bluuebunny/crossref_metadata_2025 huggingface dataset:
Tweaking Progranulin Expression: Therapeutic Avenues and Opportunities
Authors: Terryn Joke , Verfaillie Catherine M. , Van Damme Philip
Published: July 2021

Frontotemporal dementia (FTD) is a neurodegenerative disease, leading to behavioral changes and language difficulties. Heterozygous loss-of-function mutations in progranulin (GRN) induce haploinsufficiency of the protein and are associated with up to one-third of all genetic FTD cases worldwide. While the loss of GRN is primarily associated with neurodegeneration, the biological functions of the secreted growth factor-like protein are more diverse, ranging from wound healing, inflammation, vasculogenesis, and metabolic regulation to tumor cell growth and metastasis. To date, no disease-modifying treatments exist for FTD, but different therapeutic approaches to boost GRN levels in the central nervous system are currently being developed (including AAV-mediated GRN gene delivery as well as anti-SORT1 antibody therapy). In this review, we provide an overview of the multifaceted regulation of GRN levels and the corresponding therapeutic avenues. We discuss the opportunities, advantages, and potential drawbacks of the diverse approaches. Additionally, we highlight the therapeutic potential of elevating GRN levels beyond patients with loss-of-function mutations in GRN.
Chaya Leaf Decreased Triglycerides and Improved Oxidative Stress in Subjects With Dyslipidemia
Authors: Guevara-Cruz Martha , Medina-Vera Isabel , Cu-Cañetas Trinidad Eugenia , Cordero-Chan Yusef , Torres Nimbe , Tovar Armando R. , Márquez-Mota Claudia , Talamantes-Gómez José Moisés , Pérez-Monter Carlos , Lugo Roberto , Gutiérrez-Solis Ana Ligia , Avila-Nava Azalia
Published: July 2021

Chaya is an edible leaf popular in Mexico and Central America because of its high nutritional value. Studies in animal models have demonstrated the beneficial effects of Chaya, which include reduction of circulating lipids and increase in antioxidant activity. However, its hypolipidemic and antioxidant effects have not been demonstrated in humans. Thus, the aim of the present study was to evaluate the effect of Chaya on the lipid profile, lipid peroxidation, inflammation, and peripheral blood mononuclear cell gene expression in a population with dyslipidemia. We performed a single-arm trial in 30 participants with dyslipidemia who consumed 500 mL of Chaya beverage per day over a 6-week period. Interestingly, we observed a significant decrease in serum triglyceride concentration (P < 0.05) and an increase in plasma antioxidant activity and polyphenol concentration (P < 0.005) after 6 weeks of Chaya consumption. This was accompanied by a reduction in the oxidative stress marker MDA (P < 0.0001) and by an increase in the antioxidant enzyme CAT expression in peripheral blood mononuclear cells (P < 0.001). Altogether, our results demonstrate that consumption of Chaya has hypotriglyceridemic and antioxidant effects in subjects with dyslipidemia.
Moringa oleifera Supplementation Improves Antioxidant Status and Biochemical Indices by Attenuating Early Pregnancy Stress in Beetal Goats
Authors: Afzal Ali , Hussain Tarique , Hameed Amjad
Published: July 2021

This study investigated the effects of supplementing different levels of Moringa oleifera leaf powder (MOLP) on antioxidant status and blood biochemical indices during early gestation in Beetal goats. A total of 30 goats were randomly divided into three groups (n = 10) comprising control (basal diet without MOLP), the 1.6% MOLP supplemented group (basal diet + 1.6% MOLP), and the 3.2% MOLP supplemented group (basal diet + 3.2% MOLP). The experiment started 5 days before estrus synchronization and lasted till day 60 of gestation. The MOLP significantly increased plasma flavonoids in 1.6% as well as 3.2% supplemented group on days 40 and 60 of pregnancy, while total phenolic contents were observed to be higher in the 3.2% MOLP supplemented group throughout the experiment in comparison with the control group. The supplementation improved plasma total antioxidant capacity (TAC) by decreasing malondialdehyde (MDA) and total oxidant status (TOS) in contrast to the control group. The activities of superoxide dismutase (SOD) and peroxidase (POD) were enhanced in both supplemented groups, whereas catalase (CAT) activity was noticed to be significantly high in the 3.2% MOLP supplemented group. The protein contents were significantly elevated with 1.6 and 3.2% supplementation levels from day 40 to day 60 of the experiment. Plasma sugar level, carotenoids, progesterone profile, and hydrolytic (protease and amylase) enzymes activities were improved only when supplemented with 3.2% MOLP. The findings suggest that supplementing with 3.2% MOLP provides beneficial effects on early pregnancy stress in Beetal goats.
Mixed Photon and Carbon-Ion Beam Radiotherapy in the Management of Non-Metastatic Nasopharyngeal Carcinoma
Authors: Hu Jiyi , Huang Qingting , Gao Jing , Hu Weixu , Yang Jing , Guan Xiyin , Qiu Xianxin , Zhang Wenna , Kong Lin , Lu Jiade J.
Published: July 2021

Background

Carbon-ion radiotherapy (CIRT) may further increase the therapeutic ratio for patients with newly diagnosed nasopharyngeal carcinoma (NPC). The purpose of the current study is to examine the effectiveness and toxicity profile of photon-based intensity-modulated radiotherapy (IMRT) plus CIRT boost in a relatively large cohort of NPC patients.

