bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrolyzation of mogrosides: Immobilized β‐glucosidase for mogrosides deglycosylation from Lo Han Kuo
Authors: Wang Hsueh‐Ting , Yang Jin‐tong , Chen Kuan‐I , Wang Tan‐Ying , Lu Ting‐Jang , Cheng Kuan‐Chen
Published: January 2019

An immobilized enzyme system for bioconversion of Lo Han Kuo (LHK) mogrosides was established. β‐Glucosidase which was covalently immobilized onto the glass spheres exhibited a significant bioconversion efficiency from pNPG to pnitrophenol over other carriers. Optimum operational pH and temperature were determined to be pH 4 and 30°C. Results of storage stability test demonstrated that the glass sphere enzyme immobilization system was capable of sustaining more than 80% residual activity until 50 days, and operation reusability was confirmed for at least 10 cycles. The Michaelis constant (Km) of the system was determined to be 0.33 mM. The kinetic parameters, rate constant (K) at which Mogrosides conversion was determined, the τ50 in which 50% of mogroside V deglycosylation/mogroside IIIE production was reached, and the τ complete of complete mogroside V deglycosylation/mogroside IIIE production, were 0.044/0.017 min−1, 15.6/41.1 min, and 60/120 min, respectively. Formation of the intermediates contributed to the kinetic differences between mogroside V deglycosylation and mogroside IIIE formation.
Composite Membranes of PVDF Nanofibers Impregnated with Nafion for Increased Fuel Concentrations in Direct Methanol Fuel Cells
Authors: Li Y. , Hui J. , Kawchuk J. , O'Brien A. , Jiang Z. , Hoorfar M.
Published: January 2019

Serious methanol crossover of Nafion greatly limits the use of increased fuel concentrations in methanol fuel cells, which results in a decreased power density. To lower the methanol crossover of Nafion, thin layers of PVDF nanofibers were successfully electrospun and impregnated with a Nafion solution to create novel fuel cell membranes. The morphological structures, mechanical properties, thermal stabilities, chemical resistance and proton conductivity were investigated for each composite membrane. The performances of membranes with different layers of PVDF nanofibers were evaluated, using a single cell direct methanol fuel cell with 10M methanol fuel. In comparison with membranes of pure Nafion, the introduction of PVDF fiber mats greatly enhanced the membrane's thermal and oxidation stabilities, suppressed swelling ratios and water uptake, and increase fuel cell performance.
Study of Toxic Elements in River Water and Wetland Using Water Hyacinth (Eichhornia crassipes) as Pollution Monitor
Authors: Srivastava Alok , Chahar Vikas , Sharma Vishal , Swain Kollola K. , Hoyler Friedrich , Murthy Ganti S. , Scherer Ulrich W. , Rupp Hildegard , Knolle Friedhart , Maekawa Miyuki , Schnug Ewald
Published: January 2019

The concentration of toxic elements present in surface water of Sutlej River and Harike wetland besides Eichhornia crassipes, commonly known as water hyacinth, is estimated employing inductively coupled plasma mass spectrometry (ICP‐MS). Toxic elements such as cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), uranium (U), and zinc (Zn) are identified in the river as well as in Harike wetland catchment. Accumulation of elements in different parts of the water hyacinth plant is observed with the roots exhibiting maximum affinity followed by stem and then leaves. The removal efficacy of pollutants by water hyacinth is estimated using bioconcentration factor (BCF) index. It is found to be different for different elements, with Mn showing the highest and U the lowest magnitude. The study carried out in the present work indicates that rhizofiltration could play an important role in controlling pollutant load.
Carbon dioxide separation using α‐alumina ceramic tube supported cellulose triacetate‐tributyl phosphate composite membrane
Authors: Shankar Kunalan , Kandasamy Palanivelu
Published: January 2019

Carbon dioxide emissions to the atmosphere lead to global warming and unpredictable climate change via the greenhouse effect. Carbon dioxide from industrial sources can be captured by the membrane separation technique to mitigate the greenhouse effect. In this research, a polymer solution was prepared by blending a cellulose triacetate (CTA) polymer with a tri‐n‐butyl phosphate (TBP) additive. The polymer solution was coated on an alumina (α‐Al2O3) tube, which acted as a support material, to prepare a composite membrane for the CO2 separation. The composite membrane that was prepared was characterized by Fourier‐transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermo‐gravimetric analysis (TGA), and differential scanning calorimetry (DSC) analyses. The CO2 permeance and the selectivity for the prepared composite membrane were evaluated using a constant pressure‐variable volume method. The influence of the concentration of CTA and TBP, polymer solution preparation time, number of sequential dip coating, and the feed gas pressure on the CO2, N2, and CH4 gas separation performances was examined. The highest CO2 permeance of 129 GPU and the selectivity of 19.9 versus N2 and 10.6 against CH4 were obtained for the pure gases, and a CO2 permeance of 116 GPU and selectivity of 17.1 against N2 were obtained for a mixture of gases (15% CO2/85% N2). © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.
Outcomes following radiation for cutaneous squamous cell carcinoma of the head and neck: Associations between immune suppression and recurrence
Authors: Arbab Mona , Margalit Danielle N. , Tishler Roy B. , Rabinowits Guilherme , Pashtan Itai M. , Borgelt Bruce B. , Powlis William , Holdsworth Clay H. , Warren Laura E. , Schoenfeld Jonathan D.
Published: January 2019

Background

Data evaluating outcomes and patterns of recurrence following radiation therapy (RT) for cutaneous squamous cell carcinoma (cSCC) of the head and neck are limited.

