bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network Pharmacology Uncovers Anticancer Activity of Mammea-Type Coumarins from Calophyllum brasiliense
Authors: Gómez-Verjan Juan , Rivero-Segura Nadia , Estrella-Parra Edgar , Rincón-Heredia Ruth , Madariaga-Mazón Abraham , Flores-Soto Edgar , González-Meljem Mario , Cerbón Marco , Reyes-Chilpa Ricardo 
Published: July 2018

AbstractMammea-type coumarins are a particular type of secondary metabolites biosynthesized by the tropical rainforest tree Calophyllum Brasiliense, which is distributed from South America to Mexico. Particularly, mammea A/BA and A/BB (alone or as a mixture) possess biological properties such as cytotoxic and antitumoral activities, however, most of its molecular targets remain unknown. In this context, novel bioinformatic approaches, such as network pharmacology analysis, have been successfully used in herbal medicine to accelerate research in this field, and the support of experimental validations has been shown to be quite robust. In the present study, we performed a network pharmacology analysis to assess the possible molecular biological networks that interact with mammea A/BA and A/BB. Moreover, we validated the most relevant networks experimentally in vitro on K562 cancer cells. The results of the network pharmacology analysis indicate that mammea A/BA and A/BB interacts with cell death, PI3K/AKT, MAPK, Ras, and cancer pathways. The in vitro model shows that mammea A/BA and A/BB induce apoptosis through the overexpression of the proapoptotic proteins Bax and Bak, disrupt the autophagic flux as seen by the cytosolic accumulation of LC3-II and p62, disrupting the mitochondria ultrastructure and concomitantly increase the intracellular calcium concentration. Additionally, docking analysis predicted a possible interaction with a rapamycin-binding domain of mTOR. In conclusion, we validated network pharmacology analysis and report, for the first time, that mammea A/BA and A/BB coumarins induce apoptosis through the inhibition of the autophagic flux, possibly interacting with mTOR.
Recent Advances in Copper-Catalyzed Asymmetric Hydroboration of Electron-Deficient Alkenes: Methodologies and Mechanism
Authors: Whiting Andrew , Chen Jing-Biao 
Published: July 2018

The efficient synthesis of enantioenriched organoboron compounds has been recognized as an important topic in recent years. As an update review, this article aims to select key achievements in copper-catalyzed, electron-deficient alkene enantioselective hydroboration methodologies since the beginning of 2017. In addition, it covers relevant mechanistic investigations developed over the last six years, as well as total synthesis applications for preparing 1,3-diols as important medicinal intermediates.1	Introduction2	Methodologies for Copper-Catalyzed Hydroboration2.1	α,β-Unsaturated Ketones and Imines2.2	α,β-Unsaturated Esters and Cyanides2.3	Aryl Alkenes and Alkyl Alkenes3	Mechanistic Investigations on the Copper-Catalyzed Hydroboration3.1	A Cu–BX2 Intermediate3.1.1	Experimental Analysis3.1.2	Borylative Difunctionalization Methodologies3.1.3	Density Functional Theory3.2	A Cu–H Intermediate3.3	Other Mechanistic Proposals4	Synthetic Applications: Chiral 1,3-Diols5	Conclusions and Outlook
Bone Recontouring by Guided Surgical Navigation Integrating “Mirroring” Computational Planning in the Management of Severe Fronto-orbital Asymmetry in Fibrous Dysplasia
Authors: Guatta Ramona , Scolozzi Paolo 
Published: July 2018

AbstractWe report the successful treatment of severe fronto-orbital asymmetry in a 20-year-old man with fibrous dysplasia by bone recontouring using a specific approach combining “mirroring” virtual computational planning with intraoperative guided surgical navigation.
Anterior Cervical Fusion with Stand-alone Trabecular Metal Cages to Treat Cervical Myelopathy Caused by Degenerative Disk Disease. Observations in 88 Cases with Minimum 12-month Follow-up
Authors: Roperto Raffaelino , Cacciotti Guglielmo , Calvosa Francesco , Mastronardi Luciano 
Published: July 2018

