bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of Faraday effect of transparent ferromagnetic Co‐MgF2 granular film by introducing Fabry–Pérot resonant structure
Authors: Miyamoto Mitsunori , Kubo Toshiya , Fujishiro Yuta , Shiota Kenta , Sonehara Makoto , Sato Toshiro
Published: February 2019

To detect the magnetic field using polarization of a light, transparent magnetic material having a Faraday effect is required. The Co‐MgF2 granular film is promising as a candidate of the Faraday element for the magnetic field sensing. In this study, Fabry–Pérot resonant structure was introduced into the Co‐MgF2 granular film to enhance the Faraday effect. It was found that the Faraday effect per unit film thickness [deg/μm] was enhanced due to a light localized in the Co‐MgF2 granular layer sandwiched by Bragg mirror of the insulator multilayer. The maximum Faraday effect of the proposed structure was −1.24°/μm, which was about 3.4 times enhancement compared with a single Co‐MgF2 film, when the number of layer period x in Fabry–Pérot resonant multilayer was 5, where the structure was substrate/(Ta2O5/SiO2)x/Co‐MgF2/(SiO2/Ta2O5)2/Air. Furthermore, the multicavity structure, consisting of the Fabry–Pérot resonant multilayer film continuously placed, exhibited a 50% increase of figure of merit (FOM) defined as Faraday rotation angle per transmission loss [deg/dB].
Effect of air space in waterproof sealed case containing transmitter and receiver of wireless power transfer in sea water
Authors: Gonda Takatoshi , Mototani Suguru , Doki Kae , Torii Akihiro
Published: February 2019

In this study, the effect of air space in waterproof sealed case of undersea magnetic field resonance type wireless power transfer (WPT) is reported. It has been reported that the transmission power is increased by the air space between the transmitter and receiver coil in the waterproofing case and the wall surface of the case. We evaluated the dependence of the thickness of the air space from measurement and magnetic field analysis. The measurement and magnetic field analysis results indicated the similar tendency to increase the transmission power by 9.8% with the 10‐mm air space at the transmitter side and the 30‐mm air space at the receiver side.
New Findings in Metal Complexes with Antiproliferative Activity Containing 1,3,5‐Triaza‐7‐phosphaadamantane (PTA) and Derivative Ligands
Authors: Scalambra Franco , Lorenzo‐Luis Pablo , de los Ríos Isaac , Romerosa Antonio
Published: February 2019

This minireview summarizes some of the most significant findings published in the last years on metal complexes containing PTA and PTA derivatives ligands such as dmoPTA, with antiproliferative activity [PTA = 1,3,5‐triaza‐7‐phosphaadamantane; dmoPTA = 3,7‐dimethyl‐1,3,7‐triaza‐5‐phosphabicyclo[3.3.1]nonane (dmoPTA)]. Comments on other biological properties of the complexes are also included.
Important Phase Control of Indium Sulfide Nanomaterials by Choice of Indium(III) Xanthate Precursor and Thermolysis Temperature
Authors: Masikane Siphamandla C. , McNaughter Paul D. , Lewis David J. , Vitorica‐Yrezabal Inigo , Doyle Bryan P. , Carleschi Emanuela , O'Brien Paul , Revaprasadu Neerish
Published: February 2019

Four In(III) xanthate complexes, [In(S2COR)3] where R = Me, Et, iPr and sBu, respectively, were synthesized, characterized and subsequently used as single source molecular precursors via a solventless thermolysis route to obtain indium sulfide materials. By choice of precursor and reaction temperature crystalline powders of tetragonal In2S3, cubic In2S3 and cubic In2.77S4 were acquired. The phase identification and purity were conducted through examination of the experimental powder X‐ray diffraction patterns relative to the simulated patterns for single X‐ray crystal diffraction.
Analysis and interpretation of mixture DNA using AS‐PCR of mtDNA
Authors: Xu Feng‐ling , Ding Mei , Xia Xi , Wu Xue , Zhang Jing‐jing , Xing Jia‐xin , Xuan Jin‐feng , Yao Jun , Wang Bao‐jie
Published: February 2019

Semi‐nested PCR with allele‐specific (AS) primers and sequencing of mitochondrial DNA (mtDNA) were performed to analyze and interpret DNA mixtures, especially when biological materials were degraded or contained a limited amount of DNA. SNP‐STR markers were available to identify the minor DNA component using AS‐PCR; moreover, SNPs in mtDNA could be used when the degraded or limited amounts of DNA mixtures were not successful with SNP‐STR markers. Five pairs of allele‐specific primers were designed based on three SNPs (G15043A, T16362C, and T16519C). The sequence of mtDNA control region of minor components was obtained using AS‐PCR and sequencing. Sequences of the amplification fragments were aligned and compared with the sequences of known suspects or databases. When this assay was used with the T16362C and T16519C SNPs, we found it to be highly sensitive for detecting small amounts of DNA (∼30 pg) and analyzing DNA mixtures of two contributors, even at an approximately 1‰ ratio of minor and major components. An exception was tests based on the SNP G15043A, which required approximately 300 pg of a 1% DNA mixture. In simulated three contributor DNA mixtures (at rate of 1:1:1), control region fragments from each contributor were detected and interpreted. AS‐PCR combined with semi‐nested PCR was successfully used to identify the mtDNA control region of each contributor, providing biological evidence for excluding suspects in forensic cases, especially when biological materials were degraded or had a limited amount of DNA.
Enantioseparation of tryptophan and its unnatural derivatives by nano‐LC on CSP‐teicoplanin silica based
Authors: D'Orazio Giovanni , Fanali Chiara , Gentili Alessandra , Fanali Salvatore
Published: February 2019