Methods

We performed a retrospective analysis of 111 head and neck cSCC patients treated with RT at 4 affiliated institutions.

Results

With median follow‐up of 7 months, there were 29 (26%) recurrences, 73% of which were nodal (n = 21). Immunosuppression (IS) was the only factor associated with recurrence (47% in IS, 22% in non‐IS, P = .04), and also with time to recurrence in multivariate analysis (HR 5.5; P = .03). No factors were associated with recurrence among patients who received definitive RT. The majority of patients who recurred were salvaged with surgery (n = 20, 69%).

Conclusion

In a cohort of cSCC treated with radiotherapy, there was an association between IS and increased failure risk. The majority of failures were salvaged surgically.
Ethnopsychopharmacology study of patients' beliefs regarding concerns about and necessity of taking psychiatric medications
Authors: De las Cuevas Carlos , Motuca Mariano , Baptista Trino , Villasante‐Tezanos Alejandro G. , de Leon Jose
Published: January 2019

Objective

The aim of this study was to examine whether or not cultural differences influence beliefs about the necessity of taking prescribed psychiatric drugs and concern about their adverse effects in psychiatric outpatients in Spain, Argentina, and Venezuela.

Methods

This cross‐sectional study included 1,372 adult psychiatric outpatients using 2,438 psychotropic drugs and was designed to assess outpatients' beliefs about their prescribed medication. Patients completed sociodemographic, clinical questionnaires, and the Beliefs about Medicines Questionnaire Specific Scale and registered scores ranging from 1 to 5 on each of two subscales: concern and necessity. A “necessity‐concern differential” was obtained by calculating the difference (range −4 to +4).

Results

The global score, including all drugs in the total sample, had a mean necessity score of 3.50 ± 0.95, a mean concern score of 2.97 ± 0.99, and a mean differential score of 0.54 ± 1.42. The concern and necessity mean scores varied significantly across these three culturally Hispanic countries, probably across drug classes, and were associated with treatment duration. On the other hand, age and education played a very limited role.

Conclusions

Understanding the diverse effects of culture and society on these attitudes is highly relevant for the development of responsive mental health services in multicultural societies.
Evaporation from seasonally frozen bare and vegetated ground at various groundwater table depths in the Ordos Basin, Northwest China
Authors: Zhang Zaiyong , Wang Wenke , Gong Chengcheng , Wang Zhoufeng , Duan Lei , Yeh Tian‐chyi Jim , Yu Peiyuan
Published: January 2019

In cold climates, the process of freezing–thawing significantly affects the ground surface heat balance and water balance. To better understand the mechanism of evaporation from seasonally frozen soils, we performed field experiments at different water table depths on vegetated and bare ground in a semiarid region in China. Soil moisture and temperature, air temperature, precipitation, and water table depths were measured over a 5‐month period (November 1, 2016, to March 14, 2017). The evaporation, which was calculated by a mass balance method, was high in the periods of thawing and low in the periods of freezing. Increased water table depth in the freezing period led to high soil moisture in the upper soil layer, whereas lower initial groundwater levels during freezing–thawing decreased the cumulative evaporation. The extent of evaporation from the bare ground was the same in summer as in winter. These results indicate that a noteworthy amount of evaporation from the bare ground is present during freezing–thawing. Finally, the roots of Salix psammophila could increase the soil temperature. This study presents an insight into the joint effects of soil moisture, temperature, ground vegetation, and water table depths on the evaporation from seasonally frozen soils. Furthermore, it also has important implications for water management in seasonally frozen areas.
Assessing urban flood and drought risks under climate change, China
Authors: Liang Chen , Li Dingqiang , Yuan Zaijian , Liao Yishan , Nie Xiaodong , Huang Bin , Wu Xinliang , Xie Zhenyue
Published: January 2019

Risk analysis of urban flood and drought can provide useful guidance for urban rainwater management. Based on an analysis of urban climate characteristics in 2,264 Chinese cities from 1958 to 2017, this study evaluated urban flood and drought risks. The results demonstrated that the annual average values of precipitation, aridity index, frequency and intensity of extreme precipitation and extreme drought events differed significantly in these cities. The values of the above six climatic indicators in the cities ranged from 9.29–2639.30 mm, 0.47–54.73, 1.08–8.79 time, 7.82–107.25 mm, 0.76–2.99 time, and 10.30–131.19 days, respectively. The geographical patterns of urban precipitation, aridity index, intensity and frequency of extreme precipitation and drought events in China fit well to the Hu‐Huanyong Line that was created in 1940s to identify the pattern of population distribution. Extreme precipitation in most cities has upward trends, except for those around the Hu‐Huanyong Line. The extreme drought events had upward trends in the cities east of the Hu‐Huanyong Line, but there were downward trends in the cities west of the line. The risk assessment indicated that 3.80% cities were facing serious flood and 6.01% cities were facing serious drought risks, which are located in the coast of southern China and northwestern China, respectively, and other 90.19% cities were facing different types of drought and flood risks in terms of their intensity and frequency.
Topical film prepared with Rhus verniciflua extract‐loaded pullulan hydrogel for atopic dermatitis treatment
Authors: Jeong Ji Heun , Back Seung Keun , An Jong Hun , Lee Nam‐Seob , Kim Do‐Kyung , Na Chun Soo , Jeong Young‐Gil , Han Seung Yun
Published: January 2019

