bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncovering the Hidden Credentials ofBrucellaVirulence
Authors: Roop R. Martin , Barton Ian S. , Hopersberger Dariel , Martin Daniel W.
Published: February 2021

Bacteria in the genusBrucellaare important human and veterinary pathogens. The abortion and infertility they cause in food animals produce economic hardships in areas where the disease has not been controlled, and human brucellosis is one of the world’s most common zoonoses.Brucellastrains have also been isolated from wildlife, but we know much less about the pathobiology and epidemiology of these infections than we do about brucellosis in domestic animals.
Mortality, survival and residual injury burden of Royal Navy and Royal Marine combat casualties sustained in 11-years of operations in Iraq and Afghanistan
Authors: Penn-Barwell J , Fries C A , Bennett P M , Midwinter M J , Baker A
Published: February 2021

We present eleven years of prospectively-gathered data defining the full spectrum of the United Kingdom’s (UK) Naval Service (Royal Navy and Royal Marines) casualties, and characterise the injury patterns, recovery and residual functional burden from the conflicts of the last decade. The UK Military Trauma Registry was searched for all Naval Service personnel injured between March 2003 and April 2013. These records were then cross-referenced with the records of the Naval Service Medical Board of Survey (NSMBOS), which evaluates injured Naval Service personnel for medical discharge, continued service in a reduced capacity or Return to Full Duty (RTD). Population at risk data was calculated from service records.

There were 277 casualties in the study period: 63 (23%) of these were fatalities. Of the 214 survivors, 63 or 29% (23% of total) were medically discharged; 24 or 11% (9% of total) were placed in a reduced fitness category with medical restrictions placed on their continued military service. A total of 127 individuals (46% of the total and 59% of survivors) RTD without any restriction. The greatest number of casualties was sustained in 2007. There was a 3% casualty risk per year of operational service for Naval Service personnel. The most common reason cited by Naval Service Medical Board of Survey (NSMBOS) for medical downgrading or discharge was injury to the lower limb, with upper limb trauma the next most frequent.

This study characterises the spectrum of injuries sustained by the Naval Service during recent conflicts with a very high rate of follow-up. Extremity injuries pose the biggest challenge to reconstructive and rehabilitative services striving to maximise the functional outcomes of injured service personnel.
The current thinking on colorectal cancer
Authors: Spreadborough P , Doran C
Published: February 2021

Colorectal cancer (CRC) is the fourth most common cancer in the UK and the incidence has increased over recent decades. Although only 1.5% of cases are diagnosed in those aged under 40 years, it remains an important condition to be aware of in the military population. Patients who are genetically predisposed can have a lifetime risk of 80-100% of developing CRC and are likely to develop symptoms during their service. 20% of patients will present with metastatic disease. While surgical and oncological treatments have improved outcomes, early diagnosis of CRC is essential to reducing mortality. This paper provides an overview of the aetiology, investigations and treatment options for CRC. Explanation of primary surgical options and the principles of adjuvant therapies are included to aid informed discussions with patients.
Writing your postgraduate dissertation: a basic framework
Authors: Walker S
Published: February 2021

This paper provides a basic framework for those embarking upon a postgraduate dissertation. The dissertation experience can offer many opportunities for self and academic development once ethical approval has been obtained. A good dissertation is the result of a sound methodological framework, where some thought has been given to the strengths and weaknesses of qualitative and quantitative methods of inquiry. The research question needs to be given careful consideration so that the aims and objectives of the postgraduate research project are fulfilled.
Femoral Acetabular Impingement: the sex- and agelinked distribution of alpha angles in 146 patients of service age without pre-existing osteoarthritic or other hip pathology
Authors: Heil K M , Wood A M , Penn-Barwell J , Keenan A C M , McKie S
Published: February 2021

The use of the alpha angle to help the diagnosis of Femoral Acetabular Impingement (FAI) is common. However, there is currently no standard value available across an asymptomatic pre-arthritic population. We present the first large cohort of Computerised Tomography (CT) based alpha angles in patients with no history of hip pathology, including intra– and interobserver validation. We carried out a retrospective analysis of 73 consecutive individuals (146 hip joints) with ages ranging from 18 to 39 years. The age range 18–39 represents 82.4% of those currently serving in the UK Armed Forces. The cohort was drawn from those patients who had received a CT scan in the Lothian Region between 1 Jan 2011 and 31 Dec 2011 due to abdominal pathology. These patients had their electronic patient record checked to rule out any hip–related problems. The alpha angle of Nötzli was measured on the axial view bilaterally. The mean value for the 18–39 age range was found to be 51.89° for the left hip and 52.53° for the right.