This work deals with the potentiality of nano liquid chromatography (Nano‐LC) for the chiral separation of racemic mixture of tryptophan and some selected derivatives by using 100 µm i.d. fused silica capillary packed with teicoplanin bonded to 5 µm diol silica stationary phase. The experiments were carried out by using a cheap and laboratory‐assembled nano‐LC–UV system. Elution was done in an isocratic mode using a polar organic mobile phase. In order to find the optimum chiral separation of the studied enantiomers, some chromatographic experimental parameters were systematically studied and optimized. Among them, mobile phase composition, namely organic modifier type and concentration, buffer type and pH and aqueous content and sample solvent dilution on retention time, retention factor and enantioresolution factor were studied. Baseline enantioresolution and good peak shape was achieved utilizing the mobile phase containing 40 mM ammonium formate at pH pH 2.5 in ACN/water/acetone (60:30:10, v/v/v) at 520 nL/min in less than 8 min analysis time.
Double‐Shelled Nanostructure of SnO2@C Tube‐in‐SnO2@C Tube Boosts Lithium‐Ion Storage
Authors: Tian Qinghua , Zhang Feng , Yang Li , Chen Peng
Published: February 2019

In the case of SnO2‐based lithium‐ion battery anodes, the double‐shelled hollow nanostructures are expected to possess better performances than their single‐shelled counterparts, but the fabrication of double‐shelled hollow nanostructures is more difficult than those with single shell because of the increased complexity of structures. Herein, a complex quasi‐SnO2@C tube‐in‐SnO2@C tube nanocomposite (SnO2@C DHNWs) is successfully fabricated by a well‐designed facile strategy. The possible formation mechanism of SnO2@C DHNWs is also speculated. More importantly, the as‐prepared SnO2@C DHNWs show outstanding electrochemical performance as a lithium‐ion battery anode, that is, 774.5 and 462.5 mAh g−1 are retained at 200 and 1000 mA g−1 after 450 and even 1000 cycles, respectively, demonstrating high capacity, long lifespan, and good rate performances. Thus, excellent performance makes SnO2@C DHNWs a promising anode material for advanced lithium‐ion batteries. Moreover, it is worth noting that this work may open up a new route to prepare complex nanostructures of SnO2@C composites with various morphologies.
Reconstructing human–landscape interactions in the context of ancient iron smelting on Elba Island, Italy, using sedimentological evidence
Authors: Becker Fabian , Eser Raphael , Hoelzmann Philipp , Schütt Brigitta
Published: February 2019

We reconstruct human–landscape interactions in the context of ancient bloomery smelting on Elba Island, Tyrrhenian Sea, based on sedimentological evidence. Elba was, together with Populonia, the center of iron production in antiquity (mid‐6th century B.C.E. to 1st century C.E.). The sediment sequences obtained by vibracoring in the Campo plain reveal that the Holocene transgression triggered aggradation during the Early–Middle Holocene (>5.4 ka cal BP). Nevertheless, wetland conditions prevailed in low‐lying areas during Roman times. Correspondingly, ancient smelting sites are found only on elevated areas along the edge of the plain. The palaeolandscape thus plays a key role in understanding location factors for smelting sites in antiquity. Our sediment sequences indicate that during Etrusco–Roman times (2.4–2.0 ka cal BP) morphodynamics on the island increased, as is evident from the alteration of slope deposits and slack water deposits in upstream positions, and the change from lacustrine to alluvial deposition in downstream areas. The charcoal record shows that fire dynamics increased simultaneously. The sediments that are synsedimentary to the ancient smelting period show significantly increased arsenic contents and high sediment magnetic susceptibility, whereas overall concentrations of heavy metals remain in the range of the geogenic background signal.
Boßlertunnel – Anwendung von Schubdübeln bei den Sondertübbingen im Bereich der Verbindungsbauwerke
Authors: Mihaylov Vladislav , Zenz Reinhard
Published: February 2019

In the course of the construction of the new Wendlingen–Ulm line, the Boßler Tunnel with a length of 8,806 m is under construction between Aichelberg and Filstal. Both single‐track main tunnel tubes are for the most part excavated by TBM and lined with segments. The main tunnel tubes have an overburden of up to 280 m and are separated by a rock pillar ranging in width from 5 to 30 m. For safety reasons, seventeen cross passages connect the main tunnels, each at a spacing maximum of 500 m. Cross passage excavation requires the opening of the main tunnel lining and therefore the removal of lining segments. In order to ensure stability of the tunnel lining during the construction phase, special lining segments are used for the main tunnel in cross passage areas. Special lining segments are adapted with additional reinforcement and built‐in components. Shear forces in the circumferential joints are transmitted by shear dowels.
Familial recurrence risk with varying amount of family history
Authors: Schaid Daniel J. , McDonnell Shannon K. , Thibodeau Stephen N.
Published: February 2019

The familial recurrence risk is the probability a person will have disease, given a reported family history. When family histories are obtained as simple counts of disease among family members, as often obtained in cancer registries or surveys, we propose methods to estimate recurrence risks based on truncated binomial distributions. By this approach, we are able to obtain unbiased estimates of risk for a person with at least k‐affected relatives, where k can be specified to determine how risk varies with k. We also derive robust variances of the recurrence risk estimate, to account for correlations within families, such as those induced by shared genes or shared environment, without explicitly modeling the factors that cause familial correlations. Furthermore, we illustrate how mixture models can be used to account for a sample composed of low‐ and high‐risk families. Using simulations, we illustrate the properties of the proposed methods. Application of our methods to a family history survey of prostate cancer shows that the recurrence risk for prostate cancer increased from 16%, when there was at least one affected relative, to 52%, when there was at least five affected relatives.
Patients' preferences concerning follow‐up after curative head and neck cancer treatment: A cross‐sectional pilot study
Authors: Mueller Simon Andreas , Riggauer Julia , Elicin Olgun , Blaser Daniela , Trelle Sven , Giger Roland
Published: February 2019

Background

Evidence of the oncological benefit of scheduled follow‐up in head and neck squamous cell carcinoma is weak; symptom‐oriented self‐referral may be an alternative. Patients’ preferences regarding follow‐up remain poorly investigated.

