bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Insights Into the Differentiation of Megakaryocytes From Hematopoietic Progenitors
Authors: Noetzli Leila J. , French Shauna L. , Machlus Kellie R. 
Published: May 2019

Megakaryocytes are hematopoietic cells, which are responsible for the production of blood platelets. The traditional view of megakaryopoiesis describes the cellular journey from hematopoietic stem cells, through a hierarchical series of progenitor cells, ultimately to a mature megakaryocyte. Once mature, the megakaryocyte then undergoes a terminal maturation process involving multiple rounds of endomitosis and cytoplasmic restructuring to allow platelet formation. However, recent studies have begun to redefine this hierarchy and shed new light on alternative routes by which hematopoietic stem cells are differentiated into megakaryocytes. In particular, the origin of megakaryocytes, including the existence and hierarchy of megakaryocyte progenitors, has been redefined, as new studies are suggesting that hematopoietic stem cells originate as megakaryocyte-primed and can bypass traditional lineage checkpoints. Overall, it is becoming evident that megakaryopoiesis does not only occur as a stepwise process, but is dynamic and adaptive to biological needs. In this review, we will reexamine the canonical dogmas of megakaryopoiesis and provide an updated framework for interpreting the roles of traditional pathways in the context of new megakaryocyte biology.

Visual Overview—
An online visual overview is available for this article.
Inhibition of MPO (Myeloperoxidase) Attenuates Endothelial Dysfunction in Mouse Models of Vascular Inflammation and Atherosclerosis
Authors: Cheng David , Talib Jihan , Stanley Christopher P. , Rashid Imran , Michaëlsson Erik , Lindstedt Eva-Lotte , Croft Kevin D. , Kettle Anthony J. , Maghzal Ghassan J. , Stocker Roland 
Published: May 2019

Objective—
Inflammation-driven endothelial dysfunction initiates and contributes to the progression of atherosclerosis, and MPO (myeloperoxidase) has been implicated as a potential culprit. On release by circulating phagocytes, MPO is thought to contribute to endothelial dysfunction by limiting NO bioavailability via formation of reactive oxidants including hypochlorous acid. However, it remains largely untested whether specific pharmacological inhibition of MPO attenuates endothelial dysfunction. We, therefore, tested the ability of a mechanism-based MPO inhibitor, AZM198, to inhibit endothelial dysfunction in models of vascular inflammation.

Approach and Results—

Three models of inflammation were used: femoral cuff, the tandem stenosis model of plaque rupture in
Apoe
−/−
mice, and C57BL/6J mice fed a high-fat, high-carbohydrate diet as a model of insulin resistance. Endothelial dysfunction was observed in all 3 models, and oral administration of AZM198 significantly improved endothelial function in the femoral cuff and tandem stenosis models only. Improvement in endothelial function was associated with decreased arterial MPO activity, determined by the in vivo conversion of hydroethidine to 2-chloroethidium, without affecting circulating inflammatory cytokines or arterial MPO content. Mechanistic studies in
Mpo
−/−
mice confirmed the contribution of MPO to endothelial dysfunction and revealed oxidation of sGC (soluble guanylyl cyclase) as the underlying cause of the observed limited NO bioavailability.

Conclusions—
Pharmacological inhibition of MPO is a potential strategy to limit endothelial dysfunction in vascular inflammation.

Visual Overview—
An online visual overview is available for this article.
Perioperative/Postoperative Atrial Fibrillation and Risk of Subsequent Stroke and/or Mortality
Authors: Lin Meng-Hsin , Kamel Hooman , Singer Daniel E. , Wu Yi-Ling , Lee Meng , Ovbiagele Bruce 
Published: May 2019

Background and Purpose—
Although believed to be transient and self-limiting, new-onset perioperative/postoperative atrial fibrillation (POAF) might be a risk factor for stroke and mortality. We conducted a systematic review and meta-analysis to qualitatively and quantitatively evaluate the relationship of POAF with early and late risks of mortality and stroke.

Methods—
We searched Pubmed, EMBASE, and Cochrane Library (1966 through March 2018) to identify cohort studies that reported stroke and mortality associated with POAF. We computed a random-effects estimate based on the Mantel-Haenszel method. Odds ratios with 95% CI were used as a measure of the association between POAF and early (in-hospital or within 30 days of surgery) stroke and mortality, while hazard ratios (HR) were used for long-term outcomes.

