bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous Three-Dimensional Surface Structures and Tamm Surface State Characteristic of Silicon Cluster Superlattice
Authors: Orita Nozomi , Iwata Yasushi
Published: December 2019

A silicon cluster superlattice was theoretically investigated with OpenMX code. Silicon (Si) clusters were quarried from monocrystalline Si to construct the initial crystallographic structures to faithfully reproduce the experimental results: Si clusters retained the sp3 structure to coalesce into a body-centered cubic (bcc) superlattice with lattice constant 2.134 nm. The Si211 and Si235 cluster superlattices can construct crystallographically stable bcc superlattice structures in good agreement with the experimental results. The stable Si211 cluster superlattice formed characteristic gap states to create a high-density-of-states peak near the Fermi level. The gap states, which are characterized as Tamm states, were induced by the endogenous surface network three-dimensionally formed in the Si211 cluster superlattice. The Tamm states clearly appearing in the Si L2,3 core-loss spectrum was reproduced by calculations of the oxidation of surface Si atoms in the Si211 cluster superlattice. The endogenous surfaces enclose a narrow region in the stable Si235 cluster superlattice to form an indigenous huge multivacancy. The gap states exhibited a p-type semiconductor quality. Retaining the sp3 structure, the Si cluster superlattice exhibited a high-symmetry structure, while their variation with the cluster size is very large. The symmetry causes the scale of the electronic properties of silicon to extend so widely from metallic quality to dielectrics.
Estimation of Performance Parameters of Turbine Engine Components Using Experimental Data in Parametric Uncertainty Conditions
Authors: Khustochka Olexandr , Yepifanov Sergiy , Zelenskyi Roman , Przysowa Radoslaw
Published: December 2019

Gas Path Analysis and matching turbine engine models to experimental data are inverse problems of mathematical modelling which are characterized by parametric uncertainty. This results from the fact that the number of measured parameters is significantly lower than the number of components’ performance parameters needed to describe the real engine. In these conditions, even small measurement errors can result in a high variation of results, and obtained efficiency, loss factors etc. can appear out of the physical range. The current methods of engine model identification have developed considerably to provide stable, precise and physically adequate solutions. Presented in this work is an estimation method of engine components’ parameters based on multi-criteria identification which provides stable estimations of parameters and their confidence intervals with the known measurement errors. A priori information about the engine, its parameters and performance is used directly in the regularised identification procedure. The mathematical basis for this approach is the fuzzy sets theory. Forming objective functions and scalar convolutions synthesis of these functions is used to estimate gas-path components’ parameters. A comparison of the proposed approach with traditional methods showed that its main advantage is high stability of estimation in the parametric uncertainty conditions. Regularization reduces scattering, excludes incorrect solutions which do not correspond to a priori assumptions, and also helps to implement the Gas Path Analysis at the limited number of measured parameters. The method can be used for matching thermodynamic models to experimental data, Gas Path Analysis and also adapting dynamic models for the needs of the engine control system.
Point-of-Care Urine LAM Tests for Tuberculosis Diagnosis: A Mini-Review
Authors: Bulterys Michelle A. , Wagner Bradley , Redard-Jacot Maël , Suresh Anita , Pollock Nira R. , Moreau Emmanuel , Denkinger Claudia M. , Drain Paul K. , Broger Tobias
Published: December 2019

Most diagnostic tests for tuberculosis (TB) rely on sputum samples, which are difficult to obtain and have low sensitivity in immunocompromised patients, patients with disseminated TB, and children, delaying treatment initiation. The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of TB at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker which can be detected in urine, an easily collected sample. This review discusses the characteristics of LAM as a biomarker, describes the performance of first-generation urine LAM tests and reasons for slow uptake, and presents considerations for developing the next-generation of more sensitive and impactful tests. Next-generation urine LAM tests have the potential to reach adult and pediatric patients regardless of HIV status or site of infection and facilitate global TB control. Implementation and scale-up of existing LAM tests and development of next-generation assays should be prioritized.
Annual Projections of Future Built-Settlement Expansion Using Relative Changes in Projected Small Area Population and Short Time-Series of Built-Extents
Authors: Nieves Jeremiah J. , Bondarenko Maksym , Sorichetta Alessandro , Steele Jessica E. , Kerr David , Carioli Alessandra , Stevens Forrest R. , Gaughan Andrea E. , Tatem Andrew J.
Published: December 2019

Advances in the availability of multitemporal and global built-/human-settlements datasets as derived from Remote Sensing (RS) can now provide globally consistent definitions of “human-settlement” at unprecedented spatial fineness. Yet, these data only provide a time-series of past extents and urban growth/expansion models have not had parallel advances at high-spatial resolution. We present a flexible modelling framework for producing annual built-settlement extents in the near future past last observed extents as provided by RS-based data. Using a random forest and autoregressive temporal models with short time-series of built-settlement extents and subnational level data, we predict annual 100m resolution binary settlement extents five years beyond the last observations. We applied this framework within varying contexts and predicted annual extents from 2010 to 2015. We found that our model framework preformed consistently across all sample countries and, when compared to time-specific imagery, demonstrated the capacity to capture human-settlement missed by the input time-series and validation extents. When comparing building footprints of small settlements to forecast extents, we saw that the modelling framework had a 12 percent increase in ground-truth accuracy. This framework shows promise for predicting near-future settlement extents, and provides a foundation for forecasts further into the future.
An Attempt to Grasp the Disaster Situation of “The 2018 Hokkaido Eastern Iburi Earthquake” Using SNS Information
Authors: Cui Qinglin ,   National Research Institute for Earth Science and Disaster Resilience (NIED) 3-1 Tennodai, Tsukuba, Ibaraki 305-0006, Japan, Hanashima Makoto , Sano Hiroaki , Ikeda Masaki , Handa Nobuyuki , Taguchi Hitoshi , Usuda Yuichiro
Published: December 2019

