bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuation of structure–activity relationship study of novel benzamide derivatives as potential antipsychotics
Authors: Xu Mingshuo , Guo Shuang , Yang Feipu , Wang Yu , Wu Chunhui , Jiang Xiangrui , Zhao Qingjie , Chen Weiming , Tian Guanghui , Zhu Fuqiang , Xie Yuanchao , Hu Tianwen , Wang Zhen , He Yang , Shen Jingshan
Published: January 2019

A series of benzamide derivatives possessing potent dopamine D2, serotonin 5‐HT1A, and 5‐HT2A receptor properties were synthesized and evaluated as potential antipsychotics. Among them, 5‐(4‐(4‐(benzo[d]isothiazol‐3‐yl)piperazin‐1‐yl)butoxy)‐N‐cyclopropyl‐2‐fluorobenzamide (4k) held the best pharmacological profile. It not only exhibited potent and balanced activities for the D2, 5‐HT1A, and 5‐HT2A receptors, but was also endowed with low to moderate activities for the 5‐HT2C, H1, and M3 receptors, suggesting a low propensity for inducing weight gain or diabetes. In animal models, compound 4k reduced phencyclidine‐induced hyperactivity with a high threshold for catalepsy or muscle relaxation induction. On the basis of its robust in vitro potency and in vivo efficacy in preclinical models of schizophrenia, 4k was selected as a candidate for further development.
Neuroanatomy, the Achille’s Heel of Medical Students. A Systematic Analysis of Educational Strategies for the Teaching of Neuroanatomy
Authors: Sotgiu Maria Alessandra , Mazzarello Vittorio , Bandiera Pasquale , Madeddu Roberto , Montella Andrea , Moxham Bernard
Published: January 2019

Neuroanatomy has been deemed crucial for clinical neurosciences. It has been one of the most challenging parts of the anatomical curriculum and is one of the causes of “neurophobia,” whose main implication is a negative influence on the choice of neurology in the near future. In the last decades, several educational strategies have been identified to improve the skills of students and to promote a deep learning. The aim of this study was to systematically review the literature to identify the most effective method/s to teach human neuroanatomy. The search was restricted to publications written in English language and to articles describing teaching tools in undergraduate medical courses from January 2006 through December 2017. The primary outcome was the observation of improvement of anatomical knowledge in undergraduate medical students. Secondary outcomes were the amelioration of long‐term retention knowledge and the grade of satisfaction of students. Among 18 selected studies, 44.4% have used three‐dimensional (3D) teaching tools, 16.6% near peer teaching tool, 5.55% flipped classroom tool, 5.55% applied neuroanatomy elective course, 5.55% equivalence‐based instruction‐rote learning, 5.55% mobile augmented reality, 5.55% inquiry‐based clinical case, 5.55% cadaver dissection, and 5.55% Twitter. The high in‐between study heterogeneity was the main issue to identify the most helpful teaching tool to improve neuroanatomical knowledge among medical students. Data from this study suggest that a combination of multiple pedagogical resources seems to be the more advantageous for teaching neuroanatomy.
Identification of Wiener models for dynamic and steady‐state performance with application to solid oxide fuel cell
Authors: Ławryńczuk Maciej
Published: January 2019

This work is concerned with identification of Wiener models (a linear dynamic part connected in series with a nonlinear dynamic one). A neural network with one hidden layer is used as the nonlinear block of the model, two network configurations are considered. For model identification three algorithms are described. In the first case model accuracy only in transient conditions is considered, only the dynamic data is used for model training. In the next two algorithms model accuracy in both transient and steady‐state conditions is considered, dynamic and steady‐state data sets are used. The steady‐state model errors are taken into account by an additional term in the minimized cost‐function or by additional inequality constraints. For comparison of discussed algorithms and model structures, identification of a Wiener model of a solid oxide fuel cell (SOFC) process is considered. It is shown that the best results are obtained by the algorithm 2 which minimizes at the same time both dynamic and steady‐state model errors, additional constraints used in the algorithm 3 are computationally quite demanding.
Zone model predictive control for pressure management of water distribution network
Authors: Liu Dongming , Zheng Yi , Wu Jing , Li Shaoyuan
Published: January 2019

In the water distribution network (WDN), although the water demand of the node is changing constantly, the water quantity and water pressure of the node need to be met at each moment. To realize energy saving and consumption reduction, it is proposed to control the nodal water head of WDN in an appropriate narrow range. The frequent large fluctuation of the water demand, which may lead the water pressure exceed the expected range, increases the difficulty of the zone control. To realize optimized WND control, a novel zone predictive control is proposed, where two switching cases are considered. The switching condition is whether there are feasible solutions to keep the pressure within the expected region over the prediction horizon. When the condition is satisfied, the controller minimizes the variation of inputs with constraints of pressure range for ensuring the tank level staying within the expected zone and obtaining optimal economic cost. When the current pressure is out of the expected region or the condition is not satisfied due to the large variation of water demand, a reference trajectory of outputs is introduced, which is combined with the inputs as an optimization variable, and the constraints of expected zone are moved from the output to the introduced reference trajectory. Through minimizing the distance between reference trajectory and output, the controller will keep the tank level from deviating too far from the expected zone and will drive the tank level rapidly into the expected zone once the tank level exceeds the expected range. An application of the proposed zone MPC to WDN in Shinan District of Shanghai is given to illustrate its effectiveness.
Total cloud cover climatology over the United Arab Emirates
Authors: Yousef Latifa A. , Temimi Marouane , Wehbe Youssef , Al Mandous Abdulla
Published: January 2019

Cloud climatologies are of great importance in the study of cloud dynamics and interactions with land, oceans and atmosphere. This study analyzes the climatology of Total Cloud Cover (TCC) over the United Arab Emirates (UAE). Monthly mean TCC data between 1984 and 2009 from ground observations at six UAE airport stations and the satellite‐based (CLARA A2) product are utilized.

