bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA methylation instability by BRAF-mediated TET silencing and lifestyle-exposure divides colon cancer pathways
Authors: Noreen Faiza , Küng Taya , Tornillo Luigi , Parker Hannah , Silva Miguel , Weis Stefan , Marra Giancarlo , Rad Roland , Truninger Kaspar , Schär Primo
Published: December 2019

Background

Aberrations in DNA methylation are widespread in colon cancer (CC). Understanding origin and progression of DNA methylation aberrations is essential to develop effective preventive and therapeutic strategies. Here, we aimed to dissect CC subtype-specific methylation instability to understand underlying mechanisms and functions.

Methods

We have assessed genome-wide DNA methylation in the healthy normal colon mucosa (HNM), precursor lesions and CCs in a first comprehensive study to delineate epigenetic change along the process of colon carcinogenesis. Mechanistically, we used stable cell lines, genetically engineered mouse model of mutant BRAFV600Eand molecular biology analysis to establish the role of BRAFV600E-mediated-TET inhibition in CpG-island methylator phenotype (CIMP) inititation.

Results

We identified two distinct patterns of CpG methylation instability, determined either by age–lifestyle (CC-neutral CpGs) or genetically (CIMP-CpGs). CC-neutral-CpGs showed age-dependent hypermethylation in HNM, all precursors, and CCs, while CIMP-CpGs showed hypermethylation specifically in sessile serrated adenomas/polyps (SSA/Ps) and CIMP-CCs.BRAFV600E-mutated CCs and precursors showed a significant downregulation ofTET1andTET2DNA demethylases. Stable expression ofBRAFV600Ein nonCIMP CC cells and in a genetic mouse model was sufficient to repress TET1/TET2 and initiate hypermethylation at CIMP-CpGs, reversible byBRAFV600Einhibition.BRAFV600E-driven CIMP-CpG hypermethylation occurred at genes associated with established CC pathways, effecting functional changes otherwise achieved by genetic mutation in carcinogenesis.

Conclusions

Hence, while age–lifestyle-driven hypermethylation occurs generally in colon carcinogenesis,BRAFV600E-driven hypermethylation is specific for the “serrated” pathway. This knowledge will advance the use of epigenetic biomarkers to assess subgroup-specific CC risk and disease progression.
Molecular patterning during the development of Phoronopsis harmeri reveals similarities to rhynchonelliform brachiopods
Authors: Andrikou Carmen , Passamaneck Yale J. , Lowe Chris J. , Martindale Mark Q. , Hejnol Andreas
Published: December 2019

Background

Phoronids, rhynchonelliform and linguliform brachiopods show striking similarities in their embryonic fate maps, in particular in their axis specification and regionalization. However, although brachiopod development has been studied in detail and demonstrated embryonic patterning as a causal factor of the gastrulation mode (protostomy vs deuterostomy), molecular descriptions are still missing in phoronids. To understand whether phoronids display underlying embryonic molecular mechanisms similar to those of brachiopods, here we report the expression patterns of anterior (otx,gsc,six3/6,nk2.1), posterior (cdx, bra) and endomesodermal (foxA,gata4/5/6,twist) markers during the development of the protostomic phoronidPhoronopsis harmeri.

Results

The transcription factorsfoxA, gata4/5/6andcdxshow conserved expression in patterning the development and regionalization of the phoronid embryonic gut, withfoxAexpressed in the presumptive foregut,gata4/5/6demarcating the midgut andcdxconfined to the hindgut. Furthermore,six3/6,usually a well-conserved anterior marker, shows a remarkably dynamic expression, demarcating not only the apical organ and the oral ectoderm, but also clusters of cells of the developing midgut and the anterior mesoderm, similar to what has been reported for brachiopods, bryozoans and some deuterostome Bilateria. Surprisingly,brachyury, a transcription factor often associated with gastrulation movements and mouth and hindgut development, seems not to be involved with these patterning events in phoronids.

Conclusions

Our description and comparison of gene expression patterns with other studied Bilateria reveals that the timing of axis determination and cell fate distribution of the phoronid shows highest similarity to that of rhynchonelliform brachiopods, which is likely related to their shared protostomic mode of development. Despite these similarities, the phoronidPh. harmerialso shows particularities in its development, which hint to divergences in the arrangement of gene regulatory networks responsible for germ layer formation and axis specification.
Applications of miRNAs in cardiac development, disease progression and regeneration
Authors: Pang Jeremy Kah Sheng , Phua Qian Hua , Soh Boon-Seng
Published: December 2019