Atopic dermatitis (AD) is characterized by relapsing pruritus and skin dryness. Due to the pathogenic multiplicity and the adverse effects associated with the current therapeutics, development of transdermal drug delivery system is becoming an area of interest. Here, a novel topical film prepared with Rhus verniciflua extract (RVE)‐loaded pullulan hydrogel (RVE@PH) was synthesized and tested its therapeutic efficacy on the AD rats modeled by neonatal capsaicin injection method. The RVE@PH was characterized by a Fourier‐transform infrared spectroscopy and an in vitro release assay. Rat pups were randomly divided into two groups: vehicle‐treated (VEH; n = 5) and capsaicin‐treated (n = 15). The latter were given capsaicin subcutaneously at 24 h after birth for AD induction and further divided into three groups (n = 5 per each): not treated (CAP), pullulan hydrogel‐applied (PH), and RVE@PH‐applied (RVE‐PH). The pullulan hydrogel and RVE@PH were topically applied on shoulder lesions for 14 days (from 42 to 56 days after birth). Their phenotypes were compared based on the dermatitis score, epidermal thickness, mast cell infiltration, and serum myeloperoxidase (MPO) activities. The PH group showed significant attenuation in all the aforementioned values compared to the CAP group, suggesting that pullulan hydrogel itself has therapeutic activity against AD. Notably, the attenuations were more potent in the RVE‐PH group than the PH group, indicating that the therapeutic efficacy against AD is augmented by the presence of RVE, a loaded pharmaceutic. Collectively, these results indicate that RVE@PH inhibits AD through exerting the dual roles, that is, the pullulan hydrogel‐mediated physical and RVE‐mediated pharmaceutical actions. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2325–2334, 2019.
Density Functional Theory Calculations of Structural, Electronic, and Magnetic Properties of the 3d Metal Trifluorides MF3 (M = Ti‐Ni) in the Solid State
Authors: Mattsson Stefan , Paulus Beate
Published: January 2019

We employ density functional theory with Hubbard U correction or hybrid functionals to study the series of magnetic 3d metal trifluorides MF3 (M = Ti‐Ni). Experimental lattice parameters are reproduced with an error margin of 0.5%–4.3%. Cooperative Jahn–Teller distortions are reproduced for MnF3, but also found in TiF3 and CoF3 at smaller levels compared to MnF3. Trends in electronic structure with respect to positions of the d bands are linked to the magnetic properties where M = Ti‐Cr are weak magnetic Mott–Hubbard insulators, M = Fe‐Ni are strong magnetic charge‐transfer insulators and MnF3 falls in between. Our work contributes to the characterization of the relatively unknown NiF3, since FeF3 and CoF3 have similar electronic and magnetic properties. However, NiF3 does not show a Jahn–Teller distortion as present in CoF3. © 2019 Wiley Periodicals, Inc.
Improved cellular response on functionalized polypyrrole interfaces
Authors: Naghavi Alhosseini Sanaz , Moztarzadeh Fathollah , Karkhaneh Akbar , Dodel Masumeh , Khalili Mahsa , Eslami Arshaghi Tarlan , Elahirad Elnaz , Mozafari Masoud
Published: January 2019

Neuroregeneration strategies involve multiple factors to stimulate nerve regeneration. Neural support with chemical and physical cues to optimize neural growth and replacing the lesion neuron and axons are crucial for designing neural scaffolds, which is a promising treatment approach. In this study, polypyrrole polymerization and its functionalization at the interface developed by glycine and gelatin for further optimization of cellular response. Nanofibrous scaffolds were fabricated by electrospinning of polyvinyl alcohol and chitosan solutions. The electrospun scaffolds were polymerized on the surface by pyrrole monomers to form an electroactive interface for further applications in neural tissue engineering. The polymerized polypyrrole showed a positive zeta potential value of 57.5 ± 5.46 mV. The in vitro and in vivo biocompatibility of the glycine and gelatin‐functionalized polypyrrole‐coated scaffolds were evaluated. No inflammatory cells were observed for the implanted scaffolds. Further, DAPI nucleus staining showed a superior cell attachment on the gelatin‐functionalized polypyrrole‐coated scaffolds. The topography and tuned positively charged polypyrrole interface with gelatin functionalization is expected to be particularly efficient physical and chemical simultaneous factors for promoting neural cell adhesion.
Virtual screening identifies a PIN1 inhibitor with possible antiovarian cancer effects
Authors: Russo Spena Concetta , De Stefano Lucia , Poli Giulio , Granchi Carlotta , El Boustani Maguie , Ecca Fabrizio , Grassi Gabriele , Grassi Mario , Canzonieri Vincenzo , Giordano Antonio , Tuccinardi Tiziano , Caligiuri Isabella , Rizzolio Flavio
Published: January 2019

Peptidyl‐prolyl cis–trans isomerase, NIMA‐interacting 1 (PIN1) is a peptidyl‐prolyl isomerase that binds phospho‐Ser/Thr‐Pro motifs in proteins and catalyzes the cis–trans isomerization of proline peptide bonds. PIN1 is overexpressed in several cancers including high‐grade serous ovarian cancer. Since few therapies are effective against this cancer, PIN1 could be a therapeutic target but effective PIN1 inhibitors are lacking. To identify molecules with in vivo inhibitory effects on PIN1, we used consensus docking to model existing PIN1‐ligand X‐ray structures and to screen a chemical database for candidate inhibitors. Ten molecules were selected and tested in cellular assays, leading to the identification of VS10 that bound and inhibited PIN1. VS10 treatment reduced the viability of ovarian cancer cell lines by inducing proteasomal PIN1 degradation, without effects on PIN1 transcription, and also reduced the levels of downstream targets β‐catenin, cyclin D1, and pSer473‐Akt. VS10 is a selective PIN1 inhibitor that may offer new opportunities for treating PIN1‐overexpressing tumors.
An efficient method for extracting next‐generation sequencing quality RNA from liver tissue of recalcitrant animal species
Authors: Sharma Davinder , Golla Naresh , Singh Sudhakar , Singh Pankaj Kumar , Singh Dheer , Onteru Suneel Kumar
Published: January 2019