The hourly ground observations are first filtered to match the overpass times of CLARA‐A2 satellites over the UAE. Comparison between the datasets reveals higher TCC reports by CLARA‐A2. These are attributed to several factors, such as the underestimation of TCC by human observers and the region's aerosol loading, surface albedo and emissivity, which impact the quality of remote sensing retrievals. Satellites utilized for CLARA‐A2 are known to have undergone changes in their numbers and orbits over the years, prompting an investigation of its homogeneity. Change points are found to occur in 1991 and 1998, related to increased satellite measurements and sensor changes, respectively. Further investigations of the homogeneity of means and variances before and after the change points are also conducted, resulting in confirmation of the inhomogeneity induced by artifacts.

Monthly means of hourly ground observations are then used for analysis of TCC climatology over the six stations. Fujairah has the highest TCC on average, due to its proximity to the Hajar mountains and the Oman gulf. Most of the stations exhibit significant decreasing trends, in addition to a change point occurring in 1998. This is theorized to be related to the El Niño Southern Oscillation phase change occurring in the same period. The potential teleconnection is explored further through testing for correlations of TCC with the Oceanic Niño Index, with results showing a strong link in the fall–winter seasons.
Testicular function in cultured postnatal mouse testis fragments is similar to that of animals during the first wave of spermatogenesis
Authors: Pence Lisa M. , Schmitt Thomas C. , Beger Richard D. , Del Valle Pedro L. , Nakamura Noriko
Published: January 2019

Background

Previously, we evaluated optimal organ culture conditions to produce elongated spermatids in an in vitro mouse testis culture system. However, differences in testicular function between the cultured testis fragments and animal testis have not been determined.

Methods

To examine how closely cultured testis fragments in vitro approximates what typically occurs during the first wave of spermatogenesis in vivo, C57BL/6J mouse testis fragments obtained on postnatal day (PND) 5 were cultured in AlbuMAX™ I/ α‐Minimal Essential Medium for 15, 23, 30, 35, 42, and 49 days, and compared to mouse testes obtained at PND 5, 14, 20, 24, 28, 30, 35, and 40. At the specified days of culture or PND of mice, the following analyses were conducted: histology, flow cytometry for haploid cell detection, qPCR for spermatid markers, and liquid chromatography/mass spectrometry for testosterone levels.

Results

Round spermatids were initially observed at 23 days, and their percentage of the total number of cells continued to increase with culture time, as did gene expression of the spermatid markers and haploid cell percentage in the cultured testis fragments. These results were similar in temporal sequence to those in animals. Testosterone levels in the testis fragments reached a maximum at Day 49.

Conclusion

These findings show this in vitro mouse testis organ culture model may be a useful and convenient tool for mechanistic studies. However, because germ cell differentiation in all seminiferous tubules was not observed, improvements in the system/methods are needed to more closely replicate spermatogenesis as observed in animals.
Perioperative olfactory dysfunction in patients with meningiomas of the anteromedial skull base
Authors: Hendrix Philipp , Fischer Gerrit , Linnebach Alan‐Christopher , Krug Julian B. , Linsler Stefan , Griessenauer Christoph J. , Oertel Joachim
Published: January 2019

Olfactory dysfunction represents a main symptom in olfactory groove meningiomas (OGM). Besides this, olfactory function has been sparsely investigated in patients suffering from supratentorial meningiomas. Here, the authors explore pre‐ and postoperative variables associated with olfactory dysfunction in supratentorial meningioma patients. This is a retrospective study on supratentorial meningioma patients who underwent meningioma resection between January 2015 and January 2016. Preoperative and postoperative olfactory performance was quantified using a lateralized sniffin' stick odor identification test. Meningiomas affecting the olfactory system (n = 23) were compared to meningiomas in other locations among the control group (n = 40). Meningiomas that affected the olfactory system had odds of 3.6 and 3.7 in being associated with ipsilateral (lesional) and bilateral anosmia, respectively. Subgroup analysis revealed that meningiomas causing a midline shift across the frontal base and older age represented risk factors for preoperative anosmia. The odds of experiencing acquired postoperative ipsilateral anosmia were significantly increased in olfactory system affecting meningiomas (OR 11.1). Subgroup analysis highlighted OGMs to represent the predominant location associated with deterioration. General surgical complications predisposed patients to loss of contralateral (OR 12.3) and bilateral olfactory function (OR 27.8). Older age and meningiomas causing a midline shift across the frontal base predispose patients to preoperative olfactory dysfunction. Resection of OGMs and surgical complications are risk factors for postoperative olfactory deterioration to anosmia. Likely, olfactory dysfunction is underrecognized even in OGMs. In OGM surgery, however, preoperative lateralized testing might be critical to selecting an appropriate surgical route to preserve olfactory function. Clin. Anat. 32:524–533, 2019. © 2019 Wiley Periodicals, Inc.
Sulfated Ceria Catalyzed Synthesis of Imidazopyridines and Their Implementation as DNA Minor Groove Binders
Authors: Mohan Surender , Rangappa Shobith , Anilkumar Nirvanappa C. , Fuchs Julian E. , Bender Andreas , Basappa  , Rangappa Kanchugarakoppal S. , Bhatnagar Rakesh
Published: January 2019

