bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic obstructive pulmonary disease alters the genetic landscape and tumor immune microenvironment in lung cancer patients
Authors: Zhang Qiurui , Feng Xijia , Hu Weiting , Li Chengqiang , Sun Debin , Peng Zhao , Wang Shengzhou , Li Hecheng , Zhou Min
Published: June 2023

Background

Chronic obstructive pulmonary disease (COPD) and lung cancer are leading causes of morbidity and mortality worldwide. Studies have reported molecular alterations in patients with lung cancer and in patients with COPD. However, few investigation has been conducted on the molecular characteristics of lung cancer patients with COPD.

Materials and methods

We performed a retrospective cohort study that included 435 patients with pathologically confirmed lung cancer at the Ruijin Hospital. For patients with documented spirometry, Global Initiative for Chronic Obstructive Lung Disease criteria were used to define COPD. For patients without documented spirometry, chest computed tomography and other clinical information were used to define COPD. Tumor tissue DNA was extracted from formalin-fixed paraffin-embedded samples. DNA mutation analysis, multiplex immunohistochemistry (mIHC), calculation of tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and predication of neoantigens were performed.

Results

Although SNV mutations in lung cancer patients with COPD (G1 group) were generally higher than those in lung cancer patients without COPD (G2 group), the difference in the number of mutations was insignificant between the two groups. Of the 35 mutated genes, the number of them was higher in G1 than in G2, except that of EGFR. PI3K-Akt signaling pathway was enriched from significantly different genes. While TMB and MATH levels were not significantly different, the tumor neoantigen burdenwas markedly higher in G1 than that in G2. The level of CD68+ macrophages was significant higher in the stroma and total areas in the G1 group than in G2 group. The level of CD8+ lymphocytes was markedly higher in the stroma and showed a clear tendency forhigher expression in the G1 group than inthe G2 group. No significant differences were observed for the level of programmed death-ligand 1+ (PD-L1+), programmed death 1+ (PD-1+), and CD68PD-L1 in the stroma, tumor and total areas.

Conclusion

Our study revealed different genetic aberrations and pathways, higher neoantigen burden, and higher level of CD68+ macrophages and CD8+ T lymphocytes in lung cancer patients with COPD. Our investigation implies that the existence of COPD should be considered and immunotherapy is a potential choice when treating lung cancer patients with COPD.
ITGAL as a prognostic biomarker correlated with immune infiltrates in melanoma
Authors: Deng TengFei , Wang Chaoyong , Gao Cong , Zhang Qiang , Guo Jun
Published: June 2023

This study investigates the relationship between ITGAL expression and immune infiltration, clinical prognosis, and specific types of T cells in melanoma tissue. The findings reveal the key role of ITGAL in melanoma and its potential mechanism of regulating tumor immune infiltrating cells, highlighting its potential as a diagnostic biomarker and therapeutic target for advanced melanoma.
The role of EBV-encoded miRNA in EBV-associated gastric cancer
Authors: Liu Ting , Zhou Xiaoying , Zhang Zhe , Qin Yutao , Wang Rensheng , Qin Yanning , Huang Yuqi , Mo Yingxi , Huang Tingting
Published: June 2023

Epstein-Barr virus (human herpesvirus 4, EBV) is a linear double-stranded DNA virus that infects over 90% of the population worldwide. However, our understanding of EBV’s contribution to tumorigenesis of EBV-associated GC (EBVaGC) remains incomplete. Recent advancements in EBVaGC research have highlighted that EBV-encoded microRNAs (miRNAs) play prominent roles in critical cellular processes such as migration, cell cycle, apoptosis, cell proliferation, immune response, and autophagy. Notably, the largest group of EBV-encoded miRNAs, known as BamHI-A rightward transcripts (BARTs), exhibit bidirectional effects in EBVaGC. For instance, they present both anti-apoptotic and pro-apoptotic functions and enhance chemosensitivity while also conferring resistance to 5-fluorouracil. Despite these findings, the comprehensive mechanisms through which miRNAs contribute to EBVaGC are yet to be fully elucidated. In this work, we summarize the current evidence of the roles of miRNA in EBVaGC, particularly with the application of multi-omic techniques. Additionally, we discuss the application of miRNA in EBVaGC in retrospective analyses and provide novel perspectives on the use of miRNA in EBVaGC in translational medicine.
Progression of C-reactive protein from birth through preadolescence varies by mode of delivery
Authors: Sitarik Alexandra R. , Johnson Christine C. , Levin Albert M. , Lynch Susan V. , Ownby Dennis R. , Rundle Andrew G. , Straughen Jennifer K. , Wegienka Ganesa , Woodcroft Kimberley J. , Cassidy-Bushrow Andrea E.
Published: June 2023

Introduction

Delivery via caesarean section (C-section) has been associated with an increased risk of childhood chronic diseases such as obesity and asthma, which may be due to underlying systemic inflammation. However, the impact of specific C-section types may be differential, as emergency C-sections typically involve partial labor and/or membrane rupture. Our objectives were to determine if mode of delivery associates with longitudinal profiles of high sensitivity CRP (hs-CRP) —a marker of systemic inflammation—from birth through preadolescence, and to examine if CRP mediates the association between mode of delivery and preadolescent body mass index (BMI).

