bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypereosinophilia in Solid Tumors—Case Report and Clinical Review
Authors: Zalewska Ewa , Obołończyk Łukasz , Sworczak Krzysztof
Published: March 2021

Background

Renal cell cancer may cause various paraneoplastic syndromes; however, paraneoplastic hypereosinophilia occurs exceedingly rare. Thus far, only two cases of clear cell renal cell carcinoma (CCRCC) associated with hypereosinophilia have been reported. In this paper, we present a case of paraneoplastic hypereosinophilia associated with renal cell carcinoma and a review of the reported cases of hypereosinophilia in solid tumors.

Methods

The review is based on an electronic literature search performed in the PubMed database in September 2020 with the following key terms: eosinophilia & neoplasm; eosinophilia & cancer; eosinophilia & paraneoplastic syndrome. Papers were included based on screening the titles and/or abstracts. We also included the case of our patient in the analysis.

Case presentation

A 68-year-old Caucasian female patient with recurrent CCRCC was admitted to our Clinic for exacerbating dyspnea and chest and right upper abdominal pain, accompanied by confusion. Preliminary blood tests showed an increased white blood cell count of 40,770/μl, and an increased eosinophil count of 6,530/μl indicating eosinophilia. Several tests were carried out to rule out the noncancer causes of hypereosinophilia. The temporal appearance of eosinophilia and the recurrence of CCRCC without any other apparent potential causes led to the diagnosis of paraneoplastic hypereosinophilia. Despite treating with high doses of corticosteroids, only a transient decrement in eosinophil count was observed along with further deterioration of the patient’s condition. The patient succumbed to the disease 6 months following the tumor surgery and 2 months after the diagnosis of hypereosinophilia and tumor recurrence.

Conclusion

Our observations are in agreement with the majority of reports showing that the occurrence of eosinophilia following tumor resection may indicate a poor prognosis, tumor recurrence, and rapid disease progression.
Construction of Competitive Endogenous RNA Network and Verification of 3-Key LncRNA Signature Associated With Distant Metastasis and Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma
Authors: Su Yang , Zhang Tianxiang , Tang Jieqiong , Zhang Li , Fan Song , Zhou Jun , Liang Chaozhao
Published: March 2021

Clear cell renal cell carcinoma (ccRCC) is a common malignancy with high distant metastasis rate. Long non-coding RNAs (LncRNAs) are reported to be upregulated or downregulated in multiple cancers and play a crucial role in the metastasis of tumors or prognosis. Therefore, the purpose of our study is to construct a prognostic signature for ccRCC based on distant metastasis-related lncRNAs and explore the involved potential competitive endogenous RNA (ceRNA) network. The differentially expressed genes (DEGs) screened from the database of the cancer genome atlas (TCGA) were used to construct a co-expression network and identify the distant metastasis-related module by weighted gene co-expression network analysis (WGCNA). Key genes with metastatic and prognostic significance were identified through rigorous screening, including survival analysis, correlation analysis, and expression analyses in stage, grade, and distant metastasis, and were verified in the data set of gene expression omnibus (GEO) and the database from gene expression profiling interactive analysis (GEPIA). The potential upstream miRNAs and lncRNAs were predicted via five online databases and LncBase. Here, we constructed a ceRNA network of key genes that are significantly associated with the distant metastasis and prognosis of patients with ccRCC. The distant metastasis-related lncRNAs were used to construct a risk score model through the univariate, least absolute shrinkage selection operator (LASSO), and multivariate Cox regression analyses, and the patients were divided into high- and low-risk groups according to the median of the risk score. The Kaplan–Meier survival analysis demonstrated that mortality was significantly higher in the high-risk group than in the low-risk group. Considering the other clinical phenotype, the Cox regression analyses indicated that the lncRNAs model could function as an independent prognostic factor. Quantitative real-time (qRT)-PCR in the tissues and cells of ccRCC verified the high-expression level of three lncRNAs. Gene set enrichment analysis (GSEA) revealed that the lncRNA prognostic signature was mainly enriched in autophagy- and immune-related pathways, indicating that the autophagy and immune functions may play an important role in the distant metastasis of ccRCC. In summary, the constructed distant metastasis-related lncRNA signature could independently predict prognosis in patients with ccRCC, and the related ceRNA network provided a new sight on the potential mechanism of distant metastasis and a promising therapeutic target for ccRCC.
Targeting Nrf2-Mediated Oxidative Stress Response Signaling Pathways as New Therapeutic Strategy for Pituitary Adenomas
Authors: Zhan Xianquan , Li Jiajia , Zhou Tian
Published: March 2021