Methods

We conducted a cross‐sectional survey among patients undergoing follow‐up at a tertiary outpatient clinic, focusing on their preferences, correlating factors, fear of recurrence, and willingness for participation in a randomized trial on follow‐up.

Results

Of 101 patients, 89.1% preferred scheduled follow‐up to self‐referral, 57% favored fewer visits than the current standard, and 85.1% endorsed regular imaging. Recurrence or second primary was associated with preference of intensive follow‐up schedules (P = 0.02). There were trends for women and patients with high fear of recurrence score to favor intensive follow‐up. Two‐third of the participants declared willingness to participate in a randomized controlled trial.

Conclusions

Patients' preferences only partially correspond to current follow‐up guidelines. Recruitment for randomized controlled studies evaluating the value of follow‐up seems feasible.
Leveraging Fluorescent Emission to Unitary Yield: Dimerization of Polycyclic Aromatic Hydrocarbons
Authors: Miletić Tanja , Biot Nicolas , Demitri Nicola , Brancato Giuseppe , Kariuki Benson M. , Bonifazi Davide
Published: February 2019

We report on the synthesis and characterization of novel substituted 1,1′‐biperylene‐2,2′‐diols in which the dihedral angle between the two polycyclic aromatic hydrocarbon (PAH) units is tailored from ca. 60° to ca. 90° in the solid state by introduction of cyclo‐etheric straps or sterically hindered groups such as the triisopropylsilyl (TIPS) group. Depending on the type of substitution, we lock the dihedral angle between the perylenyl moieties enabling fine‐tuning of the molecular optoelectronic properties, with the molecules displaying the smallest angles acting as exceptionally strong emitters with unitary quantum yields.
Exploring a potential mechanistic role of DNA methylation in the relationship between in utero and post‐natal environmental exposures and risk of childhood acute lymphoblastic leukaemia
Authors: Timms Jessica A. , Relton Caroline L. , Sharp Gemma C. , Rankin Judith , Strathdee Gordon , McKay Jill A.
Published: February 2019

The aetiology of childhood acute lymphoblastic leukaemia (ALL) is unclear. Genetic abnormalities have been identified in a number of ALL cases, although these alone are not sufficient for leukaemic transformation. Various in utero and post‐natal environmental exposures have been suggested to alter risk of childhood ALL. DNA methylation patterns can be influenced by environmental exposures, and are reported to be altered in ALL, suggesting a potential mediating mechanism between environment and ALL disease risk. To investigate this, we used a ‘meet in the middle’ approach, investigating the overlap between exposure‐associated and disease‐associated methylation change. Genome‐wide DNA methylation changes in response to possible ALL‐risk exposures (i.e. breast feeding, infection history, day care attendance, maternal smoking, alcohol, caffeine, folic acid, iron and radiation exposure) were investigated in a sub‐population of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort using an epigenome‐wide association study (EWAS) approach (n = 861–927), and compared to a list of ALL disease‐associated methylation changes compiled from published data. Hypergeometric probability tests suggested that the number of directionally concordant gene methylation changes observed in ALL disease and in response to the following exposures; maternal radiation exposure (p = 0.001), alcohol intake (p = 0.006); sugary caffeinated drink intake during pregnancy (p = 0.045); and infant day care attendance (p = 0.003), were not due to chance. Data presented suggests that DNA methylation may be one mediating mechanism in the multiple hit pathway needed for ALL disease manifestation.
Epithelial sealing effectiveness against titanium or zirconia implants surface
Authors: Atsuta Ikiru , Ayukawa Yasunori , Furuhashi Akihiro , Narimatsu Ikue , Kondo Ryosuke , Oshiro Wakana , Koyano Kiyoshi
Published: February 2019

The aims of implant treatment now involve not only restoration of mastication function, but also recovery of esthetics. Currently, zirconia is widely used as an esthetic material for implant abutment. Therefore, it is very important to understand the efficacy of zirconia for epithelial sealing as an implant material. We compared the effects of materials on the sealing of the peri‐implant epithelium (PIE) to titanium (Ti) or zirconia (Zr) implants, for application to clinical work. Maxillary first molars were extracted from rats and replaced with Ti or Zr implants. The sealing of the PIE to the implants was evaluated with immunohistochemistry observation and HRP analysis. The morphological and functional changes in rat oral epithelial cells (OECs) cultured on Ti or Zr plates were also evaluated. After 4 weeks, the PIE on the Ti and Zr implants showed similar structures. The Zr implants appeared to form a weak epithelial seal at the tissue–implant interface, and exhibited markedly less adhesive structures than the Ti implants under electron microscopic observation. In the in vitro experiments, decreased expression levels of adhesion proteins were observed in OECs cultured on Zr plates compared with those cultured on Ti plates. In addition, the cell adherence on Zr plates was reduced, while the cell migration was low on Ti plates. Zr is a better choice for an esthetic implant material, but needs further improvement for integration with the epithelial wound healing process around a dental implant. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.
Fabrication of a self‐doped TiO2 nanotube array electrode for electrochemical degradation of methyl orange
Authors: Mo Chenghao , Wei Huixian , Wang Tongjun
Published: February 2019

