bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplemental Material: Petrology and geochronology of Cretaceous–Eocene plutonic rocks in northeastern Washington, USA: Crustal thickening, slab rollback, and origin of the Challis episode
Authors: Tepper Jeffrey H. , et al.
Published: April 2023

Supplemental File S1: Sample locations and elemental and isotopic data. Supplemental File S2: U-Pb ranked age plots and concordia diagrams. Supplemental File S3: U-Pb method details and all individual point analyses. 
Supplemental Material: Petrology and geochronology of Cretaceous–Eocene plutonic rocks in northeastern Washington, USA: Crustal thickening, slab rollback, and origin of the Challis episode
Authors: Tepper Jeffrey H. , et al.
Published: April 2023

Supplemental File S1: All sample locations, elemental and isotopic data. Supplemental File S2: U-Pb ranked age plots and concordia diagrams. Supplemental File S3: U-Pb method details and all individual point analyses.
Supplemental Material: Initiation of Mesoarchean nascent subduction zone in the North China Craton
Authors: Yao Jiachen , Wang Wei , et al.
Published: April 2023

Supplemental Texts S1–S3 (analytical methods and additional discussions), Supplemental Figures S1–S8, and Supplemental Tables S1–S9 are included.
Supplemental Material: Progressive fracturing in alluvial clasts
Authors: Shaanan Uri , et al.
Published: April 2023

Table S1. Fracture number density measurements (XLS spreadsheet). Figure S1. Fracture strike data (PDF). Supplemental Data S1. Roughness analyses (data—3-D scans as referenced images).
Supplemental Material: Age and origin of Early Cretaceous magmatism in the southernmost Omineca belt, northern U.S. Cordillera
Authors: Gaschnig Richard M. , et al.
Published: April 2023

Supplemental Text S1: Kaniksu batholith geochronology results, with sample by sample descriptions. Figure S1: Tera-Wasserburg diagrams (left panels) and associated weighted mean plots (right panels) showing U-Pb zircon results for the Kaniksu peraluminous suite. Error ellipses and bars represent internal two standard errors. Figure S2: Tera-Wasserburg diagrams (left panels) and associated weighted mean plots (right panels) showing U-Pb zircon results for the Kaniksu metaluminous suite. Figure S3: Tera Wasserburg diagrams (left panels) and associated weighted mean plots (right panels) showing U-Pb zircon results for the Kaniksu alkalic suite. Table S1: Zircon U-Pb data. Table S2: Zircon Hf isotope data.
Supplemental Material: Roles and perspectives of A- and I-type magmas in rare earth element and gold mineralization
Authors: Qiu Kun-Feng , Deng Jun , et al.
Published: April 2023

Table S1: Compilation of new and previously published whole-rock geochemical data for igneous complexes within the Luxi and Jiaobei terranes. Table S2: Compilation of new and previously published zircon Lu-Hf data for igneous complexes within the Luxi and Jiaobei terranes. Table S3: Compilation of previously published zircon O isotopic data for igneous complexes within the Luxi and Jiaobei terranes. Table S4: Compilation of previously published whole-rock Sr-Nd isotopic data for igneous complexes within the Luxi and Jiaobei terranes.
Amyloid transthyretin cardiac amyloidosis with different manifestations, test findings and types
Authors: Budweg Jeffery , Al-Ani Mohammad , Assaf Yazan , Parker Alex , Aranda Juan
Published: April 2023

Amyloid transthyretin amyloidosis usually presents with cardiac amyloidosis manifestations, most commonly with a heart failure syndrome. The history and physical examination offer clues of other cardiac and extracardiac manifestations. Taking a detailed history is essential in elucidating pertinent family and medical history that may increase suspicion for amyloidosis. Further, certain findings on electrocardiogram and imaging should raise suspicion and trigger further workup that can confirm the diagnosis, since treatment is evolving.
Actuation behavior of PNIPAM-based bilayer hydrogel regulated by polyvinyl alcohol polymer film
Authors: Li Jiaxin , Wang Ruofei , Ruan Diqing , Wu Huaping , Cheng Lin , Liu Aiping
Published: April 2023

Responsive hydrogels based on Poly(N-isopropylacrylamide) (PNIPAM) are known to exhibit distinctive thermosensitive properties. However, isotropic PNIPAM hydrogels with weak mechanical properties and low deformation rates tend to exhibit only regular volume expansion/contraction, which limits them to promising applications such as intelligent actuators. In order to prepare programmable hydrogel actuators with satisfactory mechanical properties and fast deformation capability, a polyvinyl alcohol/PNIPAM (PVA/PNIPAM) bilayer hydrogel with anisotropic structure is proposed by combining preprepared PVA polymer film with outstanding mechanical properties as the passive layer and thermosensitive PNIPAM hydrogel as the active layer, forming a semi-interpenetrating network structure at the interface via the hydrogen-bond interaction between PNIPAM and PVA. The microstructures, mechanical properties and actuation behaviors of bilayer hydrogel were studied by scanning electron microscope, Fourier transform infrared spectrograph, mechanical testing machine and actuation test device. Results show that the introduction of PVA can improve the tensile stress of the bilayer hydrogel from 23.6 kPa to 62.6 kPa, and favor the hydrogel actuator excellent actuation preformation with a maximum bending amplitude of 500° and a maximum bending velocity of 13°/s within first 40 s. The bilayer hydrogel is further designed to work as a fluidic system valve that can recognize various temperature solutions and control solution flow rate. This design provides a simple and practical strategy to construct responsive hydrogels with anisotropic structure for further development in the field of intelligent actuators and flexible microfluidic systems.
Testing the Predictive Power of Hydro-Economic Supply-Side Input–Output Models Under Different Water Availability and Economic Conditions Over Time in a Transboundary River Basin
Authors: Eamen Leila , Brouwer Roy , Razavi Saman
Published: April 2023

