bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel miRNA Located in the HER2 Gene Shows an Inhibitory Effect on Wnt Signaling and Cell Cycle Progression
Authors: Shabaninejad Zahra , Mowla Seyed Javad , Yousefi Fatemeh , Soltani Bahram Mohammad
Published: June 2022

Human epidermal growth factor receptor 2 (HER2) is involved in the development of the majority of cancers. Therefore, it can be a potential target for cancer therapy. It was hypothesized that some of the broad effects of HER2 could be mediated by miRNAs that are probably embedded inside this gene. Here, we predicted and then empirically substantiated the processing and expression of a novel miRNA named HER2-miR1, located in the HER2 gene; transfection of a DNA fragment corresponding to HER2-miR1 precursor sequence (preHER2-miR1) resulted in ~4000‐fold elevation of HER2-miR1 mature form in HEK293t cells. Also, the detection of HER2-miR1 in 5637, NT2, and HeLa cell lines confirmed its endogenous production. Following the HER2-miR1 overexpression, TOP/FOP flash assay and RT‐qPCR results showed that Wnt signaling pathway was downregulated. Consistently, flow cytometry results revealed that overexpression of HER2-miR1 in Wnt+ cell lines (SW480 and HCT116) was ended in G1 arrest, unlike in Wnt- cells (HEK293t). Taking everything into account, our results report the discovery of a novel miRNA that is located within the HER2 gene sequence and has a repressive impact on the Wnt signaling pathway.
Application Model Construction of Traditional Cultural Elements in Illustration Design under Artificial Intelligence Background
Authors: Shi Lei
Published: June 2022

The sustainable development of modern illustration art needs to dig deep into traditional culture in content and, on the basis of spreading cultural forms and improving cultural influence, supplement its own creative forms. The influence of AI (artificial intelligence) on illustration design not only is manifested in the optimization of illustration design tools and the improvement of design efficiency, but also makes the illustration design methods more diverse and promotes new breakthroughs in the illustration design concept under the influence of new technologies. In this paper, combining the advantages of two activation functions, SoftSign and ReLU, a new activation function, SReLU, is constructed and applied to CNN (Convolutional Neural Network). The multimode property of color prediction is modeled by quantifying ab color channels in Lab color space, and the introduction of GAN (Generative Adversarial Network) structure can make the whole model show better generation effect and improve the generation ability of image style conversion network. Results. The experiment proves the effectiveness of the method with high-quality image visual effect.
Adherence to General Diabetes and Foot Care Processes, with Prompt Referral, Are Associated with Amputation-Free Survival in People with Type 2 Diabetes and Foot Ulcers: A Scottish National Registry Analysis
Authors: Meza-Torres Bernardo , Cunningham Scott G. , Heiss Christian , Joy Mark , Feher Michael , Leese Graham P. , de Lusignan Simon , Carinci Fabrizio
Published: June 2022

Aims. To compare different packages of care across care providers in Scotland on foot-related outcomes. Methods. A retrospective cohort study with primary and secondary care electronic health records from the Scottish Diabetes Registry, including 6,845 people with type 2 diabetes and a first foot ulcer occurring between 2013 and 2017. We assessed the association between exposure to care processes and major lower extremity amputation and death. Proportional hazards were used for time-to-event univariate and multivariate analyses, adjusting for case-mix characteristics and care processes. Results were expressed in terms of hazard ratios with 95% confidence intervals. Results. 2,243 (32.7%) subjects had a major amputation or death. Exposure to all nine care processes at all ages (

HR
=
0.63

; 95% CI: 0.58-0.69;

p
<
.001

) and higher foot care attendance in people aged >70 years (

HR
=
0.88

; 0.78-0.99;

p
=
.03

) were associated with longer major amputation-free survival.

Waiting
 
time
≥
12

weeks between ulceration and clinic attendance was associated with worse outcomes (

HR
=
1.59

; 1.37-1.84;

p
<
.001

). In

people
>
70

years, minor amputations were associated with improved major amputation-free survival (

HR
=
0.69

; 0.52-0.92;

p
=
.01

). Conclusions. Strict adherence to a standardised package of general diabetes care before foot ulceration, timely foot care after ulceration, and specific treatment pathways were associated with longer major amputation-free survival among a large cohort of people with type 2 diabetes in Scotland, with a larger impact on older age groups.
From Blackbox to Explainable AI in Healthcare: Existing Tools and Case Studies
Authors: Srinivasu Parvathaneni Naga , Sandhya N. , Jhaveri Rutvij H. , Raut Roshani
Published: June 2022