Self‐doped TiO2 nanotube array (DTNA) electrodes were fabricated through anodic oxidation combined with cathodic reduction. The morphology and structural features of pristine TiO2 nanotube arrays and DTNA electrodes were studied through scanning electron microscopy, X‐ray diffractometry, and X‐ray photoelectron spectroscopy. An accelerated life test was used to test the electrode service lifetime and thus the electrode's stability. The service lifetime of the DTNA electrode prepared at constant 40 V for 6 hr was approximately 338.7 hr at constant 1 mA/cm2 in a 1 M NaClO4 solution. Methyl orange (MO) was employed as the degradation probe for measuring electrochemical oxidation performance. The color removal rate of 200 mg/L MO of the DTNA electrode (85.2% at 1 mA/cm2) was greater than that of the Ti/IrO2 electrode (31.1% at 1 mA/cm2). The larger the surface area of the DTNA electrode is, the more conductive the electrode is for the degradation of organic substances. Organic degradation on the DTNA electrode occurred primarily through an indirect pathway (producing [∙OH]).
Does a history of childhood abuse moderate the association between symptoms of posttraumatic stress disorder and borderline personality disorder in survivors of intimate partner violence?
Authors: Beck J. Gayle , Woodward Matthew J. , Pickover Alison M. , Lipinski Alexandra J. , Dodson Thomas S. , Tran Han N.
Published: February 2019

Objective

This study examined whether a history of childhood abuse (CA) strengthened the association between borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD) in the aftermath of intimate partner violence (IPV). This hypothesis arises from clinical literature but has not been examined empirically. We predicted that a history of CA would enhance associations between BPD features and PTSD symptoms.

Method

Dimensional assessment of both PTSD and BPD was made in a sample of 211 women who sought mental health services following IPV. Two analyses were conducted using clinician‐assessed DSM‐IV (Diagnostic and Statistical Manual of Mental Disorders, 4th ed.) PTSD symptoms: (a) total score and (b) symptom clusters.

Results

Using path analysis, results indicated significant associations between BPD features and PTSD symptoms, but no significant interaction between BPD and CA in either analysis.

Conclusions

Results are discussed given current understanding of comorbidities involving PTSD, with particular attention to potential implications for clinical practice. Areas for future research are proposed.
Peptidomic analysis reveals multiple protection of human breast milk on infants during different stages
Authors: Zhou Yahui , Zhang Le , Yu Zhangbin , Zhang Aiqing , Wu Weimin , Chen Wenjuan , Yan Xiangyun , Liu Heng , Hu Yin , Jiang Chengyao , Xu Yan , Wang Xingyun , Han Shuping
Published: February 2019

It has been shown that human breast milk (HBM) is an important nutrient for the growth and development of newborns. Currently, peptide drugs provide promising regimes in neonatal disease treatment, especially peptides from HBM that exhibit multiple functions within cells. To explore the potential biological function peptides among the colostrum, transition and mature milk from mother of extremely low birth weight children (the samples were collected from Women's Hospital of Nanjing Medical University from December 2016 to February 2017). A total of 3,182 nonredundant peptides were identified and compared among colostrum, transitional and mature milk using liquid chromatography/mass spectrometry technology, and the numbers and fragments of peptides were various. The isoelectric point and molecular weight analysis of the differentially expressed peptides basically accord with the range of mass spectrometry identification (<3 kDa). Gene Ontology analysis and Pathway analysis, restriction sites analysis, as well as bioinformatics analysis showed that these differentially expressed peptides enriched a variety of biological processes. We identified several putative peptides that might have bioactive effects in diseases and development of newborns, which will inform further functional investigations. Our preliminary research provided a better understanding of the function of peptides during the newborn periods. Furthermore, it laid a foundation for discovering new peptide drugs in neonatal disease treatment.
Suppression of MALAT1 ameliorates chronic constriction injury‐induced neuropathic pain in rats via modulating miR‐206 and ZEB2
Authors: Chen Zhao‐Ling , Liu Jing‐Yi , Wang Fang , Jing Xu
Published: February 2019

Long noncoding RNAs (lncRNAs) are involved in multiple nervous system diseases, including neuropathic pain. Previous studies have demonstrated that lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) has been identified as a diagnostic biomarker in many diseases. Nevertheless, the function of MALAT1 in neuropathic pain progression is still unclear. Here, we established a chronic constriction injury (CCI) rat model. We found that MALAT1 was remarkably upregulated in CCI rats. In addition, neuropathic pain behaviors such as mechanical and thermal hyperalgesia were reduced by the inhibition of MALAT1. Meanwhile, the loss of MALAT1 was able to depress the neuroinflammation process via the inhibition of COX‐2, interleukin‐1β, and interleukin‐6. A previous study has indicated that miR‐206 upregulation can restrain the CCI‐induced neuropathic pain. Furthermore, we exhibited that miR‐206 was significantly downregulated and silence of MALAT1 restrained its expression in CCI rats. For another, ZEB2 was a target of miR‐206 and it was shown that ZEB2 was elevated in CCI rats in a time‐dependent manner. Overexpression of miR‐206 obviously suppressed ZEB2 levels in rat microglial cells. Subsequently, it was demonstrated that upregulation of miR‐206 rescued the neuropathic pain triggered by ZEB2 overexpression in vivo through neuroinflammation inhibition. Overall, we indicated that suppression of MALAT1 ameliorated neuropathic pain progression via miR‐206/ZEB2 axis.
A functional variant in the flanking region of pri‐let‐7f contributes to colorectal cancer risk in a Chinese population
Authors: Yuan Fang , Xiao Xiao , Che Guanglu , Wang Yanyun , Wang Tao , Luo Xiaolei , Liang Weibo , Gao Linbo , Zhang Lin
Published: February 2019

