bluuebunny/crossref_metadata_2025 huggingface dataset:
Metacarpal Locked Intramedullary Nail: Surgical Technique and Preliminary Outcome Report
Authors: Niempoog Sunyarn , Waitayawinyu Thanapong , Boonyasirikool Chinnakart
Published: May 2018

In surgically indicated metacarpal fractures, the ideal fixation should provide an ample stability for early rehabilitation. Damage to surrounding tissue should be minimized as well, to prevent stiffness which determine the outcomes. We have created the metacarpal locked intramedullary nail (MCLN) that allows immediate motion even in unstable fractures. This preliminary report is objected to demonstrate the surgical technique and outcomes of novel metacarpal fixation. Three surgical indicated metacarpal fractures were treated by MCLN. Unlimited motion was started a day after surgery without external immobilization. Clinical and radiographic control were performed up to two years after the surgery. All of patients returned to previous level of daily activities within six weeks with minimal scar. All fractures were united. The total active motions were above 260° in every patient. Complications were not observed. With this encouraged clinical results, the MCLN could be the promising alternative surgical fixation for metacarpal shaft fractures.
Hardness of Approximation for
H
-free Edge Modification Problems
Authors: Bliznets Ivan , Cygan Marek , Komosa Paweł , Pilipczuk Michał
Published: May 2018

The
H
-
free
E
dge
D
eletion
problem asks, for a given graph
G
and integer
k
, whether it is possible to delete at most
k
edges from
G
to make it
H
-free—that is, not containing
H
as an induced subgraph. The
H
-
free
E
dge
C
ompletion
problem is defined similarly, but we add edges instead of deleting them. The study of these two problem families has recently been the subject of intensive studies from the point of view of parameterized complexity and kernelization. In particular, it was shown that the problems do not admit polynomial kernels (under plausible complexity assumptions) for almost all graphs
H
, with several important exceptions occurring when the class of
H
-free graphs exhibits some structural properties.

In this work, we complement the parameterized study of edge modification problems to
H
-free graphs by considering their approximability. We prove that whenever
H
is 3-connected and has at least two nonedges, then both
H
-
free
E
dge
D
eletion
and
H
-
free
E
dge
C
ompletion
are very hard to approximate: they do not admit poly(OPT)-approximation in polynomial time, unless P=NP, or even in time subexponential in OPT, unless the exponential time hypothesis fails. The assumption of the existence of two nonedges appears to be important: we show that whenever
H
is a complete graph without one edge, then
H
-
free
E
dge
D
eletion
is tightly connected to the M
in
H
orn
D
eletion
problem, whose approximability is still open. Finally, in an attempt to extend our hardness results beyond 3-connected graphs, we consider the cases of
H
being a path or a cycle, and we achieve an almost complete dichotomy there.
Cluster Analysis Based Arc Detection in Pantograph-Catenary System
Authors: Huang Shize , Yu Liangliang , Zhang Fan , Zhu Wei , Guo Qiyi
Published: May 2018

The pantograph-catenary system, which ensures the transmission of electrical energy, is a critical component of a high-speed electric multiple unit (EMU) train. The pantograph-catenary arc directly affects the power supply quality. The Chinese Railway High-speed (CRH) is equipped with a 6C system to obtain pantograph videos. However, it is difficult to automatically identify the arc image information from the vast amount of videos. This paper proposes an effective approach with which pantograph video can be separated into continuous frame-by-frame images. Because of the interference from the complex operating environment, it is unreasonable to directly use the arc parameters to detect the arc. An environmental segmentation algorithm is developed to eliminate the interference. Time series in the same environment is analyzed via cluster analysis technique (CAT) to find the abnormal points and simplified arc model to find arc events accurately. The proposed approach is tested with real pantograph video and performs well.
Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair
Authors: Luo Lihua , He Yan , Wang Xiaoyan , Key Brian , Lee Bae Hoon , Li Huaqiong , Ye Qingsong
Published: May 2018

This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases.
The Relationship between Frequently Used Glucose-Lowering Agents and Gut Microbiota in Type 2 Diabetes Mellitus
Authors: Lv You , Zhao Xue , Guo Weiying , Gao Ying , Yang Shuo , Li Zhuo , Wang Guixia
Published: May 2018

Metabolic diseases, especially diabetes mellitus, have become global health issues. The etiology of diabetes mellitus can be attributed to genetic and/or environmental factors. Current evidence suggests the association of gut microbiota with metabolic diseases. However, the effects of glucose-lowering agents on gut microbiota are poorly understood. Several studies revealed that these agents affect the composition and diversity of gut microbiota and consequently improve glucose metabolism and energy balance. Possible underlying mechanisms include affecting gene expression, lowering levels of inflammatory cytokines, and regulating the production of short-chain fatty acids. In addition, gut microbiota may alleviate adverse effects caused by glucose-lowering agents, and this can be especially beneficial in diabetic patients who experience severe gastrointestinal side effects and have to discontinue these agents. In conclusion, gut microbiota may provide a novel viewpoint for the treatment of patients with diabetes mellitus.
The Regular Part of a Semigroup of Full Transformations with Restricted Range: Maximal Inverse Subsemigroups and Maximal Regular Subsemigroups of Its Ideals
Authors: Sommanee Worachead
Published: May 2018

