bluuebunny/crossref_metadata_2025 huggingface dataset:
APPLICATION OF MODELING TOOLS IN THE FRAMEWORK OF SMART PETROCHEMICAL PRODUCTION
Authors:   Kazan National Research Technological University, Kazan, Russian Federation, NURGALIEV RUSTAM , SHINKEVICH ALEXEY
Published: May 2022

The purpose of the research. The research is aimed at identifying the possibilities of using various modeling tools in the framework of the functioning of “smart” petrochemical production. To achieve the goal contributed to a number of tasks: to study the possibility of applying IDEF0 methodology in terms of building a “smart” production, to build the decomposition process, the introduction of new equipment in a “smart” the petrochemical industry in BPMN notation, to explore the specific neural network modeling and to develop a neural network model to predict energy consumption of petrochemical plants. Results. It is summarized that modeling is an integral element of the design and management of “smart” petrochemical production, provides process optimization, rationalization of the information and communication environment of the enterprise, energy saving, improving the quality of petrochemical products, production efficiency, reducing the negative impact on the environment; “smart” production should be accompanied by the development of a mechanism for digitalization of production processes, regulation of the algorithm for building cyberspace. We need an integrated approach to production modeling, which involves end-to-end data management at all stages of production, using various modeling methods, and consolidating the results of modeling in a single database, which serves as a relevant empirical basis for making rational management decisions. The study developed a scheme to enter the production assets to the smart production (BPMN notation), a flow of the process, taking into account the difficult situation related to the operation of production equipment; a logical and informational model of the formation of a “smart” petrochemical production (in the IDEF0 notation) is constructed, which takes into account the relationships between sub-processes and the potential effect, allowing for the development of instructions and methodological materials for the modernization of petrochemical production; A predictive model for regulating the level of energy consumption by petrochemical enterprises, depending on the costs of technological innovations and on the volume of polluting emissions generated by industrial enterprises, is proposed, based on training neural networks of different architectures and allowing, in accordance with the activation function of the hidden layer of the neural network, to identify trends in energy consumption.
DEVELOPMENT OF AN ALGORITHM FOR OPTIMIZING ENERGY CONSUMPTION IN CHEMICAL-TECHNOLOGICAL SYSTEMS BASED ON STATISTICAL TRAINING
Authors:   Kazan National Research Technological University, Kazan, Russian Federation, MALYSHEVA TATYANA
Published: May 2022

The purpose of the research. The aim of the study is to develop approaches to solving the problems of optimizing the energy resources of chemical-technological systems based on statistical training. As the main research methods, the article uses graphical and tabular tools for descriptive data analysis to study the dynamics of the structure of energy carriers and determine possible reserves for reducing consumption; method of training neural networks to predict optimal values of energy consumption. Results. The article analyzes the current trends in the energy intensity of the cost of chemical production with an assessment of the degree of transformation of the structure of the energy portfolio and possible reserves for reducing the specific weight of electrical and thermal energy. The method of training neural articles using a regression predictive model was used to determine the minimum possible values of the parameter of energy resources consumption at the upper limit of the range, taking into account the limitations of the technological regulations for the production of chemicals and chemical products. The results of the study are applicable in the development of software complexes for intelligent energy systems, in the process of determining the cause-and-effect relationships of deviations in resource consumption from a given trajectory and the optimal vector of sustainable energy consumption.
INCREASING PRODUCTIVITY OF VIBRATION HOPPER LOADERS BY INSTALLATION PLANETARY VIBRODRIVE WITH KINEMATICALLY UNBALANCED MASSES
Authors:   South Ural State University, Chelyabinsk, Russian Federation, ZAKIROV RODION , NEKRUTOV VLADIMIR
Published: May 2022

Introduction. The article considers the application of planetary vibration motor with kinematically unbalanced masses with a wide range of adjustable parameters of the operating body oscillations in vibration hopper loaders. Materials and methods. The method of oscillation generation allows adjusting the oscillation frequency and amplitude and at the same time synchronization of oscillatory movements of two working bodies is provided. The authors conducted the analysis of existing design solutions for the problem of control over oscillatory process parameters in vibration hopper loaders. Regulation of the frequency and amplitude of oscillations, and, consequently, associated with them, the speed of movement and the driving force of the working bodies is possible by changing the combination of kinematic, geometric and force parameters by planetary vibration motor with kinematically unbalanced masses. Regulation of kinematic and power parameters can be carried out automatically. They provide theoretical justification for the planetary vibration motor with kinematically unbalanced masses application in flexible industrial systems to improve the flexibility and operation efficiency of vibration hopper loaders. Experimental research. Further, the authors describe the experimental research of the developed designs for such vibration hopper loaders with planetary vibration motor with kinematically unbalanced masses. There search results are provided in comparison with the existing design options. The results of oscillatory processes, presented show the principal possibilities of the considered vibration drives in relation to the control over actuating device oscillation parameters. Conclusions. The optimal parameters and methods for the control over the designed vibration hopper loaders have been found out. They help to substantially improve the system flexibility, expand technological opportunities of hopper loaders and obtain a significant technical & economic effect in the area of flexible production.
ALGORITHM FOR DETERMINING THE INTENSITY OF ACCESS TO DATA STRUCTURES IN A COMPUTER PROGRAM
Authors:   Main Computing Center is a Branch of JSC Russian Railways (MCC), Moscow, Russian Federation, NAUMCHIK NIKOLAY
Published: May 2022

