bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional, thermodynamics, structural and biological studies of in silico-identified inhibitors of Mycobacterium tuberculosis enoyl-ACP(CoA) reductase enzyme
Authors: Martinelli Leonardo K. B. , Rotta Mariane , Villela Anne D. , Rodrigues-Junior Valnês S. , Abbadi Bruno L. , Trindade Rogério V. , Petersen Guilherme O. , Danesi Giuliano M. , Nery Laura R. , Pauli Ivani , Campos Maria M. , Bonan Carla D. , de Souza Osmar Norberto , Basso Luiz A. , Santos Diogenes S. 
Published: April 2017

AbstractNovel chemotherapeutics agents are needed to kill Mycobacterium tuberculosis, the main causative agent of tuberculosis (TB). The M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase enzyme (MtInhA) is the druggable bona fide target of isoniazid. New chemotypes were previously identified by two in silico approaches as potential ligands to MtInhA. The inhibition mode was determined by steady-state kinetics for seven compounds that inhibited MtInhA activity. Dissociation constant values at different temperatures were determined by protein fluorescence spectroscopy. van’t Hoff analyses of ligand binding to MtInhA:NADH provided the thermodynamic signatures of non-covalent interactions (ΔH°, ΔS°, ΔG°). Phenotypic screening showed that five compounds inhibited in vitro growth of M. tuberculosis H37Rv strain. Labio_16 and Labio_17 compounds also inhibited the in vitro growth of PE-003 multidrug-resistant strain. Cytotoxic effects on Hacat, Vero and RAW 264.7 cell lines were assessed for the latter two compounds. The Labio_16 was bacteriostatic and Labio_17 bactericidal in an M. tuberculosis-infected macrophage model. In Zebrafish model, Labio_16 showed no cardiotoxicity whereas Labio_17 showed dose-dependent cardiotoxicity. Accordingly, a model was built for the MtInhA:NADH:Labio_16 ternary complex. The results show that the Labio_16 compound is a direct inhibitor of MtInhA, and it may represent a hit for the development of chemotherapeutic agents to treat TB.
A salient effect of density on the dynamics of nonaqueous electrolytes
Authors: Han Sungho 
Published: April 2017

AbstractThe mobility and solvation of lithium ions in electrolytes are crucial for the performance and safety of lithium ion batteries. It has been known that a single type of solvent cannot satisfy the requirements of both mobility and solvation simultaneously for electrolytes. Therefore, complex solvent mixtures have been used to optimize both properties. Here we present the effects of density on the dynamics and solvation of organic liquid electrolytes via extensive molecular dynamics simulations. Our study finds that a small variation in density can induce a significant effect on the mobility of electrolytes but does not influence the solvation structure of a lithium ion. It turns out that an adjustment of the density of electrolytes could provide a more effective way to enhance mobility than a control of the solvent mixture ratio of electrolytes. Our study reveals that the density change of electrolytes mainly affects the residence time of solvents in the first solvation shell of a lithium ion rather than the structural change of the solvation sheath. Finally, our results suggest an intriguing point for understanding and designing electrolytes of lithium ion batteries for better performance and safety.
Synthesis and anti-obesity effects in vivo of Crotadihydrofuran C as a novel PPARγ antagonist from Crotalaria albida
Authors: Sun Qin-Hu , Zhang Yu , Chou Gui-Xin 
Published: April 2017

AbstractCrotadihydrofuran C (CC) from the herbs of Crotalaria albida is able to inhibit adipocyte differentiation and lipid accumulation. However, the effects of CC on obesity and metabolic disorders have not yet been elucidated. In our study, the first enantioselective synthesis of the 2-isopropenyl dihydrofuran isoflavone skeleton (CC) is described. The convenient and efficient synthetic protocols developed skilfully solve the problems of the ortho-para directing group and Suzuki coupling reaction using a boronic acid pinacol ester that was more stable and easy to obtain. Furthermore, CC treatment of high-fat diet (HFD)-fed obese mice remarkably reduced their body weight, fat mass, and lipid level as well as improved insulin resistance and non-alcoholic fatty liver disease (NAFLD). A TR-FRET assay showed that CC was specifically bound to PPARγ LBD, which was further confirmed by the molecular docking study. These results suggest that CC could be a useful and potential natural product for treating metabolic diseases, including obesity, hyperlipidemia insulin resistance and NAFLD, without toxic side-effects.
Development of a fluorescent ASFV strain that retains the ability to cause disease in swine
Authors: Borca Manuel V. , O’Donnell Vivian , Holinka Lauren G. , Sanford Brent , Azzinaro Paul A. , Risatti Guillermo R. , Gladue Douglas P. 
Published: April 2017

