bluuebunny/crossref_metadata_2025 huggingface dataset:
Using App Inventor as Tool for Creating Mathematics Applications for Mobile Devices with Android OS
Authors: Cioruța Bogdan , Coman Mirela , Cioruța Alin-Andrei
Published: March 2019

People are programming on their personal computers since the 1980s, but today's mobile applications are making computing as “personal” as never before. Never in the history of the use of technology in education has there been a technology so widely available to citizens as mobile technology. According to this trend, we are moving into a new era of consuming information via mobile computing, one that promises greater variety in applications, highly improved usability, and networking. Our consuming information culture gives us all sorts of opportunities for entertainment, even learning using high-tech devices, which are considered to be black boxes to most of us, because only few people can create applications. Even though, more and more students are interested in developing their own mobile applications. In this context, we present our experience with App Inventor - a user friendly platform and drag-and-drop block language to create Android apps. The present paper is an intro to the creation process for an applied mathematics app, started 4 years ago, corresponding to the requirements of our classroom consuming information culture.
Sharing of Patient Health Record (PHR) in Jelastic Cloud in a Secured Manner
Authors: Jinan Umme Afifa , Soheli Sultana Jahan
Published: March 2019

Now-a-days cloud computing is a prominent way of providing resources and services in very secure manner. Gradually more and more organizations, companies and industries are picking up cloud technology for the safe keeping of their data. The objective of this work is to apply cloud service in healthcare system by building a practical patient health record (PHR) application and deploying it in the cloud. The system is ‘doctor-centric’ health record portal where only the doctor or hospital authority is responsible for securing their patients’ health data and this labor-free, paperless system is giving relief to the doctors and hospital authorities from various error-prone traditional health record keeping systems. Jelastic cloud is used to provide cloud service to the developed application which provides security, scalability, quality of service and ease of maintenance of the application. Jelastic cloud also provides load balancing whenever the user load is high. We are developing an interactive PHR application which is dynamically storing, creating, modifying and maintaining data and deploying it in the Jelastic CloudJiffy server by the use of InMotion Hosting server. CloudJiffy is India based fully redundant, high performance and scalable cloud “Platform-as-a-Service (PaaS)” under Jelastic Cloud Union. The whole system will be an efficient way for safe keeping Patients’ health records, their medical history and sensitive health information in a pervasive, confidential manner. The system is highly compatible for preserving medical records of eminent persons of our society and for those whose health information must be kept confidential in a highly secure way.
Dominant LMAN2L mutation causes intellectual disability with remitting epilepsy
Authors: Alkhater Reem A. , Wang Peixiang , Ruggieri Alessandra , Israelian Lori , Walker Susan , Scherer Stephen W. , Smith Mary Lou , Minassian Berge A.
Published: March 2019

Mis‐secreted glycoproteins (LGI1, reelin) are emerging causes of epilepsy. LMAN2L belongs to a glycoprotein secretion chaperone family. One recessive LMAN2L missense mutation predicted to impair the chaperone's interaction with glycoproteins was reported in a family with intellectual disability (ID) and remitting epilepsy. We describe four members of a family with autosomal dominant inheritance of a similar phenotype. We show that they segregate a NM_001142292.1:c.1073delT mutation that eliminates LMAN2L's endoplasmic reticulum retention signal and mislocalizes the protein from that compartment to the plasma membrane. LMAN2L mislocalization, like impaired glycoprotein interaction, disturbs brain development, including generation of developmentally restricted epilepsy.
Silver‐Adapted Diffusive Memristor Based on Organic Nitrogen‐Doped Graphene Oxide Quantum Dots (N‐GOQDs) for Artificial Biosynapse Applications
Authors: Sokolov Andrey Sergeevich , Ali Mumtaz , Riaz Rabia , Abbas Yawar , Ko Min Jae , Choi Changhwan
Published: March 2019

Carbon‐based electronic devices are suitable candidates for bioinspired electronics due to their low cost, eco‐friendliness, mechanical flexibility, and compatibility with complementary metal‐oxide‐semiconductor technology. New types of materials such as graphene quantum dots (GQDs) have attracted attention in the search for new applications beyond solar cells and energy harvesting due to their superior properties such as elevated photoluminescence, high chemical inertness, and excellent biocompatibility. In this paper, a biocompatible/organic electronic synapse based on nitrogen‐doped graphene oxide quantum dots (N‐GOQDs) is reported, which exhibits threshold resistive switching via silver cation (Ag+) migration dynamics. In analogy to the calcium (Ca2+) ion dynamics of biological synapses, important biological synapse functions such as short‐term potentiation (STP), paired‐pulse facilitation, and transition from STP to long‐term plasticity behaviors are replicated. Long‐term depression behavior is also evaluated and specific spike‐timing dependent plasticity is assessed. In addition, elaborated switching mechanism of biosimilar Ag+ migration dynamics provides the potential for using N‐GOQD‐based artificial synapse in future biocompatible neuromorphic systems.
Design and Applications of Photoresponsive Hydrogels
Authors: Li Lei , Scheiger Johannes M. , Levkin Pavel A.
Published: March 2019