Background Anterior cervical fusion (ACF) with autologous bone was reported > 50 years ago. The continuous development of materials with elastic properties close to that of the cortical bone improves induction of osteogenesis and simplifies the technique of interbody fusion. To determine the safety and efficiency of stand-alone trabecular metal (TM) (or porous tantalum) cages for ACF, we performed a retrospective analysis of 88 consecutive patients with one-level or two-level degenerative disk disease (DDD) causing cervical myelopathy treated by interbody fusion with stand-alone TM cages.
Materials and Methods During a 65-month period, 88 consecutive patients had ACF at 105 levels between C3 and C7. All surgeries involved one- or two-segmental DDD producing mild or severe cervical spine myelopathy, in 31 patients (35.2%), associated with unilateral or bilateral radiculopathy. We implanted all disk spaces with unfilled TM trapezoidal cages (Zimmer Biomet Spine, Broomfield, Colorado, United States).
Results At a mean follow-up of 31 months (range: 12–65 months), 95.4% of patients had a good to excellent outcome, with subjective and objective improvement of myelopathy; the result was fair in two and poor in two other patients. Radicular pain and/or any deficits disappeared in 84 patients (95.4%) complaining of preoperative myeloradiculopathy. The fusion rate was 68.2% at 6 months and 100% at 1 year. Device fragmentation was never observed. In two cases, a second operation with removal of TM cages, corpectomy, expansion cages, and plating was necessary.
Conclusions TM cages appear to be safe and efficient for ACF in DDD patients with myelopathy. To confirm our preliminary impressions, larger studies with long-term follow-up are necessary.
Large Intratemporal Facial Nerve Schwannoma without Facial Palsy: Surgical Strategy of Tumor Removal and Functional Reconstruction
Authors: Yetiser Sertac 
Published: July 2018

Background Three patients with large intratemporal facial schwannomas underwent tumor removal and facial nerve reconstruction with hypoglossal anastomosis. The surgical strategy for the cases was tailored to the location of the mass and its extension along the facial nerve.
Aim To provide data on the different clinical aspects of facial nerve schwannoma, the appropriate planning for management, and the predictive outcomes of facial function.
Patients Three patients with facial schwannomas (two men and one woman, ages 45, 36, and 52 years, respectively) who presented to the clinic between 2009 and 2015 were reviewed. They all had hearing loss but normal facial function. All patients were operated on with radical tumor removal via mastoidectomy and subtotal petrosectomy and simultaneous cranial nerve (CN) 7– CN 12 anastomosis.
Results Multiple segments of the facial nerve were involved ranging in size from 3 to 7 cm. In the follow-up period of 9 to 24 months, there was no tumor recurrence. Facial function was scored House-Brackmann grades II and III, but two patients are still in the process of functional recovery.
Conclusion Conservative treatment with sparing of the nerve is considered in patients with small tumors. Excision of a large facial schwannoma with immediate hypoglossal nerve grafting as a primary procedure can provide satisfactory facial nerve function. One of the disadvantages of performing anastomosis is that there is not enough neural tissue just before the bifurcation of the main stump to provide neural suturing without tension because middle fossa extension of the facial schwannoma frequently involves the main facial nerve at the stylomastoid foramen. Reanimation should be processed with extensive backward mobilization of the hypoglossal nerve.
Thrombin-Induced Platelet Factor Va Formation in Patients with a Gray Platelet Syndrome
Authors: Baruch Dominique , Lindhout Theo , Dupuy Evelyne , Caen Jacques P 
Published: July 2018

SummaryThe present study was initiated to establish the functional factor V concentration in platelets of patients with a mild bleeding disorder ascribed to a gray platelet syndrome. This inherited platelet disorder has been characterized by a specific deficiency of alpha-granules and subsequent deficiencies in the alpha-granule proteins. We found that the concentration of plasma factor V was slightly decreased (70% of normal values). In contrast, platelet factor Va formation was severely impaired. Besides a much lower factor V content than in control platelets (10-20% of normal), the dependency of platelet factor Va formation on tlnumbin concentration was altered. Increasing the thrombin concentration 4-lold compared to the concentration that results in maximal factor Va generation from normal platelets did not result in a maximal factor Va formation from gray platelets. When a suspension of washed gray platelets was incubated with a prostacyclin analogue prior to the stimulation with thrombin, a 10-fold lower factor VQ activity was measured. Thus, thrombin-induced factor Va formation in a suspension of gray platelets is the result of a release reaction, followed by the thrombin-catalyzed activation of released factor V. Whereas the kinetics of the former reaction are apparently impaired, the kinetics of the latter one were found to be identical to those observed for normal platelet and plasma factor V activation.
Prevention of Postoperative Venous Thrombosis: A Randomized Trial Comparing Unfractionated Heparin with Low Molecular Weight Heparin in Patients Undergoing Total Hip Replacement
Authors: Planes Andrè , Vochelle Nicole , Mazas Frçngois , Mansat Christian , Zucman Jean , Landais Alain , Pascariello Jean Claude , Weill Dan , Jean Butel 
Published: July 2018