Oxidative stress and oxidative damage are the common pathophysiological characteristics in pituitary adenomas (PAs), which have been confirmed with many omics studies in PA tissues and cell/animal experimental studies. Nuclear factor erythroid 2 p45-related factor 2 (Nrf2), the core of oxidative stress response, is an oxidative stress sensor. Nrf2 is synthesized and regulated by multiple factors, including Keap1, ERK1/2, ERK5, JNK1/2, p38 MAPK, PKC, PI3K/AKT, and ER stress, in the cytoplasm. Under the oxidative stress status, Nrf2 quickly translocates from cytoplasm into the nucleus and binds to antioxidant response element /electrophile responsive element to initiate the expressions of antioxidant genes, phases I and II metabolizing enzymes, phase III detoxifying genes, chaperone/stress response genes, and ubiquitination/proteasomal degradation proteins. Many Nrf2 or Keap1 inhibitors have been reported as potential anticancer agents for different cancers. However, Nrf2 inhibitors have not been studied as potential anticancer agents for PAs. We recommend the emphasis on in-depth studies of Nrf2 signaling and potential therapeutic agents targeting Nrf2 signaling pathways as new therapeutic strategies for PAs. Also, the use of Nrf2 inhibitors targeting Nrf2 signaling in combination with ERK inhibitors plus p38 activators or JNK activators targeting MAPK signaling pathways, or drugs targeting mitochondrial dysfunction pathway might produce better anti-tumor effects on PAs. This perspective article reviews the advances in oxidative stress and Nrf2-mediated oxidative stress response signaling pathways in pituitary tumorigenesis, and the potential of targeting Nrf2 signaling pathways as a new therapeutic strategy for PAs.
Medicinal Plants in COVID-19: Potential and Limitations
Authors: Lim Xin Yi , Teh Bee Ping , Tan Terence Yew Chin
Published: March 2021

Currently, the search to identify treatments and vaccines for novel coronavirus disease (COVID-19) are ongoing. Desperation within the community, especially among the middle-and low-income groups acutely affected by the economic impact of forced lockdowns, has driven increased interest in exploring alternative choices of medicinal plant-based therapeutics. This is evident with the rise in unsubstantiated efficacy claims of these interventions circulating on social media. Based on enquiries received, our team of researchers was given the chance to produce evidence summaries evaluating the potential of complementary interventions in COVID-19 management. Here, we present and discuss the findings of four selected medicinal plants (Nigella sativa, Vernonia amygdalina, Azadirachta indica, Eurycoma longifolia), with reported antiviral, anti-inflammatory, and immunomodulatory effects that might be interesting for further investigation. Our findings showed that only A. indica reported positive antiviral evidence specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on preliminary in silico data while all four medicinal plants demonstrated differential anti-inflammatory or immunomodulatory effects. The definitive roles of these medicinal plants in cytokine storms and post-infection complications remains to be further investigated. Quality control and standardisation of medicinal plant-based products also needs to be emphasized. However, given the unprecedented challenges faced, ethnopharmacological research should be given a fair amount of consideration for contribution in this pandemic.
Allosterism vs. Orthosterism: Recent Findings and Future Perspectives on A2B AR Physio-Pathological Implications
Authors: Barresi Elisabetta , Martini Claudia , Da Settimo Federico , Greco Giovanni , Taliani Sabrina , Giacomelli Chiara , Trincavelli Maria Letizia
Published: March 2021

The development of GPCR (G-coupled protein receptor) allosteric modulators has attracted increasing interest in the last decades. The use of allosteric modulators in therapy offers several advantages with respect to orthosteric ones, as they can fine-tune the tissue responses to the endogenous agonist. Since the discovery of the first A1 adenosine receptor (AR) allosteric modulator in 1990, several efforts have been made to develop more potent molecules as well as allosteric modulators for all adenosine receptor subtypes. There are four subtypes of AR: A1, A2A, A2B, and A3. Positive allosteric modulators of the A1 AR have been proposed for the cure of pain. A3 positive allosteric modulators are thought to be beneficial during inflammatory processes. More recently, A2A and A2B AR allosteric modulators have also been disclosed. The A2B AR displays the lowest affinity for its endogenous ligand adenosine and is mainly activated as a consequence of tissue damage. The A2B AR activation has been found to play a crucial role in chronic obstructive pulmonary disease, in the protection of the heart from ischemic injury, and in the process of bone formation. In this context, allosteric modulators of the A2B AR may represent pharmacological tools useful to develop new therapeutic agents. Herein, we provide an up-to-date highlight of the recent findings and future perspectives in the field of orthosteric and allosteric A2B AR ligands. Furthermore, we compare the use of orthosteric ligands with positive and negative allosteric modulators for the management of different pathological conditions.
Discrepancies in the Time Course of Sleep Stage Dynamics, Electroencephalographic Activity and Heart Rate Variability Over Sleep Cycles in the Adaptation Night in Healthy Young Adults
Authors: Shirota Ai , Kamimura Mayo , Kishi Akifumi , Adachi Hiroyoshi , Taniike Masako , Kato Takafumi
Published: March 2021

Objective

The aim of the present study was to characterize the cyclic sleep processes of sleep-stage dynamics, cortical activity, and heart rate variability during sleep in the adaptation night in healthy young adults.

