bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and classification of microcalcification from digital mammograms with firefly algorithm, extreme learning machine and non‐linear regression models: A comparison
Authors: Sannasi Chakravarthy S. R. , Rajaguru Harikumar 
Published: August 2019

AbstractIn this study, abnormalities in medical images are analysed using three classifiers, and the results are compared. Breast cancer remains a major public health problem among women worldwide. Recently, many algorithms have evolved for the investigation of breast cancer diagnosis through medical imaging. A computer‐aided microcalcification detection method is proposed to categorise the nature of breast cancer as either benign or malignant from input mammogram images. The standard mammogram image corpus, the Mammogram Image Analysis Society database is utilised, and feature extraction is performed using five different wavelet families at level 4 and level 6 decomposition. The work is accomplished through firefly algorithm (FA), extreme learning machine (ELM) and least‐square‐based non‐linear regression (LSNLR) classifiers. The performance of the classifiers is compared by benchmark metrics, such as total error rate, specificity, sensitivity, area under the receiver operating characteristic curve, precision, F1 score and the Matthews correlation coefficient. As validation of the classifier results, a kappa analysis is included to determine the agreement among classifiers. The LSNLR classifier attains a 3% to 7% improvement in average accuracy compared with the average classification accuracy of the FA (86.75%) and ELM (90.836%) classifiers.
Injectable pegylated niclosamide (polyethylene glycol‐modified niclosamide) for cancer therapy
Authors: Ma Rui , Ma Zhen‐Gang , Gao Jin‐Lai , Tai Yu , Li Lan‐Jun , Zhu Hai‐Bin , Li Li , Dong De‐Li , Sun Zhi‐Jie 
Published: August 2019

AbstractNiclosamide is an antihelminthic drug. Recent studies show that niclosamide exerts antitumor activity through inhibiting multiple signals including Wnt/β‐catenin, mTORC1, signal transducer and activator of transcription 3, NF‐κB, notch signals; however, the insolubility and poor bioavailability limits its potential clinic use, the aim of the present work is to synthesize an injectable pegylated niclosamide (polyethylene glycol‐modified niclosamide) and investigate its antitumor activity in vitro and in vivo. The pegylated niclosamide (mPEG5000‐Nic) was synthesized and the chemical structure was identified by Fourier transform infrared spectra and 1H nuclear magnetic resonance spectra. The antitumor activity was evaluated in CT26 and HCT116 colon cancer cells in vitro and nude mouse xenograft model of CT26 cells in vivo. The water solubility of niclosamide in mPEG5000‐Nic was significantly increased. Niclosamide could be released from mPEG5000‐Nic nanoparticles in PBS solution. mPEG5000‐Nic inhibited the cell viability of CT26 and HCT116 cells in vitro. No animal death was observed in mice with intraperitoneal injection of mPEG5000‐Nic (equivalent to 1000 mg/kg niclosamide) within 24 hr, indicating that mPEG5000‐Nic was less toxic. In nude mouse, xenograft model of CT26 colon carcinoma, intraperitoneal injection of mPEG5000‐Nic (equivalent to niclosamide 50 mg/kg) inhibited tumor growth but had no effect on animal body weight and heart, liver, kidney, and lung weight in vivo. Meanwhile, in the same model, intraperitoneal injection of the positive clinic drug 5‐fluorouracil not only inhibited the tumor growth, but also reduced the animal body weight. Our study demonstrates that pegylated niclosamide is novel niclosamide delivery system with clinical perspective for cancer therapy.
Development and temperature gradient online monitoring of a vehicular rotary solid‐state bioreactor: a novel device for large‐scale preparation of Aspergillus niger spore inoculum
Authors: Zhang Xiaoran , Jiang Wenxia 
Published: August 2019

