bluuebunny/crossref_metadata_2025 huggingface dataset:
CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin’s Lymphoma
Authors: Xue YuanBo , Lai Xun , Li RuiLei , Ge ChunLei , Zeng BaoZhen , Li Zhen , Fu QiaoFen , Zhao LiuFang , Dong SuWei , Yang JinYan , Guo JiYin , Meng QingYin , Tan QingHua , Li ZhenHui , Ding HaiYan , Zhang YanLei , Liu ShaoHui , Chang Alex H. , Yao Hong , Luo RongCheng
Published: February 2021

Background

In clinical applications of CAR T-cell therapy, life-threatening adverse events including cytokine release syndrome and neurotoxicity can lead to treatment failure. Outcomes of patients treated with anti-CD30 CAR T- cell have been disappointing in relapsing/refractory (r/r) classical Hodgkin’s Lymphoma (cHL).

Methods

In order to understand the applicable population of multiple CAR T-cell therapy, we examined the expression of CD19, CD20, and CD30 by immunohistochemistry (IHC) in 38 paraffin-embedded specimens of cHL. In the past two years, we found only one patient with cHL who is eligible for combined anti-CD19 and CD30 CAR T-cell treatment. This patient’s baseline characteristics were prone to severe adverse events. We treated this patient with low doses and multiple infusions of anti-CD19 and CD30 CAR T-cell.

Results

The positive expression of CD19+ + CD30+ in Reed-Sternberg (RS) cells is approximately 5.2% (2/38). The patient we treated with combined anti-CD19 and CD30 CAR T-cell did not experience severe adverse events related to CAR T-cell therapy and received long term progression-free survival (PFS).

Conclusion

For high risk r/r cHL patients, low doses of CAR T-cell used over different days at different times might be safe and effective. More clinical trials are warranted for CD19 and CD30 CAR T-cell combination therapy.
Tumor Microenvironment Autophagic Processes and Cachexia: The Missing Link?
Authors: Gonçalves Renata de Castro , Freire Paula Paccielli , Coletti Dario , Seelaender Marilia
Published: February 2021

Cachexia is a syndrome that affects the entire organism and presents a variable plethora of symptoms in patients, always associated with continuous and involuntary degradation of skeletal muscle mass and function loss. In cancer, this syndrome occurs in 50% of all patients, while prevalence increases to 80% as the disease worsens, reducing quality of life, treatment tolerance, therapeutic response, and survival. Both chronic systemic inflammation and immunosuppression, paradoxically, correspond to important features in cachexia patients. Systemic inflammation in cachexia is fueled by the interaction between tumor and peripheral tissues with significant involvement of infiltrating immune cells, both in the peripheral tissues and in the tumor itself. Autophagy, as a process of regulating cellular metabolism and homeostasis, can interfere with the metabolic profile in the tumor microenvironment. Under a scenario of balanced autophagy in the tumor microenvironment, the infiltrating immune cells control cytokine production and secretion. On the other hand, when autophagy is unbalanced or dysfunctional within the tumor microenvironment, there is an impairment in the regulation of immune cell’s inflammatory phenotype. The inflammatory phenotype upregulates metabolic consumption and cytokine production, not only in the tumor microenvironment but also in other tissues and organs of the host. We propose that cachexia-related chronic inflammation can be, at least, partly associated with the failure of autophagic processes in tumor cells. Autophagy endangers tumor cell viability by producing immunogenic tumor antigens, thus eliciting the immune response necessary to counteract tumor progression, while preventing the establishment of inflammation, a hallmark of cachexia. Comprehensive understanding of this complex functional dichotomy may enhance cancer treatment response and prevent/mitigate cancer cachexia. This review summarizes the recent available literature regarding the role of autophagy within the tumor microenvironment and the consequences eliciting the development of cancer cachexia.
The Essential Role of Open Data and Software for the Future of Ultrasound-Based Neuronavigation
Authors: Reinertsen Ingerid , Collins D. Louis , Drouin Simon
Published: February 2021

With the recent developments in machine learning and modern graphics processing units (GPUs), there is a marked shift in the way intra-operative ultrasound (iUS) images can be processed and presented during surgery. Real-time processing of images to highlight important anatomical structures combined with in-situ display, has the potential to greatly facilitate the acquisition and interpretation of iUS images when guiding an operation. In order to take full advantage of the recent advances in machine learning, large amounts of high-quality annotated training data are necessary to develop and validate the algorithms. To ensure efficient collection of a sufficient number of patient images and external validity of the models, training data should be collected at several centers by different neurosurgeons, and stored in a standard format directly compatible with the most commonly used machine learning toolkits and libraries. In this paper, we argue that such effort to collect and organize large-scale multi-center datasets should be based on common open source software and databases. We first describe the development of existing open-source ultrasound based neuronavigation systems and how these systems have contributed to enhanced neurosurgical guidance over the last 15 years. We review the impact of the large number of projects worldwide that have benefited from the publicly available datasets “Brain Images of Tumors for Evaluation” (BITE) and “Retrospective evaluation of Cerebral Tumors” (RESECT) that include MR and US data from brain tumor cases. We also describe the need for continuous data collection and how this effort can be organized through the use of a well-adapted and user-friendly open-source software platform that integrates both continually improved guidance and automated data collection functionalities.
Metformin: Targeting the Metabolo-Epigenetic Link in Cancer Biology
Authors: Cuyàs Elisabet , Verdura Sara , Martin-Castillo Begoña , Menendez Javier A.
Published: February 2021