Development of the complex human heart is tightly regulated at multiple levels, maintaining multipotency and proliferative state in the embryonic cardiovascular progenitors and thereafter suppressing progenitor characteristics to allow for terminal differentiation and maturation. Small regulatory microRNAs (miRNAs) are at the level of post-transcriptional gene suppressors, which enhance the degradation or decay of their target protein-coding mRNAs. These miRNAs are known to play roles in a large number of biological events, cardiovascular development being no exception. A number of critical cardiac-specific miRNAs have been identified, of which structural developmental defects have been linked to dysregulation of miRNAs in the proliferating cardiac stem cells. These miRNAs present in the stem cell niche are lost when the cardiac progenitors terminally differentiate, resulting in the postnatal mitotic arrest of the heart. Therapeutic applications of these miRNAs extend to the realm of heart failure, whereby the death of heart cells in the ageing heart cannot be replaced due to the arrest of cell division. By utilizing miRNA therapy to control cell cycling, the regenerative potential of matured myocardium can be restored. This review will address the various cardiac progenitor-related miRNAs that control the development and proliferative potential of the heart.
Current understanding of the administration of mesenchymal stem cells in acute kidney injury to chronic kidney disease transition: a review with a focus on preclinical models
Authors: Zhao Lingfei , Han Fei , Wang Junni , Chen Jianghua
Published: December 2019

Incomplete recovery from acute kidney injury (AKI) can result in long-term functional deficits and has been recognized as a major contributor to chronic kidney disease (CKD), which is termed the AKI-CKD transition. Currently, an effective intervention for this disorder is still lacking. Principally, therapeutic strategies targeting the AKI-CKD transition can be divided into those reducing the severity of AKI or promoting the regenerative process towards beneficially adaptive repair pathways. Considering the fact that mesenchymal stem cells (MSCs) have the potential to address both aspects, therapeutic regimens based on MSCs have a promising future. In light of this information, we focus on the currently available evidence associated with MSC therapy involved in the treatment of the AKI-CKD transition and the underlying mechanisms. All of these discussions will contribute to the establishment of a reliable therapeutic strategy for patients with this problem, who can be easily ignored by physicians, and will lead to a better clinical outcome for them.
Community detection in networks: a game-theoretic framework
Authors: Chen Yan , Cao Xuanyu , Liu K. J. Ray
Published: December 2019

Real-world networks are often cluttered and hard to organize. Recent studies show that most networks have the community structure, i.e., nodes with similar attributes form a certain community, which enables people to better understand the constitution of the networks and thus gain more insights into the complicated networks. Strategic nodes belonging to different communities interact with each other to decide mutual links in the networks. Hitherto, various community detection methods have been proposed in the literature, yet none of them takes the strategic interactions among nodes into consideration. Additionally, many real-world observations of networks are noisy and incomplete, i.e., with some missing links or fake links, due to either technology constraints or privacy regulations. In this work, a game-theoretic framework of community detection is established, where nodes interact and produce links with each other in a rational way based on mutual benefits, i.e., maximizing their own utility functions when forming a community. Given the proposed game-theoretic generative models for communities, we present a general community detection algorithm based on expectation maximization (EM). Simulations on synthetic networks and experiments on real-world networks demonstrate that the proposed detection method outperforms the state of the art.
A new joint CTC-attention-based speech recognition model with multi-level multi-head attention
Authors: Qin Chu-Xiong , Zhang Wen-Lin , Qu Dan
Published: December 2019

A method called joint connectionist temporal classification (CTC)-attention-based speech recognition has recently received increasing focus and has achieved impressive performance. A hybrid end-to-end architecture that adds an extra CTC loss to the attention-based model could force extra restrictions on alignments. To explore better the end-to-end models, we propose improvements to the feature extraction and attention mechanism. First, we introduce a joint model trained with nonnegative matrix factorization (NMF)-based high-level features. Then, we put forward a hybrid attention mechanism by incorporating multi-head attentions and calculating attention scores over multi-level outputs. Experiments on TIMIT indicate that the new method achieves state-of-the-art performance with our best model. Experiments on WSJ show that our method exhibits a word error rate (WER) that is only 0.2% worse in absolute value than the best referenced method, which is trained on a much larger dataset, and it beats all present end-to-end methods. Further experiments on LibriSpeech show that our method is also comparable to the state-of-the-art end-to-end system in WER.
Time series behavior modeling with digital twin for Internet of Vehicles
Authors: Zhang Tianle , Liu Xiangtao , Luo Zongwei , Dong Fuqiang , Jiang Yu
Published: December 2019

Electric vehicle (EV) is considered eco-friendly with low carbon emission and maintenance costs. Given the current battery and charging technology, driving experience of EVs relies heavily on the availability and reachability of EV charging infrastructure. As the number of charging piles increases, carefully designed arrangement of resources and efficient utilization of the infrastructure is essential to the future development of EV industry. The mobility and distribution of EVs determine the charging demand and the load of power distribution grid. Then, dynamic traffic pattern of numerous interconnected EVs poses great impact on charging plans and charging infrastructure.