AbstractBACKGROUNDMechanical cultivation of Aspergillus niger spores at industrial scales as the fermentationinoculum in citric acid plants is difficult to achieve: in solid‐state cultivation, intense mechanical agitation or continuous mixing to reduce damage to the filamentous microbes is not feasible, but inadequate mixing or static cultivation would cause serious inner‐bed temperature gradients. It is therefore necessary to develop novel bioreactors coordinating the conflict between microbe protection and heat transfer, by globally investigating the inner‐bed temperature profile, an investigation that has not been reported upon previously.RESULTSA novel vehicular rotary solid‐state bioreactor was developed combining the characteristics of both a vertical packed bed and a horizontal rotating drum. Moderate and intermittent rotary mixing based on the characteristic posture‐shifting function ensured high spore yields of 3.1 × 1012 per batch (22‐cm‐thick bed, using a rich medium) and 1.3 × 1012 per batch (15‐cm‐thick bed, using a poor medium and two‐stage temperature control strategy). The two‐stage temperature control strategy effectively depressed the upper limit of bed temperature under 37.0 °C. A 16‐point temperature measuring system provided online 4D data of the culture bed including time, temperature, radius and height, globally displaying the inner‐bed temperature gradients. A cylindrical air distributor benefits inner bed radial air flow distribution, but did not affect the spore yield and average moisture content of the solid culture.CONCLUSIONSThe novel devices and methods realized large‐scale production of A. niger spores by coordinating moderate mixing and inner bed temperature field monitoring and control; they also possessed application value for other filamentous microbes. © 2019 Society of Chemical Industry
Dynamic Network Analysis of Negative Emotions and DSM‐5 Posttraumatic Stress Disorder Symptom Clusters During Conflict
Authors: Greene Talya , Gelkopf Marc , Fried Eiko I. , Robinaugh Donald J. , Lapid Pickman Liron 
Published: August 2019

AbstractInvestigating dynamic associations between specific negative emotions and PTSD symptom clusters may provide novel insights into the ways in which PTSD symptoms interact with, emerge from, or are reinforced by negative emotions. The present study estimated the associations among negative emotions and the four DSM‐5 PTSD symptom clusters (intrusions, avoidance, negative alterations in cognitions and mood [NACM], and arousal) in a sample of Israeli civilians (n = 96) during the Israel–Gaza War of July–August 2014. Data were collected using experience sampling methodology, with participants queried via smartphone about PTSD symptoms and negative emotions twice a day for 30 days. We used a multilevel vector auto‐regression model to estimate temporal and contemporaneous temporal networks. Contrary to our hypothesis, in the temporal network, PTSD symptom clusters were more predictive of negative emotions than vice versa, with arousal emerging as the strongest predictor that negative emotions would be reported at the next measurement point; fear and sadness were also strong predictors of PTSD symptom clusters. In the contemporaneous network, negative emotions exhibited the strongest associations with the NACM and arousal PTSD symptom clusters. The negative emotions of sadness, stress, fear, and loneliness had the strongest associations to the PTSD symptom clusters. Our findings suggest that arousal has strong associations to both PTSD symptoms and negative emotions during ongoing trauma and highlights the potentially relevant role of arousal for future investigations in primary or early interventions.
Evaluation of a membrane hybridization array for detection of Mycobacterium tuberculosis complex and resistance to isoniazid and rifampin in sputum specimens, mycobacterial liquid cultures, and clinical isolates
Authors: Chen Chao‐Ju , Yang Yuan‐Chieh , Huang Hsin‐Hui , Chang Tsung Chain , Lu Po‐Liang 
Published: August 2019

AbstractThe gold standard of antituberculosis susceptibility testing is based on culture method which takes weeks. Rapid detection of resistance to isoniazid (INH) and rifampin (RIF) to avoid inappropriate regimens and to prevent transmission of resistant strains are important. A membrane array (BluePoint MTBDR) was developed to identify Mycobacterium tuberculosis complex (MTBC) and the genetic mutations responsible for resistance to RIF and INH. We aimed to evaluate the performance of this array for diagnosing drug‐resistant MTBC. A total of 261 acid‐fast bacilli positive sputum specimens, 1025 positive mycobacteria growth indicator tube (MGIT) cultures and 544 clinical isolates were analyzed. Antituberculosis susceptibility testing was the gold standard and was performed on MTBC isolated from positive MGIT cultures and on 544 clinical isolates. The sensitivity and specificity of the array to detect MTBC were 62.2% and 88.1% for sputum specimens, 100% and 97.9% for MGIT cultures. For detection of drug‐resistant MTBC in positive MGIT tubes, the sensitivities of the array were 100% for RIF and 97.1% for INH, while the specificities were 99.7% and 100%, respectively. Interestingly, we noticed four genotypically RIF‐resistant but phenotypically RIF‐susceptible isolates and eight genotypically INH resistant but phenotypically INH‐susceptible isolates. Comparing with conventional culture methods for species identification and drug susceptibility testing, the BluePoint MTBDR assay demonstrated to be a rapid test with high sensitivity and specificity to identify MTBC and to detect isoniazid and rifampin resistance when it is applied to broth culture specimens and clinical isolates.
Antitumor effect of insulin‐like growth factor‐1 receptor inhibition in head and neck squamous cell carcinoma
Authors: Lehman Christine E. , Khalil Ashraf A. , Axelrod Mark J. , Dougherty Michael I. , Schoeff Stephen S. , Taniguchi Linnea E. , Mendez Rolando E. , David Abel P. , McGarey Patrick O. , Hubbard Matthew A. , Donaldson Lane , Frierson Henry F. , Stelow Edward B. , Bekiranov Stefan , Wulfkuhle Julia D. , Petricoin Emanuel F. , Gioeli Daniel G. , Jameson Mark J. 
Published: August 2019