Results—
Our analysis included 35 studies with 2 458 010 patients. Pooling the results from the random-effects model showed that POAF was associated with increased risks of early stroke (odds ratio, 1.62; 95% CI, 1.47–1.80), early mortality (odds ratios, 1.44; 95% CI, 1.11–1.88), long-term stroke (HR, 1.37; 95% CI, 1.07–1.77), and long-term mortality (HR, 1.37; 95% CI, 1.27–1.49). Analyses focusing on high-quality studies obtained similar results. In subgroup analyses, POAF was more strongly associated with stroke in patients undergoing noncardiac surgery (HR, 2.00; 95% CI, 1.70–2.35) than in patients undergoing cardiac surgery (HR, 1.20; 95% CI, 1.07–1.34).

Conclusions—
New-onset POAF is associated with an increased risk of stroke and mortality, both in the short-term and long-term. The best strategy to reduce stroke risk among these patients needs to be determined.
The Influence of Gravity Waves on the Slope of the Kinetic Energy Spectrum in Simulations of Idealized Midlatitude Cyclones
Authors: Menchaca Maximo Q. , Durran Dale R. 
Published: May 2019

Abstract
The influence of gravity waves generated by surface stress and by topography on the atmospheric kinetic energy (KE) spectrum is examined using idealized simulations of a cyclone growing in baroclinically unstable shear flow. Even in the absence of topography, surface stress greatly enhances the generation of gravity waves in the vicinity of the cold front, and vertical energy fluxes associated with these waves produce a pronounced shallowing of the KE spectrum at mesoscale wavelengths relative to the corresponding free-slip case. The impact of a single isolated ridge is, however, much more pronounced than that of surface stress. When the mountain waves are well developed, they produce a wavenumber to the −5/3 spectrum in the lower stratosphere over a broad range of mesoscale wavelengths. In the midtroposphere, a smaller range of wavelengths also exhibits a −5/3 spectrum. When the mountain is 500 m high, the waves do not break, and their KE is entirely associated with the divergent component of the velocity field, which is almost constant with height. When the mountain is 2 km high, wave breaking creates potential vorticity, and the rotational component of the KE spectrum is also strongly energized by the waves. Analysis of the spectral KE budgets shows that the actual spectrum is the result of continually shifting balances of direct forcing from vertical energy flux divergence, conservative advective transport, and buoyancy flux. Nevertheless, there is one interesting example where the −5/3-sloped lower-stratospheric energy spectrum appears to be associated with a gravity-wave-induced upscale inertial cascade.
Effective Inexpensive Management of Necrotizing Otitis Externa Is Possible in Resource-Poor Settings
Authors: Honnurappa Vijayendra , Ramdass Sangeetha , Mahajan Nilesh , Vijayendra Vinay Kumar , Redleaf Miriam 
Published: May 2019

Introduction: Necrotizing otitis externa resolves best with antimicrobial treatment. How to care for these patients and monitor their resolution remains a problem. Our protocol in Bangalore can manage these patients inexpensively and well. Materials and Methods: Patients who were referred to our patients became the subjects for this paper. They were managed through our protocol, which consists of IV ciprofloxacin and meropenem, weekly labs, weekly examinations, and photodocumention. Results: Fifty-one people presented with necrotizing otitis externa (NOE) between October 2015 and November 2017 and completed our entire protocol. Forty-six had complete resolution of their disease, while 5 had to undergo surgical removal of necrotic bone. Six of 8 patients with facial weakness had improvement in their House-Brackmann scores. Reduction of self-reported nocturnal pain, dissolution of ear canal granulations, and normalization of the erythrocyte sedimentation rate (ESR) proved to be the most accurate indicators of disease regression. Conclusion: Patients are monitored closely with review of their otalgia, examination of their canal, repeated ESRs, effective control of their diabetes, and radiological imaging. All this can be done in a resource-poor country, which in turn serves as a model for the wealthier nations.
First Report on the Publication and Conservation of the Tomb of Ramesses III in the Valley of the Kings (KV 11)
Authors: Weber Anke 
Published: May 2019

