bluuebunny/crossref_metadata_2025 huggingface dataset:
A Risk-Factor Model for Antineoplastic Drug-Induced Serious Adverse Events in Cancer Inpatients: A Retrospective Study Based on the Global Trigger Tool and Machine Learning
Authors: Zhang Ni , Pan Ling-Yun , Chen Wan-Yi , Ji Huan-Huan , Peng Gui-Qin , Tang Zong-Wei , Wang Hui-Lai , Jia Yun-Tao , Gong Jun
Published: June 2022

The objective of this study was to apply a machine learning method to evaluate the risk factors associated with serious adverse events (SAEs) and predict the occurrence of SAEs in cancer inpatients using antineoplastic drugs. A retrospective review of the medical records of 499 patients diagnosed with cancer admitted between January 1 and December 31, 2017, was performed. First, the Global Trigger Tool (GTT) was used to actively monitor adverse drug events (ADEs) and SAEs caused by antineoplastic drugs and take the number of positive triggers as an intermediate variable. Subsequently, risk factors with statistical significance were selected by univariate analysis and least absolute shrinkage and selection operator (LASSO) analysis. Finally, using the risk factors after the LASSO analysis as covariates, a nomogram based on a logistic model, extreme gradient boosting (XGBoost), categorical boosting (CatBoost), adaptive boosting (AdaBoost), light-gradient-boosting machine (LightGBM), random forest (RF), gradient-boosting decision tree (GBDT), decision tree (DT), and ensemble model based on seven algorithms were used to establish the prediction models. A series of indicators such as the area under the ROC curve (AUROC) and the area under the PR curve (AUPR) was used to evaluate the model performance. A total of 94 SAE patients were identified in our samples. Risk factors of SAEs were the number of triggers, length of stay, age, number of combined drugs, ADEs occurred in previous chemotherapy, and sex. In the test cohort, a nomogram based on the logistic model owns the AUROC of 0.799 and owns the AUPR of 0.527. The GBDT has the best predicting abilities (AUROC = 0.832 and AUPR = 0.557) among the eight machine learning models and was better than the nomogram and was chosen to establish the prediction webpage. This study provides a novel method to accurately predict SAE occurrence in cancer inpatients.
Differential Branchial Response of Low Salinity Challenge Induced Prolactin in Active and Passive Coping Style Olive Flounder
Authors: Zeng Junjia , Li Jie , Yang Kun , Yan Jiayu , Xu Tianchun , Lu Weiqun
Published: June 2022

Stress coping styles are very common in fish, and investigations into this area can greatly improve fish welfare and promote the sustainable development of aquaculture. Although most studies have focused on the behavioral and physiological differences of these fishes, the endocrine response of different coping styles fish when undergoing salinity challenge is still unclear. We examined the physiological response in olive flounder with active coping (AC) style and passive coping (PC) style after transferred from seawater (SW) to freshwater for 0, 2, 5, 8, and 14 days. The results showed that: 1) the plasma prolactin level of FW-acclimated AC flounder was substantially higher than that of FW-acclimated PC flounder at 5, 8, and 14 days, and the branchial gene expression of prolactin receptor (PRLR) in AC flounder was slightly higher than PC flounder after transfer. While there was no remarkable difference observed in cortisol (COR) levels between AC and PC flounder. After transfer, glucocorticoid receptor (GR) expression in AC flounder was significantly higher compared with PC flounder at 8 days. 2) Branchial NKA-IR ionocytes numbers were reduced in PC flounder after transfer, while ionocytes number remain stable in AC flounder. 3) The branchial stem cell transcription factor foxi1 gene expression of AC flounder was significantly higher than PC flounder at 2, 5, and 14 days after transfer, while branchial stem cell transcription factor p63 gene expression of FW-acclimated AC flounder was only substantially higher than that of PC flounder at 5 days. 4) As an apoptosis upstream initiator, the branchial gene expression of caspase-9 in PC flounder was considerably higher than in AC flounder after transfer at 8 days. This study revealed that olive flounder with active and passive coping styles have different endocrine coping strategies after facing the low-salinity challenge. AC flounder adopt an active endocrine strategy by increasing ionocyte differentiation and prolactin secretion significantly. In contrast, PC flounder employ a passive strategy of reducing ionocytes differentiation and retaining prolactin content at a low level to reduce branchial ionocytes number.
Identification of a Male Sterile Candidate Gene in Lilium x formolongi and Transfer of the Gene to Easter Lily (L. longiflorum) via Hybridization
Authors: Moriyama Takahiro , Shea Daniel John , Yokoi Naoto , Imakiire Seiro , Saito Takaaki , Ohshima Hikaru , Saito Hina , Okamoto Satoru , Fukai Eigo , Okazaki Keiichi
Published: June 2022