Femoral alpha angle is a reproducible measurement for assessing the femoral neck. However, there is wide variability in the alpha angle for patients, irrespective of the presence of symptoms. Our results would suggest that the alpha angle alone should not be used to diagnose FAI in service personnel, as even large angles may be normal.
International mine countermeasures exercise 2013: Role 2 Afloat
Authors: Matthews J J , Heames R M
Published: February 2021

In May 2013 a Role 2 Afloat team was deployed on board the Bay-class Landing Ship Dock (Auxiliary) RFA CARDIGAN BAY as part of the US-led Task Force involved in the International Mine Countermeasures Exercise 2013 (IMCMEX 13). This article introduces a series of papers from the various departments that make up the Role 2 Afloat team explaining the make-up of the team and also the overall capability of the team to deliver Role 2 care in the maritime environment.
The surgical aspects of Role 2 Afloat
Authors: Tye S , Carnie R , Chambers R , Doran C M , Matthews J J
Published: February 2021

The current configuration of the surgical component of the Role 2 Afloat team is described, including an outline of the equipment available. The lessons learned from a recent exercise, where a Role 2 Afloat team was deployed on RFA CARDIGAN BAY are outlined and expanded, emphasising the difficulties of providing damage control surgery in the maritime environment.
The time has come to extend the 14-day limit
Authors: McCully Sophia
Published: February 2021

For the past 40 years, the 14-day rule has governed and, by defining a clear boundary, enabled embryo research and the clinical benefits derived from this. It has been both a piece of legislation and a rule of good practice globally. However, methods now allow embryos to be cultured for more than 14 days, something difficult to imagine when the rule was established, and knowledge gained in the intervening years provides robust scientific rationale for why it is now essential to conduct research on later stage human embryos. In this paper, I argue that the current limit for embryo research in vitro should be extended to 28 days to permit research that will illuminate our beginnings as well as provide new therapeutic possibilities to reduce miscarriage and developmental abnormalities. It will also permit validation of potentially useful alternatives. Through consideration of current ethical arguments, I also conclude that there are no coherent or persuasive reasons to deny researchers, and through them humanity, the knowledge and the innovation that this will generate.
MicroRNA regulation of vascular smooth muscle cells and its significance in cardiovascular diseases
Authors: Nguyen Duong Ngoc Diem , Chilian William M. , Zain Shamsul Mohd , Daud Muhammad Fauzi , Pung Yuh-Fen
Published: February 2021

Cardiovascular disease (CVD) is among the leading causes of death worldwide. MicroRNAs (miRNAs), regulatory molecules that repress protein expression, have attracted considerable attention in CVD research. The vasculature plays a big role in CVD development and progression and dysregulation of vascular cells underlies the root of many vascular diseases. This review provides a brief introduction of the biogenesis of miRNAs and exosomes, followed by overview of the regulatory mechanisms of miRNAs in vascular smooth muscle cells (VSMCs) intracellular signaling during phenotypic switching, senescence, calcification, and neointimal hyperplasia. Evidence of extracellular signaling of VSMCs and other cells via exosomal and circulating miRNAs is also presented. Lastly, current drawbacks and limitations of miRNA studies in CVD research and potential ways to overcome these disadvantages are discussed in detail. In-depth understanding of VSMC regulation via miRNAs will add substantial knowledge and advance research in diagnosis, disease progression, and (or) miRNA-derived therapeutic approaches in CVD research.
Light deflection angle through velocity profile of galaxies in f(R) model
Authors: Sharma Vipin Kumar , Yadav Bal Krishna , Verma Murli Manohar
Published: February 2021

We explore a new realisation of the galactic scale dynamics via gravitational lensing phenomenon in power-law f(R) gravity theory of the type $$f(R)\propto R^{1+\delta }$$

f

(
R
)

∝

R

1
+
δ

with $$\delta<<1$$

δ
<
<
1

for interpreting the clustered dark matter effects. We utilize the single effective point like potential (Newtonian potential + f(R) background potential) obtained under the weak field limit to study the combined observations of galaxy rotation curve beyond the optical disk size and their lensing profile in f(R) frame work. We calculate the magnitude of light deflection angle with the characteristic length scale (because of Noether symmetry in f(R) theories) appearing in the effective f(R) rotational velocity profile of a typical galaxy with the model parameter $$\delta \approx O(10^{-6})$$

δ
≈
O
(

10

-
6

)

constrained in previous work. For instance, we work with the two nearby controversial galaxies NGC 5533 and NGC 4138 and explore their galactic features by analysing the lensing angle profiles in f(R) background. We also contrast the magnitudes of f(R) lensing angle profiles and the relevant parameters of such galaxies with the generalised pseudo-isothermal galaxy halo model and find consistency.
Connections of unbounded operators and some related topics: von Neumann algebra case
Authors: Hiai Fumio , Kosaki Hideki
Published: February 2021

The Kubo–Ando theory deals with connections for positive bounded operators. On the other hand, in various analysis related to von Neumann algebras, it is impossible to avoid unbounded operators. In this paper, we try to extend a notion of connections to cover various classes of positive unbounded operators (or unbounded objects such as positive forms and weights) appearing naturally in the setting of von Neumann algebras, and we must keep all the expected properties maintained. This generalization is carried out for the following classes: (i) positive [Formula: see text]-measurable operators (affiliated with a semifinite von Neumann algebra equipped with a trace [Formula: see text]), (ii) positive elements in Haagerup’s [Formula: see text]-spaces and (iii) semifinite normal weights on a von Neumann algebra. Investigation on these generalizations requires some analysis (such as certain upper semi-continuity) on decreasing sequences in various classes. Several results in this direction are proved, which may be of independent interest. Ando studied Lebesgue decomposition for positive bounded operators by making use of parallel sums. Here, such decomposition is obtained in the setting of noncommutative (Hilsum) [Formula: see text]-spaces.
Yard Template Generation in a Container Terminal Considering Time Requirement of Vessel Operation
Authors: He Junliang , Jin Zhaowei , Tan Caimao , Wang Yu , Yu Hang
Published: February 2021