Hydrogels are the most relevant biochemical scaffold due to their tunable properties, inherent biocompatibility, and similarity with tissue and cell environments. Over the past decade, hydrogels have developed from static materials to “smart” responsive materials adapting to various stimuli, such as pH, temperature, chemical, electrical, or light. Light stimulation is particularly interesting for many applications because of the capability of contact‐free remote manipulation of biomaterial properties and inherent spatial and temporal control. Moreover, light can be finely adjusted in its intrinsic properties, such as wavelength and intensity (i.e., the energy of an individual photon as well as the number of photons over time). Water is almost transparent for light in the photochemically relevant range (NIR–UV), thus hydrogels are well‐suited scaffolds for light‐responsive functionality. Hydrogels' chemical and physical variety combined with light responsiveness makes photoresponsive hydrogels ideal candidates for applications in several fields, ranging from biomaterials, medicine to soft robotics. Herein, the progress and new developments in the field of light‐responsive hydrogels are elaborated by first introducing the relevant photochemistries before discussing selected applications in detail.
Direct and Efficient C(sp3)‐H Bond Alkylation of Tetrahydroisoquinolines and Isochroman with Alkylzinc Reagents
Authors: Peng Zhihua , Wang Yilei , Yu Zhi , Wu Hao , Fu Shanshan , Song Linhua , Jiang Cuiyu
Published: March 2019

An efficient C(sp3)−H bond alkylation of tetrahydroisoquinolines and isochroman with alkylzinc reagents was demonstrated. This transformation could be readily performed under mild conditions in the absence of a heavy metal catalyst, affording a wide range of potentially biologically active compounds. In addition, this approach exhibited excellent compatibility with various sensitive functional groups such as a cyano group, an ester group as well as a boronic acid pinacol ester group.

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Enhancing Systemic Delivery of Enzymatically Generated RNAi Nanocomplexes for Cancer Therapy
Authors: Nam Hyangsu , Ku Sook Hee , Yoon Hong Yeol , Kim Kwangmeyung , Kwon Ick Chan , Kim Sun Hwa , Lee Jong Bum
Published: March 2019

Despite the superb therapeutic potential of siRNA technology, its clinical application are still limited due to the inherent instability and lack of systemic delivery issues. Recently, the development of long‐chain siRNA has been proposed as a strategy to improve in vivo stability, particularly for efficient physical integration of siRNA molecules into gene carriers. Herein, concatemeric siRNAs are enzymatically synthesized through a rolling circle transcription process, and form stable RNA interference (RNAi) nanocomplexes with a redox‐sensitive glycol chitosan derivative to systemically deliver the concatemeric siRNAs to tumor tissues. The enzymatically generated RNAi nanocomplexes (RNCs) have higher particle stability and less cytotoxicity than the conventional polyelectrolyte complexes. The therapeutic potential of the RNC formulation is verified in vivo as well as in vitro using VEGF as an antiangiogenic target for RNAi‐based anticancer therapy. After systemic administration, RNC is specifically accumulated in tumor tissues and shows a high inhibitory effect on tumor growth. According to the results, the RNC can be considered as a platform technology for efficient tumor‐targeted siRNA delivery systems.
Associations between a laboratory frailty index and adverse health outcomes across age and sex
Authors: Blodgett Joanna M. , Theou Olga , Mitnitski Arnold , Howlett Susan E. , Rockwood Kenneth
Published: March 2019

Objective

Early frailty may be captured by a frailty index (FI) based entirely on vital signs and laboratory tests. Our aim was to examine associations between a laboratory‐based FI (FI‐Lab) and adverse health outcomes, and investigate how this changed with age.

Methods

Up to 8988 individuals aged 20+ years from the 2003‐2004 and 2005‐2006 National Health and Nutrition Examination Survey cohorts were included. Characteristics of the FI‐Lab were compared to those of a self‐reported clinical FI. Associations between each FI and health care use, self‐reported health, and disability were examined in the full sample and across age groups.

Results

Laboratory‐based FI scores increased with age but did not demonstrate expected sex differences. Women aged 20‐39 years had higher FI scores than men; this pattern reversed after age 60 years. FI‐Lab scores were associated with poor self‐reported health (odds ratio[95% confidence interval]: 1.46[1.39‐1.54]), high health care use (1.35[1.29‐1.42]), and high disability (1.41[1.32‐1.50]), even among those aged 20‐39 years.

Conclusion

Higher FI‐Lab scores were associated with poor health outcomes at all ages. Associations in the youngest group support the notion that deficit accumulation occurs across the lifespan. FI‐Lab scores could be utilized as an early screening tool to identify deficit accumulation at the cellular and molecular level before they become clinically visible.
Case report and novel treatment of an autosomal recessive Leigh syndrome caused by short‐chain enoyl‐CoA hydratase deficiency
Authors: Shayota Brian J. , Soler‐Alfonso Claudia , Bekheirnia Mir Reza , Mizerik Elizabeth , Boyer Suzy W. , Xiao Rui , Yang Yaping , Elsea Sarah H. , Scaglia Fernando
Published: March 2019

Short chain enoyl‐CoA hydratase (SCEH) deficiency leads to a severe form of autosomal recessive Leigh syndrome with inevitable neurological decline and early mortality. SCEH is most notably involved in valine catabolism, a deficiency of which results in various metabolic alterations, including increased levels of the highly reactive metabolite 2‐methacrylyl‐CoA. With no proven treatments available to date, it has been speculated that patients may respond to a valine restricted diet and/or N‐acetylcysteine supplementation, as suggested by early studies of a very similar inborn error of metabolism, 3‐hydroxyisobutyryl‐CoA hydrolase deficiency. We describe a patient with typical Leigh syndrome clinical findings and identified compound heterozygous variants in ECSH1. Valine‐restricted diet was initiated at 6 months of age and N‐acetylcysteine supplementation at 9 months with subsequent improvement in growth and slow progress in developmental milestones. However, at 15 months, the patient aspirated during a breakthrough seizure from which he did not recover and died soon after from related complications. This report highlights some of the challenges that remain in the management and treatment of SCEH deficiency, while demonstrating that a valine restricted diet and N‐acetylcysteine can be safely administered with the potential for clinical improvement.
Weiterentwicklung der Substrattoleranz von Elizabethkingia meningoseptica Oleathydratase zur regio‐ und stereoselektiven Hydratisierung von Ölsäurederivaten
Authors: Engleder Matthias , Strohmeier Gernot A. , Weber Hansjörg , Steinkellner Georg , Leitner Erich , Müller Monika , Mink Daniel , Schürmann Martin , Gruber Karl , Pichler Harald
Published: March 2019

