bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic and transcriptomic characterization of canine myeloid-derived suppressor cells
Authors: Goulart Michelle R. , Hlavaty Sabina I. , Chang Yu-Mei , Polton Gerry , Stell Anneliese , Perry James , Wu Ying , Sharma Eshita , Broxholme John , Lee Avery C. , Szladovits Balazs , Turmaine Mark , Gribben John , Xia Dong , Garden Oliver A. 
Published: March 2019

AbstractMyeloid-derived suppressor cells (MDSCs) are key players in immune evasion, tumor progression and metastasis. MDSCs accumulate under various pathological states and fall into two functionally and phenotypically distinct subsets that have been identified in humans and mice: polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs. As dogs are an excellent model for human tumor development and progression, we set out to identify PMN-MDSCs and M-MDSCs in clinical canine oncology patients. Canine hypodense MHC class II−CD5−CD21−CD11b+ cells can be subdivided into polymorphonuclear (CADO48A+CD14−) and monocytic (CADO48A−CD14+) MDSC subsets. The transcriptomic signatures of PMN-MDSCs and M-MDSCs are distinct, and moreover reveal a statistically significant similarity between canine and previously published human PMN-MDSC gene expression patterns. As in humans, peripheral blood frequencies of canine PMN-MDSCs and M-MDSCs are significantly higher in dogs with cancer compared to healthy control dogs (PMN-MDSCs: p < 0.001; M-MDSCs: p < 0.01). By leveraging the power of evolution, we also identified additional conserved genes in PMN-MDSCs of multiple species that may play a role in MDSC function. Our findings therefore validate the dog as a model for studying MDSCs in the context of cancer.
The landscape of d16HER2 splice variant expression across HER2-positive cancers
Authors: Volpi Chiara Costanza , Pietrantonio Filippo , Gloghini Annunziata , Fucà Giovanni , Giordano Silvia , Corso Simona , Pruneri Giancarlo , Antista Maria , Cremolini Chiara , Fasano Elena , Saggio Serena , Faraci Simona , Di Bartolomeo Maria , de Braud Filippo , Di Nicola Massimo , Tagliabue Elda , Pupa Serenella Maria , Castagnoli Lorenzo 
Published: March 2019

AbstractThe HER2 splice variant characterized by the deletion of exon 16 and denominated as d16HER2, is associated with HER2-positive breast cancer (BC) aggressiveness, stemness, and trastuzumab susceptibility and is considered to be a “flag” of HER2 dependence. However, with the exception of quantitative real-time PCR analysis, easily reproducible assays are still lacking to clinically detect and quantify the d16HER2 expression. Further, no data on d16HER2 expression and its potential role are available in HER2-positive gastrointestinal malignancies. Here, we used a novel RNA in situ hybridization technique (BaseScope) to discriminate d16HER2 variant expression from the wild type isoform (WTHER2) and to assess their levels across different HER2-positive histological samples. Our results demonstrate the existence of outliers, with d16HER2 mRNA high scores restricted to HER2-positive gastric cancer (GC) and colorectal cancer (CRC) coupled with increased d16HER2 expression compared with BC. Consistent with previously reported data on BC, experiments performed in HER2-positive GC patient-derived xenografts suggest that increased d16HER2 expression is associated with a clinical benefit/response to single-agent trastuzumab. Therefore, d16HER2 may be considered as a “flag” of HER2 dependence in GC and can be clinically investigated as a marker of trastuzumab susceptibility in several other HER2-driven cancers, including CRC. As a clinical proof-of-concept, we indicate that high d16HER2 mRNA scores are exclusively found in patients with a long-term benefit from trastuzumab exceeding 12 months (clinical “outliers”), and that d16HER2 expression is also increased in circulating tumor-released exosomes obtained from baseline plasma samples of long-term responders.
Impaired mitochondrial oxidative phosphorylation capacity in epicardial adipose tissue is associated with decreased concentration of adiponectin and severity of coronary atherosclerosis
Authors: Nakajima Takayuki , Yokota Takashi , Shingu Yasushige , Yamada Akira , Iba Yutaka , Ujihira Kosuke , Wakasa Satoru , Ooka Tomonori , Takada Shingo , Shirakawa Ryosuke , Katayama Takashi , Furihata Takaaki , Fukushima Arata , Matsuoka Ryosuke , Nishihara Hiroshi , Dela Flemming , Nakanishi Katsuhiko , Matsui Yoshiro , Kinugawa Shintaro 
Published: March 2019