The purpose of the research. The article discusses the problem of efficient use of computational resources. Describes the hardware prefetching mechanism. The purpose of the study is to find a solution that provides the ability to evaluate the quantitative use of the memory area in a computer program. This, in turn, is necessary to improve the efficiency of using the hardware capabilities of the computer. Results. As a result of the study, the author comes to the conclusion that the desired solution is an algorithm for determining the intensity of access to data structures in a computer program. The article presents the terminology that explains the name of the indicators used in the algorithm, describes the mathematical model for calculating the indicator and its limitations. A system of equations expressing the range of values of the data access intensity indicator was formulated. A three-dimensional model and two two-plane graphs were constructed to obtain a complete picture of the perception of the range of values. A detailed description of the algorithm and the presented mathematical model of the final and intermediate calculations allow us to develop an automated solution for certain tools (for example, compilers) used in the development of a computer program. The author concludes that the obtained indicator provides a quantitative representation of the use of shares of information (data areas) in a computer program for the subsequent assessment of the effectiveness of the computer program and the data structures used. Based on the results of the assessment, decisions can be made on the conformity / non conformity of the proposed solution and the need to modify the computer program or the data structures used.
A Final Cure to the Tribulations of the Vacuum in Quantum Theory
Authors: Jean-Claude Joseph
Published: May 2022

Quantum Field Theory has seemingly been of late anything but unraveling. Undeniably, for many different reasons there is a rampant discomfort with the Standard Model as a complementing extension of QFT. Prior to the recent supersymmetry upset, the “vacuum catastrophe” or “cosmological constant problem” shook the very foundations of QFT. Effectively the enormous numeric disparity between its predicted value of the vacuum energy density, and the measured value from a Relativistic approach has been qualified by some as the biggest predictive failure of any Theory. QFT has been left searching for its soul now for almost two decades. Under the umbrella of Quanto-Geometric Theory, we offer a different approach to the problem which successfully calculates a sensible and consistent value of the vacuum energy density from first axiomatic principles, casting a close match with the cosmological quantity, thereby bridging the grueling gap between the quantum vacuum and the relativistic vacuum.
Colistin Resistance and Molecular Characterization of the Genomes of mcr-1-Positive Escherichia coli Clinical Isolates
Authors: Li Qiaoling , Qian Changrui , Zhang Xueya , Zhu Tingting , Shi Weina , Gao Mengdi , Feng Chunlin , Xu Ming , Lin Hailong , Lin Li , Lu Junwan , Lin Xi , Li Kewei , Xu Teng , Bao Qiyu , Li Changchong , Zhang Hailin
Published: May 2022

Research on resistance against polymyxins induced by the mcr-1 gene is gaining interest. In this study, using agar dilution method, polymerase chain reaction, and comparative genomic analysis, we investigated the colistin resistance mechanism of clinical E. coli isolates. The minimum inhibitory concentration (MIC) analysis results revealed that of the 515 isolates tested, bacteria with significantly increased MIC levels against colistin were isolated in 2019. Approximately one-fifth (17.14% to 19.65%) of the isolates showed MIC values ≥1 mg/L against colistin in 2015, 2016, and 2017. However, in 2019, up to three-quarters (74.11%, 146/197) of the isolates showed MIC values ≥1 mg/L against colistin indicating an increase in colistin resistance. Six isolates (EC7518, EC4968, EC3769, EC16, EC117, EC195, 1.13%, 6/515) were found to carry the mcr-1 gene and a novel mcr-1 variant with Met2Ile mutation was identified in EC3769. All six strains showed higher MIC levels (MIC=4 mg/L) than any mcr-1-negative strains (MIC ≤ 2 mg/L). Whole-genome sequencing of the six mcr-1-positive isolates revealed that EC195 carried the highest number of resistance genes (n = 28), nearly a half more than those of the following EC117 (n = 19). Thus, EC195 showed a wider resistance spectrum and higher MIC levels against the antimicrobials tested than the other five isolates. Multi-locus sequence typing demonstrated that these mcr-1-positive strains belonged to six different sequence types. The six mcr-1 genes were located in three different incompatibility group plasmids (IncI2, IncHI2 and IncX4). The genetic context of mcr-1 was related to a sequence derived from Tn6330 (ISApl1-mcr-1-pap2-ISApl1). Investigations into the colistin resistance mechanism and characterization of the molecular background of the mcr genes may help trace the development and spread of colistin resistance in clinical settings.
Time to Death and Its Determinant Factors Among Patients With Chronic Heart Failure in Northwest Ethiopia: A Retrospective Study at Selected Referral Hospitals
Authors: Moyehodie Yikeber Abebaw , Muluneh Mitiku Wale , Belay Alebachew Taye , Fenta Setegn Muche
Published: May 2022

Background

Heart failure (HF) is a major health problem that affects patients and healthcare systems worldwide. It is the leading cause of morbidity and death and negatively impacts the quality of life, healthcare costs, and longevity. However, the causes of death were not well defined. This study aimed to identify the determinants of death among patients with HF in the Amhara Region, Northwest Ethiopia.