Although the temporal transferability of input–output (IO) models has been examined before, no study has investigated the impacts of changing water availability conditions over time, e.g., due to climate change, on the predictive power of water-inclusive IO models. To address this gap, we investigate the performance of inter-regional supply-side input–output (ISIO) models that incorporate precipitation and water intake under varying climates over time in a transboundary water management context. Using the Saskatchewan River Basin in Western Canada as a case study, we develop four ISIO models based on available economic and hydrological data from years with different climatic conditions, i.e., two dry and two wet years. Accounting for price changes over these years, our findings indicate that the joint impact of changes in water availability and economic structural changes on economic output can be considerable. The results furthermore show that each model performs particularly well in predicting the economic output for similar climatic years. The models remain reliable in predicting economic outputs over several years as long as changes in water availability are within the range observed in the water-inclusive base year ISIO model.
Evaluation of the Impact of Groundwater Management Policies Under Climate and Economic Changes in Tunisia
Authors: Soula Rania , Chebil Ali , Majdoub Rajouene , Crespo Daniel , Albiac José , Kahil Taher
Published: April 2023

This study develops a hydro-economic model for the coastal aquifer Mahdia Ksour Essef in Tunisia in order to analyze how external shocks (climate change, energy price increase) and management policies can affect groundwater sustainability during the coming decades. Twenty-one scenarios covering three management policies (free market, partial cooperation, and full cooperation policy) under various potential climate and economic changes are evaluated. The results of scenario simulations show the potential impact of energy soaring prices and climate change on the aquifer’s water table level, groundwater extractions, cropland areas, and farmers’ benefits under each policy option in the future. They also show that the best scenario to address the effects of climate change would need to take into account environmental externalities and efficient energy prices. The findings of this study are very important in the context of climate change and uncertain global energy markets and provide feasible alternatives to preserve the regional economy and aquifer sustainability.
Cross-Country Study of Institutionalizing Social Participation in Health Policymaking: A Realist Analysis
Authors: Rahbari Bonab Maryam , Majdzadeh Reza , Rajabi Fatemeh
Published: April 2023

Strong evidence suggests that interventions based on community participation have a positive effect on a range of health outcomes in different settings. Community participation contributes significantly to the promotion of health at the local level, especially among the more disadvantaged groups of the society. The main goal of social participation mechanisms is to fill the gap between the views of the policymakers and the experiences and needs of the communities. An important point is that institutionalization of social participation in the development of health policies and its continuity over time are essential requirements. The question here is how participation should be institutionalized in the systems that have started this process. We conducted a realistic evaluation of a multicase study of public participation in health system policymaking. Countries including France, Chile, Iran, Thailand, and Tunisia were selected. The study objective was to determine interventions and mechanisms used by these countries for community participation in health policymaking and institutionalizing it. The data were extracted via a literature review for each country using a realistic approach analysis also known as context, intervention, mechanism, and outcome (CIMO) configurations. Thailand and France, which have applied a set of interventions such as supportive legislations, evidence production structures for informed decision making and interactions, accountability and transparency, and providing a context for development of civil society organizations, have succeeded in institutionalizing community participation in health policymaking. Iran, Tunisia, and Chile have been successful in this regard, but they are still far from institutionalizing community participation. Success in the institutionalization of participatory health governance requires a political will and commitment at the highest level in order to minimize the conflicts between economic and political interests of different stakeholders and to implement a set of interventions to maximize social participation in health policymaking.
“I Am Afraid of Positioning my Baby in Prone”: Beliefs and Knowledge about Tummy Time Practice
Authors: e Silva Bianca Fernandes Vasconcelos , Sampaio Sabrinne Suelen Santos , Moura Julia Raffin , de Medeiros Cléa Emanuela Barreto , de Lima-Alvarez Carolina Daniel , Simão Camila Rocha , Azevedo Ingrid Guerra , Pereira Silvana Alves
Published: April 2023

Objective. To identify beliefs and knowledge about tummy time (TT) practice and its repercussions on motor development. Methods. Longitudinal study carried out with parents/caregivers of infants older than 30 days of life. Two assessments were performed. A structured interview was conducted, while the babies were between one and six months old to identify beliefs, knowledge about TT, and the motor milestone achievement expected for the age. At six to 12 months, the risk of motor development delay was tracked using the survey of well-being of young infant questionnaire (SWYC). Results. 41 families responded to the SWYC questionnaire (21 were allocated to the TT group). 31.70% reported that it was not important to put the infants in a prone position while awake, and 70.70% said they are afraid their babies would become breathless when positioned in a prone position. 85.70% of infants from the TT group showed typical development, while 55% of the control group showed atypical development for their age (

p
=
0.01

). Only three infants from the control group were at risk of delayed motor development (

p
=
0.10

). Conclusions. Most of the families feel insecure about proning their babies and fear breathlessness when positioned. Acquisition of motor milestones prevailed in the TT group, suggesting an association between TT practice and motor milestone achievement.
Smart E‐Health System for Heart Disease Detection Using Artificial Intelligence and Internet of Things Integrated Next‐Generation Sensor Networks
Authors: Shafiq Muhammad , Du Changqing , Jamal Nasir , Abro Junaid Hussain , Kamal Tahir , Afsar Salman , Mia Md. Solaiman
Published: April 2023