AbstractEpicardial adipose tissue (EAT), a source of adipokines, is metabolically active, but the role of EAT mitochondria in coronary artery disease (CAD) has not been established. We investigated the association between EAT mitochondrial respiratory capacity, adiponectin concentration in the EAT, and coronary atherosclerosis. EAT samples were obtained from 25 patients who underwent elective cardiac surgery. Based on the coronary angiographycal findings, the patients were divided into two groups; coronary artery disease (CAD; n = 14) and non-CAD (n = 11) groups. The mitochondrial respiratory capacities including oxidative phosphorylation (OXPHOS) capacity with non-fatty acid (complex I and complex I + II-linked) substrates and fatty acids in the EAT were significantly lowered in CAD patients. The EAT mitochondrial OXPHOS capacities had a close and inverse correlation with the severity of coronary artery stenosis evaluated by the Gensini score. Intriguingly, the protein level of adiponectin, an anti-atherogenic adipokine, in the EAT was significantly reduced in CAD patients, and it was positively correlated with the mitochondrial OXPHOS capacities in the EAT and inversely correlated with the Gensini score. Our study showed that impaired mitochondrial OXPHOS capacity in the EAT was closely linked to decreased concentration of adiponectin in the EAT and severity of coronary atherosclerosis.
Caught in the act: LRRK2 in exosomes
Authors: Wang Shijie , West Andrew B. 
Published: March 2019

Abstract
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are a frequent genetic cause of late-onset Parkinson's disease (PD) and a target for therapeutic approaches. LRRK2 protein can influence vesicle trafficking events in the cytosol, with action both in endosomal and lysosomal pathways in different types of cells. A subset of late endosomes harbor intraluminal vesicles that can be secreted into the extracellular milieu. These extracellular vesicles, called exosomes, package LRRK2 protein for transport outside the cell into easily accessed biofluids. Both the cytoplasmic complement of LRRK2 as well as the exosome-associated fraction of protein appears regulated in part by interactions with 14-3-3 proteins. LRRK2 inside exosomes have disease-linked post-translational modifications and are relatively stable compared with unprotected proteins in the extracellular space or disrupted cytosolic compartments. Herein, we review the biology of exosome-associated LRRK2 and the potential for utility in diagnosis, prognosis, and theragnosis in PD and other LRRK2-linked diseases.
Isolated DC/DC converter with three‐level high‐frequency link and bidirectional power flow ability for electric vehicles
Authors: Zhang Chao , Gao Zhigang , Chen Te , Yang Jie 
Published: March 2019

A high‐frequency isolated bidirectional DC/DC converter based on the combination of an H‐bridge, a three‐level half‐bridge and a three‐phase full bridge topology is proposed for electric vehicle applications. The 24 V low‐voltage battery pack is the power supply of the converter and it is raised to about 144 V, which is then converted to three‐phase AC voltage to drive the induction motor. A multilevel high‐frequency link is proposed to implement the conversion from the low voltage side (LVS) to the high voltage side (HVS). The switching patterns and single‐phase three‐level pulse width modulation is proposed to maintain the voltage on HVS and to control the power flowing out of the battery. The zero voltage switching characteristics of the low rating‐voltage metal‐oxide‐semiconductor field‐effect transistors on LVS and HVS are analyzed. The algorithms to suppress DC bias of magnetising current and to equalise the capacitor voltages are also introduced. The effectiveness and the control strategy of the proposed converter are verified by simulation and experimental results.
Atherosklerose als inflammatorische Erkrankung – Pathophysiologie, klinische Relevanz und therapeutische Implikationen
Authors: Arnold Natalie , Koenig Wolfgang 
Published: March 2019

AbstractSince the early 1990 s, both experimental and clinical data have clearly demonstrated that inflammatory processes accompany atherosclerotic disease from its initiation to the development of clinical complications. Numerous biomarkers involved at various levels of the inflammation cascade have been shown to be associated with adverse cardiovascular outcomes. Among them, the classical acute phase reactant C-reactive protein (CRP) has been most intensively investigated. Recent research in this field has been driven by the observation that despite low LDL-cholesterol levels, a remarkably high number of patients are still at increased risk for recurrent cardiovascular events. This is argued to be attributable to the presence of a prolonged inflammatory response (reflected by a persistently elevated hsCRP), a concept, which is currently known as “residual inflammatory risk”. The unequivocal proof that the inflammatory process is not only a simple bystander but is also causally involved in atherogenesis, came from the recent CANTOS trial, showing a 15 % reduction of primary MACE outcomes despite aggressive statin therapy and lower LDL-cholesterol levels. Thus, an anti-inflammatory treatment strategy might represent a promising tool to improve the outcome of this still deadly disease.
Sclerostin-Antikörper als neue Therapieoption der
Osteoporose
Authors: Sebastian Simon , Resch Heinrich 
Published: March 2019