Die Addition von Wasser an nichtaktivierte Kohlenstoff‐Kohlenstoff‐Doppelbindungen von Fettsäuren wird durch Fettsäurehydratasen (FAHYs) katalysiert, und ermöglicht die hochselektive Oxyfunktionalisierung von erneuerbaren, ölhaltigen Rohstoffen. Da für die Erkennung und Bindung von Substraten die freie Carboxylatgruppe bislang als unerlässlich galt, ist der Einsatz von FAHYs gegenwärtig auf die Hydratisierung freier Fettsäuren limitiert. Diese Arbeit zeigt erstmals die Hydratisierung von Ölsäurederivaten ohne freier Carboxylatfunktion am Beispiel der Elizabethkingia meningoseptica Oleathydratase (OhyA). Im Zuge bioinformatischer Bindestudien von Substraten an die 3D‐Struktur der OhyA sowie durch Aminosäuresequenzvergleiche konnten konservierte Aminosäurereste in der Substratbindetasche des Enzyms identifiziert werden. Der rationale Austausch dieser Reste führte zu Enzymvarianten mit bis zu 18‐fach verbessertem Umsatz bestimmter Ölsäurederivate ohne Beeinträchtigung der exzellenten Regio‐ und Stereoselektivität der Olefinhydratisierung.
A Methyl‐TROSY‐Based 1H Relaxation Dispersion Experiment for Studies of Conformational Exchange in High Molecular Weight Proteins
Authors: Yuwen Tairan , Huang Rui , Vallurupalli Pramodh , Kay Lewis E.
Published: March 2019

Molecular complexes often sample conformational states that direct them to specific functions. These states can be difficult to observe through traditional biophysical approaches but they can be studied using a variety of different NMR spin relaxation experiments. However, these applications, when focused on moderate to high molecular weight proteins, are complicated by fast relaxing signals that negatively affect the sensitivity and resolution of spectra. Here a methyl 1H CPMG‐based experiment for studies of excited conformational states of protein machines is described that exploits a TROSY‐effect to increase signal‐to‐noise. Complexities from the multiplicity of methyl 1H transitions are addressed to generate a robust pulse scheme that is applied to a 320 kDa homeostasis protein, p97.
Design and development of novel Co‐MOF nanostructures as an excellent catalyst for alcohol oxidation and Henry reaction, with a potential antibacterial activity
Authors: Aryanejad Sima , Bagherzade Ghodsieh , Moudi Maryam
Published: March 2019

The novel metal–organic framework Co2(bdda)1.5(OAc)1·5H2O (UoB‐3) was synthesized via a simple method at room temperature. UoB‐3 was characterized by the different methods, including X‐ray diffraction (XRD), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT‐IR), N2‐adsorption/desorption and elemental analysis. The catalytic ability of UoB‐3 was detected to be excellent for primary and secondary alcohols oxidation reaction with high yields under solvent‐free conditions. Moreover, UoB‐3 was highly active for Henry reaction of different aldehydes with nitromethane in water as a green solvent. The nanocatalyst can be recycled for five consecutive cycles without losing its activity and structural rigidity. The antibacterial activity of UoB‐3 nanostructures towards Gram‐negative bacteria, Escherichia coli and Gram‐positive bacteria, Bacillus cereus was also evaluated by using an inhibition zone test. These nanostructures exhibited strong antibacterial effect against both of them. The purpose of this study was the developing metal–organic framework materials with the enhanced activity in various fields.
Rational Design of Transition Metal Co‐Doped Ceria Catalysts for Low‐Temperature CO Oxidation
Authors: Kim Hyung Jun , Lee Geonhee , Jang Myeong Gon , Noh Kyung‐Jong , Han Jeong Woo
Published: March 2019

We present a highly active CeO2‐based catalyst for oxidizing CO in automobile exhaust. This catalyst was systemically designed by co‐doping with transition metals (TMs). First, we used density functional theory (DFT) calculations to screen Mn and 13 dopant TMs (periods 4∼6 in groups VIII∼XI) and their 91 binary combinations for co‐doping. As a result, Cu and (Cu, Ag) were found to be the best candidates among the single and binary dopants, respectively. Next, we synthesized CeO2 nanoparticles doped with Cu or (Cu, Ag), then experimentally confirmed that the predicted (Cu, Ag) co‐doped CeO2 showed higher activity than pure CeO2 and other TM‐doped CeO2. This was attributed to the easy formation of oxygen vacancies in the lattice of CeO2. Our study demonstrates that the use of a rational design of CeO2‐based catalyst through theoretical calculations and experimental validation can effectively improve the low‐temperature catalytic activity of CO oxidation.
Identification and Integration of Career Theory: Students’ Perspectives on the Process
Authors: Lindo Natalya A. , Cartwright Angie D. , Ceballos Peggy , Conner Charmaine , Edwards Josh , Blalock Sarah
Published: March 2019