Introduction. Artificial intelligence (AI) models have been employed to automate decision-making, from commerce to more critical fields directly affecting human lives, including healthcare. Although the vast majority of these proposed AI systems are considered black box models that lack explainability, there is an increasing trend of attempting to create medical explainable Artificial Intelligence (XAI) systems using approaches such as attention mechanisms and surrogate models. An AI system is said to be explainable if humans can tell how the system reached its decision. Various XAI-driven healthcare approaches and their performances in the current study are discussed. The toolkits used in local and global post hoc explainability and the multiple techniques for explainability pertaining the Rational, Data, and Performance explainability are discussed in the current study. Methods. The explainability of the artificial intelligence model in the healthcare domain is implemented through the Local Interpretable Model-Agnostic Explanations and Shapley Additive Explanations for better comprehensibility of the internal working mechanism of the original AI models and the correlation among the feature set that influences decision of the model. Results. The current state-of-the-art XAI-based and future technologies through XAI are reported on research findings in various implementation aspects, including research challenges and limitations of existing models. The role of XAI in the healthcare domain ranging from the earlier prediction of future illness to the disease’s smart diagnosis is discussed. The metrics considered in evaluating the model’s explainability are presented, along with various explainability tools. Three case studies about the role of XAI in the healthcare domain with their performances are incorporated for better comprehensibility. Conclusion. The future perspective of XAI in healthcare will assist in obtaining research insight in the healthcare domain.
The Dissemination and Evaluation of Campus Ideological and Political Public Opinion Based on Internet of Things Monitoring
Authors: Xu Xiao , Sun Bei
Published: June 2022

With the advent of the information age, the rapid development of Internet of Things technology makes monitoring methods more flexible and changeable. As an intelligent application, the development of the Internet of Things brings convenience to public opinion monitoring. However, at present, due to the high price of transmission equipment, inconvenient maintenance, information delay, and other unfavorable conditions, real-time and controllable public opinion monitoring cannot be carried out on a large scale, and there are still many deficiencies in campus ideological and political public opinion monitoring. We found an effective transmission method, explored the network energy saving, dig deep into the transmission function of the signal system, and reduced the interference and mutual influence of various transmission accessories. In the application of the Internet of Things, the network public opinion is remotely monitored, the campus public opinion information is mastered, and its dissemination and development orientation are controlled. The exploration and research of online public opinion monitoring are in line with the goal of smart campus, and its theoretical development is constantly enriched.
Chemotherapy with a TP Regimen in Combination with Stereotactic Radiotherapy Could Significantly Optimize the Clinical Efficacy of NSCLC Treatment
Authors: Wu Chenglin , Chen Biyu , Wang Meifang , Tang Yijun
Published: June 2022

The changes in lifestyle and bad living habits have a significant impact on the health of people, resulting in an increasing prevalence of lung cancer. The most prevalent kind of lung cancer is nonsmall cell lung cancer (NSCLC), which accounts for around 80% of all cases. Chemotherapy is a common treatment method in clinical practice with certain negative effects. The primary goal of this study is to investigate the clinical efficacy of stereotactic radiotherapy in combination with a docetaxel plus cisplatin (TP) chemotherapy regimen in patients with nonsmall cell lung cancer (NSCLC) and their impact on the levels of cytokeratin fragment 21-1 (CYFRA21-1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in NSCLC patients. Eighty patients who were admitted to the hospital between November 2016 and November 2019 were recruited and assigned to receive either chemotherapy with a TP regimen (the control group) or chemotherapy with a TP regimen plus stereotactic radiotherapy (the observation group). The WHO response evaluation criteria (REC) for solid tumors were adopted to analyze short-term efficacy, and the Karnofsky performance status (KPS) score was used to assess the quality of life by recording adverse reactions in the blood system, kidney, gastrointestinal tract, bladder, nervous system, and heart. The levels of CYFRA21-1 and MALAT1 in serum before and after the treatment were determined and compared. As a result, the observation group showed higher total efficacy and MALAT1 level, better quality of life, and lower CYFRA21-1 level than the control group (

P
<
0.05

). Stereotactic radiotherapy plus TP regimen chemotherapy resulted in significantly better progression-free survival, overall survival, survival rate, and long-term prognosis versus chemotherapy alone. Moreover, combined therapy was associated with a lower incidence of hemoglobin reduction, gastrointestinal reaction, and renal impairment versus TP regimen chemotherapy (

P
<
0.05

). Therefore, we concluded that stereotactic radiotherapy plus chemotherapy with a TP regimen significantly optimizes the clinical efficacy of the NSCLC treatment.
Mathematical Model and Simulation Calculation Method Based on the Exfoliation of Single‐Layer Graphene from Dispersed Carbon Nanotubes
Authors: Sha Xudong , Zhao Li
Published: June 2022

Graphene is a two‐dimensional material with excellent performance and unique structure. Since its successful manufacturing in 2004, it has quickly become a research hotspot in the fields of materials, chemistry, physics, and engineering. This article focuses on the study of exfoliated single‐layer graphene based on dispersed carbon nanotubes and understands the related theories of carbon nanotubes and exfoliated single‐layer graphene on the basis of literature data. The mathematical model and simulation calculation method are analyzed, and then, the effect of the single‐layer graphene peeling based on the dispersed carbon nanotubes is tested, mainly to the experimental verification of the peeling process parameters and the influence of the dispersant on the peeling effect, and then, the peeled graphite quality of the graphene was tested, and the test results showed that the thickness of single‐layer pure graphene is 0.6‐0.9 nm, and the experimental statistics show that the graphene of single‐layer and double‐layer occupies 81% of the experimental sample; most of the single‐layer graphene exfoliated based on dispersed carbon nanotubes in this paper is single‐layer, two‐layer graphene, and a relatively small amount of multilayer graphene.
Caregivers’ Knowledge, Attitude, and Practice towards Pressure Injuries in Spinal Cord Injury at Rehabilitation Center in Bangladesh
Authors: Tharu Niraj Singh , Alam Monzurul , Bajracharya Shristi , Chaudhary Gautam Prasad , Pandey Jitendra , Kabir Mohammad A.
Published: June 2022

