bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends and Geographic Variabilities in Benzodiazepines Prescription in Primary Care to Older Adults: A 3-Year Population-Based Ecological Study in Portugal
Authors: Tavares Ana Bárbara , Placido Ana Isabel , Rodrigues Daniela Almeida , Morgado Manuel , Figueiras Adolfo , Herdeiro Maria Teresa , Roque Fátima
Published: July 2022

(1) Background: According to the World Health Organization (WHO), benzodiazepines (BZD) are considered essential medicines for the treatment of several mental disorders in older adults over 65 years old. However, the long-term use of BZD could present a harmful impact on this population, leading to cognitive deficits, drug dependence, falls, and fractures. This study aims to analyze trends of BZD prescription to Portuguese older adults in the primary care setting, and to analyze the change in the prescription rate of BZD over time, assessing the geographical variability in mainland Portugal. (2) Methods: A nationwide, retrospective ecological study was performed between January 2019 and December 2021 for BZD prescribing data reported in a national public database for all persons aged 65 and older in mainland Portugal (about 2.4 million). Trends of BZD by defined daily doses (DDD) and per 1000 older adults’ inhabitants per day (DID) were analyzed. (3) Results: A total of 19 BZD were included in this study and more than 1 million BZD prescriptions were recorded in each year of this study period. BZD prescriptions were three times higher in females than in males. Alprazolam, lorazepam, diazepam, ethyl loflazepate, and bromazepam were the most prescribed BZD over the years, presenting the higher DDD and DID values. (4) Conclusions: Despite the DID value growth of several BZD, Portugal is now showing stable BZD prescriptions in older adults, between the years 2019 to 2021. More studies are needed to access if these results are a consequence of successful health programs or just a consequence of the pandemic context that we are facing, which limited older adults’ clinical appointments.
Fetal Fibronectin and Cervical Length as Predictors of Spontaneous Onset of Labour and Delivery in Term Pregnancies
Authors: Grab Delia , Doroftei Bogdan , Grigore Mihaela , Nicolaiciuc Ovidiu Sebastian , Anton Sorana Caterina , Simionescu Gabriela , Maftei Radu , Bolota Maria , Ilea Ciprian , Costachescu Gabriel , Anton Emil
Published: July 2022

(1) Objective: This study aimed to determine whether qualitative fetal fibronectin and transvaginal sonographic measurement of cervical length are effective in predicting delivery in term pregnancies within 5 days of the test. (2) Methods: We examined 268 women with singleton pregnancies presenting themselves at 37+0–40+4 weeks (median 38 weeks + 1 day) of gestation with irregular and painful uterine contractions, intact membranes and cervical dilatation less than 2 cm. All women were admitted to hospital up to 72 h after birth. On admission, a qualitative fetal fibronectin test was performed in cervicovaginal secretions and transvaginal sonographic measurement of cervical length was carried out. The primary outcome measure was delivery within 5 days of presentation. RESULTS: Among the women who delivered within 5 days after admission, 65.2% had positive fFN assessment, 43.5% had cervical length below 26 mm, 52.2% had the age > 32.5 years, 34.8% were nulliparous and 56.5% had gestational age ≥ 275 days. Logistic regression analysis demonstrated that significant contributors to the prediction of delivery within 5 days were fibronectin positivity, cervical length ≤ 26 mm, maternal age > 32.5 years and gestational age ≥ 275 days, with no significant contribution from parity. (3) Conclusions: Qualitative fetal fibronectin test and transvaginal cervical length measurement in term pregnancies are useful tests for predicting spontaneous onset of labour within 5 days. It helps women and healthcare providers to determine the optimum time for hospital admission.
Epidemiological Role of Dictyophara europaea (Hemiptera: Dictyopharidae) in the Transmission of ‘Candidatus Phytoplasma solani’
Authors: Cvrković Tatjana , Jović Jelena , Krstić Oliver , Marinković Slavica , Jakovljević Miljana , Mitrović Milana , Toševski Ivo
Published: July 2022

Bois noir, an economically important disease of grapevine yellows that causes significant economic losses in wine production, is associated with ‘Candidatus Phytoplasma solani’ and transmitted to grapevines by cixiids Hyalesthes obsoletus and Reptalus panzeri. Polyphagous planthopper Dictyophara europaea, commonly found in natural habitats, harbors phytoplasmas from distinct groups and is an alternative vector in the open epidemiological cycles of the Flavescence dorée phytoplasma in grapevine in European vineyards. This study addresses the role of D. europaea in the transmission cycle(s) of ‘Ca. P. solani’ among wild habitats, natural reservoir plants, and the vineyard agroecosystem using MLSA and transmission trials with naturally infected adults to grapevine and Catharanthus roseus. The infection rates of D. europaea ranged from 7% to 13% in diverse locations, while reservoir herbaceous plants were infected in the amount of 29%. A total of 13 CaPsol MLSA genotypes were detected in D. europaea (7) and plants (8). Nine of them corresponded to previously identified genotypes. Two new genotypes were found in D. europaea (tuf-b1/S1/V14/Rqg50-sv1 and tuf-b1/S18/V14/Rqg50-sv1) and one in Convolvulus arvensis (tuf-b1/S1/V2-TA/Rqg31-sv1), whereas one was shared by two hosts, Crepis foetida and Daucus carota (tuf-b1/S1/V2-TA/STOL-sv1). Naturally infected D. europaea successfully transmitted the tuf-b1/S1/V2-TA/STOL type to five grapevines and six periwinkles, tuf-b1/S1/V2-TA/Rqg31 to one grapevine, and tuf-b1/S1/V2-TA/Rqg50 to one periwinkle, indicating that D. europaea is an intermediate vector in CaPsol epidemiological cycles.
Effects of Potassium Deficiency on the Growth of Tea (Camelia sinensis) and Strategies for Optimizing Potassium Levels in Soil: A Critical Review
Authors: Huang Wei , Lin Minyao , Liao Jinmei , Li Ansheng , Tsewang Wugyan , Chen Xuan , Sun Binmei , Liu Shaoqun , Zheng Peng
Published: July 2022

