bluuebunny/crossref_metadata_2025_split huggingface dataset:
FAK Promotes Osteoblast Progenitor Cell Proliferation and Differentiation by Enhancing Wnt Signaling
Authors: Sun Chunhui , Yuan Hebao , Wang Li , Wei Xiaoxi , Williams Linford , Krebsbach Paul H , Guan Jun-Lin , Liu Fei 
Published: July 2016

ABSTRACT

Decreased bone formation is often associated with increased bone marrow adiposity. The molecular mechanisms that are accountable for the negative correlation between bone mass and bone marrow adiposity are incompletely understood. Focal adhesion kinase (FAK) has critical functions in proliferation and differentiation of many cell types; however, its roles in osteoblast lineage cells are largely unknown. We show herein that mice lacking FAK in Osterix-expressing cells exhibited decreased osteoblast number and low bone mass as well as increased bone marrow adiposity. The decreased bone mass in FAK-deficient mice was accounted for by decreased proliferation, compromised osteogenic differentiation, and increased adipogenic differentiation of bone marrow Osterix-expressing cells resulting from downregulation of Wnt/β-catenin signaling due to the reduced expression of canonical Wnt ligands. In contrast, FAK loss in calvarial preosteoblasts had no adverse effect on their proliferation and osteogenic differentiation and these cells had intact Wnt/β-catenin signaling. © 2016 American Society for Bone and Mineral Research.
Interpersonal Circumplex Profiles Of Persistent Depression: Goals, Self‐Efficacy, Problems, And Effects Of Group Therapy
Authors: Locke Kenneth D. , Sayegh Liliane , Penberthy J. Kim , Weber Charlotte , Haentjens Katherine , Turecki Gustavo 
Published: July 2016

ObjectivesWe assessed severely and persistently depressed patients’ interpersonal self‐efficacy, problems, and goals, plus changes in interpersonal functioning and depression during 20 weeks of group therapy.MethodOutpatients (32 female, 26 male, mean age = 45 years) completed interpersonal circumplex measures of goals, efficacy, and problems before completing 20 weeks of manualized group therapy, during which we regularly assessed depression and interpersonal style.ResultsCompared to normative samples, patients lacked interpersonal agency, including less self‐efficacy for expressive/assertive actions; stronger motives to avoid conflict, scorn, and humiliation; and more problems with being too submissive, inhibited, and accommodating. Behavioral Activation and especially Cognitive Behavioral Analysis System of Psychotherapy interventions produced improvements in depression and interpersonal agency, with increases in “agentic and communal” efficacy predicting subsequent decreases in depression.ConclusionsWhile severely and persistently depressed patients were prone to express maladaptive interpersonal dispositions, over the course of group therapy, they showed increasingly agentic and beneficial patterns of cognitions, motives, and behaviors.
Impact of Transporter Polymorphisms on Drug Development: Is It Clinically Significant?
Authors: McLean Cheynne , Wilson Aze , Kim Richard B. 
Published: July 2016

AbstractDrug transporters are becoming increasingly recognized as relevant to the drug development process. This may be a reflection of increasing target complexity and the need for high‐affinity interaction with drug targets that minimize off‐target side effects. Moreover, as new molecular entities (NMEs) become larger in size and amphipathic in nature, interaction with drug transporters, both uptake as well as efflux, becomes increasingly likely. In some cases transporters may limit the absorption or organ‐specific entry of NMEs, whereas in other cases transporters may enhance their absorption or tissue accumulation. Indeed, in some cases, transporters may prove to be a therapeutic target. Accordingly, a better understanding of potentially clinically relevant drug transporter polymorphisms earlier in the drug development process is highly desirable. In this review we examine key transporters that are important to the absorption, distribution, and excretion of a large number of drugs in clinical use. Importantly, we provide our assessment of the potential impact of known polymorphisms in such transporters and discuss whether there is sufficient evidence to incorporate these polymorphisms in the drug development process.
Role of Hepatic Drug Transporters in Drug Development
Authors: Liu Houfu , Sahi Jasminder 
Published: July 2016