Pollen-free varieties are advantageous in promoting cut-flower production. In this study, we identified a candidate mutation which is responsible for pollen sterility in a strain of Lilium × formolongi, which was originally identified as a naturally occurred male-sterile plant in a seedling population. The pollen sterility occurred due to the degradation of pollen mother cells (PMCs) before meiotic cell division. Genetic analysis suggested that the male-sterile phenotype is attributed to one recessive locus. Transcriptome comparison between anthers of sterile and fertile plants in a segregated population identified a transcript that was expressed only in pollen-fertile plants, which is homologous to TDF1 (DEFECTIVE in TAPETAL DEVELOPMENT and FUNCTION1) in Arabidopsis, a gene encoding a transcription factor AtMYB35 that is known as a key regulator of pollen development. Since tdf1 mutant shows male sterility, we assumed that the absence transcript of the TDF1-like gene, named as LflTDF1, is the reason for pollen sterility observed in the mutant. A 30 kbp-long nanopore sequence read containing LflTDF1 was obtained from a pollen-fertile accession. PCR analyses using primers designed from the sequence suggested that at least a 30kbp-long region containing LflTDF1 was deleted or replaced by unknown sequence in the pollen-sterile mutant. Since the cross between L. × formolongi and Easter lily (L. longiflorum) is compatible, we successfully introgressed the male-sterile allele, designated as lfltdf1, to Easter lily. To our knowledge, this is the first report of molecular identification of a pollen-sterile candidate gene in lily. The identification and marker development of LflTDF1 gene will assist pollen-free lily breeding of Easter lilies and other lilies.
Multivariate Statistical Analysis of Metabolites in Anisodus tanguticus (Maxim.) Pascher to Determine Geographical Origins and Network Pharmacology
Authors: Chen Chen , Wang Bo , Li Jingjing , Xiong Feng , Zhou Guoying
Published: June 2022

Anisodus tanguticus (Maxim.) Pascher, has been used for the treatment of septic shock, analgesia, motion sickness, and anesthesia in traditional Tibetan medicine for 2,000 years. However, the chemical metabolites and geographical traceability and their network pharmacology are still unknown. A total of 71 samples of A. tanguticus were analyzed by Ultra–Performance Liquid Chromatography Q–Exactive Mass Spectrometer in combination with chemometrics developed for the discrimination of A. tanguticus from different geographical origins. Then, network pharmacology analysis was used to integrate the information of the differential metabolite network to explore the mechanism of pharmacological activity. In this study, 29 metabolites were identified, including tropane alkaloids, hydroxycinnamic acid amides and coumarins. Principal component analysis (PCA) explained 49.5% of the total variance, and orthogonal partial least-squares discriminant analysis (OPLS–DA) showed good discrimination (R2Y = 0.921 and Q2 = 0.839) for A. tanguticus samples. Nine differential metabolites accountable for such variations were identified through variable importance in the projection (VIP). Through network pharmacology, 19 components and 20 pathways were constructed and predicted for the pharmacological activity of A. tanguticus. These results confirmed that this method is accurate and effective for the geographic classification of A. tanguticus, and the integrated strategy of metabolomics and network pharmacology can explain well the “multicomponent—-multitarget” mechanism of A. tanguticus.
Cultivation Model of Entrepreneurship From the Perspective of Artificial Intelligence Ethics
Authors: Yang Chunzheng , Lin Cuixia , Fan Xiaohuan
Published: June 2022

Students are the backbone of national development and progress, and should stand at the forefront of the era of innovation and entrepreneurship. Cultivating the entrepreneurship of college students is not only a response to the national call, but also a basic requirement for implementing quality education and promoting the comprehensive development of college students. To better study the entrepreneurship of college students, cultivate a group of newcomers of the era who have patriotic feelings, dare to innovate, hardworking and sustainable struggle, and solve the problem of college students' employment difficulties from the root, the cultivation mode of college students' entrepreneurship is studied. Firstly, the impact of artificial intelligence (AI) technology on social ethics is analyzed. Secondly, it analyzes the current situation of the cultivation of science and engineering college students' entrepreneurship from three aspects: Chinese traditional cultural thoughts influence the concept of career choice, enterprises emphasize utilitarianism, and colleges and universities attach importance to knowledge education and despise spiritual education. Finally, the data statistics on the cultivation of entrepreneurship of science and engineering college students are carried out in the form of questionnaires. The results demonstrate that among the students surveyed, 21.31% have a strong willingness to start their own business, and 72.84% have the idea of starting their own business, which means that most students still want to start a business through their own efforts, not blindly looking for jobs. Simultaneously, among many majors, 87.5% of students majoring in agriculture and medicine are better at finding new ways to solve problems, while the proportion of students majoring in literature and history is the lowest. It also indicates that most students believe that schools should add more seminar courses, internship courses, design courses, experimental courses, etc., and allow students to choose learning courses across colleges and majors, to cultivate college students' entrepreneurship. The proposed method provides some ideas for the application of AI technology in the cultivation of students' entrepreneurship.
The Impact of Data Vulnerability in Online Health Communities: An Institutional Assurance Perspective
Authors: Gao Wei , Wang Huiling , Jiang Ning
Published: June 2022

In the last few years, online health communities (OHCs) have experienced rapid development due to advances in technology and the COVID-19 pandemic. However, the sensitive nature of medical information has also raised concerns from users about their privacy and reduced their intention to use OHCs. Considering the critical role of data privacy, this study explored the effect of data vulnerability on OHC users. Using online survey data collected from 438 OHC users in China, we found that data vulnerability significantly reduced psychological comfort, while the latter enhanced continuance intention. We also found that psychological comfort negatively mediated the impact of data vulnerability on continuance intention. Institutional assurance approaches, namely privacy policy, privacy protection technology, industry self-regulation, and government legislation, were also found to mitigate the negative impact of data vulnerability on psychological comfort. This study not only contributes to the data privacy, psychological comfort, and institutional assurance literature but also offers suggestions for OHC stakeholders.
Development and Validation of Simplified Delirium Prediction Model in Intensive Care Unit
Authors: Kim Min-Kyeong , Oh Jooyoung , Kim Jae-Jin , Park Jin Young
Published: June 2022

Background

The intensive care unit (ICU) is where various medical staffs and patients with diverse diseases convene. Regardless of complexity, a delirium prediction model that can be applied conveniently would help manage delirium in the ICU.