Potassium is among the three essential macronutrients for tea plants, along with nitrogen and phosphorous, and plays important roles in growth and stress response. Potassium is absorbed by plants in larger amounts than any other mineral element except nitrogen and, in some cases, calcium. At present, more than 59% of China’s tea gardens are in a state of potassium deficiency, which negatively affects tea quality and yield. This paper reviews the effects of potassium deficiency on tea plant growth and stress response, details factors affecting potassium supply and demand in tea gardens, examines the interactions between potassium and other elements in soils, and provides strategies for optimizing potassium levels in soils. Potassium is positively correlated with the elements nitrogen, copper, and zinc. Sufficient potassium dramatically improves the yield and quality of tea: it accelerates metabolism, promotes synthesis of catechins, and strengthens biotic and abiotic resistance by activating and regulating different enzymes. Moderate application of potassium fertilizers, along with potassium-solubilizing bacteria, can regulate the ratio of different forms of potassium and increase available potassium in soils of tea gardens. We suggest that research on potassium occurring in soils and its interaction with other elements be strengthened, so as to improve the efficient use of potassium fertilizers in tea gardens and maintain the balance of elements in soils.
Iodine Enhances the Nutritional Value but Not the Tolerance of Lettuce to NaCl
Authors: Maglione Giuseppe , Vitale Ermenegilda , Costanzo Giulia , Polimeno Franca , Arena Carmen , Vitale Luca
Published: July 2022

Positive stress or essential and nonessential elements can improve nutritive values (biofortification) of edible plants. In the present study, we evaluate (i) the effect of moderate salinity on lettuce biofortification, evaluated as nutritional bioactive compound accumulation, and (ii) the role of iodine in enhancing salt tolerance by increasing photorespiration and the content of antioxidants in lettuce. Physiological (gas exchange and chlorophyll fluorescence emission) and biochemical (photosynthetic pigment and bioactive compound) analyses were performed on lettuce plants grown under moderate salinity (50 mM NaCl alone or 50 mM NaCl in combination with iodine, KIO3). Our results show that NaCl + iodine treatment improves the nutritional value of lettuce in terms of bioactive compounds acting as antioxidants. More specifically, iodine enhances the accumulation of photosynthetic pigments and polyphenols, such as anthocyanins, under salt but does not improve the salt tolerance. Our findings indicate that iodine application under moderate salinity could be a valid strategy in plant biofortification by improving nutritional bioactive compound accumulation, thus exercising functional effects on human health.
Foliar Application of Some Macronutrients and Micronutrients Improves Yield and Fruit Quality of Highbush Blueberry (Vaccinium corymbosum L.)
Authors: Zydlik Zofia , Zydlik Piotr , Kafkas Nesibe Ebru , Yesil Betul , Cieśliński Szymon
Published: July 2022

Foliar fertilization makes it possible to quickly provide plants with essential nutrients, mainly micronutrients, which can significantly improve the quality of yields. The aim of this study was to evaluate the effect of foliar fertilization with fertilizers containing calcium and microelements on yielding and fruit quality of highbush blueberry (Vaccinium corymbosum L.). A two-year study was carried out in western Poland in an experimental highbush blueberry production plantation. During the growing season the bushes were treated several times with the following foliar fertilizers: Armurox, BioCal, and Stymjod. The experiment assessed bush growth vigor, yield, fruit quality characteristics, sugar, organic acid, and health-promoting substance content. It was found that as a result of fertilizing highbush blueberry bushes with foliar fertilizers, the leaf blade area and plant yield increased significantly. The fruits collected from those bushes were characterized by a higher mass, firmness, and TSS content. This also applies to blueberry fruit after storage. Foliar fertilization had no significant effect on the content of chlorophyll a and b in the leaves of northern highbush blueberry, on fruit coloration, the content of sugars, ascorbic and citric acids, and the phenolic compounds in them.
Assisting Strategies of the Parents of Students with Special Educational Needs in the Emergency Remote Learning in Poland
Authors: Knopik Tomasz , Błaszczak Anna , Oszwa Urszula , Maksymiuk Renata
Published: July 2022