Methods

Data from the WHEALS birth cohort (N = 1,258) were analyzed; 564 of the 1,258 children in the cohort had data available for analysis. Longitudinal plasma samples (birth through 10-years of age) from 564 children from were assayed for hs-CRP levels. Maternal medical records were abstracted to obtain mode of delivery. Growth mixture models (GMMs) were used to determine classes of hs-CRP trajectories. Poisson regression with robust error variance was used to calculate risk ratios (RRs).

Results

Two hs-CRP trajectory classes were identified: class 1 (76% of children) was characterized by low hs-CRP, while class 2 (24% of children) was characterized by high and steadily increasing hs-CRP. In multivariable models, children delivered via planned C-section had 1.15 times higher risk of being in hs-CRP class 2, compared to vaginal deliveries (p = 0.028), while no association was found for unplanned C-section deliveries [RR (95% CI) = 0.96 (0.84, 1.09); p = 0.49]. Further, the effect of planned C-section on BMI z-score at age 10 was significantly mediated by hs-CRP class (percent mediated = 43.4%).

Conclusions

These findings suggest potentially beneficial effects of experiencing partial or full labor, leading to a lower trajectory of systemic inflammation throughout childhood and decreased BMI during preadolescence. These findings may have implications for chronic disease development later in life.
Pulmonary hemorrhage and associated risk factors among newborns admitted to a tertiary level neonatal unit in Botswana
Authors: Gezmu Alemayehu Mekonnen , Tefera Endale , Mochankana Kagiso , Imran Fizzah , Joel Dipesalema , Pelaelo Irene , Nakstad Britt
Published: June 2023

Introduction

Pulmonary hemorrhage (PH) is a life-threatening complication seen in very sick newborns with high morbidity and mortality. There is little data on the incidence, risk factors, and ultimate survival of newborns with pulmonary hemorrhage in sub-Saharan countries, where the healthcare provision and facility differ in many ways compared to high-income countries. Hence, this study aimed to determine the incidence, identify the risk factors, and describe the outcome of pulmonary hemorrhage in newborns in a low middle income country setting.

Methods and materials

A cohort study with prospective data collection was conducted in a public, tertiary-level hospital in Botswana, the Princess Marina Hospital (PMH). All newborns admitted to the neonatal unit from 1 January 2020 to 31 December 2021 were included in the study. Data were collected using a checklist developed on the RedCap database (https//:ehealth.ub.ac.bw/redcap). The incidence rate of pulmonary hemorrhage was calculated as the number of newborns who had pulmonary hemorrhage per 1,000 newborns in the 2-year period. Group comparisons were made using X2 and Student’s t-tests. Multivariate logistic regression was used to identify risk factors independently associated with pulmonary hemorrhage.

Result

There were 1,350 newborns enrolled during the study period, of which 729 were male newborns (54%). The mean (SD) birth weight was 2,154(±997.5) g, and the gestational age was 34.3 (±4.7) weeks. In addition, 80% of the newborns were delivered in the same facility. The incidence of pulmonary hemorrhage was 54/1,350 {4% [95% CI (3%–5.2%)]} among the newborns admitted to the unit. The mortality rate in those diagnosed with pulmonary hemorrhage was 29/54 (53.7%). Multivariate logistic regression identified birth weight, anemia, sepsis, shock, disseminated intravascular coagulopathy (DIC), apnea of prematurity, neonatal encephalopathy, intraventricular hemorrhage, mechanical ventilation, and blood transfusion as risk factors independently associated with pulmonary hemorrhage.

Conclusion

This cohort study identified a high incidence and mortality rate of pulmonary hemorrhage in newborns in PMH. Multiple risk factors, such as low birth weight, anemia, blood transfusion, apnea of prematurity, neonatal encephalopathy, intraventricular hemorrhage, sepsis, shock, DIC, and mechanical ventilation, were identified as independently associated risk factors for PH.
Leave no one behind: why WHO's regional office for Europe should prioritise children and adolescents in their program of work. A position statement from the European academy of paediatrics
Authors: Jansen Danielle , Brenner Maria , Illy Károly , Dembiński Łukasz , del Torso Stefano , Grossman Zachi , Valiulis Arunas , De Guchtenaere Ann , Mazur Artur , Da Dalt Liviana , Størdal Ketil , Koletzko Berthold , Hadjipanayis Adamos
Published: June 2023

Children and adolescents are no longer a priority in the most recent European Programme of Work (EPW) 2020–2025 of the World Health Organization (WHO) Regional Office for Europe. In this position statement we provide arguments for why we think this population should be explicitly addressed in this important and influential document. We firstly emphasize the persistent health problems and inequalities in access to care for children and adolescents that are challenging to solve, and thus require a continuous focus. Secondly, we urge the WHO to prioritize children and adolescents in their EPW due to the new and emerging health problems related to global issues. Finally, we explain why permanent prioritization of children and adolescents is essential for the future of children and of society.
A bibliometric study on the utilization of lenvatinib in hepatocellular carcinoma (2014–2022)
Authors: Wang Cong-Cong , Yu Cai-Yan , Zhang Jing , Wang Rui , Kong Xiang-Shuo
Published: June 2023

Background: The REFLECT phase-III trial has demonstrated the efficacy of lenvatinib in improving the overall survival of advanced hepatocellular carcinoma (HCC) patients, comparable to sorafenib. The rapidly evolving landscape of hepatocellular carcinoma therapy presents new avenues for lenvatinib. This study aims to provide a scientometric analysis of publications and predict research hotspots in this field.

