bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensory dysregulation in tic disorders is associated with executive dysfunction and comorbidities
Authors: Soler Nicolette , Hardwick Chris , Perkes Iain E. , Mohammad Shekeeb S. , Dossetor David , Nunn Kenneth , Bray Paula , Dale Russell C.
Published: September 2019

Background

Tics are conceptualized as a sensorimotor phenomenon with a premonitory urge typically described by patients. As observed in other neurodevelopmental disorders, we have observed sensory dysregulation symptoms, such as tactile hypersensitivity to clothing, in children with tic disorders; however, formal clinical research in this area is limited.

Objective

To define the presence of sensory dysregulation symptoms in tic disorders, and their clinical associations.

Methods

Prevalence of sensory dysregulation in 102 children with tic disorders was compared to 61 age‐ and sex‐matched healthy controls. Sensory dysregulation, executive function, and quality of life data were obtained through the Short Sensory Profile‐2, Sensory Profile‐2, Sensory Processing Measure, Behaviour Rating Inventory of Executive Function‐2, and Strength and Difficulties Questionnaire and Pediatric Quality of Life Inventory. Tics were assessed with the Yale Global Tic Severity Scale.

Results

Children with tics, in the presence of comorbidity, had elevated sensory dysregulation compared to healthy controls (P < 0.001). There was a positive correlation between sensory dysregulation and global executive difficulties in children with tics and comorbidity (n = 87; rho = 0.716; P < 0.001) and a negative correlation of sensory dysregulation with quality of life (n = 87; rho = –0.595; P < 0.001). In children with tics, there was an association between sensory dysregulation and number of comorbidities (P < 0.001).

Conclusion

In the presence of comorbidity, children with tic disorders have broad sensory dysregulation symptoms beyond the premonitory urge. There was a statistically significant association between sensory dysregulation and executive function difficulties and the presence of neurodevelopmental and psychiatric comorbidity. Sensory dysregulation can be considered neurodevelopmental symptoms, providing insight into the neurobiology of tics and opportunities for therapeutic intervention. © 2019 International Parkinson and Movement Disorder Society
Approximate controllability of Hilfer fractional differential equations
Authors: Lv Jingyun , Yang Xiaoyuan
Published: September 2019

In this paper, the approximate controllability for a class of Hilfer fractional differential equations (FDEs) of order 1<α<2 and type 0 ≤ β ≤ 1 is considered. The existence and uniqueness of mild solutions for these equations are established by applying the Banach contraction principle. Further, we obtain a set of sufficient conditions for the approximate controllability of these equations. Finally, an example is presented to illustrate the obtained results.
Nonlinear impulsive Langevin equation with mixed derivatives
Authors: Rizwan Rizwan , Zada Akbar
Published: September 2019

In this paper, we consider a nonlocal boundary value problem of nonlinear impulsive Langevin equation with mixed derivatives. Some sufficient conditions are constructed to observe the existence, uniqueness, and generalized Ulam‐Hyers‐Rassias stability of our proposed model, with the help of Diaz‐Margolis' fixed‐point approach over generalized complete metric space. We give an example that supports our main result.
Nonlocal stochastic differential equations with time‐varying delay driven by G‐Brownian motion
Authors: Yin Wensheng , Cao Jinde
Published: September 2019

This article studies a class of nonlocal stochastic differential equations driven by G‐Brownian motion (G‐NSDEs for short). We show the existence and uniqueness results of solutions by means of fixed point theorem. In addition, exponential estimation of (1) has been discussed. Furthermore, we present global solution to Equation (1) with the help of G‐Lyapunov functional and ψ‐type function.
Simple circularly polarized planar monopole inverted T‐shaped antenna
Authors: Ellis Mubarak S. , Ahmed Abdul Rahman , Kponyo Jerry John , Nourinia Javad , Ghobadi Changiz , Mohammadi Bahman
Published: September 2019

This article presents a novel planar monopole antenna with circular polarization. The 3‐dB axial ratio (AR) is achieved by: shifting a vertical monopole to the left edge of the substrate in conjunction with a laterally inverted L‐shaped ground plane. When viewed from the top, the antenna resembles an uneven T‐shaped structure rotated at 90°. Measurement results show that; a 3‐dB AR bandwidth is achieved from 3.1 to 6.2 GHz (66.7% fractional bandwidth) and an S11 ≤ −10 dB bandwidth is realized from 2.5 to 6.5 GHz (88.9% fractional bandwidth). The proposed antenna is compact with an area of 20 mm2, produces stable radiation patterns, and its simple to design and fabricate without using parasitic elements or introducing slots on the antenna.
Modeling gold nanoparticle radiosensitization using a clustering algorithm to quantitate DNA double‐strand breaks with mixed‐physics Monte Carlo simulation
Authors: Liu Ruirui , Zhao Tianyu , Zhao Xiandong , Reynoso Francisco J.
Published: September 2019

Purpose

The radiosensitization properties of gold nanoparticles (GNPs) are investigated using a simple Geant4 cell model considering a realistic cell geometry and a clustering algorithm to characterize the number of DNA double‐strand breaks (DSBs).

Materials and methods

A mixed‐physics approach is taken for accurate modeling of low‐energy photon interactions in the different regions of the model using Geant4‐DNA physics within the cell, and Livermore physics within gold. Density‐based spatial clustering of applications with noise (DBSCAN), a clustering algorithm, is used to directly quantitate DNA DSBs after irradiation. The simulation was run using different sizes of GNPs, different distances of GNPs from the cell nucleus, and several combinations of these two conditions.