AbstractHepatic drug transporters can play an important role in pharmacokinetics and the disposition of therapeutic drugs and endogenous substances. Altered function of hepatic drug transporters due to drug‐drug interactions (DDIs), genetic polymorphisms, and disease states can often result in a change in systemic and/or tissue exposure and subsequent pharmacological/toxicological effects of their substrates. Regulatory agencies including the US Food and Drug Administration, European Medicines Agency, and Japan Pharmaceuticals and Medical Devices Agency have issued guidance for industry on drug interaction studies, which contain comprehensive recommendations on in vitro and in vivo study tools and cutoff values to evaluate the DDI potential of new molecular entities mediated by hepatic drug transporters. In this report we summarize the latest regulatory and scientific progress of hepatic drug transporters in clinical DDIs, pharmacogenetics, drug‐induced liver injury (DILI), as well as methods for predicting transporter‐mediated pharmacokinetics and DDIs.
Use of PET Imaging to Evaluate Transporter‐Mediated Drug‐Drug Interactions
Authors: Langer Oliver 
Published: July 2016

AbstractSeveral membrane transporters belonging to the adenosine triphosphate‐binding cassette (ABC) and solute carrier (SLC) families can transport drugs and drug metabolites and thereby exert an effect on drug absorption, distribution, and excretion, which may potentially lead to transporter‐mediated drug‐drug interactions (DDIs). Some transporter‐mediated DDIs may lead to changes in organ distribution of drugs (eg, brain, liver, kidneys) without affecting plasma concentrations. Positron emission tomography (PET) is a noninvasive imaging method that allows studying of the distribution of radiolabeled drugs to different organs and tissues and is therefore the method of choice to quantitatively assess transporter‐mediated DDIs on a tissue level. There are 2 approaches to how PET can be used in transporter‐mediated DDI studies. When the drug of interest is a potential perpetrator of DDIs, it may be administered in unlabeled form to assess its influence on tissue distribution of a generic transporter‐specific PET tracer (probe substrate). When the drug of interest is a potential victim of DDIs, it may be radiolabeled with carbon‐11 or fluorine‐18 and used in combination with a prototypical transporter inhibitor (eg, rifampicin). PET has already been used both in preclinical species and in humans to assess the effects of transporter‐mediated DDIs on drug disposition in different organ systems, such as brain, liver, and kidneys, for which examples are given in the present review article. Given the growing importance of membrane transporters with respect to drug safety and efficacy, PET is expected to play an increasingly important role in future drug development.
Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans
Authors: Momper Jeremiah D. , Tsunoda Shirley M. , Ma Joseph D. 
Published: July 2016

AbstractDrug transporters are present in various tissues and have a significant role in drug absorption, distribution, and elimination. The International Transporter Consortium has identified 7 transporters of increasing importance from evidence of clinically significant transporter‐mediated drug–drug interactions. The transporters are P‐glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter 2, organic anion transporters (OAT) 1, and OAT3. Decision trees were created based on in vitro experiments to determine whether an in vivo transporter‐mediated drug–drug interaction study is needed. Phenotyping is a methodology that evaluates real‐time in vivo transporter activity, whereby changes in a probe substrate or probe inhibitor reflect alternations in the activity of the specified transporter. In vivo probe substrates and/or probe inhibitors have been proposed for each aforementioned transporter. In vitro findings and animal models provide the strongest evidence regarding probe specificity. However, such findings have not conclusively correlated with human phenotyping studies. Furthermore, the extent of contribution from multiple transporters in probe disposition complicates the ability to discern if study findings are the result of a specific transporter and thus provide a recommendation for a preferred probe for a drug transporter.
Effect of technological factors on the activity and losses of cathepsins B, D and L during the marinating of Atlantic and Baltic herrings
Authors: Szymczak Mariusz 
Published: July 2016

AbstractBACKGROUNDThis study analyzes the effect of salt and acetic acid concentration, time, temperature and fish freezing on the activity and losses of cathepsins during the marinating of Atlantic and Baltic herrings.RESULTSThe highest contribution to meat general proteolytic activity was found for cathepsin D‐like activity. This contribution decreased during the marinating process as a result of, among other things, cathepsin losses to brine. The methods of marinating had a significant impact on cathepsin activity losses. The average ratio of cathepsin D‐like activity to L and B in brine accounted for 15:3.5:1.5, respectively. Depending on the method of calculation, cathepsin activity in brine was similar (per gram of tissue/milliliter of brine) or multiply higher (per gram protein in tissue/brine) than in the marinated herring meat. Statistical analysis demonstrated that the extent and structure of cathepsin losses were significantly correlated with the quantitative and qualitative composition of protein hydrolysis products in marinades.CONCLUSIONThe presented results depict new phenomena of cathepsin losses and explain their impact on the process of fish marinating. Results allow better optimization of the process of meat ripening. The high activity of aspartyl and cysteine cathepsins in brine indicates the real feasibility of their application in the food industry for novel food design. © 2016 Society of Chemical Industry
Novel use of non‐ablative fractional photothermolysis for café‐au‐lait macules in darker skin types
Authors: Balaraman Brundha , Ravanfar‐Jordan Parisa , Friedman Paul M. 
Published: July 2016