According to the World Health Organization, heart disease is the biggest cause of death worldwide. It may be possible to bring down the overall death rate of individuals if cardiovascular disease can be detected in its earlier stages. If the cardiac disease is detected at an earlier stage, there is a greater possibility that it may be successfully treated and managed under the guidance of a physician. Recent advances in areas such as the Internet of Things, cloud storage, and machine learning have given rise to renewed optimism over the capacity of technology to bring about a paradigm change on a global scale. At the bedside, the use of sensors to capture vital signs has grown increasingly commonplace in recent years. Patients are manually monitored using a monitor located at the patient’s bedside; there is no automatic data processing taking place. These results, which came from an investigation of cardiovascular disease carried out across a large number of hospitals, have been used in the development of a protocol for the early, automated, and intelligent identification of heart disorders. The PASCAL data set is prepared by collecting data from different hospitals using the digital stethoscope. This data set is publicly available, and it is used by many researchers around the world in experimental work. The proposed strategy for doing research includes three steps. The first stage is known as the data collection phase, the data is collected using biosensors and IoT devices through wireless sensor networks. In the second step, all of the information pertaining to healthcare is uploaded to the cloud so that it may be analyzed. The last step in the process is training the model using data taken from already‐existing medical records. Deep learning strategies are used in order to classify the sound that is produced by the heart. The deep CNN algorithm is used for sound feature extraction and classification. The PASCAL data set is essential to the functioning of the experimental environment. The deep CNN model is performing most accurately.
A Comparative Study on Electrical Resistivity and Compressive Strength Properties of Cement Composites Incorporating Conductive Materials
Authors: Park Jong-Gun , Seo Dong-Ju , Lim Doo-Yeol , Lee Yu-Jae , Heo Gwang-Hee
Published: April 2023

Conductive cement composites have attracted high attention in recent years due to the possibility of achieving multifunctional materials. The usual approach has been to incorporate steel fiber, carbon fiber, graphite, and carbon nanotube/or carbon nanofiber into the cement matrix. In this article, an experimental comparative study was conducted on the electrical resistivity and compressive strength properties of cement composites incorporating carbon fiber (CF) and steel fiber (SF), which are conductive materials. The electrical resistivity of the conductive fiber-reinforced cement composites (FRCCs) was measured using the four-probe method, and compressive strength was conducted based on the KS L ISO 679 and ASTMC109/C109M test methods. Their performance was compared and analyzed with plain cement composites (PCCs). Afterwards, the fracture surfaces of the conductive SFRCCs (steel fiber-reinforced cement composites) and CFRCCs (carbon fiber-reinforced cement composites) were also analyzed using a scanning electron microscope (SEM). The experimental results showed that, in all specimens, the electrical resistivity gradually increased as the curing ages elapsed, while the electrical resistivity decreased significantly as the fiber volume fractions increased. Overall, the addition of SF up to a fiber volume fraction of 1.25% did not significantly affect the electrical resistivity of cement composites. In contrast, however, the electrical resistivity of CF decreased slightly even at a low dosage (i.e., 0.1–0.3%), and thereafter, it was significantly decreased. The percolation threshold of the conductive CFRCC incorporating CF used in this experiment was 0.4%, and this seemed to be the optimal CF dosage that can greatly improve the conductive cement composites while maintaining the maximum performance of compressive strength. In addition, the compressive strength of conductive SFRCC was higher than that of PCC, whereas in the case of conductive CFRCC, it showed a greater tendency to decrease significantly as the fiber volume fractions increased. We expect the results of SEM image analysis to be useful as basic data for establishing microstructure mechanisms of reinforcement fibers in the cement matrix.
Soil Organic Matter Inversion Based on Imaging Spectral Data in Straw‐Covered Noncultivated Land
Authors: Lu WeiYi , Du Huishi , Chen YuHan
Published: April 2023

The rapid inversion of soil organic matter is of great significance for agricultural soil testing and fertilization in order to protect and utilize land resources effectively. This study selected the developmental base in Lishu County with typical characteristics of China’s black soil as its research area. This study established a 600 nm “bow curvature difference” spectral index and the partial least squares regression model, and the accuracy of their results was compared. The correlation between the 600 nm “bow curvature” spectral index and the soil organic matter of straw cover no‐tillage is analyzed. The average soil organic matter content in the study area was 16.67 g·kg-1, and the organic matter increased significantly from NT‐0 to NT‐100 by 16.26 g·kg-1. The study provided a deep insight to improve the quantitative inversion methods to estimate soil organic matter.
Plasma Levels of Matrix Metalloproteinases 2 and 9 in Patients with Chronic Chagas Heart Disease and Systemic Arterial Hypertension: Correlation with TGF-Beta Plasma Levels
Authors: Bestetti Reinaldo B. , Dellalibera-Joviliano Renata , Rizzi Ellen , Bonacio Giselle F. , Faria-Jr Milton , Furlan-Daniel Rosemeire , Castro-França Suzeley
Published: April 2023

