bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracing Mechanism of Sports Competition Pressure Based on Backpropagation Neural Network
Authors: Zhao Huayu , Liu Shaonan
Published: February 2021

Through the overall situation of athletes’ competition pressure, the pressure level of participating athletes can be understood and revealed. Analyzing the sources of stress and influencing factors of athletes can find measures to relieve and reduce stress and provide theoretical reference for the regulation of athletes’ competition pressure. Based on genetic algorithm and neural network theory, this paper proposes a method of tracing the sports competition pressure based on genetic algorithm backpropagation (BP) neural network to solve the problem that traditional neural network learning algorithm is slow and easy to fall into local minimum. There is no significant difference between male and female athletes in the level of competition pressure. Athletes have the same training methods and the same goals, and the competition pressure tends to be the same, with no obvious difference; athletes with different educational backgrounds have no significant differences in training, academics, sports injuries, interpersonal relationships, social expectations, and evaluations. Due to the particularity of the stage, the competition pressure of fourth‐year undergraduate and third‐year masters is significantly higher than that of other grades. The number of athletes participating in college table tennis tournaments has very significant differences in competition dimensions. There is significant difference in training and self‐expectation dimension difference. The competition pressure of athletes who participated in the college table tennis championship for the first time was significantly higher than that of athletes who participated repeatedly. There were significant differences between athletes before and after adapting to the venue. Before adapting to the venue, the competition pressure of athletes is generally greater. After adapting to the venue, the competition pressure of athletes has been relieved.
Spatiotemporal Rainfall Distribution of Soan River Basin, Pothwar Region, Pakistan
Authors: Hussain Fiaz , Nabi Ghulam , Wu Ray-Shyan
Published: February 2021

This study evaluates the spatiotemporal rainfall variability over the semimountainous Soan River Basin (SRB) of sub-Himalayan Pothwar region, Pakistan. The temporal rainfall trend analysis of sixteen rain gauges was performed on annual basis with long-term (1981–2016) data. The results depicted that there is substantial year-to-year and season-to-season variability in rainfall patterns, and rainfall patterns are generally erratic in nature. The results highlight that most of the highland rainfall stations showed decreasing trends on annual basis. The central and lowland stations of the study area recorded an increasing trend of rainfall except for Talagang station. The average annual rainfall of the study area ranges between 492 mm and 1710 mm in lowland and high-altitude areas, respectively. Of the whole year’s rainfall, about 70 to 75% fall during the monsoon season. The rainfall spatial distribution maps obtained using the inverse distance weighting (IDW) method, through the GIS software, revealed the major rainfall range within the study area. There is a lack of water during postmonsoon months (November–February) and great differences in rainfall amounts between the mountainous areas and the lowlands. There is a need for the rational management of mountainous areas using mini and check dams to increase water production and stream regulation for lowland areas water availability. The spatiotemporal rainfall variability is crucial for better water resource management schemes in the study area of Pothwar region, Pakistan.
Monitoring, Analyzing, and Modeling for Single Subsidence Basin in Coal Mining Areas Based on SAR Interferometry with L-Band Data
Authors: Wang Zhiyong , Zhang Jingzhao , Yu Yaran , Liu Jian , Liu Wei , Jiang Na , Guo Donge
Published: February 2021

Excessive exploitation of underground mine resources has caused serious land subsidence in China. This paper focused on monitoring and modeling the single subsidence basin in coal mining area based on SAR interferometry (InSAR). The optimum InSAR processing strategy to monitor the mining subsidence was built to obtain the land subsidence with large deformation. And a method of three-dimensional mathematical modeling of single subsidence basin based on InSAR measurements was presented. Using Jining Coalfield (China) as the study area, we acquired 7 L-band PALSAR images from January 2008 to February 2010 to monitor the land subsidence in Jining Coalfield. The deformation maps in Jining Coalfield in different periods were obtained. Taking the Geting Coal Mine within the Jining coalfield as an example, we finely analyzed and interpreted the deformation maps. Compared with the simultaneous filed measurements, the precision of deformation measurement using D-InSAR in mining area was analyzed. The root mean square error was 1.37 cm. The method of fine interpretation and analysis for a single subsidence basin was established. The experiments have proved that InSAR technique with L-band InSAR data is suitable for monitoring mining subsidence with large deformation. And the 3D mathematical modeling method could be used for the single subsidence basin in coal mining area.
Thermal Behaviour Analysis and Cost‐Saving Opportunities of PCM‐Integrated Terracotta Brick Buildings
Authors: Chelliah A. , Saboor Shaik , Ghosh Aritra , Kontoleon Karolos J.
Published: February 2021