In recent years, the bottleneck of yard operation in container terminals has become more and more prominent. For resolving the departure delay problem of vessels, this paper proposes a mixed integer programming model considering the operation time requirements of vessels in a container terminal. It can optimize the yard template plan by reasonably arranging the number of loading clusters of each vessel in the yard, and meanwhile, enhance the efficiency of management in yard and lower the departure delay of vessels. Moreover, a case study is presented to illustrate the proposed model and sensitivity analysis is conducted in the numerical experiments to verify the effectiveness of the proposed model.
Neuro-Fuzzy-Based Frame Pre-Emption Using Time-Sensitive Networking for Industrial Ethernet
Authors: Kannamma R. , Umadevi K. S.
Published: February 2021

IEEE802.1 Time-Sensitive Networking (TSN) makes it conceivable to convey the data traffic of time as well as critical applications using Ethernet shared by different applications having diversified Quality of Service (QoS) requirements for both TSN and non-TSN. TSN assures a guaranteed data delivery with limited latency, low jitter, and amazingly low loss of data for time-critical traffic. By holding networking resources for basic traffic, and applying different queuing and traffic shaping strategies, TSN accomplishes zero congestion loss for basic time-critical traffic. In proposed system, backpropagation algorithm is used to train the training set and fuzzy inference system methodologies such as Mamdani fuzzy inference system which has fuzzy inputs and fuzzy outputs, Sugeno FIS which has fuzzy inputs and a crisp output and adaptive-network-based fuzzy inference system has obtained from the neural network and fuzzy logic. The proposed system uses neuro-fuzzy techniques to handle frame pre-emption and reduces the time taken for decision making. It presents a decision making process using the traffic class.
Effect of chemical stabilization on index and engineering properties of a remoulded expansive soil
Authors: Raju E. Ramanjaneya , Phanikumar B. R. , Heeralal M.
Published: February 2021

This note presents the effect of lime, cement, fly ash and ground granulated blast furnace slag (GGBS) on free swell index (FSI), liquid limit (LL), plasticity index (PI), compaction characteristics, hydraulic conductivity (
k
) and strength characteristics of an expansive soil. The effect of the above chemicals on California bearing ratio (CBR) is also presented. Lime content was 0, 1, 2, 4 and 6% and the amounts of other additives were 0, 5, 10, 15 and 20% by dry weight of the soil. FSI, LL and PI decreased significantly with increasing additive contents. Compaction characteristics also improved with increasing additive contents. Strength characteristics showed improvement at higher additive contents especially at higher curing periods. CBR (determined in soaked condition) also increased significantly with increasing additive contents.
Bridging Software Engineering Research and Industrial Practice
Authors: Marijan Dusica , Zimmermann Thomas , Ham MyungJoo , Selic Bran
Published: February 2021

There is a long-standing challenge to narrow the gap between software engineering research and industrial practice. This gap is reinforced by a number of challenges, including differing timelines, metrics, expectations, and perceptions of these two communities. We believe that these and other related challenges need be analyzed and discussed, to discover synergies and strengthen collaborations between researchers and practitioners in software engineering. In this report, we present insights from the 7th International Workshop on Software Engineering Research and Industrial Practice held virtually at the International Conference on Software Engineering 2020.
Using dramatizations to teach cell signaling enhances learning and improves students’ confidence in the concept
Authors: Halpin Patricia A. , Gopalan Chaya
Published: February 2021

Certain physiology concepts can be difficult for students to understand, and new strategies need to be implemented to teach these concepts. Cell signaling is a core concept in physiology and is presented to undergraduate students starting with their first-year Principles of Biology course. Flipped teaching (FT) combined with dramatizations were used to teach steroid hormone and protein hormone cell signaling in an Animal Physiology course. Student knowledge level improved, as demonstrated by posttest scores compared to pretest scores. Their confidence level in the material improved after the dramatization activities were completed. In conclusion, the combination of FT with dramatizations enhances student learning and confidence level.
Rotational Changes in the Distal Tibial Fragment Relative to the Proximal Tibial Fragment at the Osteotomy Site after Open‐Wedge High‐Tibial Osteotomy
Authors: Sasaki Takahiro , Akamatsu Yasushi , Kobayashi Hideo , Mitsuhashi Shota , Nejima Shuntaro , Kumagai Ken , Saito Tomoyuki , Inaba Yutaka
Published: February 2021