Objective

This study aimed to develop and validate a generally applicable delirium prediction model in the ICU based on simple information.

Methods

A retrospective study was conducted at a single hospital. The outcome variable was defined as the occurrence of delirium within 30 days of ICU admission, and the predictors consisted of a 12 simple variables. Two models were developed through logistic regression (LR) and random forest (RF). A model with higher discriminative power based on the area under the receiver operating characteristics curve (AUROC) was selected as the final model in the validation process.

Results

The model was developed using 2,588 observations (training dataset) and validated temporally with 1,109 observations (test dataset) of ICU patients. The top three influential predictors of the LR and RF models were the restraint, hospitalization through emergency room, and drainage tube. The AUROC of the LR model was 0.820 (CI 0.801–0.840) and 0.779 (CI 0.748–0.811) in the training and test datasets, respectively, and that of the RF model was 0.762 (CI 0.732–0.792) and 0.698 (0.659–0.738), respectively. The LR model showed better discriminative power (z = 4.826; P < 0.001).

Conclusion

The LR model developed with brief variables showed good performance. This simplified prediction model will help screening become more accessible.
Investigating Predictive Factors of Suicidal Re-attempts in Adolescents and Young Adults After a First Suicide Attempt, a Prospective Cohort Study. Study Protocol of the SURAYA Project
Authors: Abrial Erika , Chalancon Benoît , Leaune Edouard , Brunelin Jérôme , Wallon Martine , Moll Frédéric , Barakat Nadine , Hoestlandt Benoit , Fourier Anthony , Simon Louis , Magnin Charline , Hermand Marianne , Poulet Emmanuel
Published: June 2022

Introduction

Suicide is the fourth leading cause of death in youth. Previous suicide attempts are among the strongest predictors of future suicide re-attempt. However, the lack of data and understanding of suicidal re-attempt behaviors in this population makes suicide risk assessment complex and challenging in clinical practice. The primary objective of this study is to determine the rate of suicide re-attempts in youth admitted to the emergency department after a first suicide attempt. The secondary objectives are to explore the clinical, socio-demographic, and biological risk factors that may be associated with re-attempted suicide in adolescents and young adults.

Methods

We have developed a single-center prospective and naturalistic study that will follow a cohort of 200 young people aged 16 to 25 years admitted for a first suicide attempt to the emergency department of Lyon, France. The primary outcome measure will be the incidence rate of new suicide attempts during 3 months of follow-up. Secondary outcomes to investigate predictors of suicide attempts will include several socio-demographic, clinical and biological assessments: blood and hair cortisol levels, plasma pro- and mature Brain-Derived Neurotrophic Factor (BDNF) isoforms proportion, previous infection with toxoplasma gondii, and C-Reactive Protein (CRP), orosomucoid, fibrinogen, interleukin (IL)-6 inflammatory markers.

Discussion

To our knowledge, the present study is the first prospective study specifically designed to assess the risk of re-attempting suicide and to investigate the multidimensional predictive factors associated with re-attempting suicide in youth after a first suicide attempt. The results of this study will provide a unique opportunity to better understand whether youth are an at-risk group for suicide re-attempts, and will help us identify predictive factors of suicide re-attempt risk that could be translated into clinical settings to improve psychiatric care in this population.

Clinical Trial Registration

ClinicalTrials.gov, identifier: NCT03538197, first registered on 05/29/2018. The first patient was enrolled 05/22/2018.
Technology and Older Women: Considerations Regarding Their Use and Misuse
Authors: Heine Chyrisse , Feldman Susan
Published: June 2022

Health and wellbeing are inextricably linked to an individual's capacity for continued meaningful engagement and connection with the world around them. Technological innovations designed to maximize the quality of life for older women range from sophisticated bio-medical interventions to ordinary day-to-day communication devices. Many innovations can ensure a higher quality of life for older women and support and care as required.