Buildings contribute greatly to global energy use and consumption. The energy consumption of buildings is significant due to the integration of heating, ventilation, and cooling systems. Evidently, the utilization of phase change materials (PCMs) in building design can adequately reduce air‐conditioning costs of buildings by diminishing external heat gains and losses. Moreover, the adoption of natural, eco‐friendly, and cost‐effective materials, such as terracotta bricks, can be valuable from an environmental point of view. This paper intends to assess the air‐conditioning cost‐saving potential of several PCM stuffed terracotta brick configurations. In that respect, the encapsulated PCMs were filled in the hollows of terracotta bricks. For the aims of this study, five different types of PCMs were considered, in relation to the thermophysical properties of their solid and liquid state (OM18: organic mixture, HS22: hydrated salt, OM29, OM32, and OM37). In addition, three PCM‐stuffed terracotta brick configurations were examined with reference to the number of the PCM layers (PCMTB‐A with one PCM layer, PCMTB‐B with two PCM layers, and PCMTB‐C with three PCM layers). Therefore, fifteen PCM‐stuffed terracotta brick configurations were analysed numerically, related to environmental conditions that refer to two different scenarios in India (hot dry and composite climates). Results have unveiled that the OM32 PCM assemblies have shown better thermoeconomic performance compared to the other types of PCM. With respect to the most advantageous number of PCM layers, the evidence of this analysis has exposed that the PCMTB‐C case has shown the highest annual air‐conditioning cost‐savings and the highest yearly carbon emission mitigations in both climates (Ahmedabad and Lucknow). In hot‐dry climates, the PCMTB‐C with OM32 PCM exhibited the highest annual air‐conditioning cost‐saving ($ 74.7), the highest annual carbon emission mitigation (1.43 ton/kWh), and the moderate payback period (22.5 years) compared to the other cases. To conclude, the findings of this study suggest a suitable way to improve the decision‐making process of building design, while bridging the performance gap in terms of energy efficiency and sustainability.
Preliminary Testing to Determine the Best Process Parameters for Polymer Laser Sintering of a New Polypropylene Polymeric Material
Authors: Mwania Fredrick M. , Maringa Maina , van der Walt Jakobus. G.
Published: February 2021

Polymer laser sintering is an elaborate additive manufacturing technique because it is subject to process parameters and material properties. In this regard, each polymeric material necessitates a different set of process conditions. To this end, testing was done to determine the most suitable process parameters for a new commercially available polymer (Laser PP CP 60), from Diamond Plastics GmbH. It was established that the material requires slightly different settings from those provided by the supplier for the values for the removal chamber temperature, building chamber temperatures, and laser power to achieve the best mechanical properties (ultimate tensile strength). The preliminary testing indicates that the process parameters that yielded the best mechanical properties for the laser PP CP 60 powder were 125°C, 125°C, 0.15 mm, 250 μm, 4500 mm/s, 34.7 W, 1500 mm/s, and 21.3 W for the removal chamber temperature, building chamber temperature layer thickness, hatch distance, scanning speed fill, laser power fill, scanning speed contour, and laser power contour, respectively.
Dynamic Response and Robustness Evaluation of Cable‐Supported Arch Bridges Subjected to Cable Breaking
Authors: Shao Guotao , Jin Hui , Jiang Ruinian , Xu Yue
Published: February 2021

Cable‐supported arch bridges have had many cable break accidents, which led to dramatic deck damage and even progressive collapse. To investigate the dynamic response and robustness of cable‐supported arch bridges subjected to cable breaking, numerical simulation methods were developed, compared, and analyzed, and an effective and accurate simulation method was presented. Then, the cable fracture of a prototype bridge was simulated, and the dynamic response of the cable system, deck, and arch rib was illustrated. Finally, the robustness evaluation indexes of the cable system, deck, and arch rib were constructed, and their robustness was evaluated. The results show that the dynamic response of the adjacent cables is proportional to the length of the broken cable, while the dynamic response of the deck is inversely proportional to the length of the broken cable. The dynamic amplification factor of the cable tension and deck displacement is within 2.0, while that of the arch rib bending moment exceeds 2.0. The break of a single cable will not trigger progressive collapse. When subjected to cable breaking, the deck system has the least robustness. The proposed cable break simulation procedure and the robustness evaluation method are applicable to both existing and new cable‐supported bridges.
Fail-Stop Group Signature Scheme
Authors: Chen Jonathan Jen-Rong , Chiang Yi-Yuan , Hsu Wang-Hsin , Lin Wen-Yen
Published: February 2021

In this study, a fail-stop group signature scheme (FSGSS) that combines the features of group and fail-stop signatures to enhance the security level of the original group signature is proposed. Assuming that FSGSS encounters an attack by a hacker armed with a supercomputer, this scheme can prove that the digital signature is forged. Based on the aforementioned objectives, this study proposes three lemmas and proves that they are indeed feasible. First, how does a recipient of a digitally signed document verify the authenticity of the signature? Second, when a digitally signed document is under dispute, how can the group’s manager determine the identity of the original group member who signed the document, if necessary, for an investigation? Third, how can one prove that the signature is indeed forged following an external attack from a supercomputer? Following an attack, the signature could be proved to be forged without exposing the key. In addition, the ultimate goal of the group fail-stop signature scheme is to stop using the same key immediately after the discovery of a forgery attack; this would prevent the attack from being repeated.
Finite Element Analysis of Fluid Flow through the Screen Embedded between Parallel Plates with High Reynolds Numbers
Authors: Memon Abid A. , Alotaibi Hammad , Memon M. Asif , Bhatti Kaleemullah , Shaikh Gul M. , Khan Ilyas , Mousa A. A.
Published: February 2021