In this paper, we introduce the digital twin of a real-world EV by modeling the mobility based on a time series behaviors of EVs to evaluate the charging algorithm and pile arrangement policy. The introduced digital twin EV is a virtually simulated equivalence with same traffic behaviors and charging activities as the EV in real world. The behavior and route choice of EVs is dynamically simulated base on the time-varying driving operations, travel intent, and charging plan in a simulated large-scale charging scenario composed of concurrently moving EVs and correspondingly equipped charging piles. Different EV navigation algorithms and charging algorithms of Internet of Vehicle can be exactly evaluated in the dynamic simulation of the digital twins of the moving EVs and charging infrastructure. Then we analyze the collected data such as energy consumption, charging capacity, charging frequency, and waiting time in queue on both the EV side and the charging pile side to evaluate the charging efficiency. The simulation is used to study the relations between the scheduled charging operation of EVs and the deployment of piles. The proposed model helps evaluate and validate the design of the charging recommendation and the deployment plan regarding to the arrangement and distribution of charging piles.
Asymptotic behavior for the semilinear reaction–diffusion equations with memory
Authors: Zhang Jiangwei , Xie Yongqin , Luo Qingqing , Tang Zhipiao
Published: December 2019

In this paper, we consider the dynamics of a reaction–diffusion equation with fading memory and nonlinearity satisfying arbitrary polynomial growth condition. Firstly, we prove a criterion in a general setting as an alternative method (or technique) to the existence of the bi-spaces attractors for the nonlinear evolutionary equations (see Theorem 2.14). Secondly, we prove the asymptotic compactness of the semigroup on $L^{2}(\varOmega )\times L_{\mu }^{2}(\mathbb{R}; H_{0}^{1}( \varOmega ))$L2(Ω)×Lμ2(R;H01(Ω)) by using the contractive function, and the global attractor is confirmed. Finally, the bi-spaces global attractor is obtained by verifying the asymptotic compactness of the semigroup on $L^{p}( \varOmega )\times L_{\mu }^{2}(\mathbb{R}; H_{0}^{1}(\varOmega ))$Lp(Ω)×Lμ2(R;H01(Ω)) with initial data in $L^{2}(\varOmega )\times L_{\mu }^{2}(\mathbb{R}; H_{0} ^{1}(\varOmega ))$L2(Ω)×Lμ2(R;H01(Ω)).
Multi-valued backward stochastic differential equations with regime switching
Authors: Deng Ruijuan , Ren Yong
Published: December 2019

The paper considers a class of multi-valued backward stochastic differential equations with subdifferential of a lower semi-continuous convex function with regime switching, whose generator is a continuous-time Markov chain with a finite state space. Firstly, we get the existence and uniqueness of the solution by the penalization method. Secondly, we prove that the solution of the original system is weakly convergent. Finally, we give an application to the homogenization of a class of multi-valued PDEs with Markov chain.
Convergence of solutions for functional integro-differential equations with nonlinear boundary conditions
Authors: Wang Peiguang , Wang Yameng , Jiang Cuimei , Li Tongxing
Published: December 2019

This paper is concerned with the convergence of solutions for a class of functional integro-differential equations with nonlinear boundary conditions. New comparison principles are obtained. By using the comparison principles and quasilinearization method, we present two monotone iterative sequences uniformly and monotonically converging to the unique solution with rate of order 2. Meanwhile, an example is given to demonstrate applications of the result reported.
Spectral properties and a Parseval’s equality in the singular case for q-Dirac problem
Authors: Mosazadeh Seyfollah
Published: December 2019

This paper is devoted to studying a q-analog of the singular Dirac problem. First, we investigate some spectral properties of the problem. Then we prove the existence of a spectral function and establish a Parseval’s equality, for the singular q-Dirac system in a Hilbert space. Although there were given some results for this type of problem, we think that Parseval’s equality has not been studied yet.
Predictors of psychosocial outcome of bipolar disorder: data from the Stanley Foundation Bipolar Network
Authors: Bennett Francis , Hodgetts Sophie , Close Andrew , Frye Mark , Grunze Heinz , Keck Paul , Kupka Ralph , McElroy Susan , Nolen Willem , Post Robert , Schärer Lars , Suppes Trisha , Sharma Aditya N.
Published: December 2019

Background

Impairments in psychosocial functioning have been demonstrated in 30–60% of adults with bipolar disorder (BD). However, the majority of studies investigating the effect of comorbid mental health disorders and age at onset outcomes in BD have focused on traditional outcome measures such as mood symptoms, mortality and treatment response. Therefore, this project aimed to investigate the impact of comorbid mental health disorders and age at onset on longitudinal psychosocial outcome in participants with BD.

Method

Mixed effects modelling was conducted using data from the Stanley Foundation Bipolar Network. Baseline factors were entered into a model, with Global Assessment of Functioning (GAF) score as the longitudinal outcome measure. Relative model fits were calculated using Akaike’s Information Criterion.

Results

No individual comorbidities predicted lower GAF scores, however an interaction effect was demonstrated between attention deficit hyperactivity disorder (ADHD) and any anxiety disorder (t = 2.180, p = 0.030). Participants with BD I vs BD II (t = 2.023, p = 0.044) and those in the lowest vs. highest income class (t = 2.266, p = 0.024) predicted lower GAF scores. Age at onset (t = 1.672, p = 0.095) did not significantly predict GAF scores.