The purpose of this study was to determine caregivers’ knowledge, attitude, and practice (KAP) on the prevention and care of pressure injuries (PIs) in individuals with spinal cord injury. A quantitative cross-sectional study with descriptive correlation design was used to implement a modified semistructured questionnaire using a convenient sampling method. McDonald’s standard of learning outcome measurement criteria was used to categorize caregivers’ KAP. A Pearson product-moment correlation coefficient (r) was utilized to assess the relationships between caregivers’ KAP, with a

p

value of 0.05 or less considered statistically significant. The study findings indicate that caregivers had a moderate level of knowledge (M = 73.68%, SD = 6.43), a neutral attitude (M = 70.32%, SD = 6.89), and a moderate level of practice (M = 74.77%, SD = 9.08). A positive correlation existed between caregivers’ knowledge and attitude (r = 0.30,

p
<
0.01

), as well as between knowledge and practice (r = 0.37,

p
<
0.01

). Nevertheless, there was no correlation between attitude and practice (r = 0.12,

p
>
0.05

). The study findings suggest that caregivers need to develop a positive attitude and expand their knowledge in order to improve their practice. The KAP factors that require higher priority were positioning and turning the patient, preventing skin breakdown, assessing weight changes over time, interest in patient care, additional care for PIs, frequently changing the individual’s position, priority to PI care, interest in other types of care other than PIs, using special cushions, consulting doctors on a regular basis, being aware of clothing and fabrics, proper transfer technique, pressure relief, and skin inspection, among others.
Design and Simulation Analysis of Trajectory Planning Algorithm for 6-DoF Manipulator Based on Deep Learning
Authors: Zhuang Min , Li Ge , Ding Kexin
Published: June 2022

At present, the robot developed only has partial intelligence, and it cannot be well controlled independently for some jobs, so it should optimize its path and trajectory. However, as an industrial robotic arm robot necessary for advanced industrial manufacturing enterprises, it has been replacing humans to perform simple and repetitive actions, and it is doing better and better. For the six-degree-of-freedom (6-DoF) manipulator, this paper aims to optimize the trajectory planning of the manipulator based on deep learning technology. Therefore, this paper presents a fuzzy control algorithm for the trajectory planning of the manipulator based on the neural network algorithm. The experimental results show that for the established three-joint dynamic model, the moment received by joint 1 is the largest, followed by joint 2, and joint 3 is the smallest, which can better simulate the trajectory of the robotic arm.
The Effect of the Angiotensin-Converting Enzyme Inhibitor on Bone Health in Castrated Hypertensive Rats Is Mediated via the Kinin-Kallikrein System
Authors: Zhang Na , Huo Yanan , Yao Chen , Sun Jie , Zhang Yafeng
Published: June 2022

Background. In previous studies, angiotensin-converting enzyme inhibitor (ACEI) use was associated with increased bone loss, while an angiotensin II type I receptor blocker had no effect on bone loss in elder subjects, which suggested that the effect of ACEI on bone loss was not mediated through the classical renin-angiotensin system. In this study, we set to investigate whether the effect of ACEI on bone deterioration was mediated via the kinin-kallikrein system. Methods. Six-month-old male and female spontaneously hypertensive rats were used. The effect of captopril on blood pressure, serum Ang II, and bradykinin concentration was measured in intact rats. Ovariectomy and orchidectomy were performed to establish an osteoporosis model in female and male rats, respectively. Captopril and the bradykinin receptor blocker icatibant (HOE140) were administered after operation for 12 weeks. Serum Ang II and bradykinin concentration, bone turnover markers, bone mineral density (BMD), and bone microarchitecture were evaluated. Femur samples were subjected to a mechanical test. Results. Captopril decreased blood pressure and serum Ang II concentration and increased serum bradykinin concentration in intact rats ([Formula: see text]). After castration, captopril decreased serum Ang II concentration ([Formula: see text]); in female rats, icatibant increased serum Ang II concentration ([Formula: see text]). Captopril increased serum bradykinin concentration ([Formula: see text]); in male rats, icatibant decreased serum bradykinin concentration ([Formula: see text]). Captopril increased the rat urine deoxypyridinoline-creatinine ratio (DPD/Cr) and serum osteocalcin concentration ([Formula: see text]). Icatibant decreased urine DPD/Cr in male rats ([Formula: see text]) and increased osteocalcin concentration in female rats ([Formula: see text]). Captopril increased cancellous BMD in castrated hypertensive rats ([Formula: see text]), and icatibant further increased cancellous BMD ([Formula: see text]), which was due to the increased trabecular bone number. In mechanical testing, ACEI increased bone strength ([Formula: see text]), and icatibant further improved it ([Formula: see text]). Conclusion. ACEI decreased bone deterioration in both male and female hypertensive rats, and the bradykinin receptor blocker further decreased bone deterioration.
ObjectDetect: A Real-Time Object Detection Framework for Advanced Driver Assistant Systems Using YOLOv5
Authors: Murthy Jamuna S. , Siddesh G. M. , Lai Wen-Cheng , Parameshachari B. D. , Patil Sujata N. , Hemalatha K. L.
Published: June 2022