This paper provides numerical estimation of Newtonian fluid flow past through rectangular channel fixed with screen movable from 10° to 45° by increasing the Reynolds number from 1000 to 10,000. The two-dimensional incompressible Navier Stokes equations are worked out making use of the popular software COMSOL MultiPhysics version 5.4 which implements the Galerkin’s least square scheme to discretize the governing set of equations into algebraic form. In addition, the screen boundary condition with resistance coefficient (2.2) along with resistance coefficient 0.78 is implemented along with slip boundary conditions applied on the wall. We engaged to find and observe the relationship between the optimum velocity, drag force applied by the screen, and pressure occurred in the channel with increasing Reynolds number. Because of the linear relationship between the optimum velocities and the Reynolds number, applying the linear regression method, we will estimate the linear equation so that future prediction and judgment can be done. The validity of results is doing with the asymptomatic solution for stream-wise velocity at the outlet of the channel with screens available in the literature. A nondimensional quantity, i.e., ratio from local to global Reynolds number

Re

x

/
Re

, is introduced which found stable and varies from -0.5 to 0.5 for the whole problem. Thus, we are in the position to express the general pattern of the velocity of the particles as well as the pressure on the line passing through the middle of the channel and depart some final conclusion at the end.
Innovative Marketing Framework for Enterprises Using Edge-Enabled Data Analysis
Authors: Wang Guangming , Wang Yifeng
Published: February 2021

An effective marketing strategy has become a challenging task with the development of the social economy for the reform and innovation of many domestic and foreign enterprises. The idea of edge computing is also gaining prominence and is broadly recognized. Edge-enabled solutions provide computing, analysis, storage, and control nearer to the edge of the network. The existing literature highlights the concepts of social media marketing and evaluates the advantages of social media for communication between individuals and companies. However, there is a lack of an effective marketing strategy for enterprises. This article proposes an innovative marketing framework for enterprises using data analysis and wireless networks. The proposed framework is composed of two different modules. Initially, a corporate innovation and marketing framework module is established through edge computing to carry out a wireless transmission of relevant data and information at the edges of the network. Later, the enterprise marketing resource optimization module is constructed based on the particle swarm algorithm. The proposed framework performs efficient calculation and storage using a resource optimization module. The feasibility and effectiveness of the proposed framework are verified using the analysis of the actual case test results. This proposed framework can effectively improve the innovation efficiency level of existing enterprises and the optimization of marketing management resources.
An Injectable Fibrin Scaffold Rich in Growth Factors for Skin Repair
Authors: Shao Zhengwei , Lyu Chengqi , Teng Lin , Xie Xuetao , Sun Jiayue , Zou Derong , Lu Jiayu
Published: February 2021

Platelet aggregates, such as PRP, PRF, and CGF, have been used alone or in combination with other grafting materials to enhance restoration outcomes. The process for preparing these autografting materials requires two‐step centrifugation or specific centrifuges. In this study, we obtained an injectable fibrin scaffold (IFS) rich in growth factors by one‐step centrifugation of whole blood from rabbits. The purpose of this study is to introduce some characteristics of IFS. This scaffold was characterized using various techniques, including Masson’s trichrome staining, scanning electron microscopy, porosity measurements, and cell counting. The sustained release of growth factors, including PDGF, VEGF, TGF‐β1, IGF, FGF, and EGF, was quantified using ELISA assay. The obtained IFS was tested for its effects on cell proliferation, extracellular matrix deposition, and full‐thickness skin defect repair. The prepared IFS is characterized by a loose fibrin network structure with white blood cells and platelets that slowly release growth factors and can promote the healing of skin defects via the promotion of cell proliferation, collagen deposition, and tissue revascularization. In addition, its liquid properties and porous structure are conducive to its application as a therapeutic component in tissue engineering.
A Novel Approach Based on Sine Trigonometric Picture Fuzzy Aggregation Operators and Their Application in Decision Support System
Authors: Abdullah Saleem , Khan Saifullah , Qiyas Muhammad , Chinram Ronnason
Published: February 2021

Picture fuzzy sets (PFSs) are one of the fundamental concepts for addressing uncertainties in decision problems, and they can address more uncertainties compared to the existing structures of fuzzy sets; thus, their implementation was more substantial. The well-known sine trigonometric function maintains the periodicity and symmetry of the origin in nature and thus satisfies the expectations of the decision-maker over the multiple parameters. Taking this feature and the significances of the PFSs into consideration, the main objective of the article is to describe some reliable sine trigonometric laws

STLs

for PFSs. Associated with these laws, we develop new average and geometric aggregation operators to aggregate the picture fuzzy numbers. Also, we characterized the desirable properties of the proposed operators. Then, we presented a group decision-making strategy to address the multiple attribute group decision-making (MAGDM) problem using the developed aggregation operators and demonstrated this with a practical example. To show the superiority and the validity of the proposed aggregation operations, we compared them with the existing methods and concluded from the comparison and sensitivity analysis that our proposed technique is more effective and reliable.
Investigations into the Rock Dynamic Response under Blasting Load by an Improved DDA Approach
Authors: Xie Biting , Zhang Xiuli , Wang Hao , Jiao Yuyong , Zheng Fei
Published: February 2021