Let TX be the full transformation semigroup on a set X. For a fixed nonempty subset Y of a set X, let TX,Y be the semigroup consisting of all full transformations from X into Y. In a paper published in 2008, Sanwong and Sommanee proved that the set FX,Y=α∈TX,Y:Xα=Yα is the largest regular subsemigroup of TX,Y. In this paper, we describe the maximal inverse subsemigroups of FX,Y and completely determine all the maximal regular subsemigroups of its ideals.
Analysis of Surface Sound Duct in the Northern Shelf of the South China Sea
Authors: Qu Ke , Piao Shengchun , Zhou Jianbo , Zhu Fengqin
Published: May 2018

The northern shelf of the South China Sea (NSSCS) is characterized by surface low‐salinity water due to discharge from the Pearl River. In such an environment, the surface sound duct (SSD) is the most important duct for near‐surface sonar applications. Nevertheless, the mechanism of SSD formation is very complicated and is influenced by salinity, temperature at the air‐sea interface, and various additional marine phenomena. In this study, an 8‐year conductivity‐temperature‐depth (CTD) profile of the NSSCS was used to analyze the SSD formation. An advanced diagrammatic method is proposed to provide a quantitative analysis of the contribution of salinity, temperature, and hydrostatic pressure on SSD formation. Large salinity gradient (0.25 psu/m) was shown to play a crucial role in SSD formation when a mixed layer exists. As representative examples, the sea under cold surges, typhoon genesis, and low‐salinity lenses were studied. Conversely, the absence of SSDs in low‐salinity water was also observed in upwelling regions. This study further showed that highly negative temperature gradients affect SSD formation even in low‐salinity water. Furthermore, although the duct depth of a low‐salinity SSD is usually less than 10 meters, it still can serve as an effective duct for acoustic propagation.
Clinical Features and Treatment Outcomes among Children with Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A 20-Year Study in a Tertiary Referral Hospital
Authors: Chatproedprai Susheera , Wutticharoenwong Vanvara , Tempark Therdpong , Wananukul Siriwan
Published: May 2018

Aim. To determine the probable causative factors, clinical features, and treatment outcomes of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS-TEN overlap in children.Methods. A 20-year database review of all children diagnosed with SJS/TEN/SJS-TEN overlap at the King Chulalongkorn Memorial Hospital, Thailand.Results. 36 patients (M : F, 16 : 20) with the mean age of9.2±4.0years were identified. There were 20 cases of SJS, 4 cases of SJS-TEN overlap, and 12 cases of TEN. Drugs were the leading cause for the diseases (72.3%); antiepileptics were the most common culprits (36.1%). Cutaneous morphology at presentation was morbilliform rash (83.3%), blister (38.9%), targetoid lesions (25.0%), and purpuric macules (2.8%). Oral mucosa (97.2%) and eye (83.3%) were the 2 most common mucosal involvements. Majority of the cases (77.8%) were treated with systemic corticosteroids, intravenous immunoglobulin, or both. Treatment outcomes between those who received systemic therapy and those who received only supportive care were comparable. Skin and eye were the principal sites of short-term and long-term complications.Conclusions. SJS/TEN are not common but are serious diseases which lead to significant morbidities in children. Early withdrawal of suspicious causes and meticulous supportive care are very important. This study found that the systemic therapy was not superior to supportive care because the treatment outcomes for both groups were comparable.
Inversion Model of GPR Imaging Characteristics of Point Objects and Fracture Detection of Heritage Building
Authors: Lv Gao , Li Ning , Yang Jie , Yao Xianchun , Hu Dexiu , Pang Rixuan
Published: May 2018

There are often many hidden structural defects in heritage buildings. As a convenient and effective nondestructive detecting method, ground-penetrating radar (GPR) has a technical advantage in detecting and protecting heritage buildings depending on the advanced image interpretation. The analytic relationship between buried depth and radius of point object and long and short axis of hyperbolic equation was established according to derivations of formulas. The image characteristics of hyperbolic curves with different depth and radius were studied by finite-difference time-domain method (FDTD). And then, inversion models of buried depth and radius of point object were established. The buried depth and radius can be accurately deduced by long and short axis of hyperbolic image. This result was applied in the detection of pedestal defects of the heritage building, and the depth and distribution range of hidden fracture can be accurately interpreted. It provides an effective and fast method to detect hidden defects in civil engineering.
Characterization of α-Glucosidase Inhibitor/Cyclodextrin Complex Prepared by Freeze-Drying
Authors: Inoue Yutaka , Narumi Sachie , Mitsumori Akiho , Murata Isamu , Kanamoto Ikuo
Published: May 2018

Miglitol (MT) is an α-glucosidase inhibitor with a postmeal blood glucose level lowering effect that is used to treat type 2 diabetes. In addition, α-cyclodextrin (αCD) has been reported to inhibit increases in postmeal blood glucose. The aim of this study was to prepare a freeze-dried product (FD) composed of MT and αCD or γCD (molar ratio of MT/αCD = 1/1, MT/γCD = 1/1) and to evaluate the physicochemical properties and biological activity of the FD. The PXRD profile of FD exhibited a halo pattern, and characteristic peaks derived from MT, αCD, and γCD were not observed. The TG-DTA results for FD indicated an increased weight loss temperature and the absence of an endothermic peak for MT. The NIR absorption spectrum measurement suggested an intermolecular interaction between MT and αCD or γCD in the FD. 1H-1H NOESY NMR spectroscopy (D2O) revealed an intermolecular interaction in the FD. The results of the α-glucosidase activity inhibition test and the α-amylase activity inhibition test indicated that the FD exhibited the same inhibition rate as MT alone and the effects of MT were not altered by the freeze-drying method.
Spatiotemporal Characteristics of Winter Wheat Waterlogging in the Middle and Lower Reaches of the Yangtze River, China
Authors: Chen Yuanyuan , Huang Jingfeng , Song Xiaodong , Gao Ping , Wan Suqin , Shi Lei , Wang Xiuzhen
Published: May 2018