In the recent times, there has been a lot of speculation related to advanced driver-assistance system (ADAS) which provides best driving experience for the drivers. ADAS technology helps to detect the unhealthy driving conditions which lead to road accidents today. Road accidents are basically caused due to distracted driving, over speeding, drink and drive, foggy weather, no proper headlights, or due to some object which suddenly trespasses the vehicle. Today the major advancements in ADAS include parking assistance, road traffic detection, object detection on highways, and lane detection. But the major risk limitation in ADAS system is the speed and time at which the object is detected and tracked. Several algorithms such as R-CNN, Fast R-CNN, and YOLO were used for effective object detection and tracking earlier, but sometimes, the system do fail to detect due the speed factor. Hence, the proposed work presents a novel approach called “A Real-Time Object Detection Framework for Advanced Driver Assistant Systems” by implementing the state-of-the-art object detection algorithm YOLOv5 which improves the speed in detection of object over real-time. This paper provides a comparison between other state-of-the-art object detectors such as YOLOv3 and YOLOv4. Comparison is done based on mean average precision (mAP) and frames per second (FPS) on three benchmark datasets collected as a part of research findings. YOLOv5 proves to be faster and 95% accurate than the other object detection algorithms in the comparison. This framework is used to build a mobile application called “ObjectDetect” which helps users make better decisions on the road. “ObjectDetect” consists of a simple user interface that displays alerts and warnings.
Variable Mass Control and Parameter Identification of Spacecraft Orbit Refueling Process
Authors: Han Xu , Li Zhi , Li Hui , Huang Longfei , Pang Yujia
Published: June 2022

A maintainable refueling vehicle is the future development direction of the space system. In the process of fuel filling, capture docking, and configuration transformation, the most significant factor that affects the attitude control of the system is the continuous or sudden change of the angular torque of the system. In this paper, we study the control system of the variable mass body in an on-orbit service in the process of configuration transformation. The large errors of torque of inertia may make the narrow sense TEA (torque equilibrium attitude) of the system deviate greatly from the earth-oriented attitude. In order to avoid the error caused by the partial linearization of the system model, the feedback linearization method of the nonlinear system is used to design the controller to realize the tracking of the narrow sense TEA in the process of configuration transformation. Different from the traditional attitude control method, in order to avoid the high cost of the control system caused by the change of system mass characteristics and the change of system angular torque, CMG (control moment gyroscope) angular torque is introduced into the controller. We design a joint controller of attitude control and angular torque management, which can effectively stabilize the system and reduce the angular torque saturation of the attitude control system during the on-orbit service.
Effects of Different Doses of Clopidogrel plus Early Rehabilitation Therapy on Motor Function and Inflammatory Factors in Patients with Ischemic Stroke
Authors: Zhao Zhuolin , Ma Ying , Liu Qin , Jiang Ling , Shu Huimin , Chen Daofeng , Wu Jiao
Published: June 2022

This prospective randomized controlled study was intended to assess the effects of different doses of clopidogrel plus early rehabilitation therapy on motor function and inflammatory factors in patients with ischemic stroke. Between August 2018 and October 2020, 90 cases of ischemic stroke treated in the Second People’s Hospital of Yibin were randomized at a ratio of 1 : 1 to receive either oral 50 mg/d clopidogrel plus early rehabilitation therapy (low-dose group) or oral 75 mg/d clopidogrel plus early rehabilitation therapy (high-dose group), with 45 cases in each group. The outcome measures including the Barthel Index (BI), National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer simplified scale, hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and occurrence of adverse events were collected. After treatment, the high-dose group had higher BI results than the low-dose group. All eligible patients showed significantly declined NIHSS scores, and the high-dose group had markedly lower results (

P
<
0.05

). After treatment, the Fugl-Meyer scores of both upper and lower extremities of the high-dose group were significantly higher than those in the low-dose group. The high-dose group achieved a greater decrease in inflammatory factor levels after treatment versus the low-dose group. The two groups showed a similar incidence of adverse events. High-dose clopidogrel plus early rehabilitation outperforms the low-dose treatment for patients with ischemic stroke by effectively mitigating the inflammatory response in the body, promoting the restoration of neurological function, improving the level of motor function, and enhancing the patient’s quality of life, with manageable safety.
Factors Affecting the Attractive Force of Dental Magnetic Attachment: A Literature Review for Guiding Dentists in Clinical Application
Authors: Kusumadewi An-Nissa , Damayanti Lisda , Rukiah  , Risdiana
Published: June 2022