Methods

In the current study, non-metastatic NPC patients treated with IMRT plus CIRT boost at Shanghai Proton and Heavy Ion Center between June, 2015 and June, 2018 were included. Overall survival (OS), progression-free survival (PFS), local control, regional control, and distant control were calculated with Kaplan–Meier method. Acute and late toxicities were graded using CTCAE 4.03.

Results

A total of 69 patients were included in the analysis. Among those, 74% of the patients had locoregionally advanced (stage III/IV) disease, and 92.8% had cervical lymphadenopathy. With a median follow-up of 31.9 months, the 3-year OS, PFS, local control, regional control, and distant control rates were 94.9, 85.2, 96.9, 98.4, and 89.7%, respectively. Mixed treatment of IMRT with CIRT boost was well tolerated. Severe acute toxicities induced by radiation therapy were observed in only two patients (dermatitis). No severe radiation-induced late toxicity was observed at the time of analysis. Univariable analysis showed N2/3 disease was correlated with an inferior distant control (p = 0.040).

Conclusion

Mixed treatment of IMRT plus CIRT boost provides an excellent disease control and a favorable toxicity profile for patients with non-metastatic NPC. Further follow-up is necessary to evaluate the long-term survivals and toxicities more accurately.
Effects of Inflammation on the Immune Microenvironment in Gastric Cancer
Authors: Zhao Weidan , Liu Mingqing , Zhang Mingyue , Wang Yachen , Zhang Yingli , Wang Shiji , Zhang Nan
Published: July 2021

Background

Chronic inflammation and immune cell dysfunction in the tumor microenvironment are key factors in the development and progression of gastric tumors. However, inflammation-related genes associated with gastric cancer prognosis and their relationship with the expression of immune genes are not fully understood.

Method

In this study, we established an inflammatory response model score called “Riskscore”, based on differentially expressed genes in gastric cancer. We used Survival and Survminer packages in R to analyze patient survival and prognosis in risk groups. The survival curve was plotted using the Kaplan–Meier method, and the log-rank test was used to assess statistical significance, and we performed the ROC analysis using the R language package to analyze the 1-, 3-, and 5-year survival of patients in the GEO and TCGA databases. Single-factor and multi-factor prognostic analyses were carried out for age, sex, T, N, M, and risk score. Pathway enrichment analysis indicated immune factor-related pathway enrichment in both patient groups. Next, we screened for important genes that are involved in immune cell regulation. Finally, we created a correlation curve to explore the correlation between Riskscore and the expression of these genes.

Results

The prognosis was significantly different between high- and low-risk groups, and the survival rate and survival time of the high-risk group were lower than those of the low-risk group. we found that the pathways related to apoptosis, hypoxia, and immunity were most enriched in the risk groups. we found two common tumor-infiltrating immune cell types (i.e., follicular helper T cells and resting dendritic cells) between the two risk groups and identified 10 genes that regulate these cells. Additionally, we found that these 10 genes are positively associated with the two risk groups.

Conclusion

Finally, a risk model of the inflammatory response in gastric cancer was established, and the inflammation-related genes used to construct the model were found to be directly related to immune infiltration. This model can improve the gastric cancer prognosis prediction. Our findings contribute to the development of immunotherapy for the treatment of gastric cancer patients.
CYP2D6 Allele Frequency in Five Malaria Vivax Endemic Areas From Brazilian Amazon Region
Authors: Salles Paula Ferreira , Perce-da-Silva Daiana Souza , Rossi Atila Duque , Raposo Luisa Riehl , Ramirez Ramirez Aina Danaisa , Pereira Bastos Otílio Machado , Pratt-Riccio Lilian Rose , Cassiano Gustavo Capatti , Baptista Andrea Regina Souza , Cardoso Cynthia Chester , Banic Dalma Maria , Machado Ricardo Luiz Dantas
Published: July 2021

Genetic variability was linked with individual responses to treatment and susceptibility to malaria by Plasmodium vivax. Polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. The aim of the study was to investigate whether or not CYP2D6 single nucleotide polymorphisms rs1065852, rs38920-97, rs16947 and rs28371725 are unequally distributed in malaria by Plasmodium vivax individuals from the Brazilian Amazon region. The blood samples were collected from 220 unrelated Plasmodium vivax patients from five different endemic areas. Genotyping was performed using SNaPshot® and real-time polymerase chain reaction methods. In all five areas, the rs1065852 (CYP2D6*10, C.100C > T), rs3892097 (CYP2D6*4, 1846C > T) and rs16947 (CYP2D6*2, C.2850G > A), as a homozygous genotype, showed the lowest frequencies. The rs28371725 (CYP2D6*41, 2988G > A) homozygous genotype was not detected, while the allele A was found in a single patient from Macapá region. No deviations from Hardy-Weinberg equilibrium were found, although a borderline p-value was observed (p = 0.048) for the SNP rs3892097 in Goianésia do Pará, Pará state. No significant associations were detected in these frequencies among the five studied areas. For the SNP rs3892097, a higher frequency was observed for the C/T heterozygous genotype in the Plácido de Castro and Macapá, Acre and Amapá states, respectively. The distribution of the CYP2D6 alleles investigated in the different areas of the Brazilian Amazon is not homogeneous. Further investigations are necessary in order to determine which alleles might be informative to assure optimal drug dosing recommendations based on experimental pharmacogenetics.
Magnoflorine Alleviates “M1” Polarized Macrophage-Induced Intervertebral Disc Degeneration Through Repressing the HMGB1/Myd88/NF-κB Pathway and NLRP3 Inflammasome
Authors: Zhao Feng , Guo Zhenye , Hou Fushan , Fan Wei , Wu Binqiang , Qian Zhonglai
Published: July 2021