ImportanceThe removal of café‐au‐lait macules (CALMs) in patients with darker skin phototypes poses a significant challenge due to limited available therapeutic options and increased risk of adverse effects, including permanent scarring and further dyspigmentation. Herein, we demonstrate the novel use of non‐ablative fractional photothermolysis for the safe removal of CALMs in individuals with Fitzpatrick skin type (FST) IV–V.ObservationsRetrospective analysis of four patients (FST IV–V) with CALMs revealed that three of these patients had greater than 50% clearance after multiple treatment sessions with the non‐ablative fractional 1,550‐nm erbium‐doped fiber laser.Conclusions and RelevanceThis report demonstrates the utility and safety of non‐ablative fractional resurfacing in the treatment of CALMs in darker skin phototypes. Lasers Surg. Med. 49:84–87, 2017. © 2016 Wiley Periodicals, Inc.
Enhancement of light absorption by blood to Nd:YAG laser using PEG‐modified gold nanorods
Authors: Xing Linzhuang , Li Dong , Chen Bin , Dai Yuze , Wu Wenjuan , Wang Guoxiang 
Published: July 2016

Background and ObjectiveOn the basis of the principle of selective photothermolysis, laser therapy has been the most effective treatment strategy for Port‐wine stains (PWSs) caused by the expansion of dermal capillaries. Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser at 1064 nm wavelength has great potential for deeply buried PWS, although its application is limited because of its weak absorption by blood. The purpose of this study is to investigate the effect of PEG‐modified gold nanorods (NRs) on the blood absorption enhancement for Nd:YAG laser.Materials and MethodsPEG‐modified gold nanorods (NRs) were synthesized via the seeded growth method. Then, the effect of PEG‐modified gold NRs on blood light absorbance was investigated through adding different concentration of PEG‐modified gold NRs to 1 ml of blood at room temperature. Finally, the optical properties of whole mice blood with or without PEG‐modified gold NRs under slow heating were investigated.ResultsThe average length and width of PEG‐modified gold NRs are 79.5 ± 10.5 and 13.5 ± 0.9 nm, respectively, with the aspect ratio of 5.89, and a strong absorption peak exists at ∼1050 nm in the near‐infrared range. A linear correlation between the blood absorbance at 1064 nm and the amount of PEG‐modified gold NRs was obtained. The absorbance at 1064 nm increased 17.6, 33.0, 48.3, and 65.4 times when 0.4, 0.8, 1.2, and 1.6 mg of PEG‐modified gold NRs was added to 1 ml of blood at room temperature, respectively. After adding 0.8 mg of PEG‐modified gold NRs to 1 ml of blood, blood absorbance at 1064 nm at different temperatures increased by an average of 24.0 times. After intravenously injecting PEG‐modified gold NRs (0.87 mg/ml) into Sprague–Dawley mice, the blood absorbance at 1064 nm increased from 0.014 to 0.5.ConclusionOur findings suggest that PEG‐modified gold NRs injection is an efficient way to enhance light absorption by blood to Nd:YAG laser. Lasers Surg. Med. 48:790–803, 2016. © 2016 Wiley Periodicals, Inc.
Achievement of Release Mode under Combinational Stimuli by Acid and Reduction for Reduced Adverse Effect in Antitumor Efficacy
Authors: Song Meifang , Xue Yanan , Lin Xiao , Xia Xiaoyang , Chen Lidi , Zhang Liujie , Yu Bo , Long Sihui , Huang Shiwen , Yu Faquan 
Published: July 2016