Aim. The aim of this review is to get a comprehensive description of the factors that may influence the attractive force of the dental magnetic attachment. Background. Dental magnetic attachment is a term for a magnet used as an overdenture retainer. Magnets that are widely used are permanent magnets such as neodymium iron boron (NdFeB) and samarium cobalt (SmCo). Theoretically, the magnetic attractive force in a permanent magnet has a constant retentive force, and the magnitude of the force will not decrease over time. However, several studies revealed that the magnetic attractive force can be decreased, resulting in the failure of overdenture retention. Some of the factors of reduced magnetic attraction that have been studied are corrosion and temperature. There are no articles that specifically review the factors that can influence magnetic attraction. Review Results. A total of 25,880 articles were obtained during a search on 3 journal databases: PubMed (2,647), ScienceDirect (23,184), and Scopus (229). From those publications, 15 articles reported relevant outcome data that were then extracted. Magnetic attractive force can be influenced by temperature, corrosion, keeper surface morphology, type of magnet, keeper-assembly size combination, inclination, insertion-removal cycle, gliding/loading cycle, number of magnets, crosshead speed, and force direction. Conclusion. Many factors can affect the magnetic attraction force of the dental magnetic attachment. Corrosion is the most likely factor to occur because the dental magnetic attachment is always in the oral environment which contains corrosive saliva and is susceptible to damage due to mastication forces.
Joint Design Method of Transmit-Receive for Airborne MIMO Radar Based on Feasible Point Pursuit
Authors: Huang Jianchong , Li Zhihui , Li Xiaobo , Liu Chunsheng , Niu Chaoyang , Feng Xiaoxing , Wang Qiang
Published: June 2022

Consider the moving target detection performance degradation of airborne multiple-input multiple-output (MIMO) radar in the presence of inaccurate target prior information. This paper proposes a joint design method of transmit waveform and receive filter bank of airborne MIMO radar based on feasible point pursuit successive convex approximation (FPP-SCA). Firstly, a set of receive filter banks is designed in the region where the target may appear on the angle-Doppler plane, and the worst-case output signal-to-clutter-plus-noise ratio (SCNR) is maximized as the optimization criterion. Secondly, considering the energy constraint and similarity on the transmit waveform, the maximin joint design problem is formulated to improve the robustness of the MIMO space-time adaptive processing (STAP) radar against the uncertainty of target parameters. Finally, an FPP-SCA algorithm is employed to solve the maximin nonconvex joint design problem. Simulation results demonstrate the effectiveness of the proposed method in terms of better output SCNR, lower computational load, and more robustness against the errors of target parameters.
Evaluation of Pulse Rate, Oxygen Saturation, and Respiratory Effort after Different Types of Feeding Methods in Preterm Newborns
Authors: Patel Dipen Vasudev , Shah Dharti , Kantharia Kunjal A. , Shinde Mayur K. , Ganjiwale Jaishree , Shah Kushal , Nimbalkar Somashekhar Marutirao
Published: June 2022

Background. During the initial days of hospitalization, preterm newborns are given combinations of breastfeeding, spoon/paladai feeding, and/or gavage feeding. Each method of feeding may have a different effect on vital parameters. Objective. To study changes in vital parameters in relation to different feeding methods and postmenstrual age (PMA) in preterm newborns. Study Design. This prospective observational study was carried out at a tertiary care neonatal unit. Participants. Physiologically stable preterm newborns with PMA less than 37 weeks on full enteral feeds were included in the study. Intervention. None. Outcomes. Respiratory rate (RR), pulse rate (PR), oxygen saturation (SPO2), nasal flaring, and lower chest indrawing were monitored before and up to 3 h after the breastfeeding/spoon (paladai) feeding/gavage feeding or their combinations. These vital parameters were assessed in relation to the feeding methods and PMA groups using ANOVA. Results. A total of 383 records were analyzed from 110 newborns. No infant developed chest indrawing or nasal flaring after any feeding method. During the 3 h period of monitoring, vital parameters changed significantly except in the gavage feeding group. The mean PR did not change, but the mean RR and SPO2 changed significantly at different PMA. Conclusion. Vital parameters changed after different types of feeding methods and at different PMA. A further multicentric prospective study is needed to understand the effect of different feeding methods and PMA on vital parameters.
Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?
Authors: Macauda Angelica , Clay-Gilmour Alyssa , Hielscher Thomas , Hildebrandt Michelle A.T. , Kruszewski Marcin , Orlowski Robert Z. , Kumar Shaji K. , Ziv Elad , Orciuolo Enrico , Brown Elizabeth E. , Försti Asta , Waller Rosalie G. , Machiela Mitchell J. , Chanock Stephen J. , Camp Nicola J. , Rymko Marcin , Raźny Małgorzata , Cozen Wendy , Várkonyi Judit , Piredda Chiara , Pelosini Matteo , Belachew Alem A. , Subocz Edyta , Hemminki Kari , Rybicka-Ramos Malwina , Giles Graham G. , Milne Roger L. , Hofmann Jonathan N. , Zaucha Jan Maciej , Vangsted Annette Juul , Goldschmidt Hartmut , Rajkumar S. Vincent , Tomczak Waldemar , Sainz Juan , Butrym Aleksandra , Watek Marzena , Iskierka-Jazdzewska Elżbieta , Buda Gabriele , Robinson Dennis P. , Jurczyszyn Artur , Dudziński Marek , Martinez-Lopez Joaquin , Sinnwell Jason P. , Slager Susan L. , Jamroziak Krzysztof , Reis Rui Manuel Vieira , Weinhold Niels , Bhatti Parveen , Carvajal-Carmona Luis G. , Zawirska Daria , Norman Aaron D. , Mazur Grzegorz , Berndt Sonja I. , Campa Daniele , Vachon Celine M. , Canzian Federico
Published: June 2022

Background:

Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival.

Methods:

We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed.

Results:

SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P < 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09–1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01–1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant.

Conclusions:

Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS.