The small molecules that bind to DNA minor groove are considered as potential therapeutic agents to fight against many human diseases. They induce cell death by interfering with transcription, replication and progression of cell cycle. Herein, we report the synthesis of imidazopyridine‐3‐amines using sulfated ceria catalyst by employing Groebkee–Blackburne–Bienayme reaction. We evaluated the possible antiproliferative and antimycobacterial activity against A549 cells and Mycobacterium tuberculosis, respectively. Among the tested compounds, N‐tert‐butyl‐2‐(2‐butyl‐4‐chloro‐1H‐imidazol‐5‐yl)‐5,7‐dimethylimidazo[1,2‐a]pyridin‐3‐amine (4g) was identified as cytotoxic heterocycle and antimycobacterial agent. Molecular docking studies of the imidazopyridine derivatives revealed the consistent positioning in the minor groove with a tight shape fit between receptor and ligands. Therefore, we speculate that new imidazopyridines induce their pharmacological effect by targeting the minor groove of DNA.
Predictive factors of discordance between the instantaneous wave‐free ratio and fractional flow reserve
Authors: Dérimay François , Johnson Nils P. , Zimmermann Frederik M. , Adjedj Julien , Witt Nils , Hennigan Barry , Koo Bon‐Kwon , Barbato Emanuele , Esposito Giovanni , Trimarco Bruno , Rioufol Gilles , Park Seung‐Jung , Baptista Sérgio Bravo , Chrysant George S. , Leone Antonio Maria , Jeremias Allen , Berry Colin , De Bruyne Bernard , Oldroyd Keith G. , Pijls Nico H.J. , Fearon William F.
Published: January 2019

Objectives

To identify clinical, angiographic and hemodynamic predictors of discordance between instantaneous wave‐free ratio (iFR) and fractional flow reserve (FFR).

Background

The iFR was found to be non‐inferior to the gold‐standard FFR for guiding coronary revascularization, although it is discordant with FFR in 20% of cases. A better understanding of the causes of discordance may enhance application of these indices.

Methods

Both FFR and iFR were measured in the prospective multicenter CONTRAST study. Clinical, angiographic and hemodynamic variables were compared between patients with concordant values of FFR and iFR (cutoff ≤0.80 and ≤0.89, respectively).

Results

Out of the 587 patients included, in 466 patients (79.4%) FFR and iFR agreed: both negative, n = 244 (41.6%), or positive, n = 222 (37.8%). Compared with FFR, iFR was negative discordant (FFR+/iFR‐) in 69 (11.8%) patients and positive discordant (FFR‐/iFR+) in 52 (8.9%) patients. On multivariate regression, stenosis location (left main or proximal left anterior descending) (OR: 3.30[1.68;6.47]), more severe stenosis (OR: 1.77[1.35;2.30]), younger age (OR: 0.93[0.90;0.97]), and slower heart rate (OR: 0.59[0.42;0.75]) were predictors of a negative discordant iFR. Absence of a beta‐blocker (OR: 0.41[0.22;0.78]), older age (OR: 1.04[1.00;1.07]), and less severe stenosis (OR: 0.69[0.53;0.89]) were predictors of a positive discordant iFR.

Conclusions

During iFR acquisition, stenosis location, stenosis degree, heart rate, age and use of beta blockers influence concordance with FFR and should be taken into account when interpreting iFR.
Studying Direct Electron Transfer by Site‐Directed Immobilization of Cellobiose Dehydrogenase
Authors: Meneghello Marta , Al‐Lolage Firas A. , Ma Su , Ludwig Roland , Bartlett Philip N.
Published: January 2019

Covalent coupling between a surface‐exposed cysteine residue and maleimide groups was used to immobilize variants of Myriococcum thermophilum cellobiose dehydrogenase (MtCDH) at multiwall carbon nanotube electrodes. By introducing individual cysteine residues at particular places on the surface of the flavodehydrogenase domain of the flavocytochrome, we are able to immobilize the different variants in different orientations. Our results show that direct electron transfer (DET) occurs exclusively through the haem b cofactor and that the redox potential of the haem is unaffected by the orientation of the enzyme. Electron transfer between the haem and the electrode is fast in all cases and, at high glucose concentrations, the catalytic currents are limited by the rate of inter‐domain electron transfer (IET) between the FAD and the haem. Using ferrocene carboxylic acid as a mediator, we find that the total amount of immobilized enzyme is 4 to 5 times greater than the amount of enzyme that participates in DET. The role of IET in the overall DET catalysed oxidation was also demonstrated by the effects of changing Ca2+ concentration and by proteolytic cleavage of the cytochrome domain on the DET and MET currents.
One Dimensional Enhanced Anhydrous Proton Conduction in Well Defined Molecular Columns Induced by Non‐Covalent Interactions
Authors: Kumar Avneesh , Pisula Wojciech , Müllen Klaus
Published: January 2019

1D anhydrous proton conduction is enhanced significantly in ionic channels created by self‐assembly of functionalized organic phosphonic acid and aromatic heterocyclic 1,2,4‐triazole molecules. This study reveals high proton conduction in one dimension through a well‐defined supramolecular architecture in which two different molecules undergo host–guest synergy and self‐assemble to provide two‐fold advantages: 1) formation of the ionic channels and 2) higher proton conduction in the absence of water. A clear correlation is found between the phenomena of ionic channels and anhydrous conductivity in the absolute dry state and we demonstrate that the one‐dimensional conductivity can be as high as that recorded for 3D channels in, for instance, Nafion.
Positive and Negative Effects of Cannabis and Cannabinoids on Health
Authors: Cohen Koby , Weizman Abraham , Weinstein Aviv
Published: January 2019

Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short‐ and long‐term side effects, including respiratory and cardiovascular disorders, cognitive alterations, psychosis, schizophrenia, and mood disorders. However, casual relations between cannabis use and these adverse effects are missing. On the other hand, recent research proposed promising therapeutic potential of cannabinoid‐based drugs for a wide range of medical conditions, including neurological and psychiatric disorders. The current article presents a contemporary review on the adverse effects, safety, and the therapeutic potential of cannabis and cannabinoid‐based drugs. Given the growing popularity in the use of cannabinoid‐based drugs for both recreational and medical purposes and their potential harmful effects, there is a need for further investigation in this field.
The evolution of phenotypic plasticity when environments fluctuate in time and space
Authors: King Jessica G. , Hadfield Jarrod D.
Published: January 2019

Most theoretical studies have explored the evolution of plasticity when the environment, and therefore the optimal trait value, varies in time or space. When the environment varies in time and space, we show that genetic adaptation to Markovian temporal fluctuations depends on the between-generation autocorrelation in the environment in exactly the same way that genetic adaptation to spatial fluctuations depends on the probability of philopatry. This is because both measure the correlation in parent-offspring environments and therefore the effectiveness of a genetic response to selection. If the capacity to genetically respond to selection is stronger in one dimension (e.g., space), then plasticity mainly evolves in response to fluctuations in the other dimension (e.g., time). If the relationships between the environments of development and selection are the same in time and space, the evolved plastic response to temporal fluctuations is useful in a spatial context and genetic differentiation in space is reduced. However, if the relationships between the environments of development and selection are different, the optimal level of plasticity is different in the two dimensions. In this case, the plastic response that evolves to cope with temporal fluctuations may actually be maladaptive in space, resulting in the evolution of hyperplasticity or negative plasticity. These effects can be mitigated by spatial genetic differentiation that acts in opposition to plasticity resulting in counter-gradient variation. These results highlight the difficulty of making space-for-time substitutions in empirical work but identify the key parameters that need to be measured in order to test whether space-for-time substitutions are likely to be valid.
HDR interventional radiotherapy (brachytherapy) in the treatment of primary and recurrent head and neck malignancies
Authors: Bussu Francesco , Tagliaferri Luca , Mattiucci Giancarlo , Parrilla Claudio , Rizzo Davide , Gambacorta Maria Antonietta , Lancellotta Valentina , Autorino Rosa , Fonnesu Carla , Kihlgren Caterina , Galli Jacopo , Paludetti Gaetano , Kovács György , Valentini Vincenzo
Published: January 2019

Background

Interventional radiotherapy (brachytherapy; IRT) reemerged in the last decades as a potentially useful tool in head and neck oncology after a set of clear technical improvements were developed.

Methods

Sixty‐one high dose ratio (HDR) IRT treatments were recommended and performed on 58 patients. We classified the cases into four relatively homogeneous groups based on the clinical needs that led to the recommended IRT. Also, we separately evaluated primary and recurrent cases.

Results

Disease‐specific survival was significantly different among the four treatment groups. The group with the best prognosis was the cohort treated locally by exclusive interstitial IRT for resectable midface malignancies (2‐year relapse‐free survival = 82%, disease‐specific survival = 89%).

Conclusion

HDR IRT is a valuable tool in well‐defined clinical situations and, in particular, in recurrences. In midface malignancies, it could become the preferred primary treatment.
Origin of improved depth penetration in dual‐axis optical coherence tomography: a Monte Carlo study
Authors: Zhao Yang , Chu Kengyeh K. , Jelly Evan T. , Wax Adam
Published: January 2019

Recent studies have demonstrated that extended imaging depth can be achieved using dual‐axis optical coherence tomography (DA‐OCT). By illuminating and collecting at an oblique angle, multiple forward scattered photons from large probing depths are preferentially detected. However, the mechanism behind the enhancement of imaging depth needs further illumination. Here, the signal of a DA‐OCT system is studied using a Monte Carlo simulation. We modeled light transport in tissue and recorded the spatial and angular distribution of photons exiting the tissue surface. Results indicate that the spatial separation and offset angle created by the non‐telecentric scanning configuration promote the collection of more deeply propagating photons than conventional on‐axis OCT.
Repair of cartilage defects with devitalized osteochondral tissue: A pilot animal study
Authors: Hiemer Bettina , Genz Berit , Ostwald Jürgen , Jonitz‐Heincke Anika , Wree Andreas , Lindner Tobias , Tischer Thomas , Dommerich Steffen , Bader Rainer
Published: January 2019