Whenever a natural disaster occurs, a damage assessment must be conducted to determine the extent of the damage caused, in order to quickly and effectively undertake disaster response, recovery, and reconstruction efforts. It is important to consider not only natural phenomena, but the impact of the damage on local communities as well (which is a pressing concern at any disaster site). Although a conventional, field-survey-based disaster assessment can yield solid information, it still takes time to gauge the overall implications. While an SNS system can facilitate information collection in real time, it is riddled with problems such as unreliability, and the challenge of handling vast amounts of data. In this study we analyzed Twitter content that was generated after the 2018 Hokkaido Eastern Iburi Earthquake and was related to disaster response efforts at the site of the disaster, and used it to test an approach that combines and utilizes natural language processing and geo-informatics for disaster assessment. We then verified the use of this process in two different disaster response scenarios. In this paper, we discuss some possible approaches to disaster assessment that utilize SNS information analysis technology.
Implementation and Demonstration of a System for the Forecasting of Surface Avalanche Potential Caused by Snowfall from a Cyclone
Authors: Nakamura Kazuki ,   National Research Institute for Earth Science and Disaster Resilience (NIED) 3-1 Tennodai, Tsukuba, Ibaraki 305-0006, Japan
Published: December 2019

In the avalanche on Mt. Nasu on March 27, 2017, eight persons lost their lives and many others were injured. One of the problems when an avalanche occurs is visualizing the potential occurrence of a surface avalanche. Accordingly, a system has been designed and implemented to show, in a two-dimensional model, the surface avalanche potential caused by snowfall from cyclones in a 5 km square mesh across Japan. A demonstration experiment was conducted to provide the information and verify the system. In this paper, the contents and usage of a new system for forecasting the surface avalanche potential caused by snowfall from cyclones are examined, based on the results of a questionnaire conducted after the demonstration experiment, to provide information for forecasting the potential of avalanche and comparing it with other avalanche information. This study then considers the practical use of the system. As a result, the surface avalanche potential caused by snowfall from a cyclone can be visualized over a wide area. Such forecast information is both serviceable and potentially lifesaving.
How Users of a Smartphone Weather Application Are Influenced by Animated Announcements Conveying Rainfall Intensity and Electronic Gifts Promoting Rain Evacuation
Authors: Nakajima Hiroko , Shimazaki Kan , Ishigaki Yang , Miyajima Akiko , Kuriyama Akira , Iwanami Koyuru , Mitsukura Yasue ,   Innovation Center for Meteorological Disaster Mitigation, National Research Institute for Earth Science and Disaster Resilience (NIED) 3-1 Tennodai, Tsukuba, Ibaraki 305-0006, Japan,   Correspoinding author,,   Institute of Innovation for Future Society, Nagoya University, Aichi, Japan,   Yaguchi Electric Corporation, Miyagi, Japan,   RC Solution Co., Tokyo, Japan,   Department of System Design Engineering, Keio University, Kanagawa, Japan
Published: December 2019

In this study, we assumed that animated announcements that conveyed rainfall intensity of localized heavy rain and the distribution of electronic gifts to encourage rain evacuation would promote evacuation actions. If evacuation actions could be promoted through these methods, then the transmission of weather information could be improved. Therefore, we modified the features of a weather information application for smartphones, which was already widely used, and conducted a demonstrative experiment with application users who agreed to participate in order to check the validity. We analyzed users’ behaviors by transmitting information regarding the predicted start time of rain and recording the Global Positioning System coordinates of the users’ smartphones. In addition, a questionnaire survey was administered to the users after the experiment to collect data on their conception of rainfall intensity. The participants were also interviewed. The results of the experiment showed a significant difference in user conception of rainfall intensity depending on whether they had viewed the animation. However, a behavior analysis based on location data showed no statistical bias in the relationship between the animation and rain evacuation behavior.
Migration, Transition, and Livelihoods: A Comparative Analysis of Marshallese Pre- and Post-Migration to the United States
Authors: McClain Shanna N. , Seru Jennifer , Lajar Hermon ,   Environmental Law Institute 1730 M Street NW, Suite 700, Washington, D.C. 20036, USA,   College of the Marshall Islands, Majuro, Republic of the Marshall Islands
Published: December 2019