ZusammenfassungRomosozumab ist ein humanisierter monoklonaler Antikörper gegen Sclerostin, der
inhibierend auf die Osteogenese in Osteoblasten wirkt. Der Antikörper hat sowohl
anabole als auch antiresorptive Eigenschaften. Bei postmenopausalen Frauen mit
Osteoporose senkt Romosozumab die Inzidenz sowohl von vertebralen, als auch von
non-vertebralen Frakturen und erhöht nicht nur die Knochenmineraldichte und die
Parameter der Knochenneubildung, sondern senkt ebenfalls die Parameter der
Knochenresorption. Auch bei Männern kann biochemisch eine gesteigerte
Knochenneubildung und eine Zunahme der Knochenmineraldichte beobachtet werden.
Obwohl in rezenten Publikationen Romosozumab gut toleriert wird, sollte das
Risikoprofil und die Einsetzbarkeit in weiteren Studien diskutiert werden.
Diagnostik bewegungsspezifischer Besonderheiten bei Adipositas und Magersucht: Wie zutreffend beurteilen fallführende Therapeuten und Patienten selbst Ruhe- und Aktivitätszeiten?
Authors: Oberste Max , Läuger Sandra , Hartig Philipp , Alexandridis Katharina 
Published: March 2019

ZusammenfassungDie Regulierung von Inaktivität bzw. exzessiver körperlicher Aktivität ist ein wichtiges Ziel der Bewegungstherapie mit Adipositas-Patienten bzw. mit anorektischen Patienten. Um zu untersuchen, inwieweit dieses Ziel tatsächlich erreicht wird, bedarf es valider Erfassungsmethoden der körperlichen Aktivität der Patienten. In der vorliegenden Studie wurden die Fremdbeurteilung der körperlichen Aktivität adipöser und anorektischer Patienten durch ihre fallführenden Therapeuten und die Selbstbeurteilung auf ihre Gültigkeit hin untersucht. Als Kriteriumsmaß diente die Akzelerometrie. Die Ergebnisse zeigen, dass sowohl die Angaben der Therapeuten als auch die der Patienten selbst deutlich von den Akzelerometrieergebnissen abweichen. Auch wenn die Angaben der Therapeuten bzw. der Patienten lediglich kategorial ausgewertet werden (inaktiv vs. nicht inaktiv bzw. exzessiv aktiv vs. nicht exzessiv aktiv), zeigt sich keine zufriedenstellende Genauigkeit. Die Ergebnisse werfen die Frage nach alternativen Erfassungsmöglichkeiten körperlicher Aktivität adipöser bzw. anorektischer Patienten in Wissenschaft und Klinik auf. Objektive Messinstrumente wie die Akzelerometrie könnten hierfür geeignet sein.
Leukämie durch Kollision mit Wildschwein?
Authors: Zimmermann Maximilian , Bendas Gerd , Feldmann Georg 
Published: March 2019

Zusammenfassung
Anamnese Eine 23-jährige Patientin wurde wegen Fiebers in Neutropenie unter der Verdachtsdiagnose einer akuten Leukämie in unsere Klinik verlegt. Vor einigen Tagen sei ein Wildschweinkadaver auf die Patientin gestürzt, anschließend seien starke Rückenschmerzen aufgetreten.
Untersuchungen und Diagnose Im Blutbild wurden eine Thrombozytopenie und Neutropenie mit 0,04G/L nachgewiesen. Labordiagnostisch zeigten sich erhöhte Transaminasen, derangierte Gerinnungsparameter sowie erhöhte CRP-, Procalcitonin- und Kreatininwerte im Serum.
Therapie und Verlauf Eine antiinfektive Therapie wurde unverzüglich eingeleitet. Im Verlauf entwickelte die Patientin Zeichen einer akuten Cholezystitis, die konservativ behandelt wurde. Erst auf nochmalige explizite Nachfrage und Ausschluss einer malignen hämatologischen Grunderkrankung gab die Patientin eine einmalige Einnahme von 1 g Metamizol als Eigenmedikation nachträglich an. Im Verlauf normalisierten sich sämtliche Laborparameter und die Patientin konnte nach sieben Tagen entlassen werden.
Folgerung Im Nachhinein ist die beschriebene Symptomatik als Ausdruck einer Infektkomplikation unter einer Agranulozytose nach einmaliger Einnahme von Metamizol zu werten und belegt eindrucksvoll die Notwendigkeit einer strengen Indikationsstellung bei Einsatz dieser Substanz.
Diffuse Large B-Cell Lymphoma Involvement in Two Different Localizations: A Case Report
Authors: Bulut Nilufer , Arslan Hılal , Ozaydın Ipek 
Published: March 2019