Impact:

This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.
Ecologic Analysis of Correlates of Cervical Cancer Morbidity and Mortality in Sub-Saharan Africa
Authors: Gapare Claire Ruvimbo , El-Zein Mariam , Patel Harshita , Tope Parker , Franco Eduardo L.
Published: June 2022

Background:

Cervical cancer is the fourth leading cause of death among women worldwide, with 85% of the burden falling on low- to middle- income countries. We studied the correlates of cervical cancer incidence and mortality, and case-fatality in Sub-Saharan Africa.

Methods:

Country-level data on 16 putative cervical cancer correlates for 37 Sub-Saharan African countries were collected from publicly available data sources. We performed univariate and multiple (stepwise) linear regression analyses to identify correlates of cervical cancer incidence and mortality, and case-fatality.

Results:

In univariate analyses, incidence and mortality rates were significantly correlated with contraceptive use, penile cancer incidence, and human immunodeficiency virus prevalence. Incidence rates were also correlated with literacy rates, whereas mortality rates were correlated with the proportion of rural population and screening coverage. Multiple regression analyses showed contraceptive use (P = 0.009) and penile cancer incidence (P = 0.004) as associated with cervical cancer incidence. Penile cancer incidence (P = 9.77 × 10–5) and number of medical doctors (P = 0.0433) were associated with mortality. The goodness of fit of the incidence and mortality models was moderate at best, explaining 49% and 37% of variability in the data, respectively. However, the case-fatality model had the best fit explaining most of the variation (adjusted R2 = 0.948; P = 6.822 × 10–16).

Conclusions:

To reduce the burden of cervical cancer in Sub-Saharan Africa, it would be important to design multimodal interventions that not only target screening and HPV vaccination, but also focus on cervical cancer correlates.

Impact:

Identifying contextual factors associated with cervical cancer in this region could inform targeted interventions.
Genome-Wide Association Study of Pregnancy in Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study
Authors: Rotz Seth J. , Worley Sarah , Hu Bo , Bazeley Peter , Baedke Jessica L. , Hudson Melissa M. , Kuo Dennis J. , Oeffinger Kevin C. , Robison Leslie L. , Sahoo Debashis , Wang Fan , Yasui Yutaka , Armstrong Gregory T. , Bhatia Smita
Published: June 2022

Background:

Gonadotoxic treatment-related infertility has a significant impact on quality of life in childhood cancer survivors. Genome-wide association analyses to delineate the risk of infertility in childhood cancer survivors have not been previously reported.

Methods:

Leveraging genotype data from a large survivor cohort, the Childhood Cancer Survivor Study (CCSS), we investigated the role of SNPs on future pregnancy or siring a pregnancy in survivors without pelvic, testicular, or brain radiation who had ever been married. We calculated sex-stratified hazard ratios, using Cox proportional hazards modeling, adjusting for birth cohort (before 1965 vs. 1965 or later) and doses of relevant chemotherapies; replication was attempted in the independent St. Jude Lifetime Cohort study (SJLIFE).

Results:

In the CCSS cohort, nine SNPs were found to be suggestive (P < 10–7) or statistically significantly (P < 5 × 10–8) associated with pregnancy, however, none of the SNPs were replicated in SJLIFE. Cohorts differed based on the overall pregnancy rate, frequency of sterilizing procedures, and birth cohort.

Conclusions:

We were not able to replicate our findings of SNPs associated with pregnancy in childhood cancer survivors.

Impact:

Future attempts at replication should be considered in cohorts treated in a comparable era. In addition, understanding the role of genetics in fertility in childhood cancer survivors may be better approached using more advanced sequencing techniques.
First-In-Human Phase I Study of the OX40 Agonist MOXR0916 in Patients with Advanced Solid Tumors
Authors: Kim Tae Won , Burris Howard A. , de Miguel Luken Maria J. , Pishvaian Michael J. , Bang Yung-Jue , Gordon Michael , Awada Ahmad , Camidge D. Ross , Hodi F. Stephen , McArthur Grant A. , Miller Wilson H. , Cervantes Andres , Chow Laura Q. , Lesokhin Alexander M. , Rutten Annemie , Sznol Mario , Rishipathak Deepali , Chen Shang-Chiung , Stefanich Eric , Pourmohamad Tony , Anderson Maria , Kim Jeong , Huseni Mahrukh , Rhee Ina , Siu Lillian L.
Published: June 2022

Purpose:

OX40, a receptor transiently expressed by T cells upon antigen recognition, is associated with costimulation of effector T cells and impairment of regulatory T-cell function. This first-in-human study evaluated MOXR0916, a humanized effector-competent agonist IgG1 monoclonal anti-OX40 antibody.

Patients and Methods:

Eligible patients with locally advanced or metastatic refractory solid tumors were treated with MOXR0916 intravenously once every 3 weeks (Q3W). A 3+3 dose-escalation stage (0.2–1,200 mg; n = 34) was followed by expansion cohorts at 300 mg (n = 138) for patients with melanoma, renal cell carcinoma, non–small cell lung carcinoma, urothelial carcinoma, and triple-negative breast cancer.