In many counseling programs, while students are learning about career theory, they may be tasked in a separate course with identifying a theoretical approach to counseling. This may result in a dichotomous situation in which students lack an understanding of the relationship between career theory and counseling theory. Career counselors have long recognized the artificial distinction between career counseling and general counseling. However, counselor education programs generally lag, and there is a dearth of literature regarding the process of identifying and integrating career theory and counseling theory. This phenomenological study examined 6 students’ perceptions of the process of career theory identification and integration. Analysis of in‐depth interviews yielded 5 major themes: theory identification and integration, perceptions of career counseling, resources, personal dimensions, and application across the life span. Findings of this study have the potential to inform counselor education pedagogy regarding career theory identification and its application to the counseling context.
A 15‐Year Content Analysis of Three Qualitative Research Traditions
Authors: Flynn Stephen V. , Korcuska James S. , Brady Nicole V. , Hays Danica G.
Published: March 2019

The authors conducted a qualitative content analysis on the consistency, rigor, and methodological identity of 83 phenomenological (n= 44), grounded theory (n= 25), and consensual qualitative research (n= 14) articles published between 2002 and 2016. The results indicate a distinct pattern of qualitative research practices in professional counseling.
Importance of Electrocatalyst Morphology for the Oxygen Reduction Reaction
Authors: Liang Zuozhong , Zheng Haoquan , Cao Rui
Published: March 2019

Proton/anion‐exchange membrane fuel cells (PEMFC and AEMFC), generating electricity from the H2 energy with zero‐carbon emission, have become very promising energy conversion devices to meet the increasing energy demand and reduce the dependence on fossil fuels. Currently, platinum (Pt) based materials have proven to be the most efficient electrocatalysts for the oxygen reduction reaction (ORR) at the cathode of the PEMFC and AEMFC. However, the high price and the limited reserve of Pt greatly hinder their industrial applications. Recently, transition metal‐nitrogen‐carbon (M−N−C) based material, as an efficient alternative to replace the precious metal Pt‐based material, has attracted researchers’ attention. Great contributions have been devoted to develop M−N−C based electrocatalysts. This review summarizes recent advances on M−N−C based electrocatalysts used for ORR from the point view of morphology. One‐dimensional (1D), two‐dimensional (2D), three‐dimensional (3D) and multi‐dimensional (MD) M−N−C materials were discussed thoroughly with particular attention on the relationship between the structure and the catalytic activity.
Efficient Synthesis of Mandel Acetates by Electrochemical Carboxylation of Benzal Diacetates
Authors: Senboku Hisanori , Sakai Kanae , Fukui Akihiro , Sato Yusuke , Yamauchi Yusuke
Published: March 2019

Efficient synthesis of mandel acetate, 2‐acetoxy‐2‐phenylacetic acid, from benzaldehyde was successfully performed in two steps using electrochemical carboxylation of benzal diacetate as a key step. When benzal diacetate, readily prepared from benzaldehyde and acetic anhydride in one step, in DMF containing 0.1 M Bu4NBF4 was electrolyzed in the presence of carbon dioxide using an undivided cell equipped with a platinum plate cathode and a magnesium rod anode under constant current conditions, reductive cleavage of the C‐OAc bond followed by capture of carbon dioxide took place efficiently at the benzylic position to give mandel acetate in good to high yields. Wide scope, high yields and the use of carbon dioxide as a carbon source of the carboxyl group would provide novel environmentally‐benign synthesis of mandelic acid derivatives.
Enantioselective Friedel–Crafts Alkylation Reaction of Heteroarenes with N‐Unprotected Trifluoromethyl Ketimines by Means of Chiral Phosphoric Acid
Authors: Miyagawa Masamichi , Yoshida Masaru , Kiyota Yuki , Akiyama Takahiko
Published: March 2019

An enantioselective Friedel–Crafts alkylation reaction of pyrroles and indoles with N‐unprotected trifluoromethyl ketimines by use of chiral phosphoric acid provided α‐trifluoromethylated primary amines bearing chiral tetrasubstituted carbon centers in high yields and with high to excellent enantioselectivities. The present reaction is unique to N‐unprotected trifluoromethyl ketimines. No reaction took place with N‐p‐methoxyphenyl (PMP)‐substituted ketimine. Corresponding α‐trifluoromethylated amines were transformed without loss of enantioselectivity.
ControlChain: A new stage on the IoT access control authorization
Authors: Pinno Otto Julio Ahlert , Grégio André Ricardo Abed , De Bona Luis C.E.
Published: March 2019

The IoT is changing the way we interact with the world. Very soon, almost all of our daily tasks will be made through self intelligent systems embedded in devices scattered all around us. Their mission is to turn our cities, transportation systems, buildings, homes, and bodies in smart environments. These environments will bring us more comfort, improve our performance, increase our profits, and take away time‐consuming tasks. However, besides its great benefits, the IoT is also a big source of concerns, mainly because a good part of its devices will handle private and confidential information. Recently, cases of successful IoT invasions only worsen this scenario and show us that the today's adopted access control systems need to be replaced by more efficiently and secure ones. To overcome these access control problems, in this work, we present the ControlChain. The ControlChain is an access control authorization architecture that is heavily based on Blockchain technology. We also demonstrate the viability of the ControlChain through the E‐ControlChain, a proof‐of‐concept developed to run over the Ethereum network. Our proposals follows the IoT tendency requirements and are user‐transparent, user‐friendly, fully decentralized, scalable, fault tolerant, and compatible with a wide range of today's access control models already used in the IoT. Finally, we also make a cost and a performance analysis of E‐ControlChain, using a Raspberry Pi as an IoT device.
An accurate and simplified small signal parameter extraction method for GaN HEMT
Authors: Khusro Ahmad , Hashmi Mohammad S. , Ansari Abdul Quaiyum , Mishra Aditya , Tarique Mohammad
Published: March 2019