AbstractThe genital system and skin involvement of diffuse B-cell lymphomas are quite rare. The appearance of these rare types in the same patient and the same period makes the treatment of the disease difficult. But both types respond well to anthracyclines and immunotherapies. A 74-year-old woman was treated with R-CHOP (Rituximab, cyclophosphamide, doxorubicine, vincristine, prednisolone) without surgery and/or radiotherapy, and no recurrence at 2 years follow-up. Despite the poor prognosis of these types of lymphomas, treatment responses are quite good as they are in other subtypes.
Year in Review: Synopsis of Selected Articles in Neuroanesthesia and Neurocritical Care from 2018
Authors: Rogan Kyle J. , Chowdhury Tumul , Venkatraghavan Lakshmikumar 
Published: March 2019

AbstractThis review is a synopsis of selected articles from neuroscience, neuroanesthesia, and neurocritical care from the year 2018 (January–October 2018). The journals reviewed included anesthesia journals, critical care medicine journals, neurosurgical journals as well as high-impact factor medical journals such as Lancet, Journal of American Medical Association (JAMA), New England Journal of Medicine (NEJM), and Stroke. This summary of important articles will serve to update the knowledge of anesthesiologists and other perioperative physicians who provide care to neurosurgical and neurocritical patients.
Early-Term Outcomes of Off-Pump versus On-Pump Beating-Heart Coronary Artery Bypass Surgery
Authors: Velioglu Yusuf , Isik Mehmet 
Published: March 2019

Background The current study analyzed and compared early-term outcomes of off-pump versus on-pump beating heart coronary artery bypass surgery.
Methods From January 2011 to January 2018, a total of 736 patients underwent isolated first-time elective beating-heart coronary artery bypass surgery without the use of aortic cross-clamping and cardioplegic arrest at our institution, and they were included in this study. Data of patients were collected and retrospectively analyzed. Patients were divided into two groups according to the use of cardiopulmonary bypass during the operation, as off-pump group (n = 399) and on-pump beating-heart group (n = 337). Both groups were compared with each other in terms of preoperative, intraoperative, and postoperative data.
Results Groups were statistically similar with regard to baseline clinical characteristics and demographics. When compared with off-pump group, on-pump beating-heart group had a greater number of distal bypass, longer length of hospital stay, and lower postoperative hematocrit level, and received more blood product transfusion. No statistically significant differences were detected between the groups with respect to mortality and postoperative complications except for atrial fibrillation. Atrial fibrillation was significantly frequent in on-pump beating-heart group.
Conclusion Our study suggested that off-pump and on-pump beating-heart coronary artery bypass procedures had similar early mortality and major complication rates except for atrial fibrillation. However, it seemed that off-pump procedure was superior to on-pump beating-heart procedure with regard to length of hospital stay, blood product transfusion, and atrial fibrillation development. Further prospective randomized studies with larger patient series are needed to support our research and attain more accurate data.
Intermittent Antegrade Warm Blood Cardioplegia: What Is Next?
Authors: Calafiore Antonio Maria , Pelini Piero , Foschi Massimilliano , Di Mauro Michele 
Published: March 2019

AbstractThe introduction of warm heart surgery was a radical change in the concept of myocardial protection. In 1992, we applied a protocol for intermittent antegrade warm blood cardioplegia (CPL), which acquired some popularity for its simplicity and effectiveness. The possibility to deliver the warm blood CPL intermittently using the antegrade route attracted the attention of the scientific world, as the surgical procedure was less complicated. In this report, our aim is to focus on the changes that the protocol underwent over time and the reasons why these changes were made.
Evaluation of Postoperative Deficits following Motor Cortex Tumor Resection using Small Craniotomy
Authors: Paiva Wellingson , Fonoff Erich , Beer-Furlan André , Morais Bárbara , Neville Iuri , Ramos-Filho Rogério , Teixeira Manoel 
Published: March 2019