The study had four objectives: (a) identifying and characterizing strategies for involving parents of students with SEN (students with special educational needs) in remote education during the COVID-19 pandemic; (b) comparing these strategies with those used by parents of students without SEN (non-SEN students); (c) identifying predictors of parental involvement in the remote education of students with SEN; (d) checking whether the identified strategies differentiate the perceived barriers and benefits of remote learning. In total, 421 parents of primary school students participated in the study, 83 of whom (20%) were parents of children with SEN (SEN group). Based on the factor analysis of the results (respondents completed a 66-item electronic questionnaire), three main strategies for parental involvement in children’s remote education were identified: (1) committed teacher (CT), with 40% in the SEN group and 55% in the non-SEN group; (2) autonomy-supporting coach (ASC), with 22% in the SEN group and 26% in the non-SEN group; (3) committed teacher and reliever (CTR), with 38% in the SEN group and 19% in the non-SEN group. The strongest predictor of parental involvement with SEN students in the role of committed teacher was excessive demands from school. Parents whose children showed low motivation to learn were the most likely to do some of their children’s school tasks for them and apply the committed teacher and reliever strategy. The positive aspects of remote education were mostly noticed by moderately committed parents who gave their children a lot of autonomy (autonomy-supporting coaches). The obtained results can be included in the optimization of schools’ activities in terms of organizing remote education for students with SEN and cooperating with parents.
Interdisciplinary Approach to Improve Agri-Food Safety and Quality
Authors: Serio Francesca
Published: July 2022

The agri-food sector is very broad and includes a whole series of steps in the supply chain ranging from agricultural production to the processing and marketing of final products [...]
Early Teacher–Child Relationships Promote Self-Regulation Development in Prekindergarten
Authors: Rudasill Kathleen Moritz , Acar Ibrahim , Xu Yaoying
Published: July 2022

Children’s experiences during the prekindergarten period are critical for shaping their emerging self-regulation skills. The purpose of this study was to examine the contribution of teacher–child relationship quality to children’s performance on a self-regulation task at the end of prekindergarten. Teachers rated the conflict, closeness, and dependency in their relationships with 104 children in the fall of prekindergarten, and children’s self-regulation was independently measured with a visual attention task in the spring of prekindergarten. In addition, teachers and parents rated children’s temperamental self-regulation (i.e., effortful control). Results indicate that greater teacher–child dependency predicted children’s longer time on the visual attention task, and greater teacher–child closeness predicted children’s lower accuracy on the visual attention task. In addition, children who were rated as more self-regulated by parents were more accurate on the visual attention task. The implications of the results are discussed.
Exe-Muscle: An Exercised Human Skeletal Muscle Gene Expression Database
Authors: Huang Kaiyuan , Song Jingwen , Kong Weishuai , Deng Zhongyuan
Published: July 2022

Human muscle tissue undergoes dynamic changes in gene expression during exercise, and the dynamics of these genes are correlated with muscle adaptation to exercise. A database of gene expression changes in human muscle before and after exercise was established for data mining. A web-based searchable database, Exe-muscle, was developed using microarray sequencing data, which can help users to retrieve gene expression at different times. Search results provide a complete description of target genes or genes with specific expression patterns. We can explore the molecular mechanisms behind exercise science by studying the changes in muscle gene expression over time before and after exercise. Based on the high-throughput microarray data before and after human exercise, a human pre- and post-exercise database was created using web-based database technology, which researchers can use or share their gene expression data. The Exe-muscle database is accessible online.
HBM4EU Diisocyanates Study—Research Protocol for a Collaborative European Human Biological Monitoring Study on Occupational Exposure
Authors: Jones Kate , Galea Karen S. , Scholten Bernice , Loikala Marika , Porras Simo P. , Bousoumah Radia , Ndaw Sophie , Leese Elizabeth , Louro Henriqueta , Silva Maria João , Viegas Susana , Godderis Lode , Verdonck Jelle , Poels Katrien , Gӧen Thomas , Duca Radu-Corneliu , Santonen Tiina ,   HBM4EU Diisocyanates Study Team
Published: July 2022

Diisocyanates have long been a leading cause of occupational asthma in Europe, and recently, they have been subjected to a restriction under the REACH regulations. As part of the European Human Biomonitoring project (HBM4EU), we present a study protocol designed to assess occupational exposure to diisocyanates in five European countries. The objectives of the study are to assess exposure in a number of sectors that have not been widely reported on in the past (for example, the manufacturing of large vehicles, such as in aerospace; the construction sector, where there are potentially several sources of exposure (e.g., sprayed insulation, floor screeds); the use of MDI-based glues, and the manufacture of spray adhesives or coatings) to test the usability of different biomarkers in the assessment of exposure to diisocyanates and to provide background data for regulatory purposes. The study will collect urine samples (analysed for diisocyanate-derived diamines and acetyl–MDI–lysine), blood samples (analysed for diisocyanate-specific IgE and IgG antibodies, inflammatory markers, and diisocyanate-specific Hb adducts for MDI), and buccal cells (micronucleus analysis) and measure fractional exhaled nitric oxide. In addition, occupational hygiene measurements (air monitoring and skin wipe samples) and questionnaire data will be collected. The protocol is harmonised across the participating countries to enable pooling of data, leading to better and more robust insights and recommendations.
Efficacy of a Horticultural Therapy Program Designed for Emotional Stability and Career Exploration among Adolescents in Juvenile Detention Centers
Authors: Park Kyoung-Hee , Kim Soo-Young , Park Sin-Ae
Published: July 2022