Intervertebral disc degeneration (IDD) is related to the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. The imbalance of pro-inflammatory (M1 type) and anti-inflammatory (M2 type) macrophages contributes to maintaining tissue integrity. Here, we aimed to probe the effect of Magnoflorine (MAG) on NP cell apoptosis mediated by “M1” polarized macrophages. THP-1 cells were treated with lipopolysaccharide (LPS) to induce “M1” polarized macrophages. Under the treatment with increasing concentrations of MAG, the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-18), high mobility group box protein 1 (HMGB1), as well as myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB) and NOD-like receptor 3 (NLRP3) inflammasomes in THP-1 cells were determined. What’s more, human NP cells were treated with the conditioned medium (CM) from THP-1 cells. The NP cell viability and apoptosis were evaluated. Western blot (WB) was adopted to monitor the expression of apoptosis-related proteins (Bax, Caspase3, and Caspase9), catabolic enzymes (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5), and extracellular matrix (ECM) compositions (collagen II and aggrecan) in NP cells. As a result, LPS evidently promoted the expression of pro-inflammatory cytokines and HMGB1, the MyD88-NF-κB activation, and the NLRP3 inflammasome profile in THP-1 cells, while MAG obviously inhibited the "M1″ polarization of THP-1 cells. After treatment with “M1” polarized THP-1 cell CM, NP cell viability was decreased, while cell apoptosis, the pro-inflammatory cytokines, apoptosis-related proteins, and catabolic enzymes were distinctly up-regulated, and ECM compositions were reduced. After treatment with MAG, NP cell damages were dramatically eased. Furthermore, MAG dampened the HMGB1 expression and inactivated the MyD88/NF-κB pathway and NLRP3 inflammasome in NP cells. In conclusion, this study confirmed that MAG alleviates “M1” polarized macrophage-mediated NP cell damage by inactivating the HMGB1-MyD88-NF-κB pathway and NLRP3 inflammasome, which provides a new reference for IDD treatment.
Probiotic Supplementation for Rheumatoid Arthritis: A Promising Adjuvant Therapy in the Gut Microbiome Era
Authors: Ferro Margarida , Charneca Sofia , Dourado Eduardo , Guerreiro Catarina Sousa , Fonseca João Eurico
Published: July 2021

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease that ultimately leads to joint destruction and functional disability. Although the exact etiology of RA is not fully understood, it is well established that gut microbiota (GM) plays a vital role in the pathogenesis of RA, with accumulating evidence suggesting that gut dysbiosis induces a chronic inflammatory response that may be linked to disease development. Of interest, patients with RA have significant changes in the intestinal microbiota compared to healthy controls, and several studies have suggested the use of probiotics as a possible adjuvant therapy for RA. Benefits of probiotic supplementation were reported in animal models of arthritis and human studies, but the current evidence regarding the effect of probiotic supplementation in the management of RA remains insufficient to make definite recommendations. Several different strains ofLactobacillusandBifidobacteria, as single species or in mixed culture, have been investigated, and some have demonstrated beneficial effects on disease activity in RA human subjects. As of now,L.caseiprobiotic bacteria seems to be the strongest candidate for application as adjuvant therapy for RA patients. In this review, we highlight the role of GM in the development and progression of RA and summarize the current knowledge on the use of probiotics as a potential adjuvant therapy for RA. We also review the proposed mechanisms whereby probiotics regulate inflammation. Finally, the role of fermented foods is discussed as a possible alternative to probiotic supplements since they have also been reported to have health benefits.
Certain Properties of Domination in Product Vague Graphs With an Application in Medicine
Authors: Shi Xiaolong , Kosari Saeed
Published: July 2021

The product vague graph (PVG) is one of the most significant issues in fuzzy graph theory, which has many applications in the medical sciences today. The PVG can manage the uncertainty, connected to the unpredictable and unspecified data of all real-world problems, in which fuzzy graphs (FGs) will not conceivably ensue into generating adequate results. The limitations of previous definitions in FGs have led us to present new definitions in PVGs. Domination is one of the highly remarkable areas in fuzzy graph theory that have many applications in medical and computer sciences. Therefore, in this study, we introduce distinctive concepts and properties related to domination in product vague graphs such as the edge dominating set, total dominating set, perfect dominating set, global dominating set, and edge independent set, with some examples. Finally, we propose an implementation of the concept of a dominating set in medicine that is related to the COVID-19 pandemic.
The Physical Mechanisms Behind the Change in the Precipitation Recycling Rate in the Mid- and Lower Reaches of the Yangtze River
Authors: Guo Wen-Kang , Wang Xi-Yu , Gao Wang-Ze , Yong Jia-Hua , Bao Xin-Yue , Wu Yong-Ping , Feng Guo-Lin , Dong Wen-Jie
Published: July 2021