Let‐7f was reported to be downregulated in patients with colorectal cancer (CRC). However, little is known about the role of let‐7f in CRC carcinogenesis. The aim of this study was to investigate the correlation between genetic polymorphisms in the flanking region of pri‐let‐7f and CRC risk, as well as the potential role of let‐7f in CRC cell migration and invasion. The pri‐let‐7f‐1 rs10739971 and pri‐let‐7f‐2 rs17276588 were genotyped using TaqMan (Applied Biosystems, Foster City, CA) assay. The luciferase activity was detected using Dual‐Luciferase Reporter Assay. CRC cell migration and invasion were evaluated using transwell chamber assay. The rs17276588 AG and AG/AA genotypes had a significantly increased CRC risk (AG vs. GG: adjusted odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.19–1.83, p < 0.001; AG/AA vs. GG: adjusted OR = 1.43, 95% CI = 1.17–1.75, p < 0.001). Stratification analyses showed that the increased risk was observed in CRC patients with well‐moderately differential status, patients with clinical Stages I–II, and patients without lymph node metastasis. The rs17276588A allele displayed a decreased transcriptional activity and low levels of let‐7f. Moreover, let‐7f inhibited migration and invasion in Caco‐2 and Lovo cells. These findings indicate that the rs17276588 AG/AA genotypes increased CRC risk by reducing the expression of tumor suppressor let‐7f.
LINC00628 suppresses migration and invasion of hepatocellular carcinoma by its conserved region interacting with the promoter of VEGFA
Authors: Chen Qiuxu , Wang Dan , Li Yongguo , Yan Shaoying , Dang Hao , Yue Huan , Ling Jiaji , Chen Fengjiao , Zhao Yannan , Gou Luxia , Tang Ping , Huang Ailong , Tang Hua
Published: February 2019

Accumulated evidence revealed that numerous long noncoding RNAs (lncRNAs) have been found to be involved in the development and progression of hepatocellular carcinoma (HCC). LINC00628, a member of lncRNAs, has been reported to act as a tumor suppressor in gastric cancer and breast cancer. However, its potential role in HCC still remains unknown. Herein, we characterized the function of LINC00628 in HCC. Our investigation has revealed that LINC00628 were dramatically decreased in HCC tissues and cells, and inhibited the migration and invasion of HCC cells in vitro and in vivo. Moreover, LINC00628 exerted its tumor suppressive function by repressing the vascular endothelial growth factor A (VEGFA) promoter activity. A highly conserved region element in LINC00628 was identified by a cross‐species comparative analysis, which is required for LINC00628 exerted its function. Dual‐luciferase reporter assay showed that the conserved sequence mediated the interaction with a specific region of VEGFA promoter, resulting in a decrease of VEGFA expression. In conclusion, our results demonstrated that LINC00628 could function as a tumor suppressor in HCC via its conserved sequence elements interacting with a particular region of VEGFA promoter, suggesting that LINC00628 may serve as a novel promising target for diagnosis and therapy in HCC.
A novel LncRNA‐based prognostic score reveals TP53‐dependent subtype of lung adenocarcinoma with poor survival
Authors: Kumar Pranjal , Khadirnaikar Seema , Shukla Sudhanshu Kumar
Published: February 2019

The prognostic signatures play an essential role in the era of personalised therapy for cancer patients including lung adenocarcinoma (LUAD). Long noncoding RNA (LncRNA), a relatively novel class of RNA, has shown to play a crucial role in all the areas of cancer biology. Here, we developed and validated a robust LncRNA‐based prognostic signature for LUAD patients using three different cohorts. In the discovery cohort, four LncRNAs were identified with 10% false discovery rate and a hazard ratio of >10 using univariate Cox regression analysis. A risk score, generated from the four LncRNAs’ expression, was found to be a significant predictor of survival in the discovery and validation cohort (p = 9.97 × 10
−8 and 1.41 × 10
−3, respectively). Further optimisation of four LncRNAs signature in the validation cohort, generated a three LncRNAs prognostic score (LPS), which was found to be an independent predictor of survival in both the cohorts (
p = 1.00 × 10
−6 and 7.27 × 10
−4, respectively). The LPS also significantly divided survival in clinically important subsets, including Stage I (
p = 9.00 × 10
−4 and 4.40 × 10
−2, respectively), KRAS wild‐type (WT), KRAS mutant (
p = 4.00 × 10
−3 and 4.30 × 10
−2, respectively) and EGFR WT (
p = 2.00 × 10
−4). In multivariate analysis LPS outperformed, eight previous prognosticators. Further, individual members of LPS showed a significant correlation with survival in microarray data sets. Mutation analysis showed that high‐LPS patients have a higher mutation rate and inactivation of the TP53 pathway. In summary, we identified and validated a novel LncRNA signature LPS for LUAD.
Antitumor effects of curcumin: A lipid perspective
Authors: Naeini Mehri Bemani , Momtazi Amir Abbas , Jaafari Mahmoud Reza , Johnston Thomas P. , Barreto George , Banach Maciej , Sahebkar Amirhossein
Published: February 2019