Devitalization using high hydrostatic pressure (HHP) treatment inactivates cells while matrix structure and biomechanical properties are maintained. Because of strong chondroinductive potential of HHP‐devitalized cartilage matrix, it may be used as scaffold for reconstruction of (osteo‐)chondral lesions. In this pilot study, we evaluated the feasibility of HHP‐devitalized osteochondral tissue to repair osteochondral defects in a rabbit model. Removal and reimplantation of osteochondral plugs were performed in 12 female New Zealand White rabbits. From the knee joint of each animal, osteochondral plugs (diameter = 4 mm; depth = 2.5 mm) were harvested and devitalized by HHP (452 MPa for 10 min). Afterward, the plugs were reimplanted into the respective cavity, from where they were taken. Animals were sacrificed 12 weeks postoperatively and the integration of osteochondral plugs was examined using μ‐CT, MRI, and histological staining. Furthermore, revitalization of HHP‐treated osteochondral plugs was characterized by gene expression analyses. Macroscopic evaluation of tissue repair at implantation sites of HHP‐treated osteochondral plugs showed an adequate defect filling 12 weeks after implantation. Plug margins were hardly detectable indicating successful tissue integration. Additionally, gene expression analyses demonstrated initial revitalization of the HHP‐treated tissue 12 weeks postoperatively. Our preliminary data revealed that HHP‐treated osteochondral plugs could be used to refill osteochondral defects in the knee joint and promote cell migration into defect site. Data indicated that HHP‐treated tissue has the potential to act as functional scaffolds for reconstruction of cartilage defects. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2354–2364, 2019.
SMAD3 inducing the transcription of  STYK1 to promote the EMT process and improve the tolerance of ovarian carcinoma cells to paclitaxel
Authors: Shi Yangyang , Zhang Jing , Liu Mengran , Huang Yan , Yin Ling
Published: January 2019

Objective

To figure out the relationship between SMAD3 and serine‐threonine tyrosine kinase (STYK1) in ovarian carcinoma cell's paclitaxel resistance.

Methods

The quantitative reverse transcription‐polymerase chain reactpostion and Western blot analysis were used to analyze RNA and protein content of SMAD3 and STYK1, respectively. The chromatin immunoprecipitation assay was used to confirm the binding site of SMAD3 to the STYK1 promoter region. Transwell assay was used to detect cell invasion and migration, and Western Blot was used to detect the marker proteins (vimentin and E‐cadherin) of epithelial‐mesenchymal transition (EMT) process. MTT and apoptosis assay were used to, respectively, measure cell vitality and apoptosis. In vivo experiments, rats were subcutaneously implanted with A2780 cells to establish an animal model of ovarian cancer and the survival curve was drawn.

Results

Upregulating SMAD3 induced the expression of STYK1 in ovarian cancer cell lines. STYK1 is a direct transcriptional target of SMAD3. Upregulating STYK1 improved the paclitaxel resistance of ovarian carcinoma cells. Upregulating STYK1 promoted cell invasion, migration, and the EMT process, and SMAD3 had the same effect with STYK1 on cell invasion, cell migration, and the EMT process. The animal assay showed that downregulating STYK1 inhibited the EMT process and the paclitaxel resistance, further promoting the treatment of cervical cancer.

Conclusion

SMAD3 combined with the promoter region of STYK1 to promote the transcription process of STYK1, thereby promoting the EMT process and paclitaxel resistance of ovarian cancer cells.
miR‐145‐5p inhibits tumor occurrence and metastasis through the NF‐κB signaling pathway by targeting TLR4 in malignant melanoma
Authors: Jin Canhui , Wang Aihong , Liu Linbo , Wang Gongping , Li Guangshuai , Han Zhaofeng
Published: January 2019

Compelling evidence shows that deregulated microRNAs (miRNAs) are important regulators in the progression of melanoma. miR‐145‐5p has been suggested to exhibit antitumorigenic activity in melanoma. However, the molecular mechanism underlying the biological activity of miR‐145‐5p in melanoma remains to be further understood. Herein, quantitative real‐time polymerase chain reaction was used to examine the miR‐145‐5p expression in malignant melanoma tissues and cells. The interaction between miR‐145‐5p and toll‐like receptor 4 (TLR4) was explored by bioinformatics analyses, luciferase reporter assay, and Western blot. The effects of miR‐145‐5p or combined with TLR4 on cell proliferation, colony formation, migration, and invasion abilities were investigated by (4,5‐Dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide, colony formation, wound healing, and transwell assays, respectively. The melanoma xenograft tumor models were established to determine the biological activity of miR‐145‐5p in melanoma in vivo. In addition, the changes of the nuclear factor kappa B (NF‐κB) pathway were analyzed by detecting the NF‐κB activity and the NF‐κB p65 protein level. We observed that the miR‐145‐5p expression was underexpressed in melanoma tissues and cells. miR‐145‐5p suppressed the TLR4 expression by binding to its 3′untranslated region in melanoma cells. Moreover, TLR4 overexpression abolished the inhibition of cell proliferation, colony formation, migration, and invasion abilities induced by miR‐145‐5p in melanoma cells. Meanwhile, miR‐145‐5p was confirmed to restrain melanoma tumor growth in vivo by targeting TLR4. Furthermore, miR‐145‐5p overexpression inactivated the NF‐κB pathway in melanoma in vitro and in vivo, which was reversed by TLR4 overexpression. We concluded that miR‐145‐5p hindered the occurrence and metastasis of melanoma cells in vitro and in vivo by targeting TLR4 via inactivation of the NF‐κB pathway.
Extracellular methemoglobin promotes cyto‐adherence of uninfected RBC to endothelial cells: Insight into cerebral malaria pathology
Authors: Kumar Sushant , Trivedi Vishal
Published: January 2019