The precipitation recycling rate (PRR) is an important index when trying to understand the physical mechanisms behind the effects of different sources of water vapor on regional precipitation. We studied the change in the PRR in the mid- and lower reaches of the Yangtze River (MLRYR), the correlation between the PRR and the external source of water vapor and local evaporation, and the possible reasons for the interannual variation of the PRR. Our study was based on an evaluation model of the PRR and used precipitation data from meteorological stations in China and NCEP/NCAR reanalysis datasets. Our results show that the mean PRR in the MLRYR for the time period 1961–2017 was largest in autumn (about 0.3) and smallest in summer (about 0.23), with a clear upward trend (passed the 95% significance F-test), except in summer. The highest trend coefficient of the PRR was in autumn (0.38), indicating that the contribution of an external source of water vapor to local precipitation was reduced. The PRR of the MLRYR was strongly correlated with the input of water vapor through the western and southern boundaries. Water vapor was mainly sourced from the Northwest Pacific Ocean, the South China Sea and the Bay of Bengal. The anomalous Northwest Pacific cyclone induced by the Pacific sea surface temperature restrained the input of water vapor into the MLRYR from the Western Pacific, the South China Sea and the Bay of Bengal, contributing to the upward trend in the PRR. We suggest that increases in the sea surface temperature in the Pacific Ocean, South China Sea and especially the Indian Ocean will have an important impact on precipitation in East Asia.
Electrophysiological Characterization of Human Atria: The Understated Role of Temperature
Authors: Majumder Rupamanjari , Mohamed Nazer Afnan Nabizath , Panfilov Alexander V. , Bodenschatz Eberhard , Wang Yong
Published: July 2021

Ambient temperature has a profound influence on cellular electrophysiology through direct control over the gating mechanisms of different ion channels. In the heart, low temperature is known to favor prolongation of the action potential. However, not much is known about the influence of temperature on other important characterization parameters such as the resting membrane potential (RMP), excitability, morphology and characteristics of the action potential (AP), restitution properties, conduction velocity (CV) of signal propagation, etc. Here we present the first, detailed, systematic in silico study of the electrophysiological characterization of cardiomyocytes from different regions of the normal human atria, based on the effects of ambient temperature (5−50°C). We observe that RMP decreases with increasing temperature. At ~ 48°C, the cells lose their excitability. Our studies show that different parts of the atria react differently to the same changes in temperature. In tissue simulations a drop in temperature correlated positively with a decrease in CV, but the decrease was region-dependent, as expected. In this article we show how this heterogeneous response can provide an explanation for the development of a proarrhythmic substrate during mild hypothermia. We use the above concept to propose a treatment strategy for atrial fibrillation that involves severe hypothermia in specific regions of the heart for a duration of only ~ 200 ms.
Assessment of Placental Extracellular Vesicles-Associated Fas Ligand and TNF-Related Apoptosis-Inducing Ligand in Pregnancies Complicated by Early and Late Onset Preeclampsia
Authors: Ayala-Ramírez Paola , Machuca-Acevedo Catalina , Gámez Tatiana , Quijano Sandra , Barreto Alfonso , Silva Jaime L. , Olaya-C Mercedes , García-Robles Reggie
Published: July 2021

Preeclampsia (PE) is a hypertensive disorder that affects 2–8% of pregnancies and is one of the main causes of fetal, neonatal, and maternal mortality and morbidity worldwide. Although PE etiology and pathophysiology remain unknown, there is evidence that the hyperactivation of maternal immunity cells against placental cells triggers trophoblast cell apoptosis and death. It has also been reported that placenta-derived extracellular vesicles (EV) carry Fas ligand (FasL) and Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and trigger apoptosis in Jurkat T cells. This study aimed to quantify and compare FasL and TRAIL expression in EV derived from cultures of placenta explants from women with PE (early versus late) and women with uncomplicated pregnancies. Also, the study assessed EV capacity to induce apoptosis in Jurkat T cells. The authors isolated EV from placenta explant cultures, quantified FasL and TRAIL using ELISA, and analyzed EV apoptosis-inducing capability by flow cytometry. Results showed increased FasL and TRAIL in EV derived from placenta of women with PE, and increased EV apoptosis-inducing capability in Jurkat T cells. These results offer supporting evidence that EV FasL and TRAIL play a role in the pathophysiology of PE.
Plastid-Localized EMB2726 Is Involved in Chloroplast Biogenesis and Early Embryo Development in Arabidopsis
Authors: Li Chuanling , Shang Jian-Xiu , Qiu Chenlei , Zhang Baowen , Wang Jinxue , Wang Shuo , Sun Yu
Published: July 2021