Results

Four types of radiation were simulated in the work: 80‐keV monoenergetic photons, 100‐keV monoenergetic photons, a 250‐kVp photon spectrum, and a 6‐MV flattening filter free (FFF) photon spectrum. A variable enhancement in DSB yield, nucleus dose, and cell dose was observed when there are GNPs in the cell cytoplasm, and increases with larger GNPs and proximity to the nucleus. The distance of the GNPs from the nucleus has a large impact on the DSB yield and nucleus dose, but little to no effect on the cell dose. The cell dose enhancement factor of 80 keV photons varies from 1.037–1.125 at 0.2 µm for 30–100 nm GNPs to 1.040–1.127 at 4 μm. The DSB enhancement factor varies from 1.050 to 1.174 at 0.2 µm to a marginal effect of <1.01 at 4 μm. For 100 keV, the dose enhancement factor is from 1.142–1.470 at 0.2 µm to 1.106–1.371 at 4 μm. The DSB enhancement factor varies from 1.249–1.813 at 0.2 µm to almost no effect at 4 μm. For 250 kVp, the dose enhancement factor is from 1.117–1.393 at 0.2 μm to 1.110–1.342 at 4 μm. The DSB enhancement factor varies from 1.183–1.600 at 0.2 μm to a marginal effect of ~1.03 at 4 μm. A 6‐MV FFF shows a dose enhancement factor of 1.061–1.103 at 0.2 μm and 1.053–1.107 at 4 μm. The DSB yield varies from 1.070–1.143 at 0.2 μm to a marginal effect at 4 μm.

Conclusion

The stark difference in behavior for DSB yield when compared to cell dose highlights the importance of evaluating more complex radiobiological quantities rather than dose alone when evaluating the radiosensitization properties from metallic nanomaterials. The nucleus dose showed similar characteristics to the DSB yield demonstrating the ability of the method to predict DNA damage and its relationship with nuclear dose. The proposed method provides a way to explore the radiobiological mechanisms of radiation‐induced DNA damages, and it aids to evaluate the physical radiosensitization properties of GNP‐aided radiotherapy, which can be easily combined with radiochemical DSB quantitation in order to better understand the intricate DNA damage induction mechanisms that are involved in GNP‐aided radiotherapy.
MR fingerprinting for water T1 and fat fraction quantification in fat infiltrated skeletal muscles
Authors: Marty Benjamin , Carlier Pierre G.
Published: September 2019

Purpose

To develop a fast MR fingerprinting (MRF) sequence for simultaneous estimation of water T1 (T1H2O) and fat fraction (FF) in fat infiltrated skeletal muscles.

Methods

The MRF sequence for T1H2O and FF quantification (MRF T1‐FF) comprises a 1400 radial spokes echo train, following nonselective inversion, with varying echo and repetition time, as well as prescribed flip angle. Undersampled frames were reconstructed at different acquisition time‐points by nonuniform Fourier transform, and a bi‐component model based on Bloch simulations applied to adjust the signal evolution and extract T1H2O and FF. The sequence was validated on a multi‐vial phantom, in three healthy volunteers and five patients with neuromuscular diseases. We evaluated the agreement between MRF T1‐FF parameters and reference values and confounding effects due to B0 and B1 inhomogeneities.

Results

In phantom, T1H2O and FF were highly correlated with references values measured with multi‐inversion time inversion recovery‐stimulated echo acquisition mode and Dixon, respectively (R2 > 0.99). In vivo, T1H2O and FF determined by the MRF T1‐FF sequence were also correlated with reference values (R2 = 0.98 and 0.97, respectively). The precision on T1H2O was better than 5% for muscles where FF was less than 0.4. Both T1H2O and FF values were not confounded by B0 nor B1 inhomogeneities.

Conclusion

The MRF T1‐FF sequence derived T1H2O and FF values in voxels containing a mixture of water and fat protons. This method can be used to comprehend and characterize the effects of tissue water compartmentation and distribution on muscle T1 values in patients affected by chronic fat infiltration.
Background suppressed magnetization transfer MRI
Authors: van Gelderen Peter , Duyn Jeff H.
Published: September 2019

Purpose

Up to 30% of the hydrogen atoms in brain tissue are part of molecules (“semisolids”) other than water. In MRI, their magnetization is typically not observed directly, but can influence the water magnetization through magnetization transfer (MT). Comparison of MRI scans differentially sensitized to MT allows estimation of the semisolid fraction and potential changes with disease. Here, we present an approach designed to improve this estimate by measuring the size of the MT effect in a single scan.

Methods

A stimulated echo sequence was used to generate a spatial pattern in the longitudinal water magnetization, which was then given time to exchange with semisolids. After saturating the remaining water magnetization, reverse exchange was allowed to partly re‐establish the original water magnetization pattern. The third excitation pulse then formed a stimulated echo out of this pattern.

Results

MT data were obtained on 10 human subjects at 7 T with varying exchange times. The images showed the expected time dependence of signal associated with the forward and reverse exchange processes. Excellent suppression of non‐exchanging background signal was achieved. As expected, this suppression came at the price of a substantial reduction in exchange‐related signal (by ~75% compared to the signal in saturation recovery MT), in part because of the reliance on a 2‐step exchange process.

Conclusion

The results demonstrate an MT signal can be observed in a single acquisition without subtraction. This may be advantageous for MT measurements when signal instabilities related to motion and physiological variations exceed thermal noise sources.
Compressed sensing effects on quantitative analysis of undersampled human brain sodium MRI
Authors: Blunck Yasmin , Kolbe Scott C. , Moffat Bradford A. , Ordidge Roger J. , Cleary Jon O. , Johnston Leigh A.
Published: September 2019

Purpose

The clinical application of sodium MRI is hampered due to relatively low image quality and associated long acquisition times. Compressed sensing (CS) aims at a reduction of measurement time, but has been found to encompass quantitative estimation bias when used in low SNR x‐Nuclei imaging. This work analyses CS in quantitative human brain sodium MRI from undersampled acquisitions and provides recommendations for tissue sodium concentration (TSC) estimation.