Methods

A multicenter retrospective cohort study was conducted on 285 patients in the age group 15 years or older under follow-up from 1 January 2015 to 31 December 2019. Descriptive analyses were summarized using the Kaplan–Meier survival curve and the log-rank test. Then, the Cox-proportional hazard regression model was employed to estimate the hazard of death up to 5 years after they were admitted to the HF department to follow up on their treatment.

Results

Out of 285 patients with HF, 93(32.6%) of the respondents were dying within 5 years of follow-up. Anemia was the common comorbid disease (30.5%), and valvular heart disease was the most common etiology (33.7%) of chronic heart failure in this study. This study showed a significant mortality difference between hospitals. HF patients with hypertension [adjusted hazard ratio (AHR): 3.5076, 95% confidence interval (CI): 1.43, 8.60], anemia (AHR: 2.85, 95% 1.61, 5.03), pneumonia (AHR: 2.02, 95% 1.20, 3.39), chronic kidney disease (2.23, CI: 1.31, 3.77), and diabetes mellitus (AHR: 2.42, 95% CI: 1.43, 4.09) were at a higher risk of death. Moreover, patients with symptoms listed in the New York Heart Association Class (III and IV), Ischemic Heart Disease and unknown etiologies, men (AHR: 2.76, 95%:1.59, 4.78), and those with a high pulse rate (AHR: 1.02, 95%:1.00, 1.04) were at a higher risk of death.

Conclusion

There was a mortality difference between hospitals. This study has revealed that HF patients with anemia, diabetes mellitus, pneumonia, hypertension, chronic kidney disease, HF etiologies, severe New York Heart Association Class (III and IV), men, and high pulse rate were the main factors associated with death. Health professionals could give more attention to patients whose pulse rate is high, men, and a patient who had comorbidities in the ward.
Case Report: Family Curse: An SCN5A Mutation, c.611C>A, p.A204E Associated With a Family History of Dilated Cardiomyopathy and Arrhythmia
Authors: Huang Wen , Xu Rui , Gao Ning , Wu Xia , Wen Cong
Published: May 2022

Objective

We report a 3-generation family with SCN5A c.611 C>A rare variant, whose clinical characteristics are dilated cardiomyopathy (DCM) combined with multifocal ectopic Purkinje-related premature contractions (MEPPC). We tried to explain why the same SCN5A variant carriers had different phenotypes.

Methods

We collected the clinical data from the family, and followed up this family members. Genetic testing was done for whom DNA samples could be collected.

Results

Information was collected from 15 people in this family, 8 of whom had genetic testing. The SCN5A variant was present in all patients of this family, whose clinical features showed DCM combined with MEPPC. The proband's children developed DCM and MEPPC in their childhood. They both carried a SCN5A p.A204E mutation from their mother and a mutation PRKAG2 p.D372N from their father. The son did heart transplant and his heart was both dilated and thickened. The pathology confirmed the presence of glycogen accumulation in the myocardium, which were consistent with the diagnosis of PAKAG2 syndrome.

Conclusion

SCN5A c.611 C>A variant was related to DCM combined with MEPPC. This case report is the first to demonstrate that a combination of SCN5A and PRKAG2 mutations can cause DCM plus MEPPC and PRKAG2 Syndrome.
Effect of Alirocumab on Coronary Calcification in Patients With Coronary Artery Disease
Authors: Gao Fei , Li Yue Ping , Ma Xiao Teng , Wang Zhi Jian , Shi Dong Mei , Zhou Yu Jie
Published: May 2022

Background

Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been documented with significantly reduction in LDL cholesterol levels and cardiovascular events. However, evidence regarding the impact of PCSK9 inhibitors on coronary calcification is limited.

Methods

Eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard statin therapy. Calcium score based on coronary computed tomographic angiography at baseline and follow up were compared.

Results

Compared with baseline levels, LDL cholesterol were significantly decreased in both groups, while the absolute reduction of LDL cholesterol levels were higher in patients treated with alirocumab (1.69 ± 0.52 vs. 0.92 ± 0.60, P < 0.0001). Additionally, patients in alirocumab group demonstrated a significant reduction of Lp(a) levels, whereas it was not observed in the standard statin group. Notably, greater increases in the percentage changes of CAC score (10.6% [6.3–23.3] vs. 2.9% [−6.7–8.3]; P < 0.0001) were observed in the statin group compared to the alirocumab group. Consistently, CAC progression was significantly lower in the alirocumab group than in the standard statin group (0.6 ± 2.2% vs. 2.7 ± 2.3%; P = 0.002).

Conclusions

Study indicated that administration of the PCSK9 inhibitors to statins produced significantly lower rate of CAC progression in patients with coronary artery disease. Further studies with CAC progression and their clinical outcomes are needed.