The present study is aimed at assessing the changes in tibial rotation at the osteotomy site after an open‐wedge, high‐tibial osteotomy (OWHTO) and analysing the factors that affect rotational changes in the distal tibial fragment relative to the proximal tibial fragment at the same site. This study involved 53 patients (60 knees; 16 males and 37 females) with medial osteoarthritis (OA) who underwent OWHTO and preoperative and 3‐month postoperative computed tomography (CT) scans. Rotational angles of the distal tibia were measured using Stryker OrthoMap 3D by comparing preoperative and postoperative CTs. The mean rotational angle yielded an external rotation of 2.9° ± 4.8°. There were 17 knees with internal rotations, 37 knees with external rotations, and one knee with no rotation. The rotational angle significantly correlated with the resultant change in the femorotibial angle (correction angle) and the angle between the ascending and transverse osteotomy lines on the anterior osteotomised surface on which a flange was formed with the distal tibial osteotomised surface (flange angle). The flange angle affected the rotation, but it may have been affected by our surgical technique. The rotational angle did not significantly correlate with the change in the angle of the posterior tibial slope or body mass index. There were significant correlations between the rotational angle and correction angle (r = 0.42, p < 0.05). Additionally, the rotational angle correlated with the flange angle (r = −0.41, p < 0.05).
Predicting GPR Signals from Concrete Structures Using Artificial Intelligence‐Based Method
Authors: Zatar Wael , Nguyen Tu T. , Nguyen Hai
Published: February 2021

This paper presents the application of an Artificial Intelligence‐based method in analyzing the effects of environmental conditions, chloride contamination in concrete, and surface corrosion of rebars on the amplitude of Ground Penetrating Radar (GPR) signals. Six reinforced concrete slabs with different chloride contamination mixtures were fabricated and tested. GPR data were collected under various temperature and ambient humidity combinations. A total of 288 rebar picks were used for training, validation, and testing the proposed Artificial Neural Network (ANN) model. Multiple ANN model configurations with a variation in learning algorithms and the number of nodes in the hidden layer were explored to obtain the optimal model for the nondestructive data. It is shown that the “trainlm” learning algorithm produced the high accuracy prediction of the reflection amplitude of GPR signals. The sensitivity analysis was also conducted with the ANN model to investigate the effects of the input on the output parameters. Results from the sensitivity analysis revealed that the GPR reflection amplitudes were more sensitive to the changes of temperature parameter (TEM) and chloride contamination level (CCL), while they were less sensitive to the variation of ambient relative humidity (ARH) and rust condition on the rebar surface (CSR).
Application of Big Data Complexity Analysis Hedging Operation of Derivative Financial Products
Authors: Wu Cheng Chung , Yang Menglin , Yuan Tiantong , Fu Qionghui , Tsai Ya Ju
Published: February 2021

This study is based on the situation of Taiwan listed companies as derivative financial products from 2015 to 2017, analyzing the relationship between the hedging of derivative financial products and characteristics of enterprises and the factors that affect the hedging decision‐making of companies. It is found that even after the announcement of Taiwan’s No. 34 and No. 36 bulletins, there are still some problems that are needed to improve in the disclosure of derivative financial product investment information by Taiwan’s listed companies, at least in the disclosure of the reasons for this conduct which is still insufficient. In this study, two‐stage regression analysis method is applied to empirical analysis, and it is found that hedging activities are related to corporate characteristics, such as expected financial crisis costs, corporate size, equity issues, growth investment opportunities, and information asymmetry. In the investment of derivative financial products, enterprises should evaluate their own financial characteristics as a reference for the risk avoidance decision. At the same time, it is necessary to investigate different natures of hedging tools used in appropriate risk categories, so as to fully achieve the hedging effect and maximize the hedging benefits. This study also found that companies with higher growth investment opportunities, larger size, and higher financial crisis costs will tend to use derivative financial products for hedging. As for the impact of other industries, it is found that the electronic and electrical machinery industries are more active than other industries in hedging behaviors of undertaking derivative financial products’ transaction.
Volatile Profile in Different Aerial Parts of Two Caper Cultivars (Capparis spinosa L.)
Authors: Grimalt Mar , Sánchez-Rodríguez Lucía , Hernández Francisca , Legua Pilar , Carbonell-Barrachina Ángel A. , Almansa María S. , Amorós Asunción
Published: February 2021

This research presents, for the first time, full volatile profiles of four aerial parts of caper plants (Capparis spinosa L.) from southeastern Spain. Volatile compounds in caper leaves and stems (together), flowers, flower buds, and fruits from two cultivars were identified and quantified using headspace-solid phase microextraction (HS-SPME) and gas chromatography with a mass spectrometry detector (GC-MS). Forty-three volatile compounds were identified in the caper shoots, 32 in caper flowers, with only 18, 10, and 6 compounds being found in flower buds, leaves, and fruits, respectively. The predominant compound in all studied materials was methyl isothiocyanate, with nerolidol, trans-2-hexenal, and nonanal playing key roles in flowers, leaves, and flowers buds, respectively. The two studied cultivars had the same volatile compounds but at very different concentrations, although the two studied cultivars are cultivated under the same climatic and agronomic conditions. Additionally, the predominant compounds, especially methyl isothiocyanate (6882 mg·kg−1 fw in flower buds of ORI 3 cultivar), can be separated and concentrated for future applications in food technology.
Three‐Dimensional Visualization Algorithm Simulation of Construction Management Based on GIS and VR Technology
Authors: Xu Shuhong
Published: February 2021