Methods

CS reconstructions from 3D radial acquisitions of 5 healthy volunteers were investigated over varying undersampling factors (USFs) and CS penalty weights on different sparsity domains, Wavelet, Discrete Cosine Transform (DCT), and Identity. Resulting images were compared with highly sampled and undersampled NUFFT‐based images and evaluated for image quality (i.e. structural similarity), image intensity bias, and its effect on TSC estimates in gray and white matter.

Results

Wavelet‐based CS reconstructions show highest image quality with stable TSC estimates for most USFs. Up to an USF of 4, images showed good structural detail. DCT and Identity‐based CS enable good image quality, however show a bias in TSC with a reduction in estimates across USFs.

Conclusions

The image intensity bias is lowest in Wavelet‐based reconstructions and enables an up to fourfold acquisition speed up while maintaining good structural detail. The associated acquisition time reduction can facilitate a translation of sodium MRI into clinical routine.
Impact of fluid overload and infection on respiratory adverse event development during induction therapy for childhood acute myeloid leukemia
Authors: Miller Lane H. , Keller Frank , Mertens Ann , Klein Mitchel , Allen Kristen , Castellino Sharon , Woods William G.
Published: September 2019

Background

Treatment‐related morbidity and mortality occur frequently in childhood acute myeloid leukemia (AML) induction. Yet the contributions of respiratory adverse events (AEs) within this population are poorly understood. Furthermore, the roles of fluid overload (FO) and infection in AML pulmonary complications have been inadequately examined.

Objectives

To describe the incidence, categories, and grades of respiratory AEs and to assess the associations of FO and infection on respiratory AE development in childhood AML induction.

Methods

We retrospectively examined the induction courses of a cohort of de novo pediatric AML patients for any NCI CTCAE grade 2 to 5 respiratory AE, FO, and systemic/pulmonary infection occurrence. Demographic, disease, and treatment‐related data were abstracted. Descriptive, univariate, survival, and multivariable analyses were conducted.

Results

Among 105 eligible subjects from 2009 to 2016, 49.5% (n = 52) experienced 63 discrete respiratory AEs. FO occurred in 28.6% of subjects (n = 30), with half occurring within 24 hours of hospitalization. Positive FO status < 10 days (aHR 5.5, 95% CI 2.3‐12.8), ≥ 10 days (aHR 13, 95% CI 4.1‐41.8), and positive infection status ≥ 10 days into treatment (aHR 14.9, 5.4‐41.6) were each independently associated with AE development.

Conclusions

We describe a higher incidence of respiratory AEs during childhood AML induction than previously illustrated. FO occurs frequently and early in this course. Late infections and FO at any time frame were strongly associated with AE development. Interventions focused on the prevention and management of FO and infectious respiratory complications could be instrumental in reducing preventable treatment‐related morbidity and mortality.
Clinical and neuropsychological outcome of pediatric non‐midline central nervous system germinoma treated with chemotherapy and reduced dose/volume irradiation: The Children's Hospital Los Angeles experience
Authors: Yeo Kee Kiat , Kayser Kimberly , Margol Ashley S. , Wong Kenneth K. , Robison Nathan , Finlay Jonathan , Dhall Girish
Published: September 2019

Background

Germ cell tumors (GCT) arising from non‐midline structures (basal ganglia, thalamus, and posterior fossa) are rare. Although patients with midline (pineal and suprasellar) germinoma have excellent survival with chemotherapy and whole ventricular irradiation (WVI), germinoma in non‐midline locations have traditionally been treated with craniospinal irradiation (CSI) or whole brain irradiation (WBI) to achieve similar outcomes. However, CSI and WBI are associated with significant long‐term neuropsychological sequelae.

Methods

We describe the clinical and neuropsychological outcomes of patients with non‐midline germinoma treated at the Children's Hospital Los Angeles between 1990 and 2015.

Results

Nine patients had basal ganglia/thalamic germinoma and one patient had a cerebellar primary. Eight patients received chemotherapy followed by reduced dose/volume irradiation, whereas two patients received chemotherapy alone as upfront therapy. One patient in the chemotherapy alone group relapsed after 4.3 years and was salvaged with CSI plus boost. The overall survival for the entire cohort was 100% at a median follow‐up of 8.5 years. Neuropsychological data were available for six patients at a median of five months (baseline) and 4.2 years (follow‐up) post‐diagnosis. At four‐year follow‐up, data available revealed intact overall cognitive ability, verbal memory, and executive functioning, but persistent deficits in fine motor function. Comparison of baseline to follow‐up suggests a downward trend in working memory, planning/problem‐solving, verbal memory, and visuospatial integration.