AbstractAfrican swine fever is a contagious and often lethal disease for domestic pigs with a significant economic impact for the swine industry. The etiological agent, African swine fever virus (ASFV), is a highly structurally complex double stranded DNA virus. No effective vaccines or antiviral treatment are currently commercially available. We present here the development of a strain of ASFV that has been shown to retain its ability to cause disease in swine, efficiently replicate in swine macrophage and that is fluorescently tagged. The insertion of an EGFP cassette replacing the reading frames for two neighboring genes, MGF360-13L and MGF360-14L, in highly virulent field isolate Georgia/2007, did not affect virus replication in cell cultures and did not affect disease progression in swine, the natural host for ASFV. A virulent fluorescently tagged ASFV is a suitable tool to conduct pathogenesis studies in swine, study on virus-macrophage interaction and to run large scale screens that require a sensitive high throughput output. Utilizing an EGFP reporter system for observing ASFV replication and infectivity can circumvent the time and labor-intensive steps associated with viral antigen-based assays such as the observation of hemadsorption or cytopathic effect.
Identification of pro-inflammatory CD205+ macrophages in livers of hepatitis B virus transgenic mice and patients with chronic hepatitis B
Authors: Yong Liang , Li Minmin , Gao Yimin , Deng Yanru , Liu Wenbin , Huang Dake , Ren Cuiping , Liu Miao , Shen Jijia , Hou Xin 
Published: April 2017

AbstractHepatic macrophages play a central role in disease pathogenesis during hepatitis B virus (HBV) infection. Our previous study found that CD205+ macrophages in the liver of hepatitis B surface antigen transgenic (HBs-Tg) mice increased significantly compared with those in wild-type mice, and these increased CD205+ macrophages were involved in CpG-oligodeoxynucleotide-induced liver injury in HBs-Tg mice. Here, we analysed the phenotype and function of CD205+ macrophages derived from the liver of HBs-Tg mice and patients with chronic hepatitis B (CHB). We found that HBs-Tg mice-derived hepatic macrophages produced larger amounts of pro-inflammatory cytokines, including IL-6, IL-12, TNF-α, and of the anti-inflammatory cytokine IL-10 after stimulation with CpG-oligodeoxynucleotides or commensal bacteria DNA than B6 mice-derived hepatic macrophages. Furthermore, hepatic CD205+ macrophages from HBs-Tg mice showed an activated phenotype and expressed higher levels of inflammatory cytokine genes, chemokine genes, and phagocytosis-related genes than hepatic CD205− macrophages. In addition, CD205+ macrophages displayed an inflammatory phenotype and were increased in the liver of patients with CHB compared with those in healthy controls. Our data suggest that hepatic CD205+ macrophages are a unique pro-inflammatory subset observed during HBV infection. Thus, development of intervention targeting these cells is warranted for immunotherapy of HBV-induced liver diseases.
Presenting Symptoms of Pituitary Apoplexy
Authors: Mavridis Ioannis , Meliou Maria , Pyrgelis Efstratios-Stylianos 
Published: April 2017