The next‐generation RNA sequencing technologies expedite the discovery of a large number of novel transcripts and genes associated with various pathophysiological conditions. These technologies involve poly(A) enrichment, which in turn requires micrograms of high‐quality total RNA. Unfortunately, the available RNA isolation approaches produce poor quality total RNA from difficult‐to‐isolate animal tissues, such as the liver with high glycogen content. Moreover, the extraction efficiencies of these approaches vary significantly depending on the animal species. To address this challenge, we optimized a three‐step protocol for the extraction of high‐yield and high‐quality total RNA from the liver tissue (LT). The procedure effectively resolved the problem of glycogen coprecipitation by its stepwise removal. No signs of RNA degradation on gel electrophoresis analysis and RNA integrity number values ≥8.5 indicated that the extracted RNA is suitable for downstream processing, such as poly(A) enrichment and transcriptome profiling. To demonstrate the robustness of the novel protocol, a comparison was made with other currently available RNA extraction approaches from diverse resources. Whereas other protocols yielded partially degraded bands with either decreased or reversed ribosomal RNA (rRNA) ratio, our protocol yielded intact rRNA with a ratio of 2.0 ± 0.1. This optimized protocol was also successfully followed for other animal tissues, such as the bone and muscles. In conclusion, the study has described a highly efficient method for the next‐generation sequencing quality RNA isolation from LT across a broad range of animal species, with extended applicability to other difficult‐to‐isolate tissues.
Muscle wasting in patients with end‐stage renal disease or early‐stage lung cancer: common mechanisms at work
Authors: Aniort Julien , Stella Alexandre , Philipponnet Carole , Poyet Anais , Polge Cécile , Claustre Agnès , Combaret Lydie , Béchet Daniel , Attaix Didier , Boisgard Stéphane , Filaire Marc , Rosset Eugénio , Burlet‐Schiltz Odile , Heng Anne‐Elisabeth , Taillandier Daniel
Published: January 2019

Background

Loss of muscle mass worsens many diseases such as cancer and renal failure, contributes to the frailty syndrome, and is associated with an increased risk of death. Studies conducted on animal models have revealed the preponderant role of muscle proteolysis and in particular the activation of the ubiquitin proteasome system (UPS). Studies conducted in humans remain scarce, especially within renal deficiency. Whether a shared atrophying programme exists independently of the nature of the disease remains to be established. The aim of this work was to identify common modifications at the transcriptomic level or the proteomic level in atrophying skeletal muscles from cancer and renal failure patients.

Methods

Muscle biopsies were performed during scheduled interventions in early‐stage (no treatment and no detectable muscle loss) lung cancer (LC), chronic haemodialysis (HD), or healthy (CT) patients (n = 7 per group; 86% male; 69.6 ± 11.4, 67.9 ± 8.6, and 70.2 ± 7.9 years P > 0.9 for the CT, LC, and HD groups, respectively). Gene expression of members of the UPS, autophagy, and apoptotic systems was measured by quantitative real‐time PCR. A global analysis of the soluble muscle proteome was conducted by shotgun proteomics for investigating the processes altered.

Results

We found an increased expression of several UPS and autophagy‐related enzymes in both LC and HD patients. The E3 ligases MuRF1 (+56 to 78%, P < 0.01), MAFbx (+68 to 84%, P = 0.02), Hdm2 (+37 to 59%, P = 0.02), and MUSA1/Fbxo30 (+47 to 106%, P = 0.01) and the autophagy‐related genes CTPL (+33 to 47%, P = 0.03) and SQSTM1 (+47 to 137%, P < 0.01) were overexpressed. Mass spectrometry identified >1700 proteins, and principal component analysis revealed three differential proteomes that matched to the three groups of patients. Orthogonal partial least square discriminant analysis created a model, which distinguished the muscles of diseased patients (LC or HD) from those of CT subjects. Proteins that most contributed to the model were selected. Functional analysis revealed up to 238 proteins belonging to nine metabolic processes (inflammatory response, proteolysis, cytoskeleton organization, glucose metabolism, muscle contraction, oxidant detoxification, energy metabolism, fatty acid metabolism, and extracellular matrix) involved in and/or altered by the atrophying programme in both LC and HD patients. This was confirmed by a co‐expression network analysis.

Conclusions

We were able to identify highly similar modifications of several metabolic pathways in patients exhibiting diseases with different aetiologies (early‐stage LC vs. long‐term renal failure). This strongly suggests that a common atrophying programme exists independently of the disease in human.
The authors reply: Letter on: “Pitfalls in the measurement of muscle mass: a need for a reference standard” by Clark et al.
Authors: Buckinx Fanny , Landi Francesco , Cesari Matteo , Fieding Roger A. , Visser Marjolein , Engelke Klaus , Maggi Stefania , Dennison Elaine , Al‐Daghri Nasser M. , Allepaerts Sophie , Bauer Jurgen , Bautmans Ivan , Brandi Maria‐Luisa , Bruyère Olivier , Cederholm Tommy , Cerreta Francesca , Cherubini Antonio , Cooper Cyrus , Cruz‐Jentoft Alphonso , McCloskey Eugene , Dawson‐Hughes Bess , Kaufman Jean‐Marc , Laslop Andrea , Petermans Jean , Reginster Jean‐Yves , Rizzoli René , Robinson Sian , Rolland Yves , Rueda Ricardo , Vellas Bruno , Kanis John A.
Published: January 2019