The endothelial cell barrier is tightly regulated, and disruption or the leaky behavior of the barrier leads to pathology. Disturbance of blood‐brain barrier is observed during viral infection, cerebral malaria, and acute hemorrhagic encephalitis. Red blood cells (RBCs) bind to the endothelial cells (ECs) and their affinity towards ECs enhances in the presence of Plasmodium falciparum infection. ECs stimulated with methemoglobin (MetHb; 20 µM) for 1 hour exhibit high levels of cyto‐adherence receptors CD36 and ICAM‐1 on their cell surface compared with unstimulated cells. These ECs have acquired affinity towards uninfected RBCs in flow at arterial shear stress. SEM analysis indicates that EC–RBC cyto‐adherence involved multiple attachment points. Initially, ECs bind single layer of RBCs and the number of RBCs increases over time to give high‐order cyto‐adherence with more than 30 RBCs adhered to each endothelial cell. The cyto‐adherence complexes are stable to high shear stress and can withstand shear stress up to 450 dyne/cm
2. MetHb‐treated ECs exhibited high reactive oxygen species level, and preincubation of ECs with antioxidant (NAC or mannitol) abolished the formation of EC–RBC cyto‐adherence complexes. In addition, gallic acid (present in red wine) and green tea extract has inhibited the formation of EC–RBC cyto‐adherence complex. A better understanding of gallic acid and tea polyphenol targeting pathological cyto‐adherence may allow us to develop a better adjuvant therapy for cerebral malaria and other noninfectious diseases.
Molybdenum dinitrosyl Schiff base complexes of dehydroacetic acid and thiourea derivatives: DFT‐experimental characterization and nosocomial anti‐infectious implications
Authors: Mir JanMohammad , Malik Bashir Ahmad , Khan Mohd Washid , Maurya Ram Charitra
Published: January 2019

Pseudomonas and E. coli microorganisms are linked with hospital acquired urinary infections. Also, Streptococcus and Aspergillus are causative agents of infection generally found associated with cancer. The enduring curiosity to design antibiotic compounds against such bugs has driven our attention to synthesize nitric oxide‐bound molybdenum complexes of pyrone‐thiourea derivative‐based Schiff bases directly from molybdate(VI). Structural elucidation of the complexes was carried out based on physicochemical analysis and DFT calculations. Geometric description has shown a suitable cis‐octahedral structure for the synthesized complexes. Molecular geometry optimization, theoretical spectroscopy, and electron density plots are the main theoretical insights presented herein. Antimicrobial studies of a representative Schiff base ligand, metal salt (ammonium heptamolybdate tetrahydrate), sodium nitrite (NO containing compound), and two of the synthesized complexes at various concentrations were carried out to find their broad spectrum antibiotic potential as nosocomial infection fighting agents. Also, the biological activity was explained in relation to molecular charge topological parameters obtained from computational investigation.
Internet‐based treatment of depressive symptoms in a Kurdish population: A randomized controlled trial
Authors: Lindegaard Tomas , Brohede David , Koshnaw Kocher , Osman Shevan Sherzad , Johansson Robert , Andersson Gerhard
Published: January 2019

Objective

Kurdish immigrants in Sweden have a doubled risk of mental health problems, and refugee and immigrant populations underutilize mental health services. The present study investigated the efficacy of culturally adapted guided internet‐based cognitive behavior therapy (ICBT) for depressive symptoms in a Kurdish population.

Method

We included 50 individuals who were randomized to either an 8‐week treatment or a wait‐list. The Beck Depression Inventory‐II was the primary outcome measure, and measures of anxiety and insomnia were secondary outcomes.

Results

Depressive symptoms were significantly reduced (intention‐to‐treat analysis) in the treatment group, with a between‐group effect size at posttreatment of Cohen's d = 1.27. Moderate to large between‐group effects were also observed on all secondary outcome measures. Treatment effects were sustained at 11‐month follow‐up.

Conclusion

The results provide preliminary support for culturally adapted ICBT as a complement to other treatment formats for treating symptoms of depression in a Kurdish population.
MicroRNA‐128 confers protection against cardiac microvascular endothelial cell injury in coronary heart disease via negative regulation of IRS1
Authors: Yan Ping , Sun Chen , Ma Jiale , Jin Zhigang , Guo Rui , Yang Bin
Published: January 2019

Objective

Cardiac microvascular endothelial cells (CMECs) play a critical role in the physiological regulation of coronary blood flow and its dysfunction is associated with myocardium ischemic injury. This study was performed to clarify the effect of microRNA‐128 (miR‐128) on the CMEC injury in coronary heart disease (CHD) by binding to insulin receptor substrate 1 (IRS1).

Methods

The rat CMECs were cultured by explant culture method and identified by CD31 immunofluorescence assay. CMECs were treated with homocysteine (Hcy), which underwent stress of CHD, followed by treatment of miR‐128 mimics/inhibitors or IRS1 siRNA. Expression of miR‐128, IRS1, and vascular endothelial growth factor (VEGF) was determined. The viability, apoptosis, migration ability, and tube formation ability of CMECs were evaluated. The superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) of CMECs were evaluated, respectively.

Results

In rat CMECs, miR‐128 was poorly expressed and IRS1 was highly expressed. Notably, miR‐128 targeted and negatively regulated IRS1. Additionally, the treatment with Hcy in CMECs led to reduced viability, migration ability, tube formation, VEGF expression, SOD activity as well as increased cell apoptosis, MDA and ROS levels. The experimental results demonstrated that miR‐128 mimics and IRS1 siRNA in rat CMECs promoted viability, migration ability, tube formation, VEGF expression, SOD activity, while repressing cell apoptosis, MDA and ROS levels. MiR‐128 inhibitors could reverse the tendencies.