Background. Chronic Chagas heart disease (CCHD) and systemic arterial hypertension (SAH) frequently coexists in areas where Chagas disease is endemic. The effects of the association of both conditions (CCHD-SAH) on the extracellular matrix (ECM) remodeling are unknown. Matrix metalloproteinases (MMP) 2 and 9 are involved in ECM remodeling. The aim of this study was to evaluate MMP 2 and MMP9 in CCHD-SAH patients and to correlate their levels with those of the profibrogenic cytokine TGF-beta. Methods. We included 19 patients with CCHD-SAH, 14 patients with CCHD alone, and 19 controls matched by sex and age. MMP-2 and MMP-9 plasma levels were studied by gel zymography and showed as optical densities (OD). TGF-beta plasma levels were measured by double-ligand ELISA and expressed as pg/mL. Results. Median (5th, 95th) MMP-2 plasma levels were 1224.7 OD (1160, 1433.5) in patients with CCHD alone, 1424.1 OD (1267.5, 1561) in patients with CCHD-SAH, and 940 OD (898.1, 1000.8) in controls (

p
=
0.001

). MMP-9 plasma levels were 1870 OD (1740, 1904.1) in patients with CCHD alone, 1754.6 OD (1650, 2049) in those with CCHD-SAH and 89.7 OD (80, 96) in controls (

p
=
0.0003

). MMP-9 plasma levels were higher than those of MMP 2 in patients with CCHD-SAH (

p
=
0.01

). No correlation was found between TGF-beta plasma levels with MMP-2 serum levels (r = 0.12;

p
=
0.7

), but a moderate negative correlation (r = −0.46;

p
=
0.048

) was observed between TGF-beta and MMP-9 plasma levels. Conclusions. MMP-2 and especially MMP-9 may play a role in the ECM remodeling process in patients with CCHD-SAH. TGF-Beta may counteract the MMP effect on the ECM remodeling process in patients with CCHD-SAH.
Analysis on Network Information Security Protection Technology of Intelligent Terminal Power Monitoring System of Substation under the Support of Multimodal Multimedia Information
Authors: Jiang Yakun , Wang Binquan
Published: April 2023

According to the perspective of multimode multimedia data, the protection technology of network information security is mainly discussed. The theoretical basic research is outlined, its meaning, level, reasons, and consequences are expounded, and the future research content and development trend are discussed. With the rapid development of online services and mobile technology, the world has entered the era of multimedia big data. There have been a large number of scientific studies in the multimedia industry, which explain the various fields of big data, including the capture, storage, reference, excavation, and search of multimedia big data. The article expounds the specific concept of power monitoring system network information security, establishes the safety regulations of electric power monitoring system, formulates the corresponding ideas for the safety guarantee level of electric power monitoring system, and promotes the long-term development of China’s electric power enterprises. The safe operation of the power monitoring system is directly related to the stable operation of all power supply systems and even the social economy. At this stage, the situation of network security management in China’s power monitoring system is still not optimistic. We take the multimode multimedia data, organize the research dynamics of the network security protection technology, and discuss the future research trend.
SLA Aware Task-Scheduling Algorithm in Cloud Computing Using Whale Optimization Algorithm
Authors: Mangalampalli Sudheer , Swain Sangram Keshari , Karri Ganesh Reddy , Mishra Satyasis
Published: April 2023

Task scheduling in Cloud Computing paradigm poses new challenges for cloud provider as heterogeneous, diversified tasks arrived on to cloud console. To schedule these type of tasks efficiently on to virtual resources in cloud paradigm, an effective scheduler is needed, which precisely maps tasks to virtual machines by considering priorities of both tasks and VMs. Existing scheduling algorithms failed to map tasks precisely to virtual resources due to high dynamic nature in cloud environment which leads to increase of makespan and SLA violations will be increased. In this paper, authors proposed a task-scheduling mechanism, which considers task priorities and VMs. To model this scheduling paradigm we have chosen whale optimization through which our scheduler will take decisions for scheduling tasks precisely onto virtual resources in cloud environment. Entire simulation was carried out on CloudSim. Initially we have chosen random generated workload to run simulation and after that, we have considered a real-time workload named as BigDataBench and ran our simulation. Finally, we compared our proposed work with classical baseline mechanisms. From simulations we observed that proposed whale scheduler improved makespan for PSO, ACO, GA, and W-schedulers by 20.07%, 17.55%, 19.9%, and 6.35%, respectively, and 17.3%, 17.86%, 17.64%, and 5.93%, respectively, for BigDataBench workloads. SLA violations improved over PSO, ACO, GA, and W-Scheduler by 56.76%, 42.17%, 35.29%, and 24.53%, respectively, and 63.42%, 23.33%, 55.51%, and 40.1%, respectively, for BigDataBench workloads. From extensive simulation results, our proposed scheduler using whale optimization approach minimizes makespan and SLA violations to a great extent.
Adhesion of Nano-ZnO Modified Asphalt and Its Influence on Moisture-Sensitive Properties of Mixtures
Authors: Chen Xiaoming , Wen Ping , Ji Qibin , Jiang Shujiang , Zhou Zhimin , Wang Aipeng , Li Lingyun , Guan Bowen
Published: April 2023

This study investigates the effect of nano-ZnO on modified asphalt’s adhesion characteristics by preparing various mixtures with 0%, 1%, 2%, and 3% nano-ZnO contents. Within the study context, the adhesion characteristics of asphalt mixtures with different nano-ZnO to limestone, basalt, and granite contents are studied using a boiling test. The surface-free energy (SFE) parameters of four asphalt and three aggregate types are evaluated using a theoretical approach and then verified by performing pull-off tests, and the adhesion work between different asphalt and aggregates is calculated. In addition, the effect of nano-ZnO on moisture-sensitive properties of the asphalt mixture is assessed using a freeze-thaw split test and semicircle bending (SCB) test. The study results have shown that nano-ZnO can enhance adhesion characteristics of the asphalt. The surface energy of modified asphalt with high ZnO content is relatively larger, and the adhesion between asphalt and limestone is better than the basalt and granite. The aggregates’ chemical composition and the SFE’s parameters significantly affect the adhesion between asphalt and aggregates. Furthermore, the correlation between the surface-free energy theory and the pull-off test results is better than the boiling test ones. Nano-ZnO enhances the asphalt mixture’s moisture sensitivity before and after freeze-thaw cycles and impacts the initial state’s tensile strength and cracks resistance, especially after freeze-thaw cycles where the improvement is obvious.
Supplementary Table S4 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas
Authors: Stinson Jordan A. , Sheen Allison , Momin Noor , Hampel Jordan , Bernstein Rebecca , Kamerer Rebecca , Fadl-Alla Bahaa , Samuelson Jonathan , Fink Elizabeth , Fan Timothy M. , Wittrup K. Dane
Published: April 2023