In this article, we consider: (1) The range of appropriate technologies currently available for older women, their families and communities. (2) The way technology contributes to the maintenance of optimum physical health and wellbeing for older women. (3) The significant challenges and considerations associated with the incorporation of technologies into their daily lives.
Transportation, Environmental Degradation, and Health Dynamics in the United States and China: Evidence From Bootstrap ARDL With a Fourier Function
Authors: Lin Meng-Chen , Wu Cheng-Feng
Published: June 2022

Transportation and environmental degradation, with indirect and direct effects, play a significant role in determining the health of a nation's citizens. This study uses bootstrap ARDL with a Fourier function to examine transportation, environmental degradation, and health dynamics in the United States and China. In the long run, the results support the cointegration relationship between transportation, environmental degradation, and health in both countries. The results show the contingency of the causality where a negative impact of transportation on environmental degradation exists in the United States while a positive impact exists in China. The effect of environmental degradation on health is negative in the United States while a positive effect exists in China. Regarding the causal direction between the variables of interest, the implications provide policymakers in developing strategy and policy for sustainable development.
Virtual Reality for Medical Annotation Tasks: A Systematic Review
Authors: Rother Anne , Spiliopoulou Myra
Published: June 2022

Virtual reality technologies are broadly used in medicine, including medical educational tasks like surgery training. Annotations are an inseparable part of many medical research and educational tasks. In this systematic review, we investigate the potential of VR for medical tasks with focus on annotation. The questions we pursue are as follows. (Q1) For which healthcare-associated tasks do we find VR-associated investigations and which involve a crowd worker-based annotation? (Q2) To what extent are there gender-specific differences in the usage of VR? To address these questions, we formulated a keyword list and inclusion/exclusion criteria for the collection of recent scientific articles according to the PRISMA Statement 2020. We queried the Medline database and included 59 free full articles available in English and published from 2017 upward. We inspected the abstracts of the retained articles and organized them into 6 categories that referred to VR in the medical context. We identified categories of medicine-related tasks, for which VR is used, and one category associated to cybersickness. We traced technologies used with a higher priority for some tasks, and we found that gender-related investigations are more widespread for some categories than for others. The main findings of our investigation on the role of VR for medical annotation tasks are as follows: VR was used widely for tasks associated with medicine, including medical research and healthcare, but the use of VR for annotation purposes in that context was very limited. Many of the relevant studies concerned VR in education, where annotations may refer to labeling or other enhancements of materials or may refer to exercises. The investigation of gender-related aspects was typically found in studies that encompassed the usage of VR on patients and controls, or on healthy participants in order to assess the potential and limitations of VR for specific tasks/medical assessments or treatments. To fully exploit the VR potential for tasks of medical annotation, especially for the creation of ground truth datasets and similar resources, more research is needed, especially on the interplay of annotator demographics and accessibility to VR technologies.
Rethinking Blended High Yielding Seed Varieties and Partial-Organic Fertilizer Climate Smart Agriculture Practices for Productivity and Farm Income Gains in the Drylands of Zimbabwe
Authors: Musara Joseph P. , Bahta Yonas T. , Musemwa Lovemore , Manzvera Joseph
Published: June 2022

Most blended climate smart agriculture (CSA) technologies focusing on seed-fertilizer combinations have either been marginally adopted or dis-adopted by smallholder farmers due to the nature of design and implementation. A data science research approach was used with 380 households in the mid-Zambezi Valley of Zimbabwe. The study examines impact of adopting a farmer initiated CSA practice combining improved sorghum seed variety and partial-organic fertilizer on household income and productivity among smallholder farmers in the drylands of Zimbabwe. A cross sectional household survey using multi stage sampling with purposive and stratified proportionate approaches was conducted. A structured questionnaire was utilized for data collection. Endogenous Switching Regression (ESR) model was utilized to account for self-selection bias of sampled farmers. Overall, a combination of farm specific factors (arable land, variable costs) and external factors (distance to the market, value of aid) have a bearing on the adoption decision and the associated impact on productivity and income. The counterfactual analysis shows that farmers who adopt the technology are relatively better off in productivity and income. Our findings highlight the significance of improving access to CSA practices which are initiated by the farmers using a bottom-up approach since they suit their operating contexts better. Tailor-made supporting programs including farmer networking platforms and decentralized markets need to be designed and scaled up by policymakers to encourage farmers to adopt blended soil fertility CSA practices in their farming practices. Networking arrangements need to be strengthened through local, government and private sector partnerships along the sorghum value chain.
Case Report: Multilevel Ossification of the Ligamentum Flavum in a Patient With Spinal Osteoblastoma
Authors: Montgomery Canada T. , Miranda Stephen P. , Nelson Ernest , Louka Katie , Nasrallah MacLean , Zhang Paul J. , Stein Joel , Petrov Dmitriy
Published: June 2022

Introduction

Spinal osteoblastomas are primary benign bone tumors most commonly presenting as diffuse back pain in young adults. Rarely, spinal osteoblastoma is associated with ossification of the ligamentum flavum (OLF), a form of ectopic bone formation, which can present with myelopathy. This report highlights a unique case of a patient with spinal osteoblastoma, associated OLF, and thoracic myelopathy.

Case Description

The patient presented with subtle myelopathy consisting of mid-thoracic back pain, paresthesias, and gait instability. Imaging findings were suggestive of spinal osteoblastoma with multifocal OLF. The patient was consented for thoracic decompression and stabilization at the T6-10 levels. Histopathology confirmed osteoblastoma with associated OLF. At follow up, the patient’s neurological symptoms had completely resolved.