In this paper, development of a small signal model for 2 × 200 μm GaN HEMT based on the conventional 20‐element model is presented. The proposed model presents a direct parameter extraction algorithm, instead of the hybrid optimization approach, that provides simplification, accuracy, and less computational complexity. The extrinsic elements are extracted using a modified cold pinch‐off condition while discarding the unwanted forward biasing of the gate. The negative drain to source capacitance Cds is also observed in the ohmic region (for smaller VDS). An excellent agreement found between the measured and modeled data for a wide range of frequencies and bias values shows the effectiveness of the proposed approach. The proposed modeling technique is validated with a good agreement between the achieved bias dependency of intrinsic parameter values and the respective theoretical parameter values.
Application of micellar electrokinetic chromatography for detection of silver nanoparticles released from wound dressing
Authors: Konop Marek , Kłodzińska Ewa , Borowiec Joanna , Laskowska Anna Katarzyna , Czuwara Joanna , Konieczka Piotr , Cieślik Bartłomiej , Waraksa Emilia , Rudnicka Lidia
Published: March 2019

The recent emergence of nanotechnology has provided a new therapeutic modality in case of silver nanoparticles. Dressings containing silver form the basis for the treatment of burns and wounds, either acute or chronic ones. The aim of the study was to examine silver release from the different wound dressings: commercially available (Atrauman Ag, Aquacel Ag) and experimental (FKDP‐AgNPs) using MEKC. In order to characterize prepared keratin based wound dressing before and after its modification with AgNPs, a compositional analysis was conducted using energy dispersive X‐ray spectroscopy. Nanosilver toxicity was evaluated with the 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4 sulfophenyl)‐2H‐tetrazolium test. Silver release from wound dressings was assessed using MEKC. The best separation was observed for MEKC in 20 mM borate buffer at pH 9 with 20 mM SDS addition. In vitro studies showed silver at higher concentration than 10 ppm exerted a toxic effect on fibroblasts isolated from diabetic mice versus. NIH/3T3 and BJ cell lines (p < 0.05). We observed silver was released more gradually from experimental FKDP‐AgNPs wound dressing, in compare to commercially available wound dressings. The fast and low‐cost method utilizing MEKC can be used in clinical practice to detect silver release from the wound dressings.
Molecular analysis of glycosylphosphatidylinositol anchor deficient aerolysin resistant isolates in gulf war i veterans exposed to depleted uranium
Authors: Nicklas Janice A. , Vacek Pamela M. , Carter Elizabeth W. , McDiarmid Melissa , Albertini Richard J.
Published: March 2019

During the First Gulf War (1991) over 100 servicemen sustained depleted uranium (DU) exposure through wound contamination, inhalation, and shrapnel. The Department of Veterans Affairs has a surveillance program for these Veterans which has included genotoxicity assays. The frequencies of glycosylphosphatidylinositol anchor (GPIa) negative (aerolysin resistant) cells determined by cloning assays for these Veterans are reported in Albertini RJ et al. (2019: Environ Mol Mutagen). Molecular analyses of the GPIa biosynthesis class A (PIGA) gene was performed on 862 aerolysin‐resistant T‐lymphocyte recovered isolates. The frequencies of different types of PIGA mutations were compared between high and low DU exposure groups. Additional molecular studies were performed on mutants that produced no PIGA mRNA or with deletions of all or part of the PIGA gene to determine deletion size and breakpoint sequence. One mutant appeared to be the result of a chromothriptic event. A significant percentage (>30%) of the aerolysin resistant isolates, which varied by sample year and Veteran, had wild‐type PIGA cDNA (no mutation). As described in Albertini RJ et al. (2019: Environ Mol Mutagen), TCR gene rearrangement analysis of these isolates indicated most arose from multiple T‐cell progenitors (hence the inability to find a mutation). It is likely that these isolates were the result of failure of complete selection against nonmutant cells in the cloning assays. Real‐time studies of GPIa resistant isolates with no PIGA mutation but with a single TCR gene rearrangement found one clone with a PIGV deletion and several others with decreased levels of GPIa pathway gene mRNAs implying mutation in other GPIa pathway genes. Environ. Mol. Mutagen. 60:470–493, 2019. © 2019 Wiley Periodicals, Inc.
Pathways to specialist care for eating disorders: An Italian multicentre study
Authors: Volpe Umberto , Monteleone Alessio M. , Ricca Valdo , Corsi Elisa , Favaro Angela , Santonastaso Paolo , De Giorgi Serafino , Renna Caterina , Abbate Daga Giovanni , Amianto Federico , Balestrieri Matteo , Luxardi Gian Luigi , Clerici Massimo , Alamia Alberto , Segura‐Garcia Cristina , Rania Marianna , Monteleone Palmiero , Maj Mario
Published: March 2019

Two hundred forty six patients with eating disorders (EDs) recruited from eight Italian specialized treatment centres were administered with the World Health Organization “Encounter Form,” a standardized schedule that makes it possible to characterize the clinical pathways that patients follow to reach specialized care.