Conclusion

Collectively, our study provides evidence that miR‐128 targeted and negatively regulated IRS1 expression, whereby the functional injury of CMECs induced by Hcy was ameliorated. Furthermore, protection of miR‐128 was stimulated by reducing oxidative stress.
A novel chemically defined serum‐ and feeder‐free medium for undifferentiated growth of porcine pluripotent stem cells
Authors: Zhang Xue , Xue Binghua , Li Yan , Wei Renyue , Yu Zhuoran , Jin Junxue , Zhang Yu , Liu Zhonghua
Published: January 2019

Development and improvement of in vitro culture system supporting self‐renewal and unlimited proliferation of porcine pluripotent stem cells (pPSCs) is an indispensable process for the naïve pPSCs establishment. In this study, we modified the previous culture system and attempted to develop a novel chemically defined medium (KOFL) for the establishment of pPSCs. It has been cultured >45 passages with flat colony morphology and normal karyotypes in in vitro environment. These cells exhibited alkaline phosphatase activity and expressed pluripotency markers such as OCT4, SOX2, and NANOG, and also possessed differentiation abilities both in vitro and in vivo, proving by the formation of embryonic bodies and teratomas into three germ layers. Then the cells transfected with a green fluorescent protein (GFP) and the GFP positive cells contribute to the porcine preimplantation embryo development. In addition, these cells maintained long duration under feeder‐free condition. In conclusion, our results demonstrated that the pPSCs could be derived from preimplantation porcine embryos in serum‐free medium and cultured under the feeder‐free condition, providing an effective reference for further optimization of the pPSCs culture system.
HIV‐1 Tat protein induces aberrant activation of AICDA in human B‐lymphocytes from peripheral blood
Authors: Sall Fatimata Bintou , El Amine Rawan , Markozashvili Diana , Tsfasman Tatyana , Oksenhendler Eric , Lipinski Marc , Vassetzky Yegor , Germini Diego
Published: January 2019

Individuals infected with human immunodeficiency virus (HIV) are at increased risk for Burkitt lymphoma, a B‐cell malignancy which occurs after a chromosomal translocation rearranging the MYC oncogene with an immunoglobulin gene locus, usually the IGH heavy chain gene locus. We have previously reported that the HIV protein Tat which circulates in all HIV‐positive individuals whatever their immune status caused an increased rate of colocalization between IGH and MYC in B‐cells nuclei. We here present in vitro evidence that Tat activates the expression of the AICDA gene that encodes the activation‐induced cytidine deaminase whose physiological function is to create double‐strand breaks for immunoglobulin gene maturation. In the presence of Tat, DNA damage was observed concomitantly in both MYC and IGH, followed by DNA repair by nonhomologous end joining. AICDA was further found overexpressed in vivo in peripheral blood B‐cells from HIV‐infected individuals. Thus, the capacity of Tat to spontaneously penetrate B‐cells could be sufficient to favor the occurrence of MYC‐IGH oncogenic rearrangements during erroneous repair, a plausible cause for the increased incidence of Burkitt lymphoma in the HIV‐infected population.
Expanding the phenotype of phospholipid remodelling disease due to MBOAT7 gene defect
Authors: Yalnızoǧlu Dilek , Özgül R. Köksal , Oǧuz Kader K. , Özer Buǧra , Yücel‐Yılmaz Didem , Gürbüz Berrak , Serdaroǧlu Esra , Erol İlknur , Topçu Meral , Dursun Ali
Published: January 2019

MBOAT7 gene codes O‐acyltransferase domain containing seven proteins which is one of four enzymes involved in remodeling of phosphoinositol phosphate (PIP) in LANDs cycle. We present clinical, neuroimaging, and genetic findings of 12 patients from 7 families with MBOAT7 gene defect, a recently defined novel phospholipid remodelling disease. To the best of our knowledge, our case series is the second report on patients with MBOAT7 gene defect. The patients present with global developmental delay particularly in speech and language skills, intellectual disability, stereotypical behavior, ataxic gait, early onset epilepsy with well response to medical treatment, strabismus and similar facial features. Common neuroimaging findings of the patients were folium dysgenesis of the cerebellum with a particular appearance, mild‐to‐moderate cerebellar atrophy, T2 hyperintensity of bilateral globus pallidius and dentate nuclei, enlarged perivascular areas, and mild thinning of the corpus callosum. Genome‐wide genotyping and exome sequencing identified five different types of homozygous mutations in the MBOAT7 gene in all seven families which are p.Arg87*, p.Leu227ProfsX65, p.Gln376Lys, p.Trp426*, and chr19:54.666.173‐54.677.766/11594 bp del. We conclude that clinical and neuroimaging findings of MBOAT7 gene defect may suggest the diagnosis and guide genetic tests.
Water–fat separation and parameter mapping in cardiac MRI via deep learning with a convolutional neural network
Authors: Goldfarb James W. , Craft Jason , Cao J. Jane
Published: January 2019

Background

Water–fat separation is a postprocessing technique most commonly applied to multiple‐gradient‐echo magnetic resonance (MR) images to identify fat, provide images with fat suppression, and to measure fat tissue concentration. Recently, Numerous advancements have been reported. In contrast to early methods, the process of water–fat separation has become complicated due to multiparametric analytic models, optimization methods, and the absence of a unified framework for diverse source data.

Purpose

To determine the feasibility and performance of MRI water–fat separation and parametric mapping via deep learning (DL) with a range of inputs.

Study Type

Retrospective data usage.

Population/Subjects

Ninety cardiac MR examinations from normal control, acute, subacute, and chronic myocardial infarction subjects were obtained, providing 1200 multiple gradient‐echo acquisitions.

Field Strength/Sequence

1.5 T/2D multiple gradient‐echo pulse sequence

Assessment

Ground‐truth training and validation water–fat separation were obtained using a graph cut method with R2*, off‐resonance correction, and a multipeak fat spectrum. U‐Net DL training with single and multiecho, complex, and magnitude inputs were compared using quantitative and three‐observer subjective analysis.