We aimed to develop a horticultural therapy program to prepare adolescents at the Dae san juvenile detention center (D-JDC) for their return to society. The effects of the program on emotional stability and career exploration were investigated. Adolescents who wished to participate in the horticultural therapy program were recruited from the D-JDC. Data were collected using various questionnaires before and after the program was implemented. Thirty-five (mean age, 15.74 ± 1.65 years; 11 males, 24 females) students were enrolled. The program mainly consisted of plant cultivation activities, such as seeding, transplanting plants, cutting, harvesting, and post-harvest utilization. To evaluate emotional health, the ego-resiliency scale was used. To evaluate social behavior, the inventory of parent and peer attachment, peer attachment scale, and social skills scale were used. Career exploration was assessed using the career preparation behavior scale and the career decision-making self-efficacy-short form. Peer attachment, social skills, and career preparation behavior showed significant improvements after the program, with the students responding positively in the post-program surveys. Our horticultural therapy program helped improve the career exploration and social skills of D-JDC students and positively affected their emotional stability. Based on our findings, horticultural therapy can be used as a correctional program for adolescents in D-JDC to help them return to society.
Socioeconomic Status and Distance to Reference Centers for Complex Cancer Diseases: A Source of Health Inequalities? A Population Cohort Study Based on Catalonia (Spain)
Authors: Manchon-Walsh Paula , Aliste Luisa , Borràs Josep M. , Coll-Ortega Cristina , Casacuberta Joan , Casanovas-Guitart Cristina , Clèries Montse , Cruz Sergi , Guarga Àlex , Mompart Anna , Planella Antoni , Pozuelo Alfonso , Ticó Isabel , Vela Emili , Prades Joan
Published: July 2022

The centralization of complex surgical procedures for cancer in Catalonia may have led to geographical and socioeconomic inequities. In this population-based cohort study, we assessed the impacts of these two factors on 5-year survival and quality of care in patients undergoing surgery for rectal cancer (2011–12) and pancreatic cancer (2012–15) in public centers, adjusting for age, comorbidity, and tumor stage. We used data on the geographical distance between the patients’ homes and their reference centers, clinical patient and treatment data, income category, and data from the patients’ district hospitals. A composite ‘textbook outcome’ was created from five subindicators of hospitalization. We included 646 cases of pancreatic cancer (12 centers) and 1416 of rectal cancer (26 centers). Distance had no impact on survival for pancreatic cancer patients and was not related to worse survival in rectal cancer. Compared to patients with medium–high income, the risk of death was higher in low-income patients with pancreatic cancer (hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.15–1.86) and very-low-income patients with rectal cancer (HR 5.14, 95% CI 3.51–7.52). Centralization was not associated with worse health outcomes in geographically dispersed patients, including for survival. However, income level remained a significant determinant of survival.
Resistance Circuit Training or Walking Training: Which Program Improves Muscle Strength and Functional Autonomy More in Older Women?
Authors: Ramos Ayrton Moraes , Marcos-Pardo Pablo Jorge , Vale Rodrigo Gomes de Souza , Vieira-Souza Lucio Marques , Camilo Bruno de Freitas , Martin-Dantas Estélio Henrique
Published: July 2022

To evaluate the effects of two programs (resistance and walking training) on the functional autonomy and muscle strength (isometric and dynamic) of older women, 67 subjects were divided randomly into three groups: resistance training (RTG; Mean = 64.70 ± 6.74 years), walking (WG, Mean = 65.56 ± 7.82 years), and control (CG; Mean = 64.81 ± 4.34). The experimental groups underwent a 16-week intervention. Muscle strength (isometric and dynamic) and functional autonomy were assessed. The subjects participating in the RTG showed improvements in the comparison pre to post-test in the maximal forces of upper limb (MULS) (Δ% = 49.48%; p = 0.001) and lower limb (MLLS) (Δ% = 56.70%; p = 0.001), isometric biceps forces (BIS) (Δ% = 30.13%; p = 0.001) and quadriceps forces (QIS) (Δ% = 65.92%; p = 0.001), and in the general index (GI) of functional autonomy (Δ% = −18.32%; p = 0.002). The WG improved in all functional autonomy tests, except for the standing up from prone position test (SVDP). In strength tests, the WG obtained improvements only in the QIS (Δ% = 41.80%; p = 0.001) and MLLS (Δ% = 49.13%; p = 0.001) tests. The RTG obtained better results (p < 0.05) when compared to the WG and CG. The results allow us to infer that resistance exercise programs are more effective in increasing strength and functional autonomy, a fact that may mitigate the deleterious effects on health of aging.
Neurobiological Mechanisms Modulating Emotionality, Cognition and Reward-Related Behaviour in High-Fat Diet-Fed Rodents
Authors: Ziemens Dorothea , Touma Chadi , Rappeneau Virginie
Published: July 2022