SummaryA double blind randomized trial comparing subcutaneous enoxaparin (40 mg once daily) with standard unfractionated calcium heparin administered at a dose of 5,000 units every 8 hours in patients undergoing elective hip replacement has been performed. Treatment regimens began 12 hours preoperatively with enoxaparin, 2 hours preoperatively with standard unfractionated calcium heparin, and were continued for 15 days or until discharge. Venography was performed in all patients. Two hundred thirty-seven patients were included in the study: 113 received unfractionated heparin and 124 received enoxaparin. The incidence of proximal deep vein thrombosis was reduced from 18.5% in the unfractionated heparin group to 7.5% in the enoxaparin group (p = 0.014), and the incidence of total deep vein thrombosis was similarly reduced from 25% to 12.5% (p = 0.03). There were two major bleeding episodes and one minor bleed in the enoxaparin group compared to two minor bleeds in the unfractionated heparin group. Patients who received enoxaparin required fewer red blood cell transfusions and had a significantly higher hemoglobin on postoperative days 3 and 4. Thus prophylaxis with enoxaparin, 40 mg once daily, is simple, safe and more effective than standard low dose unfractionated heparin in preventing deep vein thrombosis in patients undergoing elective hip replacement.
Zur Morphologie und Biochemie der Wundheilung: eine Übersicht
Authors: Huber P. , Lindner J. 
Published: July 2018

ZusammenfassungDie Wundheilung wird mit morphologischenund biochemischen Methoden untersuchL Die Ergebnissezeigen, daß die Wundsetzung zur Störungdes Gleichgewichtes zwischen physiologischen Auf- und Abbauvorgängen von Zellen, Grundsubstanzund Fasern (mit Erhöhung ihrer Umsatzraten) fiihrt, Die ä Zunahmedes Katabolismus ist ftir das AusmaB der sekundären kompensatorischen Steigerung des Anabolismus verantwortlich, speziell von Zellen, Proteoglykanen und Kollageno Art, Größe und Lokalisation der Wunde bestimmen den Heilungsablauf und damit das Ausmaß der Anpassung von Struktm, Funktion und Biomechanik an das umgebende, unverletzte Gewebeo Die Kapillarisierung und die Epithelisierung der Wunde start en ebenfalls rasch nach Wundsetzung und werden mit 3H-Thymidin-autoradiographischen Verfahren lokalisiert und quantifizierL Neben sogo reifen Narben können atrophische oder hypertrophe Narben entstehen, schlieBlich auch Keloideo In diesem Zusammenhang werden Regulationen und StOrungen der verschiedenen Wundheilungsphasen besprochen, insbesondere hinsichtlich sogo Zell- und Matrixhyperplasien und ihrer unzureichenden Riickbildung bei diesen pathologischen Wundheilungsverlaufeno Diese Ergebnisse der Bindegewebsforschung sind von praktischer und klinischer Bedeutung.
Mathematical Models for Tumor Growth and the Reduction of Overtreatment
Authors: Heesterman Berdine , Bokhorst John-Melle , de Pont Lisa , Verbist Berit , Bayley Jean-Pierre , van der Mey Andel , Corssmit Eleonora , Hes Frederik , van Benthem Peter , Jansen Jeroen 
Published: July 2018

Background To improve our understanding of the natural course of head and neck paragangliomas (HNPGL) and ultimately differentiate between cases that benefit from early treatment and those that are best left untreated, we studied the growth dynamics of 77 HNPGL managed with primary observation.
Methods Using digitally available magnetic resonance images, tumor volume was estimated at three time points. Subsequently, nonlinear least squares regression was used to fit seven mathematical models to the observed growth data. Goodness of fit was assessed with the coefficient of determination (R
2) and root-mean-squared error. The models were compared with Kruskal–Wallis one-way analysis of variance and subsequent post-hoc tests. In addition, the credibility of predictions (age at onset of neoplastic growth and estimated volume at age 90) was evaluated.
Results Equations generating sigmoidal-shaped growth curves (Gompertz, logistic, Spratt and Bertalanffy) provided a good fit (median R
2: 0.996–1.00) and better described the observed data compared with the linear, exponential, and Mendelsohn equations (p < 0.001). Although there was no statistically significant difference between the sigmoidal-shaped growth curves regarding the goodness of fit, a realistic age at onset and estimated volume at age 90 were most often predicted by the Bertalanffy model.
Conclusions Growth of HNPGL is best described by decelerating tumor growth laws, with a preference for the Bertalanffy model. To the best of our knowledge, this is the first time that this often-neglected model has been successfully fitted to clinically obtained growth data.
Musik und Medizin
Authors: Evers S. 
Published: July 2018