However, semantics aside, we think that DXA can indeed serve as a reference standard for measuring muscle mass. Obviously, CT and MRI are advanced techniques that can and have been used to obtain important information such as muscle size/volume and more recently amount and distribution of intra‐ and intermuscular adipose tissue. Also individual muscles can be assessed separately. However, with respect to muscle mass, the comparison of DXA with CT/MRI is rather difficult because DXA and QCT/MRI measure different physical parameters
2‐Deoxyribose‐5‐phosphate aldolase from Thermotoga maritima in the synthesis of a statin side‐chain precursor: characterization, modeling and optimization
Authors: Švarc Anera , Findrik Blažević Zvjezdana , Vasić‐Rački Đurđa , Szekrenyi Anna , Fessner Wolf‐Dieter , Charnock Simon J , Vrsalović Presečki Ana
Published: January 2019

BACKGROUND

Producing statin side‐chains by sequential aldol condensation catalyzed by 2‐deoxyribose‐5‐phosphate aldolase (DERA) (EC 4.1.2.4) is the best‐known and most promising synthetic route. The advantage of this process is the formation of two stereocenters in a single step starting from inexpensive achiral components, acetaldehyde and chloroacetaldehyde. The limitation for the industrial‐scale application is enzyme inactivation caused by substrates as well by the intermediate produced by single aldol addition.

RESULTS

The DERA enzyme from Thermotoga maritima (DERATm) was investigated extensively in this work. The influence of aldehydes on DERATm stability was studied in detail. Mathematical models in different reactor configurations were developed based on experimentally determined kinetic parameters of all reactions included in the synthesis of statin side‐chain. Models also included enzyme inactivation by all compounds with negative impact on its stability. Mathematical model‐based optimization enabled optimization of process conditions and reactor configuration. The fed‐batch reactor proved to be the most suitable choice achieving product concentration of 78 g L−1, productivity of 56 g L day−1 and yield of 95% under an optimal condition.

CONCLUSION

The validated mathematical model and applied methodology can be exploited for further process improvement and for process design of similar systems. © 2019 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Cloud‐based decision support system for the detection and classification of malignant cells in breast cancer using breast cytology images
Authors: Saba Tanzila , Khan Sana Ullah , Islam Naveed , Abbas Naveed , Rehman Amjad , Javaid Nadeem , Anjum Adeel
Published: January 2019

The advancement of computer‐ and internet‐based technologies has transformed the nature of services in healthcare by using mobile devices in conjunction with cloud computing. The classical phenomenon of patient–doctor diagnostics is extended to a more robust advanced concept of E‐health, where remote online/offline treatment and diagnostics can be performed. In this article, we propose a framework which incorporates a cloud‐based decision support system for the detection and classification of malignant cells in breast cancer, while using breast cytology images. In the proposed approach, shape‐based features are used for the detection of tumor cells. Furthermore, these features are used for the classification of cells into malignant and benign categories using Naive Bayesian and Artificial Neural Network. Moreover, an important phase addressed in the proposed framework is the grading of the affected cells, which could help in grade level necessary medical procedures for patients during the diagnostic process. For demonstrating the e effectiveness of the proposed approach, experiments are performed on real data sets comprising of patients data, which has been collected from the pathology department of Lady Reading Hospital of Pakistan. Moreover, a cross‐validation technique has been performed for the evaluation of the classification accuracy, which shows performance accuracy of 98% as compared to physical methods used by a pathologist for the detection and classification of the malignant cell. Experimental results show that the proposed approach has significantly improved the detection and classification of the malignant cells in breast cytology images.
Synthesis, Characterization, and Structure of Quinoline‐based Benzimidazole Derivatives
Authors: Raj Manaswini , Padhi Sumanta Kumar
Published: January 2019

Quinoline‐based benzimidazole compounds have been successfully synthesized and characterized by various spectroscopic techniques like FT‐IR, 1H NMR, 13C NMR, and mass spectral analysis, and the structures have been authenticated by single crystal X‐ray diffraction method. Here, we report an economical, mild, and efficient procedure that involves condensation of 8‐hydroxyquinoline‐2‐carbaldehyde with various diamines as substrates to give bis‐imines. A systematic study towards both aliphatic and aromatic bis‐imines has been conducted to investigate the ring‐closure reaction that generates the benzimidazole moiety in the heterocyclic compounds discussed in this study. Aliphatic bis‐imines does not undergo cyclization; however, the bis‐imines derived from o‐phenylenediamine and derivatives generates heterocyclic compounds with benzimidazole moiety. In contrast to synthetic procedures reported earlier for benzimidazoles, the reaction conditions herein reported are simpler. Path for reactions holds initial condensation with one equivalent of 8‐hydroxyquinoline‐2‐carbaldehyde to form mono‐imine followed by immediate intramolecular ring closure. The subsequent nupleophilic attack to another equivalent of 8‐hydroxyquinoline‐2‐carbaldehyde and migration of hydride generates the benzimidazole moiety and the active methylene group. The ─CH2 group was confirmed from 1H and 13C NMR, wherein the two hydrogens appeared at around 6.40–6.52 ppm and the carbon center appeared at 51.54–51.77 ppm. The single crystal X‐ray diffraction also confirmed the formation of benzimidazole moiety and the active methylene group in the heterocyclic compounds discussed in this study.
A Green Protocol for Simple One‐pot Synthesis of New Pyrimidine Derivatives Both Microwave Irradiation and Conventional Heating: Reactions, Characterization, and Theoretical Calculations
Authors: Akbas Esvet , Ruzgar Adem , Sahin Ertan , Ergan Erdem
Published: January 2019