ObjectivesThe insulin‐like growth factor‐1 receptor (IGF1R) has been implicated in therapeutic resistance in head and neck squamous cell carcinoma (HNSCC), and small molecule tyrosine kinase inhibitors (TKIs) of IGF1R activity may have anticancer activity. Therefore, the relationship between survival and IGF1R expression was assessed for oral cavity (OC) cancer, and the antitumor effects of two IGF1R‐TKIs, OSI‐906 and BMS‐754807, were evaluated in HNSCC cell lines in vitro.MethodsClinical outcome data and tissue microarray immunohistochemistry were used to generate IGF1R expression‐specific survival curves. Immunoblot, alamarBlue proliferation assay, trypan blue exclusion viability test, clonogenic assay, flow cytometry, and reverse phase protein array (RPPA) were used to evaluate in vitro responses to IGF1R‐TKIs.ResultsFor patients with stage III/IV OCSCC, higher IGF1R expression was associated with poorer overall 5‐year survival (P = 0.029). Both BMS‐754807 and OSI‐906 caused dose‐dependent inhibition of IGF1R and Akt phosphorylation and inhibited proliferation; BMS‐754807 was more potent than OSI‐906. Both drugs reduced HNSCC cell viability; only OSI‐906 was able to eliminate all viable cells at 10 μM. The two drugs similarly inhibited clonogenic cell survival. At 1 μM, only BMS‐754807 caused a fourfold increase in the basal apoptotic rate. RPPA demonstrated broad effects of both drugs on canonical IGF1R signaling pathways and also inhibition of human epidermal growth factor receptor‐3 (HER3), Src, paxillin, and ezrin phosphorylation.ConclusionOSI‐906 and BMS‐754807 inhibit IGF1R activity in HNSCC cell lines with reduction in prosurvival and proliferative signaling and with concomitant antiproliferative and proapoptotic effects. Such antagonists may have utility as adjuvants to existing therapies for HNSCC.Level of EvidenceNA Laryngoscope, 130:1470–1478, 2020
3D Printing of Silk Protein Structures by Aqueous Solvent‐Directed Molecular Assembly
Authors: Mu Xuan , Wang Yu , Guo Chengchen , Li Yamin , Ling Shengjie , Huang Wenwen , Cebe Peggy , Hsu Huan‐Hsuan , De Ferrari Fabio , Jiang Xiaocheng , Xu Qiaobing , Balduini Alessandra , Omenetto Fiorenzo G. , Kaplan David L. 
Published: August 2019

AbstractHierarchical molecular assembly is a fundamental strategy for manufacturing protein structures in nature. However, to translate this natural strategy into advanced digital manufacturing like three‐dimensional (3D) printing remains a technical challenge. This work presents a 3D printing technique with silk fibroin to address this challenge, by rationally designing an aqueous salt bath capable of directing the hierarchical assembly of the protein molecules. This technique, conducted under aqueous and ambient conditions, results in 3D proteinaceous architectures characterized by intrinsic biocompatibility/biodegradability and robust mechanical features. The versatility of this method is shown in a diversity of 3D shapes and a range of functional components integrated into the 3D prints. The manufacturing capability is exemplified by the single‐step construction of perfusable microfluidic chips which eliminates the use of supporting or sacrificial materials. The 3D shaping capability of the protein material can benefit a multitude of biomedical devices, from drug delivery to surgical implants to tissue scaffolds. This work also provides insights into the recapitulation of solvent‐directed hierarchical molecular assembly for artificial manufacturing.
Redox Polymer–Based Nano‐Objects via Polymerization‐Induced Self‐Assembly
Authors: Boujioui Fadoi , Zhuge Flanco , Gohy Jean‐François 
Published: August 2019