Affective and substance-use disorders are associated with overweight and obesity-related complications, which are often due to the overconsumption of palatable food. Both high-fat diets (HFDs) and psychostimulant drugs modulate the neuro-circuitry regulating emotional processing and metabolic functions. However, it is not known how they interact at the behavioural level, and whether they lead to overlapping changes in neurobiological endpoints. In this literature review, we describe the impact of HFDs on emotionality, cognition, and reward-related behaviour in rodents. We also outline the effects of HFD on brain metabolism and plasticity involving mitochondria. Moreover, the possible overlap of the neurobiological mechanisms produced by HFDs and psychostimulants is discussed. Our in-depth analysis of published results revealed that HFDs have a clear impact on behaviour and underlying brain processes, which are largely dependent on the developmental period. However, apart from the studies investigating maternal exposure to HFDs, most of the published results involve only male rodents. Future research should also examine the biological impact of HFDs in female rodents. Further knowledge about the molecular mechanisms linking stress and obesity is a crucial requirement of translational research and using rodent models can significantly advance the important search for risk-related biomarkers and the development of clinical intervention strategies.
Thermomagnetic Resonance Effect of the Extremely Low Frequency Electromagnetic Field on Three-Dimensional Cancer Models
Authors: Bergandi Loredana , Lucia Umberto , Grisolia Giulia , Salaroglio Iris Chiara , Gesmundo Iacopo , Granata Riccarda , Borchiellini Romano , Ponzetto Antonio , Silvagno Francesca
Published: July 2022

In our recent studies, we have developed a thermodynamic biochemical model able to select the resonant frequency of an extremely low frequency electromagnetic field (ELF-EMF) specifically affecting different types of cancer, and we have demonstrated its effects in vitro. In this work, we investigate the cellular response to the ELF electromagnetic wave in three-dimensional (3D) culture models, which mimic the features of tumors in vivo. Cell membrane was modelled as a resistor–capacitor circuit and the specific thermal resonant frequency was calculated and tested on two-dimensional (2D) and three-dimensional (3D) cell cultures of human pancreatic cancer, glioblastoma and breast cancer. Cell proliferation and the transcription of respiratory chain and adenosine triphosphate synthase subunits, as well as uncoupling proteins, were assessed. For the first time, we demonstrate that an ELF-EMF hampers growth and potentiates both the coupled and uncoupled respiration of all analyzed models. Interestingly, the metabolic shift was evident even in the 3D aggregates, making this approach particularly valuable and promising for future application in vivo, in aggressive cancer tissues characterized by resistance to treatments.
Structural Basis of Mutation-Dependent p53 Tetramerization Deficiency
Authors: Rigoli Marta , Spagnolli Giovanni , Lorengo Giulia , Monti Paola , Potestio Raffaello , Biasini Emiliano , Inga Alberto
Published: July 2022

The formation of a tetrameric assembly is essential for the ability of the tumor suppressor protein p53 to act as a transcription factor. Such a quaternary conformation is driven by a specific tetramerization domain, separated from the central DNA-binding domain by a flexible linker. Despite the distance, functional crosstalk between the two domains has been reported. This phenomenon can explain the pathogenicity of some inherited or somatically acquired mutations in the tetramerization domain, including the widespread R337H missense mutation present in the population in south Brazil. In this work, we combined computational predictions through extended all-atom molecular dynamics simulations with functional assays in a genetically defined yeast-based model system to reveal structural features of p53 tetramerization domains and their transactivation capacity and specificity. In addition to the germline and cancer-associated R337H and R337C, other rationally designed missense mutations targeting a significant salt-bridge interaction that stabilizes the p53 tetramerization domain were studied (i.e., R337D, D352R, and the double-mutation R337D plus D352R). The simulations revealed a destabilizing effect of the pathogenic mutations within the p53 tetramerization domain and highlighted the importance of electrostatic interactions between residues 337 and 352. The transactivation assay, performed in yeast by tuning the expression of wild-type and mutant p53 proteins, revealed that p53 tetramerization mutations could decrease the transactivation potential and alter transactivation specificity, in particular by better tolerating negative features in weak DNA-binding sites. These results establish the effect of naturally occurring variations at positions 337 and 352 on p53’s conformational stability and function.
Interleukin-35 Prevents the Elevation of the M1/M2 Ratio of Macrophages in Experimental Type 1 Diabetes
Authors: Luo Zhengkang , Soläng Charlotte , Larsson Rasmus , Singh Kailash
Published: July 2022

Macrophages play an important role in the early development of type 1 diabetes (T1D). Based on the phenotype, macrophages can be classified into pro-inflammatory (M1) and anti-inflammatory (M2) macrophages. Despite intensive research in the field of macrophages and T1D, the kinetic response of M1/M2 ratio has not been studied in T1D. Thus, herein, we studied the M1 and M2 macrophages in the early development of T1D using the multiple low dose streptozotocin (MLDSTZ) mouse model. We determined the proportions of M1 and M2 macrophages in thymic glands, pancreatic lymph nodes and spleens on days 3, 7 and 10 after the first injection of STZ. In addition, we investigated the effect of IL-35 in vivo on the M1/M2 ratio and IL-35+ plasmacytoid dendritic cells in diabetic mice and in vitro on the sorted macrophages. Our results revealed that the M1/M2 ratio is higher in STZ-treated mice but this was lowered upon the treatment with IL-35. Furthermore, IL-35 treated mice had lower blood glucose levels and a higher proportion of IL-35+ cells among pDCs. Macrophages treated with IL-35 in vitro also had a higher proportion of M2 macrophages. Together, our data indicate that, under diabetic conditions, pro-inflammatory macrophages increased, but IL-35 treatment decreased the pro-inflammatory macrophages and increased anti-inflammatory macrophages, further suggesting that IL-35 prevents hyperglycemia by maintaining the anti-inflammatory phenotype of macrophages and other immune cells. Thus, IL-35 should be further investigated for the treatment of T1D and other autoimmune disorders.
Therapeutic Benefits of Selenium in Hematological Malignancies
Authors: Ehudin Melanie A. , Golla Upendarrao , Trivedi Devnah , Potlakayala Shobha D. , Rudrabhatla Sairam V. , Desai Dhimant , Dovat Sinisa , Claxton David , Sharma Arati
Published: July 2022