Conclusion

Chemotherapy followed by reduced dose/volume of irradiation is an effective strategy resulting in long‐term survival in patients with non‐midline germinoma. Neuropsychological data suggest relatively minimal morbidity over time.
Cediranib phase‐II study in children with metastatic alveolar soft‐part sarcoma (ASPS)
Authors: Cohen Julia W. , Widemann Brigitte C. , Derdak Joanne , Dombi Eva , Goodwin Anne , Dompierre Jessica , Onukwubiri Uzoma , Steinberg Seth M. , O'Sullivan Coyne Geraldine , Kummar Shivaani , Chen Alice P. , Glod John
Published: September 2019

Background

Alveolar soft‐part sarcoma (ASPS), a rare vascular sarcoma with a clinically indolent course, frequently presents with metastases. Vascular endothelial growth factor (VEGF) is a promising therapeutic target. In a phase‐II trial of the VEGF receptor inhibitor cediranib for adults with ASPS, the partial response (PR) rate (response evaluation criteria in solid tumors [RECIST] v1.0) was 35% (15/43; 95% confidence interval: 21‐51%). We evaluated cediranib in the pediatric population.

Procedure

Patients <16 years old with metastatic, unresectable ASPS received cediranib at the pediatric maximum tolerated dose of 12 mg/m2 (≈70% of the fixed adult phase‐II dose orally daily). Tumor response was assessed every two cycles (RECIST v1.0). A Simon two‐stage optimal design (target response rate 35%, rule out 5%) was used.

Results

Seven patients (four females), with a median age of 13 years, (range 9‐15), were enrolled on stage 1. The most frequent grade 2 or 3 adverse events were neutropenia, diarrhea, hypertension, fatigue, and proteinuria. The best response was stable disease (SD) (median cycle number = 34). Three patients were removed from the study treatment for disease progression (cycles 4, 5, and 36). Five of seven patients had SD for ≥14 months. Two patients with SD remain on study (34‐57+ cycles).

Conclusions

Cediranib did not reach the target response rate in this small pediatric cohort, in contrast to the adult 35% PR rate. The pediatric dosing was 30% lower compared to the adult dosing, which may have contributed to response differences. Prolonged SD was observed in five patients, but given the indolent nature of ASPS, SD cannot be clearly attributed to cediranib. Cediranib has an acceptable safety profile.
The Response of Haloferax volcanii to Salt and Temperature Stress: A Proteome Study by Label‐Free Mass Spectrometry
Authors: Jevtić Živojin , Stoll Britta , Pfeiffer Friedhelm , Sharma Kundan , Urlaub Henning , Marchfelder Anita , Lenz Christof
Published: September 2019

In‐depth proteome analysis of the haloarchaeal model organism Haloferax volcanii has been performed under standard, low/high salt, and low/high temperature conditions using label‐free mass spectrometry. Qualitative analysis of protein identification data from high‐pH/reversed‐phase fractionated samples indicates 61.1% proteome coverage (2509 proteins), which is close to the maximum recorded values in archaea. Identified proteins match to the predicted proteome in their physicochemical properties, with only a small bias against low‐molecular‐weight and membrane‐associated proteins. Cells grown under low and high salt stress as well as low and high temperature stress are quantitatively compared to standard cultures by sequential window acquisition of all theoretical mass spectra (SWATH‐MS). A total of 2244 proteins, or 54.7% of the predicted proteome, are quantified across all conditions at high reproducibility, which allowed for global analysis of protein expression changes under these stresses. Of these, 2034 are significantly regulated under at least one stress condition. KEGG pathway enrichment analysis shows that several major cellular pathways are part of H. volcanii’s universal stress response. In addition, specific pathways (purine, cobalamin, and tryptophan) are affected by temperature stress. The most strongly downregulated proteins under all stress conditions, zinc finger protein HVO_2753 and ribosomal protein S14, are found oppositely regulated to their immediate genetic neighbors from the same operon.
Investigation of mode interconversion for interfacial pattern formation through plasma–surface interaction
Authors: Liu Zhijie , Xu Han , Zhou Chunxi , Wang Wei , Liu Dingxin , Kong Michael G.
Published: September 2019

The appropriate understanding of the plasma–surface interaction is crucial in optimizing the atmospheric pressure plasma jet (APPJ) to suit a particular application. In this study, we mainly focus on the behavior of mode interconversion for interfacial patterns regarding APPJ interacting with a indium tin oxide (ITO) glass substrate. By regulating the pulse voltage, annular interfacial pattern formation on ITO surface displays two types of modes, that is, the diffuse pattern and the streamer pattern. Furthermore, these two modes are not independent and are transformed into each other by introducing additive N2 and O2. The reason is mainly attributed to the difference of the N2+(B)/O(3p) ratio and local electric field distribution. This information on the operation mode and interconversion between them provides deep insights into the nature of the physicochemistry during plasma–surface interaction processes.
Restriction of lung volumes but normal function of pulmonary tissue in mulibrey nanism
Authors: Sivunen Johanna , Piirilä Päivi , Karlberg Susann , Kajosaari Merja , Valmari Pekka , Kupari Markku , Lipsanen‐Nyman Marita , Jalanko Hannu , Sovijärvi Anssi RA
Published: September 2019

Background

Mulibrey nanism (MUL) is a rare growth restriction disorder with multiple organ manifestations caused by genetic defects affecting the TRIM37 protein. A perimyocardial heart disease is the most serious manifestation. Many MUL children appear to suffer from airway obstruction related to infection or exercise, prompting use of inhaled therapies. Asthma medication is continued up to adolescence or even to adulthood due to persisting of symptoms. The pulmonary pathophysiology has previously not been evaluated in any MUL cohort.

Methods

Thirty three finnish MUL patients (median age 20 years) were investigated with several lung function tests: spirometry with bronchodilatation test, single‐breath diffusing capacity for carbon monoxide, single‐breath lung volume measurements with helium dilution, and thoracic gas volume, airway resistance and specific conductance measurements with a body plethysmograph. As MUL typically affects body proportions, all variables were compared with reference values and with predicted values calculated from sitting height.