Methods: Relevant publications were sourced from the Web of Science Core Collection (WoSCC) database up until November 2022. The bibliometrix tool in R was employed for scientometric analysis and visualization.

Results: A total of 879 publications from 2014 to 2022 were obtained from WoSCC that met the established criteria. These studies involved 4,675 researchers from 40 countries, with an average annual growth rate of 102.5%. The highest number of publications was from Japan, followed by China, Italy, and the United States. The largest proportion of studies, 14.0% (n = 123), was contributed by FUDAN UNIV. The studies were published in 274 journals, with CANCERS (n = 53) being the top journal, followed by FRONTIERS IN ONCOLOGY (n = 51) and HEPATOLOGY RESEARCH (n = 36). The top ten journals accounted for 31.5% of the 879 studies. The most prolific authors were Kudo M (n = 51), Hiraoka A (n = 43), and Tsuji K (n = 38). A total of 1,333 keywords were analyzed, with the present research hotspots being “immune checkpoint inhibitors,” “prognosis,” and “pd-1.” Co-occurrence clustering analysis revealed the top keywords, authors, publications, and journals. Strong collaboration was identified in the field.

Conclusion: This scientometric and visual analysis provides a comprehensive summary of the published articles on lenvatinib in HCC during 2014–2022, highlighting the research hotspots, knowledge domain, and frontiers. The results can provide insights into future research directions in this field.
Inappropriate activation of the renin-angiotensin system improves cardiac tolerance to ischemia/reperfusion injury in rats with late angiotensin II-dependent hypertension
Authors: Husková Zuzana , Kikerlová Soňa , Miklovič Matúš , Kala Petr , Papoušek František , Neckář Jan
Published: June 2023

The aim of the study was to clarify the role of the interplay between hypertension and the renin-angiotensin system (RAS) in the pathophysiology of myocardial ischemia/reperfusion (I/R) injury. We hypothesized that in the late phase of hypertension with already developed signs of end-organ damage, inappropriate RAS activation could impair cardiac tolerance to I/R injury. Experiments were performed in male Cyp1a1-Ren-2 transgenic rats with inducible hypertension. The early phase of ANG II-dependent hypertension was induced by 5 days and the late phase by the 13 days dietary indole-3-carbinol (I3C) administration. Noninduced rats served as controls. Echocardiography and pressure-volume analysis were performed, angiotensins’ levels were measured and cardiac tolerance to ischemia/reperfusion injury was studied. The infarct size was significantly reduced (by 50%) in 13 days I3C-induced hypertensive rats with marked cardiac hypertrophy, this reduction was abolished by losartan treatment. In the late phase of hypertension there are indications of a failing heart, mainly in reduced preload recruitable stroke work (PRSW), but only nonsignificant trends in worsening of some other parameters, showing that the myocardium is in a compensated phase. The influence of the RAS depends on the balance between the vasoconstrictive and the opposed vasodilatory axis. In the initial stage of hypertension, the vasodilatory axis of the RAS prevails, and with the development of hypertension the vasoconstrictive axis of the RAS becomes stronger. We observed a clear effect of AT1 receptor blockade on maximum pressure in left ventricle, cardiac hypertrophy and ANG II levels. In conclusion, we confirmed improved cardiac tolerance to I/R injury in hypertensive hypertrophied rats and showed that, in the late phase of hypertension, the myocardium is in a compensated phase.
Tumour associated endothelial cells: origin, characteristics and role in metastasis and anti-angiogenic resistance
Authors: Yao Xinghong , Zeng Ye
Published: June 2023

Tumour progression and metastasis remain the leading causes of cancer-related death worldwide. Tumour angiogenesis is essential for tumour progression. The vasculature surrounding tumours is not only a transport channel for nutrients, oxygen, and metabolites, but also a pathway for metastasis. There is a close interaction between tumour cells and endothelial cells in the tumour microenvironment. Recent studies have shown that tumour-associated endothelial cells have different characteristics from normal vascular endothelial cells, play an important role in tumour progression and metastasis, and are expected to be a key target for cancer therapy. This article reviews the tissue and cellular origin of tumour-associated endothelial cells and analyses the characteristics of tumour-associated endothelial cells. Finally, it summarises the role of tumour-associated endothelial cells in tumour progression and metastasis and the prospects for their use in clinical anti-angiogenic therapy.
Streptomyces and their specialised metabolites for phytopathogen control – comparative in vitro and in planta metabolic approaches
Authors: Dow Lachlan , Gallart Marta , Ramarajan Margaret , Law Simon R. , Thatcher Louise F.
Published: June 2023