Conclusions

This is the first study to demonstrate the negative psychosocial effects of comorbid anxiety disorders and ADHD in BD. This study adds to the growing database suggesting that comorbid mental health disorders are a significant factor hindering psychosocial recovery.
Glycine-alanine dipeptide repeats spread rapidly in a repeat length- and age-dependent manner in the fly brain
Authors: Morón-Oset Javier , Supèr Tessa , Esser Jacqueline , Isaacs Adrian M. , Grönke Sebastian , Partridge Linda
Published: December 2019

Hexanucleotide repeat expansions of variable size in C9orf72 are the most prevalent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Sense and antisense transcripts of the expansions are translated by repeat-associated non-AUG translation into five dipeptide repeat proteins (DPRs). Of these, the polyGR, polyPR and, to a lesser extent, polyGA DPRs are neurotoxic, with polyGA the most abundantly detected DPR in patient tissue. Trans-cellular transmission of protein aggregates has recently emerged as a major driver of toxicity in various neurodegenerative diseases. In vitro evidence suggests that the C9 DPRs can spread. However, whether this phenomenon occurs under more complex in vivo conditions remains unexplored. Here, we used the adult fly brain to investigate whether the C9 DPRs can spread in vivo upon expression in a subset of neurons. We found that only polyGA can progressively spread throughout the brain, which accumulates in the shape of aggregate-like puncta inside recipient cells. Interestingly, GA transmission occurred as early as 3 days after expression induction. By comparing the spread of 36, 100 and 200 polyGA repeats, we found that polyGA spread is enhanced upon expression of longer GA DPRs. Transmission of polyGA is greater in older flies, indicating that age-associated factors exacerbate the spread. These data highlight a unique propensity of polyGA to spread throughout the brain, which could contribute to the greater abundance of polyGA in patient tissue. In addition, we present a model of early GA transmission that is suitable for genetic screens to identify mechanisms of spread and its consequences in vivo.
Computational storage: an efficient and scalable platform for big data and HPC applications
Authors: Torabzadehkashi Mahdi , Rezaei Siavash , HeydariGorji Ali , Bobarshad Hosein , Alves Vladimir , Bagherzadeh Nader
Published: December 2019

In the era of big data applications, the demand for more sophisticated data centers and high-performance data processing mechanisms is increasing drastically. Data are originally stored in storage systems. To process data, application servers need to fetch them from storage devices, which imposes the cost of moving data to the system. This cost has a direct relation with the distance of processing engines from the data. This is the key motivation for the emergence of distributed processing platforms such as Hadoop, which move process closer to data. Computational storage devices (CSDs) push the “move process to data” paradigm to its ultimate boundaries by deploying embedded processing engines inside storage devices to process data. In this paper, we introduce Catalina, an efficient and flexible computational storage platform, that provides a seamless environment to process data in-place. Catalina is the first CSD equipped with a dedicated application processor running a full-fledged operating system that provides filesystem-level data access for the applications. Thus, a vast spectrum of applications can be ported for running on Catalina CSDs. Due to these unique features, to the best of our knowledge, Catalina CSD is the only in-storage processing platform that can be seamlessly deployed in clusters to run distributed applications such as Hadoop MapReduce and HPC applications in-place without any modifications on the underlying distributed processing framework. For the proof of concept, we build a fully functional Catalina prototype and a CSD-equipped platform using 16 Catalina CSDs to run Intel HiBench Hadoop and HPC benchmarks to investigate the benefits of deploying Catalina CSDs in the distributed processing environments. The experimental results show up to 2.2× improvement in performance and 4.3× reduction in energy consumption, respectively, for running Hadoop MapReduce benchmarks. Additionally, thanks to the Neon SIMD engines, the performance and energy efficiency of DFT algorithms are improved up to 5.4× and 8.9×, respectively.
Educational games and the new forms of interactions
Authors: Zaina Luciana , Castro Elisa , Martinelli Suellen , Sakata Tiemi
Published: December 2019

Games are seen as environments that promote the engagement of children to the learning of Computational Thinking (CT) concepts. The new forms of interaction using body movements and gestures have increased in particular in video-games. However, few studies have been conducted to investigate how children feel and interact when using hand gestures in the context of learning tools. And this number becomes low when we look at studies about CT learning. In this article, we explored the feedback of 29 children about their interaction by using hand gestures in a game to stimulate the CT, i.e. a CT game. In the analysis, we explored how these forms of interaction impacted on the accomplishing of the game phases. Our findings revealed the children kept more engaged when using hand gestures, and consequently, this affected their concentration on the game purpose. To complement our investigation, we interviewed 8 elementary school teachers to gather their perceptions about the potential of using hand gestures and our game. The findings showed the teachers agreed that hand gestures are suitable to be used in learning tools. They also demonstrated interested in introducing the CT fundamentals in their classes. However, these teachers demonstrated some concerns about how to match the use of that technology to their teaching activities.
RASAL1 induces to downregulate the SCD1, leading to suppression of cell proliferation in colon cancer via LXRα/SREBP1c pathway
Authors: Wang Guangchuan , Li Zhen , Li Xiao , Zhang Chunqing , Peng Lipan
Published: December 2019

Background

Recent studies have confirmed that RASAL1 has an antitumor effect in many cancers, but its functional role and the molecular mechanism underlying in colon cancer has not been investigated.