Embryogenesis is a critical developmental process that establishes the body organization of higher plants. During this process, the biogenesis of chloroplasts from proplastids is essential. A failure in chloroplast development during embryogenesis can cause morphologically abnormal embryos or embryonic lethality. In this study, we isolated a T-DNA insertion mutant of the Arabidopsis gene EMBRYO DEFECTIVE 2726 (EMB2726). Heterozygous emb2726 seedlings produced about 25% albino seeds with embryos that displayed defects at the 32-cell stage and that arrested development at the late globular stage. EMB2726 protein was localized in chloroplasts and was expressed at all stages of development, such as embryogenesis. Moreover, the two translation elongation factor Ts domains within the protein were critical for its function. Transmission electron microscopy revealed that the cells in emb2726 embryos contained undifferentiated proplastids and that the expression of plastid genome-encoded photosynthesis-related genes was dramatically reduced. Expression studies of DR5:GFP, pDRN:DRN-GFP, and pPIN1:PIN1-GFP reporter lines indicated normal auxin biosynthesis but altered polar auxin transport. The expression of pSHR:SHR-GFP and pSCR:SCR-GFP confirmed that procambium and ground tissue precursors were lacking in emb2726 embryos. The results suggest that EMB2726 plays a critical role during Arabidopsis embryogenesis by affecting chloroplast development, possibly by affecting the translation process in plastids.
Insertion of Badnaviral DNA in the Late Blight Resistance Gene (R1a) of Brinjal Eggplant (Solanum melongena)
Authors: Serfraz Saad , Sharma Vikas , Maumus Florian , Aubriot Xavier , Geering Andrew D. W. , Teycheney Pierre-Yves
Published: July 2021

Endogenous viral elements (EVEs) are widespread in plant genomes. They result from the random integration of viral sequences into host plant genomes by horizontal DNA transfer and have the potential to alter host gene expression. We performed a large-scale search for co-transcripts including caulimovirid and plant sequences in 1,678 plant and 230 algal species and characterized 50 co-transcripts in 45 distinct plant species belonging to lycophytes, ferns, gymnosperms and angiosperms. We found that insertion of badnavirus EVEs along with Ty-1 copia mobile elements occurred into a late blight resistance gene (R1) of brinjal eggplant (Solanum melongena) and wild relatives in genus Solanum and disrupted R1 orthologs. EVEs of two previously unreported badnaviruses were identified in the genome of S. melongena, whereas EVEs from an additional novel badnavirus were identified in the genome of S. aethiopicum, the cultivated scarlet eggplant. Insertion of these viruses in the ancestral lineages of the direct wild relatives of the eggplant would have occurred during the last 3 Myr, further supporting the distinctiveness of the group of the eggplant within the giant genus Solanum.
Modeling Agrobacterium-Mediated Gene Transformation of Tobacco (Nicotiana tabacum)—A Model Plant for Gene Transformation Studies
Authors: Niedbała Gniewko , Niazian Mohsen , Sabbatini Paolo
Published: July 2021

The multilayer perceptron (MLP) topology of an artificial neural network (ANN) was applied to create two predictor models in Agrobacterium-mediated gene transformation of tobacco. Agrobacterium-mediated transformation parameters, including Agrobacterium strain, Agrobacterium cell density, acetosyringone concentration, and inoculation duration, were assigned as inputs for ANN–MLP, and their effects on the percentage of putative and PCR-verified transgenic plants were investigated. The best ANN models for predicting the percentage of putative and PCR-verified transgenic plants were selected based on basic network quality statistics. Ex-post error calculations of the relative approximation error (RAE), the mean absolute error (MAE), the root mean square error (RMS), and the mean absolute percentage error (MAPE) demonstrated the prediction quality of the developed models when compared to stepwise multiple regression. Moreover, significant correlations between the ANN-predicted and the actual values of the percentage of putative transgenes (R2 = 0.956) and the percentage of PCR-verified transgenic plants (R2 = 0.671) indicate the superiority of the established ANN models over the classical stepwise multiple regression in predicting the percentage of putative (R2 = 0.313) and PCR-verified (R2= 0.213) transgenic plants. The best combination of the multiple inputs analyzed in this investigation, to achieve maximum actual and predicted transgenic plants, was at OD600 = 0.8 for the LB4404 strain of Agrobacterium × 300 μmol/L acetosyringone × 20 min immersion time. According to the sensitivity analysis of ANN models, the Agrobacterium strain was the most important influential parameter in Agrobacterium-mediated transformation of tobacco. The prediction efficiency of the developed model was confirmed by the data series of Agrobacterium-mediated transformation of an important medicinal plant with low transformation efficiency. The results of this study are pivotal to model and predict the transformation of other important Agrobacterium-recalcitrant plant genotypes and to increase the transformation efficiency by identifying critical parameters. This approach can substantially reduce the time and cost required to optimize multi-factorial Agrobacterium-mediated transformation strategies.
Dimensionality of the Mental Toughness Questionnaire (MTQ48)
Authors: Perry John L. , Strycharczyk Doug , Dagnall Neil , Denovan Andrew , Papageorgiou Kostas A. , Clough Peter J.
Published: July 2021

Currently there is debate as to whether mental toughness is a unidimensional or multidimensional construct. To investigate the dimensionality of the Mental Toughness Questionnaire 48-items (MTQ48), a widely used measure of mental toughness, we examined data from a sample of 78,947 participants. A series of exploratory structural equation models (ESEM) assessed unidimensional, multidimensional, and bifactor solutions. Overall, results supported a bifactor conceptualization of mental toughness. Bifactor analysis was consistent with the use of a general factor score. In conclusion, the authors argue that mental toughness should be considered as an umbrella term representing a general trait comprised of related constructs that provide a psychological advantage in performance and promote positive mental health. Finally, this article identifies limitations in the existing measurement of mental toughness and proposes necessary directions in future research.
The Role of Geographical Area and Entrepreneurs' Personality
Authors: Yurrebaso Amaia , Picado Eva María , Paiva Teresa
Published: July 2021

