. , Voermans Carlijn , van der Poll Tom , Zeerleder Sacha 
Published: February 2019

Key PointsDuring a systemic inflammatory response, cell-free DNA is first released by hematopoietic cells and thereafter by nonhematopoietic cells.
Zebrafish prdm12b acts independently of nkx6.1 repression to promote eng1b expression in the neural tube p1 domain
Authors: Yildiz Ozge , Downes Gerald B. , Sagerström Charles G. 
Published: February 2019

Abstract
Background
Functioning of the adult nervous system depends on the establishment of neural circuits during embryogenesis. In vertebrates, neurons that make up motor circuits form in distinct domains along the dorsoventral axis of the neural tube. Each domain is characterized by a unique combination of transcription factors (TFs) that promote a specific fate, while repressing fates of adjacent domains. The prdm12 TF is required for the expression of eng1b and the generation of V1 interneurons in the p1 domain, but the details of its function remain unclear.

Methods
We used CRISPR/Cas9 to generate the first germline mutants for prdm12 and employed this resource, together with classical luciferase reporter assays and co-immunoprecipitation experiments, to study prdm12b function in zebrafish. We also generated germline mutants for bhlhe22 and nkx6.1 to examine how these TFs act with prdm12b to control p1 formation.

Results
We find that prdm12b mutants lack eng1b expression in the p1 domain and also possess an abnormal touch-evoked escape response. Using luciferase reporter assays, we demonstrate that Prdm12b acts as a transcriptional repressor. We also show that the Bhlhe22 TF binds via the Prdm12b zinc finger domain to form a complex. However, bhlhe22 mutants display normal eng1b expression in the p1 domain. While prdm12 has been proposed to promote p1 fates by repressing expression of the nkx6.1 TF, we do not observe an expansion of the nkx6.1 domain upon loss of prdm12b function, nor is eng1b expression restored upon simultaneous loss of prdm12b and nkx6.1.

Conclusions
We conclude that prdm12b germline mutations produce a phenotype that is indistinguishable from that of morpholino-mediated loss of prdm12 function. In terms of prdm12b function, our results indicate that Prdm12b acts as transcriptional repressor and interacts with both EHMT2/G9a and Bhlhe22. However, bhlhe22 function is not required for eng1b expression in vivo, perhaps indicating that other bhlh genes can compensate during embryogenesis. Lastly, we do not find evidence for nkx6.1 and prdm12b acting as a repressive pair in formation of the p1 domain – suggesting that prdm12b is not solely required to repress non-p1 fates, but is specifically needed to promote p1 fates.
Short-time work in the Great Recession: firm-level evidence from 20 EU countries
Authors: Lydon Reamonn , Mathä Thomas Y. , Millard Stephen 
Published: February 2019

Abstract
Using firm-level data from a large-scale European survey among 20 countries, we analyse the determinants of firms using short-time work (STW). We show that firms are more likely to use STW in case of negative demand shocks. We show that STW schemes are more likely to be used by firms with high degrees of firm-specific human capital, high firing costs, and operating in countries with stringent employment protection legislation and a high degree of downward nominal wage rigidity. STW use is higher in countries with formalised schemes and in countries where these schemes were extended in response to the recent crisis. On the wider economic impact of STW, we show that firms using the schemes are significantly less likely to lay off permanent workers in response to a negative shock, with no impact for temporary workers. Relating our STW take-up measure in the micro data to aggregate data on employment and output trends, we show that sectors with a high STW take-up exhibit significantly less cyclical variation in employment.
Preoperative Breast Magnetic Resonance Imaging in Women With Local Ductal Carcinoma in Situ to Optimize Surgical Outcomes: Results From the Randomized Phase III Trial IRCIS
Authors: Balleyguier Corinne , Dunant Ariane , Ceugnart Luc , Kandel Marguerite , Chauvet Marie-Pierre , Chérel Pascal , Mazouni Chafika , Henrot Philippe , Rauch Philippe , Chopier Jocelyne , Zilberman Sonia , Doutriaux-Dumoulin Isabelle , Jaffre Isabelle , Jalaguier Aurélie , Houvenaeghel Gilles , Guérin Nicole , Callonnec Françoise , Chapellier Claire , Raoust Ines , Mathieu Marie-Christine , Rimareix Françoise , Bonastre Julia , Garbay Jean-Rémi 
Published: February 2019