Conclusion

This case describes management for a rare presentation of osteoblastoma with associated OLF and myelopathy. Surgeons should be wary of disproportionate neurological compromise when spinal osteoblastoma is associated with OLF. Further study is required to elucidate the pathogenesis of this condition.
Feed Composition and Isolate of Histomonas meleagridis Alter Horizontal Transmission of Histomonosis in Turkeys. Proof of Concept
Authors: Barros Thaina L. , Vuong Christine N. , Latorre Juan D. , Cuesta Roberto S. , McGill Elizabeth , Rochell Samuel J. , Tellez-Isaias Guillermo , Hargis Billy M.
Published: June 2022

Outbreaks of histomonosis in turkeys are typically initiated by the ingestion of contaminated embryonated eggs of Heterakis gallinarum, potentially present in earthworms and mechanical vectors. Once an outbreak is started, infected turkeys can transmit the disease by horizontal transmission. Factors influencing horizontal transmission of histomonosis are poorly understood. Replication of horizontal transmission in experimental conditions has not been consistent, presenting an obstacle in searching for alternatives to prevent or treat the disease. Two pilot experiments and three validation experiments were conducted in the present study. In pilot experiment 1, one isolate of Histomonas meleagridis (named Buford) was used. Turkeys were fed a low-nutrient density diet corn-soy based (LOW-CS) and raised in floor pens. In pilot experiment 2, another isolate of H. meleagridis was used (named PHL). Turkeys were fed a low-nutrient density diet with the addition of wheat middlings (LOW-WM) and raised in floor pens. In experiment 3, conducted on floor pens, both isolates and diets were used in different groups. In experiment 4, turkeys were raised on battery cages and only the PHL isolate was used. Both diets (LOW-WM and LOW-CS) were used, in addition to a diet surpassing the nutritional needs of young poults (turkey starter, TS). In experiment 5, conducted in battery cages, only the PHL isolate was used, and the LOW-WM and TS diets were in different groups. The horizontal transmission was achieved only with the PHL isolate from all experiments. The transmission rate varied among experimental diets, with the TS diet having the lowest transmission rate in experiments 4 and 5. Variation was observed between experiments and within experimental groups.
A Mathematical Model and Two Fuzzy Approaches Based on Credibility and Expected Interval for Project Cost-Quality-Risk Trade-Off Problem in Time-Constrained Conditions
Authors: Haghighi Mohammad Hossein , Mousavi Seyed Meysam
Published: June 2022

To successfully finalize projects and attain their determined purposes, it is indispensable to control all success criteria of a project. The time–cost trade-off (TCT) is known as a prevalent and efficient approach applied when the planned finish date of a project is not admitted by stakeholders, and consequently, the project duration must be decreased. This paper proposes a new mathematical model under fuzzy uncertainty to deal with the project cost–risk–quality trade-off problem (CRQT) under time constraints. Because of the unique nature of projects and their uncertain circumstances, applying crisp values for some project parameters does not seem appropriate. Hence, this paper employs fuzzy sets to resolve these weaknesses. In this study, two approaches are presented to handle proposed fuzzy multi-objective mathematical model. First, fuzzy credibility theory and then goal attainment method are used. Secondly, the model is solved by a fuzzy method based on expected interval and value and augmented ɛ-constraint method. A project from the literature review is adopted and solved by the presented methodology. The results demonstrate the accuracy and efficiency of the two proposed approaches for the introduced practical problem.
EDITORIAL: Stroke—Pathophysiology and New Therapeutic Strategies
Authors: Kelley Roger E.
Published: June 2022

This Special Issue of Biomedicines highlights recent advances in stroke evaluation and management and provides some pertinent information about potential new directions of stroke intervention in the research realm [...]
Novel Inflammasome-Based Risk Score for Predicting Survival and Efficacy to Immunotherapy in Early-Stage Non-Small Cell Lung Cancer
Authors: Tsao Chih-Cheng , Wu Hsin-Hung , Wang Ying-Fu , Shen Po-Chien , Wu Wen-Ting , Chen Huang-Yun , Dai Yang-Hong
Published: June 2022

Immune checkpoint inhibitors (ICI) for early-stage non-small cell lung cancer (NSCLC) have been approved to improve outcomes and reduce recurrence. Biomarkers for patient selection are needed. In this paper, we proposed an inflammasome-based risk score (IRS) system for prognosis and prediction of ICI response for early-stage NSCLC. Cox regression analysis was used to identify significant genes (from 141 core inflammasome genes) for overall survival (OS) in a microarray discovery cohort (n = 467). IRS was established and independently validated by other datasets (n = 1320). We evaluated the inflammasome signaling steps based on five gene sets, which were IL1B-, CASP-1-, IL18-, GSDMD-, and inflammasome-regulated genes. Gene set enrichment analysis, the Kaplan–Meier curve, receiver operator characteristic with area under curve (AUC) analysis, and advanced bioinformatic tools were used to confirm the ability of IRS in prognosis and classification of patients into ICI responders and non-responders. A 30-gene IRS was developed, and it indicated good risk stratification at 10-year OS (AUC = 0.726). Patients were stratified into high- and low-risk groups based on optimal cutoff points, and high-risk IRS had significantly poorer OS and relapse-free survival. In addition, the high-risk group was characterized by an inflamed immunophenotype and higher proportion of ICI responders. Furthermore, expression of SLAMF8 was the key gene in IRS and indicated good correlation with biomarkers associated with immunotherapy. It could serve as a therapeutic target in the clinical setting of immunotherapy.
Shaking Table Seismic Experimental Investigation of Lightweight Rigid Bodies
Authors: Cocuzza Avellino Giuseppe , Cannizzaro Francesco , Impollonia Nicola
Published: June 2022