With the development and application of information technology, the digitization of information management and the virtualization of physical models have become very important technical application fields in the world. The establishment of the 3D landscape model and the realization of the 3D geographic information system (GIS) are based on this, and there is not only a wide range of development prospects in many aspects such as urban planning and management, planning and design, local government construction, housing industry development, land monitoring and management, and environmental monitoring and evaluation. There are not only research studies and formulations but also a practical significance in other analysis, evaluation, decision making, and other departments. In recent years, the research of 3D city modeling has been developed rapidly, and most of the existing 2D‐GIS can be transformed into 3D visual landscape. Based on the three‐dimensional geographic information system and desktop drawing software AutoCAD, this paper takes the two‐dimensional line drawing (DLG) of a residential district as the base map, expounds the design process of the three‐dimensional simulation model of the urban community from the aspects of map preprocessing, building simulation model construction, texture mapping, and virtual visualization, and discusses the problems encountered in it. The main contributions of this paper are that this technology puts forward a new solution for the integrated corridor operation and maintenance management, greatly improves the intelligent management level of the integrated corridor operation and maintenance work, and simplifies the complex integrated corridor operation and maintenance management. It is helpful to improve the work efficiency of operation and maintenance, reduce the dependence of personnel, and respond to the long‐term construction needs of the smart city at the same time.
Experimental Study of the Development of Soil Microstructure under the Electroosmosis Dewatering Process
Authors: Liu Yimin , Zheng Lingwei , Rao Shaohua
Published: February 2021

Several laboratory experiments using scanning electron microscopy and mercury intrusion porosimetry were conducted to study the development of soil microstructure during electroosmosis dewatering process. The test results indicate that the moisture content in different treating areas shows remarkable temporal difference; the reasons could be attributed to the distance to the drainage outlets and the treatment duration. On a microscopic level, the affected pore sizes are mainly 0.01–1 and 1–10 μm, and their proportions start to vary when the moisture content reaches the liquid limit. The total volume for pores in anodic soil decreases nearly 50% after the first 20% of total drainage water is exported and is not linearly related to the amount of discharged water. The surface of the soils becomes smoother, and clay particle connection changes from edge‐to‐edge to face‐to‐face. Pores are hard to be observed at the end of the process.
Kinematics Analysis of 6-DoF Articulated Robot with Spherical Wrist
Authors: Asif Seemal , Webb Philip
Published: February 2021

The aim of the paper is to study the kinematics of the manipulator. The articulated robot with a spherical wrist has been used for this purpose. The Comau NM45 Manipulator has been chosen for the kinematic model study. The manipulator contains six revolution joints. Pieper’s approach has been employed to study the kinematics (inverse) of the robot manipulator. Using this approach, the inverse kinematic problem is divided into two small less complex problems. This reduces the time of analysing the manipulator kinematically. The forward and inverse kinematics has been performed, and mathematical solutions are detailed based on D-H (Denavit–Hartenberg) parameters. The kinematics solution has been verified by solving the manipulator’s motion. It has been observed that the model is accurate as the motion trajectory was smoothly followed by the manipulator.
Fenofibrate Ameliorates Hepatic Ischemia/Reperfusion Injury in Mice: Involvements of Apoptosis, Autophagy, and PPAR-α Activation
Authors: Zhang Jie , Cheng Ping , Dai Weiqi , Ji Jie , Wu Liwei , Feng Jiao , Wu Jianye , Yu Qiang , Li Jingjing , Guo Chuanyong
Published: February 2021

Hepatic ischemia and reperfusion injury is characterized by hepatocyte apoptosis, impaired autophagy, and oxidative stress. Fenofibrate, a commonly used antilipidemic drug, has been verified to exert hepatic protective effects in other cells and animal models. The purpose of this study was to identify the function of fenofibrate on mouse hepatic IR injury and discuss the possible mechanisms. A segmental (70%) hepatic warm ischemia model was established in Balb/c mice. Serum and liver tissue samples were collected for detecting pathological changes at 2, 8, and 24 h after reperfusion, while fenofibrate (50 mg/kg, 100 mg/kg) was injected intraperitoneally 1 hour prior to surgery. Compared to the IR group, pretreatment of FF could reduce the inflammatory response and inhibit apoptosis and autophagy. Furthermore, fenofibrate can activate PPAR-α, which is associated with the phosphorylation of AMPK.
The Association of Inflammatory Biomarker of Neutrophil-to-Lymphocyte Ratio with Spontaneous Preterm Delivery: A Systematic Review and Meta-analysis
Authors: Vakili Sina , Torabinavid Parham , Tabrizi Reza , Shojazadeh Alireza , Asadi Nasrin , Hessami Kamran
Published: February 2021