The waterlogging is a serious agrometeorological disaster caused by excessive soil water during crop growth stages. The middle and lower reaches of the Yangtze River are one of the major winter wheat growing regions in China and at the same time they are waterlogging-prone due to their specific climatic conditions. In this study, we integrated a set of tools to analyze the spatiotemporal features of winter wheat waterlogging in this region. We proposed a waterlogging precipitation index (WPI) based on winter wheat yield loss rate and precipitation anomaly percentage and analyzed the frequency, scope, and intensity of winter wheat waterlogging. The results showed that the spring rainfall had a direct and significant effect on winter wheat yield, and the meteorological yield of winter wheat was negatively correlated with precipitation abnormal event from jointing to maturity stages (March to May) across the whole study area. The matching between the waterlogging severity identified by the WPI and historical winter wheat waterlogging records was relatively high. We also discussed the influences of the other nonmeteorological factors, for example, soil texture, topographic and geomorphic conditions, and local disaster-resisting ability, on the extent of waterlogging damage.
Exploring Travel Time Distribution and Variability Patterns Using Probe Vehicle Data: Case Study in Beijing
Authors: Chen Peng , Tong Rui , Lu Guangquan , Wang Yunpeng
Published: May 2018

Exploring travel time distribution and variability patterns is essential for reliable route choices and sophisticated traffic management and control. State-of-the-art studies tend to treat different types of roads equally, which fails to provide more detailed analysis of travel time characteristics for each specific road type. In this study, based on a vast amount of probe vehicle data, 200 links inside the Third Ring Road of Beijing, China, were investigated. Four types of roads were covered including urban expressways, auxiliary roads of urban expressways, major roads, and secondary roads. The day-of-week distributions of unit distance travel time were first analyzed. Kolmogorov-Smirnov test, Anderson-Darling test, and chi-squared test were employed to test the goodness-of-fit of different distributions and the results showed lognormal distribution was best-fitted for different time periods and road types compared with normal, gamma, and Weibull distribution. In addition, four reliability measures, that is, unit distance travel time, coefficient of variation, buffer time index, and punctuality rate, were used to explore the day-of-week travel time variability patterns. The results indicated that urban expressways, auxiliary roads of urban expressways, and major roads have regular and distinct morning and afternoon peaks on weekdays. It is noteworthy that in daytime the travel times on auxiliary roads of urban expressways and major roads share similar variability patterns and appear relatively stable and reliable, while urban expressways have most reliable travel times at night. The results of analysis help enable a better understanding of the volatile travel time characteristics of each road type in urban network.
Adaptive Resource Allocation Scheme for Micromotion Feature Extraction Based on Track-Before-Detect
Authors: Chen Yijun , Zhang Qun , Luo Ying , Yeo Tat Soon
Published: May 2018

The micromotion feature extraction method based on track-before-detect (TBD) can save the radar resource and improve the real-time performance of micromotion feature extraction by implementing target detecting, tracking, and micromotion feature extraction simultaneously. Usually, multitargets will exist in different areas, and the limited radar resources should be allocated for different areas to achieve the maximal performance of radar. For single-beam phased array radar, an adaptive resource allocation optimization model is established according to the processing steps of the micromotion feature extraction method based on TBD, and an adaptive resource allocation strategy is proposed. With the method, the radar efficiency can be significantly improved. The effectiveness of the proposed method is demonstrated by simulations.
Awareness of Environmental Change, Climate Variability, and Their Role in Prevalence of Mosquitoes among Urban Dwellers in Southern Ghana
Authors: Mattah Precious Agbeko Dzorgbe , Futagbi Godfred , Mattah Memuna Mawusi
Published: May 2018

This study evaluates the extent to which urban residents of Accra and Sekondi-Takoradi (all of southern Ghana) were aware of environment and climate-related variability. A total of 150 questionnaires were given to adults of 40 years and above who lived in the cities for at least 35 years. SPSS version 16 was used to process the data. Results show that all respondents in Accra Metropolitan Area (AMA) and 96% of them in Sekondi-Takoradi Metropolitan Area (STMA) noted the deteriorating vegetation cover over the cities. Similarly, 93% and 83% of them in AMA and STMA, respectively, observed that land use pattern of the two cities has changed considerably. There was positive and statistically significant correlation between respondents’ educational attainment and their awareness of changes in land use/land cover (r=0.18, n=140, p=0.03). Also, 71% in AMA and 89% in STMA stated that temperature of the cities had been increasing over the years. In all, 82.9% of the respondents mentioned that they had problem with the increasing population of mosquitoes. Respondents demonstrated ample knowledge of environment and climate variability and should be engaged in preventing further environmental degradation. The top-down approach to environmental issues has failed; the bottom-up approach to environmental maintenance is needed.
The Age at Diagnosis of Autism Spectrum Disorder in Children in Japan
Authors: Kurasawa Shigeki , Tateyama Kiyomi , Iwanaga Ryoichiro , Ohtoshi Taro , Nakatani Ken , Yokoi Katsushi
Published: May 2018