AbstractThe classical term “pituitary apoplexy” (PA) describes a clinical syndrome usually characterized by abrupt onset of headache accompanied by neurologic and/or endocrinologic deterioration due to sudden expansion of a mass within the sella turcica as a result of hemorrhage or infarction within a pituitary tumor and adjacent pituitary gland. PA is a medical emergency and a difficult diagnosis to establish. Thus this article reviews the presenting symptoms of PA patients to help clinicians recognize or at least suspect this critical condition early on. PA commonly occurs in the setting of a preexisting adenoma, and several patients are unaware of its existence prior to the onset of apoplexy symptoms, which are mainly of a neurologic, ophthalmologic, and endocrinologic nature. Neurologic symptoms include sudden-onset severe headache and other symptoms of subarachnoid hemorrhage, symptoms from compression of the cavernous sinus contents, nausea/vomiting, impaired consciousness, and symptoms of meningeal irritation. Ophthalmologic symptoms include visual field defects, visual loss, diplopia, and ophthalmoplegia. Endocrinologic disturbances include pituitary adenoma symptoms, cortisol deficiency, panhypopituitarism, diabetes insipidus, and syndrome of inappropriate secretion of antidiuretic hormone. Magnetic resonance imaging is the imaging method of choice to aid the PA diagnosis. Its differential diagnoses include cerebrovascular accidents, infectious diseases, and other causes of endocrinologic imbalance. Transsphenoidal surgery is the treatment of choice, especially if there are associated visual abnormalities and ophthalmoplegia. Clinicians should be aware of the presenting symptoms because early diagnosis may reduce the morbidity and mortality of this neurosurgical emergency.
Symptomatic Outcome after Bone-only Suboccipital Decompression in Adult Patients with Chiari Type I Malformations in the Absence of Hydromyelia or Hydrocephalus
Authors: Abuhusain Hazem , Gunawardena Manuri , Auschwitz Tyler , Teo Charles , Koechlin Nicolas 
Published: April 2017

Background Type I Chiari malformation presents without an associated hydromyelia in 30 to 70% of cases, yet there is no agreement regarding the optimal surgical treatment for these patients. We review our experience for treating symptomatic adult type I Chiari malformation without hydromyelia using a suboccipital bone decompression of the hindbrain and no duraplasty in 12 adult patients. Outcome was measured according to the Chicago Chiari Outcome Scale (CCOS).
Results Nine of 12 patients were female; average age at surgery was 34.4 years (range: 17–67 years). Average duration of symptoms prior to surgery was 9.6 years (2 months–29 years). The most common symptom was head and/or neck pain (11/12 patients). All patients additionally presented with at least one non-pain symptom. Mean degree of tonsillar herniation on magnetic resonance imaging was 6.8 mm (range: 5–12 mm) below McRae's line. Operative time was on average 68 minutes (range: 47–120 minutes). No surgical complications were noted in any patient. Length of hospital stay was 2 days (1 overnight) for all patients. Mean follow-up was 167 weeks (range: 13–378 weeks). CCOS for all patients on average was 14.50 (range: 12–16). Pain symptoms underwent improvement (7/11 [63.6%]) or complete resolution (4/11 [36.4%]) in all affected patients. A shorter duration of preoperative symptoms significantly correlated with a better CCOS (p = 0.03). Degree of tonsillar herniation had no significant effect on CCOS (p = 0.67). Of non-pain symptoms, paresthesias/dysesthesias and visual symptoms improved or resolved completely in all affected patients. No patient experienced a worsening of either pain or non-pain symptoms.
Conclusion In the subset of adult patients with a type I Chiari malformation and no associated hydromyelia, a craniectomy without an additional opening of the dura may achieve good overall results according to the CCOS.
REMISSIONPLUS eine Initiative zur Integration moderner Bildgebung in die rheumatologische Versorgung Rückblick, Einblick, Ausblick: Auswertung der Niederfeld-MRT Daten
Authors: Sewerin Philipp , Klein Sabine , Brinks Ralph , Hoyer Annika , Schleich Christoph , Miese Falk , Blaschke Sabine , Edelmann Edmund , Gao Ino , Georgi Joachim , Kellner Herbert , Keyßer Gernot , Lorenz Hanns-Martin , Müller-Ladner Ulf , Pott Hans-Georg , Schulze-Koops Hendrik , Walther Marisa , Schmidt Wolfgang , Schneider Matthias , Ostendorf Benedikt 
Published: April 2017