Background. Neutrophil-to-lymphocyte ratio (NLR), as an inflammatory biomarker, has been investigated in several studies for early prediction of preterm delivery. However, their findings seem to be controversial. Thus, this systematic review and meta-analysis was conducted to evaluate the role of NLR in predicting preterm delivery as compared to term controls. Methods. PubMed, Web of Science, Embase, Scopus, and Google Scholar were systematically searched from inception up to December 2020. Interstudy heterogeneity was assessed using Cochrane’sQtest and theI2statistic. The random-effects model was employed to pool the weighted mean differences (WMDs) and the corresponding 95% confidence intervals (CIs). Results. Out of a total of 4369 recodes, fifteen articles including 3327 participants were enrolled. The meta-analysis finding using the random-effects model produced a pooled estimate suggesting a significantly higher NLR (WMD=1.23, 95% CI: 0.40–2.07) in women with preterm delivery (P=0.01). We found significant heterogeneity across the included studies (P<0.001,I2=92.33%). However, interstudy heterogeneity exists mainly due to differences in the definition of preterm delivery (I2=0.0%). In the metaregression analysis, there was no significant effect of publication year (B=−0.288,P=0.088), total sample size (B=−0.002,P=0.276), and the mean age of cases (B=−0.06,P=0.692) on the association between NLR and preterm delivery. Conclusion. The results of this meta-analysis revealed that the NLR value is higher in patients with preterm delivery. The NLR could be a useful biomarker for predicting preterm delivery; however, further prospective case-control studies are required to produce stronger evidence.
[Retracted] Flood Simulation Analysis of the Biliu River Basin Based on the MIKE Model
Authors: Liu Qi , Wang Dianwu , Zhang Yulong , Wang Li
Published: February 2021

The Biliu River is the largest river in Dalian. The occurrence of floods and droughts in this basin has extremely important impacts on local industry, agriculture, and urban development. For a long time, the annual distribution of precipitation in the Biliu River Basin is extremely uneven, the river runoff varies greatly from year to year and season to year, floods and droughts occur frequently, and serious soil erosion results in fragile ecological environment and severe shortage of water resources. In this paper, the spatial and temporal changes of rainfall and runoff in the Biliu River Basin are studied through the coupling of the MIKE 11 model and the MIKE SHE model. The hydrological changes in the Biliu River Basin are simulated. The coupled model is verified by monthly runoff data from 1996 to 2015, and the simulation values are found to be true. The values match well. Based on the cyclical pattern of precipitation and runoff in the Biliu River Basin, the rainfall and runoff data in the Biliu River Basin from 2016 to 2030 are derived. The MIKE SHE/MIKE 11 coupling model is used to predict the Biliu River from 2016 to 2030. The results show that flood disasters are expected to occur in August 2020, July 2025, and July 2030, which can provide a basis for hydrological management in the Biliu River Basin.
Baicalin Improves Cardiac Outcome and Survival by Suppressing Drp1‐Mediated Mitochondrial Fission after Cardiac Arrest‐Induced Myocardial Damage
Authors: Wu Jun , Chen Hui , Qin Jiahong , Chen Nan , Lu Shiqi , Jin Jun , Li Yi
Published: February 2021

Myocardial injury after cardiac arrest (CA) often results in severe myocardial dysfunction and death involving mitochondrial dysfunction. Here, we sought to investigate whether baicalin, a natural flavonoid compound, exerts cardioprotection against CA‐induced injury via regulating mitochondrial dysfunction. We subjected the rats to asphyxia CA after a daily baicalin treatment for 4 weeks. After the return of spontaneous circulation, baicalin treatment significantly improved cardiac function performance, elevated survival rate from 35% to 75%, prevented necrosis and apoptosis in the myocardium, which was accompanied by reduced phosphorylation of Drp1 at serine 616, inhibited Drp1 translocation to the mitochondria and mitochondrial fission, and improved mitochondrial function. In H9c2 cells subjected to simulated ischemia/reperfusion, increased phosphorylation of Drp1 at serine 616 and subsequently enhanced mitochondrial Drp1 translocation as well as mitochondrial fission, augmented cardiomyocyte death, increased reactive oxygen species production, released cytochrome c from mitochondria and injured mitochondrial respiration were efficiently improved by baicalin and Drp1 specific inhibitor with Mdivi‐1. Furthermore, overexpression of Drp1 augmented excessive mitochondrial fission and abolished baicalin‐afforded cardioprotection, indicating that the protective impacts of baicalin are linked to the inhibition of Drp1. Altogether, our findings disclose for the first time that baicalin offers cardioprotection against ischemic myocardial injury after CA by inhibiting Drp1‐mediated mitochondrial fission. Baicalin might be a prospective therapy for the treatment of post‐CA myocardial injury.
Cooperative Targeting of Immunotherapy-Resistant Melanoma and Lung Cancer by an AXL-Targeting Antibody–Drug Conjugate and Immune Checkpoint Blockade
Authors: Boshuizen Julia , Pencheva Nora , Krijgsman Oscar , Altimari Daniela D'Empaire , Castro Patricia Garrido , de Bruijn Beaunelle , Ligtenberg Maarten A. , Gresnigt-Van den Heuvel Elke , Vredevoogd David W. , Song Ji-Ying , Visser Nils , Apriamashvili Georgi , Janmaat Maarten L. , Plantinga Theo S. , Franken Patrick , Houtkamp Mischa , Lingnau Andreas , Jure-Kunkel Maria , Peeper Daniel S.
Published: February 2021