The median time from symptoms onset to specialized care was 114 weeks. Primary “points of access to care” were general practitioners (25%), psychiatrists (18%), and clinical nutritionists (17%), followed by various other carers. All patients received specific psychotherapy, whereas only 11% of them were given psychotropic drugs. EDs are characterized by complex care pathways, with low rates of direct access to specialized care. Although the role of general practitioners remains crucial, they tend to follow different clinical routes to refer ED patients. Educational programmes on EDs should be addressed to general practitioners and clinical nutritionists, in order to ease the transition of ED patients to a mental health care setting.
Aqueous leaf extract of Clinacanthus nutans improved metabolic indices and sorbitol‐related complications in type II diabetic rats (T2D)
Authors: Umar Imam Mustapha , Ismail Maznah , George Annie , Chinnappan Sasikala M. , Yusof Ashril
Published: March 2019

Clinacanthus nutans (Burm. f.) Lindau (C. nutans) has been reported to lower blood glucose level; however, evidence on its efficacy in lowering diabetic complications is limited. The antidiabetic properties of C. nutans aqueous leaf extract on serum metabolic indices, sorbitol production, and aldose reductase enzyme activities in the kidneys, lens, and sciatic nerve of type II diabetic (T2D) rats were evaluated. All rats except normal control rats were fed with a high‐fat diet for 8 weeks to induce obesity and subsequently injected with 35 mg/kg streptozotocin to induce type II diabetes. Aqueous leaf extract of C. nutans (100 and 200 mg kg−1 day−1) and quercetin (10 mg kg−1 day−1) were fed orally for 4 weeks. Diabetic rats administered with C. nutans at 100, 200 mg kg−1 day−1 and quercetin had significantly (p < 0.05) lower fasting blood glucose levels post‐intervention: 14.2, 14.0, and 19.9 mm, respectively, compared with the untreated group (22.1 mm). Total cholesterol was significantly (p < 0.05) lower in the C. nutans groups in comparison with the diabetic control group. Levels of F2‐isoprostane, a marker of oxidative stress, were attenuated in the presence of the extract. Aldose reductase enzyme activity increased by 64, 99, and 0% and total antioxidant activities by 22, 29, and 126%, respectively. Sorbitol levels in the kidney, lens, and nerve were reduced in diabetic rats administered with C. nutans and quercetin group (by 8, 16, and 3%, respectively). The protective effect of the extract to the liver and kidney was confirmed through liver and kidney enzyme markers and histological analyses. The C. nutans has the potential to attenuate T2D‐induced metabolic perturbations and complications related to sorbitol accumulation.
The mafic–ultramafic complex of Salem, southern India: An analogue for Neoproterozoic Alaskan‐type complex
Authors: Yellappa Thoti , Santosh M. , Manju S.
Published: March 2019

The Salem Mafic–Ultramafic Complex occurs within the northern part of Cauvery Suture Zone (CSZ), Southern Granulite Terrane (SGT), India. The complex occurs as semicircular to elongated linear body with a thick mantle section and comparatively well‐developed crustal section comprising different lithological units, also referred to as the Chalk Hills of Salem. The major rock types in the complex comprise ultramafic cumulates of dunite, peridotite, wherlite, pyroxenite, and hornblendite, mafic and felsic intrusions of gabbros and amphibolites, and quartzo–feldspathic alkaline rocks together with several ultrapotassic dykes. Geochemical studies of amphibolites from this complex indicate tholeiitic parent magma with enrichment of LIL elements (Rb, Ba, Th, and Sr) and are relatively more enriched than N‐MORB as compared with arc‐related rocks. The enrichment of LIL elements over the HFS elements and with distinct Nb, Ta, and Ti depletion relative to other HFS elements suggest the involvement of subduction‐related components in the depleted mantle source and that the magmatism occurred in an oceanic convergent realm. The mineral chemistry of dunite and peridotite shows high content of forsterite (86.9–92.2) in olivine and high Cr# value (80.85–98.73) for spinel. The tectonic discrimination plots of spinel and olivine mineral chemistry together with clinopyroxene chemistry of amphibolites reveal arc signature typical of Alaskan type of complex. The U–Pb zircon analysis of quartz monzonite intrusion within the hornblendite from the complex yielded a weighted mean age of 819 ± 2.4 Ma, suggesting that the complex formed during the Neoproterozoic and can be correlated to the Alaskan‐type complexes described from the Arabian–Nubian Shield.
Non‐Planar and Flexible Hole‐Transporting Materials from Bis‐Xanthene and Bis‐Thioxanthene Units for Perovskite Solar Cells
Authors: Urieta‐Mora Javier , García‐Benito Inés , Zimmermann Iwan , Aragó Juan , García‐Fernández Pedro D. , Grancini Giulia , Molina‐Ontoria Agustín , Ortí Enrique , Martín Nazario , Nazeeruddin Mohammad Khaja
Published: March 2019

Two new hole‐transporting materials (HTMs), BX‐OMeTAD and BTX‐OMeTAD, based on xanthene and thioxanthene units, respectively, and bearing p‐methoxydiphenylamine peripheral groups, are presented for their use in perovskite solar cells (PSCs). The novelty of the newly designed molecules relies on the use of a single carbon‐carbon bond ‘C−C’ as a linker between the two functionalized heterocycles, which increases the flexibility of the molecule compared with the more rigid structure of the widely used HTM spiro‐OMeTAD. The new HTMs display a limited absorbance in the visible region, due to the lack of conjugation between the two molecular halves, and the chemical design used has a remarkably impact on the thermal properties when compared to spiro‐OMeTAD. BX‐OMeTAD and BTX‐OMeTAD have been tested in ([(FAPbI3)0.87(MAPbBr3)0.13]0.92[CsPbI3]0.08)‐based PSC devices exhibiting power conversion efficiencies of 14.19 and 16.55 %, respectively. The efficiencies reached, although lower than those measured for spiro‐OMeTAD (19.63 %), are good enough to consider the chemical strategy used as an interesting via to design HTMs for PSCs.
Throughfall partitioning by trees
Authors: Levia Delphis F. , Nanko Kazuki , Amasaki Hiromasa , Giambelluca Thomas W. , Hotta Norifumi , Iida Shin'ichi , Mudd Ryan G. , Nullet Michael A. , Sakai Naoki , Shinohara Yoshinori , Sun Xinchao , Suzuki Masakazu , Tanaka Nobuaki , Tantasirin Chatchai , Yamada Kozo
Published: March 2019