This study presents the findings of an extensive shaking table experimental campaign conducted on nine free-standing wooden specimens, aiming at providing insights on the rigid body motion of free-standing objects. The specimens, which differ in slenderness and size, are characterized by impairments in their base surface and most likely in their shapes, which also lead to asymmetric responses. The imperfections of the tested objects are an additional source of uncertainty with respect to the intrinsic chaotic character of the rigid body motion, which is a crucial factor that prevents the reproducibility of the tests and induces discrepancies between specimen responses and those of their ideal models. A contactless measurement strategy is employed to assure unaltered data acquisition. The experimental campaign includes free vibration tests, pulse excitation, and natural ground motions tests; the dynamic responses of the specimens are organized and rearranged, aiming at providing a comprehensive set of data that could be employed for calibrating numerical models accounting for imperfect conditions. The damping properties of the specimens are discussed, providing a novel estimation of the coefficient of restitution based on the free vibration tests. The limits of the ideal simple rigid model are highlighted, and the roles of size factor and aspect ratio are discussed according to the obtained results.
The Occluded Epitope Residing in Spike Receptor-Binding Motif Is Essential for Cross-Neutralization of SARS-CoV-2 Delta Variant
Authors: Thongkum Weeraya , Thongheang Kanyarat , Tayapiwatana Chatchai
Published: June 2022

Concerns over vaccine efficacy after the emergence of the SARS-CoV-2 Delta variant prompted revisiting the vaccine design concepts. Monoclonal antibodies (mAbs) have been developed to identify the neutralizing epitopes on spike protein. It has been confirmed that the key amino acid residues in epitopes that induce the formation of neutralizing antibodies do not have to be on the receptor-binding domain (RBD)- angiotensin-converting enzyme 2 (ACE2) contact surface, and may be conformationally hidden. In addition, this epitope is tolerant to amino acid mutations of the Delta variant. The antibody titers against RBD in health care workers in Thailand receiving two doses of CoronaVac, followed by a booster dose of BNT162b2, were significantly increased. The neutralizing antibodies against the Delta variant suggest that the overall neutralizing antibody level against the Wuhan strain, using the NeutraLISA, was consistent with the levels of anti-RBD antibodies. However, individuals with moderate anti-RBD antibody responses have different levels of a unique antibody population competing with a cross-neutralizing mAb clone, 40591-MM43, determined by in-house competitive ELISA. Since 40591-MM43 mAb indicates cross-neutralizing activity against the Delta variant, this evidence implies that the efficiency of the vaccination regimen should be improved to facilitate cross-protective antibodies against Delta variant infections. The RBD epitope recognized by 40591-MM43 mAb is hidden in the close state.
State of Charge and Capacity Tracking in Vanadium Redox Flow Battery Systems
Authors: Schofield Kalvin , Musilek Petr
Published: June 2022

The vanadium redox flow battery electrolyte is prone to several capacity loss mechanisms, which must be mitigated to preserve electrolyte health and battery performance. This study investigates a simple and effective technique for the recovery of capacity loss arising from symmetrical mechanisms via automatic electrolyte rebalancing. However, chemical or electrochemical techniques must be used to mitigate capacity loss from asymmetrical mechanisms (e.g., air oxidation of V2+), which requires knowledge of the oxidation states present in the electrolytes. As such, this study assesses the suitability of SOC tracking via electrolyte absorption for independent monitoring of the anolyte and catholyte within an existing VRFB system. Testing is performed over cycling of a 40 cell, 2.5 kW with 40 L of electrolyte. Optical monitoring is performed using a custom-made flow cell with optical paths (interior cavity thicknesses) ranging from 1/4″ to 1/16″. Light transmitted through the cell by a 550 lumen white light source is monitored by a simple photodiode. The electrolyte rebalancing mechanism displayed success in recovering symmetrical capacity losses, while optical monitoring was unsuccessful due to the high absorbance of the electrolyte. Potential improvements to the monitoring system are presented to mitigate this issue.
Side-Channel Attacks on Masked Bitsliced Implementations of AES
Authors: Rădulescu Anca , Choudary Marios O.
Published: June 2022

In this paper, we provide a detailed analysis of CPA and Template Attacks on masked implementations of bitsliced AES, targeting a 32-bit platform through the ChipWhisperer side-channel acquisition tool. Our results show that Template Attacks can recover the full AES key successfully within 300 attack traces even on the masked implementation when using a first-order attack (no pre-processing). Furthermore, we confirm that the SubBytes operation is overall a better target for Template Attacks due to its non-linearity, even in the case of bitsliced implementations, where we can only use two bits per key byte target. However, we also show that targeting the AddRoundKey can be used to attack bitsliced implementations and that, in some cases, it can be more efficient than the SubBytes attack.
Studies on the Crystal Forms of Istradefylline: Structure, Solubility, and Dissolution Profile
Authors: Wang Yiyun , Xu Youwei , Zheng Zhonghui , Xue Min , Meng Zihui , Xu Zhibin , Li Jiarong , Lin Qing
Published: June 2022