Background. No large-scale study of the timing of autism spectrum disorder (ASD) diagnosis has been performed in Japan to date. The aim of this study was to examine sex differences and annual trends in age at diagnosis of ASD using clinical data. Methods. Clinical data for children aged less than 18 years diagnosed with ASD between January 1, 2009, and December 31, 2013, and in whom follow-up was possible 1 year after diagnosis, were extracted. Results. The mean age at ASD diagnosis was 7.2 ± 4.2 years and the mode age was 3 years. No sex difference was observed for age at diagnosis (p=0.157). An annual trend of earlier diagnosis was observed when fiscal years were compared (p<0.001). Conclusion. This study highlighted the need to develop and provide appropriate early intervention methods and services for ASD children in Japan.
Delusions in Patients with Dementia with Lewy Bodies and the Associated Factors
Authors: Tzeng Ray-Chang , Tsai Ching-Fang , Wang Ching-Tsu , Wang Tzu-Yuan , Chiu Pai-Yi
Published: May 2018

Objective. Delusions are common neuropsychiatric symptoms in patients with dementia with Lewy bodies (DLB). The aim of this study was to investigate the associated factors of delusions in patients with DLB.Method. A retrospective study of outpatients with DLB registered in a regional hospital’s database was performed. The associated factors including cognitive performance, clinical features, vascular risk factors, and neuropsychiatric symptoms between delusional and nondelusional patients with DLB were compared.Results. Among 207 patients with DLB, 106 (51.2%) were delusional and 101 (48.8%) were not. Delusion of other persons are stealing was the most common symptom (35.3%). The delusional group had a significantly higher diagnostic rate of probable than possible DLB, higher disease severity, poorer cognitive performance, more severe neuropsychiatric symptoms, and higher caregiver burden (allp<0.05). In addition, the delusional group had a significantly lower frequency of diabetes compared to the nondelusional group (oddsratio=0.28,p<0.001).Conclusion. Delusion of other persons are stealing was the most common delusional symptom. The patients with DLB who presented with delusions had poorer cognitive function and more severe neuropsychiatric symptoms. A novel finding is that the DLB patients with diabetes had a lower frequency of delusions.
CORDIC‐Based Multi‐Gb/s Digital Outphasing Modulator for Highly Efficient Millimeter‐Wave Transmitters
Authors: Zhao Dixian , He Pingyang
Published: May 2018

This paper describes a high‐speed CORDIC‐based digital outphasing modulator. Fixed‐point Matlab model of the outphasing modulator is developed to evaluate the system performance and define the circuit design parameters. Design issues such as signal quantization error, delay mismatch, and phase overflowing are addressed to enable hardware implementation. The complete outphasing modulator is fully custom designed in 40 nm CMOS, which can be integrated in a millimeter‐wave outphasing transmitter to enhance the system average efficiency. Tested with 10.56 Gb/s 64‐QAM, this work achieves an EVM of 3.2% and fulfils the IEEE 802.11ad spectral mask requirements.
International Scope of Emergency Ultrasound: Barriers in Applying Ultrasound to Guide Central Line Placement by Providers in Nairobi, Kenya
Authors: Zaver Fareen , Boniface Keith , Wachira Benjamin , Wanjiku Grace , Shokoohi Hamid
Published: May 2018

Background. While ultrasound (US) use for internal jugular central venous catheter (CVC) placement is standard of care in North America, most developing countries have not adopted this practice. Previous surveys of North American physicians have identified lack of training and equipment availability as the most important barriers to the use of US. Objective. We sought to identify perceived barriers to the use of US to guide CVC insertion in a resource-constrained environment. Methods. Prior to an US-guided CVC placement training course conducted at the Aga Khan University Hospital in Nairobi, Kenya, physicians were asked to complete a survey to determine previous experience and perceived barriers. Survey responses were analyzed using summary statistics and the Rank-Sum test based on different specialty, gender, and previous US experience. Results. There were 23 physicians who completed the course and the survey. 52% (95% CI: 0.30–0.73) had put in >20 CVCs. 21.7% (95% CI: 0.08–0.44) of participants had previous US training, but none in the use of US for CVC insertion. The respondents expressed agreement with statements describing the ease of the use and improved success rate with US guidance. There was less agreement to statements describing the relative convenience and cost effectiveness of US CVC placement compared to the landmark technique. The main perceived barriers to utilization of US guidance included lack of training and limited availability of US equipment and sterile sheaths. Conclusion. Perceived barriers to US-guided CVC placement in our population closely mirrored those found among North American physicians, including lack of training and limited availability of US machines and equipment. These barriers have the potential to be addressed by targeted educational and administrative interventions.
Myoblast Myogenic Differentiation but Not Fusion Process Is Inhibited via MyoD Tetraplex Interaction
Authors: Testa Stefano , D’Addabbo Pietro , Fornetti Ersilia , Belli Roberta , Fuoco Claudia , Bernardini Sergio , Cannata Stefano , Frezza Domenico , Gargioli Cesare
Published: May 2018