Soft tissue sarcoma subtype classifications
Supplementary Table S3 from Randomized Trial of Tepotinib Plus Gefitinib Versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis
Authors: Liam Chong Kin , Ahmad Azura Rozila , Hsia Te-Chun , Zhou Jianying , Kim Dong-Wan , Soo Ross Andrew , Cheng Ying , Lu Shun , Shin Sang Won , Yang James Chih-Hsin , Zhang Yiping , Zhao Jun , Berghoff Karin , Bruns Rolf , Johne Andreas , Wu Yi-Long
Published: April 2023

Demographic data in the patient subgroup with MET overexpression
Supplementary Table S3 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas
Authors: Stinson Jordan A. , Sheen Allison , Momin Noor , Hampel Jordan , Bernstein Rebecca , Kamerer Rebecca , Fadl-Alla Bahaa , Samuelson Jonathan , Fink Elizabeth , Fan Timothy M. , Wittrup K. Dane
Published: April 2023

Soft tissue sarcoma canine patient information
Supplementary Table S1 from Randomized Trial of Tepotinib Plus Gefitinib Versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis
Authors: Liam Chong Kin , Ahmad Azura Rozila , Hsia Te-Chun , Zhou Jianying , Kim Dong-Wan , Soo Ross Andrew , Cheng Ying , Lu Shun , Shin Sang Won , Yang James Chih-Hsin , Zhang Yiping , Zhao Jun , Berghoff Karin , Bruns Rolf , Johne Andreas , Wu Yi-Long
Published: April 2023

Demographic data of all individuals enrolled
Supplementary Table S1 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas
Authors: Stinson Jordan A. , Sheen Allison , Momin Noor , Hampel Jordan , Bernstein Rebecca , Kamerer Rebecca , Fadl-Alla Bahaa , Samuelson Jonathan , Fink Elizabeth , Fan Timothy M. , Wittrup K. Dane
Published: April 2023

Protein sequences of canine cytokine fusion proteins
Supplementary Methods S1 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas
Authors: Stinson Jordan A. , Sheen Allison , Momin Noor , Hampel Jordan , Bernstein Rebecca , Kamerer Rebecca , Fadl-Alla Bahaa , Samuelson Jonathan , Fink Elizabeth , Fan Timothy M. , Wittrup K. Dane
Published: April 2023

Supplementary Methods S1
Supplementary Figure S7 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas
Authors: Stinson Jordan A. , Sheen Allison , Momin Noor , Hampel Jordan , Bernstein Rebecca , Kamerer Rebecca , Fadl-Alla Bahaa , Samuelson Jonathan , Fink Elizabeth , Fan Timothy M. , Wittrup K. Dane
Published: April 2023

Pathway scores from mouse Nanostring nSolver analysis
Supplementary Figure S3 from Randomized Trial of Tepotinib Plus Gefitinib Versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis
Authors: Liam Chong Kin , Ahmad Azura Rozila , Hsia Te-Chun , Zhou Jianying , Kim Dong-Wan , Soo Ross Andrew , Cheng Ying , Lu Shun , Shin Sang Won , Yang James Chih-Hsin , Zhang Yiping , Zhao Jun , Berghoff Karin , Bruns Rolf , Johne Andreas , Wu Yi-Long
Published: April 2023

Outcomes of treatment for the patient subgroup with MET overexpression
Supplementary Figure S6 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas
Authors: Stinson Jordan A. , Sheen Allison , Momin Noor , Hampel Jordan , Bernstein Rebecca , Kamerer Rebecca , Fadl-Alla Bahaa , Samuelson Jonathan , Fink Elizabeth , Fan Timothy M. , Wittrup K. Dane
Published: April 2023

Pathway scores from canine Nanostring nSolver analysis
Supplementary Figure S2 from Randomized Trial of Tepotinib Plus Gefitinib Versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis
Authors: Liam Chong Kin , Ahmad Azura Rozila , Hsia Te-Chun , Zhou Jianying , Kim Dong-Wan , Soo Ross Andrew , Cheng Ying , Lu Shun , Shin Sang Won , Yang James Chih-Hsin , Zhang Yiping , Zhao Jun , Berghoff Karin , Bruns Rolf , Johne Andreas , Wu Yi-Long
Published: April 2023

Duration of PFS in the patient subgroup with MET amplification
Supplementary Figure S1 from Randomized Trial of Tepotinib Plus Gefitinib Versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis
Authors: Liam Chong Kin , Ahmad Azura Rozila , Hsia Te-Chun , Zhou Jianying , Kim Dong-Wan , Soo Ross Andrew , Cheng Ying , Lu Shun , Shin Sang Won , Yang James Chih-Hsin , Zhang Yiping , Zhao Jun , Berghoff Karin , Bruns Rolf , Johne Andreas , Wu Yi-Long
Published: April 2023