In this research, 5‐benzoyl‐6‐phenyl‐4‐(4‐trifluoromethylphenyl)‐2‐{oxo and thioxo}‐3,4‐dihydro‐1H‐pyrimidines (1, 2) were synthesized by using multicomponent cyclocondensation reaction under microwave irradiation and classical heating. Compounds 3, 4, 6, 7, and 8 obtained reactions of 5‐benzoyl‐6‐phenyl‐4‐(4‐trifluoromethylphenyl)‐2‐thioxo‐3,4‐dihydro‐1H‐pyrimidine (1) and acetic anhydride, diethyl 2‐bromomalonate, bromoacetic acid, 3‐bromopropionic acid, methyl iodide, respectively. Compound 4 was both acetylated and hydrolyzed in acetic acid to give compound 5. The structures of all compounds were determined by using spectroscopic techniques like FT‐IR, 1H/13C NMR, and elemental analyses, and the structures of compounds 1 and 3 were analyzed by X‐ray crystal analysis. In addition, the quantum chemical parameters and full geometry optimizations for all compounds were computed using density functional theory based on B3LYP and the 6‐31G (d, p) basis set.
Direct Synthesis of Multi‐functional Pyrimidine, Pyrazine, and Pyridine Scaffolds via Inter‐ and Intramolecular Annulations of 3‐Amino‐thieno[2,3‐b]pyridine‐2‐carboxylate
Authors: El‐Sayed Hassan A. , Said Said A.
Published: January 2019

The synthesis of a new series of annulated thieno[2,3‐b]pyridines was performed. Ester compound 1 underwent heterocyclization upon reaction with phenylisothiocyanate and formamide to afford pyrimidines 2 and 3, respectively. Thienopyrimidine 5 was resulted via reaction of amino derivative 1 with triethyl orthoformate to afford the non‐isolable intermediate 4, which allowed hydrazinolysis with hydrazine hydrate to afford the target compound. Pyrimidine type 5 was condensed with p‐nitrobenzaldehyde to afford Schiff base 6. Refluxing of ester 1 with ethyl cyanoacetate and diethyl malonate followed by base‐mediated heterocyclization afforded condensed pyridines 8 and 9, respectively. The tetracyclic pyrazine derivative 14 was obtained from the reaction of amino compound 1 with 2,5‐dimethoxytetrahydrofuran followed by hydrazinolysis to give carbohydrazide 11, which undergo diazotization followed by Curtius rearrangement. The antibacterial results illustrated no significant results for the investigated compounds except compound 5, which has moderate activity against Gram‐positive bacteria.
Design, Synthesis, and Anticancer Activity of New Oxadiazolyl‐Linked and Thiazolyl‐Linked Benzimidazole Arylidines, Thioglycoside, and Acyclic Analogs
Authors: Nassar Ibrahim F. , El kady Dina S. , Awad Hanem M. , El‐Sayed Wael A.
Published: January 2019

2‐[(4‐Thiazolylmethyl)thio]‐1H‐benzimidazole 3 was prepared and was allowed to react with ethyl chloroactate then with hydrazine hydrate to afford the hydrazide derivative 5, which was then reacted with aromatic aldehydes to afford the corresponding arylidine derivatives 6–9. Heterocyclization of the latter hydrazones with acetic anhydride afforded the substituted 1,3,4‐oxadiazoline derivatives 10–13. In addition, new ((thiazolyl)imidazolyl) oxadiazole thioglycoside and acyclic‐C nucleoside analog were prepared via heterocylization of the hydrazide 5 then glycosylation with α‐acetobromoglucose or condensation with D‐xylose, respectively. All the new compounds were structurally characterized. The anticancer activity of some of the newly synthesized compounds was studied against human breast cancer cells (MCF‐7). The results of the anticancer activity showed that compounds 8, 11, 12, 17, and 18 revealed high activities superior to Doxorubicin; however, the other derivatives showed moderate to low inhibition activities against human breast cancer cells. Docking studies into CDK2 enzyme were investigated, which supported the anticancer activity results.
Trends and predictors of non‐communicable disease multimorbidity among adults living with HIV and receiving antiretroviral therapy in Brazil
Authors: Castilho Jessica L , Escuder Maria M , Veloso Valdiléa , Gomes Jackeline O , Jayathilake Karu , Ribeiro Sayonara , Souza Rosa A , Ikeda Maria L , de Alencastro Paulo R , Tupinanbas Unai , Brites Carlos , McGowan Catherine C , Grangeiro Alexandre , Grinsztejn Beatriz
Published: January 2019

Introduction

People living with HIV (PLHIV) on antiretroviral therapy (ART) experience high rates of non‐communicable diseases (NCDs). These co‐morbidities often accumulate and older adults may suffer from multimorbidity. Multimorbidity has been associated with loss of quality of life, polypharmacy, and increased risk of frailty and mortality. Little is known of the trends or predictors NCD multimorbidity in PLHIV in low‐ and middle‐income countries.

Methods

We examined NCD multimorbidity in adult PLHIV initiating ART between 2003 and 2014 using a multi‐site, observational cohort in Brazil. NCDs included cardiovascular artery disease, hyperlipidemia (HLD), diabetes, chronic kidney disease, cirrhosis, osteoporosis, osteonecrosis, venous thromboembolism and non‐AIDS‐defining cancers. Multimorbidity was defined as the incident accumulation of two or more unique NCDs. We used Poisson regression to examine trends and Cox proportional hazard models to examine predictors of multimorbidity.