With growing numbers of Marshallese immigrating to the United States, increasing attention is given to the enabling factors that support migration both pre-departure and post-arrival. This article provides an analysis of structured interviews and surveys between College of the Marshall Islands students living in Majuro in comparison to first generation Marshallese living in Springdale, Arkansas. The analysis sought to understand the intent of Marshallese students to move to the United States, their reasons for emigrating, and their expectations regarding life outside of the Marshall Islands in contrast to the current lives and livelihoods of Marshallese living in Arkansas. This article identifies the disparities between expectations, opportunities, and information exchange and provides options for improving the immigration and accommodation of Marshallese into the United States.
Motivations for Students in the Republic of the Marshall Islands and the Federated States of Micronesia to Emigrate Abroad
Authors: Moriya Kanae ,   Graduate School of Frontier Sciences, The University of Tokyo 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8563, Japan
Published: December 2019

This study aims to find out the basis of Marshallese students’ aspirations to migrate abroad, determine whether intellectuals in the same country share such aspirations, observe how well Japanese university students and intellectuals understand why Marshallese students migrate, and compare the Marshallese students’ motivations to emigrate with those of students from the Federated States of Micronesia. I conducted a survey by interview and questionnaire in the Marshall Islands, Federated States of Micronesia, and Japan. I found that 65% of the students in the Republic of the Marshall Islands (RMI) felt education was the primary reason to migrate abroad, followed by work (15%), health (8%), family (7%), climate change (3%), and natural disasters (2%). The RMI intellectuals correctly guessed the relative importance students granted the factors (education, work, health, etc.). However, they underestimated the importance of education for the students. Eleven percent of the Japanese students assumed that Marshallese students would wish to migrate abroad because of climate change, which overestimates the students’ feelings about the issue. Interestingly, no Japanese student considered health or family to be possible reasons for RMI students to emigrate abroad. Perhaps, Japanese students were not aware of the prevalence of very strong family ties and inadequate medical facilities in RMI. There were similar percentages of students who wished to migrate because of climate change between the RMI (3%) and the Federated States of Micronesia (FSM) (4%). However, the RMI is an atoll country that may be submerged by climate change, and the FSM is mostly composed of volcanic islands that will not be submerged.
Challenge to Build the Science of Human Survival from Disaster Starting from Analysis for the 2011 Tohoku Tsunami
Authors: Seto Shuji , Imamura Fumihiko , Suppasri Anawat ,   International Research Institute of Disaster Science (IRIDeS), Tohoku University 468-1 Aza-Aoba, Aramaki, Aoba-ku, Sendai, Miyagi 980-8572, Japan,   Core Research Cluster of Disaster Science, Tohoku University, Miyagi, Japan
Published: December 2019

The 2011 Tohoku earthquake and tsunami caused the loss of 20,000 lives in Japan. According to the National Police Agency (2012), 90% of deaths in the Iwate, Miyagi, and Fukushima prefectures were due to drowning. On the other hand, this report also showed that the remaining 10% died from circumstances other than drowning, as suggested by the Japanese Society of Legal Medicine (2012). A new solution is needed to propose practical measures against a tsunami. In this paper, the authors suggest the science of human survival from disaster as one of the solutions and illustrate the research design implemented to build it. Constructing the science of human survival shall be important to mitigate human damages in future tsunami disasters.
Spatial Characteristics of Flooded Areas in the Mun and Chi River Basins in Northeastern Thailand
Authors: Zenkoji Shingo , Oda Shigehiko , Tebakari Taichi , Archevarahuprok Boonlert ,   Graduate School of Engineering, Toyama Prefectural University 5180 Kurokawa, Imizu, Toyama 939-0398, Japan,   Project Management Department, Energy Business Division, NIPPON KOEI Co., Ltd., Tokyo, Japan,   Thai Meteorological Department, Bangkok, Thailand
Published: December 2019

The objectives of this study are to conduct an analysis on rainfall change tendencies, calculate the inundation in the basins of Mun and Chi Rivers in the northeastern region of Thailand, and clarify the flood risk in the long term, taking the spatial characteristics of flooding into consideration. To grasp the rainfall change tendencies, two statistical analyses are conducted using the Mann-Kendall test and the generalized extreme value distribution. The inundation analysis is conducted using the Rainfall-Runoff-Inundation (RRI) model. As a result of the statistical analysis on the rainfall characteristics, it can be observed that the annual rainfall has significant increasing tendencies at the significance level of 5% in a wide area of the upper reaches. In addition, inundation calculation indicates that the maximum inundation depth and inundation area have increased in recent years.
Histological and Physiological Studies on the Long-term Effect of Different Concentrations of Energy Drink (Tiger) on the Renal and Hepatic Systems of Young Mice
Authors: Ali Luma Qasim
Published: December 2019

The present study aims to investigate the long-term histopathological, and physiological effects of different concentrations of a commercially available energy drink (Tiger) on liver and kidney of young mice. Sixteen Balb/c male mice,6 -week old, were divided into 4 groups (n=4). Two groups consumed the energy drink at a concentration of 28µl energy drink/ml water. One group were killed after 10 days (T1), another group were killed after 20 days (T2). Other group of mice consumed the energy drink at a final concentration of 14µl/ml for 20 days (T3). The last group was provided only with water and served as control. Mice of all groups drank around 3 ml per day. The histopathological study on liver of treated groups showed many changes such as inflammatory cells infiltration and aggregation with hepatocyts necrosis, some of these necrosis replaced by RBCs and inflammatory cells, while the pathohistological changes in kidney of treated groups limited to aggregation of RBCs and inflammatory cells between renal tubules which expressed vacuolar degeneration. These changes based on elevated liver function enzymes (Glutamic Oxaloacetic Transaminase (GOT), Glutamic Pyruvic Transaminase (GPT) and Alkaline phosphatase (ALP)) and blood urea and creatinine. These changes were more in the T2 groups, so it could be concluded that long term of energy drink consuming effect histopathologically and physiologically on kidney and liver of young mice depending on its concentration and period of consuming.
Molecular Identification of Fusobacterium Isolates and limitation of Biofilm Formation Adhesion Gene (fadA) in Dental Outpatients
Authors: Sulaiman Aws Ibrahim
Published: December 2019