To reduce the adverse effect in antitumor therapy, a superparamagnetic doxorubicin (DOX)‐loaded nanogel with the release mode under the combinational stimuli present in intracellular environments of solid tumors is presented. Dextran is first modified to involve both thiol groups and carboxyl groups. The dextran derivative is then covalently coupled with previously thiolated and aminated magnetic iron oxide nanoparticles through both the linkage of disulfide bond and electrostatic interaction. Upon the optimal conditions, a nanogel is fabricated via the dual cross‐linking. The nanogel features the targeting release under combinational stimuli by acid and reduction environment with low release level in healthy tissues. In vitro release profiles reveal these release modes as expected. Cytotoxicity assay exhibits a much lower toxicity of the DOX‐loaded nanogel to COS‐7 cells than free DOX. Prussian blue staining and confocal laser scanning microscopy observation reveal the cellular uptake and subcellular release in nuclei of the nanogel. In vivo study exhibits that the nanogel presented 67.3% of inhibition rate of tumor growth and a healthy appearance. The present nanogel expresses high efficacy with low systemic adverse effect and is thus believed to offer a promising candidate for highly effective cancer therapy.image
Nanomarketing: A New Frontier for Neuromarketing
Authors: Mileti Antonio , Guido Gianluigi , Prete M. Irene 
Published: July 2016

ABSTRACTThe emergence of neuromarketing has significantly advanced conventional marketing research, illuminating how unconscious responses and emotions impact consumers’ perceptions and decision‐making processes. Neuromarketing is founded on the assumption that individual sensory and motor systems can be identified in specific networks of brain cells, the observation of which can reveal the unconscious or emotional characteristics of consumer decision making. Yet, neuromarketing technologies present several limitations that can impede the extension and validation of their application: (i) the development of high‐priced and time‐restricted neuroimaging experiments; (ii) the employment of large and immovable devices confined to artificial laboratory environments; (iii) the use of a single neuroimaging technology at a time (usually the functional magnetic resonance imaging); (iv) the use of a single nonneuroimaging device at a time; and (v) the potentially unethical manipulation of research subjects. One way to address these issues involves nanotechnologies, which present a ground‐breaking opportunity for neuromarketing research. These technologies encompass not only the traditional notion of structures, devices, and systems created by limiting shape and size at the nanometer scale, but also the new miniaturized tools based on one or more nanocomponents. The integration of neuromarketing and nanotechnologies could start a new field of research, which is termed here nanomarketing. Nanomarketing makes it possible to: (i) carry out noninvasive and nonintrusive experiments in shopping places; (ii) monitor consumers’ mental processes in real time; (iii) combine different technologies to corroborate results obtained by different neuroscientific tools; (iv) integrate neurophysiological field indicators with laboratory neuroimaging results; and (v) highlight ethical issues raised by the use of these novel, portable, and easy‐to‐use nanodevices. This study thus has a twofold aim: (i) investigating both the limitations and opportunities, for researchers and practitioners, that accompany the miniaturization process and application of nanotechnologies to neuromarketing; and (ii) providing a critical review of the aforementioned limitations, highlighting the theoretical and managerial implications, and summarizing the discussion for future research.
Quantitative gait analysis in parkin disease: Possible role of dystonia
Authors: Castagna Anna , Frittoli Serena , Ferrarin Maurizio , Del Sorbo Francesca , Romito Luigi M. , Elia Antonio E. , Albanese Alberto 
Published: July 2016

ABSTRACTIntroductionParkin disease (PARK2, OMIM 602544) is an autosomal‐recessive early‐onset parkinsonism characterized by an early occurrence of lower limb dystonia. The aim of this study was to analyze spatiotemporal, kinematic, and kinetic gait parameters in patients with parkin disease in the OFF and ON conditions compared to healthy age‐matched controls.MethodsFifteen patients with parkin disease and 15 healthy age‐matched controls were studied in a gait analysis laboratory with an integrated optoelectronic system. Spatiotemporal, kinematic, and kinetic gait parameters at a self‐selected speed were recorded in the OFF and ON conditions. A jerk index was computed to quantify the possible reduction of smoothness of joint movements.ResultsCompared to controls, parkin patients had, either in the OFF or in the ON conditions, significant reduction of walking velocity, increased step width, and decreased percentage of double support. Kinematic analysis in both conditions showed: increased ankle dorsiflexion and knee flexion at the initial contact; maximal flexion and increased range of motion in mid stance; increased hip flexion and max extension in stance at pelvis; and increased mean tilt antiversion. Kinetics showed increased hip and knee power generation in stance in either condition. The jerk index was increased at all joints both in OFF and ON. There were no correlations between individual gait parameters and clinical ratings.ConclusionParkin patients have an abnormal gait pattern that does not vary between the OFF and the ON conditions. Variations recorded with instrumented analysis are more evident for kinematic than kinetic parameters at lower limbs. Severity of dystonia does not correlate with any individual kinematic parameter. © 2016 International Parkinson and Movement Disorder Society
Cellular infiltrates in skin and sural nerve of patients with polyneuropathies
Authors: Üçeyler Nurcan , Braunsdorf Silvia , Kunze Ekkehard , Riediger Nadja , Scheytt Sarah , Divisova Šarka , Bekircan‐kurt Can Ebru , Toyka Klaus Viktor , Sommer Claudia 
Published: July 2016