Evaluation of blasting‐induced rock damage and fragmentation is very important for safety control of construction in the jointed rock mass. The discontinuous numerical models are commonly applied due to the advantages in modeling fragmentation and treating discontinuities. In this paper, the rock fracturing algorithm and rate dependent strength law are incorporated into the discontinuous deformation analysis (DDA) to study the wave propagation and rock fragmentation phenomena in dynamic problems. By reproducing Hopkinson pressure bar tests under different loading rates, the improved method is validated to be capable of solving dynamic failure problem. Finally, taking the Xiucun tunnel as an example, its failure process under the action of the explosive wave is simulated, and some failure features are captured. In addition, the explosion wave propagation and its induced particle vibration in surrounding rock are studied. The reasonable simulation results indicate that the modified DDA method can effectively model the stress wave propagation and joint growth process in the jointed rock under blasting load.
Effect of Locally Delivered Melatonin as an Adjunct to Nonsurgical Therapy on GCF Antioxidant Capacity and MMP-9 in Stage II Periodontitis Patients: A Randomized Controlled Clinical Trial
Authors: Ahmed Enji , Shaker Olfat G. , Yussif Nermin , Ghalwash Dalia M.
Published: February 2021

Objectives. Periodontitis is characterized by inflammatory destruction of periodontal tissue, loss of attachment, and bone resorption. The increase in reactive oxygen species (ROS) is responsible for the oxidative damage occurring in periodontal tissues. Melatonin has important immunomodulatory, anti-inflammatory, and powerful antioxidant functions. The current study was carried out to evaluate the effect of topical melatonin gel as an adjunct to nonsurgical periodontal therapy. Methods. This split-mouth randomized controlled clinical trial was performed on 24 patients with grade II periodontitis. Two sites in each patient were randomly assigned; test sites were treated by nonsurgical therapy followed by intrapocket application of 5% melatonin gel. Control sites were treated by nonsurgical therapy followed by intrapocket application of placebo gel. Both the melatonin and placebo gel were applied weekly once for four weeks. Assessment of clinical parameters (PD and CAL) was done at baseline and 3 months after therapy. Total antioxidative capacity (TAC) and matrix metalloproteinase-9 (MMP-9) levels in GCF were also evaluated utilizing commercially available enzyme-linked immunosorbent assay kits (ELISA) at baseline and 3 months after therapy. Results. Treatment with topical melatonin was associated with a reduction in periodontal inflammation reflected as an improvement in the clinical periodontal parameters. Melatonin-treated sites showed a more statistically significant percent reduction in PD and more statistically significant percent gain in CAL than the control site. Additionally, a significant increase in TAC and a significant decrease in MMP-9 levels in GCF were found in melatonin-treated sites in comparison to control sites. Conclusions. The adjunctive use of topical melatonin gel with nonsurgical periodontal therapy has potent anti-inflammatory and antioxidant activity in the treatment of grade II periodontitis patients.
Multielement Analysis of Pakchoi (Brassica rapa L. ssp. chinensis) by ICP-MS and Their Classification according to Different Small Geographical Origins
Authors: Nguyen-Quang Trung , Do-Hoang Giang , Truong-Ngoc Minh
Published: February 2021

Statistical interpretation of the concentrations of 42 elements, determined using solution-based inductively coupled plasma mass spectrometry (ICP-MS) analysis and multivariate statistical methods, such as principal components analysis (PCA), was used to establish the provenance of pakchoi (Brassica rapa L. ssp. chinensis) from 6 areas in Ha Noi, Vietnam. Although pakchoi is widely cultivated and manufactured, no universal method is used to discriminate the origin of this vegetable. Our study introduced for the first time a method to classify pakchoi in small geographical areas. 42 metallic elements of pakchoi were detected by ICP-MS, which were further analyzed using multivariate statistical analysis to perform clusters based on the geographical locations. Eleven elements, i.e., 28Si; 56Fe; 59Co; 63Cu; 69Ga; 75As; 85Rb; 93Nb; 107Ag; 118Sn, and 137Ba, were identified as discriminators to distinguish pakchoi from those areas. Results from this study presented a new method to discriminant the geographical origins of pakchoi, which could apply to other types of vegetables on the food market.
A Study on the Application of Two Different Material Constitutive Models Used in the FE Simulation of the Cyclic Plastic Behavior of a Steel Beam‐Column T‐Stub Connection
Authors: Wang Wei , Zhang Chenchen , Li Zeshen , Gan Xuehong
Published: February 2021

Seismic actions inevitably cause cyclic plastic deformations in steel frame connections, which is a common cause of failure in steel structures. Nonlinear finite element (FE) static analysis has been employed in the study of the cyclic plastic behavior of a T‐stub connection based on the reported cyclic test on the corresponding extensively tested T‐stub connection made of Q235 steel. In particular, the isotropic‐hardening and Chaboche constitutive models were employed to predict both the stress distribution and plastic development on the T‐stub and the hysteretic curves of the entire T‐stub connection. The two constitutive models were calibrated by four material tests to describe the yield and hardening behaviors of the Q235 steel used to make this T‐stub connection. The two sets of simulation results obtained from the simulations of the two FE models employed by the two different constitutive models were compared with each other and with the experimental results. The comparisons reveal that the simulation results are similar and in good agreement with the experimental results when the cumulative plastic deformation in the T‐stub is small. However, the results of the FE analysis using the Chaboche model are in better agreement with the experimental results when the cumulative deformation in the T‐sub is large. This study can provide a reference for FE simulation of the cyclic plastic behavior of steel connections, including the T‐stub connection.
The Diagnostic Value of Serum PIVKA-II Alone or in Combination with AFP in Chinese Hepatocellular Carcinoma Patients
Authors: Xu Fei , Zhang Lulu , He Wenting , Song Di , Ji Xiaomeng , Shao Jianyong
Published: February 2021