Metabolism can directly drive or indirectly enable an aberrant chromatin state of cancer cells. The physiological and molecular principles of the metabolic link to epigenetics provide a basis for pharmacological modulation with the anti-diabetic biguanide metformin. Here, we briefly review how metabolite-derived chromatin modifications and the metabolo-epigenetic machinery itself are both amenable to modification by metformin in a local and a systemic manner. First, we consider the capacity of metformin to target global metabolic pathways or specific metabolic enzymes producing chromatin-modifying metabolites. Second, we examine its ability to directly or indirectly fine-tune the activation status of chromatin-modifying enzymes. Third, we envision how the interaction between metformin, diet and gut microbiota might systemically regulate the metabolic inputs to chromatin. Experimental and clinical validation of metformin’s capacity to change the functional outcomes of the metabolo-epigenetic link could offer a proof-of-concept to therapeutically test the metabolic adjustability of the epigenomic landscape of cancer.
Pulmonary Involvement in Children With Systemic Lupus Erythematosus
Authors: Dai Ge , Li Linlin , Wang Ting , Jiang Wujun , Ma Jie , Yan Yongdong , Chen Zhengrong
Published: February 2021

Background: Symptomatic pulmonary involvement in systemic lupus erythematosus (SLE) seems not uncommon in children. However, there are few data on the characteristics and laboratory parameters of SLE patients with pulmonary involvement.

Methods: This was a hospital-based study involving 111 SLE patients from 1 January 2012 to 31 December 2016. The demographic, clinical, and laboratory data of the patients were prospectively collected. They were followed as outpatients until December 2019. Clinical characteristics and laboratory parameters of patients with and without pulmonary involvement were compared.

Results: Of the 111 patients with SLE, we identified 18 patients (16.2%) with pulmonary involvement. The most common HRCT findings were ground glass opacity, interlobular septal thickening, bilateral diffuse infiltrates, and pleurisy/pleural effusion (55.6, 50, 50, and 44.4%, respectively). SLE patients with pulmonary involvement tended to have a longer disease duration (14 [12–24.5] vs. 5 [2–9] months, P < 0.01). We also observed a significant association between the presence of anti-Sm antibody, ANCA, Anti-RNP and the presence of pulmonary involvement of SLE (all P < 0.001).

Conclusions: Lung involvement was frequent in SLE patients from Southeast China. Patients with a longer duration of symptoms before SLE diagnosis tended to have pulmonary involvement. When children with SLE are found to have anti-RNP antibody and positive ANCA, it should be alert to the occurrence of pulmonary involvement.
Anthocyanin Protects Cardiac Function and Cardiac Fibroblasts From High-Glucose Induced Inflammation and Myocardial Fibrosis by Inhibiting IL-17
Authors: Yue Er , Yu Yahan , Wang Xinyao , Liu Bing , Bai Yunlong , Yang Baofeng
Published: February 2021

Diabetic cardiomyopathy (DCM) is one of the major causes of death in diabetic patients. Its pathogenesis involves inflammation and fibrosis that damages the heart tissue and impairs cardiac function. Interleukin (IL)-17, a pro-inflammatory cytokine that plays an important role in a variety of chronic inflammatory processes can serve as an attractive therapeutic target. Anthocyanin, a water-soluble natural pigment, possesses impressive anti-inflammatory activity. However, its role in DCM is unclear. Hence, we investigated the protective effect of anthocyanin on the cardiovascular complications of diabetes using a mouse type 1 diabetes mellitus model induced by streptozotocin. Cardiac function and structural alterations in diabetic mice were tested by echocardiography, hematoxylin and eosin staining, and Masson trichrome staining. Immunohistochemistry was performed to evaluate the distribution and deposition of IL-17 and collagen I and III from the left ventricular tissues of diabetic mice. Cell viability was measured using the methyl thiazolyl tetrazolium assay. Protein levels of IL-17, tumor necrosis factor α, IL-1β, and IL-6 were determined using enzyme-linked immunosorbent assay. IL-17 and collagen I and III were detected by western blotting and immunofluorescence, and their mRNA levels were quantified using quantitative reverse transcription PCR. We observed that anthocyanin lowered blood glucose, improved cardiac function, and alleviated inflammation and fibrosis in the heart tissue of diabetic mice. Meanwhile, anthocyanin reduced the expression of IL-17 in high-glucose-treated cardiac fibroblasts and exhibited an anti-inflammatory effect. Deposition of collagen I and III was also decreased by anthocyanin, suggesting that anthocyanin contributes to alleviating myocardial fibrosis. In summary, anthocyanin could protect cardiac function and inhibit IL-17-related inflammation and fibrosis, which indicates its therapeutic potential in the treatment of diabetes mellitus-related complications.
The Potential of Cryptophyte Algae in Biomedical and Pharmaceutical Applications
Authors: Abidizadegan Maryam , Peltomaa Elina , Blomster Jaanika
Published: February 2021