The tomb of Ramesses III (KV 11) in the Valley of the Kings is one of the archaeological sites of ancient Egypt that has received very little attention from the scientific community. The tomb was open to the public for a long time and is in danger of quick deterioration. The site was closed from August 2016 until October 2017 for the installation of new walkways, glass panels, and an improved lighting system. The Ramesses III (KV 11) Publication and Conservation Project now aims to record, document, and preserve the entire tomb. This article is a first report on the planned publication and conservation of the tomb of Ramesses III (KV 11) in the Valley of the Kings. Like so many other tombs in the wadi, it presents the astonishing case of a tomb that has been known for a long time but was never thoroughly studied. In the following, we present the research aims of the newly formed Ramesses III (KV 11) Publication and Conservation Project1 as well as the preparatory work that has been undertaken by our team members. All observations and notes were made over the last six years during short campaigns, partly within the framework of a previous research project,2 which constitutes the basis of preliminary work in KV 11. The article focuses on the historical background of the tomb, its research history, including former investigators and concessions, supposed causes of destruction, suggestions for preservation, and procedures for research and documentation. We present the main problems we have to deal with at the outset of the project and describe the methods we propose to adopt. Further annual reports on the progress and first results of our work in order to preserve this important site of Egypt’s cultural heritage will follow in due course.
Pre-diabetes mellitus newly diagnosed after myocardial infarction adversely affects prognosis in patients without known diabetes
Authors: Chattopadhyay Sudipta , George Anish , John Joseph , Sathyapalan Thozhukat 
Published: May 2019

Background: Effect of pre-diabetes mellitus on post-myocardial infarction prognosis is unclear. Methods: Retrospective cohort analysis of 1056 myocardial infarction survivors with fasting plasma glucose and 2-h post-load plasma glucose measured. Major adverse cardiovascular events included death, non-fatal reinfarction and ischaemic stroke. Cox proportional hazard regression identified predictors of event-free survival. Continuous net reclassification improvement and integrated discrimination improvement determined the added predictive value of glycaemic indices. Results: Major adverse cardiovascular events occurred in 25.1% and 16.4% patients with and without pre-diabetes mellitus (hazard ratio with pre-diabetes mellitus: 1.56; 95% confidence interval: 1.17–2.08; p = 0.003) in the whole cohort and in 24.1% and 17.2% patients (hazard ratio with pre-diabetes mellitus, 1.43; 95% confidence interval: 1.03–1.98; p = 0.033) in the matched cohort, respectively. Pre-diabetes mellitus predicted major adverse cardiovascular events–free survival in whole (hazard ratio: 1.39; 95% confidence interval: 1.03–1.89; p = 0.033) and matched cohorts (hazard ratio: 1.42; 95% confidence interval: 1.01–1.99; p = 0.043). The 2-h post-load plasma glucose, but not fasting plasma glucose, predicted major adverse cardiovascular events–free survival in the whole (hazard ratio: 1.16; 95% confidence interval: 1.07–1.26; p < 0.0001) and matched cohorts (hazard ratio: 1.20; 95% confidence interval: 1.09–1.31; p < 0.0001). Adding 2-h post-load plasma glucose to models containing fasting plasma glucose, significantly improved net reclassification improvement and integrated discrimination improvement for both cohorts, but not vice versa. Conclusion: Pre-diabetes mellitus predicts major adverse cardiovascular events after myocardial infarction. The 2-h post-load plasma glucose predicts prognosis better than fasting plasma glucose in these patients.
Immuno-PET Imaging of the Programmed Cell Death-1 Ligand (PD-L1) Using a Zirconium-89 Labeled Therapeutic Antibody, Avelumab
Authors: Jagoda Elaine M. , Vasalatiy Olga , Basuli Falguni , Opina Ana Christina L. , Williams Mark R. , Wong Karen , Lane Kelly C. , Adler Steve , Ton Anita Thein , Szajek Lawrence P. , Xu Biying , Butcher Donna , Edmondson Elijah F. , Swenson Rolf E. , Greiner John , Gulley James , Eary Janet , Choyke Peter L. 
Published: May 2019

Objective: The goal is to evaluate avelumab, an anti-PD-L1 monoclonal immunoglobulin G antibody labeled with zirconium-89 in human PD-L1-expressing cancer cells and mouse xenografts for clinical translation. Methods: [89Zr]Zr-DFO-PD-L1 monoclonal antibody (mAb) was synthesized using avelumab conjugated to desferrioxamine. In vitro binding studies and biodistribution studies were performed with PD-L1+MDA-MB231 cells and MDA-MB231 xenograft mouse models, respectively. Biodistributions were determined at 1, 2, 3, 5, and 7 days post coinjection of [89Zr]Zr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 µg). Results: [89Zr]Zr-DFO-PD-L1 mAb exhibited high affinity (Kd ∼ 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest [89Zr]Zr-DFO-PD-L1 mAb uptakes in all time points, while MDA-MB231 tumor uptakes were lower but highly retained. In the unlabeled avelumab dose escalation studies, spleen tissue–muscle ratios decreased in a dose-dependent manner indicating specific [89Zr]Zr-DFO-PD-L1 mAb binding to PD-L1. In contrast, lymph node and tumor tissue–muscle ratios increased 4- to 5-fold at 20 and 40 µg avelumab doses. Conclusions: [89Zr]Zr-DFO-PD-L1 mAb exhibited specific and high affinity for PD-L1 in vitro and had target tissue uptakes correlating with PD-L1 expression levels in vivo. [89Zr]Zr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.
Importance of coding co-morbidities for APR-DRG assignment: Focus on cardiovascular and respiratory diseases
Authors: Souza Julio , Santos João Vasco , Canedo Veronica Bolon , Betanzos Amparo , Alves Domingos , Freitas Alberto 
Published: May 2019