ZusammenfassungBildgebende Verfahren nehmen heute bei der Diagnosestellung und Therapiekontrolle der Rheumatoiden Arthritis (RA) eine unverzichtbare Rolle ein. Die Initiative REMISSIONPLUS hat seit 2006 über 10 Jahre das Ziel verfolgt, moderne bildgebende Verfahren wie die Arthrosonografie und die Magnetresonanztomografie (MRT) in den klinischen Alltag des Rheumatologen zu implementieren. Neben Schulungen (über 3 000 Rheumatologen in über 200 Veranstaltungen) wurden zahlreiche Bildgebungs- Studien durchgeführt. Erstmals werden jetzt zusammenhängend alle Niederfeld-MRT Daten aus der Initiative vorgestellt. Die Ergebnisse dieser multizentrischen Studie zeigen, dass die Niederfeld-MRT für RA Patienten eine komfortable Untersuchungsmethode darstellt und für den Rheumatologen die Möglichkeit bietet, effektiv und sehr genau Therapieeffekte (DMARD, Biologika) zu kontrollieren. Die MRT-Daten korrelierten hierbei signifikant mit Klinik und Labor. Mit der Methode ist es ferner möglich bei RA-Patienten subklinische Arthritiszeichen zu detektieren, zum anderen konnte fortschreitende radiologische Progression (Erosivität), trotz klinischer Remission („silent progression") erkannt werden. Diese Ergebnisse sind konventionell radiologisch nicht zu gewinnen, sodass der Einsatz der MRT neue Einblicke in die Pathogenese und konsekutiv neue Informationen für das Management der RA liefert. Die Bewertung dieser Vorteile und der Benefit für den Patienten im klinischen Alltag muss in weiteren Studien untersucht und diskutiert werden.
Die hereditäre Hämochromatose: Eine interdisziplinäre diagnostische und therapeutische Herausforderung
Authors: Rihl Markus 
Published: April 2017

ZusammenfassungDie hereditäre Hämochromatose (HH) ist mit einer Homozygoten-Frequenz von 1:200–400 die häufigste autosomal-rezessiv vererbte Stoffwechselstörung in der mittel-/nordeuropäischen Bevölkerung. Die genetischen Defekte bei der HH werden derzeit in 4 Typen unterschieden und zeigen Mutationen im HFE-, Hemojuvelin-, Hepcidin-, TfR2- oder dem Ferroportin 1-Gen. Typ 1 ist die klassische und häufigste Form der HH, bei der 2 Mutationen (C282Y und H63D) im HFE-Gen auf Chromosom 6 identifiziert wurden; wobei mittlerweile zahlreiche Längsschnittstudien eine relativ niedrige Penetranz der Mutationen nachgewiesen haben. Die genetische Testung wird empfohlen für Patienten, bei denen eine erhöhte Transferrinsättigung besteht und für gesunde Personen, die einen Verwandten 1. Grades mit einer HH haben. Bei der HH kommt es über Jahre zu einer stark erhöhten Eisenresorption aus der Nahrung, die zunehmende Eisenüberladung führt unbehandelt u. a. zu Hepatomegalie, Diabetes mellitus, Hautverfärbung („Bronzediabetes“), Kardiomyopathie, Libidoverlust/Infertilität und Leberzirrhose bis hin zum hepatozellulären Karzinom. Häufiges und im Krankheitsverlauf schon früh auftretendes Leitsymptom der Erkrankung sind Arthralgien, die als Manifestation der Hämochromatose-Arthropathie (HCA) zu sehen sind. Typisch sind Arthrosen im Bereich der MCP-Gelenke, letztlich können aber alle Gelenke von degenerativen Veränderungen betroffen sein; auch die Chondrokalzinose (CPPD-Kristallarthropathie) mit akuten, anfallsartigen Arthritiden ist charakteristisch für die HCA. Die Gelenkbeteiligung korreliert nicht zwangsläufig mit dem Grad der Eisenüberladung und im Gegensatz zu den meisten anderen Manifestationen lassen sich die Beschwerden bzw. die klinischen Manifestationen am Bewegungssystem durch therapeutische Aderlässe nicht bessern, auch immunmodulierende Therapien bleiben häufig ohne Ansprechen, sodass letztlich die symptomatische Therapie im Vordergrund steht. Bei der Aderlasstherapie sollten zunächst alle 1–2 Wochen 400–500 ml Blut entfernt werden, Therapieziel sollten niedrignormale Serumferritinwerte sein (20–150 µg/l), bei Auftreten einer Anämie werden die Aderlässe pausiert. Diese Übersicht stellt die aktuellen klinischen, pathogenetischen, diagnostischen sowie therapeutischen Aspekte dieser Erkrankung dar.
Surveillance after resection of pancreatic ductal adenocarcinoma with curative intent – a multicenter survey in Germany and review of the literature
Authors: Ettrich Thomas , Schulte Lucas , Eitel Natalie , Ettrich Kristin , Berger Andreas , Perkhofer Lukas , Seufferlein Thomas 
Published: April 2017

Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with high risk of relapse even after curative-intended resection. There are no evidence-based recommendations for surveillance in actual guidelines. Given this situation and as a basis for prospective studies, we wanted to determine the current practice of surveillance after pancreatic cancer resection in German institutions.
Methods A web-based questionnaire was sent in 2015 to 300 German institutions (hospitals, outpatient clinics, and private practices) experienced in the care of patients with PDAC. The questionnaire comprised 23 items including the respective institution, the level of care, the annual case load of pancreatic cancer surgery, the surveillance algorithms used, and the most frequently used means for surveillance as well as their evaluation by the users with respect to the effectiveness of these means. Additionally, we perform a review of the literature.
Results The final analysis comprised 161 questionnaires (response rate 53.7 %). Mainly high-volume centers (82.5 % with > 300 hospital beds) participated. In 46.6 % of centers, more than 80 % of patients received adjuvant chemotherapy after surgery. Between 60 – 80 % of these patients completed the recommended 6 months of adjuvant treatment, and 47 % of the patients received the whole treatment (surgery, adjuvant therapy) and surveillance in the same center. Upon completion of adjuvant treatment, 96 % of centers survey their patients, and 82 % of these centers already employ diagnostic means during the course of adjuvant chemotherapy. The most commonly used diagnostic means were taking patient history, conducting physical examination, performing laboratory tests including CA19 – 9, and imaging. Of those employed, CA19 – 9 and imaging followed by patient history were considered the most efficient to detect disease relapse by the centers. Half of the institutions perform surveillance for 5 years after surgery.
Conclusion This is the first systematic analysis of self-reported surveillance strategies used in Germany after resection of PDAC with curative intent. Surveillance after resection of PDAC with curative intent is common in Germany. Alterations of CA19 – 9 levels as well as imaging and taking patient history are considered the most efficient means to detect relapse of disease by the physicians participating in our survey.
Pourquoi Requiem ?
Authors: Forest Philippe 
Published: April 2017

Abstract
Camus’s interest in stage adaptations and mainly the problem of evil as it is raised in Faulkner’s Requiem for a Nun tempted the French writer into adapting it for the stage. The reference found in this version to Dostoïevski’s Brothers Karamazov is not meant to assert a Christian faith, but on the contrary to grow away from it. Hence Camus keeps his distance with the part played by Nancy. His adaptation of the Requiem breaks away from the religious interpretations it has been submitted to, so in reality Camus moves along the same line taken by Faulkner, when he was re-writing his first version of the Requiem for a Nun, as Noël Polk has shown. So Faulkner has structured a modern tragedy. The revolt against destiny finally makes it possible to compare the Requiem to Les Justes, making it possible to read it in the light of L’Homme Révolté
Antecedents and consequences of work significance in Indian organizations
Authors: Aggarwal Yogita , Singh Sanjay 
Published: April 2017

The purpose of the present study was to investigate the nature of work significance and identify its key antecedents and consequences in Indian organizations. Partial least squares modeling (N = 300 working Indian managers) confirmed the reliability and validity of the proposeda priorimodel. Furthermore, a mediation-moderation analysis suggested that work significance had a significant mediating influence between antecedent and consequent variables, and its influence was not moderated by the type of organization studied in the research. The applied values of the research along with its limitations and future directions are briefly discussed.
New possibilities using additive manufacturing with materials that are difficult to process and with complex structures
Authors: Olsson Anders , Hellsing Maja S , Rennie Adrian R 
Published: April 2017

Abstract
Additive manufacturing (or 3D printing) opens the possibility of creating new designs and manufacturing objects with new materials rapidly and economically. Particularly for use with polymers and polymer composites, simple printers can make high quality products, and these can be produced easily in offices, schools and in workshops and laboratories. This technology has opened a route for many to test ideas or to make custom devices. It is possible to easily manufacture complex geometries that would be difficult or even impossible to create with traditional methods. Naturally this technology has attracted attention in many fields that include the production of medical devices and prostheses, mechanical engineering as well as basic sciences. Materials that are highly problematic to machine can be used. We illustrate process developments with an account of the production of printer parts to cope with polymer fillers that are hard and abrasive; new nozzles with ruby inserts designed for such materials are durable and can be used to print boron carbide composites. As with other materials, complex parts can be printed using boron carbide composites with fine structures, such as screw threads and labels to identify materials. General ideas about design for this new era of manufacturing customised parts are presented.