Fusobacterium are compulsory anaerobic gram-negative bacteria, long thin with pointed ends, it causes several illnesses to humans like pocket lesion gingivitis and periodontal disease; therefore our study is constructed on molecular identification and detection of the fadA gene which is responsible for bacterial biofilm formation. In this study, 10.2% Fusobacterium spp. were isolated from pocket lesion gingivitis. The isolates underwent identification depending on several tests under anaerobic conditions and biochemical reactions. All isolates were sensitive to Imipenem (IPM10) 42.7mm/disk, Ciprofloxacin (CIP10) 27.2mm/disk and Erythromycin (E15) 25mm/disk, respectively. 100% of Fusobacterium spp. isolates had 16S rDNA gene (360bp.), whereas two isolates had fadA gene (232bp.)
Studying the Crystal Structure, Topography, and Anti-bacterial of a Novel Titania (TiO2 NPs) Prepared by a Sol-gel Manner
Authors: Et al. Fayyadh
Published: December 2019

In this research, titanium dioxide nanoparticles (TiO2 NPs) were prepared through the sol-gel process at an acidic medium (pH3).TiO2 nanoparticles were prepared from titanium trichloride (TiCl3) as a precursor with Ammonium hydroxide (NH4OH) with 1:3 ratio at 50 °C. The resulting gel was dried at 70 °C to obtain the Nanocrystalline powder. The powder from the drying process was treated thermally at temperatures 500 °C and 700 °C. The crystalline structure, surface morphology, and particle size were studied by using X-ray diffraction (XRD), Atomic Force Microscopy (AFM), and Scanning Electron Microscope (SEM). The results showed (anatase) phase of titanium dioxide with the average grain size of 110 nm at 500 °C calcination temperature, and (anatase- rutile) mixed phase of titanium dioxide with the average particle size of 118.1 nm at 700 °C calcination temperature. The anti-bacterial activity of the synthesis specimens was recorded through the Kirby-Bauer disc method (disc devotion method). The results displayed a pretty excellent antibacterial activity of TiO2 NPs to bacteria strains: Gram positive staphylococcus aureus, gram negative pseudomonas aeruginosa, and "gram negative escherichia coli. The sensitivity of the tested bacteria to TiO2 NPs depends on the oxidation state of the TiO2 NPs, particle size, volume, and the density of the unit cell. The small- average particle size of titanium dioxide particles showed high antibacterial activity against bacteria, while the larger- average particle size of titanium dioxide particles showed less antibacterial activity. The novelty of this production is the manufacturing of a novel kind of TiO2 NPs and achievement its best antibacterial activity.
Principally Quasi-Injective Semimodules
Authors: Et al. Aljebory
Published: December 2019

In this work, the notion of principally quasi- injective semimodule is introduced, discussing the conditions needed to get properties and characterizations similar or related to the case in modules.

      Let  be an -semimodule with endomorphism semiring Ș. The semimodule  is called principally quasi-injective, if every  -homomorphism from any cyclic subsemimodule of  to  can be extended to an endomorphism of .
Does chemoradiotherapy benefit elderly patients with esophageal squamous cell cancer? A propensity-score matched analysis on multicenter data ( 3JECROG R-03A )
Authors: Chen Mingqiu , Liu Xiao hong , Han Chun , Wang Xin , Zhao Yidian , Pang Qingsong , Sun Xinchen , Li Gaofeng , Zhang Kaixian , Li Ling , Qiao Xueying , Lin Yu , Chen Junqiang , Xiao Zefen
Published: December 2019

Aim

The aim of the present study was to assess the efficacy of concurrent chemoradiotherapy (CRT) or radiotherapy alone (RT-alone) in elderly patients with esophageal squamous cell carcinoma (ESCC).

Methods

The clinical data of patients with ESCC treated with RT-alone or CRT were collected and retrospectively reviewed. The 1-, 3- and 5-year overall survival (OS) rates and the clinical characteristics correlated with survival were analyzed statistically. Propensity score matching (PSM) analyses were used to compensate for differences in baseline characteristics between the CRT and RT-alone groups to confirm the survival difference.

Results

A total of 729 patients fulfilling the inclusion criteria were reviewed. Diabetes, primary tumor volume (pTV), primary tumor location (pTLo), clinical T stage,(cT) clinical N stage (cN), clinical M stage (cM) and short-term response to RT were independent factors influencing OS (P=0.002-0.044). The 5-year OS rate was 26.6%, 26.0% and 30.1% in the whole cohort, RT-alone and CRT groups, respectively. The survival difference between RT alone and CRT was not significant before or following PSM. Compared with the corresponding subgroups treated with RT alone, CRT significantly benefited patients with diabetes (P=0.003), cT4 (P=0.030) and cN0 (P=0.049), whereas no benefit was identified between CRT and RT alone in the other subgroups, including cT1-3, cN1, cM, pTLo, pTV, age and gender.