The presence of tetraplex structures in the promoter region of the myogenic differentiation 1 gene (MyoD1) was investigated with a specific tetraplex‐binding porphyrin (TMPyP4), to test its influence on the expression of MyoD1 itself and downstream‐regulated genes during myogenic differentiation. TMPyP4‐exposed C2C12 myoblasts, blocking MyoD1 transcription, proliferated reaching confluence and fused forming elongated structures, resembling myotubes, devoid of myosin heavy chain 3 (MHC) expression. Besides lack of MHC, upon MyoD1 inhibition, other myogenic gene expressions were also affected in treated cells, while untreated control cell culture showed normal myotube formation expressing MyoD1, Myog, MRF4, Myf5, and MHC. Unexpectedly, the myomaker (Mymk) gene expression was not affected upon TMPyP4 exposure during C2C12 myogenic differentiation. At the genomic level, the bioinformatic comparison of putative tetraplex sites found that three tetraplexes in MyoD1 and Myog are highly conserved in mammals, while Mymk and MHC did not show any conserved tetraplexes in the analysed regions. Thus, here, we report for the first time that the inhibition of the MyoD1 promoter function, stabilizing the tetraplex region, affects downstream myogenic genes by blocking their expression, while leaving the expression of Mymk unaltered. These results reveal the existence of two distinct pathways: one leading to cell fusion and one guaranteeing correct myotube differentiation.
Preparation of Hierarchical CaSO4 Whisker and Its Reinforcing Effect on PVC Composites
Authors: Ma Pengyang , Chen Haoyuan , Zhang Qingjie , Wang Jing , Xiang Lan
Published: May 2018

CaSO4 whiskers (CSW) can be used to reinforce PVC matrix to produce light and strong composites. However, the weak interfacial interaction between the smooth CSW and PVC matrix limited the fabrication of PVC composite with perfect mechanical properties. In this work, CaCO3 nanoparticles were coated on CSW surface by wet modification of CSW in Na2CO3 solution at 80°C, which increased the surface roughness of CSW from 56.8 nm to 115.6 nm. The use of the hierarchical CSW rather than the raw CSW in the fabrication of CSW/PVC composite led to the increase of the flexural strength from 86.3 MPa to 113.2 MPa and the impact strength from 56.7 kJ·m−2 to 82.5 kJ·m−2 owing to the enhanced mechanical interlocking between CSW and PVC matrix.
High-Order Iterative Methods for the DMP Inverse
Authors: Liu Xiaoji , Cai Naping
Published: May 2018

We investigate two iterative methods for computing the DMP inverse. The necessary and sufficient conditions for convergence of our schemes are considered and the error estimate is also derived. Numerical examples are given to test the accuracy and effectiveness of our methods.
Path Hopping: An MTD Strategy for Long-Term Quantum-Safe Communication
Authors: Safavi-Naini Reihaneh , Poostindouz Alireza , Lisy Viliam
Published: May 2018

Moving target defense (MTD) strategies have been widely studied for securing computer systems. We consider using MTD strategies to provide long-term cryptographic security for message transmission against an eavesdropping adversary who has access to a quantum computer. In such a setting, today’s widely used cryptographic systems including Diffie-Hellman key agreement protocol and RSA cryptosystem will be insecure and alternative solutions are needed. We will use a physical assumption, existence of multiple communication paths between the sender and the receiver, as the basis of security, and propose a cryptographic system that uses this assumption and an MTD strategy to guarantee efficient long-term information theoretic security even when only a single path is not eavesdropped. Following the approach of Maleki et al., we model the system using a Markov chain, derive its transition probabilities, propose two security measures, and prove results that show how to calculate these measures using transition probabilities. We define two types of attackers that we call risk-taking and risk-averse and compute our proposed measures for the two types of adversaries for a concrete MTD strategy. We will use numerical analysis to study tradeoffs between system parameters, discuss our results, and propose directions for future research.
Dystrophic Adipocytes Mimicking Metastatic Signet Ring Cell Adenocarcinoma: A Diagnostic Pitfall in a Cachectic Patient
Authors: Zhang Xin , Findeis-Hosey Jennifer J.
Published: May 2018

Cachexia is a debilitating condition and complex syndrome commonly associated with a variety of chronic diseases. It is caused by metabolic dysregulation and characterized by profound loss of adipose tissue and skeletal muscles. While pathological changes of cachectic conditions on adipose tissue have been studied and documented in tumor-bearing animal models, similar morphological changes in human surgical specimens are rare. Here we report a case of a cachectic patient with pancreatic adenocarcinoma whose adipocytes underwent dramatic lipodystrophy mimicking signet ring cell adenocarcinoma. The patient had presented with a large bowel obstruction, a mass extending between the pancreas and colon, and radiographic concern for carcinomatosis. A moderately differentiated adenocarcinoma was identified invading externally into the colon, with extensive signet ring-like cells throughout the specimen, including those adjacent to the colon and lymph nodes and around nerves. These signet ring-like cells were round with variably clear to eosinophilic cytoplasm and a peripherally displaced round to oval nucleus. Immunohistochemical staining demonstrated that these signet ring-like cells were negative for AE1/AE3, CD138, or Kreyberg staining, while they were positive for S-100 staining, confirming these as dystrophic adipocytes. Here we examine dystrophic adipocytes in a cachetic patient, examining the differential diagnosis and potential ancillary studies.
Weak Convergence Theorems on the Split Common Fixed Point Problem for Demicontractive Continuous Mappings
Authors: Cui Huanhuan , Ceng Luchuan , Wang Fenghui
Published: May 2018