Trial Registration

ClinicalTrials.gov, Identifier: NCT04851769.
ECGAssess: A Python-Based Toolbox to Assess ECG Lead Signal Quality
Authors: Kramer Linus , Menon Carlo , Elgendi Mohamed
Published: May 2022

Electrocardiography (ECG) is the method most often used to diagnose cardiovascular diseases. To obtain a high-quality recording, the person conducting an ECG must be a trained expert. When these experts are not available, this important diagnostic tool cannot be used, consequently impacting the quality of healthcare. To avoid this problem, it must be possible for untrained healthcare professionals to record diagnostically useful ECGs so they can send the recordings to experts for diagnosis. The ECGAssess Python-based toolbox developed in this study provides feedback regarding whether ECG signals are of adequate quality. Each lead of the 12-lead recordings was classified as acceptable or unacceptable. This feedback allows people to identify and correct errors in the use of the ECG device. The toolbox classifies the signals according to stationary, heart rate, and signal-to-noise ratio. If the limits of these three criteria are exceeded, this is indicated to the user. To develop and optimize the toolbox, two annotators reviewed a data set of 1,200 ECG leads to assess their quality, and each lead was classified as acceptable or unacceptable. The evaluation of the toolbox was done with a new data set of 4,200 leads, which were annotated the same way. This evaluation shows that the ECGAssess toolbox correctly classified over 94% of the 4,200 ECG leads as either acceptable or unacceptable in comparison to the annotations.
Metabolism and Endocrine Disorders: What Wnt Wrong?
Authors: Franco Carolina N. , Noe May M. , Albrecht Lauren V.
Published: May 2022

A fundamental question in cell biology underlies how nutrients are regenerated to maintain and renew tissues. Physiologically, the canonical Wnt signaling is a vital pathway for cell growth, tissue remodeling, and organ formation; pathologically, Wnt signaling contributes to the development of myriad human diseases such as cancer. Despite being the focus of intense research, how Wnt intersects with the metabolic networks to promote tissue growth and remodeling has remained mysterious. Our understanding of metabolism has been revolutionized by technological advances in the fields of chemical biology, metabolomics, and live microscopy that have now made it possible to visualize and manipulate metabolism in living cells and tissues. The application of these toolsets to innovative model systems have propelled the Wnt field into new realms at the forefront answering the most pressing paradigms of cell metabolism in health and disease states. Elucidating the basis of Wnt signaling and metabolism in a cell-type and tissue-specific manner will provide a powerful base of knowledge for both basic biomedical fields and clinician scientists, and has the promise to generate new, transformative therapies in disease and even processes of aging.
Low NAD+ Levels Are Associated With a Decline of Spermatogenesis in Transgenic ANDY and Aging Mice
Authors: Meyer-Ficca Mirella L. , Zwerdling Alexie E. , Swanson Corey A. , Tucker Abby G. , Lopez Sierra A. , Wandersee Miles K. , Warner Gina M. , Thompson Katie L. , Chini Claudia C.S. , Chen Haolin , Chini Eduardo N. , Meyer Ralph G.
Published: May 2022

Advanced paternal age has increasingly been recognized as a risk factor for male fertility and progeny health. While underlying causes are not well understood, aging is associated with a continuous decline of blood and tissue NAD+ levels, as well as a decline of testicular functions. The important basic question to what extent ageing-related NAD+ decline is functionally linked to decreased male fertility has been difficult to address due to the pleiotropic effects of aging, and the lack of a suitable animal model in which NAD+ levels can be lowered experimentally in chronologically young adult males. We therefore developed a transgenic mouse model of acquired niacin dependency (ANDY), in which NAD+ levels can be experimentally lowered using a niacin-deficient, chemically defined diet. Using ANDY mice, this report demonstrates for the first time that decreasing body-wide NAD+ levels in young adult mice, including in the testes, to levels that match or exceed the natural NAD+ decline observed in old mice, results in the disruption of spermatogenesis with small testis sizes and reduced sperm counts. ANDY mice are dependent on dietary vitamin B3 (niacin) for NAD+ synthesis, similar to humans. NAD+-deficiency the animals develop on a niacin-free diet is reversed by niacin supplementation. Providing niacin to NAD+-depleted ANDY mice fully rescued spermatogenesis and restored normal testis weight in the animals. The results suggest that NAD+ is important for proper spermatogenesis and that its declining levels during aging are functionally linked to declining spermatogenesis and male fertility. Functions of NAD+ in retinoic acid synthesis, which is an essential testicular signaling pathway regulating spermatogonial proliferation and differentiation, may offer a plausible mechanism for the hypospermatogenesis observed in NAD+-deficient mice.
Forest Proximity Positively Affects Natural Enemy Mediated Control of Fall Armyworm in Southern Africa
Authors: Clarkson Juliet , Borah Joli R. , Baudron Frédéric , Sunderland Terry C. H.
Published: May 2022

The fall armyworm (FAW, Spodoptera frugiperda) is a major crop pest in southern Africa. It threatens the livelihoods and food security of smallholder farmers in the region by negatively impacting maize yield. Although scientific evidence suggests that natural enemy-mediated predation can potentially reduce FAW infestation, the effectiveness of natural enemies such as birds, bats, parasitoids, and generalist predators on FAW is poorly understood. This study reviews existing literature to assess how birds, bats, parasitoids, and generalist predators’ control FAW infestation, as well as the role of forest or tree cover in natural enemy mediated pest control of FAW in maize in southern Africa. We then present a case study to examine the role of forest proximity in reducing FAW infestation in maize in Zimbabwe. We conclude that birds, bats, parasitoids, and generalist predators are likely drivers of the reduced success of FAW near forests in southern Africa. While predators influence FAW survival and development, their role is largely undermined by parasitoids, which are more efficient in affecting FAW populations. Birds, bats, parasitoids, and generalist predators play an important role in controlling FAW on farms in heterogenous landscapes with diverse vegetation and near-forest proximity. The findings of our case study from Zimbabwe suggest that the distance to forest had a much higher impact on FAW incidence than maize variety, planting date, or the rate of nitrogen applied. Lack of enough case studies from maize in southern Africa makes it challenging to assess the mechanism and the effectiveness of bird predation on FAW. For this reason, further research is necessary to examine how predation by birds, bats and arthropods and parasitism impacts maize yield. We discuss research barriers, recommend appropriate methods for experimental studies, and suggest possible management options to control FAW in southern Africa.
Gradient Boosting Machine Learning Model for Defective Endometrial Receptivity Prediction by Macrophage-Endometrium Interaction Modules
Authors: Li Bohan , Duan Hua , Wang Sha , Wu Jiajing , Li Yazhu
Published: May 2022