Conclusions

CRT with the current chemotherapy regimens may not improve the survival of elderly ESCC patients compared to RT-alone, except in patients with cT4 stage, cN0 stage or diabetes. However, due to the limitation of the retrospective nature of the current study, further clinical trials are required for confirmation.

Key words: Concurrent chemoradiotherapy; Elderly; Esophageal squamous cell carcinoma; Survival
The grapevine homeobox gene VvHB58 influences seed and fruit development through multiple hormonal signaling pathways
Authors: Li Yunduan , Zhang Songlin , Dong Ruzhuang , Wang Li , Yao Jin , Nocker Steve van , Wang Xiping
Published: December 2019

Background: The homeobox transcription factor has a diversity of functions during plant growth and development process. Previous transcriptome analyses of seed development in grape hybrids suggested that specific homeodomain transcription factors are involved in seed development in seedless cultivars. However, the molecular mechanism of homeobox gene regulating seed development in grape is rarely reported.
Results: Here, we report that the grapevine VvHB58 gene, encoding a homeodomain-leucine zipper (HD-Zip I) transcription factor, participates in regulating fruit size and seed number. The VvHB58 gene was differentially expressed during seed development between seedless and seeded cultivars. Subcellular localization assays revealed that the VvHB58 protein was located in the nucleus. Transgenic expression of VvHB58 in tomato led to loss of apical dominance, a reduction in fruit pericarp expansion, reduced fruit size and seed number, and larger endosperm cells. Analysis of the cytosine methylation levels within the VvHB58 promoter indicated that the differential expression during seed development between seedless and seeded grapes may be caused by different transcriptional regulatory mechanisms rather than promoter DNA methylation. Measurements of five classic endogenous hormones and expression analysis of hormone-related genes between VvHB58 transgenic and nontransgenic control plants showed that expression of VvHB58 resulted in significant changes in auxin, gibberellin and ethylene signaling pathways. Additionally, several DNA methylation-related genes were expressed differentially during seed development stages in seedless and seeded grapes, suggesting changes in methylation levels during seed development may be associated with seed abortion.
Conclusion: VvHB58 has a potential function in regulating fruit and seed development by impacting multiple hormonal pathways. These results expand understanding of homeodomain transcription factors and potential regulatory mechanism of seed development in grapevine, and provided insights into molecular breeding for grapes.
Association of childhood socioeconomic status with edentulism among Chinese in mid-late adulthood
Authors: ZHANG XIAONING , CHEN SHUANG
Published: December 2019

Background: The aim of this study was to examine the association between childhood socioeconomic status (SES) and edentulism. Methods: The edentulous status of Chinese in mid-late adulthood was determined using self-reported lost all of teeth from the Health and Retirement Longitudinal Study (CHARLS). Childhood SES was determined based on the following parameters: the education, occupation and working status of the parents; financial situation of the family; relationship with the parents; care, love and affection from the mother; quarrels and fights between parents; primary residence; neighbors’ willingness to help and with close-knit relationships. Adulthood SES was assessed by educational achievements. This study used principal component analysis (PCA) to select variables and binary logistic regression models to determine the association between childhood SES and edentulism.Results: Data were available from a total of 17,713 respondents, 984 of whom were edentulous (2.9%). The prevalence of edentulism in mid- to late-age Chinese individuals was higher in those with poor childhood SES. In final regression model, edentulism was significantly associated with willingness of neighbors to help with close-knit relationships (OR = 0.89, 95% CI = 0.79 – 0.99), parents with high school education or above (OR = 1.18, 95% CI = 1.01 – 1.39) and drinking and smoking habits of the father (OR = 1.10, 95% CI = 0.97 – 1.24).Conclusion: Childhood SES was significantly associated with the prevalence of edentulism in mid- to late-age Chinese individuals. In particular, parents with high school education or above, unwillingness of neighbor to help with close-knit relationships, drinking and smoking habits of the father independent of adulthood SES were significantly associated with edentulism. Accordingly, the development of optimal recommendations and more effective intervention strategies requires considering the experiences in early life associated with poor SES contributes to poor oral health.
Pharmacodynamics of Pre-Operative PD1 Checkpoint Blockade and Receptor Activator of NFkB Ligand (RANKL) Inhibition in Non-Small Cell Lung Cancer (NSCLC): study protocol for a multicentre open-label phase 1B/2 translational trial (POPCORN)
Authors: Ahern Elizabeth Stephanie , Cubitt Annette , Ballard Emma , Teng Michele W. L. , Dougall William C. , Smyth Mark J. , Godbolt David , Naidoo Rishendran , Goldrick Amanda , Hughes Brett G. M.
Published: December 2019