Microalgae produce a variety of bioactive components that provide benefits to human and animal health. Cryptophytes are one of the major groups of microalgae, with more than 20 genera comprised of 200 species. Recently, cryptophytes have attracted scientific attention because of their characteristics and biotechnological potential. For example, they are rich in a number of chemical compounds, such as fatty acids, carotenoids, phycobiliproteins and polysaccharides, which are mainly used for food, medicine, cosmetics and pharmaceuticals. This paper provides a review of studies that assess protective algal compounds and introduce cryptophytes as a remarkable source of bioactive components that may be usable in biomedical and pharmaceutical sciences.
Biomarkers of Response to Biologic Therapy in Juvenile Idiopathic Arthritis
Authors: Choida Varvara , Hall-Craggs Margaret , Jebson Bethany R. , Fisher Corinne , Leandro Maria , Wedderburn Lucy R. , Ciurtin Coziana
Published: February 2021

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthritis of childhood, characterized by various clinical phenotypes associated with variable prognosis. Significant progress has been achieved with the use of biologic treatments, which specifically block pro-inflammatory molecules involved in the disease pathogenesis. The most commonly used biologics in JIA are monoclonal antibodies and recombinant proteins targeting interleukins 1 (IL-1) and 6 (IL-6), and tumor necrosis factor α (TNF-α). Several biomarkers have been investigated in JIA.

Aims: To assess the level of evidence available regarding the role of biomarkers in JIA related to guiding clinical and therapeutic decisions, providing disease prognostic information, facilitating disease activity monitoring and assessing biologic treatment response in JIA, as well as propose new strategies for biologic therapy-related biomarker use in JIA.

Methods: We searched PubMed for relevant literature using predefined key words corresponding to several categories of biomarkers to assess their role in predicting and assessing biologic treatment response and clinical remission in JIA.

Results: We reviewed serological, cellular, genetic, transcriptomic and imaging biomarkers, to identify candidates that are both well-established and widely used, as well as newly investigated in JIA on biologic therapy. We evaluated their role in management of JIA as well as identified the unmet needs for new biomarker discovery and better clinical applications.

Conclusion: Although there are no ideal biomarkers in JIA, we identified serological biomarkers with potential clinical utility. We propose strategies of combining biomarkers of response to biologics in JIA, as well as routine implementation of clinically acceptable imaging biomarkers for improved disease assessment performance.
Targeting the Endothelium to Achieve Cardioprotection
Authors: Herrera-Zelada Nicolas , Zuñiga-Cuevas Ursula , Ramirez-Reyes Andres , Lavandero Sergio , Riquelme Jaime A.
Published: February 2021

Despite considerable improvements in the treatment of myocardial infarction, it is still a highly prevalent disease worldwide. Novel therapeutic strategies to limit infarct size are required to protect myocardial function and thus, avoid heart failure progression. Cardioprotection is a research topic with significant achievements in the context of basic science. However, translation of the beneficial effects of protective approaches from bench to bedside has proven difficult. Therefore, there is still an unmet need to study new avenues leading to protecting the myocardium against infarction. In line with this, the endothelium is an essential component of the cardiovascular system with multiple therapeutic targets with cardioprotective potential. Endothelial cells are the most abundant non-myocyte cell type in the heart and are key players in cardiovascular physiology and pathophysiology. These cells can regulate vascular tone, angiogenesis, hemostasis, and inflammation. Accordingly, endothelial dysfunction plays a fundamental role in cardiovascular diseases, which may ultimately lead to myocardial infarction. The endothelium is of paramount importance to protect the myocardium from ischemia/reperfusion injury via conditioning strategies or cardioprotective drugs. This review will provide updated information on the most promising therapeutic agents and protective approaches targeting endothelial cells in the context of myocardial infarction.
Peripheral Sensory Organs Contribute to Temperature Synchronization of the Circadian Clock in Drosophila melanogaster
Authors: George Rebekah , Stanewsky Ralf
Published: February 2021

Circadian clocks are cell-autonomous endogenous oscillators, generated and maintained by self-sustained 24-h rhythms of clock gene expression. In the fruit fly Drosophila melanogaster, these daily rhythms of gene expression regulate the activity of approximately 150 clock neurons in the fly brain, which are responsible for driving the daily rest/activity cycles of these insects. Despite their endogenous character, circadian clocks communicate with the environment in order to synchronize their self-sustained molecular oscillations and neuronal activity rhythms (internal time) with the daily changes of light and temperature dictated by the Earth’s rotation around its axis (external time). Light and temperature changes are reliable time cues (Zeitgeber) used by many organisms to synchronize their circadian clock to the external time. In Drosophila, both light and temperature fluctuations robustly synchronize the circadian clock in the absence of the other Zeitgeber. The complex mechanisms for synchronization to the daily light–dark cycles are understood with impressive detail. In contrast, our knowledge about how the daily temperature fluctuations synchronize the fly clock is rather limited. Whereas light synchronization relies on peripheral and clock-cell autonomous photoreceptors, temperature input to the clock appears to rely mainly on sensory cells located in the peripheral nervous system of the fly. Recent studies suggest that sensory structures located in body and head appendages are able to detect temperature fluctuations and to signal this information to the brain clock. This review will summarize these studies and their implications about the mechanisms underlying temperature synchronization.
Use of Contemporary Groups in the Construction of Multi-Environment Trial Datasets for Selection in Plant Breeding Programs
Authors: Smith Alison , Ganesalingam Aanandini , Lisle Christopher , Kadkol Gururaj , Hobson Kristy , Cullis Brian
Published: February 2021