We are concerned with the split common fixed point problem in Hilbert spaces. We propose a new method for solving this problem and establish a weak convergence theorem whenever the involved mappings are demicontractive and Lipschitz continuous. As an application, we also obtain a new method for solving the split equality problem in Hilbert spaces.
Enhanced Coffee-Ring Effect via Substrate Roughness in Evaporation of Colloidal Droplets
Authors: Zhang Yongjian , Chen Xubo , Liu Fenggang , Li Lei , Dai Jun , Liu Teng
Published: May 2018

The analysis of dried drop patterns has various applications in research fields like archeology, medical practice, printing, and so on. In this paper, we studied the evaporation and pattern formation of polytetrafluoroethylene (PTFE) colloid droplets on smooth substrate and rough substrates with different roughness. We found that the evaporation of droplets shows remarkable coffee-ring effect on smooth substrate and that the cross-section of the ring is wedge-shaped with its thickness decreasing from the edge to the center. However, with increasing roughness, the effect strengthened, with the section of the coffee-ring changing from wedge- to hill-shaped. The contact angle decreased with increasing roughness, leading to an increase in evaporation rate. Moreover, wicking led to additional evaporation, which also enhanced capillary flow, moving more particles to the edge. In addition, the rough structure of the substrate inhibited the back-flow of the capillary flow, preventing the particles’ move to the center. The formation of radial wrinkles on the edge also led to particle retention, preventing them from moving to the center. All these factors contribute to the decreased width and increased height of the coffee-ring pattern after evaporation on rough surfaces. It is an effective method to regulate the deposition pattern of evaporating droplet by changing the substrate roughness.
HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
Authors: Wang Sophia S. , Carrington Mary , Berndt Sonja I. , Slager Susan L. , Bracci Paige M. , Voutsinas Jenna , Cerhan James R. , Smedby Karin E. , Hjalgrim Henrik , Vijai Joseph , Morton Lindsay M. , Vermeulen Roel , Paltiel Ora , Vajdic Claire M. , Linet Martha S. , Nieters Alexandra , de Sanjose Silvia , Cozen Wendy , Brown Elizabeth E. , Turner Jennifer , Spinelli John J. , Zheng Tongzhang , Birmann Brenda M. , Flowers Christopher R. , Becker Nikolaus , Holly Elizabeth A. , Kane Eleanor , Weisenburger Dennis , Maynadie Marc , Cocco Pierluigi , Albanes Demetrius , Weinstein Stephanie J. , Teras Lauren R. , Diver W. Ryan , Lax Stephanie J. , Travis Ruth C. , Kaaks Rudolph , Riboli Elio , Benavente Yolanda , Brennan Paul , McKay James , Delfau-Larue Marie-Hélène , Link Brian K. , Magnani Corrado , Ennas Maria Grazia , Latte Giancarlo , Feldman Andrew L. , Doo Nicole Wong , Giles Graham G. , Southey Melissa C. , Milne Roger L. , Offit Kenneth , Musinsky Jacob , Arslan Alan A. , Purdue Mark P. , Adami Hans-Olov , Melbye Mads , Glimelius Bengt , Conde Lucia , Camp Nicola J. , Glenn Martha , Curtin Karen , Clavel Jacqueline , Monnereau Alain , Cox David G. , Ghesquières Hervé , Salles Gilles , Bofetta Paulo , Foretova Lenka , Staines Anthony , Davis Scott , Severson Richard K. , Lan Qing , Brooks-Wilson Angela , Smith Martyn T. , Roman Eve , Kricker Anne , Zhang Yawei , Kraft Peter , Chanock Stephen J. , Rothman Nathaniel , Hartge Patricia , Skibola Christine F.
Published: May 2018

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.

Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.
Nuclear IGF1R Interacts with Regulatory Regions of Chromatin to Promote RNA Polymerase II Recruitment and Gene Expression Associated with Advanced Tumor Stage
Authors: Aleksic Tamara , Gray Nicki , Wu Xiaoning , Rieunier Guillaume , Osher Eliot , Mills Jack , Verrill Clare , Bryant Richard J. , Han Cheng , Hutchinson Kathryn , Lambert Adam G. , Kumar Rajeev , Hamdy Freddie C. , Weyer-Czernilofsky Ulrike , Sanderson Michael P. , Bogenrieder Thomas , Taylor Stephen , Macaulay Valentine M.
Published: May 2018