Background Neoadjuvant immunotherapy targeting the immune checkpoint programmed death-1 (PD-1) is under investigation in various tumour settings including non-small-cell lung cancer (NSCLC). Preclinical models demonstrate the superior power of immunotherapy given in the neoadjuvant (pre-operative) compared with adjuvant (post-operative) setting to eradicate metastatic disease and induce long-lasting antigen-specific immunity. Novel effective immunotherapy combinations are widely sought in the oncology field, targeting non-redundant mechanisms of immune evasion. A promising combination partner with anti-PD1 in NSCLC is denosumab, a monoclonal antibody blocking Receptor Activator of NF-κB Ligand (RANKL). In preclinical cancer models, and a large retrospective case series in NSCLC, anti-cancer activity of combination immune checkpoint inhibition (ICI) and denosumab has been reported. Furthermore, clinical trials of ICI and denosumab are underway in advanced melanoma and clear-cell renal cell carcinoma. However, the mechanism of action of combination anti-PD1 and anti-RANKL is poorly defined. Methods This open-label multicentre trial will randomise by minimisation 30 patients with resectable stage IA (primary > 2cm) to IIIA NSCLC to a neoadjuvant treatment regime of either two doses of nivolumab (3 mg/kg every 2 weeks) or two doses of nivolumab (same regimen) plus denosumab (120 mg every 2 weeks, following nivolumab). Each treatment arm is of equal size, and be approximately balanced with respect to histology (squamous vs. non-squamous) and clinical stage (I-II vs IIIA). All patients will receive surgery for their tumour two weeks after the final dose of neoadjuvant therapy. The primary outcome will be translational research to define the tumour-immune correlates of combination therapy compared with monotherapy. Key secondary outcomes will include a comparison of rates of the following between each arm: toxicity, response (pathological and radiological), and microscopically complete resection. Discussion The POPCORN study provides a unique platform for translational research to determine the mechanism of action of a novel proposed combination immunotherapy for cancer. Trial registration Prospectively registered on Australian New Zealand Clinical Trials Registry (ACTRN12618001121257) on 06/07/2018.
Plastome phylogenomics, biogeography, and clade diversification of Paris (Melanthiaceae)
Authors: Ji Yunheng , Yang Lifang , Chase Mark W. , Liu Changkun , Yang Zhenyan , Yang Jin , Yang Jun-Bo , Yi Ting-Shuang
Published: December 2019

Background: Paris (Melanthiaceae) is an economically important but taxonomically difficult genus, which is unique in angiosperms because some species have extremely large nuclear genomes. Phylogenetic relationships within Paris have long been controversial. Based on complete plastomes and nuclear ribosomal DNA (nrDNA) sequences, this study aims to reconstruct a robust phylogenetic tree and explore historical biogeography and clade diversification in the genus.
Results: All 29 species currently recognized in Paris were sampled. Whole plastomes and nrDNA sequences were generated by the genome skimming approach. Phylogenetic relationships were reconstructed using the maximum likelihood and Bayesian inference methods. Based on the phylogenetic framework and molecular dating, biogeographic scenarios and historical diversification of Paris were explored. Significant conflicts between plastid and nuclear datasets were identified, and the plastome tree is highly congruent with past interpretations of the morphology. Ancestral area reconstruction indicated that Paris may have originated in northeastern Asia and northern China, and has experienced multiple dispersal and vicariance events during its diversification. The rate of clade diversification has sharply accelerated since the Miocene/Pliocene boundary.
Conclusions: Our results provide important insights for clarifying some of the long-standing taxonomic debates in Paris . Cytonuclear discordance may have been caused by ancient and recent hybridizations in the genus. The climatic and geological changes since the late Miocene, such as the intensification of Asian monsoon and the rapid uplift of Qinghai-Tibet Plateau, as well as the climatic fluctuations during the Pleistocene, played essential roles in driving range expansion and radiative diversification in Paris . Our findings challenge the theoretical prediction that large genome sizes may limit speciation.
Disease characteristics and treatment patterns of Chinese patients with colorectal cancer: a retrospective study using medical records from China
Authors: Xu Ruihua , Wang Wei , Zhu Bo , Lin Xiaoyan , Ma Dong , Zhu Lingjun , Zhao Qingchuan , Nie Yongzhan , Cai Xiaohong , Li Qi , Fang Weijia , Li Hongyan , Wang Ning , Chen Yun , Peng Cike , Fang Honghao , Shen Lin
Published: December 2019

Background: Colorectal cancer (CRC) is the third most prevalent cancer in China but few large-scale studies were conducted to understand CRC patients. The current study is aimed to gain a real-world perspectives of CRC patients in China. Methods: Using electronic medical records of sampled patients between 2011 and 2016 from 12 hospitals in China, a retrospective cohort study was conducted to describe demographics and disease prognosis of CRC patients, and examine treatment sequences among metastatic CRC (mCRC) patients. Descriptive, comparative and survival analyses were conducted. Results: Among mCRC patients (3,878/8,136, 48%), the fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and other oxaliplatin-based regimens were the most widely-used first-line treatment (42%). Fluorouracil, leucovorin, irinotecan (FOLFIRI) and other irinotecan-based regimens dominated the second-line (40%). There was no a dominated regimen for the third-line. The proportion of patients receiving chemotherapy with targeted biologics increased from less than 20% for the first- and second- lines to 34% for the third-line (p<0.001). The most common sequence from first- to second-line was from FOLFOX and other oxaliplatin-based regimens to FOLFIRI and other irinotecan-based regimens (286/1,200, 24%). Conclusions: Our findings reflected a lack of consensus on the choice of third-line therapy and limited available options in China. It is evident o continue promoting early CRC diagnosis and to increase the accessibility of treatment options for mCRC patients. As the only nationwide large-scale study among CRC and mCRC patients before more biologics became available in China, our results can also be used as the baseline to assess treatment pattern changes before and after more third-line treatment were approved and covered into the National Health Insurance Plan in China between 2017 - 2018.
Immunosenescence profile and expression of the aging biomarker (p16INK4a) in testicular cancer survivors treated with chemotherapy.
Authors: Bourlon Maria Teresa , Velazquez Hugo E , Hinojosa Juan , Orozco Luis , Rios-Corzo Ricardo , Lima Guadalupe , Llorente Luis , Hernandez-Ramirez Diego F , Valentin-Cortez Francisco J , Medina-Rangel Irene , Atisha-Fregoso Yemil
Published: December 2019