This study proposed a line of research on entrepreneurship based on the analysis of personality traits and geographical area. Its objective is to identify whether certain personality traits or sociocultural variables typical of a particular geographical area influence those who have already started an entrepreneurial activity to keep it up, in other words, to maintain their entrepreneurial intention. The research results reach a sample of 479 entrepreneurs from two Iberian Peninsula geographical areas. The analyse of the psychometric properties on the Entrepreneurial Orientation Questionnaire (EOQ) identified five dimensions of the enterprising personality. They also evidence that geographical location is a factor that contributes to the development of the entrepreneurial intentions that determine the business profile. The results show that entrepreneurs in the northern area tend to maintain their business than those in the central zone.
Rural Tourism and the Sustainable Development Goals. A Study of the Variables That Most Influence the Behavior of the Tourist
Authors: López-Sanz José María , Penelas-Leguía Azucena , Gutiérrez-Rodríguez Pablo , Cuesta-Valiño Pedro
Published: July 2021

Tourism is an activity that contributes directly and indirectly to the development of rural areas. But this development needs to be sustainable. To do this, appropriate policies that positively influence these areas from an economic, social and cultural point of view must be implemented. All this in accordance with the Sustainable Development Goals. This study will analyze the contribution of rural tourism to develop and implement policies to promote sustainable tourism that creates jobs and promotes local culture and products. The variables that most influence the tourist behavior, motivation, the destination image, and the satisfaction obtained by the tourist will be analyzed. After an exhaustive review of the literature, an empirical investigation was carried out with 1,658 valid surveys among rural tourists in Soria, a Spanish province with one of the highest levels of depopulation. A structural equation model was drawn up to discover the relationships between the variables. The results demonstrated the importance of the motivation in the formation of the destination image, as well as satisfaction with the trip. In the same way, we will verify which component of the image of the destination (affective or cognitive) has the most influence on their formation, and how the image of the destination, like motivation, influences tourist satisfaction. The proposed model could be used in many studies that analyze the different variables that influence consumer behavior since its reliability and predictive capacity have been proven. The results of the study can also be used by the authorities to design or modify the most appropriate strategies that influence rural tourism, specially promoting the destination image as a variable that positively influences tourist satisfaction.
Multimodal Investigations of Reward Circuitry and Anhedonia in Adolescent Depression
Authors: Ely Benjamin A. , Nguyen Tram N. B. , Tobe Russell H. , Walker Audrey M. , Gabbay Vilma
Published: July 2021

Depression is a highly prevalent condition with devastating personal and public health consequences that often first manifests during adolescence. Though extensively studied, the pathogenesis of depression remains poorly understood, and efforts to stratify risks and identify optimal interventions have proceeded slowly. A major impediment has been the reliance on an all-or-nothing categorical diagnostic scheme based solely on whether a patient endorses an arbitrary number of common symptoms for a sufficiently long period. This approach masks the well-documented heterogeneity of depression, a disorder that is highly variable in presentation, severity, and course between individuals and is frequently comorbid with other psychiatric conditions. In this targeted review, we outline the limitations of traditional diagnosis-based research and instead advocate an alternative approach centered around symptoms as unique dimensions of clinical dysfunction that span across disorders and more closely reflect underlying neurobiological abnormalities. In particular, we highlight anhedonia—the reduced ability to anticipate and experience pleasure—as a specific, quantifiable index of reward dysfunction and an ideal candidate for dimensional investigation. Anhedonia is a core symptom of depression but also a salient feature of numerous other conditions, and its severity varies widely within clinical and even healthy populations. Similarly, reward dysfunction is a hallmark of depression but is evident across many psychiatric conditions. Reward function is especially relevant in adolescence, a period characterized by exaggerated reward-seeking behaviors and rapid maturation of neural reward circuitry. We detail extensive work by our research group and others to investigate the neural and systemic factors contributing to reward dysfunction in youth, including our cumulative findings using multiple neuroimaging and immunological measures to study depressed adolescents but also trans-diagnostic cohorts with diverse psychiatric symptoms. We describe convergent evidence that reward dysfunction: (a) predicts worse clinical outcomes, (b) is associated with functional and chemical abnormalities within and beyond the neural reward circuitry, (c) is linked to elevated peripheral levels of inflammatory biomarkers, and (d) manifests early in the course of illness. Emphasis is placed on high-resolution neuroimaging techniques, comprehensive immunological assays, and data-driven analyses to fully capture and characterize the complex, interconnected nature of these systems and their contributions to adolescent reward dysfunction.
The Impact of THC and CBD in Schizophrenia: A Systematic Review
Authors: Ahmed Saeed , Roth Robert M. , Stanciu Corneliu N. , Brunette Mary F.
Published: July 2021

Background: People with schizophrenia are more likely to develop cannabis use disorder (CUD) and experience worse outcomes with use. Yet as cannabis is legalized for medical and recreational use, there is interest in its therapeutic potential.