Results

We collected human colon cancer tissues and adjacent non-tumor tissues, human colon cancer cell lines LoVo, CaCo2, SW1116, SW480 and HCT-116, and normal colonic mucosa cell line NCM460. RT-qPCR was used to detect the RASAL1 level in the clinical tissues and cell lines. In LoVo and HCT-116, RASAL1 was artificially overexpressed. Cell viability and proliferation were measured using CCK-8 assays, and cell cycle was detected via PI staining and flow cytometry analysis. RASAL1 significantly inhibited the cell proliferation via inducing cell cycle arrest, suppressed cell cycle associated protein expression, and decreased the lipid content and inhibited the SCD1 expression. Moreover, SCD1 overexpression induced and downregulation repressed cell proliferation by causing cell cycle arrest. Additionally, luciferase reporter assays were performed to confirm the direct binding between SREBP1c, LXRα and SCD1 promoter, we also demonstrated that RASAL1 inhibit SCD1 3′-UTR activity. RASAL1 inhibited tumor growth in xenograft nude mice models and shows inhibitory effect of SCD1 expression in vivo.

Conclusion

Taken together, we concluded that RASAL1 inhibited colon cancer cell proliferation via modulating SCD1 activity through LXRα/SREBP1c pathway.
An analytical investigation of elastic-plastic deformation of FGM hollow rotors under a high centrifugal effect
Authors: Torabnia Shams , Aghajani Sepideh , Hemati Mohammadreza
Published: December 2019

Functionally graded material shafts are the main part of many modern rotary machines such as turbines and electric motors. The purpose of this study is to present an analytical solution of the elastic-plastic deformation of functionally graded material hollow rotor under a high centrifugal effect and finally determine the maximum allowed angular velocity of a hollow functionally graded material rotating shaft. Introducing non-dimensional parameters, the equilibrium equation has been analytically solved. The results for variable material properties are compared with the homogeneous rotor and the case in which Young’s modulus is the only variable while density and yield stress are considered to be constant. It is shown that material variation has a considerable effect on the stress and strain components and radial displacement. Considering variable density and yield stress causes yielding onset from inner, outer, or simultaneously from both inner and outer rotor shaft radius in contrast to earlier researches that modulus of elasticity was the only variable. The effects of the density on the failure of a functionally graded material elastic fully plastic in a hollow rotating shaft are investigated for the first time in this study with regard to Tresca’s yield criterial. Numerical simulations are used to verify the derived formulations which are in satisfying agreement.
Dental implants in immunocompromised patients: a systematic review and meta-analysis
Authors: Duttenhoefer Fabian , Fuessinger Marc Anton , Beckmann Yasmin , Schmelzeisen Rainer , Groetz Knut A. , Boeker Martin
Published: December 2019

Objective

Impaired health conditions and related lack of adequate host healing are among the most important conditions that account for dental implant failure. Today clinicians face an increasing number of immunocompromised patients requesting implant-based rehabilitation. To provide clinical evidence for prospective decision-making, the aim of this systematic review and meta-analysis was to analyse the influence of immunodeficiency on dental implant survival.

Methods

The study was conducted according to the PRISMA Statement and the principles of the Cochrane Collaboration. MEDLINE and Web of Science were searched. Results were calculated by the pooled incidence of implant loss. Reported odds ratios (OR) from fully adjusted models were preferred. Distinct risk estimates were synthesised with 95% confidence intervals.

Results

A total of 62 publications including 1751 endosseous implants placed in immunocompromised patients were included. For the follow-up of 24 months and longer, the mean survival rate of implants in patients with HIV was 93.1%, chemotherapy was 98.8%, autoimmune disease was 88.75%, after organ transplantation was 100%. Crohn’s disease showed a significant effect on early implant failure and resulted in increased, however not significant, implant loss.

Conclusion

No significant effect of immunocompromised conditions on implant survival was detectable. Implant-based therapy in immunocompromised patients should not aggravate the general morbidity and must not interfere in life-saving therapies. A careful risk stratification prior implant therapy is fundamental. To further decipher the role of immunosuppression on dental implantology, more data from controlled and randomised studies are needed.
Clinic-based ultra-wide field retinal imaging in a pediatric population
Authors: Kothari Nikisha , Pineles Stacy , Sarraf David , Velez Federico , Heilweil Gad , Holland Gary , McCannel Colin A. , Onclinx Tania , McCannel Tara A. , Sadda SriniVas R. , Schwartz Steven D. , Tsui Irena
Published: December 2019

Background

Pediatric retinal disorders, although uncommon, can be challenging to assess in the clinic setting and often requires an exam under anesthesia. The purpose of our study was to evaluate the use of ultra-wide field retinal imaging in children without sedation in an outpatient clinic.

Methods

We performed a retrospective case series of patients 18 years or younger who received ultra-wide field imaging over a one year period. The age, gender, and clinical course were documented. Color fundus and red-free images were reviewed to assess field of view. Ultra-wide field autofluorescence (UWF-FAF) was evaluated for abnormal autofluorescence patterns and ultra-wide field fluorescein angiography (UWF-FA) was assessed for angiographic phase and field of view.