AbstractPoly(2,2,6,6‐tetramethylpiperidinyloxy‐4‐yl‐methacrylate) (PTMA) redox polymer–based nano‐objects are synthesized by polymerization‐induced self‐assembly with poly[oligo(ethylene glycol) methyl ether methacrylate] and poly[(4‐methacryloyloxy)‐2,2,6,6‐tetramethylpiperidinium chloride] as hydrophilic macro‐chain transfer agents. These hydrophilic blocks are used in order to stabilize hydrophobic PTMA blocks in aqueous medium. The accordingly obtained spherical nano‐objects are observed via transmission electron microscopy analysis. Cyclic voltammetry measurements indicate that the nature and the length of coronal blocks influence the redox process of the PTMA core blocks. Moreover, these electroactive nano‐objects display low viscosities with a shear‐thinning behavior, making them suitable as cathode‐active materials for aqueous flow‐assisted electrochemical systems.
Biofabrication of Gelatin Tissue Scaffolds with Uniform Pore Size via Microbubble Assembly
Authors: Bayram Cem , Jiang Xinyue , Gultekinoglu Merve , Ozturk Sukru , Ulubayram Kezban , Edirisinghe Mohan 
Published: August 2019

AbstractThe control of pore size and uniform porosity remains as an important challenge in gelatin scaffolds. The precise control in building blocks of tissue scaffolds without any additional porogen is possible with costly equipment and techniques, though some pre‐requirements for polymeric material, such as photo‐polymerizability or sintering ability, may be needed prior to construction. Herein, a method for the fabrication of gelatin scaffolds with homogenous porosity using simple T‐junction microfluidics is described. The size of the microbubbles is precisely controlled with 5% deviation from the average. Porous gelatin scaffolds are obtained by building‐up the monodispersed microbubbles in dilute cross‐linker solutions. The effect of cross‐linker density on pore diameter is also investigated. After cross‐linking, pore size of the resultant five scaffold groups are precisely controlled as 135 ± 11, 193 ± 11, 216 ± 9, 231 ± 5, and 250 ± 12 µm. Porosity ratios above 65% are achieved in every sample group. According to the cell culture experiments, structures support high cell adhesion, viability, and migration through the porous network via interconnectivity. This study offers a practical and economical approach for the preparation of porous gelatin scaffolds with homogenous porosity which can be utilized in diverse tissue engineering applications.
Cortical network fingerprints predict deep brain stimulation outcome in dystonia
Authors: Gonzalez‐Escamilla Gabriel , Muthuraman Muthuraman , Reich Martin M. , Koirala Nabin , Riedel Christian , Glaser Martin , Lange Florian , Deuschl Günther , Volkmann Jens , Groppa Sergiu 
Published: August 2019

AbstractBackgroundDeep brain stimulation (DBS) is an effective evidence‐based therapy for dystonia. However, no unequivocal predictors of therapy responses exist. We investigated whether patients optimally responding to DBS present distinct brain network organization and structural patterns.MethodsFrom a German multicenter cohort of 82 dystonia patients with segmental and generalized dystonia who received DBS implantation in the globus pallidus internus, we classified patients based on the clinical response 3 years after DBS. Patients were assigned to the superior‐outcome group or moderate‐outcome group, depending on whether they had above or below 70% motor improvement, respectively. Fifty‐one patients met MRI‐quality and treatment response requirements (mean age, 51.3 ± 13.2 years; 25 female) and were included in further analysis. From preoperative MRI we assessed cortical thickness and structural covariance, which were then fed into network analysis using graph theory. We designed a support vector machine to classify subjects for the clinical response based on individual gray‐matter fingerprints.ResultsThe moderate‐outcome group showed cortical atrophy mainly in the sensorimotor and visuomotor areas and disturbed network topology in these regions. The structural integrity of the cortical mantle explained about 45% of the DBS stimulation amplitude for optimal response in individual subjects. Classification analyses achieved up to 88% of accuracy using individual gray‐matter atrophy patterns to predict DBS outcomes.ConclusionsThe analysis of cortical integrity, informed by group‐level network properties, could be developed into independent predictors to identify dystonia patients who benefit from DBS. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Tremor habituation to deep brain stimulation: Underlying mechanisms and solutions
Authors: Fasano Alfonso , Helmich Rick C. 
Published: August 2019