Background

A receptive endometrium is a prerequisite for successful embryo implantation. Mounting evidence shows that nearly one-third of infertility and implantation failures are caused by defective endometrial receptivity. This study pooled 218 subjects from multiple datasets to investigate the association of the immune infiltration level with reproductive outcome. Additionally, macrophage-endometrium interaction modules were constructed to explore an accurate and cost-effective approach to endometrial receptivity assessment.

Methods

Immune-infiltration levels in 4 GEO datasets (n=218) were analyzed and validated through meta-analysis. Macrophage-endometrium interaction modules were selected based on the weighted gene co-expression network in GSE58144 and differentially expressed genes dominated by GSE19834 dataset. Xgboost, random forests, and regression algorithms were applied to predictive models. Subsequently, the efficacy of the models was compared and validated in the GSE165004 dataset. Forty clinical samples (RT-PCR and western blot) were performed for expression and model validation, and the results were compared to those of endometrial thickness in clinical pregnancy assessment.

Results

Altered levels of Mϕs infiltration were shown to critically influence embryo implantation. The three selected modules, manifested as macrophage-endometrium interactions, were enrichment in the immunoreactivity, decidualization, and signaling functions and pathways. Moreover, hub genes within the modules exerted significant reproductive prognostic effects. The xgboost algorithm showed the best performance among the machine learning models, with AUCs of 0.998 (95% CI 0.994-1) and 0.993 (95% CI 0.979-1) in GSE58144 and GSE165004 datasets, respectively. These results were significantly superior to those of the other two models (random forest and regression). Similarly, the model was significantly superior to ultrasonography (endometrial thickness) with a better cost-benefit ratio in the population.

Conclusion

Successful embryo implantation is associated with infiltration levels of Mϕs, manifested in genetic modules involved in macrophage-endometrium interactions. Therefore, utilizing the hub genes in these modules can provide a platform for establishing excellent machine learning models to predict reproductive outcomes in patients with defective endometrial receptivity.
Current Understanding of Long-Term Cognitive Impairment After Sepsis
Authors: Li Ying , Ji Muhuo , Yang Jianjun
Published: May 2022

Sepsis is recognized as a life-threatening multi-organ dysfunction resulting from a dysregulated host response to infection. Although the incidence and mortality of sepsis decrease significantly due to timely implementation of anti-infective and support therapies, accumulating evidence suggests that a great proportion of survivors suffer from long-term cognitive impairment after hospital discharge, leading to decreased life quality and substantial caregiving burdens for family members. Several mechanisms have been proposed for long-term cognitive impairment after sepsis, which are not mutually exclusive, including blood-brain barrier disruption, neuroinflammation, neurotransmitter dysfunction, and neuronal loss. Targeting these critical processes might be effective in preventing and treating long-term cognitive impairment. However, future in-depth studies are required to facilitate preventive and/or treatment strategies for long-term cognitive impairment after sepsis.
Functionalized Lineage Tracing Can Enable the Development of Homogenization-Based Therapeutic Strategies in Cancer
Authors: Gutierrez Catherine , Vilas Caroline K. , Wu Catherine J. , Al’Khafaji Aziz M.
Published: May 2022

The therapeutic landscape across many cancers has dramatically improved since the introduction of potent targeted agents and immunotherapy. Nonetheless, success of these approaches is too often challenged by the emergence of therapeutic resistance, fueled by intratumoral heterogeneity and the immense evolutionary capacity inherent to cancers. To date, therapeutic strategies have attempted to outpace the evolutionary tempo of cancer but frequently fail, resulting in lack of tumor response and/or relapse. This realization motivates the development of novel therapeutic approaches which constrain evolutionary capacity by reducing the degree of intratumoral heterogeneity prior to treatment. Systematic development of such approaches first requires the ability to comprehensively characterize heterogeneous populations over the course of a perturbation, such as cancer treatment. Within this context, recent advances in functionalized lineage tracing approaches now afford the opportunity to efficiently measure multimodal features of clones within a tumor at single cell resolution, enabling the linkage of these features to clonal fitness over the course of tumor progression and treatment. Collectively, these measurements provide insights into the dynamic and heterogeneous nature of tumors and can thus guide the design of homogenization strategies which aim to funnel heterogeneous cancer cells into known, targetable phenotypic states. We anticipate the development of homogenization therapeutic strategies to better allow for cancer eradication and improved clinical outcomes.
Liver Stiffness by Transient Elastography Correlates With Degree of Portal Hypertension in Common Variable Immunodeficiency Patients With Nodular Regenerative Hyperplasia
Authors: DiGiacomo Daniel V. , Shay Jessica E. , Crotty Rory , Yang Nancy , Bloom Patricia , Corey Kathleen , Barmettler Sara , Farmer Jocelyn R.
Published: May 2022