Results

Total lung capacity and forced vital capacity were markedly reduced (total lung capacity [TLC] and forced vital capacity [FVC], P < .001, 51%‐63% of predicted) and also forced expiratory volume in the first second was reduced (FEV1; P < .001, 47%‐57%). No signs of airway obstruction was seen (normal FEV1/FVC and specific airway conductance SGaw). Diffusing capacity (DLCO) was decreased (P < .001, 60%‐67%) but when related to alveolar volume it was increased (DLCO/VA, P < .001, 130%‐148%). Bronchodilatation suggesting active asthma (FEV1 change ≥12% and ≥​​200 mL) was found only in one patient.

Conclusion

MUL patients typically have volume restriction of the lungs, but function of the pulmonary tissue remains intact. Evidence of asthma in lung function testing at adult age is rare.
The LUFS domain, its transcriptional regulator proteins, and drug resistance in the fungal pathogen Candida auris
Authors: Misas Elizabeth , Escandón Patricia , McEwen Juan G. , Clay Oliver K.
Published: September 2019

The LUFS domain (LUG/LUH, Flo8, single‐strand DNA‐binding protein [SSBP]) is a well‐conserved and apparently ancient region found in diverse proteins and taxa. This domain, which has as its most obvious structural feature a series of three helices, has been identified in transcriptional regulator proteins of animals, plants, and fungi. Recently, in these pages (Wang et al., Protein Sci., 2019, 28:788–793), the first crystal structure of a LUFS domain was reported, for the human SSBP2, a transcriptional repressor. We briefly address how the new insights into LUFS structures might contribute to a better understanding of an important transcriptional activator of yeasts that contains the LUFS domain, Flo8, and consider how a focus on the LUFS domain and its variation could help us to understand etiologies of drug resistance in a recently emerged pathogenic fungus, Candida auris.
Functional validation of metabolic genes that distinguish Gleason 3 from Gleason 4 prostate cancer foci
Authors: Roberto Domenica , Selvarajah Shamini , Park Paul C. , Berman David , Venkateswaran Vasundara
Published: September 2019

Background

Gleason grade is among the most powerful clinicopathological classification systems used to assess risk of lethal potential in prostate cancer, yet its biologic basis is poorly understood. Notably, pure low‐grade cancers, comprised predominantly of Gleason pattern 3 (G3) are typically indolent, with lethal potential emerging with the progression of higher‐grade Gleason patterns 4 (G4) or 5. One of the hallmarks of more aggressive cancer phenotypes is the stereotyped set of metabolic characteristics that transformed cells acquire to facilitate unregulated growth. In the present study, we profiled expression signatures of metabolic genes that are differentially expressed between G3 and G4 cancer foci and investigated the functional role of two of the profiled genes, PGRMC1 and HSD17B4, in prostate cancer cells.

Methods

Gene expression profiling was conducted using 32 G3 and 32 G4 cancer foci from patients with 3+3 and ≥4+3 tumors, respectively. A 95‐gene Nanostring probe set was used to probe genes associated with energy metabolism. Two out of five genes (PGRMC1 and HSD17B4) that significantly distinguish between G3 and G4 were functionally validated in vitro using established prostate cancer cells (PC3, DU145). Expression of PGRMC1 and HSD17B4 was knocked down and subsequent studies were performed to analyze cell proliferation, migration, invasion, and apoptosis. Mechanistic studies that explored the epidermal growth factor receptor (EGFR) pathway were performed by Western blot.

Results

Multivariate analysis identified five metabolic genes that were differentially expressed between G3 and G4 stroma (P < .05). Functional validation studies revealed that knockdown of PGRMC1 and HSD17B4 significantly decreased cell proliferation, migration, and invasion, and increased apoptosis in PC3 and DU145 cells. Mechanistic studies showed that these effects, after PGRMC1 knockdown, were possibly mediated through alterations in downstream components of the EGFR, protein kinase B, and nuclear factor kappa‐light‐chain‐enhancer of activated B cells pathways.

Conclusion

The following study provides evidence supporting the use of metabolic genes PGRMC1 and HSD17B4 as a prognostic biomarker for the distinction between G3 and G4 prostate cancers.
Analytically validated protein biomarkers of chronic pancreatitis and pancreatic cancer for potential clinical diagnosis with mass spectrometry
Authors: Chou Che‐Yi , Chang Chiz‐Tzung , Chen Chao‐Jung
Published: September 2019

Rationale

Chronic pancreatitis (CP) is a pancreatic disease with poor prognosis and pancreatic cancer (PC) is one of the most lethal types of cancer that is symptomless in the early stage. Because the clinical and image findings of CP can overlap that of pancreatic cancer (PC) which leads to confusion in the diagnosis and treatment of PC, discovery/verification/validation of more accurate protein biomarkers to diagnose CP and PC is in urgent need.

Methods

The PubMed, Web of Science, and Google Scholar were searched using the keywords: ‘biomarker’, ‘marker’, ‘chronic pancreatitis’, “pancreatic cancer” or “proteomics” for highly related researches. We focused on the articles published after the year 2005 in this review.

Results

We introduce the background to CP and PC and summarize the diagnosis of CP and PC, analytically validated protein biomarkers, and proteomic approaches for discovery/verification/validation. The potential use of mass spectrometry (MS) in clinical diagnosis is also discussed.