Plant breeding programs use multi-environment trial (MET) data to select superior lines, with the ultimate aim of increasing genetic gain. Selection accuracy can be improved with the use of advanced statistical analysis methods that employ informative models for genotype by environment interaction, include information on genetic relatedness and appropriately accommodate within-trial error variation. The gains will only be achieved, however, if the methods are applied to suitable MET datasets. In this paper we present an approach for constructing MET datasets that optimizes the information available for selection decisions. This is based on two new concepts that characterize the structure of a breeding program. The first is that of “contemporary groups,” which are defined to be groups of lines that enter the initial testing stage of the breeding program in the same year. The second is that of “data bands,” which are sequences of trials that correspond to the progression through stages of testing from year to year. MET datasets are then formed by combining bands of data in such a way as to trace the selection histories of lines within contemporary groups. Given a specified dataset, we use the A-optimality criterion from the model-based design literature to quantify the information for any given selection decision. We demonstrate the methods using two motivating examples from a durum and chickpea breeding program. Datasets constructed using contemporary groups and data bands are shown to be superior to other forms, in particular those that relate to a single year alone.
Co-opetition Relationships and Evolution of the World Dairy Trade Network: Implications for Policy-Maker Psychology
Authors: Hu Feng , Xi Xun , Zhang Yueyue , Wu Rung-Tai
Published: February 2021

This study conducted a social network analysis of the evolutionary characteristics of the world dairy trade network based on the overall trade pattern. In addition, the evolution of trade blocs and the co-opetition relationships involving dairy products in major countries were analyzed in terms of supply and demand. The results show that continuous and complex changes have taken place in the world’s dairy trade network since 2001. The number of trade entities in dairy products has stabilized since 2012. At present, approximately 94% of countries (regions) are involved in dairy product trade, such that the world dairy trade network exhibits the small-world effect and scale-free property. The world import pattern for dairy products has changed. While export centers have not changed, import centers have shifted from Europe, America, and East Asia to North America, East Asia, and the Middle East. The world dairy trade network consists of the EU trade bloc headed by Germany, the former Soviet Union–Brazil trade bloc, and the Asia–Australia–America trade bloc. The trade blocs have evolved due to geographical positions, historical cultures, and political relations. In a trade bloc, the diversification of import sources is more prominent in demand countries. European and Asian markets have become the main markets of the major exporters. In this study, the evolutionary characteristics of the world dairy trade network and the co-opetition relationships were analyzed to provide scientific support to inform the development of dairy trade policies. The results can provide technical and psychological support to policy-makers in various countries in their dairy trade decision-making.
A Static-99R Validation Study on Individuals With Mental Disorders: 5 to 20 Years of Fixed Follow-Up After Sexual Offenses
Authors: Baudin Christian , Nilsson Thomas , Sturup Joakim , Wallinius Märta , Andiné Peter
Published: February 2021

‘The Static-99R is one of the most commonly used risk assessment instruments for individuals convicted of sexual offenses. It has been validated for use on many populations, but few studies specifically target and describe individuals with mental disorders. Additionally, research on the discriminative properties (how well the instrument separates recidivists from non-recidivists) of the instrument over longer follow-up periods is scarce. This article evaluated the validity of the Static-99R using a cohort of individuals with mental disorders convicted of sexual offenses in Sweden (N = 146) with fixed 5-year (n = 100), 10-year (n = 91), 15-year (n = 79), and 20-year (n = 36) follow-up periods. A Static-99R cut score of 6 demonstrated the highest Youden index, maximizing sensitivity (72.7%) and specificity (74.2%), with 25.8% of recidivists correctly assumed to reoffend sexually and 95.7% of non-recidivists correctly assumed not to. The Static-99R instrument demonstrated adequate discrimination (AUC = 0.79, CI 95% = 0.70–0.87, and OR = 1.45, CI 95% = 1.14–1.84, p < 0.001, 5-year fixed follow-up), with only marginal differences for 10-, 15-, and 20-year fixed follow-up (AUC = 0.73, 0.74, and 0.74 and OR = 1.31, 1.36, and 1.40, respectively). Calibration (quantifying risk and correspondence with the instrument’s norms) was acceptable (Brier = 0.088, P/E = 0.70, E/O = 1.43), with the routine sample norms displaying a decisively better fit to the study cohort compared to the high-risk/high-need sample norms. The results affirm the recommendation that, when in doubt and where there is no recent local norm group large enough available, the Static-99R routine sample found in the evaluators’ workbook should be used.
Case Report: When Does Puberty Become Traumatic?
Authors: Tarazi-Sahab Layla , El Husseini Mayssa , Moro Marie-Rose
Published: February 2021