Nodular regenerative hyperplasia (NRH) is associated with high morbidity and mortality in patients with common variable immunodeficiency (CVID). While liver biopsy is the gold standard for NRH diagnosis, a non-invasive technique could facilitate early disease recognition, monitoring, and/or immune intervention. We performed a cross-sectional analysis of ultrasound-based transient elastography (TE) in patients with CVID to evaluate liver stiffness and compared this between patients with (N = 12) and without (N = 6) biopsy-proven NRH. Additionally, these data were compared to a cohort followed at our institution for non-alcoholic fatty liver disease (NAFLD) (N = 527), a disease for which TE has routine diagnostic use. Clinical and pathologic features of NRH were evaluated as correlates of liver stiffness, and receiver operating characteristic curves were used to define a liver stiffness cutoff with diagnostic utility for NRH among CVID patients. CVID patients with NRH had a more severe disease presentation compared to those without. This included increased autoinflammatory disease comorbidities, combined B-cell and T-cell dysfunction, and abnormal liver biochemistries (specifically an increased mean alkaline phosphatase level [proximal to TE, 250 vs. 100 U/L; p = 0.03; peak, 314 vs. 114 U/L; p = 0.02). Results of TE demonstrated a significantly elevated liver stiffness in CVID patients with NRH (mean 13.2 ± 6.2 kPa) as compared to both CVID patients without NRH (mean 4.6 ± 0.9 kPa) and non-CVID patients with NAFLD (mean 6.9 ± 5.5 kPa) (p < 0.01). No single or composite histopathologic feature of NRH correlated with liver stiffness including nodule size, nodule density, sinusoidal dilation, fibrosis, and/or lymphocytosis. In contrast, liver stiffness by TE was significantly correlated with clinical parameters of portal hypertension, including an elevated hepatic venous pressure gradient, an increased splenic longitudinal diameter, presence of varices, and presence of peripheral edema. A liver stiffness of greater than or equal to 6.2 kPa was a clinically significant cutoff for NRH in CVID patients. We propose that TE has diagnostic utility in CVID, particularly in the presence of immunophenotypic features such as combined B-cell and T-cell dysfunction, autoinflammatory comorbidities, and/or abnormal liver tests. Elevated liver stiffness by TE should raise suspicion for NRH in patients with CVID and prompt expedited evaluation by hepatology.
Antigen and Cell-Based Assays for the Detection of Non-HLA Antibodies
Authors: Lammerts Rosa G. M. , Altulea Dania , Hepkema Bouke G. , Sanders Jan-Stephan , Born Jacob van den , Berger Stefan P.
Published: May 2022

To date, human leukocyte antigens (HLA) have been the major focus in the approach to acute and chronic antibody-mediated rejection (AMBR) in solid-organ transplantation. However, evidence from the clinic and published studies has shown that non-HLA antibodies, particularly anti-endothelial cell antibodies (AECAs), are found either in the context of AMBR or synergistically in the presence of donor-specific anti-HLA antibodies (DSA). Numerous studies have explored the influence of AECAs on clinical outcomes, yet the determination of the exact clinical relevance of non-HLA antibodies in organ transplantation is not fully established. This is due to highly heterogeneous study designs including differences in testing methods and outcome measures. Efforts to develop reliable and sensitive diagnostic non-HLA antibody tests are continuously made. This is essential considering the technical difficulties of non-HLA antibody assays and the large variation in reported incidences of antibodies. In addition, it is important to take donor specificity into account in order to draw clinically relevant conclusions from non-HLA antibody assays. Here, we provide an overview of non-HLA solid-phase and cell-based crossmatch assays for use in solid-organ transplantation that are currently available, either in a research setting or commercially.
Proteome Profiling Identifies Serum Biomarkers in Rheumatoid Arthritis
Authors: Hu Congqi , Dai Zhao , Xu Jia , Zhao Lianyu , Xu Yanping , Li Meilin , Yu Jiahui , Zhang Lu , Deng Hui , Liu Lijuan , Zhang Mingying , Huang Jiarong , Wu Linping , Chen Guangxing
Published: May 2022

Rheumatoid arthritis (RA) causes serious disability and productivity loss, and there is an urgent need for appropriate biomarkers for diagnosis, treatment assessment, and prognosis evaluation. To identify serum markers of RA, we performed mass spectrometry (MS)-based proteomics, and we obtained 24 important markers in normal and RA patient samples using a random forest machine learning model and 11 protein–protein interaction (PPI) network topological analysis methods. Markers were reanalyzed using additional proteomics datasets, immune infiltration status, tissue specificity, subcellular localization, correlation analysis with disease activity-based diagnostic indications, and diagnostic receiver-operating characteristic analysis. We discovered that ORM1 in serum is significantly differentially expressed in normal and RA patient samples, which is positively correlated with disease activity, and is closely related to CD56dim natural killer cell, effector memory CD8+T cell, and natural killer cell in the pathological mechanism, which can be better utilized for future research on RA. This study supplies a comprehensive strategy for discovering potential serum biomarkers of RA and provides a different perspective for comprehending the pathological mechanism of RA, identifying potential therapeutic targets, and disease management.
Hematological Prognostic Scoring System Can Predict Overall Survival and Can Indicate Response to Immunotherapy in Patients With Osteosarcoma
Authors: Li Longqing , Wang Yang , He Xuanhong , Li Zhuangzhuang , Lu Minxun , Gong Taojun , Chang Qing , Lin Jingqi , Liu Chuang , Luo Yi , Min Li , Zhou Yong , Tu Chongqi
Published: May 2022