AbstractDBS of the ventral intermediate nucleus is an extremely effective treatment for essential tremor, although a waning benefit is observed after a variable time in a variable proportion of patients (ranging from 0% to 73%), a concept historically defined as “tolerance.” Tolerance is currently an established concept in the medical community, although there is debate on its real existence. In fact, very few publications have actually addressed the problem, thus making tolerance a typical example of science based on “eminence rather than evidence.” The underpinnings of the phenomena associated with the progressive loss of DBS benefit are not fully elucidated, although the interplay of different—not mutually exclusive—factors has been advocated. In this viewpoint, we gathered the evidence explaining the progressive loss of benefit observed after DBS. We grouped these factors in three categories: disease‐related factors (tremor etiology and progression); surgery‐related factors (electrode location, microlesional effect and placebo); and stimulation‐related factors (not optimized stimulation, stimulation‐induced side effects, habituation, and tremor rebound). We also propose possible pathophysiological explanations for the phenomenon and define a nomenclature of the associated features: early versus late DBS failure; tremor rebound versus habituation (to be preferred over tolerance). Finally, we provide a practical approach for preventing and treating this loss of DBS benefit, and we draft a possible roadmap for the research to come. © 2019 International Parkinson and Movement Disorder Society
Potential Interplay between Dietary Saturated Fats and Genetic Variants of the NLRP3 Inflammasome to Modulate Insulin Resistance and Diabetes Risk: Insights from a Meta‐Analysis of 19 005 Individuals
Authors: Murphy Aoife M. , Smith Caren E. , Murphy Leanne M. , Follis Jack L. , Tanaka Toshiko , Richardson Kris , Noordam Raymond , Lemaitre Rozenn N. , Kähönen Mika , Dupuis Josée , Voortman Trudy , Marouli Eirini , Mook‐Kanamori Dennis O. , Raitakari Olli T. , Hong Jaeyoung , Dehghan Abbas , Dedoussis George , de Mutsert Renée , Lehtimäki Terho , Liu Ching‐Ti , Rivadeneira Fernando , Deloukas Panagiotis , Mikkilä Vera , Meigs James B. , Uitterlinden Andre , Ikram Mohammad A. , Franco Oscar H. , Hughes Maria , O' Gaora Peadar , Ordovás José M. , Roche Helen M. 
Published: August 2019

ScopeInsulin resistance (IR) and inflammation are hallmarks of type 2 diabetes (T2D). The nod‐like receptor pyrin domain containing‐3 (NLRP3) inflammasome is a metabolic sensor activated by saturated fatty acids (SFA) initiating IL‐1β inflammation and IR. Interactions between SFA intake and NLRP3‐related genetic variants may alter T2D risk factors.MethodsMeta‐analyses of six Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 19 005) tested interactions between SFA and NLRP3‐related single‐nucleotide polymorphisms (SNPs) and modulation of fasting insulin, fasting glucose, and homeostasis model assessment of insulin resistance.ResultsSFA interacted with rs12143966, wherein each 1% increase in SFA intake increased insulin by 0.0063 IU mL−1 (SE ± 0.002, p = 0.001) per each major (G) allele copy. rs4925663, interacted with SFA (β ± SE = −0.0058 ± 0.002, p = 0.004) to increase insulin by 0.0058 IU mL−1, per additional copy of the major (C) allele. Both associations are close to the significance threshold (p < 0.0001). rs4925663 causes a missense mutation affecting NLRP3 expression.ConclusionTwo NLRP3‐related SNPs showed potential interaction with SFA to modulate fasting insulin. Greater dietary SFA intake accentuates T2D risk, which, subject to functional validation, may be further elaborated depending on NLRP3‐related genetic variants.
Lactobacillus and Bifidobacterium Improves Physiological Function and Cognitive Ability in Aged Mice by the Regulation of Gut Microbiota
Authors: Ni Yinhua , Yang Xin , Zheng Liujie , Wang Zhe , Wu Lianxin , Jiang Jinlu , Yang Tianqi , Ma Lingyan , Fu Zhengwei 
Published: August 2019

ScopeAge‐related degeneration is associated with imbalances of gut microbiota and its related immune system, thus gut microbiota dysbiosis is considered to be a key target to improve senescence. The potential roles of probiotics on physiological function and cognitive ability in aged mice are investigated in this study.Methods and resultsLactobacillus casei LC122 or Bifidobacterium longum BL986, are orally administrated for 12 weeks, and the anti‐aging effects, as well as the composition and function of gut microbiota, are investigated in aged mice. Probiotics supplementation ameliorates hepatic lipid accumulation, enhances muscle strength and function, attenuates oxidative stress and inflammation in peripheral tissues, and improves gut barrier function. These results are associated with improved learning and memory ability as assessed by behavioral tests and upregulation of neurodegenerative and neurotrophic factors expressions in hippocampus. Moreover, the diversity and composition of gut microbiota are altered in aged mice, and both probiotics treatment display distinguished features of gut microbiota. Comparisons of two probiotic strains reveal significant differences in the taxa at family and genus level, leading to the functional profile change of the microbial community.ConclusionL. casei LC122 and B. longum BL986 might be used as novel and promising anti‐aging agents in human.