Puberty provokes physiological upheaval that can be psychologically traumatic and destabilizing for the child. Before the transformations of puberty, the body is a protective vessel that acts as a stable reference for the child. A child's emotional security is derived from a sense of predictability and well-being. However, the nascent sexuality and burgeoning libido experienced during puberty can trigger unsettling changes in the psycho-affective and psycho-dynamic equilibrium of the child as he or she transforms into an adolescent. This article presents puberty as a transformative experience with traumatic impact that needs to be considered in therapy conducted with adolescents. At best, pubescent trauma can cause superficial issues in a child's adaptive abilities; at worse, it can lead to pathological symptoms. This article presents a qualitative study derived from a clinical case of an adolescent girl who expresses her pubescent suffering through social withdrawal and mutism. The study determines several symptomatic and traumatic indicators caused by the sudden physiological transformations of puberty, such as perceived breaches in a child's sense of safety and the child's ability to predict. The study also explores the feelings of helplessness, vulnerability, and aloneness that pubescent adolescents endure, which are then exacerbated by the sensed inability to turn to parents for help or peers for support.
Case Report: PANDAS and Persistent Lyme Disease With Neuropsychiatric Symptoms: Treatment, Resolution, and Recovery
Authors: Cross Amy , Bouboulis Denis , Shimasaki Craig , Jones Charles Ray
Published: February 2021

This case report describes the diagnosis and treatment of a pre-pubertal (onset at age 7) Caucasian female with serological evidence of Lyme disease accompanied by multiple neuropsychiatric symptoms 6 months following a vacation in a tick endemic area of the United States. Prior to the diagnosis of Lyme disease, the patient also met the clinical diagnostic criteria for PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Strep), with serological evidence of three distinct episodes of streptococcal pharyngitis. All three episodes of strep occurred during the 6-months interval between suspected Lyme disease exposure and the onset of multiple neuropsychiatric symptoms. Her sometimes incapacitating symptoms followed a relapsing and remitting course that impacted her personal, family, social, and academic domains. Over a span of 31 consecutive months of treatment with various antimicrobials and three courses of intravenous immunoglobulins (IVIg) she experienced complete remission and remains symptom free at the time of this publication. Written permission was obtained from the minor patient's mother allowing the submission and publication of this case study.
Longitudinal Structural MRI Findings in Individuals at Genetic and Clinical High Risk for Psychosis: A Systematic Review
Authors: Merritt Kate , Luque Laguna Pedro , Irfan Ayela , David Anthony S.
Published: February 2021

Background: Several cross-sectional studies report brain structure differences between healthy volunteers and subjects at genetic or clinical high risk of developing schizophrenia. However, longitudinal studies are important to determine whether altered trajectories of brain development precede psychosis onset.

Methods: We conducted a systematic review to determine if brain trajectories differ between (i) those with psychotic experiences (PE), genetic (GHR) or clinical high risk (CHR), compared to healthy volunteers, and (ii) those who transition to psychosis compared to those who do not.

Results: Thirty-eight studies measured gray matter and 18 studies measured white matter in 2,473 high risk subjects and 990 healthy volunteers. GHR, CHR, and PE subjects show an accelerated decline in gray matter primarily in temporal, and also frontal, cingulate and parietal cortex. In those who remain symptomatic or transition to psychosis, gray matter loss is more pronounced in these brain regions. White matter volume and fractional anisotropy, which typically increase until early adulthood, did not change or reduced in high risk subjects in the cingulum, thalamic radiation, cerebellum, retrolenticular part of internal capsule, and hippocampal–thalamic tracts. In those who transitioned, white matter volume and fractional anisotropy reduced over time in the inferior and superior fronto-occipital fasciculus, corpus callosum, anterior limb of the internal capsule, superior corona radiate, and calcarine cortex.

Conclusion: High risk subjects show deficits in white matter maturation and an accelerated decline in gray matter. Gray matter loss is more pronounced in those who transition to psychosis, but may normalize by early adulthood in remitters.
Revisiting the Relative Age Effect From a Multidisciplinary Perspective in Youth Basketball: A Bayesian Analysis
Authors: Gonçalves Carlos Eduardo , Carvalho Humberto Moreira
Published: February 2021

Relative age effect (RAE) is considered to bias the selection of young athletes and a cause of exclusion of many participants. The goal of the study was to unveil the effects of the birth quarter on physical performances and a set of psychological constructs in the age groups corresponding to the specialization years. A set of surveys with cross-sectional data collected from 2015 to 2019 in youth basketball was used. Three hundred and twenty-seven Brazilian players (127 females, 100 males), mean age 14.0 years, participated in the study. Counter-movement jump, line-drill, yoyo intermittent test, achievement goals, motivation for deliberate practice, and enjoyment were measured. Bayesian multilevel regression was performed. RAE was observed but its advantages did not persist and did not differentiate the players in the variables under scrutiny. The only predictor of athletic and psychological outcomes was chronological age. The initial advantage that triggered the coaches' decision to select individual players disappears during the specialization years. Coaches must overcome the superficial observation of young athletes based only on age groups and actual performances, avoiding hasty decisions that, unlike RAE, last in time and cannot be reversed.
Safe Approximation—An Efficient Solution for a Hard Routing Problem
Authors: Faragó András , Mojaveri Zohre R.
Published: February 2021