Osteosarcoma is the most common primary malignant bone tumor with a high metastatic potential. Nowadays, there is a lack of new markers to identify prognosis of osteosarcoma patients with response to medical treatment. Recent studies have shown that hematological markers can reflect to some extent the microenvironment of an individual with the potential to predict patient prognosis. However, most of the previous studies have studied the prognostic value of a single hematological index, and it is difficult to comprehensively reflect the tumor microenvironment of patients. Here, we comprehensively collected 16 hematological markers and constructed a hematological prognostic scoring system (HPSS) using LASSO cox regression analysis. HPSS contains many indicators such as immunity, inflammation, coagulation and nutrition. Our results suggest that HPSS is an independent prognostic factor for overall survival in osteosarcoma patients and is an optimal addition to clinical characteristics and well suited to further identify high-risk patients from clinically low-risk patients. HPSS-based nomograms have good predictive ability. Finally, HPSS also has some hints for immunotherapy response in osteosarcoma patients.
GATA2 Deficiency in Adult Life Is Characterized by Phenotypic Diversity and Delayed Diagnosis
Authors: Shamriz Oded , Zahalka Naseem , Simon Amos J. , Lev Atar , Barel Ortal , Mor Nofar , Tal Yuval , Segel Michael J. , Somech Raz , Yonath Hagith , Toker Ori
Published: May 2022

The transcription factor GATA2 plays a key role in the survival and self-renewal of hematopoietic stem and progenitor cells. Autosomal dominant variants in GATA2 cause a broad spectrum of heterogeneous phenotypes. Here, we present our experience with GATA2 deficiency in a retrospective multicenter analysis of computerized medical records of adult patients (age ≥18 years) treated between 2018 and 2022 at Shaare Zedek Medical Center in Jerusalem and Sheba Tel-Hashomer Medical Center in Ramat Gan, Israel. Two male and two female patients with GATA2 deficiency were identified. Three of the patients presented with symptoms in adult life and all patients were diagnosed as adults. Age at presentation was 10.5-36 years and age at diagnosis 24-47 years. Diagnosis was delayed in all patients by 1-24.5 years. The phenotypic diversity was notable. Patients presented with myelodysplastic syndrome (n=2), pulmonary alveolar proteinosis (n=1), and recurrent viral (n=1), bacterial (n=3), and mycobacterial (n=1) infections. Bone marrow biopsy revealed cytogenetic abnormalities in one patient (monosomy 7). Patients were diagnosed by exome sequencing (n=3) and Sanger sequencing of the coding exons in GATA2 (n=1). Novel heterozygous GATA2 variants (c.177C>A, p.Y59* and c.610dup, p.R204Pfs*78) were identified in two patients. Immune workup revealed B cell lymphopenia and monocytopenia in all tested patients. One patient died from overwhelming sepsis despite all patients being treated with antibiotics and anti-mycobacterials. Our cohort highlights the phenotypic diversity, late presentation, and delayed diagnosis of GATA2 deficiency. Increased awareness of this primary immune deficiency presenting in adult life is needed and should involve a high index of suspicion.
Potential Utility of Systemic Plasma Biomarkers for Evaluation of Pediatric Schistosomiasis in Western Kenya
Authors: Ondigo Bartholomew N. , Hamilton Rachael E. , Magomere Edwin O. , Onkanga Isaac O. , Mwinzi Pauline N. , Odiere Maurice R. , Ganley-Leal Lisa
Published: May 2022

Introduction

Current diagnostic tools for schistosomiasis are limited, and new tests are necessary to enhance disease diagnosis and surveillance. Identification of novel disease-specific biomarkers may facilitate the development of such tests. We evaluated a panel of biomarkers used in sepsis and parasitic diseases for their potential suitability in the diagnosis of schistosomiasis.

Objective

The study evaluated the levels of systemic plasma biomarkers in relation to Schistosoma mansoni infection and parasite burden.

Methods

Six biomarkers were measured in the plasma of children from schistosomiasis-endemic regions using ELISA. The concentration of soluble CD23 (sCD23) and lipopolysaccharide (LPS) was tested in 199 and 124 plasma samples, respectively, while interleukin-6 (IL-6), soluble triggering receptor expressed on myeloid (sTREM) cells, eotaxin-1, and fatty acid-binding protein (FABP) concentrations were tested in 30 plasma samples.

Results

The concentration of IL-6, eotaxin-1, FABP, and LPS was similar between schistosome-infected and uninfected children. The schistosome-infected children had higher median levels of sTREM and sCD23 as compared to uninfected children, 119.0 (29.9–208.9) versus 10.7 (0.0–73.4) (p = 0.046) and 2,549.0 (1,899.0–3,356.0) vs. 2,035.0 (1,448.0–2,939.0) (p = 0.05), respectively. In addition, sTREM was positively correlated with egg density (p = 0.017).