Supplementing chemotherapy and radiotherapy with selenium has been shown to have benefits against various cancers. This approach has also been shown to alleviate the side effects associated with standard cancer therapies and improve the quality of life in patients. In addition, selenium levels in patients have been correlated with various cancers and have served as a diagnostic marker to track the efficiency of treatments or to determine whether these selenium levels cause or are a result of the disease. This concise review presents a survey of the selenium-based literature, with a focus on hematological malignancies, to demonstrate the significant impact of selenium in different cancers. The anti-cancer mechanisms and signaling pathways regulated by selenium, which impart its efficacious properties, are discussed. An outlook into the relationship between selenium and cancer is highlighted to guide future cancer therapy development.
Improving the Therapeutic Index of Smp24, a Venom-Derived Antimicrobial Peptide: Increased Activity against Gram-Negative Bacteria
Authors: Rawson Kirstie M. , Lacey Melissa M. , Strong Peter N. , Miller Keith
Published: July 2022

Antimicrobial peptides (AMPs) are naturally occurring compounds which possess a rapid killing mechanism and low resistance potential. Consequently, they are being viewed as potential alternatives to traditional antibiotics. One of the major factors limiting further development of AMPs is off-target toxicity. Enhancements to antimicrobial peptides which can maximise antimicrobial activity whilst reducing mammalian cytotoxicity would make these peptides more attractive as future pharmaceuticals. We have previously characterised Smp24, an AMP derived from the venom of the scorpion Scorpio maurus palmatus. This study sought to better understand the relationship between the structure, function and bacterial selectivity of this peptide by performing single amino acid substitutions. The antimicrobial, haemolytic and cytotoxic activity of modified Smp24 peptides was determined. The results of these investigations were compared with the activity of native Smp24 to determine which modifications produced enhanced therapeutic indices. The structure–function relationship of Smp24 was investigated by performing N-terminal, mid-chain and C-terminal amino acid substitutions and determining the effect that they had on the antimicrobial and cytotoxic activity of the peptide. Increased charge at the N-, mid- and C-termini of the peptide resulted in increased antimicrobial activity. Increased hydrophobicity at the N-terminus resulted in reduced haemolysis and cytotoxicity. Reduced antimicrobial, haemolytic and cytotoxic activity was observed by increased hydrophobicity at the mid-chain. Functional improvements have been made to modified peptides when compared with native Smp24, which has produced peptides with enhanced therapeutic indices.
Synthesis of Metal–Organic Frameworks Quantum Dots Composites as Sensors for Endocrine-Disrupting Chemicals
Authors: Ajibade Peter A. , Oloyede Solomon O.
Published: July 2022

Hazardous chemical compounds such as endocrine-disrupting chemicals (EDCs) are widespread and part of the materials we use daily. Among these compounds, bisphenol A (BPA) is the most common endocrine-disrupting chemical and is prevalent due to the chemical raw materials used to manufacture thermoplastic polymers, rigid foams, and industrial coatings. General exposure to endocrine-disrupting chemicals constitutes a serious health hazard, especially to reproductive systems, and can lead to transgenerational diseases in adults due to exposure to these chemicals over several years. Thus, it is necessary to develop sensors for early detection of endocrine-disrupting chemicals. In recent years, the use of metal–organic frameworks (MOFs) as sensors for EDCs has been explored due to their distinctive characteristics, such as wide surface area, outstanding chemical fastness, structural tuneability, gas storage, molecular separation, proton conductivity, and catalyst activity, among others which can be modified to sense hazardous environmental pollutants such as EDCs. In order to improve the versatility of MOFs as sensors, semiconductor quantum dots have been introduced into the MOF pores to form metal–organic frameworks/quantum dots composites. These composites possess a large optical absorption coefficient, low toxicity, direct bandgap, formidable sensing capacity, high resistance to change under light and tunable visual qualities by varying the size and compositions, which make them useful for applications as sensors for probing of dangerous and risky environmental contaminants such as EDCs and more. In this review, we explore various synthetic strategies of (MOFs), quantum dots (QDs), and metal–organic framework quantum dots composites (MOFs@QDs) as efficient compounds for the sensing of ecological pollutants, contaminants, and toxicants such as EDCs. We also summarize various compounds or materials used in the detection of BPA as well as the sensing ability and capability of MOFs, QDs, and MOFs@QDs composites that can be used as sensors for EDCs and BPA.
Drought Stress Pre-Treatment Triggers Thermotolerance Acquisition in Durum Wheat
Authors: De Pascali Mariarosaria , De Caroli Monica , Aprile Alessio , Miceli Antonio , Perrotta Carla , Gullì Mariolina , Rampino Patrizia
Published: July 2022