Internalization of ligand-activated type I IGF receptor (IGF1R) is followed by recycling to the plasma membrane, degradation or nuclear translocation. Nuclear IGF1R reportedly associates with clinical response to IGF1R inhibitory drugs, yet its role in the nucleus is poorly characterized. Here, we investigated the significance of nuclear IGF1R in clinical cancers and cell line models. In prostate cancers, IGF1R was predominantly membrane localized in benign glands, while malignant epithelium contained prominent internalized (nuclear/cytoplasmic) IGF1R, and nuclear IGF1R associated significantly with advanced tumor stage. Using ChIP-seq to assess global chromatin occupancy, we identified IGF1R–binding sites at or near transcription start sites of genes including JUN and FAM21, most sites coinciding with occupancy by RNA polymerase II (RNAPol2) and histone marks of active enhancers/promoters. IGF1R was inducibly recruited to chromatin, directly binding DNA and interacting with RNAPol2 to upregulate expression of JUN and FAM21, shown to mediate tumor cell survival and IGF-induced migration. IGF1 also enriched RNAPol2 on promoters containing IGF1R–binding sites. These functions were inhibited by IGF1/II–neutralizing antibody xentuzumab (BI 836845), or by blocking receptor internalization. We detected IGF1R on JUN and FAM21 promoters in fresh prostate cancers that contained abundant nuclear IGF1R, with evidence of correlation between nuclear IGF1R content and JUN expression in malignant prostatic epithelium. Taken together, these data reveal previously unrecognized molecular mechanisms through which IGFs promote tumorigenesis, with implications for therapeutic evaluation of anti-IGF drugs.

Significance: These findings reveal a noncanonical nuclear role for IGF1R in tumorigenesis, with implications for therapeutic evaluation of IGF inhibitory drugs. Cancer Res; 78(13); 3497–509. ©2018 AACR.
Epigenetic Regulation of CXCL12 Plays a Critical Role in Mediating Tumor Progression and the Immune Response In Osteosarcoma
Authors: Li Binghao , Wang Zhan , Wu Hao , Xue Mingfeng , Lin Peng , Wang Shengdong , Lin Nong , Huang Xin , Pan Weibo , Liu Meng , Yan Xiaobo , Qu Hao , Sun Lingling , Li Hengyuan , Wu Yan , Teng Wangsiyuan , Wang Zenan , Zhou Xingzhi , Chen Huabiao , Poznansky Mark C. , Ye Zhaoming
Published: May 2018

The mechanism by which osteosarcomas metastasize is elusive, and challenges remain regarding its treatment with modalities including immunotherapy. CXCL12 is deeply involved in the process of tumor metastasis and T-cell homing, which is driven by a chemokine gradient, but healthy bones are supposed to preferentially express CXCL12. Here, we show for the first time that osteosarcomas epigenetically downregulate CXCL12 expression via DNA methyltransferase 1 (DNMT1) and consequently acquire the ability to metastasize and to impair cytotoxic T-cell homing to the tumor site. Analysis of human osteosarcoma cases further revealed that CXCL12 expression strongly correlated with overall survival. Evaluations on fresh human chemotherapy-free osteosarcoma samples also showed a positive correlation between CXCL12 concentration and the number of intratumoral lymphocytes. Critically, treatment targeting DNMT1 in immunocompetent mouse models significantly elevated expression of CXCL12 in tumors, resulting in a robust immune response and consequently eradicating early lung metastases in addition to suppressing subcutaneous tumor growth. These antitumor effects were abrogated by CXCL12–CXCR4 blockade or CD8+ T-cell depletion. Collectively, our data show that CXCL12 regulation plays a significant role in both tumor progression and immune response, and targeting CXCL12 is promising for therapeutics against osteosarcoma.

Significance: Epigenetic regulation of CXCL12 controls metastasis and immune response in osteosarcoma, suggesting epigenetic therapies or therapies targeting CXCL12 have potential for therapeutic intervention in osteosarcoma. Cancer Res; 78(14); 3938–53. ©2018 AACR.
Mechanistic Distinctions between CHK1 and WEE1 Inhibition Guide the Scheduling of Triple Therapy with Gemcitabine
Authors: Koh Siang-Boon , Wallez Yann , Dunlop Charles R. , Bernaldo de Quirós Fernández Sandra , Bapiro Tashinga E. , Richards Frances M. , Jodrell Duncan I.
Published: May 2018

Combination of cytotoxic therapy with emerging DNA damage response inhibitors (DDRi) has been limited by tolerability issues. However, the goal of most combination trials has been to administer DDRi with standard-of-care doses of chemotherapy. We hypothesized that mechanism-guided treatment scheduling could reduce the incidence of dose-limiting toxicities and enable tolerable multitherapeutic regimens. Integrative analyses of mathematical modeling and single-cell assays distinguished the synergy kinetics of WEE1 inhibitor (WEE1i) from CHEK1 inhibitor (CHK1i) by potency, spatiotemporal perturbation, and mitotic effects when combined with gemcitabine. These divergent properties collectively supported a triple-agent strategy, whereby a pulse of gemcitabine and CHK1i followed by WEE1i durably suppressed tumor cell growth. In xenografts, CHK1i exaggerated replication stress without mitotic CDK hyperactivation, enriching a geminin-positive subpopulation and intratumoral gemcitabine metabolite. Without overt toxicity, addition of WEE1i to low-dose gemcitabine and CHK1i was most effective in tumor control compared with single and double agents. Overall, our work provides quantitative insights into the mechanisms of DDRi chemosensitization, leading to the rational development of a tolerable multitherapeutic regimen.