The Disjoint Connecting Paths problem and its capacitated generalization, called Unsplittable Flow problem, play an important role in practical applications such as communication network design and routing. These tasks are NP-hard in general, but various polynomial-time approximations are known. Nevertheless, the approximations tend to be either too loose (allowing large deviation from the optimum), or too complicated, often rendering them impractical in large, complex networks. Therefore, our goal is to present a solution that provides a relatively simple, efficient algorithm for the unsplittable flow problem in large directed graphs, where the task is NP-hard, and is known to remain NP-hard even to approximate up to a large factor. The efficiency of our algorithm is achieved by sacrificing a small part of the solution space. This also represents a novel paradigm for approximation. Rather than giving up the search for an exact solution, we restrict the solution space to a subset that is the most important for applications, and excludes only a small part that is marginal in some well-defined sense. Specifically, the sacrificed part only contains scenarios where some edges are very close to saturation. Since nearly saturated links are undesirable in practical applications, therefore, excluding near saturation is quite reasonable from the practical point of view. We refer the solutions that contain no nearly saturated edges as safe solutions, and call the approach safe approximation. We prove that this safe approximation can be carried out efficiently. That is, once we restrict ourselves to safe solutions, we can find the exact optimum by a randomized polynomial time algorithm.
Modeling and Control of a Modular Iron Bird
Authors: Blasi Luciano , Borrelli Mauro , D’Amato Egidio , di Grazia Luigi Emanuel , Mattei Massimiliano , Notaro Immacolata
Published: February 2021

This paper describes the control architecture and the control laws of a new concept of Modular Iron Bird aimed at reproducing flight loads to test mobile aerodynamic control surface actuators for small and medium size aircraft and Unmanned Aerial Vehicles. The iron bird control system must guarantee the actuation of counteracting forces. On one side, a hydraulic actuator simulates the hinge moments acting on the mobile surface due to aerodynamic and inertial effects during flight; on the other side, the actuator to be tested applies an active hinge moment to control the angular position of the same surface. Reference aerodynamic and inertial loads are generated by a flight simulation module to reproduce more realistic conditions arising during operations. The design of the control action is based on a dynamic model of the hydraulic plant used to generate loads. This system is controlled using a Proportional Integral Derivative control algorithm tuned with an optimization algorithm taking into account the closed loop dynamics of the actuator under testing, uncertainties and disturbances in the controlled plant. Numerical simulations are presented to show the effectiveness of the proposed architecture and control laws.
Response of Interspecific Geraniums to Waste Wood Fiber Substrates and Additional Fertilization
Authors: Zawadzińska Agnieszka , Salachna Piotr , Nowak Jacek S. , Kowalczyk Waldemar
Published: February 2021

Promotion of sustainable horticulture via wider use of peat substrate substitutes makes wood fiber an increasingly popular substrate component. Interspecific geraniums are plants of huge potential in the floriculture market, but there are not enough specific guidelines on their cultivation. This study investigated the effectiveness of enriching peat substrate with 10%, 20%, 30%, or 40% (by volume) waste wood fiber in the pot cultivation of interspecific geraniums cv. ‘Calliope Dark Red’. It also examined plant response to additional fertilization with nitrogen in the form of Ca(NO3)2. Plants grown in the substrate with 10% and 20% of wood fiber did not differ in the leaf greening index, flower weight, and visual score from the plants grown in control (100% peat substrate). Wood fiber content of 40% negatively affected all growth parameters and leaf content of macro- and micronutrients. The plants growing in the peat substrate enriched with 20% of waste wood fiber and fertilized with nitrogen had the highest leaf greenness index, the greatest number of flowers, and the highest content of N, P, Ca, Na, Fe, Mn, Cu, and Zn. In summary, the study demonstrated that high quality ornamental plants can be successfully grown in peat substrate containing 20% of waste wood fiber and additionally fertilized with nitrogen.
Potential Non-Invasive Technique for Accessing Plant Water Contents Using a Radar System
Authors: Santos Luís Carlos , dos Santos Filipe Neves , Morais Raul , Duarte Cândido
Published: February 2021

Sap flow measurements of trees are today the most common method to determine evapotranspiration at the tree and the forest/crop canopy level. They provide independent measurements for flux comparisons and model validation. The most common approach to measure the sap flow is based on intrusive solutions with heaters and thermal sensors. This sap flow sensor technology is not very reliable for more than one season crop; it is intrusive and not adequate for low diameter trunk trees. The non-invasive methods comprise mostly Radio-frequency (RF) technologies, typically using satellite or air-born sources. This system can monitor large fields but cannot measure sap levels of a single plant (precision agriculture). This article studies the hypothesis to use of RF signals attenuation principle to detect variations in the quantity of water present in a single plant. This article presents a well-defined experience to measure water content in leaves, by means of high gains RF antennas, spectrometer, and a robotic arm. Moreover, a similar concept is studied with an off-the-shelf radar solution—for the automotive industry—to detect changes in the water presence in a single plant and leaf. The conclusions indicate a novel potential application of this technology to precision agriculture as the experiments data is directly related to the sap flow variations in plant.
Open Transparent Communication about Animals in Laboratories: Dialog for Multiple Voices and Multiple Audiences
Authors: Carbone Larry
Published: February 2021