In the search for new crop protection microbial biocontrol agents, isolates from the genus Streptomyces are commonly found with promising attributes. Streptomyces are natural soil dwellers and have evolved as plant symbionts producing specialised metabolites with antibiotic and antifungal activities. Streptomyces biocontrol strains can effectively suppress plant pathogens via direct antimicrobial activity, but also induce plant resistance through indirect biosynthetic pathways. The investigation of factors stimulating the production and release of Streptomyces bioactive compounds is commonly conducted in vitro, between Streptomyces sp. and a plant pathogen. However, recent research is starting to shed light on the behaviour of these biocontrol agents in planta, where the biotic and abiotic conditions share little similarity to those of controlled laboratory conditions. With a focus on specialised metabolites, this review details (i) the various methods by which Streptomyces biocontrol agents employ specialised metabolites as an additional line of defence against plant pathogens, (ii) the signals shared in the tripartite system of plant, pathogen and biocontrol agent, and (iii) an outlook on new approaches to expedite the identification and ecological understanding of these metabolites under a crop protection lens.
A conceptual framework for the dynamic modeling of time-resolved phenotypes for sets of genotype-environment-management combinations: a model library
Authors: van Voorn George A. K. , Boer Martin P. , Truong Sandra Huynh , Friedenberg Nicholas A. , Gugushvili Shota , McCormick Ryan , Bustos Korts Daniela , Messina Carlos D. , van Eeuwijk Fred A.
Published: June 2023

Introduction

Dynamic crop growth models are an important tool to predict complex traits, like crop yield, for modern and future genotypes in their current and evolving environments, as those occurring under climate change. Phenotypic traits are the result of interactions between genetic, environmental, and management factors, and dynamic models are designed to generate the interactions producing phenotypic changes over the growing season. Crop phenotype data are becoming increasingly available at various levels of granularity, both spatially (landscape) and temporally (longitudinal, time-series) from proximal and remote sensing technologies.

Methods

Here we propose four phenomenological process models of limited complexity based on differential equations for a coarse description of focal crop traits and environmental conditions during the growing season. Each of these models defines interactions between environmental drivers and crop growth (logistic growth, with implicit growth restriction, or explicit restriction by irradiance, temperature, or water availability) as a minimal set of constraints without resorting to strongly mechanistic interpretations of the parameters. Differences between individual genotypes are conceptualized as differences in crop growth parameter values.

Results

We demonstrate the utility of such low-complexity models with few parameters by fitting them to longitudinal datasets from the simulation platform APSIM-Wheat involving in silico biomass development of 199 genotypes and data of environmental variables over the course of the growing season at four Australian locations over 31 years. While each of the four models fits well to particular combinations of genotype and trial, none of them provides the best fit across the full set of genotypes by trials because different environmental drivers will limit crop growth in different trials and genotypes in any specific trial will not necessarily experience the same environmental limitation.

Discussion

A combination of low-complexity phenomenological models covering a small set of major limiting environmental factors may be a useful forecasting tool for crop growth under genotypic and environmental variation.
Long-term effects of biochar application on the growth and physiological characteristics of maize
Authors: Cong Mengfei , Hu Yang , Sun Xia , Yan Han , Yu Guangling , Tang Guangmu , Chen Shuhuang , Xu Wanli , Jia Hongtao
Published: June 2023

Biochar, as a soil conditioner, has been widely used to promote the growth of maize, but most of the current research is short-term experiments, which limits the research on the long-term effects of biochar, especially the physiological mechanism of biochar on maize growth in aeolian sandy soil is still unclear. Here, we set up two groups of pot experiments, respectively after the new biochar application and one-time biochar application seven years ago (CK: 0 t ha-1, C1: 15.75 t ha-1, C2: 31.50 t ha-1, C3: 63.00 t ha-1, C4: 126.00 t ha-1), and planted with maize. Subsequently, samples were collected at different periods to explore the effect of biochar on maize growth physiology and its after-effect. Results showed that the plant height, biomass, and yield of maize showed the highest rates of increase at the application rate of 31.50 t ha-1 biochar, with 22.22% increase in biomass and 8.46% increase in yield compared with control under the new application treatment. Meanwhile, the plant height and biomass of maize increased gradually with the increase of biochar application under the one-time biochar application seven years ago treatment (increased by 4.13%-14.91% and 13.83%-58.39% compared with control). Interestingly, the changes in SPAD value (leaf greenness), soluble sugar and soluble protein contents in maize leaves corresponded with the trend of maize growth. Conversely, the changes of malondialdehyde (MDA), proline (PRO), catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) manifested an opposite trend to the growth of maize. In conclusion, 31.50 t ha-1 biochar application can promote the growth of maize by inducing changes in its physiological and biochemical characteristics, but excessive biochar application rates ranging from 63.00-126.00 t ha-1 inhibited the growth of maize. After seven years of field aging, the inhibitory effect of 63.00-126.00 t ha-1 biochar amount on maize growth disappeared and changed to promoting effect.
Transcriptome and metabolome analysis of flavonol synthesis in apricot fruits
Authors: Han Xueping , Wang Jinzheng , Wang Guiping , Dong Fang , Nie Peixian , Xue Xiaomin
Published: June 2023

Introduction

Apricot fruits are edible and serve as a source of medicinal compounds. Flavonols are important plant secondary metabolites that have antioxidant and antitumor effects and may promote cardiovascular health.

Methods

The flavonoid content in three stages of the ‘Kuijin’ and the ‘Katy’ was observed, followed by the combination of metabolome and transcriptome analysis to explore the metabolic basis of flavonol synthesis.