Objectives: To conduct a systematic review summarizing the design and results of controlled trials using defined doses of THC and CBD in schizophrenia.

Method: A keyword search of eight online literature databases identified 11 eligible reports.

Results: One placebo controlled trial (13 stable patients without CUD) found that intravenous THC increased psychosis and worsened learning/recall. Two reports of a functional magnetic resonance (fMRI) study of smoked or oral THC in 12 abstinent patients with schizophrenia and CUD found no change in symptoms and cognition, and an amelioration of impaired resting state brain function in areas implicated in reward function and the default mode network. One 4 week trial in acutely psychotic inpatients without CUD (mean age 30 y) found 800 mg CBD to be similarly efficacious to amisupride in improving psychosis and cognition. Two 6 week studies of CBD augmentation of antipsychotics in stable outpatients reported mixed results: CBD 600 mg was not more effective than placebo; CBD 1,000 mg reduced symptoms in a sample that did not exclude cannabis use and CUD. A brain fMRI and proton magnetic resonance spectroscopy study of single dose CBD in a sample that did not exclude CUD and cannabis use found that CBD improved symptoms and brain function during a learning/recall task and was associated with increased hippocampal glutamate.

Discussion: There is substantial heterogeneity across studies in dose, method of drug delivery, length of treatment, patient age, whether patients with cannabis use/CUD were included or excluded, and whether patients were using antipsychotic medication.

Conclusion: There is insufficient evidence for an effect of THC or CBD on symptoms, cognition, and neuroimaging measures of brain function in schizophrenia. At this time, research does not support recommending medical cannabis (THC or CBD) for treating patients with schizophrenia. Further research should examine THC and CBD in schizophrenia with and without comorbid CUD and consider the role of CBD in mitigating symptom exacerbation from THC.
Effects of Mindfulness-Based Cognitive Therapy on Stigma in Female Patients With Schizophrenia
Authors: Tang Qiubi , Yang Shuixian , Liu Cuixia , Li Liyan , Chen Xiaodong , Wu Fengchun , Huang Xingbing
Published: July 2021

Mindfulness-based cognitive therapy (MBCT) has been increasingly recognized as effective in different mental illnesses, but these effects are limited in schizophrenia. For patients with schizophrenia, stigma is one of the most negative factors that affects treatment, rehabilitation and social function. This research aimed to determine the effects of MBCT on stigma in patients with schizophrenia. In total, 62 inpatients with schizophrenia were recruited and randomly assigned to the experimental group or control group. The experimental group received an 8-week MBCT intervention, and the control group were treated as usual. Link's Stigma Scales (with three subscales, including perceived devaluation-discrimination (PDD), stigma-coping orientation, and stigma-related feeling), Five Facet Mindfulness Questionnaire (FFMQ), and Insight and Treatment Attitudes Questionnaire (ITAQ) were used to collect data before and after intervention. After intervention, the post-test score of PDD, stigma-coping orientation, FFMQ, and ITAQ were significantly different between the experimental group and the control group. In the experimental group, the PDD and stigma-coping orientation scores significantly decreased, and FFMQ and ITAQ scores increased remarkably (P < 0.05). In addition, correlation analysis revealed a significant negative correlation between mindfulness and stigma. MBCT was effective in reducing stigma in patients with schizophrenia, which mainly manifested as changes in the patients' perception of stigma as well as the withdrawal and avoidance caused by schizophrenia. Enhancing mindfulness will help reduce the stigma level. MBCT is worthy of promotion and application in patients with schizophrenia.
Knowledge, Attitudes, and Risk Perception Toward Avian Influenza Virus Exposure Among Cuban Hunters
Authors: Delgado-Hernández Beatriz , Mugica Lourdes , Acosta Martin , Pérez Frank , Montano Damarys de las Nieves , Abreu Yandy , Ayala Joel , Percedo María Irian , Alfonso Pastor
Published: July 2021

A critical step for decreasing zoonotic disease threats is to have a good understanding of the associated risks. Hunters frequently handle potentially infected birds, so they are more at risk of being exposed to zoonotic avian pathogens, including avian influenza viruses (AIVs). The objective of the current study was to gain a better understanding of Cuban hunters' general hunting practices, focusing on their knowledge and risk perception on avian influenza. An anonymous and voluntary semi-structured questionnaire was designed and applied to 398 hunters. Multiple correspondence analyses found relationships with potential exposure of AIVs to people and domestic animals. The main associated risks factors identified were not taking the annual flu vaccine (60.1%) and not cleaning hunting knives (26.3%); Direct contact with water (32.1%), cleaning wild birds at home (33.2%); receiving assistance during bird cleaning (41.9%), keeping poultry at home (56.5%) and feeding domestic animals with wild bird leftovers (30.3%) were also identified as significant risk factors. The lack of use of some protective measures reported by hunters had no relationship with their awareness on avian influenza, which may imply a lack of such knowledge. The results evidenced that more effective risk communication strategies about the consequences of AIVs infecting human or other animals, and the importance of reducing such risks, are urgently needed.
Future Challenges of Nursing in Health System of Iran
Authors: Barasteh Salman , Rassouli Maryam , Karimirad Mohammad Reza , Ebadi Abbas
Published: July 2021

Purpose: Nursing development is considered as one of the most important ways to achieve the universal health coverage and sustainable development goals in different countries. Nursing in Iran has the potential to provide services at all levels of universal health coverage. Therefore, planning for nursing in Iran needs to recognize the future challenges. This study aims to explore the future challenges of nursing in the health system of Iran from the perspective of nursing experts.