Background. At present, the diagnostic accuracy of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is insufficient. It remains controversial whether prothrombin induced by vitamin K absence II (PIVKA-II) has a better diagnostic value than AFP for HCC patients. Objective. To investigate the diagnostic role of PIVKA-II alone or in combination with AFP in Chinese HCC patients. Methods. Serum AFP and PIVKA-II levels were detected and analyzed in 308 HCC afflicted patients and 120 unafflicted controls. The receiver operator curve (ROC) and area under the curve (AUC) were conducted to evaluate the clinical value of AFP and PIVKA-II for diagnosing HCC and early HCC. Results. In the whole HCC cohort, the diagnostic values of PIVKA-II were better than that of AFP. The AUC of PIVKA-II and AFP was 0.90 (95% CI 0.87-0.94) and 0.79 (95% CI 0.74-0.84), respectively. “AFP + PIVKA-II” yielded a high sensitivity of 95.1% and a specificity of 83.3%, with the AUC 0.89 (95% CI 0.85-0.93). In the early stage HCC group, the diagnostic accuracy of PIVKA-II was also better than that of AFP. The AUC of PIVKA-II and AFP was 0.83 (95% CI 0.77-0.89) and 0.75 (95% CI 0.68-0.81), respectively. “AFP + PIVKA-II” achieved the sensitivity of 83.3% and specificity of 89.1%, with an AUC of 0.86 (95% CI 0.81-0.91). Moreover, for AFP-negative HCC patients, serum PIVKA-II showed good diagnostic performance, with an AUC of 0.804 (95% CI 0.720-0.887). Besides, elevated PIVKA-II level was a strong independent risk factor for HCC patients with portal vein tumor thrombus (PVTT) (

OR
=
4.890

,

P
=
0.020

). Conclusion. PIVKA-II is superior to AFP in HCC screening, and AFP in combination with PIVKA-II significantly improves the diagnostic value for Chinese HCC patients. PIVKA-II could effectively indicate HCC accompanied by PVTT and help to optimize the therapeutic strategy.
Output Feedback Recursive Dynamic Surface Control with Antiwindup Compensation
Authors: Sun Guofa , Du Hui , Wang Gang , Yu Hanbo
Published: February 2021

Actuator saturation phenomenon often exists in the actual control system, which could destroy the closed‐loop performance of the system and even lead to unstable behavior. Our main contribution is to provide an antiwindup recursive dynamic surface control (RDSC) for a discrete‐time system with an unknown state and actuator saturation. The fuzzy compensator is added to perform as an active disturbance rejection term in the feedforward path to avoid windup caused by input saturation. To construct output feedback control, the system is transformed into the form of pure‐feedback and an improved HOSM observer is designed to carry out future output prediction. Based on which RDSC is synthesized, only one fuzzy logic system (FLS) is used and the controller singularity is completely avoided. In addition, the simulation and numeral examples using a continuous stirred tank reactors (CSTRs) system with actuator saturation are provided and the results show that the strategy owns good robustness and effectively compensates for the disturbance caused by actuator saturation in the presence of a discrete‐time system with an unmeasurable state.
Surgical Selection of Unstable Intertrochanteric Fractures: PFNA Combined with or without Cerclage Cable
Authors: Huang Chaoqing , Wu Xing
Published: February 2021

Due to the instability of unstable intertrochanteric fractures, the selection of a suitable internal fixation has always been a challenge for orthopedic surgeons. This study is aimed at comparing the clinical efficacy of PFNA combined with cerclage cable and without cerclage cable and finally recommend a stable internal fixation method to provide the basis for clinical therapy. From January 2014 to January 2018, we retrospectively analyzed all cases of unstable intertrochanteric fractures who received treatment in the Orthopedics Department of our hospital and finally screened 120 cases, 51 of whom were treated with cerclage cable, 69 without cerclage cable. The follow‐up period was one year. HHS, BI, and RUSH scores were given within the specified time. We divided the patients into the PFNA+cable (PFNA combined with cerclage cable) group and the PFNA group. The time of fracture healing and weight‐bearing in the PFNA+cable group was shorter than that in the PFNA group. With regard to HHS, BI, and RUSH, the PFNA+cable group was higher than the PFNA group at 1 month, 3 months, 6 months, and 12 months after operation. For HHS rating, the PFNA+cable group has a higher excellent rate than the PFNA group, which was 96.1% and 84.1%, respectively. All the results mentioned above were statistically significant. Compared with the group without cerclage cable, the application of cerclage cable can reduce the incidence of complications. From the comparison between the two groups, it can be seen that the surgical method of PFNA combined with cerclage cable can not only help to improve the stability of fracture reduction, shorten the time of fracture healing and postoperative weight‐bearing, and significantly improve patients’ self‐care ability but also reduce the incidence of postoperative complications. Therefore, we think PFNA combined with cerclage cable is a good choice.
Varied Age of First Presentation of Sickle Cell Disease: Case Presentations and Review
Authors: Claeys Alexis , Van Steijn Susanne , Van Kesteren Lydia , Damen Elizabet , Van Den Akker Machiel
Published: February 2021