In this article, I offer insights and proposals to the current movement for increased openness and transparency about animal use in laboratories. Increased transparency cannot be total transparency—as no story or picture can ever be complete. When research advocates share their stories, they must decide which words and pictures to edit out. I ask here: Who of the listening “public” gets a chance to revisit this editing, and find the information that is important to them? To the extent that (what I call) the “new openness” attempts to speak to a “lay public” and exclude animal activists, I suggest that refinement-focused animal protectionists deserve enhanced avenues of openness and inclusion—which some research advocates might fear giving to more extreme activists and which a less invested “lay public” may not want or need. I conclude with some specific examples and suggestions to not just invite inquiry from animal advocates, but to bring them in as witnesses and participants, to learn from and incorporate their concerns, priorities, expertise, and suggestions. This can bring a diversity of ideas and values that could improve the quality of science, the credibility of animal researchers, and the welfare of the animals in laboratories.
The Digestive Function of Pseudoplatystoma punctifer Early Juveniles Is Differentially Modulated by Dietary Protein, Lipid and Carbohydrate Content and Their Ratios
Authors: Castro-Ruiz Diana , Andree Karl B. , Solovyev Mikhail M. , Fernández-Méndez Christian , García-Dávila Carmen , Cahu Chantal , Gisbert Enric , Darias Maria J.
Published: February 2021

Pseudoplatystoma punctifer is an Amazonian catfish highly appreciated for its high flesh quality, size, and commercial value. Its aquaculture is pursued to satisfy the demands of an increasing population in the region. However, knowledge of the nutritional needs during the early life stages is necessary for improving growth and reducing the incidence of cannibalism, factors that limit the success of its commercial farming. This study aimed at evaluating the influence of four diets containing different protein and lipid levels (30:15, 30:10, 45:15, or 45:10 in %) in the digestive physiology and performance of early juveniles. The results showed that the dietary protein:lipid as well as carbohydrate levels and ratios influenced differently the whole-body proximate composition, the digestive physiology and development, and hence growth and survival. The 45:15 diet promoted the best growth, survival, and the most rapid development of the digestive system, as shown at histological (higher number of hepatocytes, goblet cells in the anterior intestine and enterocytes in all intestinal portions, and longer folds in the posterior intestine), molecular (highest amylase, lipoprotein lipase, phospholipase, trypsinogen, and pepsinogen gene expression), and biochemical (highest lipase and pepsin activities and higher alkaline phosphatase:leucine alanine peptidase activity ratio) levels. Lipids were favored over carbohydrates as source of energy, with lipids promoting a protein-sparing effect at adequate energy:protein ratio. Carbohydrate content higher than 25% was excessive for this species, leading to unbalanced lipid metabolism and fat deposition in the liver.
Application of a Natural Antioxidant from Grape Pomace Extract in the Development of Bioactive Jute Fibers for Food Packaging
Authors: Cejudo-Bastante Cristina , Arjona-Mudarra Paloma , Fernández-Ponce María Teresa , Casas Lourdes , Mantell Casimiro , Martínez de la Ossa Enrique J. , Pereyra Clara
Published: February 2021

There is an increasing demand for the use of new food packaging materials. In this study, natural jute fibers impregnated with a Petit Verdot Red Grape Pomace Extract (RGPE) was proposed as a new active food packaging material. Pressurized Liquid Extraction (PLE) and Enhanced Solvent Extraction (ESE) techniques were employed to obtain the bioactive RGPE. Afterward the supercritical solvent impregnation conditions to obtain RGPE-natural jute fibers were studied, by varying pressure, modifier percentage and dried RGPE mass. PLE technique offered the highest bioactive extract at 20 MPa, 55 °C, 1 h residence time using C2H5OH:H2O (1:1 v/v), providing an EC50 of 3.35 ± 0.25 and antibacterial capacity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa (MIC of 12.0, 1.5 and 4.0 mg/mL RGPE respectively). The natural jute fibers impregnated with 3 mL of that RGPE (90 mg/mL) at 50 MPa and 55 °C generated the most efficient packing material with regards to its food preservation potential.
Modulation of Human Sperm Mitochondrial Respiration Efficiency by Plant Polyphenols
Authors: Ferramosca Alessandra , Lorenzetti Stefano , Di Giacomo Mariangela , Lunetti Paola , Murrieri Francesco , Capobianco Loredana , Dolce Vincenza , Coppola Lamberto , Zara Vincenzo
Published: February 2021

Plant bioactives, such as polyphenols, can differentially affect (positively or negatively) sperm quality, depending on their concentration. These molecules have been proposed as natural scavengers of reactive oxygen species (ROS) for male infertility treatment. However, few data are available about their effects on the molecular mechanisms related to sperm quality and, in particular, to sperm mitochondrial function. We investigated the effects of quercetin, naringenin, genistein, apigenin, luteolin, and resveratrol at the concentration of 0.1–1000 nM on mitochondrial respiration efficiency. Upon chemical exposure, spermatozoa were swollen in a hypotonic solution and used for polarographic assays of mitochondrial respiration. All tested compounds, except for apigenin, caused a significant increase in the mitochondrial respiration efficiency at the concentration of 0.1 nM, and a significant decrease starting from concentrations of 10 nM. The analysis of oxygen consumption rate in the active and in the resting state of mitochondrial respiration suggested different mechanisms by which the tested compounds modulate mitochondrial function. Therefore, by virtue of their ability to stimulate the respiration active state, quercetin, genistein, and luteolin were found to improve mitochondrial function in asthenozoospermic samples. Our results are relevant to the debate on the promises and perils of natural antioxidants in nutraceutical supplementation.
Cocrystal Prediction Using Machine Learning Models and Descriptors
Authors: Mswahili Medard Edmund , Lee Min-Jeong , Martin Gati Lother , Kim Junghyun , Kim Paul , Choi Guang J. , Jeong Young-Seob
Published: February 2021