Methods

Seventy-four healthy adults participated in polysomnographic recordings on two consecutive nights. Conventional sleep variables were assessed according to standard criteria. Sleep-stage continuity and dynamics were evaluated by sleep runs and transitions, respectively. These variables were compared between the two nights. Electroencephalographic and cardiac activities were subjected to frequency domain analyses. Cycle-by-cycle analysis was performed for the above variables in 34 subjects with four sleep cycles and compared between the two nights.

Results

Conventional sleep variables reflected lower sleep quality in the adaptation night than in the experimental night. Bouts of stage N1 and stage N2 were shorter, and bouts of stage Wake were longer in the adaptation night than in the experimental night, but there was no difference in stage N3 or stage REM. The normalized transition probability from stage N2 to stage N1 was higher and that from stage N2 to N3 was lower in the adaptation night, whereas that from stage N3 to other stages did not differ between the nights. Cycle-by-cycle analysis revealed that sleep-stage distribution and cortical beta EEG power differed between the two nights in the first sleep cycle. However, the HF amplitude of the heart rate variability was lower over the four sleep cycles in the adaptation night than in the experimental night.

Conclusion

The results suggest the distinct vulnerability of the autonomic adaptation processes within the central nervous system in young healthy subjects while sleeping in a sleep laboratory for the first time.
Atypical Resting-State Functional Connectivity of Intra/Inter-Sensory Networks Is Related to Symptom Severity in Young Boys With Autism Spectrum Disorder
Authors: Wang Jia , Wang Xiaomin , Wang Runshi , Duan Xujun , Chen Heng , He Changchun , Zhai Jinhe , Wu Lijie , Chen Huafu
Published: March 2021

Autism spectrum disorder (ASD) has been reported to have altered brain connectivity patterns in sensory networks, assessed using resting-state functional magnetic imaging (rs-fMRI). However, the results have been inconsistent. Herein, we aimed to systematically explore the interaction between brain sensory networks in 3–7-year-old boys with ASD (N = 29) using independent component analysis (ICA). Participants were matched for age, head motion, and handedness in the MRI scanner. We estimated the between-group differences in spatial patterns of the sensory resting-state networks (RSNs). Subsequently, the time series of each RSN were extracted from each participant’s preprocessed data and associated estimates of interaction strength between intra- and internetwork functional connectivity (FC) and symptom severity in children with ASD. The auditory network (AN), higher visual network (HVN), primary visual network (PVN), and sensorimotor network (SMN) were identified. Relative to TDs, individuals with ASD showed increased FC in the AN and SMN, respectively. Higher positive connectivity between the PVN and HVN in the ASD group was shown. The strength of such connections was associated with symptom severity. The current study might suggest that the abnormal connectivity patterns of the sensory network regions may underlie impaired higher-order multisensory integration in ASD children, and be associated with social impairments.
Brassinosteroid Signaling, Crosstalk and, Physiological Functions in Plants Under Heavy Metal Stress
Authors: Kour Jaspreet , Kohli Sukhmeen Kaur , Khanna Kanika , Bakshi Palak , Sharma Pooja , Singh Arun Dev , Ibrahim Mohd , Devi Kamini , Sharma Neerja , Ohri Puja , Skalicky Milan , Brestic Marian , Bhardwaj Renu , Landi Marco , Sharma Anket
Published: March 2021

Brassinosteroids (BRs) are group of plant steroidal hormones that modulate developmental processes and also have pivotal role in stress management. Biosynthesis of BRs takes place through established early C-6 and late C-6 oxidation pathways and the C-22 hydroxylation pathway triggered by activation of the DWF4 gene that acts on multiple intermediates. BRs are recognized at the cell surface by the receptor kinases, BRI1 and BAK1, which relay signals to the nucleus through a phosphorylation cascade involving phosphorylation of BSU1 protein and proteasomal degradation of BIN2 proteins. Inactivation of BIN2 allows BES1/BZR1 to enter the nucleus and regulate the expression of target genes. In the whole cascade of signal recognition, transduction and regulation of target genes, BRs crosstalk with other phytohormones that play significant roles. In the current era, plants are continuously exposed to abiotic stresses and heavy metal stress is one of the major stresses. The present study reveals the mechanism of these events from biosynthesis, transport and crosstalk through receptor kinases and transcriptional networks under heavy metal stress.
Measuring Cognitive Load Using In-Game Metrics of a Serious Simulation Game
Authors: Sevcenko Natalia , Ninaus Manuel , Wortha Franz , Moeller Korbinian , Gerjets Peter
Published: March 2021