Istradefylline as a selective adenosine A2A-receptor antagonist is clinically used to treat Parkinson’s disease and improve dyskinesia in its early stages. However, its crystal form, as an important factor in the efficacy of the drug, is rarely studied. Herein, three kinds of crystal forms of istradefylline prepared from ethanol (form I), methanol (form II), and acetonitrile (form III) are reported by use of a crystal engineering strategy. These three crystal forms were characterized and made into tablets for dissolution testing. Both the solubility and the dissolution rates were also determined. The dissolution rate of form I and form III is significantly higher than form II at pH 1.2 (87.1%, 58.2%, and 87.7% for form I, form II, and form III, respectively), pH 4.5 (88.1%, 58.9%, and 87.1% for form I, form II, and form III, respectively) and pH 6.8 (87.5%, 58.2%, and 86.0% for form I, form II, and form III, respectively) at 60 min. Considering the prepared solution and the proper dissolution profile, form I is anticipated to possess promising absorption for bioavailability.
Achieving Consensus for Management of Hormone-Sensitive, Low-Volume Metastatic Prostate Cancer in Italy
Authors: Verzoni Elena , Pappagallo Giovanni , Alongi Filippo , Arcangeli Stefano , Francolini Giulio , Galanti Daniele , Galli Luca , Maruzzo Marco , Rossetti Sabrina , Siepe Giambattista , Triggiani Luca , Zucali Paolo Andrea , D’Angelillo Rolando Maria
Published: June 2022

Metastatic hormone-sensitive prostate cancer (mHSPC) is usually categorized as high- or low-volume disease. This is relevant because low- and high-volume metastatic disease are associated with different outcomes, and thus management of the two forms should differ. Although some definitions have been reported, the concept of oligometastatic disease is not so clearly defined, giving rise to further variability in the choice of treatment, mainly between systemic agents and radiotherapy, especially in the era of metastasis-directed therapy. With the aim of providing clinicians with guidance on best practice, a group of medical and radiation oncologists, experts in prostate cancer, used the round robin method to generate a series of consensus statements on management of low-volume mHSPC. Consensus was obtained on three major areas of controversy: (1) with regard to clinical definitions of mHSPC, it was held that oligometastatic and low-volume disease refer to different concepts and should not be used interchangeably; (2) regarding therapy of de novo low-volume metastatic disease, androgen deprivation therapy alone can be considered undertreatment, and all patients should be evaluated for systemic treatment combinations; local therapy should not be denied in patients with mHSPC, regardless of the intensity of systemic therapy, and metastasis-directed therapy can be proposed in selected cases; (3) with regard to treatment of metachronous metastatic disease, patients should be evaluated for systemic treatment combinations. Metastasis-directed therapy can be proposed to delay systemic treatment in selected cases, especially if prostate-specific membrane antigen positron emission tomography staging has been performed and when indolent disease occurs. It is hoped that clinicians treating patients with mHSPC in daily practice will find this expert opinion of value.
Trajectory Tracking within a Hierarchical Primitive-Based Learning Approach
Authors: Radac Mircea-Bogdan
Published: June 2022

A hierarchical learning control framework (HLF) has been validated on two affordable control laboratories: an active temperature control system (ATCS) and an electrical rheostatic braking system (EBS). The proposed HLF is data-driven and model-free, while being applicable on general control tracking tasks which are omnipresent. At the lowermost level, L1, virtual state-feedback control is learned from input–output data, using a recently proposed virtual state-feedback reference tuning (VSFRT) principle. L1 ensures a linear reference model tracking (or matching) and thus, indirect closed-loop control system (CLCS) linearization. On top of L1, an experiment-driven model-free iterative learning control (EDMFILC) is then applied for learning reference input–controlled outputs pairs, coined as primitives. The primitives’ signals at the L2 level encode the CLCS dynamics, which are not explicitly used in the learning phase. Data reusability is applied to derive monotonic and safely guaranteed learning convergence. The learning primitives in the L2 level are finally used in the uppermost and final L3 level, where a decomposition/recomposition operation enables prediction of the optimal reference input assuring optimal tracking of a previously unseen trajectory, without relearning by repetitions, as it was in level L2. Hence, the HLF enables control systems to generalize their tracking behavior to new scenarios by extrapolating their current knowledge base. The proposed HLF framework endows the CLCSs with learning, memorization and generalization features which are specific to intelligent organisms. This may be considered as an advancement towards intelligent, generalizable and adaptive control systems.
Joint Detection of Community and Structural Hole Spanner of Networks in Hyperbolic Space
Authors: Nie Qi , Jiang Hao , Zhong Si-Dong , Wang Qiang , Wang Juan-Juan , Wang Hao , Wu Li-Hua
Published: June 2022