Background: The All Patient-Refined Diagnosis-Related Groups (APR-DRGs) system has adjusted the basic DRG structure by incorporating four severity of illness (SOI) levels, which are used for determining hospital payment. A comprehensive report of all relevant diagnoses, namely the patient’s underlying co-morbidities, is a key factor for ensuring that SOI determination will be adequate. Objective: In this study, we aimed to characterise the individual impact of co-morbidities on APR-DRG classification and hospital funding in the context of respiratory and cardiovascular diseases. Methods: Using 6 years of coded clinical data from a nationwide Portuguese inpatient database and support vector machine (SVM) models, we simulated and explored the APR-DRG classification to understand its response to individual removal of Charlson and Elixhauser co-morbidities. We also estimated the amount of hospital payments that could have been lost when co-morbidities are under-reported. Results: In our scenario, most Charlson and Elixhauser co-morbidities did considerably influence SOI determination but had little impact on base APR-DRG assignment. The degree of influence of each co-morbidity on SOI was, however, quite specific to the base APR-DRG. Under-coding of all studied co-morbidities led to losses in hospital payments. Furthermore, our results based on the SVM models were consistent with overall APR-DRG grouping logics. Conclusion and implications: Comprehensive reporting of pre-existing or newly acquired co-morbidities should be encouraged in hospitals as they have an important influence on SOI assignment and thus on hospital funding. Furthermore, we recommend that future guidelines to be used by medical coders should include specific rules concerning coding of co-morbidities.
Spontaneous Regression of Swollen Submandibular Glands in IgG4-Related Disease
Authors: Suzuki Masanobu , Nakamaru Yuji , Takagi Dai , Honma Aya , Suzuki Takayoshi , Takakuwa Emi , Morita Shinya , Vreugde Sarah , Homma Akihiro 
Published: May 2019

Background IgG4-related disease is a new clinical entity frequently associated with swelling of the submandibular glands (SMGs). The long-term outcome of SMG swelling without steroid therapy remains unknown. Objective To examine whether swollen SMGs spontaneously regress without steroid therapy in the context of IgG4-related disease and to identify biomarkers that can predict the spontaneous regression of SMG swelling. Methods The SMG volume of 49 patients diagnosed with IgG4-related disease was calculated by measuring the axial and coronal planes of computed tomography scans. The change in SMG volume over time was measured and examined by treatment regimen, clinical data, and serum complement level. Results We found 28 of 49 (57%) IgG4-related disease patients to have swollen SMGs, with 15 of 20 (75%) of the swollen SMGs regressing without steroid therapy. The time required for the SMGs swelling to regress was significantly shorter in the steroid therapy group than in the no-steroid therapy group. Serum complement components at the initial visit were significantly lower in the regressed SMG group than in the nonregressed SMG group. Conclusion We observed 75% of swollen SMGs spontaneously regressed in patients with IgG4-related disease. The time required for the swollen SMGs to regress was longer in patients without steroid therapy than in those with steroid therapy. Serum complement level could be used as a predictor for the spontaneous regression of swollen SMGs in patients with IgG4-related disease.
Preoperative Assessment of the Feasibility of Pedicle Screw Insertion at the Proximal Thoracic Curve in Lenke Type 2 Idiopathic Scoliosis
Authors: Taniguchi Yuki , Matsubayashi Yoshitaka , Kato So , Ono Takashi , Oshima Yasushi , Tanaka Sakae 
Published: May 2019