Results

The differences in the metabolite contents between stages (of the same cultivar) and between cultivars (at the same stage) revealed decreases in the flavonoid content as fruits developed (i.e., from 0.28 mg/g to 0.12 mg/g in ‘Kuijin’ and from 0.23 mg/g to 0.05 mg/g in ‘Katy’). To decipher the regulation of flavonol synthesis in apricot (Prunus armeniaca L.), the metabolomes and transcriptomes of fruit pulp at three developmental stages of ‘Kuijin’ and the ‘Katy’ were analyzed. A total of 572 metabolites were detected in ‘Kuijin’ and the ‘Katy’ pulp, including 111 flavonoids. The higher flavonol content young ‘Kuijin’ fruits at 42 days after full bloom is mainly due to 10 types of flavonols. Three pairs of significant differences in flavonol content were identified. From these three comparison groups, three structural genes were strongly correlated with the levels of 10 types of flavonols (Pearson correlation coefficients > 0.8, p value < 0.05), including PARG09190, PARG15135, and PARG17939. The weighted gene co-expression network analysis showed that the turquoise module genes were highly correlated with flavonol contents (P < 0.01). There were 4897 genes in this module. Out of 4897 genes, 28 transcription factors are associated with 3 structural genes based on weight value. Two of the transcription factors are not only associated with PARG09190 but also with PARG15135, indicating their critical importance in the flavonols biosynthesis. The two TFs are PARG27864 and PARG10875.

Discussion

These findings provide new insights into the biosynthesis of flavonols and may explain the significant differences in flavonoid content between the ‘Kuijin’ and the ‘Katy’ cultivars. Moreover, it will aid in genetic improvement to enhance the nutritional and health value of apricots.
Low-temperature at booting reduces starch content and yield of wheat by affecting dry matter transportation and starch synthesis
Authors: Zhang Wenjing , Zhang Anmin , Zhou Qirui , Fang Ranran , Zhao Yan , Li Zihong , Zhao Jiawen , Zhao Mengting , Ma Shangyu , Fan Yonghui , Huang Zhenglai
Published: June 2023

With the continuous change of global climate, the frequency of low-temperature stress (LTS) in spring increased greatly, which led to the increase of wheat yield decline. The effects of LTS at booting on grain starch synthesis and yield were examined in two wheat varieties with differing low-temperature sensitivities (insensitive variety Yannong 19 and sensitive variety Wanmai 52). A combination of potted and field planting was employed. For LTS treatment at booting, the wheat plants were placed in a climate chamber for 24 h at −2°C, 0°C or 2°C from 19:00 to 07:00 then 5°C from 07:00 to 19:00. They were then returned to the experimental field. The effects of flag leaf photosynthetic characteristics, the accumulation and distribution of photosynthetic products, enzyme activity related to starch synthesis and relative expression, the starch content, and grain yield were determined. LTS at booting caused a significant reduction in the net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (Tr) of the flag leaves at filling. The development of starch grains in the endosperm is also hindere, there are obvious equatorial grooves observed on the surface of the A-type starch granules, and a reduction in the number of B-type starch granules. The abundance of 13C in the flag leaves and grains decreased significantly. LTS also caused a significant reduction in translocation amount of pre-anthesis stored dry matte from vegetative organs to grains and amount of post-anthesis transfer of accumulated dry matte into grains, and the distribution rate of dry matter in the grains at maturity. The grain filling time was shortened, and the grain filling rate decreased. A decrease in the activity and relative expression of enzymes related to starch synthesis was also observed, with a decrease in the total starch content. As a result, a decrease in the grain number per panicle and 1000-grain weight were also observed. These findings highlight the underlying physiological cause of decreased starch content and grain weight after LTS in wheat.
A bidirectional Mendelian randomization study about the role of morning plasma cortisol in attention deficit hyperactivity disorder
Authors: Jue Hu , Fang-fang Li , Dan-fei Chen , Nuo Chen , Chun-lu Ye , Ke-pin Yu , Jian Chen , Xiao-bo Xuan
Published: June 2023

Context

Cortisol, a hormone regulated by the hypothalamic-pituitary-adrenal (HPA) axis, has been linked to attention deficit hyperactivity disorder (ADHD). The nature of the relationship between cortisol and ADHD, and whether it is causal or explained by reverse causality, remains a matter of debate.

Objective

This study aims to evaluate the bidirectional causal relationship between morning plasma cortisol levels and ADHD.

Methods

This study used a bidirectional 2-sample Mendelian randomization (MR) design to analyze the association between morning plasma cortisol levels and ADHD using genetic information from the authoritative Psychiatric Genomics Collaboration (PGC) database (n = 55,347) and the ADHD Working Group of the CORtisol NETwork (CORNET) Consortium (n = 12,597). MR analyses were employed: inverse variance weighting (IVW), MR-Egger regression, and weighted medians. OR values and 95% CI were used to evaluate whether there was a causal association between morning plasma cortisol levels on ADHD and ADHD on morning plasma cortisol levels. The Egger-intercept method was employed to test for level pleiotropy. Sensitivity analysis was performed using the “leave-one-out” method, MR pleiotropy residual sum, and MR pleiotropy residual sum and outlier (MR-PRESSO).