Conclusions

Continuously improving sensitivity of MS can provide deeper proteome for new marker discovery and high reliability for protein marker verification, validation, and clinical diagnosis. The analytically validated protein markers could be considered as targeted protein biomarkers for developing a MS platform in the clinical validation process or clinical diagnosis of CP and PC.
Fault‐tolerant spacecraft attitude control under actuator saturation and without angular velocity
Authors: Wang Xianghua , Tan Chee Pin
Published: September 2019

In this paper, a fault‐tolerant control scheme is proposed to control the attitude of a rigid spacecraft subject to external disturbances and multiple system uncertainties, as well as actuator faults and saturation. More challengingly, it is assumed that the angular velocity is unavailable. A super‐twisting observer with time‐varying gain is firstly designed to accurately estimate the angular velocity in finite time. The choice of the time‐varying gain is dependent on a state‐norm estimate. Then, using the information from the observer (estimate of angular velocity), a fault‐tolerant controller is proposed, where an adaptive law is introduced to address the unknown loss of effectiveness and neural networks are used to approximate the unknown nonlinear functions. It is proved that the attitude orientations converge to the desired values at a fixed time. Finally, a simulation example is utilized to verify the effectiveness of the proposed scheme.
One‐Pot Synthesis of 2‐Amino‐6‐(1,2‐dihydro‐4‐hydroxy‐2‐oxoquinolin‐3‐yl)‐4‐arylpyridine‐3‐carbonitriles Catalysed by NbCl5 and Their In Vitro Antimicrobial Studies
Authors: Krishna Alla. , Sarveswari S.
Published: September 2019

Synthesis of 2‐amino‐6‐(1, 2‐dihydro‐4‐hydroxy‐2‐oxoquinolin‐3‐yl)‐4‐arylpyridine‐3‐carbonitrile has been accomplished via NbCl5 catalysed multicomponent reaction (MCR). The tested compounds showed better potency than Neomycin and a broad spectrum of antibacterial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli. Similarly some of these have showed good activity against Staphylococcus aureus, Klebsiella planticola and Escherichia coli that were comparable to Ciprofloxacin. Also these compounds possess good antifungal activity that was better than Miconazole and comparable to Ciprofloxacin hydrochloride.
Control of Circularly Polarised Luminescence Using a Suitable Wired Structure Connecting a Binaphthyl with Two Pyrenes
Authors: Hara Nobuyuki , Okuda Koji , Shizuma Motohiro , Tajima Nobuo , Imai Yoshitane
Published: September 2019

The sign, wavelength, and intensity of circularly polarised luminescence, generated from two photoexcited pyrene moieties, were successfully controlled by selecting a suitable achiral wired structure to connect two achiral fluorescent pyrenes with an axially chiral binaphthyl backbone. Especially, these circularly polarised luminescence and circular dichroism signs were found to be influenced by the achiral wire structures, i. e., the chiral structures of S1 and S0 states were affected by the achiral wire structure employed.
Interplay between Conformation and Crystal Packing in Aryl Propargyl Ethers: Structural and Spectroscopic Properties of 2‐(prop‐2‐yn‐1‐yloxy)acene Derivatives
Authors: Saeed Aamer , Shehzadi Syeda Aaliya , Bolte Michael , Franca Carlos A. , Erben Mauricio F.
Published: September 2019

The 2‐(prop‐2‐yn‐1‐yloxy)naphthalene (compound I) and 1‐nitro‐2‐(prop‐2‐yn‐1‐yloxy)benzene (compound II) were prepared in excellent yields by the reaction of propargyl bromide with 2‐naphthol and 2‐nitrophenol, respectively. Structural and conformational properties of both compounds have been analyzed using a combined approach including single‐crystal X‐ray diffraction and quantum chemical calculations. Two forms are found to be stable and nearly isoenergetic conformers, depending on the mutual orientation of the C≡C triple bond and the O–C single bond of the prop‐2‐yn‐1‐yloxy group. The gauche conformation is the most stable form for the vacuum isolated species, with the anti conformation higher in energy by 1.00 and 1.89 kcal/mol computed at the M06‐2X/6‐311++G(d,p) level of approximation, for I and II, respectively. The gauche form is observed in the crystal of I but the nearly planar anti conformation is adopted in the crystalline phase of compound II. The occurrence of C–H⋅⋅⋅π and C–H⋅⋅⋅O intermolecular interactions involving the acidic ‐C≡C–H hydrogen donor and ‐C≡C‐ and ‐OCH2– acceptors is discussed. Furthermore, vibrational features of the prop‐2‐yn‐1‐yloxy moiety are analyzed by infrared and Raman spectroscopy. The UV‐Vis spectrum shows the presence of well‐defined absorption at ca. 280 and 320 nm assigned to the π→π* transitions in the naphtyl/benzyl and prop‐2‐yn‐1‐yloxy groups, respectively.
Merocyanine‐Benzothiazole Chromophore‐Based Sensor for Selective Picric Acid Detection
Authors: Patil Pramod D. Jawale , Wagalgave Sopan M. , Ingle Rajita D. , Nanubolu Jagadeesh B. , Bhosale Rajesh S. , Bhosale Sidhanath V. , Pawar Rajendra P. , Bhosale Sheshanath V.
Published: September 2019