Although immune checkpoint blockade (ICB) has shown remarkable clinical benefit in a subset of patients with melanoma and lung cancer, most patients experience no durable benefit. The receptor tyrosine kinase AXL is commonly implicated in therapy resistance and may serve as a marker for therapy-refractory tumors, for example in melanoma, as we previously demonstrated. Here, we show that enapotamab vedotin (EnaV), an antibody–drug conjugate targeting AXL, effectively targets tumors that display insensitivity to immunotherapy or tumor-specific T cells in several melanoma and lung cancer models. In addition to its direct tumor cell killing activity, EnaV treatment induced an inflammatory response and immunogenic cell death in tumor cells and promoted the induction of a memory-like phenotype in cytotoxic T cells. Combining EnaV with tumor-specific T cells proved superior to either treatment alone in models of melanoma and lung cancer and induced ICB benefit in models otherwise insensitive to anti–PD-1 treatment. Our findings indicate that targeting AXL-expressing, immunotherapy-resistant tumors with EnaV causes an immune-stimulating tumor microenvironment and enhances sensitivity to ICB, warranting further investigation of this treatment combination.

Significance:

These findings show that targeting AXL-positive tumor fractions with an antibody–drug conjugate enhances antitumor immunity in several humanized tumor models of melanoma and lung cancer.
Pan-Cancer Drivers Are Recurrent Transcriptional Regulatory Heterogeneities in Early-Stage Luminal Breast Cancer
Authors: Singh Shambhavi , Sutcliffe Matthew D. , Repich Kathy , Atkins Kristen A. , Harvey Jennifer A. , Janes Kevin A.
Published: February 2021

The heterogeneous composition of solid tumors is known to impact disease progression and response to therapy. Malignant cells coexist in different regulatory states that can be accessed transcriptomically by single-cell RNA sequencing, but these methods have many caveats related to sensitivity, noise, and sample handling. We revised a statistical fluctuation analysis called stochastic profiling to combine with 10-cell RNA sequencing, which was designed for laser-capture microdissection (LCM) and extended here for immuno-LCM. When applied to a cohort of late-onset, early-stage luminal breast cancers, the integrated approach identified thousands of candidate regulatory heterogeneities. Intersecting the candidates from different tumors yielded a relatively stable set of 710 recurrent heterogeneously expressed genes (RHEG), which were significantly variable in >50% of patients. RHEGs were not strongly confounded by dissociation artifacts, cell-cycle oscillations, or driving mutations for breast cancer. Rather, RHEGs were enriched for epithelial-to-mesenchymal transition genes and, unexpectedly, the latest pan-cancer assembly of driver genes across cancer types other than breast. These findings indicate that heterogeneous transcriptional regulation conceivably provides a faster, reversible mechanism for malignant cells to evaluate the effects of potential oncogenes or tumor suppressors on cancer hallmarks.

Significance:

Profiling intratumor heterogeneity of luminal breast carcinoma cells identifies a recurrent set of genes, suggesting sporadic activation of pathways known to drive other types of cancer.

See related articles by Schaff and colleagues, p. 1853 and Sutcliffe and colleagues, p. 1868
RINT1 Regulates SUMOylation and the DNA Damage Response to Preserve Cellular Homeostasis in Pancreatic Cancer
Authors: Arnold Frank , Gout Johann , Wiese Heike , Weissinger Stephanie E. , Roger Elodie , Perkhofer Lukas , Walter Karolin , Scheible Jeanette , Prelli Bozzo Caterina , Lechel André , Ettrich Thomas J. , Azoitei Ninel , Hao Li , Fürstberger Axel , Kaminska Ewa K. , Sparrer Konstantin M.J. , Rasche Volker , Wiese Sebastian , Kestler Hans A. , Möller Peter , Seufferlein Thomas , Frappart Pierre-Olivier , Kleger Alexander
Published: February 2021

Pancreatic ductal adenocarcinoma (PDAC) still presents with a dismal prognosis despite intense research. Better understanding of cellular homeostasis could identify druggable targets to improve therapy. Here we propose RAD50-interacting protein 1 (RINT1) as an essential mediator of cellular homeostasis in PDAC. In a cohort of resected PDAC, low RINT1 protein expression correlated significantly with better survival. Accordingly, RINT1 depletion caused severe growth defects in vitro associated with accumulation of DNA double-strand breaks (DSB), G2 cell cycle arrest, disruption of Golgi–endoplasmic reticulum homeostasis, and cell death. Time-resolved transcriptomics corroborated by quantitative proteome and interactome analyses pointed toward defective SUMOylation after RINT1 loss, impairing nucleocytoplasmic transport and DSB response. Subcutaneous xenografts confirmed tumor response by RINT1 depletion, also resulting in a survival benefit when transferred to an orthotopic model. Primary human PDAC organoids licensed RINT1 relevance for cell viability. Taken together, our data indicate that RINT1 loss affects PDAC cell fate by disturbing SUMOylation pathways. Therefore, a RINT1 interference strategy may represent a new putative therapeutic approach.