Introduction Surgical treatment of brain tumors in eloquent areas has always been considered a major challenge because removal-related cortical damage can cause serious functional impairment. However, few studies have investigated the association between small craniotomies and the higher risk of incidence of motor deficits and prolonged recovery time. Here, we analyzed neurologic deficits and the prognostic variables after surgery guided by navigation for motor cortex tumors under general anesthesia.
Methods This was a prospective study that included 47 patients with tumors in the precentral gyrus. All surgeries were performed with neuronavigation and cortical mapping, with direct electrical stimulation of the motor cortex. We evaluated the prognostic evolution of patients with pre- and postoperative Karnofsky Performance Scale using the Eastern Cooperative Oncology Group scale.
Results Complete resection was verified in all 18 cases of metastasis, 13 patients with glioblastoma multiforme, and 5 patients with low-grade gliomas. An analysis of the motor deficits revealed that 11 patients experienced worsening of the deficit on the first day after surgery. Only four patients developed new deficits in the immediate postoperative period, and these improved after 3 weeks. After 3 months, only two patients had deficits that were worse those experienced prior to surgery; both patients had glioblastoma multiforme.
Conclusion In our series, motor deficits prior to surgery were the most important factors associated with persistent postoperative deficits. Small craniotomy with navigation associated with intraoperative brain mapping allowed a safe resection and motor preservation in patients with motor cortex brain tumor.
Finding Understudied Disorders Potentially Associated with Maternal Morbidity and Mortality
Authors: Rodriguez Laritza , Fushman Dina 
Published: March 2019

Objective Clinical research literature focuses primarily on the most common causes of maternal morbidity and mortality (MMM). We explore sections of the discharge summaries of pregnant or postpartum women admitted to an intensive care unit (ICU) to identify associated disorders and mine the literature to identify knowledge gaps in clinical research.
Methods Data for the study were discharge summaries in the MIMIC (Medical Information Mart for Intensive Care) database. We extracted a control cohort to study if there is a difference in comorbidities between pregnant and not pregnant patients with similar reasons for admission. We identified comorbidities of the Unified Medical Language System (UMLS) semantic types disease or syndrome, Mental or behavioral dysfunction, and injury, or poisoning. We used Entrez programming utilities (E-utilities) to query PubMed®.
Results We identified 246 pregnant and postpartum patients. A control group of 587 not pregnancy related admissions matched on age and admit diagnosis. We found overlap of 24.3% discharge diagnoses between the two groups, and 7.5% of the codes exclusively in the pregnancy group. We identified 33 disease mentions not included in the most common reported causes of MMM.
Conclusion Our results demonstrate that clinical text provides additional comorbidities associated with maternal complications that need further clinical research.
Ultrasound-Guided Thrombin Injection for Iliopsoas Pseudoaneurysm
Authors: Weissmann Jonathan , Griton Yigal , Mahajna Shadi , Ajaj Moanis , Fajer Simone 
Published: March 2019

AbstractBilateral iliopsoas hematoma is an uncommon phenomenon, which has been described in individuals receiving anticoagulation therapy. The hematoma is caused by bleeding of arteries to the muscle. In rare cases, pseudoaneurysms can also be formed. We present a case of an adolescent, with partial factor XI deficiency, who experienced a mild fall. Imaging studies revealed large bilateral iliopsoas hematomas and bilateral iliopsoas pseudoaneurysms. One pseudoaneurysm was demonstrated by angiography and was embolized with micro coils. The second, more persistent one, was sealed via ultrasound-guided thrombin injection, with excellent morphological and clinical results.
Symbolic labeling in 5-month-old human infants
Authors: Kabdebon Claire , Dehaene-Lambertz Ghislaine 
Published: March 2019

Significance
Humans naturally entertain complex representations of the world based on various symbolic systems, from natural language to mathematical or musical notation. They recode the input into abstract symbolic representations that can be internally manipulated and projected back onto the external world. We show that preverbal infants can redescribe complex percepts into abstract mental variables, which they can readily map onto arbitrary labels. Importantly, we show that, beyond associative learning, infants can readily infer a bidirectional relation between the abstracted representations and the associated labels, a capacity that animals do not spontaneously exhibit. Our findings buttress the hypothesis of symbolic representations in preverbal infants, which may serve as a foundation for our distinctively human learning abilities.