Sickle cell disease is a multisystem condition characterized by hemolytic anemia and vasoocclusion. Not only are the symptoms of the first presentation but also the ages of presentation are very variable. Following three case reports, different causes of possible late presentation are discussed. Many factors are responsible for the age at which sickle cell disease is diagnosed: doctor’s delay (unfamiliarity with the disease), patient’s delay (education and financial position of the parents, cultural factors), high- versus low-resource country (availability of newborn screening), fetal hemoglobin, reticulocyte count, and genetic modulators, such as SCD genotype, alpha-thalassemia, fetal hemoglobin concentration, and G6PD deficiency. The individual course of sickle cell disease depends on (epi) genetic and environmental properties and the underlying interactions. In further studies, the role of each factor should be evaluated more deeply, and its use as a marker of disease severity or activity should be assessed.
A Chimeric GM-CSF/IL18 Receptor to Sustain CAR T-cell Function
Authors: Lange Shannon , Sand Laurens G.L. , Bell Matthew , Patil Sagar L. , Langfitt Deanna , Gottschalk Stephen
Published: February 2021

The inability of chimeric antigen receptor (CAR) T cells to sustain their effector function after repeated exposure to tumor cells is a major obstacle to their success in patients with solid tumors. To overcome this limitation, we designed a novel chimeric cytokine receptor to create an autocrine loop that links activation-dependent GM-CSF production by CAR T cells to IL18 receptor signaling (GM18). Expression of GM18 in CAR T cells enhanced their effector function in an antigen- and activation-dependent manner. In repeat stimulation assays, which mimic chronic antigen exposure, CAR.GM18 T cells had a significantly greater ability to expand and produce cytokines in comparison with their unmodified counterparts targeting EPHA2 or HER2. In vivo, CAR.GM18 T cells induced tumor regression at cell doses at which standard CAR T cells were ineffective in two solid tumor xenograft models. Thus, our study highlights the potential of hijacking cytokines that are physiologically secreted by T cells to bolster their antitumor activity.

Significance:

We designed a chimeric cytokine receptor (GM18) that links CAR T-cell activation to MYD88 signaling. GM18 endows CAR T cells with sustained effector function in the setting of chronic antigen exposure, resulting in potent antitumor activity in preclinical solid tumor models.

This article is highlighted in the In This Issue feature, p. 1601
Mutations in the RAS/MAPK Pathway Drive Replication Repair–Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition
Authors: Campbell Brittany B. , Galati Melissa A. , Stone Simone C. , Riemenschneider Alexandra N. , Edwards Melissa , Sudhaman Sumedha , Siddaway Robert , Komosa Martin , Nunes Nuno M. , Nobre Liana , Morrissy A. Sorana , Zatzman Matthew , Zapotocky Michal , Joksimovic Lazar , Kalimuthu Sangeetha N. , Samuel David , Mason Gary , Bouffet Eric , Morgenstern Daniel A. , Aronson Melyssa , Durno Carol , Malkin David , Maris John M. , Taylor Michael D. , Shlien Adam , Pugh Trevor J. , Ohashi Pamela S. , Hawkins Cynthia E. , Tabori Uri
Published: February 2021

The RAS/MAPK pathway is an emerging targeted pathway across a spectrum of both adult and pediatric cancers. Typically, this is associated with a single, well-characterized point mutation in an oncogene. Hypermutant tumors that harbor many somatic mutations may obscure the interpretation of such targetable genomic events. We find that replication repair–deficient (RRD) cancers, which are universally hypermutant and affect children born with RRD cancer predisposition, are enriched for RAS/MAPK mutations (P = 10−8). These mutations are not random, exist in subclones, and increase in allelic frequency over time. The RAS/MAPK pathway is activated both transcriptionally and at the protein level in patient-derived RRD tumors, and these tumors responded to MEK inhibition in vitro and in vivo. Treatment of patients with RAS/MAPK hypermutant gliomas reveals durable responses to MEK inhibition. Our observations suggest that hypermutant tumors may be addicted to oncogenic pathways, resulting in favorable response to targeted therapies.

Significance:

Tumors harboring a single RAS/MAPK driver mutation are targeted individually for therapeutic purposes. We find that in RRD hypermutant cancers, mutations in the RAS/MAPK pathway are enriched, highly expressed, and result in sensitivity to MEK inhibitors. Targeting an oncogenic pathway may provide therapeutic options for these hypermutant polyclonal cancers.