We report synthesis of (2E,4E)‐2‐(benzo[d]thiazol‐2‐yl)‐4‐(1,3,3‐trim ethylindolin‐2‐ylidene) but‐2‐enenitrile (MC‐BTH‐1) chromophore and employed for picric acid sensing. MC‐BTH‐1 was prepared by Knoevenagel condensation of 2‐(benzo[d]thiazol‐2‐yl) acetonitrile and (Z)‐2‐(1,3,3‐trimethylindolin‐2‐ylidene)acetaldehyde in the presence of catalytic amount of piperidine in dry ethanol. The MC‐BTH‐1 conjugate displayed a remarkable sensing property towards picric acid in presence of interfering nitroaromatic compounds. The sensing of nitroaromatic compounds was investigated by means of UV‐vis absorption, fluorescence and 1H NMR spectroscopic. Furthermore, colorimetric visualization of receptor MC‐BTH‐1 with the addition of various analytes under 365 nm UV light shows only color change from green to dark green for 2,4,6‐trinitrophenol (TNP) and no significant color change was observed for other analytes. Under optimized condition the detection limit towards TNP and 2,4‐dinitrophenol (DNP) are 1.58×10−9 M and 1.48×10−9 M, respectively. These results clearly show high sensitivity of system at low concentration with fluorescence quenching quantum efficiency ∼88%.
Preparation and In Vivo Antinociceptive Behavior of Four New 2‐Amino‐6‐trifuromethoxybenzothiazole Carboxylic Acid Derivatives
Authors: Wu Xianglong , Wang Qingchuan , Zhang Fei , Liu Hao , Lu Tingli , Zhang Qichun
Published: September 2019

Four novel N‐substituted riluzole derivatives (4 a‐4 d) have been prepared and characterized. Their antinociceptive activities have been carefully investigated by hot‐plate test and writhing test. Our results indicated that at dose of 18 mg kg−1, 2‐(N‐propionic acid)‐6‐trifluoromethoxy‐benzothiazole (4 a), 2‐(N‐butanoic acid)‐6‐trifluoromethoxy‐benzothiazole (4 b) and 2‐(N‐n‐caproic acid)‐6‐trifluoromethoxy‐benzothiazole (4 c) significantly increased the nociceptive response latency under hot plate test while chemical nociception induced by intraperitoneal acetic acid was significantly inhibited by 4 a and 2‐(N‐proline)‐6‐trifluoromethoxy‐benzothiazole (4 d) at same dosage. Our research clearly indicates that N‐substituted Riluzole derivatives could be new alternative candidates as potential antinociceptive medicines.
Microfluidics for Biomedical Analysis
Authors: Yang Yong , Chen Yong , Tang Hao , Zong Nan , Jiang Xingyu
Published: September 2019

Many new techniques and materials have been applied to microfluidic systems in the past decade, and integrated microfluidic chips have become powerful platforms for realizing highly sensitive, high throughput, and low‐cost analysis. This article reviews the latest advancements of microfluidic platforms for biological and biomedical analysis in the fields of fundamental biology research, clinical application, food safety, and environmental monitoring, with a focus on nucleic acid‐based molecular diagnosis and protein‐based immunodiagnosis. The combination of microfluidics with advanced techniques (e.g., nanotechnology, 3D printing, deep learning) would offer innovative new tools for bioanalyses. The current challenges and the future developments of microfluidic technologies for clinical applications are also discussed. It is anticipated that this review will be beneficial to promoting microfluidics toward a broad range of applications in the future.
Katian (Ordovician) to Aeronian (Silurian, Llandovery) graptolite biostratigraphy of theYD‐1 drill core, Yuanan County, Hubei Province, China
Authors: Maletz Jörg , Wang Chuanshang , Wang Xiaofeng
Published: September 2019

The graptolite succession of theYD‐1 drill core provides a new view into the lower Silurian (Llandovery) biostratigraphy of the Yichang region on the Yangtze platform of China. A thick succession of black to greenish, fine to silty shales and siltstones with a variable amount of poorly to well‐preserved graptolite faunas ranges from the upper OrdovicianDicellograptus ornatusBiozone (upper Katian) to the lower SilurianLituigraptus convolutusBiozone (mid Aeronian). TheMetabolograptus extraordinarius/Metabolograptus persculptusandAkidograptus ascensus/Parakidograptus acuminatusBiozone intervals are strongly condensed and bear poorly preserved graptolite faunas. A considerable gap can be detected above theCystograptus vesiculosusBiozone, as the succeeding graptolite fauna indicates the upperPribylograptus leptothecaBiozone. The interval of the upper RhuddanianCoronograptus cyphusBiozone to the Lower AeronianCoronograptus gregariusBiozone is missing.Lituigraptus convolutuswas found from 1322.85 to 950.20 m, indicating a thickness of theLituigraptus convolutusBiozone of at least 378.47 m. The age of the highest available graptolite faunas from the 729.40–750.70 m is inconclusive, but the level may still belong to theLituigraptus convolutusBiozone. The correlation of the succession with other successions on the Yangtze platform of China indicates the need for a considerable modification of the graptolite biostratigraphy of the Yangtze platform in the Yichang region and revision of the described faunas. The Llandovery appears to be highly incomplete in the eastern flank of the Huangling anticline and the age of the biostratigraphically younger part of the succession cannot be dated precisely with graptolite faunas.
Integrated transcriptomic, phenotypic, and functional study reveals tissue-specific immune properties of mesenchymal stromal cells
Authors: Ménard Cédric , Dulong Joëlle , Roulois David , Hébraud Benjamin , Verdière Léa , Pangault Céline , Sibut Vonick , Bezier Isabelle , Bescher Nadège , Monvoisin Céline , Gadelorge Mélanie , Bertheuil Nicolas , Flécher Erwan , Casteilla Louis , Collas Philippe , Sensebé Luc , Bourin Philippe , Espagnolle Nicolas , Tarte Karin
Published: September 2019