Serious games have become an important tool to train individuals in a range of different skills. Importantly, serious games or gamified scenarios allow for simulating realistic time-critical situations to train and also assess individual performance. In this context, determining the user’s cognitive load during (game-based) training seems crucial for predicting performance and potential adaptation of the training environment to improve training effectiveness. Therefore, it is important to identify in-game metrics sensitive to users’ cognitive load. According to Barrouillets’ time-based resource-sharing model, particularly relevant for measuring cognitive load in time-critical situations, cognitive load does not depend solely on the complexity of actions but also on temporal aspects of a given task. In this study, we applied this idea to the context of a serious game by proposing in-game metrics for workload prediction that reflect a relation between the time during which participants’ attention is captured and the total time available for the task at hand. We used an emergency simulation serious game requiring management of time-critical situations. Forty-seven participants completed the emergency simulation and rated their workload using the NASA-TLX questionnaire. Results indicated that the proposed in-game metrics yielded significant associations both with subjective workload measures as well as with gaming performance. Moreover, we observed that a prediction model based solely on data from the first minutes of the gameplay predicted overall gaming performance with a classification accuracy significantly above chance level and not significantly different from a model based on subjective workload ratings. These results imply that in-game metrics may qualify for a real-time adaptation of a game-based learning environment.
Developmental Changes in ANS Precision Across Grades 1–9: Different Patterns of Accuracy and Reaction Time
Authors: Malykh Sergey , Kuzmina Yulia , Tikhomirova Tatiana
Published: March 2021

The main aim of this study was to analyze the patterns of changes in Approximate Number Sense (ANS) precision from grade 1 (mean age: 7.84 years) to grade 9 (mean age: 15.82 years) in a sample of Russian schoolchildren. To fulfill this aim, the data from a longitudinal study of two cohorts of children were used. The first cohort was assessed at grades 1–5 (elementary school education plus the first year of secondary education), and the second cohort was assessed at grades 5–9 (secondary school education). ANS precision was assessed by accuracy and reaction time (RT) in a non-symbolic comparison test (“blue-yellow dots” test). The patterns of change were estimated via mixed-effect growth models. The results revealed that in the first cohort, the average accuracy increased from grade 1 to grade 5 following a non-linear pattern and that the rate of growth slowed after grade 3 (7–9 years old). The non-linear pattern of changes in the second cohort indicated that accuracy started to increase from grade 7 to grade 9 (13–15 years old), while there were no changes from grade 5 to grade 7. However, the RT in the non-symbolic comparison test decreased evenly from grade 1 to grade 7 (7–13 years old), and the rate of processing non-symbolic information tended to stabilize from grade 7 to grade 9. Moreover, the changes in the rate of processing non-symbolic information were not explained by the changes in general processing speed. The results also demonstrated that accuracy and RT were positively correlated across all grades. These results indicate that accuracy and the rate of non-symbolic processing reflect two different processes, namely, the maturation and development of a non-symbolic representation system.
Competitive Anxiety, and Guilt and Shame Proneness From Perspective Type D and Non-type D Football Players
Authors: Kaplánová Adriana
Published: March 2021

The precompetitive, competitive, and postcompetitive mental states of athletes are currently not sufficiently researched. Long-term exposure to stressors contributes to the formation of mental blocks and leads to various health problems. One of the factors that can explain the variability of athletes' reactions to stress is their personality. This study is the first to examine competitive anxiety, and guilt and shame proneness in the context of the reaction of football players to distress in sports. The study consists of 112 male football players aged 16–24 (21.00 ± 1.90) who were divided into type D and non-type D football players according to scoring on the Denollet Scale (DS14). Football players also filled out the Sport Anxiety Scale (SAS-2) and the Guilt and Shame Proneness Scale (GASP). The taxonomic approach was conducted to test and to examine differences in stressor intensity as a function of type D personality. A correlation, multivariate analysis of variance, and regression analysis were performed in the study. We found that type D football players were more afraid of failures in sports (worry), felt more often autonomous excitement concentrated in the stomach and muscles (somatic anxiety), and showed more frequent concentration disruption than did non-type D football players. We also found that although type D football players were more likely to rate their behavior as negative and inappropriate, they showed a much greater effort to correct it than did non-type D football players. Negative affectivity and social inhibition of type D football players were positively correlated with competitive anxiety. In addition, we noted lower levels of somatic anxiety and lower concentration disruption for football players who used escape strategies to manage stress. The shame proneness subscale monitoring negative self-evaluation was also closely related to the concentration disruption of football players. We found that the examination of athletes by type D personality is necessary due to the fact that negative affectivity and social inhibition are significant predictors of competitive anxiety of football players, which explains their worries at 24.0%, somatic anxiety at 8.2%, and concentration disruption at 10.6%.
“Who Champions or Mentors Others”? The Role of Personal Resources in the Perceived Organizational Politics and Job Attitudes Relationship
Authors: Khan Hira Salah ud din , Siddiqui Shakira Huma , Zhiqiang Ma , Weijun Hu , Mingxing Li
Published: March 2021