Results

Of the 6206 adults, 332 (5%) developed multimorbidity during the study period. Parallel to the ageing of the cohort, the prevalence of multimorbidity rose from 3% to 11% during the study period. Older age, female sex (adjusted hazard ratio (aHR) = 1.30 (95% confidence interval (CI) 1.03 to 1.65)) and low CD4 nadir (<100 vs. ≥200 cells/mm3 aHR = 1.52 (95% CI: 1.15 to 2.01)) at cohort entry were significantly associated with increased risk of multimorbidity. Among patients with incident multimorbidity, the most common NCDs were HLD and diabetes; however, osteoporosis was also frequent in women (16 vs. 35% of men and women with multimorbidity respectively).

Conclusions

Among adult PLHIV in Brazil, NCD multimorbidity increased from 2003 to 2014. Females and adults with low CD4 nadir were at increased risk in adjusted analyses. Further studies examining prevention, screening and management of NCDs in PLHIV in low‐ and middle‐income countries are needed.
Mitochondria as emerging targets for therapies against T cell acute lymphoblastic leukemia
Authors: Olivas-Aguirre Miguel , Pottosin Igor , Dobrovinskaya Oxana
Published: January 2019

Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of hematologic malignancies, arising from diverse genetic alterations in the early lymphocyte development. T-cell subtype of ALL (T-ALL) accounts for about 15% and 25% of ALL in children and adults, respectively. Being less frequent among ALL subtypes, T-ALL represents a high-risk factor for poor prognosis due to its aggressiveness and resistance to common antileukemic drugs. Mitochondria were widely explored recently as a target for anticancer treatment because they are involved in a metabolic reprogramming of a cancer cell and play key roles in reactive oxygen species generation, Ca2+ signaling, and cell death induction. Accordingly, a new class of anticancer compounds named mitocans has been developed, which target mitochondria at distinct crucial points to promote their dysfunction and subsequent cell death. The present review analyses the role of mitochondria in malignant reprogramming and emerging therapeutic strategies targeting mitochondria as an “Achilles’ heel” in T-ALL, with an emphasis on BH3 mimetics, sequestering pro-survival BCL proteins and voltage-dependent anion channel (VDAC)1-directed drugs, which promote the suppression of aerobic glycolysis, VDAC1 closure, mitochondrial Ca2+ overload, stoppage of the oxidative phosphorylation, oxidative stress, and release of proapoptotic factors.
Uptake and nutrient balance of nitrogen, sulfur, and boron for optimal canola production in eastern Canada
Authors: Ma Bao-Luo , Zheng Zhiming , Whalen Joann K. , Caldwell Claude , Vanasse Anne , Pageau Denis , Scott Peter , Earl Hugh , Smith Don L.
Published: January 2019

Balanced plant nutrition is essential to achieve high yields of canola (Brassica napus L.) and get the best economic return from applied fertilizers. A field study was conducted at nine site‐years across eastern Canada to investigate the effects of nitrogen (N), sulfur (S) and boron (B) fertilization on canola nutrient uptake, nutrient balance, and their relationship to canola yields. The factorial experiment consisted of four N rates of 0 (N0), 50 (N50), 100 (N100), and 150 (N150) kg ha−1, two S rates of 0 (S0) and 20 (S20) kg ha−1, and three B treatments of 0 (B0), 2 kg ha−1 at preplant (B2.0P), and 0.5 kg B ha−1 foliar‐applied at early flowering stage (B0.5F). Each site‐year used the same experimental design and assigned treatments in a randomized complete block design with four replications. Fertilizer S application greatly improved seed yields at six out of nine site‐years, and the highest N use efficiency was in the N150+S20 treatment. Sulfur application generally increased seed S concentration, seed S removal, and plant total S uptake, while B fertilization mainly elevated straw B concentration and content, with minimal effect on seed yields. At the early flowering stage, plant tissue S ranged from 2.2 to 6.6 mg S g−1, but the N : S ratio was over or close to the critical value of 12 in the N150+S0 combination at five site‐years. On average across nine site‐years, canola reached a plateau yield of 3580 kg ha−1 when plants contained 197 kg N ha−1, 33 kg S ha−1 and 200 g B ha−1, with a seed B content of 60 g B ha−1. The critical N, S, and B values identified in this work and their potential for a posteriori nutrient diagnosis of canola should be useful to validate fertilizer requirements for canola production in eastern Canada.
The Raman signature of protonic species as a potential tool for dating or authentication of glazed pottery
Authors: Kırmızı Burcu , Chen Stephen , Colomban Philippe
Published: January 2019

In this study, the potential of Raman spectroscopy is discussed for the comparative dating or authentication of glazed pottery based on the Raman signature of protonic species incorporated in the glazes due to the corrosion processes as a function of time, chemical composition, and environmental conditions. According to the literature and analyses on a reference set of glass samples that had previously been subjected to heavy corrosion in laboratory conditions and extensively studied by Infrared spectroscopy, the accumulation of protonic species such as water and hydroxyl groups on the surface of glassy silicates gives rise to a specific Raman signature in the 2,000–3,800 cm−1 range. The relative intensity of this Raman signature is mainly considered to act as a means of discriminating between old and modern artefacts. In order to check this hypothesis, glazed pottery with different origins (Chinese and Vietnamese stoneware or celadons, blue‐and‐white and painted enamelled porcelains, Islamic terra cottas) and different chemical compositions or processing conditions from a wide time span (~1000 to the present) were analysed by Raman microspectroscopy. Further comparative data was obtained by modifying the experimental parameters such as laser wavelength, objective magnification, and confocal hole. The results showed that Raman intensity of the protonic species shows a correlation with age for lead free glazed pottery in the case of celadons and porcelains. The intensity strongly depends on the chemical composition of the glaze as well as the preservation conditions to a certain degree.
Control of antioxidant efficiency of chlorogenates in emulsions: modulation of antioxidant interfacial concentrations
Authors: Meireles Mafalda , Losada‐Barreiro Sonia , Costa Marlene , Paiva‐Martins Fátima , Bravo‐Díaz Carlos , Monteiro Luís S
Published: January 2019