Outcomes of treatment for all individuals enrolled
Supplementary Figure S4 from Collagen-Anchored Interleukin-2 and Interleukin-12 Safely Reprogram the Tumor Microenvironment in Canine Soft-Tissue Sarcomas
Authors: Stinson Jordan A. , Sheen Allison , Momin Noor , Hampel Jordan , Bernstein Rebecca , Kamerer Rebecca , Fadl-Alla Bahaa , Samuelson Jonathan , Fink Elizabeth , Fan Timothy M. , Wittrup K. Dane
Published: April 2023

IFN-γ and IL-10 individual replicates from Milliplex, sarcoma patients
Data from Randomized Trial of Tepotinib Plus Gefitinib Versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis
Authors: Liam Chong Kin , Ahmad Azura Rozila , Hsia Te-Chun , Zhou Jianying , Kim Dong-Wan , Soo Ross Andrew. , Cheng Ying , Lu Shun , Shin Sang Won , Yang James Chi-Hsin , Zhang Yiping , Zhao Jun , Berghoff Karin , Bruns Rolf , Johne Andreas , Wu Yi-Long
Published: April 2023

Abstract
Purpose: The final analyses of the INSIGHT phase II study evaluating tepotinib (a selective MET inhibitor) plus gefitinib versus chemotherapy in patients with MET-altered EGFR-mutant NSCLC (data cut-off: September 3, 2021). Patients and methods: Adults with advanced/metastatic EGFR-mutant NSCLC, acquired resistance to first-/second-generation EGFR inhibitors, and MET gene copy number (GCN) ≥5, MET:CEP7 ≥2, or MET IHC 2+/3+ were randomized to tepotinib 500 mg (450 mg active moiety) plus gefitinib 250 mg once daily, or chemotherapy. Primary endpoint was investigator-assessed progression-free survival (PFS). MET-amplified subgroup analysis was preplanned. Results: Overall (N=55), median PFS was 4.9 versus 4.4 months (stratified HR 0.67 [90% CI: 0.35, 1.28]) with tepotinib plus gefitinib versus chemotherapy. In 19 patients with MET amplification (median age 60.4 years; 68.4% never-smokers; median GCN 8.8; median MET/CEP7 2.8; 89.5% with MET IHC 3+), tepotinib plus gefitinib improved PFS (HR 0.13; 90% CI: 0.04, 0.43) and overall survival (OS; HR 0.10; 90% CI: 0.02, 0.36) versus chemotherapy. Objective response rate was 66.7% with tepotinib plus gefitinib versus 42.9% with chemotherapy; median duration of response was 19.9 versus 2.8 months. Median duration of tepotinib plus gefitinib was 11.3 months (range: 1.1–56.5), with treatment >1 year in six (50.0%) and >4 years in three patients (25.0%). Seven patients (58.3%) had treatment-related grade ≥3 adverse events with tepotinib plus gefitinib, and five (71.4%) with chemotherapy. Conclusions: Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors.
Supplementary Table S3 from Reallocating Cervical Cancer Preventive Service Spending from Low- to High-Value Clinical Scenarios
Authors: Rockwell Michelle S. , Armbruster Shannon D. , Capucao Jillian C. , Russell Kyle B. , Rockwell John A. , Perkins Karen E. , Huffstetler Alison N. , Mafi John N. , Fendrick A. Mark
Published: April 2023

Supplementary Table S3 shows CPT codes used in the analysis of colposcopy and related cervical services.
Supplementary Table S2 from Reallocating Cervical Cancer Preventive Service Spending from Low- to High-Value Clinical Scenarios
Authors: Rockwell Michelle S. , Armbruster Shannon D. , Capucao Jillian C. , Russell Kyle B. , Rockwell John A. , Perkins Karen E. , Huffstetler Alison N. , Mafi John N. , Fendrick A. Mark
Published: April 2023

Supplementary Table S2 displays specifications for high and low-value cervical cancer screening as specified by the Milliman Medinsight Health Waste Calculator.
Supplementary Table S1 from Reallocating Cervical Cancer Preventive Service Spending from Low- to High-Value Clinical Scenarios
Authors: Rockwell Michelle S. , Armbruster Shannon D. , Capucao Jillian C. , Russell Kyle B. , Rockwell John A. , Perkins Karen E. , Huffstetler Alison N. , Mafi John N. , Fendrick A. Mark
Published: April 2023

Supplementary Table S1 includes codes used to identify cervical cancer screening tests within claims data.
Figure S5 from Systemic LRG1 Expression in Melanoma is Associated with Disease Progression and Recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L.M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C.J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: April 2023

Figure S5 shows that complement factor B (CFB), component 7 (C7) and alpha-1B-glycoportein (A1BG) expression are increased upon melanoma progression and recurrence.
Figure S3 from Systemic LRG1 Expression in Melanoma is Associated with Disease Progression and Recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L.M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C.J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: April 2023

Figure S3 shows that SAA1, CRP and LDHB are associated with melanoma disease progression.
Figure S2 from Systemic LRG1 Expression in Melanoma is Associated with Disease Progression and Recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L.M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C.J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: April 2023

Figure S2 shows a flowchart of patients PRADO study
Comparisons of Handheld Retinal Imaging with Optical Coherence Tomography for the Identification of Macular Pathology in Patients with Diabetes
Authors: Jacoba Cris Martin P , Salongcay Recivall P. , Rageh Abdulrahman K , Aquino Lizzie Anne C. , Alog Glenn P , Saunar Aileen V , Peto Tunde , Silva Paolo S.
Published: April 2023