Lipid metabolism plays an important role in cancer development due to the necessities of rapidly dividing cells to increase structural, energetic, and biosynthetic demands for cell proliferation. Basically, obesity, type 2 diabetes, and other related diseases, and cancer are associated with a common hyperactivated “lipogenic state.” Recent evidence suggests that metabolic reprogramming and overproduction of enzymes involved in the synthesis of fatty acids are the new hallmarks of cancer, which occur in an early phase of tumorigenesis. As the first evidence to confirm dysregulated lipid metabolism in cancer cells, the overexpression of fatty acid synthase (FAS) was observed in breast cancer patients and demonstrated the role of FAS in cancer. Other enzymes of fatty acid synthesis have recently been found to be dysregulated in cancer, including ATP‐dependent citrate lyase and acetyl‐CoA carboxylase, which further underscores the connection of these metabolic pathways with cancer cell survival and proliferation. The degree of overexpression of lipogenic enzymes and elevated lipid utilization in tumors is closely associated with cancer progression. The question that arises is whether the progression of cancer can be suppressed, or at least decelerated, by modulating gene expression related to fatty acid metabolism. Curcumin, due to its effects on the regulation of lipogenic enzymes, might be able to suppress, or even cause regression of tumor growth. This review discusses recent evidence concerning the important role of lipogenic enzymes in the metabolism of cancer cells and whether the inhibitory effects of curcumin on lipogenic enzymes is therapeutically efficacious.
Current approaches in identification and isolation of cancer stem cells
Authors: Akbarzadeh Maryam , Maroufi Nazila Fathi , Tazehkand Abbas Pirpour , Akbarzadeh Moloud , Bastani Sepideh , Safdari Reza , Farzane Ali , Fattahi Amir , Nejabati Hamid Reza , Nouri Mohammad , Samadi Nasser
Published: February 2019

Cancer stem cells (CSCs) are tumor cells with initiating ability, self‐renewal potential, and intrinsic resistance to conventional therapeutics. Efficient isolation and characterization of CSCs pave the way for more comprehensive knowledge about tumorigenesis, heterogeneity, and chemoresistance. Also a better understanding of CSCs will lead to novel era of both basic and clinical cancer research, reclassiﬁcation of human tumors, and development of innovative therapeutic strategies. Finding novel diagnostic and effective therapeutic strategies also enhance the success of treatment in cancer patients. There are various methods based on the characteristics of the CSCs to detect and isolate these cells, some of which have recently developed. This review summarized current techniques for effective isolation and characterization of CSCs with a focus on advantages and limitations of each method with clinical applications.
Defining early hematopoietic‐fated primitive streak specification of human pluripotent stem cells by the orchestrated balance of Wnt, activin, and BMP signaling
Authors: Shen Jun , Lyu Cuicui , Zhu Yaoyao , Feng Zicen , Zhang Shuo , Hoyle Dixie L. , Ji Guangzhen , Brodsky Robert A. , Cheng Tao , Wang Zack Z.
Published: February 2019

Distinct regions of the primitive streak (PS) have diverse potential to differentiate into several tissues, including the hematopoietic lineage originated from the posterior region of PS. Although various signaling pathways have been identified to promote the development of PS and its mesoderm derivatives, there is a large gap in our understanding of signaling pathways that regulate the hematopoietic fate of PS. Here, we defined the roles of Wnt, activin, and bone morphogenetic protein (BMP) signaling pathways in generating hematopoietic‐fated PS from human pluripotent stem cells (hPSCs). We found that the synergistic balance of these signaling pathways was crucial for controlling the PS fate determination towards hematopoietic lineage via mesodermal progenitors. Although the induction of PS depends largely on the Wnt and activin signaling, the PS generated without BMP4 lacks the hematopoietic potential, indicating that the BMP signaling is necessary for the PS to acquire hematopoietic property. Appropriate levels of Wnt signaling is crucial for the development of PS and its specification to the hematopoietic lineage. Although the development of PS is less sensitive to activin or BMP signaling, the fate of PS to mesoderm progenitors and subsequent hematopoietic lineage is determined by appropriate levels of activin or BMP signaling. Collectively, our study demonstrates that Wnt, activin, and BMP signaling pathways play cooperative and distinct roles in regulating the fate determination of PS for hematopoietic development. Our understanding of the regulatory networks of hematopoietic‐fated PS would provide important insights into early hematopoietic patterning and possible guidance for generating functional hematopoietic cells from hPSCs in vitro.
A systematic review of radiation‐induced testicular toxicities following radiotherapy for prostate cancer
Authors: Farhood Bagher , Mortezaee Keywan , Haghi‐Aminjan Hamed , Khanlarkhani Neda , Salehi Ensieh , Nashtaei Maryam Shabani , Najafi Masoud , Sahebkar Amirhossein
Published: February 2019

Background

Prostate cancer is the second most common malignancy in men in the world, and radiotherapy is used as a standard treatment modality for this cancer. Although this treatment modality effectively kills prostate cancerous cells, it unavoidably irradiates the organs/tissues that are away from the treatment site. In this regard, radiation‐induced testicular toxicities following prostate radiotherapy can affect sexual function, reproduction, and quality of life in cancer survivors. This review summarizes the available data on testicular exposure to radiation during prostate radiotherapy and the consequences on testicular function.

Methods

To illuminate the radiation‐induced testicular toxicities following prostate radiotherapy, a systematic search was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guideline in PubMed, Web of Science, Scopus, Embase, and clinical trials electronic databases up to September 2018. According to a set of prespecified inclusion and exclusion criteria, 31 eligible articles providing data on testicular function following radiotherapy in patients with prostate cancer were included in the study.