Clinical-grade mesenchymal stromal cells (MSCs) can be expanded from bone marrow and adipose tissue to treat inflammatory diseases and degenerative disorders. However, the influence of their tissue of origin on their functional properties, including their immunosuppressive activity, remains unsolved. In this study, we produced paired bone marrow-derived mesenchymal stromal cell (BM-MSC) and adipose-derived stromal cell (ASC) batches from 14 healthy donors. We then compared them using transcriptomic, phenotypic, and functional analyses and validated our results on purified native MSCs to infer which differences were really endowed by tissue of origin. Cultured MSCs segregated together owing to their tissue of origin based on their gene expression profile analyzed using differential expression and weighted gene coexpression network analysis. This translated into distinct immune-related gene signatures, phenotypes, and functional cell interactions. Importantly, sorted native BM-MSCs and ASCs essentially displayed the same distinctive patterns than their in vitro-expanded counterparts. As a whole, ASCs exhibited an immune profile consistent with a stronger inhibition of immune response and a lower immunogenicity, supporting the use of adipose tissue as a valuable source for clinical applications.
Multilingual Interactions and Learning in High School ESL Classrooms
Authors: Davila Liv T.
Published: September 2019

This article explores how peer and teacher–student interactions in linguistically diverse high school English as a Second Language (ESL) classrooms produce changes in learners’ uptake of different languages and cultures. Data presented are from a 2‐year ethnography of communication focusing on adolescent multilingual English learners’ language use in three ESL classrooms in the United States. The study participants’ primary languages were French, Lingala, and Tshiluba, and the dominant language spoken by the students in class was Spanish. The data include recordings of peer group classroom interactions, individual and focus group interviews, and field notes from classroom observations. Analyzed through an ecology of language framework (van Lier, 2004) and heteroglossic perspectives on language learning and use (Bakhtin, 1981), the findings reveal a gradual ideological and pragmatic shift among the focal students from resenting the predominant use of Spanish by their teachers and peers during Year 1 of the study to using Spanish words and phrases during Year 2 for two distinct purposes: peer socialization and learning English. The article concludes by highlighting the importance of attending to students’ language experiences to harness metacognitive thinking, critical multilingual language awareness, and linguistic creativity.
Natural history of pregnancy‐related enhanced myometrial vascularity following miscarriage
Authors: Grewal K. , Al‐Memar M. , Fourie H. , Stalder C. , Timmerman D. , Bourne T.
Published: September 2019

Objectives

Our primary aim was to report the incidence of enhanced myometrial vascularity (EMV) in consecutive women attending our early pregnancy assessment unit, following first‐trimester miscarriage. We aimed further to evaluate the clinical presentation and complications associated with expectant and surgical management of EMV in these women.

Methods

This was a prospective cohort study conducted in a London teaching hospital between June 2015 and June 2018, including consecutive patients with an observation of EMV on transvaginal ultrasonography following first‐trimester miscarriage. The diagnosis was made following the subjective identification of EMV using color Doppler ultrasonography and a peak systolic velocity (PSV) ≥ 20 cm/s within the collection of vessels. Women were followed up with repeat scans every 14 days. Management was expectant unless intervention was indicated because of excessive or prolonged bleeding, persistent presence of retained tissue in the endometrial cavity or patient choice. The final clinical outcome was recorded. Time to resolution of EMV was defined as the interval from detection of EMV until resolution.

Results

During the study period, there were 2627 first‐trimester fetal losses in the department and, of these, 40 patients were diagnosed with EMV, hence the incidence of EMV following miscarriage was 1.52%. All cases were associated with ultrasound evidence of retained products of conception (RPOC) at presentation (mean dimensions, 22 × 20 × 20 mm). Thirty‐one patients opted initially for expectant management, of which 18 had successful resolution without intervention, five were lost to follow‐up and eight subsequently had surgical evacuation due to patient choice. No expectantly managed case required emergency intervention. Nine patients chose surgical evacuation as primary treatment. No significant correlation was seen between PSV within the EMV at presentation and blood loss at surgery. Median PSV was 47 (range, 20–148) cm/s. The estimated blood loss in all cases managed surgically ranged from 20–300 mL. Presence of RPOC was confirmed in all specimens that were sent for analysis following surgery. For cases successfully managed expectantly, the mean time to resolution was 48 (range, 21–84) days. In the nine cases managed surgically from the beginning, the mean time to resolution of EMV was 10.6 (range, 3–29)
days.

Conclusions

This study suggests that EMV is an uncommon finding following miscarriage and is associated with the presence of RPOC. Expectant management was a safe option in our cohort, with minimal bleeding, although it was associated with protracted time to resolution. In patients who opted for surgery, the maximum blood loss was 300 mL and no patient required blood transfusion or embolization. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Post‐truth and anthropogenic climate change: Asking the right questions
Authors: Groves Christopher
Published: September 2019

The connection between climate skepticism and climate denial and what has become known as post‐truth culture has become the subject of much interest in recent years. This has lead to intense debates among scientists and activists about how to respond to this changed cultural context and the ways in which it is held to obstruct wider acceptance of climate science. Drawing on research in the sociology of scientific knowledge, science and technology studies, social psychology, and philosophical reflections on evidential reasoning, it is argued that these debates are focused on the wrong topic. The idea of post‐truth implies that a once‐straightforward linear relationship between scientific evidence and decision‐making has been eroded. But such an idealized relationship never existed. The proper role of scientific evidence in informing belief and action in response to the prospect of anthropogenic climate change needs reconsideration. A key part of this is to make uncertainties related to processes within the climate system and their potential outcomes into the main focus of public discussion around climate change. Instead of keeping the focus of debate on how to “get the science right,” such a reframing makes precautionary questions about the prospect of unacceptable losses into the main focus. This brings a variety of ethical and political values into the debate, perhaps creating better conditions for a minimal consensus about what to do.

This article is categorized under:

Perceptions, Behavior, and Communication of Climate Change > Communication