Community detection and structural hole spanner (the node bridging different communities) identification, revealing the mesoscopic and microscopic structural properties of complex networks, have drawn much attention in recent years. As the determinant of mesoscopic structure, communities and structural hole spanners discover the clustering and hierarchy of networks, which has a key impact on transmission phenomena such as epidemic transmission, information diffusion, etc. However, most existing studies address the two tasks independently, which ignores the structural correlation between mesoscale and microscale and suffers from high computational costs. In this article, we propose an algorithm for simultaneously detecting communities and structural hole spanners via hyperbolic embedding (SDHE). Specifically, we first embed networks into a hyperbolic plane, in which, the angular distribution of the nodes reveals community structures of the embedded network. Then, we analyze the critical gap to detect communities and the angular region where structural hole spanners may exist. Finally, we identify structural hole spanners via two-step connectivity. Experimental results on synthetic networks and real networks demonstrate the effectiveness of our proposed algorithm compared with several state-of-the-art methods.
Corporate Entrepreneurship and Innovation Performance: The Mediating Effect of Employee Engagement through Leader’s Supervision
Authors: Cherif Fatma Makhlouf
Published: June 2022

The purpose of this paper was to investigate the mediated moderating effect of employee engagement (EE) by leader’s supervision in the effects of corporate entrepreneurship (CE) on innovation performance (IP). The study applied the cross-sectional analysis with our own survey that provided the data for this design. A total of 248 participants (12 managers, and 236 employees) were recruited for this study. The relationship of CE and IP was mediated by EE. Additionally, leader’s supervision moderated the relationship between CE and IP. Furthermore, leader’s supervision had a mediated moderation effect from CE to the IP, through the EE. The significance of this study lies in its contribution to CE, IP, EE and leader’s supervision literatures. It was revealed that CE behavior was found in the organizational learning processes that strengthen employees’ ability to analyze markets and formulate new products.
Global m6A RNA Methylation in SARS-CoV-2 Positive Nasopharyngeal Samples in a Mexican Population: A First Approximation Study
Authors: Batista-Roche Jorge Luis , Gómez-Gil Bruno , Lund Gertrud , Berlanga-Robles César Alejandro , García-Gasca Alejandra
Published: June 2022

The Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the causal agent of COVID-19 (Coronavirus Disease-19). Both mutation and/or recombination events in the SARS-CoV-2 genome have resulted in variants that differ in transmissibility and severity. Furthermore, RNA methylation of the N6 position of adenosine (m6A) is known to be altered in cells infected with SARS-CoV-2. However, it is not known whether this epitranscriptomic modification differs across individuals dependent on the presence of infection with distinct SARS-CoV-2 variants, the viral load, or the vaccination status. To address this issue, we selected RNAs (n = 60) from SARS-CoV-2 sequenced nasopharyngeal samples (n = 404) of 30- to 60-year-old outpatients or hospitalized individuals from the city of Mazatlán (Mexico) between February 2021 and March 2022. Control samples were non-infected individuals (n = 10). SARS-CoV-2 was determined with real-time PCR, viral variants were determined with sequencing, and global m6A levels were determined by using a competitive immunoassay method. We identified variants of concern (VOC; alpha, gamma, delta, omicron), the variant of interest (VOI; epsilon), and the lineage B.1.1.519. Global m6A methylation differed significantly across viral variants (p = 3.2 × 10−7). In particular, we found that m6A levels were significantly lower in the VOC delta- and omicron-positive individuals compared to non-infected individuals (p = 2.541236 × 10−2 and 1.134411 × 10−4, respectively). However, we uncovered no significant correlation between global m6A levels and viral nucleocapsid (N) gene expression or age. Furthermore, individuals with complete vaccination schemes showed significantly lower m6A levels than unvaccinated individuals (p = 2.6 × 10−4), and differences in methylation levels across variants in unvaccinated individuals were significant (p = 3.068 × 10−3). These preliminary results suggest that SARS-CoV-2 variants show differences in global m6A levels.
Recent Advances in Passive Acoustic Localization Methods via Aircraft and Wake Vortex Aeroacoustics
Authors: Joshi Arnav , Rahman Mustafa M. , Hickey Jean-Pierre
Published: June 2022

Passive acoustic aircraft and wake localization methods rely on the noise emission from aircraft and their wakes for detection, tracking, and characterization. This paper takes a holistic approach to passive acoustic methods and first presents a systematic bibliographic review of aeroacoustic noise of aircraft and drones, followed by a summary of sound generation of wing tip vortices. The propagation of the sound through the atmosphere is then summarized. Passive acoustic localization techniques utilize an array of microphones along with the known character of the aeroacoustic noise source to determine the characteristics of the aircraft or its wake. This paper summarizes the current state of knowledge of acoustic localization with an emphasis on beamforming and machine learning techniques. This review brings together the fields of aeroacoustics and acoustic-based detection the advance the passive acoustic localization techniques in aerospace.
Did We Need Another Emma? The Anxiety of Influence in the Bollywood Adaptation of Emma
Authors: Bharat Meenakshi
Published: June 2022

The multiple screen adaptations of Jane Austen’s novels, and in particular, those of Emma (1815–1816), willy-nilly direct audience attention to the problematic continuities between the original novel and Rajshri Ojha’s twenty-first century Bollywood adaptation, Aisha (2010). This essay addresses the issue of the competing influence of Austen and the global cinematic adaptations that precede this Hindi adaptation, even as it assesses the film for its engagement with the adaptation of Austenian social concerns to the particularities of the contemporary upper-middle-class urban existence in India.