Significance: Multiple lines of mechanistic insight regarding DNA damage response inhibitors rationally guide the preclinical development of a tolerable multitherapeutic regimen.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/11/3054/F1.large.jpg. Cancer Res; 78(11); 3054–66. ©2018 AACR.
Burden of Oral Mucositis: A Systematic Review and Implications for Future Research
Authors: Berger Karin , Schopohl Dorothee , Bollig Antonia , Strobach Dorothea , Rieger Christina , Rublee Dale , Ostermann Helmut
Published: May 2018

Background: Surprisingly little is known about the burden of oral mucositis (OM). We provide a systematic review of studies on the burden of OM (incidence, economic impact, health-related quality of life (HRQoL)). Methods: Systematic literature searches were made in BIOSIS, EMBASE, and MEDLINE. Inclusion criteria were studies on OM in hematology/oncology patients of ≥ 18 years, journal articles, English language, and published between 2000 and 2016; OM treatment studies were excluded. Quality assessment was performed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: We screened 4,996 hits, and identified 68 studies of which 13 were without transparency on OM grading. The evidence level of 65 studies was rated ‘low' or ‘very low' in 58.5%, ‘moderate' in 20% and ‘high' in 21.5%. Mean value of incidence (7 studies) was 83.5% for all grades of OM with hematopoietic stem cell transplantation. OM incidence for all grades in head and neck cancer patients was 59.4-100%. Considering the economic impact, 16 studies showed highly variable numbers. HRQoL was measured in 16 studies using 13 different instruments. Statistically significant changes in HRQoL scores were demonstrated. Conclusion: OM is common, burdensome, costly and imposes major reductions in HRQoL. However, from a quality standpoint, the level of current evidence in OM is disappointing. The field needs continued attention to address methodological challenges.
Cadherin Expression Shift Could Well Distinguish Esophageal Squamous Cell Carcinoma from Non- Cancerous Esophageal Tissues
Authors: Zhu Shengtao , Liu Juan , Min Li , Sun Xiujing , Guo Qingdong , Li Hengcun , Zhang Zheng , Zhao Yu , Gu Junchao , Zhang Shutian
Published: May 2018

Background: Biomarkers for esophageal squamous cell carcinoma (ESCC) identification with high sensitivity are not well established. Since abnormal expression of cadherins has been widely reported in cancer, we explored its feasibility as an ESCC biomarker. Methods: Expression of E-cadherin and N-cadherin were detected in 150 esophageal tissues by immunohistochemistry. Staining strength and percentage in different subcellular structures of each specimen were evaluated by 2 independent pathologists. A logistic regression-based classifier derived from E-cadherin and N-cadherin staining was generated. Results: E-cadherin exhibited decreased membrane expression in ESCC, while N-cadherin exhibited decreased expression in the nucleus but elevated expression in the cytoplasm. Both E-cadherin and N-cadherin could distinguish ESCC tissues from non-cancerous tissues (area under the curve (AUC) = 0.748, 0.801, respectively). E-cadherin and N-cadherin staining scores could be merged into a cadherin (CDH) logistic index, which showed better discrimination (AUC = 0.909) than E-cadherin or N-cadherin alone. Further investigation indicated that the CDH logistic index was significantly correlated with tumor size and differentiation in ESCC. Conclusion: Both E-cadherin and N-cadherin had a strong expression shift in ESCC compared with non-cancerous tissues. The CDH logistic index, a parameter integrating the expression data of both cadherins, could be used as a marker with high sensitivity and specificity in the identification of ESCC.
Abnormal Repetitive Behaviours of Confiscated Slow Loris (Nycticebus spp.) in Thailand
Authors: Khudamrongsawat Jenjit , Nakchamnan Kanyamas , Laithong Phadet , Kongrit Chalita
Published: May 2018

The illegal wildlife trade, especially of live animals, is a major threat to slow lorises. Large numbers of confiscated slow lorises are sent to rescue facilities. We aimed to describe the occurrence and types of abnormal repetitive behaviours (ARBs) in 36 confiscated Bengal slow lorises (Nycticebus bengalensis), and examined factors influencing the occurrence of ARBs. We recorded behaviours of the slow lorises using instantaneous scans every 5 min from 19: 00 to 06: 00 h, and observed 6 types of ARBs in 14 (38.9%) individuals. Each individual exhibited 1 type of ARB. The most prevalent ARBs were pacing, rocking and up-down movement, and represented 29.9 ± 13.6% of the activity budget. Sex did not significantly influence the occurrence of ARB. Animals who had been at the centre for longer had a greater tendency to exhibit ARBs, but this was not statistically significant. We suggest that housing slow lorises in large semi-natural enclosures with conspecifics may reduce ARBs. Other factors potentially influencing ARBs, such as cage size, should be further investigated.
Challenges in Infectious Diseases for Haematologists
Authors: von Lilienfeld-Toal Marie , Maschmeyer Georg
Published: May 2018

Infections remain a threat for patients with haematological malignancies. In accordance with the European Hematology Association roadmap we provide a concise overview regarding the most relevant current challenges in infectious diseases for haematologists. These include bacterial infections and the need for antibiotic stewardship as well as infections with community-acquired respiratory viruses, infections in patients receiving targeted therapies, re-activations of latent infections and vaccination strategies. The following review intends to summarise the most relevant information for clinicians currently caring for patients with haematological malignancies. Recommendations given are based on the guidelines published by the Infectious Diseases Working Party of the German Society of Haematology and Medical Oncology.