Durum wheat is strongly affected by climatic constraints such as high temperatures and drought, which frequently lead to yield reduction. Damages due to high temperatures are related to plant thermotolerance, a trait determined by two components: basal and acquired thermotolerance. In this study, the effect of drought and heat stress imposed singularly or sequentially was investigated in ten durum wheat cultivars (cvs) at the physiological and molecular level. The traits analyzed were cell membrane stability, relative water content, proline content, and expression level of several genes for heat shock proteins (HSPs). Our results indicate that drought priming can induce the acquisition of thermotolerance in most cultivars already classified as able to acquire thermotolerance by heat pre-treatment. Proline accumulation was correlated to cell membrane stability, meaning that the most thermotolerant cvs were able to accumulate higher levels of proline. Acquired thermotolerance is also due to the activation of HSP gene expression; similarly, pre-treatment with water stress was able to activate HSPs expression. The results reported indicate that water stress plays an important role in inducing thermotolerance, comparable to mild heat stress pre-treatment. This is the first report on the effect of drought stress on the acquisition of thermotolerance.
The Transcription Factors TaTDRL and TaMYB103 Synergistically Activate the Expression of TAA1a in Wheat, Which Positively Regulates the Development of Microspore in Arabidopsis
Authors: Wu Baolin , Xia Yu , Zhang Gaisheng , Wang Junwei , Ma Shoucai , Song Yulong , Yang Zhiquan , Dennis Elizabeth S. , Niu Na
Published: July 2022

Pollen fertility plays an important role in the application of heterosis in wheat (Triticum aestivum L.). However, the key genes and mechanisms underlying pollen abortion in K-type male sterility remain unclear. TAA1a is an essential gene for pollen development in wheat. Here, we explored the mechanism involved in its transcriptional regulation during pollen development, focusing on a 1315-bp promoter region. Several cis-acting elements were identified in the TAA1a promoter, including binding motifs for Arabidopsis thaliana AtAMS and AtMYB103 (CANNTG and CCAACC, respectively). Evolutionary analysis indicated that TaTDRL and TaMYB103 were the T. aestivum homologs of AtAMS and AtMYB103, respectively, and encoded nucleus-localized transcription factors containing 557 and 352 amino acids, respectively. TaTDRL and TaMYB103 were specifically expressed in wheat anthers, and their expression levels were highest in the early uninucleate stage; this expression pattern was consistent with that of TAA1a. Meanwhile, we found that TaTDRL and TaMYB03 directly interacted, as evidenced by yeast two-hybrid and bimolecular fluorescence complementation assays, while yeast one-hybrid and dual-luciferase assays revealed that both TaTDRL and TaMYB103 could bind the TAA1a promoter and synergistically increase its transcriptional activity. Furthermore, TaTDRL-EAR and TaMYB103-EAR transgenic Arabidopsis plants displayed abnormal microspore morphology, reduced pollen viability, and lowered seed setting rates. Additionally, the expression of AtMS2, a TAA1a homolog, was significantly lower in the two repressor lines than in the corresponding overexpression lines or WT plants. In summary, we identified a potential transcriptional regulatory mechanism associated with wheat pollen development.
Prenatal Exposure to Delta-9-tetrahydrocannabinol (THC) Alters the Expression of miR-122-5p and Its Target Igf1r in the Adult Rat Ovary
Authors: Martínez-Peña Annia A. , Lee Kendrick , Pereira Madison , Ayyash Ahmed , Petrik James J. , Hardy Daniel B. , Holloway Alison C.
Published: July 2022

As cannabis use during pregnancy increases, it is important to understand its effects on the developing fetus. Particularly, the long-term effects of its psychoactive component, delta-9-tetrahydrocannabinol (THC), on the offspring’s reproductive health are not fully understood. This study examined the impact of gestational THC exposure on the miRNA profile in adult rat ovaries and the possible consequences on ovarian health. Prenatal THC exposure resulted in the differential expression of 12 out of 420 evaluated miRNAs. From the differentially expressed miRNAs, miR-122-5p, which is highly conserved among species, was the only upregulated target and had the greatest fold change. The upregulation of miR-122-5p and the downregulation of its target insulin-like growth factor 1 receptor (Igf1r) were confirmed by RT-qPCR. Prenatally THC-exposed ovaries had decreased IGF-1R-positive follicular cells and increased follicular apoptosis. Furthermore, THC decreased Igf1r expression in ovarian explants and granulosa cells after 48 h. As decreased IGF-1R has been associated with diminished ovarian health and fertility, we propose that these THC-induced changes may partially explain the altered ovarian follicle dynamics observed in THC-exposed offspring. Taken together, our data suggests that prenatal THC exposure may impact key pathways in the developing ovary, which could lead to subfertility or premature reproductive senescence.
DNA Methylation Signature for JARID2-Neurodevelopmental Syndrome
Authors: Verberne Eline A. , van der Laan Liselot , Haghshenas Sadegheh , Rooney Kathleen , Levy Michael A. , Alders Mariëlle , Maas Saskia M. , Jansen Sandra , Lieden Agne , Anderlid Britt-Marie , Rafael-Croes Louise , Campeau Philippe M. , Chaudhry Ayeshah , Koolen David A. , Pfundt Rolph , Hurst Anna C. E. , Tran-Mau-Them Frederic , Bruel Ange-Line , Lambert Laetitia , Isidor Bertrand , Mannens Marcel M. A. M. , Sadikovic Bekim , Henneman Peter , van Haelst Mieke M.
Published: July 2022