Drawing insight from affective events theory, this study presents a new dimension of perceived organizational politics and job attitudes. The motivation for this study was based on the fact that perceived organizational politics affect job attitudes and that personal resources (political skill and work ethic) moderate the direct relationship between perceived organizational politics and job attitudes in the context of the higher-education sector. In this regard, the data was collected through purposive sampling from 310 faculty members from higher-education institutions in Pakistan. To test the relationships among the variables, we employed structural equation modeling via the AMOS software version 24.0. The results indicated that perceived organizational politics were significantly negatively related to job satisfaction. Moreover, perceived organizational politics were non-significantly related to job involvement. Political skill and work ethic weakened the relationship between perceived organizational politics and job satisfaction. We anticipated that these personal resources could mitigate the negative effect of perceived organizational politics and job attitudes. This study also suggests organizations to train their employees to develop essential personal skills.
Meta-Analysis: Hemodynamic Responses to Sub-anesthetic Doses of Ketamine in Patients With Psychiatric Disorders
Authors: Vankawala Jay , Naples Garrett , Avila-Quintero Victor J. , Ramírez Karina L. , Flores José M. , Bloch Michael H. , Dwyer Jennifer B.
Published: March 2021

Ketamine, a medication traditionally used as an anesthetic, has increasingly been recognized as an effective treatment for psychiatric disorders. At sub-anesthetic doses (defined here as ≤ 0.5 mg/kg), ketamine treatment has been studied in patients with treatment-resistant depression (TRD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and social anxiety disorder (SAD). Transient increases in hemodynamic activity have been reported during and after ketamine treatment, which may be desirable properties in some anesthesia settings, but are generally undesirable in psychiatric settings. While ketamine doses used in psychiatry are lower than those used in anesthesia, there are published instances of early termination of psychiatric ketamine infusions due to elevations in blood pressure and heart rate. No unifying study has been conducted to examine the impact of sub-anesthetic ketamine doses on hemodynamic parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR)] in psychiatric populations and to evaluate these changes across adult age groups. Here, data from 15 articles comprising a totalN= 2,252 ketamine or esketamine treatments in adult participants were used to conduct a meta-analysis of treatment-induced hemodynamic changes. Ketamine/esketamine produced modest but significant increases in the variables of interest with an average SBP increase of 12.61 mm Hg (95% CI 10.40–14.82 mm Hg,z= 11.18,p< 0.0001), average DBP increase of 8.49 mm Hg (95% CI 6.89–10.09 mmHg,z= 10.41,p< 0.0001), and average heart rate increase of 4.09 beats per minute (95% CI 0.55–7.63 BPM),z= 2.27,p= 0.0235). Stratified subgroup analysis indicated no significant differences between ketamine and esketamine effects on blood pressure. Further analysis indicated that there was no significant effect of age on ketamine-induced changes in SBP, DBP, and HR. Taken together these data show that sub-anesthetic ketamine and esketamine induce small but significant increases in hemodynamic parameters that are transient in nature in adult psychiatric populations. While these data are reassuring, it is important for each treatment case to fully explore potential cardiovascular risks prior to initiating treatment.
Deep Brain Stimulation for Obsessive-Compulsive Disorder: Real World Experience Post-FDA-Humanitarian Use Device Approval
Authors: Kahn Lora , Sutton Brianne , Winston Helena R. , Abosch Aviva , Thompson John A. , Davis Rachel A.
Published: March 2021

Background: While case series have established the efficacy of deep brain stimulation (DBS) in treating obsessive-compulsive disorder (OCD), it has been our experience that few OCD patients present without comorbidities that affect outcomes associated with DBS treatment. Here we present our experience with DBS therapy for OCD in patients who all have comorbid disease, together with the results of our programming strategies.

Methods: For this case series, we assessed five patients who underwent ventral capsule/ventral striatum (VC/VS) DBS for OCD between 2015 and 2019 at the University of Colorado Hospital. Every patient in this cohort exhibited comorbidities, including substance use disorders, eating disorder, tic disorder, and autism spectrum disorder. We conducted an IRB-approved, retrospective study of programming modifications and treatment response over the course of DBS therapy.

Results: In addition to patients' subjective reports of improvement, we observed significant improvement in the Yale-Brown Obsessive-Compulsive Scale (44%), the Montgomery-Asberg Depression Rating Scale (53%), the Quality of Life Enjoyment and Satisfaction Questionnaire (27%), and the Hamilton Anxiety Rating scales (34.9%) following DBS. With respect to co-morbid disease, there was a significant improvement in a patient with tic disorder's Total Tic Severity Score (TTSS) (p = 0.005).

Conclusions: DBS remains an efficacious tool for the treatment of OCD, even in patients with significant comorbidities in whom DBS has not previously been investigated. Efficacious treatment results not only from the accurate placement of the electrodes by the surgeon but also from programming by the psychiatrist.
Assessing the Impact of an Intervention Project by the Young women's Christian Association of Malawi on Psychosocial Well-Being of Adolescent Mothers and Their Children in Malawi
Authors: Kachingwe Mtisunge , Chikowe Ibrahim , van der Haar Lotte , Dzabala Nettie
Published: March 2021