BACKGROUND

Controlling the interfacial concentrations of antioxidants (AOs) in oil‐in‐water emulsions can be regarded as a unique approach for increasing the efficiency of AOs in inhibiting the oxidation of lipids. Classical methods to determine the AO distribution in binary systems cannot be employed and their distribution needs to be assessed in the intact emulsion.

RESULTS

We have employed a well‐established kinetic method to determine the distribution of a homologous series of AOs derived of chlorogenic acid in olive oil‐in‐water emulsions and analyse the effects of AO hydrophobicity on their distributions and their efficiencies. Results indicate that variations in the efficiency of chlorogenates in emulsions are due to differences in their interfacial concentrations. Their interfacial concentrations AOI were much higher (20‐ to 150‐fold) than their stoichiometric concentrations. On the other hand, their concentrations in the oil region were 1.5‐ to 0.1‐fold. Results also show the complex effect of the oil‐to‐water ratio employed in the preparation of the emulsions on the (AOI) values.

CONCLUSION

Results highlight the key role of the interfacial region and of its composition (interfacial AO molarity, emulsifier concentration, oil‐to‐water ratio) in interpreting the efficiency of AOs in inhibiting lipid oxidation in emulsions. Thus, a careful modulation of these parameters is necessary to ensure optimum AO efficiency. © 2019 Society of Chemical Industry
Engineering of scaffold‐free tri‐layered auricular tissues for external ear reconstruction
Authors: Chiu Loraine L. Y. , Weber Joanna F. , Waldman Stephen D.
Published: January 2019

Objectives

Current strategies for external ear reconstruction can lead to donor site morbidity and/or surgical complications. Tissue‐engineered auricular tissues may provide readily available reconstructive materials that resemble native auricular tissue, which is composed of a cartilaginous region sandwiched between two perichondrial layers. We previously developed scaffold‐free bi‐layered auricular tissues, consisting of a perichondrial layer and a cartilaginous layer, by cultivating chondrocytes and perichondrial cells in a continuous flow bioreactor. Here, we aimed to improve construct properties and develop strategies to engineer tri‐layered auricular constructs that better mimic native auricular tissue.

Study Design

Experimental study.

Methods

Different concentrations of insulin‐like growth factor (IGF)‐1 and insulin were supplemented during bioreactor culture to determine conditions for engineering bi‐layered constructs. We also investigated two methods of engineering tri‐layered constructs. Method 1 used Ficoll separation to isolate perichondrial cells, followed by the seeding of isolated perichondrial cells onto the opposing side of the bi‐layered constructs. Method 2 involved the growth of the bi‐layered constructs in osteogenic culture medium.

Results

The combination of 10 nM IGF‐1 and 100 nM insulin led to increased collagen content in the engineered bi‐layered constructs. For developing tri‐layered constructs, method 2 yielded thicker constructs with better mechanical and biochemical properties compared to method 1. In addition, the presence of the perichondrial layers protected the engineered constructs from tissue calcification.

Conclusion

Auricular tissues with a biomimetic microstructure can be created by growing chondrocytes and perichondrial cells in a continuous flow bioreactor, followed by cultivation in osteogenic medium.

Level of Evidence

NA

Laryngoscope, 129:E272–E283, 2019
The Brain Oxylipin Profile Is Resistant to Modulation by Dietary n‐6 and n‐3 Polyunsaturated Fatty Acids in Male and Female Rats
Authors: Ferdouse Afroza , Leng Shan , Winter Tanja , Aukema Harold M.
Published: January 2019

Oxylipins are bioactive lipids formed by the monooxygenation of polyunsaturated fatty acids (PUFA). Eicosanoids derived from arachidonic acid (ARA) are the most well‐studied class of oxylipins that influence brain functions in normal health and in disease. However, comprehensive profiling of brain oxylipins from other PUFA with differing functions, and the examination of the effects of dietary PUFA and sex differences in oxylipins are warranted. Therefore, female and male Sprague–Dawley rats were provided standard rodent diets that provided additional levels of the individual n‐3 PUFA α‐linolenic acid (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), or the n‐6 PUFA linoleic acid (LNA) alone or with ALA (LNA + ALA) compared to essential fatty acid‐sufficient control diets. Oxylipins and PUFA were quantified in whole brains using HPLC‐MS/MS and GC, respectively. Eighty‐seven oxylipins were present at quantifiable levels: 51% and 17% of these were derived from ARA and DHA, respectively. At the mass level, ARA and DHA oxylipins comprised 81–90% and 6–12% of total oxylipins, while phospholipid ARA and DHA represented 25–35% and 49–62% of PUFA mass, respectively. Increasing dietary n‐3 PUFA resulted in higher levels of oxylipins derived from their precursor PUFA; otherwise, the brain oxylipin profile was largely resistant to modulation by diet. Approximately 25% of oxylipins were higher in males, and this was largely unaffected by diet, further revealing a tight regulation of brain oxylipin levels. These fundamental data on brain oxylipin composition, diet effects, and sex differences will help guide future studies examining the functions of oxylipins in the brain.