Results

Findings from bidirectional MR demonstrated that lower morning plasma cortisol levels were associated with ADHD (ADHD-cortisol OR = 0.857; 95% CI, 0.755–0.974; P = 0.018), suggesting there is a reverse causal relationship between cortisol and ADHD. However, morning plasma cortisol levels were not found to have a causal effect on the risk of ADHD (OR = 1.006; 95% CI, 0.909–1.113; P = 0.907), despite the lack of genetic evidence. The MR-Egger method revealed intercepts close to zero, indicating that the selected instrumental variables had no horizontal multiplicity. The “leave-one-out” sensitivity analysis revealed stable results, with no instrumental variables significantly affecting the results. Heterogeneity tests were insignificant, and MR-PRESSO did not detect any significant outliers. The selected single-nucleotide polymorphisms (SNPs) F were all >10, indicating no weak instrumental variables. Thus, the overall MR analysis results were reliable.

Conclusion

The study findings suggest a reverse causal relationship between morning plasma cortisol levels and ADHD, with low cortisol levels associated with ADHD. No genetic evidence was found to support a causal relationship between morning plasma cortisol levels and the risk of ADHD. These results suggest that ADHD may lead to a significant reduction in morning plasma cortisol secretion.
A step toward restoring hand functions in patients with multiple sclerosis—a study protocol
Authors: Zoghi Maryam , Jaberzadeh Shapour
Published: June 2023

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation, demyelination of axons, and oligodendrocyte loss in the central nervous system. This leads to neurological dysfunction, including hand impairment, which is prevalent among patients with MS. However, hand impairment is the least targeted area for neurorehabilitation studies. Therefore, this study proposes a novel approach to improve hand functions compared to current strategies. Studies have shown that learning new skills in the motor cortex (M1) can trigger the production of oligodendrocytes and myelin, which is a critical mechanism for neuroplasticity. Transcranial direct current stimulation (tDCS) has been used to enhance motor learning and function in human subjects. However, tDCS induces non-specific effects, and concurrent behavioral training has been found to optimize its benefits. Recent research indicates that applying tDCS during motor learning can have priming effects on the long-term potentiation mechanism and prolong the effects of motor training in health and disease. Therefore, this study aims to assess whether applying repeated tDCS during the learning of a new motor skill in M1 can be more effective in improving hand functions in patients with MS than current neurorehabilitation strategies. If this approach proves successful in improving hand functions in patients with MS, it could be adopted as a new approach to restore hand functions. Additionally, if the application of tDCS demonstrates an accumulative effect in improving hand functions in patients with MS, it could provide an adjunct intervention during rehabilitation for these patients. This study will contribute to the growing body of literature on the use of tDCS in neurorehabilitation and could have a significant impact on the quality of life of patients with MS.
A computational framework for identifying chemical compounds to bind Apolipoprotein E4 for Alzheimer’s disease intervention
Authors: Zhai Tianhua , Krass Emily , Zhang Fangyuan , Huang Zuyi
Published: June 2023

Alzheimer’s disease (AD), a neurodegenerative disorder, is characterized by its ability to cause memory loss and damage other cognitive functions. Aggregation of amyloid beta (Aβ) plaques and neurofibrillary tangles in the brain are responsible for the development of Alzheimer’s disease (AD). While attempts targeting Aβ and tau proteins have been extensively conducted in the past decades, only two FDA-approved drugs (i.e., monoclonal antibodies) tackle the underlying biology of Alzheimer’s disease. In this study, an integrated computational framework was developed to identify new drug targets for Alzheimer’s disease and identify small molecules as potential therapeutical options. A systematic investigation of the gene networks firstly revealed that the Apolipoprotein E4 (ApoE4) gene plays a central role among genes associated with Alzheimer’s disease. The ApoE4 protein was then chosen as the protein target based on its role in the main pathological hallmarks of AD, which has been shown to increase Aβ accumulation by directly binding to Aβ as well as interfering with Aβ clearance that is associated with other receptors. A library of roughly 1.5 million compounds was then virtually screened via a ligand-protein docking program to identify small-molecule compounds with potential binding capacity to the ApoE4 N-terminal domain. On the basis of compound properties, 312 compounds were selected, analyzed and clustered to further identify common structures and essential functional groups that play an important role in binding ApoE4. The in silico prediction suggested that compounds with four common structures of sulfon-amine-benzene, 1,2-benzisothiazol-3-amine 1,1-dioxide, N-phenylbenzamide, and furan-amino-benzene presented strong hydrogen bonds with residues E27, W34, R38, D53, D153, or Q156 in the N terminal of ApoE4. These structures might also form strong hydrophobic interactions with residues W26, E27, L28, L30, G31, L149, and A152. While the 312 compounds can serve as drug candidates for further experiment assays, the four common structures, along with the residues for hydrogen bond or hydrophobic interaction, pave the foundation to further optimize the compounds as better binders of ApoE4.
Hepatic transcriptome analysis provides new insights into ghrelin regulation of the liver in Nile tilapia (Oreochromis niloticus)
Authors: Zhong Huan , Lou Chenyi , Ren Bingxin , Pi Jiamin , Dai Tao , Qin Weiling , Zhou Yi
Published: June 2023