Results

A total of 107 eyes of 55 patients with a mean age of 11.1 years (SD 3.7 years, range 3–18 years) were evaluated. Twenty-seven (49%) patients were male. The most common diagnosis was retinopathy of prematurity (7 of 55 patients, 12.7%) followed by trauma (7.4%), Coats disease (7.4%), and rhegmatogenous retinal detachment (7.4%). The number of quadrants visualized anterior to the equator correlated with patient age (r = 0.4, p < 0.01). On UWF-FA, 6 of 14 patients (43%) had images of the arterial phase captured and 14 of 14 patients (100%) had images of the venous phase or later captured.

Conclusions

We demonstrated that UWF imaging is obtainable in children as young as 3 years old without sedation. UWF fundus photography, UWF-FAF and UWF-FA were useful clinical adjuvants to examination and provide additional information for documenting and monitoring pediatric retinal diseases.
Service quality evaluation of international freight forwarders: an empirical research in East Asia
Authors: Huang Sheng Teng , Bulut Emrah , Duru Okan
Published: December 2019

The purpose of this paper is to improve service quality of international freight forwarders and explore practical business solutions to enhance customer service level. Freight forwarder usually acts as an agent to source logistics service for shipper and work closely with carriers such as shipping line and airline companies. This business is characterized by lower capital investment and entry barrier comparing with carriers, and most of their major customers are small or medium size manufactures or traders. Providing high quality service to enhance customer satisfaction is the key mission since competition is extremely severe. This paper empirically investigates the leading freight forwarders to find important customer requirements in East Asian region such as Japan, Korea and Taiwan. Furthermore, the feature of the study by using quality function deployment approach would not only identify key technical measures but also explore meaningful business solutions as direction of quality improvement. The finding reveals key customer requirements are cheaper agency fees, door to door ability and instant response, and the key technical measures are customer relationship management, overall information system, service point and network. We would further discuss the empirical result and conclude managerial meaning for decision makers.
Case study of “Meilong model” ecological animal husbandry shareholding cooperatives in Qinghai
Authors: Yin Hubin , Gao Yaqi , Liu Wenyuan , Dongzhu Cairang , Jiang Wei
Published: December 2019

This article examines Meilong animal husbandry cooperatives in the Haixi Prefecture of Qinghai Province, China as a study case, using information gathered through field surveys and questionnaires to explore the systemic structure and operational mechanisms of Meilong Cooperatives, as well as its impacts on pastoral areas and herdsmen. Based on the results, the main contribution of the Meilong Model is providing a new way for pastoral villages to pursue development through joint-stock cooperatives, and thus represents the long-term direction of pastoral area development. This model reforms the traditional cooperative concept that naturally arises among herdsmen; Meilong Share-holding Cooperative guarantees the equal rights of small or poor households to participate in the management of cooperatives on the basis of “one household, one vote”, rather than the principle of “shareholders have the right to manage, vote and speak according to the proportion of shareholding” found in the joint-stock systems of modern enterprises. It localizes the shareholding system theory to be more acceptable and feasible in order to ensure the survival of animal husbandry cooperatives.
Valuation of ecosystem services in the organic carbon of the Pinus densiflora forest at Mt. Namsan, Seoul Metropolitan City
Authors: Lee Eung-Pill , Lee Soo-In , Jeong Heon-Mo , Han Young-Sub , Lee Seung-Yeon , Park Jae-Hoon , Jang Rae-Ha , Hong Youg-Sik , Jung Young-Ho , Kim Eui-Joo , Lee Sang-Hun , You Young-Han
Published: December 2019

Background

Standing biomass, litter production, rate of litter decomposition, amount of litter on forest floor, and amount of soil organic carbon distribution were investigated from March 2016 to November 2018 in order to evaluate the ecosystem value through organic carbon distribution in the Pinus densiflora forest at Namsan, Seoul Metropolitan City.

Results

The amount of organic carbon in the Pinus densiflora forest was 261.09 ton C ha−1 during the research period, and fixed organic carbon in plant through net photosynthesis was 3.2 ton C ha−1 year−1. The organic carbon in plant was 62.77 ton C ha−1 (24.04%), in litter on the forest floor was 3.65 ton C ha−1 (1.40%), and in soil was 194.67 ton C ha−1 (74.56%). The value of plant, litter on forest floor, and soil organic carbon distribution were each 6,277,000 won ha−1, 365,000 won ha−1, and 19,467,000 won ha−1. The value per ton of fixed organic carbon in plant through net photosynthesis was 320,000 won ha−1 year−1 and the value of ecosystem services stored in carbon in the Namsan forest ecosystem was about 26.1 million won ha−1 for 3 years.

Conclusions

The results of this study suggest that the pine forests of Namsan rapidly decompose leaves due to the high atmospheric temperature and accumulate a large amount of organic carbon in the soil to provide climate control regulatory service function.
Phosphogypsum waste as additives to lime stabilization of bentonite
Authors: Oumnih Safae , Bekkouch Nadia , Gharibi El Khadir , Fagel Nathalie , Elhamouti Kamal , El Ouahabi Meriam
Published: December 2019

Waste recycling with increasing the lifecycle of resource is a novel approach for enhancing circular economy. Within this context, this study aims to give a second life cycle to phosphogypsum (PG) waste, which is a by-product from phosphoric acid manufacture, as useful resources. This study evaluates the sustainability of this harmful waste, which is accumulated in large stockpiles and becomes hazardous during storage, and to stabilize bentonite-based concrete intended for road construction.