Conclusion

Our data show that active schistosomiasis per se is associated with elevated levels of sTREM and sCD23. sTREM has potential diagnostic and prognostic values. However, these biomarkers did not distinguish between children with low egg burden and uninfected children.
Engineering γδ T Cells: Recognizing and Activating on Their Own Way
Authors: Dong Ruoyu , Zhang Yixi , Xiao Haowen , Zeng Xun
Published: May 2022

Adoptive cell therapy (ACT) with engineered T cells has emerged as a promising strategy for the treatment of malignant tumors. Among them, there is great interest in engineered γδ T cells for ACT. With both adaptive and innate immune characteristics, γδ T cells can be activated by γδ TCRs to recognize antigens in a MHC-independent manner, or by NK receptors to recognize stress-induced molecules. The dual recognition system enables γδ T cells with unique activation and cytotoxicity profiles, which should be considered for the design of engineered γδ T cells. However, the current designs of engineered γδ T cells mostly follow the strategies that used in αβ T cells, but not making good use of the specific characteristics of γδ T cells. Therefore, it is no surprising that current engineered γδ T cells in preclinical or clinical trials have limited efficacy. In this review, we summarized the patterns of antigen recognition of γδ T cells and the features of signaling pathways for the functions of γδ T cells. This review will additionally discuss current progress in engineered γδ T cells and provide insights in the design of engineered γδ T cells based on their specific characteristics.
Effect of Wii Fit Exercise With Balance and Lower Limb Muscle Strength in Older Adults: A Meta-Analysis
Authors: Liu Haoyan , Xing Yu , Wu Ying
Published: May 2022

Background

Falls and fall-related injuries are not uncommon among older adults and may lead to serious health deterioration and decreased quality of life. Numerous types of physical activity have been proposed to improve balance and strength in older adults with varying degrees of success. Nintendo's Wii Fit video exergame uses body movement as a game controller and provides real-time feedback for games designed to enhance balance and muscle strength. However, whether Wii Fit exercise improves the balance and lower limb muscle strength of older adults remains uncertain.

Objective

To evaluate the current literature by using meta-analyses to assess whether Wii Fit exercise is associated with improved balance and lower limb muscle strength in older adults.

Methods

We searched PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, and Wanfang Data from inception to February 16, 2022, for relevant studies and conducted a manual search of the literature. Data extraction of the included studies were independently performed by two authors. The methodologic quality of each included study was assessed using the Physical Therapy Evidence Database (PEDro) scale. Meta-analyses were conducted using Review Manager 5.3.

Results

Of 991 articles initially identified, 10 articles (379 participants; aged ≥65 years, range 65–92 years; 188 participants in Wii Fit exercise groups, and 191 participants in control groups), including 8 randomized controlled trials, were assessed in this meta-analysis. The methodologic quality of the included studies evaluated with the PEDro average score was 6.4 and ranged from 5 to 8 points, indicating moderate quality. Compared with no exercise, Wii Fit exercise was associated with significant improved scores on the Berg Balance Scale, which evaluates functional balance (mean difference, 1.38; 95% CI, 0.61–2.16; I2 = 31%; P = 0.0005) and on the Timed Up and Go test, which evaluates static and dynamic balance (standardized mean difference, −0.51; 95% CI,−0.88 to −0.14; I2 = 52%; P = 0.007). However, for the three studies assessed, Wii Fit exercise did not significantly improve scores on the 30-s chair stand test, which evaluates the functional strength and endurance of the lower limb muscles (mean difference, 0.82; 95% CI, −0.14 to 1.77; z = 1.68; P = 0.09).

Conclusions

Our findings indicated that Wii Fit exercise is an effective approach to improve functional, static, and dynamic balance among older adults. Additional meta-analyzes with higher numbers of randomized controlled trials are suggested to confirm the benefits of Wii Fit exercise on balance in older adults, to establish whether functional strength and endurance of lower limb muscles are improved, and to explore the relationship between improved balance and fall prevention in this population.
Efficacy of Raman Spectroscopy in the Diagnosis of Uterine Cervical Neoplasms: A Meta-Analysis
Authors: Shen Zhuo-Wei , Zhang Li-Jie , Shen Zhuo-Yi , Zhang Zhi-Feng , Xu Fan , Zhang Xiao , Li Rui , Xiao Zhen
Published: May 2022

Background

Uterine cervical neoplasms is widely concerned due to its high incidence rate. Early diagnosis is extremely important for prognosis. The purpose of this article is evaluating the efficacy of Raman spectroscopy in the diagnosis of suspected uterine cervical neoplasms.

Methods

We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of science up to September 1, 2021. By analyzing the true positive (TP), false positive (FP), true negative (TN) and false negative (FN) of six included study, we evaluated the pooled and grouping sensitivity, specificity, positive, and negative likelihood ratios (LR), and diagnostic odds ratio (DOR), with 95% confidence intervals (CI), based on random effects models. The overall diagnostic accuracy of Raman spectrum was evaluated by SROC curve analysis and AUC.

Results

After screening with inclusion and exclusion criteria, a total of six study were included in the study. The pooled sensitivity and specificity was 0.98 (95% Cl, 0.93–0.99) and 0.95 (95% Cl, 0.89–0.98). The total PLR and NLR were 21.05 (95% CI, 8.23–53.86) and 0.03 (95% CI, 0.01–0.07), respectively. And the AUC of the SROC curve which show the overall diagnostic accuracy was 0.99 (0.98–1.00).

Conclusion

Through analysis, we confirmed the role of Raman spectroscopy (RS) in the diagnosis of suspected uterine cervical tumors.

Systematic Review Registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021284966].