Cocrystals are of much interest in industrial application as well as academic research, and screening of suitable coformers for active pharmaceutical ingredients is the most crucial and challenging step in cocrystal development. Recently, machine learning techniques are attracting researchers in many fields including pharmaceutical research such as quantitative structure-activity/property relationship. In this paper, we develop machine learning models to predict cocrystal formation. We extract descriptor values from simplified molecular-input line-entry system (SMILES) of compounds and compare the machine learning models by experiments with our collected data of 1476 instances. As a result, we found that artificial neural network shows great potential as it has the best accuracy, sensitivity, and F1 score. We also found that the model achieved comparable performance with about half of the descriptors chosen by feature selection algorithms. We believe that this will contribute to faster and more accurate cocrystal development.
Unravelling the Role of LncRNA WT1-AS/miR-206/NAMPT Axis as Prognostic Biomarkers in Lung Adenocarcinoma
Authors: Li Wen , Liu Yu , Li Zi Jin , Shi Yi , Deng Jing , Bai Jie , Ma Liang , Zeng Xiao Xi , Feng Shan Shan , Ren Jia Li , Luo Fei Jun , Rong Duo Yan , Chen Xiao Qi , Yin Hua Qun , Chen Zhu , Da Fu
Published: February 2021

Lung cancer is the world’s highest morbidity and mortality of malignant tumors, with lung adenocarcinoma (LUAD) as a major subtype. The competitive endogenous RNA (ceRNA) regulative network provides opportunities to understand the relationships among different molecules, as well as the regulative mechanisms among them in order to investigate the whole transcriptome landscape in cancer pathology. We designed this work to explore the role of a key oncogene, MYC, in the pathogenesis of LUAD, and this study aims to identify important long noncoding RNA (lncRNA)-microRNA (miRNA)- transcription factor (TF) interactions in non-small cell lung cancer (NSCLC) using a bioinformatics analysis. The Cancer Genome Atlas (TCGA) database, containing mRNA expression data of NSCLC, was used to determine the deferentially expressed genes (DEGs), and the ceRNA network was composed of WT1-AS, miR-206, and nicotinamide phosphoribosyltransferase (NAMPT) bashing on the MYC expression level. The Kaplan–Meier univariate survival analysis showed that these components may be closely related prognostic biomarkers and will become new ideas for NSCLC treatment. Moreover, the high expression of WT1-AS and NAMPT and low expression of miR-206 were associated with a shortened survival in NSCLC patients, which provided a survival advantage. In summary, the current study constructing a ceRNA-based WT1-AS/miR-206/NAMPT axis might be a novel important prognostic factor associated with the diagnosis and prognosis of LUAD.
The Role of Mental Imagery in Parkinson’s Disease Rehabilitation
Authors: Abraham Amit , Duncan Ryan P. , Earhart Gammon M.
Published: February 2021

Parkinson’s disease (PD) is a disabling neurodegenerative disease whose manifestations span motor, sensorimotor, and sensory domains. While current therapies for PD include pharmacological, invasive, and physical interventions, there is a constant need for developing additional approaches for optimizing rehabilitation gains. Mental imagery is an emerging field in neurorehabilitation and has the potential to serve as an adjunct therapy to enhance patient function. Yet, the literature on this topic is sparse. The current paper reviews the motor, sensorimotor, and sensory domains impacted by PD using gait, balance, and pain as examples, respectively. Then, mental imagery and its potential for PD motor and non-motor rehabilitation is discussed, with an emphasis on its suitability for addressing gait, balance, and pain deficits in people with PD. Lastly, future research directions are suggested.
Association of RERG Expression with Female Survival Advantage in Malignant Pleural Mesothelioma
Authors: De Rienzo Assunta , Coleman Melissa H. , Yeap Beow Y. , Severson David T. , Wadowski Benjamin , Gustafson Corinne E. , Jensen Roderick V. , Chirieac Lucian R. , Richards William G. , Bueno Raphael
Published: February 2021

Sex differences in incidence, prognosis, and treatment response have been described for many cancers. In malignant pleural mesothelioma (MPM), a lethal disease associated with asbestos exposure, men outnumber women 4 to 1, but women consistently live longer than men following surgery-based therapy. This study investigated whether tumor expression of genes associated with estrogen signaling could potentially explain observed survival differences. Two microarray datasets of MPM tumors were analyzed to discover estrogen-related genes associated with survival. A validation cohort of MPM tumors was selected to balance the numbers of men and women and control for competing prognostic influences. The RAS like estrogen regulated growth inhibitor (RERG) gene was identified as the most differentially-expressed estrogen-related gene in these tumors and predicted prognosis in discovery datasets. In the sex-matched validation cohort, low RERG expression was significantly associated with increased risk of death among women. No association between RERG expression and survival was found among men, and no relationship between estrogen receptor protein or gene expression and survival was found for either sex. Additional investigations are needed to elucidate the molecular mechanisms underlying this association and its sex specificity.