The effect of raw bentonite (Ca-Na montmorillonite), PG, and lime on the properties of cementitious materials has been investigated through various tests. The properties examined include chemistry (X-ray Fluorescence Spectrometry), mineralogy (X-ray Powder Diffraction and Fourier-Transform Infrared Spectroscopy), calorimetry (Differential Thermal Analysis/Thermogravimetry) and microstructure (Scanning Electron Microscopy) of the mortar based on different mixtures of bentonite, PG and lime. The result show that lime and PG addition involves in the formation of new nanocrystalline phases and the disappearance of certain minerals as portlandite. Calcium silicate hydrate gel appeared in the mixture with 8% of lime, whereas strätlingite was neoformed in the mixture with 8% of lime and 8% of PG. These nanocrystalline phases are responsible for enhancing mechanical strength through the pozzoloanic reaction.
Ameliorated in vitro anticancer efficacy of methotrexate d-α-Tocopheryl polyethylene glycol 1000 succinate ester against breast cancer cells
Authors: Manjappa Arehalli S. , Kumbhar Popat S. , Kasabe Rohini , Diwate Sonali K. , Disouza John I.
Published: December 2019

Background

Methotrexate (MTX), a folate anti-metabolite, has been used widely in the treatment of plenty of malignancies. However, the clinical use is limited because of its poor water solubility (BCS class II drug), nonspecific distribution, drug resistance, short circulation half-life, and toxicity. The objective of the present research was to synthesize the ester prodrug of MTX with d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and characterize for in vitro anticancer efficacy.

Results

The FTIR and NMR results revealed the successful synthesis of the prodrug. The assay and saturation solubility of the prodrug is found to be 23 ± 2.5% and 6.7 ± 1.3 mg/mL (MTX equivalent) respectively. The CMC of the prodrug in distilled water at room temperature is found to be 36.9 ± 2.6 μg/mL. The prepared prodrug micelles showed a mean particle size of 166 ± 10 nm (PDI, 0.325 ± 0.09). Further, the TEM results confirmed the self-assembling character of the prodrug into micelles with a nearly spherical shape. The prodrug caused the significantly (p < 0.01) less hemolysis (16.8 ± 1.5%) when compared to plain MTX solution and significantly higher (p < 0.01) in vitro cytotoxicity, cell cycle arresting, and apoptosis against human breast cancer cells (MCF-7 and MDA-MB-231).

Conclusion

Our study results revealed the remarkable in vitro anticancer activity of MTX following its esterification with TPGS. However, further, in vivo studies are needed to prove its efficacy against different cancers.
Accurate porosity prediction for tight sandstone reservoir: A case study from North China
Authors: Wang Pu , Chen Xiaohong , Li Jingye , Wang Benfeng
Published: December 2019

Tight sandstone reservoirs have complex petrophysical properties, which introduce difficulties to rock-physics modeling. Besides, weak reflection events appear with a high probability in the seismic profile for tight sandstones. By combining the soft-porosity model and Gassmann’s relation, weak reflection events are analyzed in detail, which can be contaminated by remaining internal multiples and the amplitudes may be lowered by the transmission loss. These pose challenges for the porosity prediction. To obtain the porosity estimate accurately of tight sandstone reservoirs, porosity prediction is performed in two steps. First, within the framework of Bayesian inversion, the elastic parameters are obtained with high accuracy by using the reflectivity method, which can effectively describe transmission loss and internal multiples. Second, the Bayes discriminant method is applied to predict porosity from the estimated elastic parameters. It avoids using deterministic rock-physics modeling because the difficulties in rock-physics modeling of tight sandstones make it hard to predict their petrophysical properties. To ensure the prediction accuracy, detailed lithology identification and sensitivity parameters analysis are performed. Different examples of well-logging data and seismic data demonstrate that our approach can well predict the porosity.
Investigation of the resonance of nonwetting droplets in constricted capillary tubes
Authors: Zeng Chao , Deng Wen , Fan Jing , Liu Kelly H.
Published: December 2019

Fluids in porous media could resonate due to passing seismic waves when meeting certain conditions of excitation frequency and pore geometry. This study of the resonance of fluids can contribute to applications in hydrocarbon microtremor analysis, enhanced oil recovery methods, and environmental remediation of nonaqueous phase liquid contamination. In this study, the analytical expression of the frequency response function and temporal response function is derived to characterize the resonance of two-phase immiscible fluids in the constricted tube. The computational fluid dynamics modeling is used to validate this resonance theory by achieving a good agreement in the prediction of output/input amplification ratio in the frequency and time domains.
The clinical assessment of acts of violence: mental mechanisms and subjectivity
Authors: Nathan Rajan , Wilson Peter
Published: December 2019