ZusammenfassungBeziehungen von Musik und Medizin sind in der Medizingeschichte schon immer von Interesse gewesen. In den letzten Jahrzehnten hat sich dieses interdisziplinäre Feld jedoch zu einem eigenständigen Forschungs- und Versorgungsgebiet entwickelt. In diesem Beitrag sollen die Überschneidungsgebiete von Musik und Medizin systematisch dargestellt werden. Nach propädeutischen Hinweisen wird Musik als Objekt der Medizin erläutert. Hierunter fallen die Bereiche der verschiedenen physiologischen und pathologischen Wirkungen von Musik, der Erkrankungen durch Musizieren und die Musiktherapie. Danach wird dann Medizin als Gegenstand der Musik(wissenschaft) diskutiert. Hierzu gehören Darstellungen von medizinischen Sachverhalten in der Musik, die Pathografien von berühmten Komponisten/Musikern und auch musikalische Aktivitäten von Medizinern. Insbesondere wird eine seriöse und nicht eine romantisierende Beschäftigung mit den Beziehungen zwischen Musik und Medizin gefordert.
Neue Antibiotika für die Therapie von multiresistenten gramnegativen Bakterien
Authors: Probst-Kepper Michael , Geginat Gernot 
Published: July 2018

ZusammenfassungDie stetige Zunahme an bakteriellen Resistenzen und von multiresistenten Erregern (MRE) – vor allem im gramnegativen Bereich – ist ein weltweites Problem. Die Entwicklung neuer Wirkstoffe gegen Infektionen mit multiresistenten gramnegativen Erregern (MRGN) besitzt daher höchste Priorität. Im Folgenden werden kürzlich zugelassene oder in der fortgeschrittenen klinischen Prüfung befindliche Antibiotika mit Wirksamkeit gegen MRGN vorgestellt.
Tethered multifluorophore motion reveals equilibrium transition kinetics of single DNA double helices
Authors: Schickinger Matthias , Zacharias Martin , Dietz Hendrik 
Published: July 2018

Significance
Understanding cellular functions and dysfunctions often begins with quantifying the interactions between the binding partners involved in the processes. Learning about the kinetics of the interactions is of particular importance to understand the dynamics of cellular processes. We created a tethered multifluorophore motion assay using DNA origami that enables over 1-hour-long recordings of the statistical binding and unbinding of single pairs of biomolecules directly in equilibrium. The experimental concept is simple and the data interpretation is very direct, which makes the system easy to use for a wide variety of researchers. Due to the modularity and addressability of the DNA origami-based assay, our system may be readily adapted to study various other molecular interactions.
Eda-activated RelB recruits an SWI/SNF (BAF) chromatin-remodeling complex and initiates gene transcription in skin appendage formation
Authors: Sima Jian , Yan Zhijiang , Chen Yaohui , Lehrmann Elin , Zhang Yongqing , Nagaraja Ramaiah , Wang Weidong , Wang Zhong , Schlessinger David 
Published: July 2018

SignificanceSpecific gene regulation in organ development remains poorly understood. Here, we report that skin-specific ectodysplasin A (Eda) signaling triggers the formation of a protein complex that includes a BAF complex, an NF-kB dimer of p50/RelB, and a specific “linker” protein, Tfg. We further find that Eda-activated RelB recruits BAF complex to specific gene loci for local chromatin remodeling of target genes. These findings may exemplify a more general model for specific gene regulation involving unique ligand–receptor complexes leading to selective activation of transcription factors, specific linkers, and tissue-specific chromatin-remodeling complex.
Switching of the folding-energy landscape governs the allosteric activation of protein kinase A
Authors: England Jeneffer P. , Hao Yuxin , Bai Lihui , Glick Virginia , Hodges H. Courtney , Taylor Susan S. , Maillard Rodrigo A. 
Published: July 2018

Significance
Mutations, deletions, or gene fusions in protein kinases have been associated with the development of many diseases in humans and have led to the emergence of the protein kinase family as an important therapeutic drug target. In the cell, kinase activity is often turned on and off allosterically by intramolecular regulatory domains, flexible linkers, or other interacting proteins. Here, we use single-molecule optical tweezers to investigate the mechanism of allosteric regulation of the cAMP-dependent PKA. This approach allowed us to determine the thermodynamic driving forces that enable PKA to transduce cAMP-binding signals to turn on its kinase activity.
Unbiased classification of mosquito blood cells by single-cell genomics and high-content imaging
Authors: Severo Maiara S. , Landry Jonathan J. M. , Lindquist Randall L. , Goosmann Christian , Brinkmann Volker , Collier Paul , Hauser Anja E. , Benes Vladimir , Henriksson Johan , Teichmann Sarah A. , Levashina Elena A. 
Published: July 2018