Statistical Tests

DL methods' image structural similarity, and quantitative proton density fat fraction (PDFF), R2*, and off‐resonance quantitative values were statistically compared with the GraphCut reference standard using Student's t‐test and Pearson's correlation.

Results

Myocardial fat deposition in chronic myocardial infarction and intramyocardial hemorrhage in acute myocardial infarction were well visualized in the DL results. Predicted values for R2*, off‐resonance, water, and fat signal intensities were well correlated with a conventional model‐based water fat separation (R2 ≥ 0.97, P < 0.001) with appropriate inputs. DL parameter maps had a 14% higher signal‐to‐noise ratio (P < 0.001) when compared with a conventional method.

Data Conclusion

DL water–fat separation is feasible with a wide range of inputs, while R2* and off‐resonance mapping requires multiple echoes and complex images. With appropriate inputs, DL provides quantitative and subjective results comparable to conventional model‐based methods.

Level of Evidence: 1

Technical Efficacy Stage: 1

J. Magn. Reson. Imaging 2019;50:655–665.
Imbalance in the ratio of CpG and polyG contributes to impaired interferon‐α expression
Authors: Lv Shujuan , Li Suping , Wang Zifeng , Xia Jing
Published: January 2019

The secretion of interferon‐α (IFN‐α) is impaired during hepatitis B virus (HBV) infection. DNA sequences purified from distinct viruses, for example, HBV versus members of Herpesviridae, have been shown to differ in their IFN‐α signaling properties. The present study found that DNA from HBV inhibited, while DNA from members of Herpesviridae induced, the expression of IFN‐α. Furthermore, stimulatory cytosine‐phosphate‐guanosine (CpG) sequences derived from these DNA viruses could induce the secretion of IFN‐α, while inhibitory guanosine‐rich oligodeoxynucleoti (polyG) oligonucleotide sequences derived from these DNA viruses could inhibit CpG‐induced IFN‐α secretion. Using a computational analysis of genomic DNA sequences, the discrimination between the genomes of HBV and those of other DNA viruses that can also cause inflammation of the liver is based on different frequencies of the CpG and polyG motifs. The underrepresentation of stimulatory CpG motifs and overrepresentation of inhibitory polyG motifs were documented in HBV genomes, whereas the DNA from other viral genomes displayed the opposite trend. Moreover, it was demonstrated that HBV could suppress the activation of IFN‐α via its own DNA through the high proportion of polyG motifs. To our knowledge, this is the first demonstration of a specific role for polyG motifs in the inhibition of the IFN‐α response following DNA virus infection.
A novel large‐signal FET model considering trapping‐induced dispersions
Authors: Yuan Ye , Zhong Zheng , Guo Yong‐xin , Mu Shanxiang
Published: January 2019

A novel large‐signal model construction technique is proposed in this paper. High‐order current and charge sources with additional dimensions derived from pulsed small‐signal measurement data are used to describe the dispersive behaviour of FETs. Added dimensions can effectively account for trapping‐induced dispersions. Instead of look‐up tables, empirical functions and artificial neural network are adopted to implement the model into simulators, which can reduce the volume of the model and the possible oscillation caused by interpolation and provide better prediction performance beyond the measurement data range. The validity of proposed modelling technique has been verified by a 2 × 75um GaAs pHEMT. This proposed technique can be easily extended to GaN devices with the similar procedure.
Gaussian random number generator: Implemented in FPGA for quantum key distribution
Authors: Hu Yue , Wu Yan , Chen Yi , Wan Guo Chun , Tong Mei Song
Published: January 2019

Quantum key distribution is the process of using quantum communication to establish a shared key between two parties. It has been demonstrated the unconditional security and effective communication of quantum communication system can be guaranteed by an excellent Gaussian random number (GRN) generator with high speed and an extended random period. In this paper, we propose to construct the Gaussian random number generator by using field‐programmable gate array (FPGA), which is able to process large data in high speed. We also compare three algorithms of GRN generation: Box‐Muller algorithm, polarization decision algorithm, and central limit algorithm. We demonstrate that the polarization decision algorithm implemented in FPGA requires less computing resources and also produces a high‐quality GRN through the null hypothesis test.
Knowledge hiding as a barrier to thriving: The mediating role of psychological safety and moderating role of organizational cynicism
Authors: Jiang Zhou , Hu Xiaowen , Wang Zhongmin , Jiang Xuan
Published: January 2019

Research demonstrates that knowledge hiding has a detrimental effect on the knowledge hider himself or herself. Extending this area, the present research examines how and when knowledge hiders struggle to thrive at work. Integrating self‐perception theory and the socially embedded model of thriving, we propose that knowledge hiding negatively influences employees' thriving through psychological safety, and this influence is contingent on organizational cynicism. In Study 1a, a cross‐sectional survey of 214 Chinese participants from a general working population supported the mediating role of psychological safety in the knowledge hiding and thriving relationship. Study 1b verified this result using two‐wave data collected from 392 working adults in a panel that recruited participants mainly in Europe and North America. In addition to confirming the mediation with a two‐wave field survey conducted among 205 employees in three Chinese organizations, Study 2 supported the moderating role of organizational cynicism. Specifically, the negative effect of knowledge hiding on psychological safety was greater under higher levels of organizational cynicism, as was the indirect effect of knowledge hiding on thriving via psychological safety. These findings contribute to both the knowledge hiding and the thriving literature and provide practical implications for both the manager and the employee.