Significance:

These findings provide new insights into the aggressive behavior of PDAC, showing that RINT1 directly correlates with survival in patients with PDAC by disturbing the SUMOylation process, a crucial modification in carcinogenesis.
Preexisting Type 2 Diabetes and Survival among Patients with Colorectal Cancer
Authors: Yuan Chen , Zhang Xuehong , Babic Ana , Morales-Oyarvide Vicente , Zhang Yin , Smith-Warner Stephanie A. , Wu Kana , Wang Molin , Wolpin Brian M. , Meyerhardt Jeffrey A. , Chan Andrew T. , Hu Frank B. , Fuchs Charles S. , Ogino Shuji , Giovannucci Edward L. , Ng Kimmie
Published: February 2021

Background:

Type 2 diabetes increases risk of developing colorectal cancer, but the association of preexisting diabetes with colorectal cancer survival remains unclear.

Methods:

We analyzed survival by diabetes status at cancer diagnosis among 4,038 patients with colorectal cancer from two prospective U.S. cohorts. Cox proportional hazards regression was used to calculate HRs and 95% confidence intervals (CI) for overall and cause-specific mortality, with adjustment for tumor characteristics and lifestyle factors.

Results:

In the first 5 years after colorectal cancer diagnosis, diabetes was associated with a modest increase in overall mortality in women (HR, 1.22; 95% CI, 1.00–1.49), but not in men (HR, 0.83; 95% CI, 0.62–1.12; P heterogeneity by sex = 0.04). Beyond 5 years, diabetes was associated with substantially increased overall mortality with no evidence of sex heterogeneity; in women and men combined, the HRs were 1.45 (95% CI, 1.09–1.93) during >5–10 years and 2.58 (95% CI, 1.91–3.50) during >10 years. Compared with those without diabetes, patients with colorectal cancer and diabetes had increased mortality from other malignancies (HR, 1.78; 95% CI, 1.18–2.67) and cardiovascular disease (HR, 1.93; 95% CI, 1.29–2.91). Only women with diabetes for more than 10 years had increased mortality from colorectal cancer (HR, 1.33; 95% CI, 1.01–1.76).

Conclusions:

Among patients with colorectal cancer, preexisting diabetes was associated with increased risk of long-term mortality, particularly from other malignancies and cardiovascular disease.

Impact:

Our findings highlight the importance of cardioprotection and cancer prevention to colorectal cancer survivors with diabetes.
Sufficient 25-Hydroxyvitamin D Levels 2 Years after Colorectal Cancer Diagnosis are Associated with a Lower Risk of All-cause Mortality
Authors: Wesselink Evertine , Kok Dieuwertje E. , de Wilt Johannes H.W. , Bours Martijn J.L. , van Zutphen Moniek , Keulen Eric T.P. , Kruyt Flip M. , Breukink Stephanie O. , Kouwenhoven Ewout A. , van den Ouweland Jody , Weijenberg Matty P. , Kampman Ellen , van Duijnhoven Fränzel J.B.
Published: February 2021

Background:

Whether changes in 25 hydroxy vitamin D3 (25(OH)D3) levels after colorectal cancer diagnosis influence clinical outcomes is unclear. We investigated the association of trajectories of 25(OH)D3 levels with recurrence and all-cause mortality.

Methods:

In total, 679 patients were included in our data analyses. Trajectories of 25(OH)D3 levels were defined on the basis of vitamin D status at diagnosis, at 6 months, and 2 years after diagnosis. Observed trajectories of 25(OH)D3 levels were consistent deficient levels (20%), consistent sufficient levels (39%), increasing levels (20%), and a temporary drop in levels (13%). Associations of trajectories of 25(OH)D3 with recurrence and all-cause mortality were assessed using multivariable Cox proportional hazards regression models.

Results:

During a follow-up time of 2.2 years for recurrence and 3.5 years for all-cause mortality, 31 and 65 events occurred, respectively. No statistically significant associations were observed for vitamin D trajectories and the risk of recurrence. Patients who were consistently sufficient compared with patients who were consistently deficient had a lower risk of all-cause mortality [HR 0.39; 95% confidence interval (CI), 0.21–0.73]. The risk of all-cause mortality seems lower in patients with increasing levels or a temporary drop in levels (HR 0.54; 95% CI, 0.27–1.10 and HR 0.40 95% CI, 0.17–0.93) relative to patients with consistent deficient levels.

Conclusions:

Patients with colorectal cancer following a trajectory characterized by sufficient levels of 25(OH)D3 2 years after diagnosis all appeared to have a lower risk of all-cause mortality compared with patients having consistent deficient levels.

Impact:

Further studies should investigate how trajectories of 25(OH)D3 levels are associated with colorectal cancer recurrence.
Abstract IA017: Molecular classification and stratification: Diving deeper
Authors: McAlpine Jessica N.
Published: February 2021

As we move forward with integration of molecular classification into clinical care the assessment of additional clinicopathological and molecular features in the context of molecular subtype will enable us to further refine prognosis. In addition, molecular classification can enable stratification of clinical cohorts that have been often thought of as homogeneous but are clearly more diverse than recognized. These last few years have produced an abundance of literature supporting not only the value of consistent categorization and prognostic value but also predictive implications enabling action/change in practice. Molecular classification-driven care in endometrial cancer will reduce variation in practice with improved knowledge translation critical to implementation and uptake.

Citation Format: Jessica N. McAlpine. Molecular classification and stratification: Diving deeper [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr IA017.