This article is highlighted in the In This Issue feature, p. 1307
Nongenetic Evolution Drives Lung Adenocarcinoma Spatial Heterogeneity and Progression
Authors: Tavernari Daniele , Battistello Elena , Dheilly Elie , Petruzzella Aaron S. , Mina Marco , Sordet-Dessimoz Jessica , Peters Solange , Krueger Thorsten , Gfeller David , Riggi Nicolo , Oricchio Elisa , Letovanec Igor , Ciriello Giovanni
Published: February 2021

Cancer evolution determines molecular and morphologic intratumor heterogeneity and challenges the design of effective treatments. In lung adenocarcinoma, disease progression and prognosis are associated with the appearance of morphologically diverse tumor regions, termed histologic patterns. However, the link between molecular and histologic features remains elusive. Here, we generated multiomics and spatially resolved molecular profiles of histologic patterns from primary lung adenocarcinoma, which we integrated with molecular data from >2,000 patients. The transition from indolent to aggressive patterns was not driven by genetic alterations but by epigenetic and transcriptional reprogramming reshaping cancer cell identity. A signature quantifying this transition was an independent predictor of patient prognosis in multiple human cohorts. Within individual tumors, highly multiplexed protein spatial profiling revealed coexistence of immune desert, inflamed, and excluded regions, which matched histologic pattern composition. Our results provide a detailed molecular map of lung adenocarcinoma intratumor spatial heterogeneity, tracing nongenetic routes of cancer evolution.

Significance:

Lung adenocarcinomas are classified based on histologic pattern prevalence. However, individual tumors exhibit multiple patterns with unknown molecular features. We characterized nongenetic mechanisms underlying intratumor patterns and molecular markers predicting patient prognosis. Intratumor patterns determined diverse immune microenvironments, warranting their study in the context of current immunotherapies.

This article is highlighted in the In This Issue feature, p. 1307
An Inflammatory Reaction to Stored Fascia Lata 37 Years Postimplantation
Authors: Esmail Kaisra , Jordan David Ronald , Brownstein Seymour , Tang Tina , Burns Bruce
Published: February 2021

We report a rare case of a suspected inflammatory reaction to stored fascia lata 37 years post-placement. Clinical, imaging, histopathological, and immunohistochemical findings are presented, with a literature review on reactions to stored fascia lata. A 39-year-old woman had upper eyelid congenital ptosis repaired successfully at 2 years with bilateral frontalis suspension procedures using stored fascia lata. Thirty-seven years later, the patient presented with swelling of her eyelids and forehead, which was tender to the touch, in the same pattern as the fascia lata slings placed earlier. Histopathological examination disclosed a non-necrotizing granulomatous inflammatory infiltrate with numerous asteroid bodies. Initially, it was responsive to oral prednisone, but with recurrent inflammation, long-term methotrexate was required to control the inflammation. To our knowledge, this type of delayed inflammatory reaction has not been previously reported. It raises a concern about the use of allogeneic donor tissue and accepted sterilization techniques that may not be 100% effective in deactivating all components of the donor graft, including potential infectious pathogens, leading to a subsequent latent reaction.
Efficacy and Safety of Long-Term Corticosteroid Monotherapy in 26 Cases of Nephrotic Syndrome with Biopsy-Proven Membranous Nephropathy Induced by Seronegative Hepatitis B Virus-Associated Glomerulonephritis
Authors: Zhang Yan , Chen Sha , Yang Dingping , Liu Junyun , Zhang Xiaoxiao , Yang Xueyan , Han Hongling , Yang Dingwei
Published: February 2021

Background: Hepatitis B virus-associated glomerulonephritis (HBV-GN) can occur in patients with negative HBV serological antigens. Little is known about the treatment of seronegative HBV-GN (sn HBV-GN). The aim of this prospective study was to evaluate the efficacy and safety of corticosteroids in the treatment of sn HBV-GN. Methods: Twenty-six patients with nephrotic syndrome induced by seronegative HBV-associated membranous nephropathy were enrolled. The patients were given methylprednisolone (0.8 mg/kg/day) for 12–24 weeks, tapered by a 2-mg reduction every 1–3 months. Patients were followed up for 6–36 months. Complete remission (CR) was defined as proteinuria <0.3 g/24 h. Partial remission (PR) was defined as proteinuria of 0.3–3.5 g/24 h that was reduced ≥50% of the baseline level. Results: The effective remission (including CR and PR) rates of nephrotic syndrome were 23.1%, 61.5%, 73.1%, 76.2%, 90.5%, and 81.0%, respectively, after 1, 3, 6, 12, 24, and 36 months. Nineteen patients achieved effective remission after 11.68 ± 7.15 months. The level of serum albumin improved from 24.34 ± 6.71 g/L at baseline to 39.61 ± 7.45 g/L at the 36th month significantly. After treatment, the level of serum Cr was similar to the baseline. Only 2 patients relapsed. The primary adverse reaction was infection. None of the patients showed evidence of HBV replication. Conclusion: The long-term middle-dose corticosteroid therapy without antiviral drugs is effective and safe for membranous sn HBV-GN patients. For sn HBV-GN patients, the monitoring of HBV DNA and HBV markers in the serum is necessary during the corticosteroid monotherapy. Trial Registration: The Chinese Clinical Trial Registry (ChiCTR1900022518).
Tuberculin Skin Testing versus Interferon-Gamma Release Assay among Users of a Public Health Unit in Northeast Portugal
Authors: Afonso Andrea Luísa Fernandes , Pires Bruno Miguel Morais , Teixeira Cristina Martins , Nogueira António José
Published: February 2021