Background Cytotoxic chemotherapy can cure advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16 INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy. Patients and methods Case-control study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. p16 INK4a expression in T cells was measured using qPCR. Percentage of lymphocyte subpopulations associated with immunosenescence and p16 INK4a expression in TCS compared to controls using the Wilcoxon signed-rank test. Results We included 16 cases and 16 controls. The median of age was 27 years (24-54) and median time on surveillance was 26.5 months (3-192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had a lower naïve CD4+ and an increased memory CD4+ cells. Within the CD8+ T lymphocytes, TCS exhibited a decrease in the percentage of naïve cells and an increase in CD8+CD45RA+CD57+ cells. TCS also exhibited a decreased memory CD19+ B cells compared to the controls. The relative expression of p16 INK4a in T cells was higher in TCS compared to the controls [1.33 (IQR 0.93-2.23): p=0.048). Conclusion TCS showed an increase in the expression of the aging biomarker p16 INK4a and a lymphocyte phenotype associated with immunosenescence; characterized by a decrease in naïve cells, and concomitant increment of memory cells. This phenomenon might contribute to the development of an immune risk profile, which is associated with an increased rate of infections and a diminished effect of vaccination in the elderly population. Further studies are warranted to define the clinical implications of this alteration in TCS.
Preoperative Risk Stratification for Early Recurrence of HBV-related Hepatocellular Carcinoma After Deceased Donor Liver Transplantation:A Five-Eight Model Development and Validation
Authors: Al-Ameri Abdulahad Abdulrab Mohammed , Wei Xuyong , Lin Lidan , Shao Zhou , Guo Haijun , Xie Haiyang , Zhou Lin , Zheng Shusen , Xu Xiao
Published: December 2019

Background: Early recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is associated with poor surgical outcomes. This study aims to construct a preoperative model to predict individual risk of post-LT HCC recurrence.
Methods: Data of 748 adult patients who underwent deceased donor LT for HCC between January 2015, and February 2019 were collected retrospectively from the China Liver Transplant Registry database and randomly divided into training (n=486) and validation(n=262) cohorts. A multivariate analysis was performed and the five-eight model was developed.
Results: A total of 748 patients were included in the study; of them, 96% had hepatitis B virus (HBV) and 84 % had cirrhosis. Pre-LT serum alpha-fetoprotein (AFP), tumor number and largest tumor diameter were incorporated to construct the 5-8 model which can stratify patients accurately according to their risk of recurrence into three prognostic subgroups; low-(0-5 points), medium-(6–8 points) and high-risk (>8 points) with 2-year post-LT recurrence rate of (5%,20% and 51%,p<0.001) respectively.The 5-8 model was better than Milan, Hangzhou, and AFP-model for prediction of HCC early recurrence. These findings were confirmed by the results of the validation cohort.
Conclusions: The 5-8 model is a simple validated and accurate tool for preoperative stratification of early recurrence of HCC after LT.
The trend of full vaccination coverage in infants and inequalities by wealth quintile and maternal education: Analysis from four recent Demographic and Health Surveys in Nepal
Authors: Acharya Kiran , Paudel Yuba Raj , Dharel Dinesh
Published: December 2019

Background

Despite policy intention to reach disadvantaged populations, inequalities in child health care use and health outcomes persist in Nepal. The current study aimed to investigate the trend of full vaccination coverage among infants and its equity gaps between Nepal Demographic and Health Surveys (NDHS) 2001 and 2016.Methods

Using data from NDHS conducted in 2001, 2006, 2011 and 2016, we investigated the trend of coverage of six antigens:Bacille Calmette Guerin (BCG), Diptheria, Pertussis, Tetanus (DPT), Polio, and Measles during their infancy among children aged 12-23 months. We presented trends and correlates of vaccination coverage by different socio-demographic factors. We measured inequalities in full vaccination coverage by wealth quintile and maternal education using absolute measure (slope index of inequality) and relative measures (Relative index of inequality, concentration index) of inequalities.Results