Although we know that rainfall interception (the rain caught, stored, and evaporated from aboveground vegetative surfaces and ground litter) is affected by rain and throughfall drop size, what was unknown until now is the relative proportion of each throughfall type (free throughfall, splash throughfall, canopy drip) beneath coniferous and broadleaved trees. Based on a multinational data set of >120 million throughfall drops, we found that the type, number, and volume of throughfall drops are different between coniferous and broadleaved tree species, leaf states, and timing within rain events. Compared with leafed broadleaved trees, conifers had a lower percentage of canopy drip (51% vs. 69% with respect to total throughfall volume) and slightly smaller diameter splash throughfall and canopy drip. Canopy drip from leafless broadleaved trees consisted of fewer and smaller diameter drops (D50_DR, 50th cumulative drop volume percentile for canopy drip, of 2.24 mm) than leafed broadleaved trees (D50_DR of 4.32 mm). Canopy drip was much larger in diameter under woody drip points (D50_DR of 5.92 mm) than leafed broadleaved trees. Based on throughfall volume, the percentage of canopy drip was significantly different between conifers, leafed broadleaved trees, leafless broadleaved trees, and woody surface drip points (p ranged from <0.001 to 0.005). These findings are partly attributable to differences in canopy structure and plant surface characteristics between plant functional types and canopy state (leaf, leafless), among other factors. Hence, our results demonstrating the importance of drop‐size‐dependent partitioning between coniferous and broadleaved tree species could be useful to those requiring more detailed information on throughfall fluxes to the forest floor.
Identification of mutations associated with acquired resistance to sunitinib in renal cell cancer
Authors: Elgendy Mohamed , Fusco Juan Pablo , Segura Victor , Lozano Maria Dolores , Minucci Saverio , Echeveste Jose Ignacio , Gurpide Alfonso , Andueza Mapi , Melero Ignacio , Sanmamed Miguel F. , Ruiz Maria Rodriguez , Calvo Alfonso , Pascual Juan Ignacio , Velis Jose María , Miñana Bernardino , Valle Ricardo Diez , Pio Ruben , Agorreta Jackeline , Abengozar Marta , Colecchia Maurizio , Brich Silvia , Renne Salvatore Lorenzo , Guruceaga Elisabet , Patiño‐García Ana , Perez‐Gracia Jose Luis
Published: March 2019

Sunitinib is one of the most widely used targeted therapeutics for renal cell carcinoma (RCC), but acquired resistance against targeted therapies remains a major clinical challenge. To dissect mechanisms of acquired resistance and unravel reliable predictive biomarkers for sunitinib in RCC, we sequenced the exons of 409 tumor‐suppressor genes and oncogenes in paired tumor samples from an RCC patient, obtained at baseline and after development of acquired resistance to sunitinib. From newly arising mutations, we selected, using in silico prediction models, six predicted to be deleterious, located in G6PD, LRP1B, SETD2, TET2, SYNE1, and DCC. Consistently, immunoblotting analysis of lysates derived from sunitinib‐desensitized RCC cells and their parental counterparts showed marked differences in the levels and expression pattern of the proteins encoded by these genes. Our further analysis demonstrates essential roles for these proteins in mediating sunitinib cytotoxicity and shows that their loss of function renders tumor cells resistant to sunitinib in vitro and in vivo. Finally, sunitinib resistance induced by continuous exposure or by inhibition of the six proteins was overcome by treatment with cabozantinib or a low‐dose combination of lenvatinib and everolimus. Collectively, our results unravel novel markers of acquired resistance to sunitinib and clinically relevant approaches for overcoming this resistance in RCC.
Case–contrast study about parent–infant interaction in a Brazilian sample of siblings of children with autism spectrum disorders
Authors: Garcia Durand Julia , Batista Geraldini Stephania A. R. , Perez Paschoal Ligia , Cangueiro Larissa , Tamarozzi Mamede Denise , Scandiuzzi de Brito Tayná , Vaz Marques Monique , David Vinicius , Lerner Rogério
Published: March 2019

Siblings of children with autism spectrum disorders (ASD) present greater susceptibility to developmental problems, in comparison with siblings of typically developing children. The greater prevalence of mental health disorders among parents of children with ASD increases younger siblings’ vulnerability to emotional problems. The aim of this study is to compare the interaction between carers and babies aged 2 to 26 months (M = 11.7, SD = 6.9) who are siblings of children with ASD (ASD dyads) with the interaction of dyads of siblings of typically developing children (TD dyads). The protocol of Clinical Indicators of Risk for Child Development and the Coding Interactive Behaviour measures were used to evaluate interaction. ASD dyads presented higher scores of constriction in their interaction, P = .024, with babies presenting higher scores of withdrawal behavior, P = .003, and carers presenting higher scores of depressive mood, P = .008, when compared to TD dyads. The ASD dyads have interactive impairments more frequently than do the TD dyads.
Overexpression of Axl reverses endothelial cells dysfunction in high glucose and hypoxia
Authors: Pei‐Yuan Zuo , Yu‐Wei Liu , Xiang‐Nan Zha , Song Tong , Rong Zhang , Xiao‐Xiao He , Sheng‐Shuai Shan , Kun Wang , Cheng‐Yun Liu
Published: March 2019