Results

According to the different radiotherapeutic techniques used for prostate cancer treatment, the total tumor dose and scattered testicular dose values were ranging from 36.25 to 78.00 Gy and 0.06 to 6.48 Gy, respectively. Luteinizing hormone and follicle‐stimulating hormone levels after prostate radiotherapy were signiﬁcantly higher in comparison with the pretreatment levels. Around 60% of the studies showed that testosterone levels after prostate radiotherapy were signiﬁcantly lower than the pretreatment levels. Furthermore, erectile dysfunction (ED), as an adverse side effect resulting from prostate radiotherapy, was reported and this complication is signiﬁcantly correlated with lower satisfaction with sexual life. Testicular atrophy following prostate radiotherapy has also been observed and its frequency in patients with prior prostate radiotherapy is 2.5 times more than that in the patients without prior radiotherapy.

Conclusion

The data revealed that the scattered dose to testicular tissues during prostate radiotherapy can lead to testicular atrophy, variation of the male sex hormones, and quality of sexual life.
Population Pharmacokinetics of Vamorolone (VBP15) in Healthy Men and Boys With Duchenne Muscular Dystrophy
Authors: Mavroudis Panteleimon D. , van den Anker John , Conklin Laurie S. , Damsker Jesse M. , Hoffman Eric P. , Nagaraju Kanneboyina , Clemens Paula R. , Jusko William J.
Published: February 2019

Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder occurring in boys and caused by mutations in the dystrophin gene. Vamorolone is a first‐generation delta‐9,11 compound that has favorable efficacy and side effect profiles relative to classical glucocorticoids. The pharmacokinetics (PK) of oral vamorolone were assessed in parallel‐group studies in healthy men (phase 1, n = 86) and boys with DMD (phase 2a, n = 48) during 14 days of once‐daily dosing with a range of doses. Vamorolone exhibited moderate variability in PK, with the maximum plasma concentration usually occurring at 2‐4 hours and a half‐life of approximately 2 hours for all doses and days examined. Population PK modeling of all data together indicated that the PK of vamorolone can be well described by a 1‐compartment model with zero‐order absorption. Both men and boys showed a dose‐linearity of PK parameters for the doses examined, with no accumulation of the drug during daily dosing. Ingestion with food resulted in markedly enhanced absorption of the drug, as tested in healthy men. There were similar PK of vamorolone in healthy men and DMD boys with apparent clearance averaging 2.0 L/h/kg in men and 1.7 L/h/kg in boys. Overall, vamorolone exhibited well‐behaved linear PK, with similar profiles in healthy men and boys with DMD, moderate variability in PK parameters, and absorption and disposition profiles similar to those of classical glucocorticoids.
Induced subgraphs of graphs with large chromatic number. XII. Distant stars
Authors: Chudnovsky Maria , Scott Alex , Seymour Paul
Published: February 2019

The Gyárfás‐Sumner conjecture asserts that if is a tree then every graph with bounded clique number and very large chromatic number contains as an induced subgraph. This is still open, although it has been proved for a few simple families of trees, including trees of radius two, some special trees of radius three, and subdivided stars. These trees all have the property that their vertices of degree more than two are clustered quite closely together. In this paper, we prove the conjecture for two families of trees which do not have this restriction. As special cases, these families contain all double‐ended brooms and two‐legged caterpillars.
Keeping an eye on congenital disorders of O‐glycosylation: A systematic literature review
Authors: Francisco Rita , Pascoal Carlota , Marques‐da‐Silva Dorinda , Morava Eva , Gole Glen A. , Coman David , Jaeken Jaak , dos Reis Ferreira Vanessa
Published: February 2019

Congenital disorders of glycosylation (CDG) are a rapidly growing family comprising >100 genetic diseases. Some 25 CDG are pure O‐glycosylation defects. Even among this CDG subgroup, phenotypic diversity is broad, ranging from mild to severe poly‐organ/system dysfunction. Ophthalmic manifestations are present in 60% of these CDG. The ophthalmic manifestations in N‐glycosylation‐deficient patients have been described elsewhere. The present review documents the spectrum and incidence of eye disorders in patients with pure O‐glycosylation defects with the aim of assisting diagnosis and management and promoting research.
Inborn errors of coenzyme A metabolism and neurodegeneration
Authors: Di Meo Ivano , Carecchio Miryam , Tiranti Valeria
Published: February 2019

Two inborn errors of coenzyme A (CoA) metabolism are responsible for distinct forms of neurodegeneration with brain iron accumulation (NBIA), a heterogeneous group of neurodegenerative diseases having as a common denominator iron accumulation mainly in the inner portion of globus pallidus. Pantothenate kinase‐associated neurodegeneration (PKAN), an autosomal recessive disorder with progressive impairment of movement, vision and cognition, is the most common form of NBIA and is caused by mutations in the pantothenate kinase 2 gene (PANK2), coding for a mitochondrial enzyme, which phosphorylates vitamin B5 in the first reaction of the CoA biosynthetic pathway. Another very rare but similar disorder, denominated CoPAN, is caused by mutations in coenzyme A synthase gene (COASY) coding for a bi‐functional mitochondrial enzyme, which catalyzes the final steps of CoA biosynthesis. It still remains a mystery why dysfunctions in CoA synthesis lead to neurodegeneration and iron accumulation in specific brain regions, but it is now evident that CoA metabolism plays a crucial role in the normal functioning and metabolism of the nervous system.
The decision to discontinue screening for carnitine uptake disorder in New Zealand
Authors: Wilson Callum , Knoll Detlef , de Hora Mark , Kyle Campbell , Glamuzina Emma , Webster Dianne
Published: February 2019