Methods: In this qualitative study, 11 semi-structured interviews were conducted with nursing experts by purposive sampling in 2017–2018. Interviews were recorded and transcribed and framework analysis method was used to analysis the data.

Results: The results showed that a favorable future requires planning in three areas of nursing “governance challenges” including centralized nursing stewardship, policy-making and legislation, monitoring and evaluation, and cooperation and communication with other institutions, “inadequacy of professional development with social demands” including community-based nursing, nursing upgrades with disease patterns, expanding home care, expanding care centers, and use of technology, “human resource challenges “including nursing education tailored to the needs of the community, empowering nursing managers, recruiting and retaining nurses, and specialized nursing.

Conclusions: A favorable future requires a coherent nursing government, professional development of nursing based on social demands, and enhancing human resources in line with the emerging needs of the future.
Accessibility to Reproductive Technologies by Low-Income Beef Farmers in South Africa
Authors: Nengovhela Nkhanedzeni Baldwin , Mugwabana Thinawanga Joseph , Nephawe Khathutshelo Agree , Nedambale Tshimangadzo Lucky
Published: July 2021

This study address historical legacy of South Africa that has dual economies resembling low and high income beef sectors. Low-income herds are farmed mainly under communal village or land reform farms. The study focused on providing assisted reproductive technologies (ARTs) to the low-income sector including finding challenges to its implementation and adoption. The study was conducted in Limpopo, Mpumalanga and KwaZulu-Natal provinces using mixed methods that looked at cows and sectors stakeholders. Data collected and evaluated on cows included breed type, frame size, body condition, age parity, and lactation status. Cows were exposed to ART through synchronisation, oestrus detection, fixed time artificial insemination and pregnancy diagnosis. Qualitative data was collected to study perception of key stakeholders on ART implementation and adoption. Chi-Square Test was computed to determine the association among cow factors. Qualitative data was collected, coded and managed into themes using Nvivo Version 11. Themes that emerged were interpreted using critical social and systems thinking. Conception rate was not independent of provinces (P < 0.05), cow body condition score (BCS) and body frame size. KwaZulu-Natal cows had the highest conception rate at 66% (P < 0.05) than Limpopo (44%) and Mpumalanga (60%) provinces. Cows with a BCS higher than 3.5 had higher conception rate (P < 0.05) than those with BCS of <2.5 and 3. Interestingly, large framed cow size had higher conception rate than medium and small framed (P < 0.05) cows. The study achieved a 100% calf survival rate. Calving rate was influenced by body BCS, province and district (P < 0.05). Calving rate of 58% in Mpumalanga and 54% in KwaZulu-Natal was higher than that recorded in Limpopo at 36% (P < 0.05). Interestingly, cows with BCS of <2.5 had a higher calving rate than those with a higher body condition score of 3 (P < 0.05). Perception study results revealed many factors that could affect the adoption and implementation of ART in the study areas. The high success rate and above average reproductive performance led to North West and KwaZulu-Natal provinces adopting ART as part of their low-income beef sector support.
A Review of the Evolution of Dairy Policies and Regulations in Rwanda and Its Implications on Inputs and Services Delivery
Authors: Habiyaremye Naphtal , Ouma Emily Awuor , Mtimet Nadhem , Obare Gideon Aiko
Published: July 2021

The dairy sector in Rwanda plays a key role in improving nutrition and generating income mostly for rural households. Despite the Rwandan 1994 genocide that left around 80% of dairy cows decimated, the dairy sector has experienced significant growth in the past two decades through government, development organisations, and donor programs, and through the nascent vibrant public–private partnership. In this paper, we reviewed and documented the evolution of the dairy policies, programs, and regulations in Rwanda and how they have contributed to the development of the dairy sector. The policy change has impacted the provision and use of inputs and services that have shaped the sector's milk production and productivity, milk quality, and demand. The results suggest that various policy- and program-level interventions have positively contributed to the growth of the dairy sector and improved the livelihoods of low-income households. This has been achieved through increased access to inputs and services, enhanced capacities of the public and private sector to deliver services, strengthened dairy cooperatives' governance, and increased value proposition to members of various farmer groups and promotion of milk consumption. We find that some of the implemented policies and programs, such as the “Girinka” (one cow per poor family) program, Rwanda Dairy Competitiveness Program II, and Rwanda Dairy Development Project, have resulted in improved farmer access to improved cow breeds and improved milk quality and cow productivity through enhanced health inputs and other services. While the dairy policies, programs, and regulations in Rwanda have paved the way for the development of the dairy sector and contributed to the provision and use of inputs and services, there are still challenges that need to be addressed. Accessibility and use of veterinary and artificial insemination services are limited by the quality of veterinary products, while the inadequate quality of feeds leads to low productivity of improved cow breeds. Consequently, farmers' uptake and use of inputs and services can be enhanced through a strengthened capacity of milk collection centres and health and animal feed policies that guide and control the quality of veterinary products and feeds sold in the markets.