Results:

MOXR0916 was well tolerated with no dose-limiting toxicities observed. An MTD was not reached. Most patients (95%) experienced at least one adverse event (AE); 56% of AEs, mostly grade 1–2, were related to MOXR0916. Most common treatment-related AEs included fatigue (17%), diarrhea (8%), myalgia (7%), nausea (6%), decreased appetite (6%), and infusion-related reaction (5%). Pharmacokinetic (PK) parameters were dose proportional between 80 and 1,200 mg and supported Q3W administration. The recommended expansion dose based on PK and OX40 receptor saturation was 300 mg Q3W. Immune activation and upregulation of PD-L1 was observed in a subset of paired tumor biopsies. One renal cell carcinoma patient experienced a confirmed partial response. Overall, 33% of patients achieved stable disease.

Conclusions:

Although objective responses were rarely observed with MOXR0916 monotherapy, the favorable safety profile and evidence of tumor immune activation in a subset of patients support further investigation in combination with complementary agents such as PD-1/PD-L1 antagonists.
The Predictive Value of Interleukin-8 in the Development of Cytomegalovirus Retinitis in HIV-Negative Patients
Authors: Qian Zhuyun , Fan Hua , Chen Xu , Tao Yong
Published: June 2022

Introduction: The aim of this study was to evaluate the value of interleukin (IL)-8 in the development and management of cytomegalovirus retinitis (CMVR) in HIV-negative patients. Methods: A retrospective case series from January 2014 to May 2018 was conducted. Forty patients (40 eyes) received intravitreal injection of ganciclovir (IVG). The aqueous levels of the cytomegalovirus (CMV) DNA and IL-8 in each follow-up visit were tested. The initial and final best-corrected visual acuity (BCVA), the course of treatment, the recurrence rate, and the occurrence of complications were recorded and analyzed. Results: The aqueous value of IL-8 was significantly correlated with the aqueous level of the CMV DNA during treatment but was not associated with the BCVA or the number of IVG. No recurrence occurred in the condition in which a low aqueous IL-8 level was set as the endpoint of the treatment. Conclusion: In HIV-negative patients with CMVR, IL-8 was closely associated with CMV DNA concentration in the aqueous humor. The real-time aqueous level of IL-8 could be used as one of the evidences of disease recovery.
Investigación y co-construcción de conocimientos sobre migraciones contemporáneas con niños, niñas y adolescentes
Authors:   Universidad de Manizales y el Cinde, Granda Indira
Published: June 2022

En esta entrevista, la doctora en antropología Valentina Glockner reflexiona sobre el protagonismo de las niñas, niños y adolescentes en las migraciones continentales. Destaca que la migración infantil tiene valor por sí misma, y no debería ser comprendida como supeditada a la migración adulta. También, habla de la coproducción de conocimiento en el «Mosaico Etnográfico Multimedia sobre las experiencias de niñas, niños y adolescentes migrantes en el continente americano» www.infanciasenmovimiento.org; un proyecto colaborativo de la Colectiva Infancias. Muy relacionado con esto, la antropóloga convoca a no perder el asombro que despierta la escucha sensible de las infancias, una escucha inseparable del reconocimiento político de los saberes, las memorias y las prácticas de libertad que emergen en el vaivén de sus migraciones —que es ya forma de vida y de producción y reproducción de la comunidad.
Protective Effects of MicroRNA‐200b‐3p Encapsulated by Mesenchymal Stem Cells–Secreted Extracellular Vesicles in Myocardial Infarction Via Regulating BCL2L11
Authors: Wan Jun , Lin Shaoyan , Yu Zhuo , Song Zhengkun , Lin Xuefeng , Xu Rongning , Du Songlin
Published: June 2022

Background

Extracellular vesicles (EVs) are a popular treatment candidate for myocardial injury. This work investigated the effects of mesenchymal stem cells (MSCs)–secreted EVs–derived miR‐200b‐3p on cardiomyocyte apoptosis and inflammatory response after myocardial infarction (MI) through targeting BCL2L11 (Bcl‐2–like protein 11) .

Methods and Results

EVs from MSCs were isolated and identified. EVs from MSCs with transfection of miR‐200b‐3p for overexpression were injected into MI mice. The effect of miR‐200b‐3p on cardiac function, infarction area, myocardial fibrosis, cardiomyocyte apoptosis, and inflammatory response was determined in MI mice. The targeting relationship between miR‐200b‐3p and BCL2L11 was verified, and the interaction between BCL2L11 and NLR family pyrin domain containing 1 (NLRP1) was also verified. MI mice were injected with an overexpressing BCL2L11 lentiviral vector to clarify whether BCL2L11 can regulate the effect of miR‐200b‐3p on MI mice. EVs from MSCs were successfully extracted. MSCs‐EVs improved cardiac function and reduced infarction area, apoptosis of cardiomyocytes, myocardial fibrosis, and inflammation in MI mice. Upregulation of miR‐200b‐3p further enhanced the effects of MSCs‐EVs on the myocardial injury of MI mice. BCL2L11 was targeted by miR‐200b‐3p and bound to NLRP1. Upregulation of BCL2L11 negated the role of miR‐200b‐3p–modified MSCs‐EVs in MI mice.