When screening for carnitine uptake disorder (CUD), the New Zealand (NZ) newborn screening (NBS) service identified infants as screen‐positive if they had initial and repeat free carnitine (C0) levels of less than 5.0 μmol/L. Since 2006, the NBS service has identified two infants with biochemical and genetic features consistent with neonatal CUD and nine mothers with features consistent with maternal CUD. A review of the literature suggests that these nine women reflect less than half the true prevalence and that CUD is relatively common. However, the NZ results (two infants) suggest a very low sensitivity and positive predictive value of NBS. While patients presenting with significant disease due to CUD are well described, the majority of adults with CUD are asymptomatic. Nonetheless, treatment with high‐dose oral L‐carnitine is recommended. Compliance with oral L‐carnitine is likely to be poor long term. This may represent a specific risk as treatment could repress the usual compensatory mechanisms seen in CUD, such that a sudden discontinuation of treatment may be dangerous. L‐carnitine is metabolized to trimethylamine‐N‐oxide (TMAO) and treated patients have extremely high plasma TMAO levels. TMAO is an independent risk factor for atherosclerosis and, thus, caution should be exercised regarding long‐term treatment with high‐dose carnitine of asymptomatic patients who may have a biochemical profile without disease. Due to these concerns, the NZ Newborn Metabolic Screening Programme (NMSP) initiated a review via a series of advisory and governance committees and decided to discontinue screening for CUD.
Patterns, evolution, and severity of striatal injury in insidious‐ vs acute‐onset glutaric aciduria type 1
Authors: Boy Nikolas , Garbade Sven F. , Heringer Jana , Seitz Angelika , Kölker Stefan , Harting Inga
Published: February 2019

Background

Striatal injury in patients with glutaric aciduria type 1 (GA1) results in a complex, predominantly dystonic, movement disorder. Onset may be acute following acute encephalopathic crisis (AEC) or insidious without apparent acute event.

Methods

We analyzed clinical and striatal magnetic resonance imaging (MRI) findings in 21 symptomatic GA1 patients to investigate if insidious‐ and acute‐onset patients differed in timing, pattern of striatal injury, and outcome.

Results

Eleven patients had acute and ten had insidious onset, two with later AEC (acute‐on‐insidious). The median onset of dystonia was 10 months in both groups, and severity was greater in patients after AEC (n = 8 severe, n = 5 moderate) than in insidious onset (n = 4 mild, n = 3 moderate, n = 1 severe). Deviations from guideline‐recommended basic metabolic treatment were identified in six insidious‐onset patients. Striatal lesions were extensive in all acute‐onset patients and restricted to the dorsolateral putamen in eight of ten insidious‐onset patients. After AEC, the two acute‐on‐insidious patients had extensive striatal changes superimposed on pre‐existing dorsolateral putaminal lesions. Two insidious‐onset patients with progressive dystonia without overt AEC also had extensive striatal changes, one with sequential striatal injury revealed by diffusion‐weighted imaging. Insidious‐onset patients had a latency phase of 3.5 months to 6.5 years between detection and clinical manifestation of dorsolateral putaminal lesions.

Conclusions

Insidious‐onset type GA1 is characterized by dorsolateral putaminal lesions, less severe dystonia, and an asymptomatic latency phase, despite already existing lesions. Initially normal MRI during the first months and deviations from guideline‐recommended treatment in a large proportion of insidious‐onset patients substantiate the protective effect of neonatally initiated treatment.
Proposal for an individualized dietary strategy in patients with very long‐chain acyl‐CoA dehydrogenase deficiency
Authors: Bleeker Jeannette C. , Kok Irene L. , Ferdinandusse Sacha , de Vries Maaike , Derks Terry G.J. , Mulder Margot F. , Williams Monique , Gozalbo Estela Rubio , Bosch Annet M. , van den Hurk Dorine T. , de Sain‐van der Velden Monique G.M. , Waterham Hans R. , Wijburg Frits A. , Visser Gepke
Published: February 2019

Background

Patients with very long chain acyl‐CoA dehydrogenase deficiency (VLCADD), a long chain fatty acid oxidation disorder, are traditionally treated with a long chain triglyceride (LCT) restricted and medium chain triglyceride (MCT) supplemented diet. Introduction of VLCADD in newborn screening (NBS) programs has led to the identification of asymptomatic newborns with VLCADD, who may have a more attenuated phenotype and may not need dietary adjustments.

Objective

To define dietary strategies for individuals with VLCADD based on the predicted phenotype.

Method

We evaluated long‐term dietary histories of a cohort of individuals diagnosed with VLCADD identified before the introduction of VLCADD in NBS and their beta‐oxidation (LC‐FAO) flux score (rate of oleate oxidation) in cultured skin fibroblasts in relation to the clinical outcome. Based on these results a dietary strategy is proposed.

Results

Sixteen individuals with VLCADD were included. One had an LC‐FAO flux score >90%, was not on a restricted diet and is asymptomatic to date. Four patients had an LC‐FAO flux score <10%, and significant VLCADD related symptoms despite the use of strict diets including LCT restriction, MCT supplementation and nocturnal gastric drip feeding. Patients with an LC‐FAO flux score between 10 and 90% (n = 11) showed a more heterogeneous phenotype.

Conclusions

This study shows that a strict diet cannot prevent poor clinical outcome in severely affected patients and that the LC‐FAO flux is a good predictor of clinical outcome in individuals with VLCADD identified before its introduction in NBS. Hereby, we propose an individualized dietary strategy based on the LC‐FAO flux score.