Adolescent mothers in Malawi face psychosocial challenges such as low resilience level, low self-esteem, poor maternal-infant interaction, and exposure to intimate partner violence (IPV). Children of adolescent mothers often face numerous risks such as low birth-weight, stunted growth, infant death, low school enrolment, increased grade repetition, and dropouts that put them at greater risk of poor developmental outcomes and socio-emotional problems. This study assessed the impact of components of a community project conducted by the Young Women's Christian association of Malawi in providing psychosocial support to adolescent mothers and their children. The goals of the project were; (1) to improve early childhood development in babies born to adolescent mothers; and (2) to enhance the psychosocial well-being of adolescent mothers (self-esteem, resilience stress, and parenting skills). This descriptive mixed methods evaluation study comprised an intervention and control groups of adolescent mothers respectively. The project had 3 centers in southern region districts of Malawi. Target population was adolescent mothers 18 years of age and below. At baseline we enrolled 267 mothers and at the end of the project we had 211 mothers. The project involved monthly meetings with adolescent mothers imparting knowledge and skills and early childhood education activities. From July 2017 to June 2019, 58 sessions were conducted. In the first year the control group had no meetings, however they received the intervention in the second year. Overall results in the intervention group showed statistically significant increase in knowledge on parenting skills (p < 0.01), nutritional practice (p < 0.01), motor skills and cognitive functions in children (p < 0.01) as well as expressive language and socio-emotional capacities in children (p < 0.01), while the change in confidence and psychosocial well-being was not statistically significant (p = 0.8823). Community projects such as these enhance parenting skills and improve development of children born to adolescent mothers. Improving psychosocial support is complex and requires further research and a more holistic approach.
Efficient Irrigation of Maize Through Soil Moisture Monitoring and Modeling
Authors: Camporese Matteo , Gumiere Silvio J. , Putti Mario , Botter Gianluca
Published: March 2021

Agriculture is the major user of water resources, accounting for 70% of global freshwater demand. As the demand for clean water increases, so does the need to implement more efficient strategies for water management in irrigated agriculture. While the benefits of precision irrigation in high-value crops, such as cannabis, tomatoes, and potatoes, are fully recognized, there is still need to investigate and implement cheap and efficient irrigation strategies for widespread low-value crops such as maize. In this study, the soil moisture dynamics in a sprinkler-irrigated maize field in Veneto (Northeastern Italy) was monitored using six time domain reflectometry (TDR) probes for the entire growing season. The TDR sensors were positioned at different depths into two separate sites: an Uninformed Site irrigated based on the farmer's experience and an Informed Site in which a water balance irrigation strategy was applied based on soil moisture measurements. A parsimonious hydrological model was then implemented and calibrated to quantify the different water balance terms (precipitation, evapotranspiration, lateral fluxes, and deep percolation). The comparison between the water budget terms in the two sites highlights that soil moisture monitoring during agriculture activities leads to substantial savings in terms of irrigation water volumes requirements and cost, without compromising the productivity of the crop field. A simplified upscaling of the results at the regional scale, assuming average conditions as in this study site and growing season, reveals that potentially significant economic savings, compared to the total profits linked to maize crops, could be possible.
Antimicrobial Resistance and Livestock Trade for Low and Middle Income Countries: Regional Analysis of Global Coordination Policies
Authors: Avraam Charalampos , Lambrou Anastasia S. , Jiang Wei , Siddiqui Sauleh
Published: March 2021

Antimicrobial resistance is a threat to global health, aggravated by the use of antimicrobials in livestock production. Mitigating the growing economic costs related to antimicrobial use in livestock production requires strong global coordination, and to that end policy makers can leverage global and national food animal trade policies, such as bans and user fees. Evaluation of such policies requires representing the interactions between competing producers in the global meat market, which is usually out of the scope of statistical models. For that, we developed a game-theoretic food system model of global livestock production and trade between 18 countries and aggregate world regions. The model comprises the largest producing and consuming countries, the explicit interconnections between countries, and the use of antimicrobials in food animal production. Our model allows us to provide policy insights beyond standard literature and assess the trade-off between trade, cost of a policy, and antimicrobials-induced productivity. We studied three scenarios: global increased user fees on antimicrobials, a global ban of meat imports from Brazil, and a decrease in China's meat consumption. We found that a user fee that increases the price of antimicrobials by 50% globally leads to a 33% reduction in global antimicrobial use. However, participation of developing and emerging countries in the coordination scheme is jeopardized, since they become less competitive for meat sales compared to developed countries. When meat imports from Brazil are banned globally, importers of Brazil's meat would turn primarily to the U.S. to supplement their demand. Lastly, meeting China's medium-term lower meat consumption target would not affect global antimicrobial use, but could increase China's antimicrobial use by 11%. We highlighted the importance of trade for the outcome of a policy and concluded that global cooperation is required to align the incentives of all countries toward tackling antimicrobial resistance.
PRRSV Promotes MARC-145 Cells Entry Into S Phase of the Cell Cycle to Facilitate Viral Replication via Degradation of p21 by nsp11
Authors: Wen Xuexia , Ge Xinna , Zhou Lei , Zhang Yongning , Guo Xin , Yang Hanchun
Published: March 2021

Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most economically significant pathogens that seriously affect the global swine industry. Despite sustained efforts, the factors that affect PRRSV replication in host cells are far from being fully elucidated and thus warrants further investigation. In this study, we first demonstrated that PRRSV infection can cause downregulation of endogenous p21 protein in MARC-145 cells in a virus dose-dependent manner. Next, we analyzed the effect of p21 knockdown by RNA interference on cell cycle progression using flow cytometric analysis, and found that knockdown of p21 promotes MARC-145 cells entry into S phase of the cell cycle. Interestingly, we further discovered PRRSV infection is also able to promote MARC-145 cells entry into the S phase. Subsequently, we synchronized MARC-145 cells into G0/G1, S and G2/M phases, respectively, and then determined PRRSV replication in these cells. Results here show that the MARC-145 cells synchronized into the S phase exhibited the highest viral titer among the cells synchronized to different phases. Additionally, to reliably analyze the potential role of endogenous p21 protein in PRRSV replication, we constructed a p21 gene-knockout MARC-145 cell line (p21−/−) using CRISPR/Cas9 technology and evaluated its capability to support PRRSV replication. Our results indicate that knockout of p21 is conducive to PRRSV replication in MARC-145 cells. Furthermore, through construction of a series of eukaryotic plasmids expressing each of individual PRRSV proteins combined with cell transfection, we demonstrated that the nonstructural protein 11 (nsp11) of PRRSV mediates p21 degradation, which was further confirmed by generating a stable MARC-145 cell line constitutively expressing nsp11 using a lentivirus system. Notably, we further demonstrated that the endoribonuclease activity rather than the deubiquitinating activity of nsp11 is essential for p21 degradation via mutagenic analysis. Finally, we demonstrated that nsp11 mediates p21 degradation via a ubiquitin-independent proteasomal degradation manner. Altogether, our study not only uncovers a new pathogenesis of PRRSV, but also provides new insights into development of novel antiviral strategies.
Towards a Sustainable Reproduction Management of Dairy Sheep: Glycerol-Based Formulations as Alternative to eCG in Milked Ewes Mated at the End of Anoestrus Period
Authors: Sotgiu Francesca D. , Porcu Cristian , Pasciu Valeria , Dattena Maria , Gallus Marilia , Argiolas Giuseppe , Berlinguer Fiammetta , Molle Giovanni
Published: March 2021

This study investigated whether the administration of equine chorionic gonadotrophin (eCG) in a protocol to induce and synchronize ovulations before mating could be replaced by the administration of glycerol-based formulations in milked ewes at the end of their seasonal anoestrus. Forty-eight late-lactation dairy ewes of the Sarda breed were synchronized using sponges impregnated with progestogen and then joined with fertile rams (day (D) 0, ram introduction). From D−4 to D−1, the ewes received by gavage either 100 mL of a glucogenic mixture (70% glycerol, 20% propylene glycol and 10% water; GLU group; n = 24) or 100 mL of water (GON group; n = 24) twice daily. Moreover, on the day of sponge withdrawal (D−1), GON ewes received 200 IU of eCG. There were no differences in reproductive performances between groups. GLU ewes showed higher glycemia (p < 0.001), insulinemia (p < 0.05), plasma glycerol (p < 0.001), triglycerides (p < 0.001) and lower cholesterol (p < 0.001), non-esterified fatty acids (NEFA; p < 0.05) and urea (p < 0.001). Plasma osmolality was higher in GLU but only 4 h after dosing (p < 0.001). Milk yield and milk composition were not affected by the treatments with exception of milk glycerol (p < 0.001) and milk urea (p < 0.001), which were higher and lower in GLU than GON ewes, respectively. In conclusion, the administration of the glucogenic mixture to late lactation dairy ewes at the end of anoestrus period resulted in reproductive responses as good as the ones obtained by the eCG treatment, suggesting that the objective of a sustainable reproductive management of dairy sheep can be successfully pursued.
Proposal of a Probabilistic Model on Rotating Bending Fatigue Property of a Bearing Steel in a Very High Cycle Regime
Authors: Sakai Tatsuo , Nakagawa Akiyoshi , Nakamura Yuki , Oguma Noriyasu
Published: March 2021

In S-N diagrams for high strength steels, the duplex S-N curves for surface-initiated failure and interior inclusion-initiated failure were usually confirmed in the very high cycle regime. This trend is more distinct in the loading type of rotating bending, due to the stress distribution across the section. In the case of interior failure mode, the fish-eye is usually observed on the fracture surface and an inclusion is also observed at the center of the fish-eye. In the present work, the authors attempted to construct a probabilistic model on the statistical fatigue property in the interior failure mode, based on the distribution characteristics of the location and the size of the interior inclusion at the crack initiation site. Thus, the P-S-N characteristics of the bearing steel (SUJ2) in the very high cycle regime were successfully explained.
Machine Learning Model for Lymph Node Metastasis Prediction in Breast Cancer Using Random Forest Algorithm and Mitochondrial Metabolism Hub Genes
Authors: Kim Byung-Chul , Kim Jingyu , Lim Ilhan , Kim Dong Ho , Lim Sang Moo , Woo Sang-Keun
Published: March 2021