ABSTRACTIntroductionThe aim of this study was to determine the diagnostic usefulness of skin punch biopsies with emphasis on visualization and quantification of T‐cells and macrophages in patients with polyneuropathies. Methods: We quantified inflammatory cells in skin samples (lower leg, upper thigh) in 187 patients and compared data with counts in their sural nerve biopsies and with skin biopsies from 32 healthy volunteers. Results: Vessel‐bound T‐cells and macrophages were increased in proximal and distal skin samples of neuropathy patients compared with controls (P < 0.001 in both). Patients with vasculitic neuropathy had increased T‐cell and macrophage counts in distal skin compared with controls (P < 0.01; for scattered macrophages/mm2 diagnostic sensitivity 71% and specificity 79%). In patients with vasculitic neuropathy, distal skin perivascular inflammatory cell counts also correlated with those in sural nerve biopsies (P < 0.001). Conclusion: Neuropathy per se may lead to skin inflammation. In cases of possible vasculitic neuropathy, skin biopsy may be an additional tool to support the diagnosis. Muscle Nerve 55: 884–893, 2017
Erdöl in seine Bestandteile zerlegen und charakterisieren
Authors: Zimmermann Ralf , Saraji‐Bozorgzad Mohammad , Grimmer Christoph , Ulbrich Anne , Streibel Thorsten 
Published: July 2016

AbstractErdöl ist eine komplexe Mischung mit vielen Komponenten. Informationen über seine Zusammensetzung liefert die Kopplung von Thermoanalyse und Massenspektrometrie. Damit die Massenspektren interpretierbar bleiben, sind weiche Ionisierungsmethoden erforderlich, welche die Moleküle nicht zu stark fragmentieren.
Frequency and outcome of pediatric acute lymphoblastic leukemia with ZNF384 gene rearrangements including a novel translocation resulting in an ARID1B/ZNF384 gene fusion
Authors: Shago Mary , Abla Oussama , Hitzler Johann , Weitzman Sheila , Abdelhaleem Mohamed 
Published: July 2016

AbstractBackgroundZNF384 gene rearrangements with multiple partner genes are recurrent in acute leukemia and are most often associated with a precursor B cell immunophenotype. The overall incidence of this genetic category of leukemia is uncertain.ProcedurePatients with ZNF384 gene rearrangements from a cohort of 240 precursor B cell acute lymphoblastic leukemia (ALL) pediatric patients over a 3.5‐year time period were characterized with detailed cytogenetic, FISH, genomic, and clinical analyses.ResultsSeven of the 240 patients were identified to have ZNF384 gene rearrangements including partner genes TCF3 (four patients), EWSR1 (one patient), EP300 (one patient), and the novel gene partner ARID1B (one patient). The translocations were confirmed by FISH analysis and with RNA sequencing for the EP300 and ARID1B partner genes. Genomic microarray analysis showed an average of 2.7 copy number alterations in each case with no evidence of imbalance at the translocation breakpoints. Six of the patients with ZNF384 gene rearrangements had precursor B cell ALL with a CD10– immunophenotype and myeloid‐associated antigens. One of the patients also had myeloperoxidase expression and was diagnosed as mixed phenotype B/myeloid acute leukemia. None of the patients have relapsed with event‐free survival ranging from 6 years 2 months to 9 years 2 months.ConclusionsThis study suggests that the frequency of ZNF384 gene rearrangement in pediatric precursor B cell ALL is approximately 3%. The ARID1B gene, commonly mutated in multiple types of cancer, was identified as an additional ZNF384 gene fusion partner.