Significance
Mosquito blood cells are central players of immunity against the vector-borne pathogens that devastate the lives of millions of people worldwide. However, their molecular identity and classification remain controversial. By applying single-cell RNA sequencing and high-content imaging flow cytometry, we defined the molecular fingerprint of a subset of mosquito blood cells and characterized two transcriptionally distinct blood cell populations that resemble previously described cell types. Surprisingly, cell population analyses at a single-cell level uncovered an active molecular transfer between the two cell types that may contribute to cellular diversity and plasticity seen across biological systems.
Orthogonal self-assembly of an organoplatinum(II) metallacycle and cucurbit[8]uril that delivers curcumin to cancer cells
Authors: Datta Sougata , Misra Santosh K. , Saha Manik Lal , Lahiri Nabajit , Louie Janis , Pan Dipanjan , Stang Peter J. 
Published: July 2018

Significance
Despite decades of research, the development of efficient strategies that can effectively deliver poorly water-soluble anticancer drugs remains a challenge. Hierarchical self-assembly strategy allows combining multiple therapeutic agents to produce a synergistic effect, thus enhancing the therapeutic efficacy. Herein we describe a hierarchical approach to solubilize a hydrophobic anticancer drug, curcumin in water via a combination of coordination-driven self-assembly and host–guest interactions. The water-soluble orthogonal self-assembly constructed by a hexagonal Pt(II) metallacycle, cucurbit[8]uril, and curcumin exhibited enhanced anticancer activity against melanoma and breast cancer cells compared with the corresponding precursors. This paper provides a platform for efficient delivery of hydrophobic anticancer drugs to cancer cells by the judicious implementation of multiple orthogonal interactions in a single process.
Liquid crystalline bacterial outer membranes are critical for antibiotic susceptibility
Authors: Paracini Nicolò , Clifton Luke A. , Skoda Maximilian W. A. , Lakey Jeremy H. 
Published: July 2018

Significance
Gram-negative bacteria possess an outer membrane (OM) which reduces antibiotic effectiveness. The OM has a dense outer layer of lipopolysaccharide (LPS), a glycolipid which is directly targeted by the last-resort antibiotic polymyxin B (PmB). However, we lack accurate molecular data on the PmB–OM interaction to inform future drug development. Here we study the PmB–OM interaction in vitro and show that in vivo results are reproduced only when the LPS is in a liquid crystalline phase, which occurs at body temperature. These findings not only explain the temperature dependence of PmB function but also support the notion that bacteria actively control the viscosity of their outer membranes as growth temperatures vary.
A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release
Authors: Alcaino Constanza , Knutson Kaitlyn R. , Treichel Anthony J. , Yildiz Gulcan , Strege Peter R. , Linden David R. , Li Joyce H. , Leiter Andrew B. , Szurszewski Joseph H. , Farrugia Gianrico , Beyder Arthur 
Published: July 2018

SignificanceMechanical forces are important for normal gastrointestinal tract function. The enterochromaffin cells in the gastrointestinal epithelium have been proposed, but not previously shown, to be specialized sensors that convert forces into serotonin release, and serotonin released from these cells is important for normal gastrointestinal secretion and motility. The findings in this study show that some enterochromaffin cells are indeed mechanosensitive, and that they use mechanosensitive Piezo2 channels to generate an ionic current that is critical for the intracellular Ca2+increase, serotonin release, and epithelial fluid secretion.
Indigenous impacts on North American Great Plains fire regimes of the past millennium
Authors: Roos Christopher I. , Zedeño María Nieves , Hollenback Kacy L. , Erlick Mary M. H. 
Published: July 2018

SignificanceThe relative importance of human activities and climate in shaping fire regimes is controversial. In North American grasslands, climate exerts strong top-down influences on fuels. For centuries before the introduction of the horse, Native American and First Nations hunters built and used landscape features on these grasslands to harvest bison en masse. Charcoal layers associated with drivelines indicate that fire was an important part of these hunting practices. Furthermore, correlation of dated fire deposits and climate records indicate that ancient bison hunters burned in response to favorable climate conditions. This study indicates that climate and human activities are not mutually exclusive factors in fire histories; even relatively small groups of hunter-gatherers can enhance climate impacts.