Breast cancer metastasis can have a fatal outcome, with the prediction of metastasis being critical for establishing effective treatment strategies. RNA-sequencing (RNA-seq) is a good tool for identifying genes that promote and support metastasis development. The hub gene analysis method is a bioinformatics method that can effectively analyze RNA sequencing results. This can be used to specify the set of genes most relevant to the function of the cell involved in metastasis. Herein, a new machine learning model based on RNA-seq data using the random forest algorithm and hub genes to estimate the accuracy of breast cancer metastasis prediction. Single-cell breast cancer samples (56 metastatic and 38 non-metastatic samples) were obtained from the Gene Expression Omnibus database, and the Weighted Gene Correlation Network Analysis package was used for the selection of gene modules and hub genes (function in mitochondrial metabolism). A machine learning prediction model using the hub gene set was devised and its accuracy was evaluated. A prediction model comprising 54-functional-gene modules and the hub gene set (NDUFA9, NDUFB5, and NDUFB3) showed an accuracy of 0.769 ± 0.02, 0.782 ± 0.012, and 0.945 ± 0.016, respectively. The test accuracy of the hub gene set was over 93% and that of the prediction model with random forest and hub genes was over 91%. A breast cancer metastasis dataset from The Cancer Genome Atlas was used for external validation, showing an accuracy of over 91%. The hub gene assay can be used to predict breast cancer metastasis by machine learning.
Bi-Temporal Anodal Transcranial Direct Current Stimulation during Slow-Wave Sleep Boosts Slow-Wave Density but Not Memory Consolidation
Authors: Ruch Simon , Fehér Kristoffer , Homan Stephanie , Morishima Yosuke , Mueller Sarah , Mueller Stefanie , Dierks Thomas , Grieder Matthias
Published: March 2021

Slow-wave sleep (SWS) has been shown to promote long-term consolidation of episodic memories in hippocampo–neocortical networks. Previous research has aimed to modulate cortical sleep slow-waves and spindles to facilitate episodic memory consolidation. Here, we instead aimed to modulate hippocampal activity during slow-wave sleep using transcranial direct current stimulation in 18 healthy humans. A pair-associate episodic memory task was used to evaluate sleep-dependent memory consolidation with face–occupation stimuli. Pre- and post-nap retrieval was assessed as a measure of memory performance. Anodal stimulation with 2 mA was applied bilaterally over the lateral temporal cortex, motivated by its particularly extensive connections to the hippocampus. The participants slept in a magnetic resonance (MR)-simulator during the recordings to test the feasibility for a future MR-study. We used a sham-controlled, double-blind, counterbalanced randomized, within-subject crossover design. We show that stimulation vs. sham significantly increased slow-wave density and the temporal coupling of fast spindles and slow-waves. While retention of episodic memories across sleep was not affected across the entire sample of participants, it was impaired in participants with below-average pre-sleep memory performance. Hence, bi-temporal anodal direct current stimulation applied during sleep enhanced sleep parameters that are typically involved in memory consolidation, but it failed to improve memory consolidation and even tended to impair consolidation in poor learners. These findings suggest that artificially enhancing memory-related sleep parameters to improve memory consolidation can actually backfire in those participants who are in most need of memory improvement.
Psychosocial Interventions for Women with a BRCA1 or BRCA2 Mutation: A Scoping Review
Authors: Boghosian Talin , McCuaig Jeanna M. , Carlsson Lindsay , Metcalfe Kelly A.
Published: March 2021

This scoping review aimed to explore the effectiveness of psychological and psychoeducational interventions for BRCA mutation carriers. Four electronic bibliographic databases were searched. After review, 23 articles that described or assessed forms of an additional psychosocial intervention for individuals with a BRCA mutation were identified and included. Intervention types discussed in the articles were telephone-based peer-to-peer counselling (5), online communities (4), in-person group counselling (8), and one-day sessions (6). Outcomes investigated within the articles included psychosocial outcomes (18), satisfaction (8), health behaviours (7), and knowledge (5). The included studies suggested that telephone-based peer-to-peer counselling and online communities improve patient knowledge and psychosocial functioning and can overcome challenges such as scheduling and travel associated with in-person support groups, but may have challenges with recruitment and retainment of participants. Group in-person education sessions satisfied the need amongst BRCA1/2 carriers in terms of accessing necessary information regarding cancer risk assessment and management; however, the impact of group education sessions on psychological outcomes was variable across the included studies. Overall, all the forms of intervention described in this scoping review were well-received by participants; some have been shown to reduce distress, depression, and anxiety.
Melanoma Brain Metastases in the Era of Targeted Therapy and Checkpoint Inhibitor Therapy
Authors: Rieth John M. , Swami Umang , Mott Sarah L. , Zanaty Mario , Henry Michael D. , Bossler Aaron D. , Greenlee Jeremy D. , Zakharia Yousef , Vanneste Marion , Jennings Brooke , Milhem Mohammed M.
Published: March 2021

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.