The screening of groups with a high risk for developing tuberculosis (TB) is a priority in order to control this disease. Since there is no gold standard for the diagnosis of latent TB infection (LTBI), both the tuberculin skin test (TST) and the interferon-gamma release assays (IGRA) have been used for this purpose. The aim of this study was to determine the proportion of LTBI by using the TST and the IGRA tests, and to assess the risk factors related with discordant results between tests across several risk groups advised for screening in Northeast Portugal. Data were collected from the database of patients with suspected LTBI and advised for the screening in a public health unit (January 2014 to December 2015). The proportion of LTBI was computed using both tests. Logistic regression models assessed risk factors for a positive test and for discordant results between tests. The adjusted odds ratio (OR) and respective 95% confidence interval (95% CI) were obtained. Out of 367 patients included in the analysis, 79.8% had a positive TST and 46.0% of them had a positive IGRA. In comparison with contacts of active TB cases, healthcare workers and inmates presented higher odds of TST positivity (OR 4.38, 95% CI 1.59–12.09 and OR 4.74, 95% CI 1.45–15.49, respectively), but immunocompromised people presented lower odds of TST positivity (OR 0.14; 95% CI 0.06–0.31). Instead, healthcare workers (OR 0.44, 95% CI 0.24–0.80) and immunocompromised people (OR 0.24, 95% CI 0.10–0.56) presented lower odds of a positive IGRA. There were 42.0% concordant positive results, 16.1% concordant negative results, and 41.9% discordant results, with healthcare workers presenting higher odds of discordant results (OR 3.34, 95% CI 1.84–6.05). The proportion of LTBI estimated by TST and IGRA among people advised for screening in our setting is high, highlighting the need of preventive strategies. Among healthcare workers, TST results should be read with caution as the higher proportion of discordant results with a positive TST suggests the impact of the booster reaction in this group.
Pharmacogenomics of the Efficacy and Safety of Colchicine in COLCOT
Authors: Dubé Marie-Pierre , Legault Marc-André , Lemaçon Audrey , Lemieux Perreault Louis-Philippe , Fouodjio René , Waters David D. , Kouz Simon , Pinto Fausto J. , Maggioni Aldo P. , Diaz Rafael , Berry Colin , Koenig Wolfgang , Lopez-Sendon Jose , Gamra Habib , Kiwan Ghassan S. , Asselin Géraldine , Provost Sylvie , Barhdadi Amina , Sun Maxine , Cossette Mariève , Blondeau Lucie , Mongrain Ian , Dubois Anick , Rhainds David , Bouabdallaoui Nadia , Samuel Michelle , de Denus Simon , L’Allier Philippe L. , Guertin Marie-Claude , Roubille François , Tardif Jean-Claude
Published: February 2021

Background:

The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine.

Methods:

There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study’s primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients’ DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients.

Results:

None of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52–2.35],
P
=7.41×10
−9
) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82–3.47];
P
=2.70×10
−8
), an intronic variant in gene
SEPHS1
. The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant.

Conclusions:

We found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.
Targeted Undersmoothing: Sensitivity Analysis for Sparse Estimators
Authors: Hansen Christian , Kozbur Damian , Misra Sanjog
Published: February 2021

This paper proposes a procedure for assessing the sensitivity of inferential conclusions for functionals of sparse high-dimensional models following model selection. The proposed procedure is called targeted undersmoothing. Functionals considered include dense functionals that may depend on many or all elements of the high-dimensional parameter vector. The sensitivity analysis is based on systematic enlargements of an initially selected model. By varying the enlargements, one can conduct sensitivity analysis about the strength of empirical conclusions to model selection mistakes. We illustrate the procedure's performance through simulation experiments and two empirical examples.
Countervailing Market Power and Hospital Competition
Authors: Barrette Eric , Gowrisankaran Gautam , Town Robert
Published: February 2021

While economic theories indicate that market power by downstream firms can potentially counteract market power upstream, antitrust policy is opaque as to whether to incorporate countervailing market power in merger analyses. We use detailed national claims data from the health care sector to evaluate whether countervailing insurer power does indeed limit hospitals' exercise of market power. We estimate willingness-to-pay models to evaluate hospital market power across analysis areas. We find that countervailing market power is important: a typical hospital merger would raise hospital prices 4.3% at the 25th percentile of insurer concentration but only 0.97% at the 75th percentile of insurer concentration.
Does Market Interaction Erode Moral Values?
Authors: Bartling Björn , Fehr Ernst , Özdemir Yagiz
Published: February 2021

The widespread use of markets leads to unprecedented material well-being in many societies. We study whether market interaction, as a side effect, erodes moral values. In an influential paper, Falk and Szech (2013) provide experimental data that seem to suggest that “market interaction erodes moral values.” Although we replicate their main treatment effect, we show that additional treatments are necessary to corroborate their conclusion. These treatments reveal that playing repeatedly, and not market interaction, causes the erosion of moral values. Our paper thus shows that neither Falk and Szech's data nor our data support the claim that markets erode morals.