The receptor tyrosine kinase Axl is involved in diabetic vascular disease. This study aims to investigate the effect of high glucose on endothelial cells injury and Axl expression in hypoxia condition in vitro, and we present details of the mechanism associated with overexpression of Axl rescue the high glucose injury. Our results showed that high glucose impaired both human umbilical vein endothelial cells (HUVECs) and EAhy926 cells angiogenesis in hypoxia condition. In addition, high glucose inhibits Axl and hypoxia‐inducible factor 1‐α (HIF‐1α) protein expression in hypoxia condition. Axl overexpression significantly reversed endothelial cells dysfunction in high glucose/hypoxia. Furthermore, Axl overexpression in EAhy926 cells increases HIF‐1α protein synthesis through PI3K/Akt/mTOR/p70
S6K signal pathway but not Mek/Erk in high glucose/hypoxia condition. This study demonstrates that high glucose can alter Axl signaling and HIF‐1α in hypoxia condition. Overexpression of Axl may rescue endothelial cells dysfunction and HIF‐1α expression through its downstream signals in high glucose/hypoxia.
Prognostic significance of X‐linked inhibitor of apoptosis protein in solid tumors: A systematic review and meta‐analysis
Authors: Li Shimeng , Pan Baoxiang , Li Lihong , Shi Bo , Xie Feng , He Chengyan
Published: March 2019

X‐linked inhibitor of apoptosis protein (XIAP) is aberrantly expressed in solid tumors. Considering conflicting data, we conducted this meta‐analysis to investigate its prognostic role. Electronic databases were searched to collect studies about associations between XIAP expressions and survival outcomes. Hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) were utilized as effect size estimates. A total of 3,794 patients from 21 published studies were included. The results revealed that high XIAP expressions correlated with age (OR = 2.02; 95% CI, 1.07–3.84), lymph node metastasis (OR = 1.69; 95% CI, 1.02–2.77), histological grade (OR = 2.04; 95% CI, 1.01–4.11), and tumor stage (OR = 2.18; 95% CI, 1.20–3.96). The combined HR revealed that high XIAP expressions associated with poor overall survival (OS) (HR = 1.60; 95% CI, 1.22–2.10). Our study suggested high XIAP expressions may be indicative of poor prognosis in solid tumors.
Prognostic comparison of the longitudinal margin status in distal bile duct cancer: R0 on first bile duct resection versus R0 after additional resection
Authors: Park Yejong , Hwang Dae Wook , Kim Jin Hee , Hong Seung‐Mo , Jun Sun‐Young , Lee Jae Hoon , Song Ki Byung , Jun Eun Sung , Kim Song Cheol , Park Kwang‐Min
Published: March 2019

Background

This study investigated survival differences following intra‐operative frozen‐section examination of bile duct resection margins and final longitudinal margin status (LMS) in distal bile duct cancer (BDC).

Methods

One hundred and ninety‐three patients underwent Whipple's operation for curative resection of distal BDC from 2008 to 2016. Patients were sorted into two and three groups according to LMS of the frozen‐sections and the final pathological specimen results: R0 on first bile duct resection (primary R0), R0 after additional resection (secondary R0), and no evidence of residual carcinoma (FR0), carcinoma in situ or high‐grade dysplasia (FR1‐CIS/HGD), or invasive carcinoma (FR1‐INV). Survival and prognostic factors according to LMS were analyzed.

Results

The final R0 ratio increased from 82.3% to 90.1% through additional resection. The 5‐year overall survival (OS) of primary and secondary R0 were 60.8%, 46.1% (P = 0.969). And disease‐free survival of primary and secondary R0 were 54.6%, 54.9% (P = 0.903). The 5‐year OS after FR0, FR1‐CIS/HGD, FR1‐INV were 59.3%, 59.5%, 14.3% (P = 0.842). LMS of the bile duct was an independent prognostic factor by multivariable analyses.

Conclusions

If R0 of final LMS was achieved, it would help to improve survival regardless of R0 through additional resection. And, it should be avoided remaining invasive cancer at the longitudinal margin whenever possible.
Proton MR spectroscopy in the breast: Technical innovations and clinical applications
Authors: Fardanesh Reza , Marino Maria Adele , Avendano Daly , Leithner Doris , Pinker Katja , Thakur Sunitha B.
Published: March 2019

Proton magnetic resonance spectroscopy (MRS) is a promising noninvasive diagnostic technique for investigation of breast cancer metabolism. Spectroscopic imaging data may be obtained following contrast‐enhanced MRI by applying the point‐resolved spectroscopy sequence (PRESS) or the stimulated echo acquisition mode (STEAM) sequence from the MR voxel encompassing the breast lesion. Total choline signal (tCho) measured in vivo using either a qualitative or quantitative approach has been used as a diagnostic test in the workup of malignant breast lesions. In addition to tCho metabolites, other relevant metabolites, including multiple lipids, can be detected and monitored. MRS has been heavily investigated as an adjunct to morphologic and dynamic MRI to improve diagnostic accuracy in breast cancer, obviating unnecessary benign biopsies. Besides its use in the staging of breast cancer, other promising applications have been recently investigated, including the assessment of treatment response and therapy monitoring. This review provides guidance on spectroscopic acquisition and quantification methods and highlights current and evolving clinical applications of proton MRS.

Level of Evidence 5

Technical Efficacy: Stage 5

J. Magn. Reson. Imaging 2019.