Full immunization coverage among infants steadily increased from 65.6% in 2001 to 87.0% in 2011; however, it decreased to 77.8% in 2016. Province 2 had a significantly lower full vaccination coverage compared to Province1.Although decreasing over time, there were significant inequalities by household wealth quintiles and maternal educational status. The slope index of inequality (SII) for wealth quintiles decreased from -32.3 [-45.5,-19.1] in 2001 to an SII of-8.4 [-18.6,-1.7] in 2016. Similarly, the SII for education decreased from -61.8 [-73.5,-50.1] in 2001 to an SII of -30.5 [-40.7,-20.2] in 2016. Similarly, the relative index of inequality (RII) also showed an improvement over time, indicating the narrowing equity gap. Additionally, concentration index on full immunization coverage by wealth quintiles dropped from 0.21 (0.12-0.28) in 2001 to 0.054 (-0.01-0.12) in 2016. Absolute and relative inequalities were persistently larger by maternal educational status compared to household wealth quintiles throughout the study period.Conclusion

Full vaccination coverage in Nepal increased from 2001 until 2011 but saw a significant decrement away from the national target after 2011. However, the equity gap by household wealth quintile and maternal education status has narrowed over time. National Immunization programs need to give higher emphasis to infants born to mothers with less education, those born in the poorer wealth quintile households, and those living in Province 2.
Effect of adjuvant chemotherapy on survival benefit in stage III colon cancer patients stratified by age: a Japanese real-world cohort study
Authors: Kawamura Hidetaka , Morishima Toshitaka , Sato Akira , Honda Michitaka , Miyashiro Isao
Published: December 2019

Background: Adjuvant chemotherapy is relatively underused in older patients with colon cancer in Japan, and its age-specific effects on clinical outcomes remain unclear. This study aimed to assess the effect of adjuvant chemotherapy on survival benefit in stage III colon cancer patients stratified by age in a Japanese real-world setting. Methods: In this multi-center retrospective cohort study, we analyzed patient-level information through a record linkage of population-based cancer registry data and administrative claims data. The study population comprised patients aged ≥18 years who received a pathological diagnosis of stage III colon cancer and underwent curative resection between 2010 and 2014 at 36 cancer care hospitals in Osaka Prefecture, Japan. Patients were divided into two groups based on age at diagnosis (<75 and ≥75 years). The effect of adjuvant chemotherapy was analyzed using Cox proportional hazards regression models for all-cause mortality with inverse probability weighting of propensity scores. Adjusted hazard ratios were estimated for both age groups. Results: A total of 783 patients were analyzed; 476 (60.8%) were aged <75 years and 307 (39.2%) were aged ≥75 years. The proportion of older patients who received adjuvant chemotherapy (36.8%) was substantially lower than that of younger patients (73.3%). In addition, the effect of adjuvant chemotherapy was different between the age groups: the adjusted hazard ratio was 0.56 (95% confidence interval: 0.33-0.94, P=0.027) in younger patients and 1.07 (0.66-1.74, P=0.78) in older patients. Conclusions: The clinical effectiveness of adjuvant chemotherapy in older patients with stage III colon cancer appears limited under current utilization practices.
Safety and use of pulmonary function tests: a retrospective study from a single center over seven years’ clinical practice
Authors: Li Fei , Huang Zhi-wen , Wang Xiao-fei , Xu Huiwen , Yu Hua , Chen Yan-bin , Huang Jian-an , Wang Jia-jia , Lei Wei
Published: December 2019

Background To promote the utilization of pulmonary function tests (PFT) through analyzing the data of PFT during the past seven years in one large teaching hospital in China.Methods Through a retrospective analysis, the allocation of full-time staff in PFT room, the demographic characteristics of patients, cost-effectiveness of PFT, positive rate and failure rate of PFT, adverse events were analyzed.Results 1) From 2012 to 2018, the numbers of PFT showed the trend of escalation year by year. The proportion of patients receiving PFT rose from 29.0/10000 in 2012 to 34.7/10000 in 2018. The best allocation of PFT room was 20-25/ person / day. 2) The number of PFT provided by Department of Pulmonary and Critical Care Medicine (PCCM) accounted for 97.2%, 97.1%, 97.3%, 97.8%, 97.8%, 98.0%, and 98.2% of the total cases of outpatient PFT in the same year. The top three departments in the inpatient department were Department of Thoracic Surgery, Department of General Surgery, and Department of Urinary Surgery, the total cases of PFT in these three departments accounted for 65.1%, 64.4%, 62.1%, 63.5%, 62.4%, 65.3% and 69.1% of the total cases of inpatient PFT in the same year. 3) Data from 2018 showed that the revenue from PFT was about 3.7 million Chinese Yuan, and that the salary of personnel and expenditure on machine maintenance and wear were about 800,000 Chinese Yuan. 4) 58.2% of the patients who had undergone PFT had ventilatory dysfunction. 5) The average failure rate of PFT in the past seven years was 1.91%. 6) The main adverse events of PFT examination were dizziness, amaurosis, limb numbness, lip numbness and falls. The incidence rates were 0.49%, 0.42%, 0.41%, 0.39%, 0.44%, 0.48%, and 0.45% respectively, with an average of 0.44%.Conclusions The number of PFT showed an upward trend in the past seven years, and the optimal staffing of PFT room was 20-25 cases per person per day. The positive rate of pulmonary dysfunction was 58.2%. The failure rate of PFT and the incidence of adverse events were very low, suggesting it is a simple and safe clinical examination. It's worthy of further popularization and promotion.