Conclusions

A summary was obtained that miR‐200b‐3p–encapsulated MSCs‐EVs protect against MI‐induced apoptosis of cardiomyocytes and inflammation via suppressing BCL2L11.
Correlation Between Cardiac Images, Biomarkers, and Amyloid Load in Wild‐Type Transthyretin Amyloid Cardiomyopathy
Authors: Morioka Mami , Takashio Seiji , Nakashima Naoya , Nishi Masato , Fujiyama Akira , Hirakawa Kyoko , Hanatani Shinsuke , Usuku Hiroki , Yamamoto Eiichiro , Kidoh Masafumi , Oda Seitaro , Matsushita Kenichi , Ueda Mitsuharu , Tsujita Kenichi
Published: June 2022

Background

Several imaging parameters and biomarkers provide diagnostic and prognostic information for wild‐type transthyretin amyloid cardiomyopathy. However, the relevance of these parameters and their association with cardiac amyloid load requires further substantiation. We aimed to elucidate the association of imaging parameters obtained using
99m
Tc‐labeled pyrophosphate scintigraphy, cardiovascular magnetic resonance imaging, global longitudinal strain (GLS), and cardiac biomarkers with cardiac amyloid load in patients with wild‐type transthyretin amyloid cardiomyopathy.

Methods and Results

Eighty‐eight patients with wild‐type transthyretin amyloid cardiomyopathy who underwent
99m
Tc‐labeled pyrophosphate scintigraphy and cardiovascular magnetic resonance were retrospectively evaluated. Quantitative cardiac amyloid load was obtained from 61 patients after myocardial biopsy. Correlations were assessed using Pearson’s correlation coefficient applied to medical record data. The mean heart to contralateral ratio, native T1, extracellular volume, and GLS were 1.91±0.36, 1419.4±56.4 ms, 56.5±13.6%, and −9.4±2.5%, respectively. Median high‐sensitivity cardiac troponin T (hs‐cTnT) and BNP (B‐type natriuretic peptide) levels were 0.0478 (0.0334‐0.0691) ng/mL and 213.8 (125.8–392.7) pg/mL, respectively. The mean cardiac amyloid load was 22.9±15.0%. The heart to contralateral ratio correlated significantly with native T1 (
r
=0.397), extracellular volume (
r
=0.477), GLS (
r
=0.363), cardiac amyloid load (
r
=0.379), and Ln (hs‐cTnT) (
r
=0.247). Further, cardiac amyloid load correlated significantly with native T1 (
r
=0.509), extracellular volume (
r
=0.310), GLS (
r
=0.446), and Ln (hs‐cTnT) (
r
=0.354). Compared with BNP, hs‐cTnT levels better correlated with several imaging parameters and cardiac amyloid load.

Conclusions

Increased cardiac amyloid load correlated with increased
99m
Tc‐labeled pyrophosphate positivity, native T1, extracellular volume, and hs‐cTnT levels, and an impaired GLS, suggesting that imaging parameters and cardiac biomarkers may reflect histological and functional changes attributable to amyloid deposition in the myocardium.
Corin Missense Variants, Blood Pressure, and Hypertension in 11 322 Black Individuals: Insights From REGARDS and the Jackson Heart Study
Authors: Parcha Vibhu , Irvin Marguerite R. , Lange Leslie A. , Armstrong Nicole D. , Pampana Akhil , Meyer Mariah , Judd Suzanne E. , Arora Garima , Arora Pankaj
Published: June 2022

Background

Corin enzyme contributes to the processing of inactive natriuretic peptides to bioactive hormones. In Black individuals, Corin gene variants (rs111253292 [Q568P] and rs75770792 [T555I]) have been previously reported to have a modest association with blood pressure (BP) and hypertension.

Methods and Results

We evaluated the association of Corin genotype with BP traits, prevalent hypertension, and incident hypertension among self‐identified 11 322 Black Americans in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study and the JHS (Jackson Heart Study) using multivariable‐adjusted regression modeling. Multivariable‐adjusted genotype‐stratified differences in NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and BNP (B‐type natriuretic peptide) levels were assessed. Genotype‐stratified
NPPA
and
NPPB
expression differences in healthy organ donor left atrial and left ventricular heart tissue (N=15) were also examined. The rs111253292 genotype was not associated with systolic BP (β±SE, 0.42±0.58; −1.24±0.82), diastolic BP (0.51±0.33; −0.41±0.46), mean arterial pressure (0.48±0.38; −0.68±0.51), and prevalent hypertension (odds ratio [OR], 0.93 [95% CI, 0.80–1.09]; OR, 0.79 [95% CI, 0.61–1.01]) in both REGARDS and JHS, respectively. The rs75770792 genotype was not associated with systolic BP (0.48±0.58; −1.26±0.81), diastolic BP (0.52±0.33; −0.33±0.45), mean arterial pressure (0.50±0.38; −0.63±0.50), and prevalent hypertension (OR, 1.02 [95% CI, 0.84–1.23]; OR, 0.87 [95% CI, 0.67–1.13]) in both cohorts, respectively. The Corin genotype was also not associated with incident hypertension (OR, 1.35 [95% CI, 0.94–1.93]; OR, 0.95 [95% CI, 0.64–1.39]) in the study cohorts. The NT‐proBNP levels in REGARDS and BNP levels in JHS were similar between the Corin genotype groups. In heart tissue, the
NPPA
and
NPPB
expression was similar between the genotype groups.

Conclusions

Corin
gene variants observed more commonly in Black individuals are not associated with differences in NP expression, circulating NP levels, and BP or hypertension as previously reported in candidate gene studies. Understanding the genetic determinants of complex cardiovascular traits in underrepresented populations requires further evaluation.