Ghrelin is a growth-promoting hormone produced by the gastrointestinal tract that plays a crucial role through the ghrelin-growth hormone secretagogue receptor (GHS-R) and growth hormone/insulin-like growth factor-1 (GH/IGF-1) axes. To explore the effect of ghrelin on the transcriptomic profile of tilapia liver, the hepatic transcriptome of tilapia was sequenced for two groups, including saline-injected control (CL) and ghrelin-injected (GL; 2 μg/g body weight) tilapia. The transcriptome of livers from the two groups was sequenced using an Illumina HiSeqTM 2000 platform and yielded approximately 310.53 million raw reads. Subsequently, approximately 308.51 million clean reads were obtained from the total raw reads using in-house Perl scripts. Approximately 92.36% clean reads were mapped to the Nile tilapia genome using RSEM. Using the DESeq package, 250 differentially expressed genes (DEGs) were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed enrichment of two pathways related to RNA transcription (ribosome biogenesis in eukaryotes pathway and RNA transport pathway), with a total of 14 functional DEGs. ATP-binding and muscle contraction terms were identified as enriched using Gene Ontology (GO), yielding a total of 28 DEGs. Finally, real-time quantitative PCR (RT-qPCR) was used to confirm the accuracy of the transcriptomic results. The results of RT-qPCR were highly consistent with the RNA-seq, indicating that results of RNA-seq were valid. The differences in gene expression between the groups indicated that ghrelin-injection altered energy metabolism and RNA transcription in the tilapia liver, which provides new information to help promote the growth of tilapia.
M2F-Net: A Deep Learning-Based Multimodal Classification with High-Throughput Phenotyping for Identification of Overabundance of Fertilizers
Authors: Dhakshayani J. , Surendiran B.
Published: June 2023

Amaranth, a pseudocereal crop which is rich in nutrients and climate resistant, can provide an opportunity to increase food security and nutritional content for the growing population. Farmers rely mainly on synthetic fertilizers to improve the quality and yield of the crop; however, this overuse harms the ecosystem. Understanding the mechanism causing this environmental deterioration is crucial for crop production and ecological sustainability. In recent years, high-throughput phenotyping using Artificial Intelligence (AI) has been thriving and can provide an effective solution for the identification of fertilizer overuse. Influenced by the strength of deep learning paradigms and IoT sensors, a novel multimodal fusion network (M2F-Net) is proposed for high-throughput phenotyping to diagnose overabundance of fertilizers. In this paper, we developed and analyzed three strategies that fuse agrometeorological and image data by assessing fusion at various stages. Initially two unimodal baseline networks were trained: Multi-Layer Perceptron (MLP) on agrometeorological data and a pre-trained Convolutional Neural Network (CNN) model DenseNet-121 on image data. With these baselines, the multimodal fusion network is developed, capable of adeptly learning from image and non-image data and the model’s performance is evaluated in terms of accuracy and Area Under Curve (AUC). Moreover, the fusion approaches that are considered outperformed the unimodal networks remarkably with 91% accuracy. From the experimental result, it is proven that incorporating agrometeorological information and images can substantially boost the classification performance for the overabundance of fertilizer.
Sodium Azide as a Chemical Mutagen in Wheat (Triticum aestivum L.): Patterns of the Genetic and Epigenetic Effects with iPBS and CRED-iPBS Techniques
Authors: Türkoğlu Aras , Haliloğlu Kamil , Tosun Metin , Szulc Piotr , Demirel Fatih , Eren Barış , Bujak Henryk , Karagöz Halit , Selwet Marek , Özkan Güller , Niedbała Gniewko
Published: June 2023

Wheat, which is scientifically known as Triticum aestivum L., is a very nutritious grain that serves as a key component of the human diet. The use of mutation breeding as a tool for crop improvement is a reasonably rapid procedure, and it generates a variety that may be used in selective breeding programs as well as functional gene investigations. The present experiment was used to evaluate the potential application of a conventional chemical mutagenesis technique via sodium azide (NaN3) for the germination and seedling growth stage in wheat. Experiments with NaN3 mutagenesis were conducted using four different treatment periods (0, 1, 2, and 3 h) and five different concentrations (0, 0.5, 1, 1.5, and 2 mM). The genomic instability and cytosine methylation of wheat using its seeds were investigated after they were treated. In order to evaluate the genomic instability and cytosine methylation in wheat that had been treated, interprimer binding site (iPBS) markers were used. The mutagenic effects of NaN3 treatments had considerable polymorphism on a variety of impacts on the cytosine methylation and genomic instability of wheat plants. The results of the experiment showed considerable changes in the iPBS profiles produced by the administration of the same treatments at different dosages and at different times. Coupled restriction enzyme digestion interprimer binding site (CRED-iPBS) assays identified changes in gDNA cytosine methylation. The highest polymorphism value was obtained during 1 h + 2 mM NaN3, while the lowest (20.7%) was obtained during 1 h + 1.5 mM NaN3. Results showed that treatments with NaN3 had an effect on the level of cytosine methylation and the stability of the genomic template in wheat plants in the germination stage. Additionally, an integrated method can be used to for mutation-assisted breeding using a molecular marker system in wheat followed by the selection of desired mutants.
Exploiting the Genetic Potential of Cowpea in An Intercropping Complex
Authors: Ongom Patrick Obia , Fatokun Christian , Togola Abou , Mohammed Saba B. , Ishaya Daniel Jockson , Bala Garba , Popoola Bosede , Mansur Ahmad , Tukur Sagir , Ibikunle Mumini , Abdulkazeem Bello , Boukar Ousmane
Published: June 2023