Introduction: Handheld retinal imaging cameras are relatively inexpensive and highly portable devices that have the potential to significantly expand diabetic retinopathy (DR) screening, allowing a much broader population to be evaluated. However, it is essential to evaluate if these devices can accurately identify vision-threatening macular diseases if DR screening programs will rely on these instruments. Thus, the purpose of this study was to evaluate the detection of diabetic macular pathology using monoscopic macula-centered images using mydriatic handheld retinal imaging compared with spectral domain optical coherence tomography (SDOCT). Methods: Mydriatic 40°–60° macula-centered images taken with 3 handheld retinal imaging devices (Aurora [AU], SmartScope [SS], RetinaVue 700 [RV]) were compared with the Cirrus 6000 SDOCT taken during the same visit. Images were evaluated for the presence of diabetic macular edema (DME) on monoscopic fundus photographs adapted from Early Treatment Diabetic Retinopathy Study (ETDRS) definitions (no DME, noncenter-involved DME [non-ciDME], and center-involved DME [ciDME]). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each device with SDOCT as gold standard. Results: Severity by ETDRS photos: no DR 33.3%, mild NPDR 20.4%, moderate 14.2%, severe 11.6%, proliferative 20.4%, and ungradable for DR 0%; no DME 83.1%, non-ciDME 4.9%, ciDME 12.0%, and ungradable for DME 0%. Gradable images by SDOCT (N = 217, 96.4%) showed no DME in 75.6%, non-ciDME in 9.8%, and ciDME in 11.1%. The ungradable rate for images (poor visualization in >50% of the macula) was AU: 0.9%, SS: 4.4%, and RV: 6.2%. For DME, sensitivity and specificity were similar across devices (0.5–0.64, 0.93–0.97). For nondiabetic macular pathology (ERM, pigment epithelial detachment, traction retinal detachment) across all devices, sensitivity was low to moderate (0.2–0.5) but highly specific (0.93–1.00). Conclusions: Compared to SDOCT, handheld macular imaging attained high specificity but low sensitivity in identifying macular pathology. This suggests the importance of SDOCT evaluation for patients suspected to have DME on fundus photography, leading to more appropriate referral refinement.
Olfactory stimulus as environmental enrichment for shelter dogs: a pilot study
Authors: Figueira Milene Paula , Silva Fernanda Fatima Rodrigues , Ribeiro Alice , Silva Ita Oliveira , Boere Vanner
Published: April 2023

Environmental enrichment techniques include olfactory stimuli for improving animal welfare. This study aimed to analyze the reactions of 41 shelter dogs exposed to odorous stimuli, such as the method used in another study on wild canids. The focal animal method analyzed the dogs’ reactions, with all behaviors recorded. Behavioral responses were classified as positive (P+), negative (N-), or other (Ot). Independent variables were all dogs and the size of the packs. The behavior between the basal (without stimulus), exposure, and after-stimulus withdrawal was analyzed. For all dogs, olfactory stimuli significantly increased P+ (P=0.001) and N- (P=0.004), contrasting with the decrement of Ot behaviors (P=0.001) from the basal to the exposure phase. After the withdrawal of the stimuli, P+, N-, and Ot behaviors returned to basal levels (P>0.05). There were no significant differences (P>0.05) in the conduct of small or large packs exposed to stimuli. Dogs are sensitive to olfactory stimuli, but arousal is generalized to P+ and N-. It is undesirable to an N- increase for improvement of animal welfare. Contrary to what was observed in a study with wild canids, the method failed in shelter dogs because N- was increased. The introduction of sudden novelty (olfactory stimulus) in an impoverished shelter environment may have caused excitement in the dogs. It is suggested that changes in the method, such as stimuli exposition to each dog in an isolated room, are necessary to increase sheltered dog well-being.
Lineage-Specific Induced Pluripotent Stem Cell–Derived Smooth Muscle Cell Modeling Predicts Integrin Alpha-V Antagonism Reduces Aortic Root Aneurysm Formation in Marfan Syndrome Mice
Authors: Nakamura Ken , Dalal Alex R. , Yokoyama Nobu , Pedroza Albert J. , Kusadokoro Sho , Mitchel Olivia , Gilles Casey , Masoudian Bahar , Leipzig Matthew , Casey Kerriann M. , Hiesinger William , Uchida Tetsuro , Fischbein Michael P.
Published: April 2023

Background:

The role of increased smooth muscle cell (SMC) integrin αv signaling in Marfan syndrome (MFS) aortic aneurysm remains unclear. Herein, we examine the mechanism and potential efficacy of integrin αv blockade as a therapeutic strategy to reduce aneurysm progression in MFS.

Methods:

Induced pluripotent stem cells (iPSCs) were differentiated into aortic SMCs of the second heart field (SHF) and neural crest (NC) lineages, enabling in vitro modeling of MFS thoracic aortic aneurysms. The pathological role of integrin αv during aneurysm formation was confirmed by blockade of integrin αv with GLPG0187 in
Fbn1
C1039G/+
MFS mice.

Results:

iPSC–derived MFS SHF SMCs overexpress integrin αv relative to MFS NC and healthy control SHF cells. Furthermore, integrin αv downstream targets (FAK [focal adhesion kinase]/Akt
Thr308
/mTORC1 [mechanistic target of rapamycin complex 1]) were activated, especially in MFS SHF. Treatment of MFS SHF SMCs with GLPG0187 reduced p-FAK/p-Akt
Thr308
/mTORC1 activity back to control SHF levels. Functionally, MFS SHF SMCs had increased proliferation and migration compared to MFS NC SMCs and control SMCs, which normalized with GLPG0187 treatment. In the
Fbn1
C1039G/+
MFS mouse model, integrin αv, p-Akt
Thr308
, and downstream targets of mTORC1 proteins were elevated in the aortic root/ascending segment compared to littermate wild-type control. Mice treated with GLPG0187 (age 6–14 weeks) had reduced aneurysm growth, elastin fragmentation, and reduction of the FAK/Akt
Thr308
/mTORC1 pathway. GLPG0187 treatment reduced the amount and severity of SMC modulation assessed by single-cell RNA sequencing.