PURPOSE We evaluated the addition of breast magnetic resonance imaging (MRI) to standard radiologic evaluation on the re-intervention rate in women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery. PATIENTS AND METHODS Women with biopsy-proven DCIS corresponding to a unifocal microcalcification cluster or a mass less than 30 mm were randomly assigned to undergo MRI or standard evaluation. The primary end point was the re-intervention rate for positive or close margins (< 2 mm) in the 6 months after randomization ( ClinicalTrials.gov identifier: NCT01112254). RESULTS A total of 360 patients from 10 hospitals in France were included in the study. Of the 352 analyzable patients, 178 were randomly assigned to the MRI arm, and 174 were assigned to the control arm. In the intent-to-treat analysis, 82 of 345 patients with the assessable end point were reoperated for positive or close margins within 6 months, resulting in a re-intervention rate of 20% (35 of 173) in the MRI arm and 27% (47 of 172) in the control arm. The absolute difference of 7% (95% CI, −2% to 16%) corresponded to a relative reduction of 26% (stratified odds ratio, 0.68; 95% CI, 0.41 to 1.1; P = .13). When considering only the per-protocol population with an assessable end point, the difference was 9% (stratified odds ratio, 0.59; 95% CI, 0.35 to 1.0; P = .05). Total mastectomy rates were 18% (31 of 176) in the MRI arm and 17% (30 of 173) in the control arm (stratified P = .93). For 100 lesions seen on MRI, nonmass-like enhancement was more predominant (82%) than mass enhancement (20%). Nevertheless, no specific morphologic and kinetic parameters for DCIS were identified. CONCLUSION The study did not show sufficient surgical improvement with the use of preoperative MRI to be clinically relevant in DCIS staging. However, this could be reconsidered with the improvement of new MRI sequences and new modalities in magnetic resonance techniques.
First-Line Treatment of Patients With Indolent Non-Hodgkin Lymphoma or Mantle-Cell Lymphoma With Bendamustine Plus Rituximab Versus R-CHOP or R-CVP: Results of the BRIGHT 5-Year Follow-Up Study
Authors: Flinn Ian W. , van der Jagt Richard , Kahl Brad , Wood Peter , Hawkins Tim , MacDonald David , Simpson David , Kolibaba Kathryn , Issa Samar , Chang Julie , Trotman Judith , Hallman Doreen , Chen Ling , Burke John M. 
Published: February 2019

PURPOSE The BRIGHT study ( ClinicalTrials.gov identifier: NCT00877006) was initiated to compare the efficacy and safety of bendamustine plus rituximab (BR) with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) for treatment-naive patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma. This publication provides long-term follow-up data. PATIENTS AND METHODS Patients were monitored for a minimum of 5 years after completion of study treatment for the time-to-event end points of progression-free survival (PFS), event-free survival, duration of response, and overall survival per investigator assessment. Data on the number of patients who received second-line anticancer treatment and the occurrence of other malignancies were also collected. RESULTS The medians were not reached for any of the time-to event end points for either the BR or R-CHOP/R-CVP study treatment groups by study completion. PFS rates at 5 years were 65.5% in the BR treatment group and 55.8% in the R-CHOP/R-CVP group. The difference in PFS was considered significant with a hazard ratio of 0.61 (95% CI, 0.45 to 0.85; P = .0025). The hazard ratio for event-free survival and duration of response ( P = .0020 and .0134, respectively) also favored the BR regimen over R-CHOP/R-CVP. However, no significant difference in overall survival was observed. The overall safety profiles of BR, R-CHOP, and R-CVP were as expected; no new safety data were collected during long-term follow-up. A higher number of secondary malignancies was noted in the BR treatment group. CONCLUSION Overall, BR demonstrated better long-term disease control than R-CHOP/R-CVP and should be considered as a first-line treatment option for patients with indolent and mantle-cell lymphoma.