In the West African sub-region, intercropping is a critical element in cowpea product profiles. This study aimed to investigate the impact of intercropping cowpea with pearl millet on genetic correlations, heritability, and response to selection. Thirty-five cowpea genotypes and one pearl millet variety were used to create three cropping patterns: sole cowpea, 1:1 (one row of millet to one row of cowpea), and 2:4 (two rows of millet to four rows of cowpea). Split-plot experiments were conducted for two years with cropping patterns considered as the main plots and genotypes as sub-plots. Data were captured on grain yield (GY), 100 seed weight (Hsdwt), pod weight (Pdwt), fodder weight (Fdwt), and harvest index (HI). Genotype, cropping pattern, year, and genotype-by-cropping pattern interactions were significant for most of the traits. Higher heritability and predicted genetic advance were depicted under sole cropping rather than in the intercropped systems. High positive genetic correlations (rg ≥ 0.9) were obtained between cropping patterns. Genetic correlations among traits were higher under sole cropping than in the intercropping. Path analysis portrayed the HI as having the highest significant and positive direct effect on GY. This study identified short duration cowpea genotypes that are stable and adapted to unique cropping systems.
Herbicide Resistance: Managing Weeds in a Changing World
Authors: Ofosu Rita , Agyemang Evans Duah , Márton Adrienn , Pásztor György , Taller János , Kazinczi Gabriella
Published: June 2023

Over the years, several agricultural interventions and technologies have contributed immensely towards intensifying food production globally. The introduction of herbicides provided a revolutionary tool for managing the difficult task of weed control contributing significantly towards global food security and human survival. However, in recent times, the successes achieved with chemical weed control have taken a turn, threatening the very existence we have tried to protect. The side effects of conventional farming, particularly the increasing cases of herbicide resistance agricultural weeds, is quite alarming. Global calls for sustainable weed management approaches to be used in food production is mounting. This paper provides detailed information on the molecular biological background of herbicide resistant weed biotypes and highlights the alternative, non-chemical weed management methods which can be used to prevent the development and spreading of herbicide-resistant weeds.
Nanofarming: Promising Solutions for the Future of the Global Agricultural Industry
Authors: El-Ramady Hassan , Abdalla Neama , Sári Daniella , Ferroudj Aya , Muthu Arjun , Prokisch József , Fawzy Zakaria F. , Brevik Eric C. , Solberg Svein Ø.
Published: June 2023

The agricultural sector is a vital source of human well-being that provides the necessities of daily life. A variety of farming systems are utilized in agriculture, such as a wide range of tillage options, no-till, agroforestry, precision farming, organic farming, cover cropping, crop rotations, etc. Each of these farming systems has unique challenges, and nanotechnology has successfully improved on many of them. Agricultural applications of nanotechnology include nanofertilizers, nanopesticides, nanosensors, nanobiotechnology, and nanoremediation. This study focuses on the application of nano-farming technologies to different farming systems. Suggested practices include nano improvement of soil quality, crop nano-protection under biotic stress, nanoremediation of polluted soil and water environments, nanomanagement of agro-wastes, nano-agrochemicals, nano-precision farming, and nanobiotechnology for modern farming. This review also addresses expected problems that may occur due to over application of nanomaterials to farming systems, such as nanopollution and nanotoxicity of agroecosystem compartments. Several dimensions are emphasized in this study, such as green energy, sustainable development, the circular bioeconomy, land biodegradation, pollution, and the one health approach, as essential for the global goals of sustainable development. Nanofarming presents both benefits and obstacles to human life. The exact balance between these benefits and challenges needs more study.
The Relevance of the Expected Value of the Proportion of Arabian Genes in Genetic Evaluations for Eventing Competitions
Authors: Sánchez-Guerrero María José , Ripollés-Lobo María , Bartolomé Ester , Perdomo-González Davinia Isabel , Valera Mercedes
Published: June 2023

The Arabian horse is a generally reliable sport horse, and continues to be a remarkable endurance horse, so the relevance of the expected value of the proportion of Arabian genes (EV%AG) in horses participating in eventing could be a relevant factor. A total of 1089 horses participating in eventing (8866 records) were used. A GLM revealed that the EV%AG was significant in dressage, show jumping and cross-country. A BLUP genetic evaluation was computed with five genetic models (without the EV%AG (0) using as a covariate (A), as a fixed effect (B), with variance heterogeneity, and in genetic groups without (C) and with (D)). Dressage heritability ranged from 0.103 to 0.210, show jumping ranged from 0.117 to 0.203 and cross-country ranged from 0.070 to 0.099. The lowest DIC value was used as a criterion of fitness. The best fits (those which included variance heterogeneity) showed fewer than two points of difference in DIC values. The highest average estimated breeding value in dressage, show jumping and cross-country was found for horses with an expected value of the proportion of Arabian genes of 0%, ≥1% to <25%, and 100%, respectively. Therefore, the best way to model the EV%AG effect seems to be by considering the variance heterogeneity.