Approaches to assessing violence in clinical practice have been influenced by developments in the field of risk assessment. As a result, there has been a focus on identifying and describing factors associated with violence. However, a factor-based approach to assessing violence in individual cases has limited clinical utility. In response, the benefits of a formulation-based approach have been promoted. This approach is enhanced by an understanding of the specific mental mechanisms that increase the likelihood of violence in the individual case. Although there is an empirical evidence base for mental mechanisms associated with violence, this literature has not been distilled and synthesised in a way that informs routine clinical practice. In this article the authors present the key mechanisms that are known to be associated with violence in a way that is relevant to the clinical assessment of violence and, in turn, can inform clinical and risk management.
Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non–Small-Cell Lung Cancer
Authors: Bradley Jeffrey D. , Hu Chen , Komaki Ritsuko R. , Masters Gregory A. , Blumenschein George R. , Schild Steven E. , Bogart Jeffrey A. , Forster Kenneth M. , Magliocco Anthony M. , Kavadi Vivek S. , Narayan Samir , Iyengar Puneeth , Robinson Clifford G. , Wynn Raymond B. , Koprowski Christopher D. , Olson Michael R. , Meng Joanne , Paulus Rebecca , Curran Walter J. , Choy Hak
Published: December 2019

PURPOSE

RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non–small-cell lung cancer (NSCLC).

METHODS

The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS).

RESULTS

Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm v 12.1% and 17.4% in the HD arm, respectively ( P = .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7 v 20.3 months ( P = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% ( P = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms.

CONCLUSION

A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.
Pediatric Somatic Tumor Sequencing Identifies Underlying Cancer Predisposition
Authors: MacFarland Suzanne P. , Zelley Kristin , Surrey Lea F. , Gallo Daniel , Luo Minjie , Raman Pichai , Wertheim Gerald , Hunger Stephen P. , Li Marilyn M. , Brodeur Garrett M.
Published: December 2019

PURPOSE

The diagnosis of cancer predisposition in pediatric patients with cancer is vital for treatment decisions, surveillance, and management of at-risk family members. Somatic tumor testing can identify potential underlying constitutional variants that confer increased cancer risk. Here, we report the characteristics of constitutional variants identified through tumor testing.

MATERIALS AND METHODS

Data were abstracted from medical record review of 1,023 patients who received in-house somatic tumor testing over a 28-month period. Patients were identified for testing using referral criteria developed as a collaboration between genomic diagnostics, pathology, and oncology. Characteristics of patients who underwent constitutional testing, including family history and variant loss of heterozygosity, were tracked.

RESULTS

From 1,023 patients who underwent somatic tumor sequencing in a 28-month period, 210 variants were identified in 141 patients (13.8%) that were concerning for cancer predisposition syndromes requiring intervention. A total of 73 variants in 41 patients have undergone clinical confirmatory testing thus far. Of these, 26 variants were confirmed to be constitutionally present (35.6%). Among patients tested, 23 (56.1%) of 41 total patients were diagnosed with a cancer predisposition syndrome.

CONCLUSION

Our data demonstrate that more than one third of variants in tumor somatic sequencing that were concerning for underlying cancer predisposition were constitutionally confirmed. Overall, somatic tumor testing identified potential cancer predisposition syndromes in pediatric patients, and some would not have been identified on the basis of clinical history alone.
Marked Influence of Adiposity on Laboratory Biomarkers in a Healthy Cohort of Children and Adolescents
Authors: Higgins Victoria , Omidi Arghavan , Tahmasebi Houman , Asgari Shervin , Gordanifar Kian , Nieuwesteeg Michelle , Adeli Khosrow
Published: December 2019

Background

The prevalence of pediatric obesity is increasing worldwide and strongly associates with metabolic abnormalities, including inflammation, insulin resistance, and dyslipidemia. This study assessed the influence of 3 measures of adiposity on levels of routinely assessed biochemical markers in apparently healthy children and adolescents.

Methods

The influence of adiposity on 35 biochemical markers was examined in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents by comparing serum biomarker levels between subjects with a normal weight, overweight, and obese body mass index (BMI). The cohort comprised 1332 subjects 5.1 to 19.0 years of age with a BMI ranging from 13.4 to 65.0 kg/m2. The association between each biochemical marker and BMI, waist circumference, and waist-to-height ratio z-scores was assessed, while adjusting for age and sex. Reference intervals were established for all biochemical markers before and after removing overweight/obese subjects.

Results

In children and adolescents, levels of 13 routinely assessed biochemical markers, including alanine aminotransferase, apolipoprotein B, complement components 3 and 4, cholinesterase, high sensitivity C-reactive protein, gamma-glutamyl transferase, haptoglobin, high-density lipoprotein cholesterol, iron, transferrin, triglycerides, and uric acid, were significantly different between BMI categories. BMI, waist circumference, and/or waist-to-height ratio were significantly associated with the serum concentration of 24 of the 35 markers examined, after adjusting for age and sex.

Conclusions

Excess adiposity significantly influences circulating levels of routinely assessed laboratory markers, most notably liver enzymes, lipids/lipoproteins, inflammatory markers, and uric acid in children and adolescents. Although it is unknown whether altered biochemical marker levels in subjects with overweight/obesity reflect health or indolent disease, clinicians should be aware of the effect of weight status on several laboratory tests.