Study Design: Retrospective cohort study. Objectives: To investigate the feasibility of inserting pedicle screws in the proximal thoracic (PT) curve in Lenke type 2 idiopathic scoliosis, using post-myelography computed tomography (CT). Methods: Post-myelography CT images of 46 Japanese patients, 10 to 30 years old, who underwent surgery for Lenke type 2 idiopathic scoliosis were analyzed. A new parameter “SAPS” (space available for pedicle screw) was introduced, which defines the minimal distance between the lateral cortex of the pedicle and the spinal cord, with a SAPS <4.5 mm being “unacceptable.” All 460 pedicles (T2 through T6) were analyzed. Pedicle diameter was classified according to the Akazawa grading system. Results: Most pedicles on the right side at T3 (84.8%) and T4 (97.8%) were unacceptable. The unacceptable rate was 58.7% and 15.2% on the right side at T5 and T6, respectively. A larger Cobb angle of the PT curve was associated with a greater incidence of unacceptable SAPS at these levels. For a Cobb angle of the PT curve >40°, most right T5 pedicles were unacceptable. On the left side, most pedicles from T2 to T5 were acceptable. When T5 was the caudal end vertebra of the PT curve, the left T6 pedicles had an unacceptable SAPS in some cases. When the width of the pedicle channel was ≥2 mm (Akazawa grade 1 or 2), all pedicles from T2 to T6, on both sides, were acceptable. Conclusions: Post-myelography CT enabled us to clearly demonstrate the feasibility of inserting pedicle screws in the PT region.
Understanding the Process of Procedural Sedation for Orthopedic Injuries in the Pediatric Emergency Department
Authors: Vukovic Adam A , Keiner Elizabeth , Hanson Holly R 
Published: May 2019

Objective: To establish a procedural sedation (PS) time line for patients in the pediatric emergency department (PED) with orthopedic injuries. Methods: Retrospective review of patients requiring PS for orthopedic injuries. Process times were collected. Ten percent of encounters were co-reviewed. Interrater reliability and descriptive statistics were calculated. Results: A total of 189 patients were included. Co-abstracted data demonstrated excellent agreement. The median time to PS and length of stay (LOS) were 214 (interquartile range [IQR]: 160-282) and 320 (IQR: 257-402) minutes, respectively. Conclusion: Patients with orthopedic injuries requiring PS experience prolonged PED visits. Interventions should target safely reducing the time to PS and LOS.
Young migrant mental health difficulties and suicidal behaviours: an alternative perspective
Authors: Petti Theodore A. , Chen Andrew 
Published: May 2019

SummaryThe Saving and Empowering Young Lives in Europe (SEYLE) study brings attention to the special needs of adolescent migrants. Alternative data analyses could lead to improved service delivery and requisite education/training of health and mental health personnel. We advocate earlier identification by using SEYLE data to shape policy about youth suicidal behaviour and ideation in prevention efforts.
Diffuse Large B-Cell Lymphoma in Kenya: MYC, BCL2, and the Cell of Origin
Authors: Wawire Jonathan , Sayed Shahin , Moloo Zahir , Sohani Aliyah R. 
Published: May 2019

PURPOSE Diffuse large B-cell lymphoma (DLBCL) is the most commonly diagnosed non-Hodgkin lymphoma in adults in Kenya. Cell of origin (COO) and double expression of MYC and BCL2 are two important prognostic factors for DLBCL. A small subset (5% to 10%) of DLBCL cases show positivity for CD5 and are associated with poor prognosis, whereas CD30 antigen, seen in up to 10% of cases, may be a useful target for therapy. We sought to determine the prevalence of MYC/BCL2 double expression, COO, and proportion of Epstein-Barr virus positivity among patients with DLBCL diagnosed at a tertiary referral laboratory in Kenya. PATIENTS AND METHODS All cases of DLBCL diagnosed from 2012 through 2015 in our pathology department were analyzed. Tumor tissue microarray sections were stained with CD20, CD3, CD5, CD30, BCL2, BCL6, CD10, MUM1, MYC, and Ki67, classified for COO on the basis of the Hans algorithm, and subjected to Epstein-Barr virus-encoded small RNAs in situ hybridization. RESULTS Among 165 DLBCL cases, the median age was 50 years, and there was no sex predilection. Only 18 (10.9%) cases showed double expression for MYC and BCL2. Germinal center B (GCB)-cell type DLBCL accounted for 67 cases (40.6%) and 97 cases (59.4%) were classified as non-GCB. The mean Ki67 proliferation index was significantly higher in the double-expressing (45%) and non-GCB groups (36%) compared with the non–double-expressing group (29%) and GCB group (26%). Sixteen cases (9.7%) were Epstein-Barr virus-encoded small RNAs positive, 12 (75%) of which were non-GCB. CONCLUSION DLBCL in Kenya is seen in much younger patients with the poor prognostic non–GCB-type accounting for 59.4% of cases. MYC and BCL2 double expression was seen in fewer tumors than reported in the literature and in significantly older patients.