Conclusions:

The integrin αv-FAK-Akt
Thr308
signaling pathway is activated in iPSC SMCs from MFS patients, specifically from the SHF lineage. Mechanistically, this signaling pathway promotes SMC proliferation and migration in vitro. As biological proof of concept, GLPG0187 treatment slowed aneurysm growth and p-Akt
Thr308
signaling in
Fbn1
C1039G/+
mice. Integrin αv blockade via GLPG0187 may be a promising therapeutic approach to inhibit MFS aneurysmal growth.
Myocardial Injury Thresholds for 4 High-Sensitivity Troponin Assays in a Population-Based Sample of US Children and Adolescents
Authors: McEvoy John W. , Wang Dan , Brady Tammy , Tang Olive , Ndumele Chiadi E. , Coresh Josef , Christenson Robert H. , Selvin Elizabeth
Published: April 2023

Background:

Myocardial injury is an important pediatric diagnosis. Establishing normative data from a representative pediatric sample is vital to provide accurate upper reference limits (URLs) for defining myocardial injury using high-sensitivity cardiac troponin.

Methods:

Among participants 1 to 18 years of age in the 1999–2004 National Health and Nutrition Examination Survey, we measured high-sensitivity troponin T using one assay (Roche) and high-sensitivity troponin I using 3 assays (Abbott, Siemens, and Ortho). In a strictly defined healthy subgroup, we estimated 97.5th and 99th percentile URLs for each assay using the recommended nonparametric method.

Results:

Of 5695 pediatric participants, 4029 met criteria for the healthy subgroup (50% males; mean age 12.6 years). Our 99th percentile URL estimates for all 4 high-sensitivity troponin assays among children and adolescents were lower than the manufacturer-reported URLs (derived from adults). The 99th percentile URLs (95% CI) were 15 ng/L (95% CI, 12–17) for high-sensitivity troponin T, 16 ng/L (95% CI, 12–19) for high-sensitivity troponin I with the Abbott assay, 38 ng/L (95% CI, 25–46) for high-sensitivity troponin I with the Siemens assay, and 7 ng/L (95% CI, 5, 12) for high-sensitivity troponin I with the Ortho assay. The 95% CIs for age-, sex-, and race and ethnicity-specific 99th percentile URLs overlapped. However, the 97.5th percentile URL for each assay was measured with superior statistical precision (ie, tighter 95% CIs) and demonstrated differences by sex. For male compared with female children and adolescents, 97.5th percentile URLs were 11 ng/L (95% CI, 10–12) versus 6 ng/L (95% CI, 6–7) for high-sensitivity troponin T, 9 ng/L (95% CI, 7–10) versus 5 ng/L (95% CI, 4–6) for high-sensitivity troponin I with the Abbott assay, 21 ng/L (95% CI, 18–25) versus 11 ng/L (95% CI, 9–13) for high-sensitivity troponin I with the Siemens assay, and 4 ng/L (95% CI, 3–5) versus 2 ng/L (95% CI, 1–3) for high-sensitivity troponin I with the Ortho assay. In contrast to the 99th percentiles, the point estimates of 97.5th percentile pediatric URLs for high-sensitivity troponin were also much more stable to differences in the analytic approaches taken to estimate URLs.

Conclusions:

Because myocardial infarction is rare in children and adolescents, the use of statistically more precise and reliable sex-specific 97.5th percentile high-sensitivity troponin URLs might be considered to define pediatric myocardial injury.
Sharing your snack: unusual observation of a chick–chick feeding occurrence in colonial king penguin (Aptenodytes patagonicus)
Authors: Cillard Anne , Fuentes Rodriguez Tatiana , Robin Jean-Patrice , Bize Pierre , Stier Antoine , Viblanc Vincent A.
Published: April 2023

King penguins (Aptenodytes patagonicus) are colonial seabirds presenting an extraordinary breeding cycle. Parents take over 14 months to raise a single chick to independence, upon which fledglings depart at sea for more than a year. Juveniles often return to the colony within the three austral summers following departure, and before the age of first reproduction (around 5–6 years old), possibly to acquire the essential skills involved in breeding. Little to nothing is known on the acquisition of parental behaviour. Here, we report an anecdotal, yet highly unusual, observation of chick–chick feeding behaviour in this species. The behaviour is highly unusual in that two non-sibling chicks, not yet independent, and hatched at different times (early and late) of the same breeding season were observed, the older chick feeding the younger one. Whereas alloparental feeding is known to occur in this species, this is the first reported observation of a chick–chick feeding event. This unusual behaviour raises the question of whether the early social environment plays a role in the acquisition of essential parenting skills in this species.
Hanako, Rodin, and the Close-up
Authors: Miyao Daisuke
Published: April 2023

Between 1906 and 1911, Auguste Rodin sculpted more than fifty heads, masks, and busts of the Japanese actress Hanako. It was the largest number of portraits that he did with a single model. This essay explores the question why Rodin was so attracted to Hanako and, in particular, to her face. At the time Rodin was creating sculptures of Hanako’s head, the technique of the close-up was being adopted dramatically in filmmaking. Critics were shocked by the excessiveness of the close-up and tried to understand it in terms of ‘new realism’: the close-up modifies reality without eliminating the realness. This essay connects the theory of the close-up to the discourse of Japonisme.