JARID2 (Jumonji, AT Rich Interactive Domain 2) pathogenic variants cause a neurodevelopmental syndrome, that is characterized by developmental delay, cognitive impairment, hypotonia, autistic features, behavior abnormalities and dysmorphic facial features. JARID2 encodes a transcriptional repressor protein that regulates the activity of various histone methyltransferase complexes. However, the molecular etiology is not fully understood, and JARID2-neurodevelopmental syndrome may vary in its typical clinical phenotype. In addition, the detection of variants of uncertain significance (VUSs) often results in a delay of final diagnosis which could hamper the appropriate care. In this study we aim to detect a specific and sensitive DNA methylation signature for JARID2-neurodevelopmental syndrome. Peripheral blood DNA methylation profiles from 56 control subjects, 8 patients with (likely) pathogenic JARID2 variants and 3 patients with JARID2 VUSs were analyzed. DNA methylation analysis indicated a clear and robust separation between patients with (likely) pathogenic variants and controls. A binary model capable of classifying patients with the JARID2-neurodevelopmental syndrome was constructed on the basis of the identified episignature. Patients carrying VUSs clustered with the control group. We identified a distinct DNA methylation signature associated with JARID2-neurodevelopmental syndrome, establishing its utility as a biomarker for this syndrome and expanding the EpiSign diagnostic test.
Patients Recovering from Severe COVID-19 Develop a Polyfunctional Antigen-Specific CD4+ T Cell Response
Authors: Paolini Annamaria , Borella Rebecca , Neroni Anita , Lo Tartaro Domenico , Mattioli Marco , Fidanza Lucia , Di Nella Alessia , Santacroce Elena , Gozzi Licia , Busani Stefano , Trenti Tommaso , Meschiari Marianna , Guaraldi Giovanni , Girardis Massimo , Mussini Cristina , Gibellini Lara , De Biasi Sara , Cossarizza Andrea
Published: July 2022

Specific T cells are crucial to control SARS-CoV-2 infection, avoid reinfection and confer protection after vaccination. We have studied patients with severe or moderate COVID-19 pneumonia, compared to patients who recovered from a severe or moderate infection that had occurred about 4 months before the analyses. In all these subjects, we assessed the polyfunctionality of virus-specific CD4+ and CD8+ T cells by quantifying cytokine production after in vitro stimulation with different SARS-CoV-2 peptide pools covering different proteins (M, N and S). In particular, we quantified the percentage of CD4+ and CD8+ T cells simultaneously producing interferon-γ, tumor necrosis factor, interleukin (IL)-2, IL-17, granzyme B, and expressing CD107a. Recovered patients who experienced a severe disease display high proportions of antigen-specific CD4+ T cells producing Th1 and Th17 cytokines and are characterized by polyfunctional SARS-CoV-2-specific CD4+ T cells. A similar profile was found in patients experiencing a moderate form of COVID-19 pneumonia. No main differences in polyfunctionality were observed among the CD8+ T cell compartments, even if the proportion of responding cells was higher during the infection. The identification of those functional cell subsets that might influence protection can thus help in better understanding the complexity of immune response to SARS-CoV-2.
Genome-Wide Association Studies Reveal Novel Loci for Herbivore Resistance in Wild Soybean (Glycine soja)
Authors: Du Haiping , Qin Rui , Li Haiyang , Du Qing , Li Xiao , Yang Hui , Kong Fanjiang , Liu Baohui , Yu Deyue , Wang Hui
Published: July 2022

The production of soybean [Glycine max (L.) Merr.] is seriously threatened by various leaf-feeding insects, and wild soybean [Glycine soja Sieb. & Zucc.] has a greater resistance capacity and genetic diversity. In this study, a natural population consisting of 121 wild soybean accessions was used for detecting insect resistance genes. The larval weight (LW) of the common cutworm (CCW), the resistance level (RL) and the index of damaged leaf (IDL) were evaluated as resistance indicators to herbivores. An association synonymous SNP AX-94083016 located in the coding region of the respiratory burst oxidase gene GsRbohA1 was identified by genome-wide association study (GWAS) analyses. The overexpression of GsRbohA1 in soybean hairy roots enhanced resistance to CCW. One SNP in the promoter region cosegregated with AX-94083016 contributing to soybean resistance to CCW by altering GsRbohA1 gene expression and reactive oxygen species (ROS) accumulation. Two major haplotypes, GsRbohA1A and GsRbohA1G, were identified based on the SNP. The resistant haplotype GsRbohA1A predominates in wild soybeans, although it has been gradually lost in landraces and cultivars. The nucleotide diversity around GsRbohA1 is much lower in landraces and cultivars than in its ancestors. In conclusion, a new resistant haplotype, GsRbohA1A, was identified in wild soybean, which will be a valuable gene resource for soybean insect resistance breeding through introducing into improvement lines, and it offers a strategy for exploring resistance gene resources from its wild relatives.
Economic Evaluation of Newborn Screening for Severe Combined Immunodeficiency
Authors: Shih Sophy T. F. , Keller Elena , Wiley Veronica , Wong Melanie , Farrar Michelle A. , Chambers Georgina M.
Published: July 2022

Evidence on the cost-effectiveness of newborn screening (NBS) for severe combined immunodeficiency (SCID) in the Australian policy context is lacking. In this study, a pilot population-based screening program in Australia was used to model the cost-effectiveness of NBS for SCID from the government perspective. Markov cohort simulations were nested within a decision analytic model to compare the costs and quality-adjusted life-years (QALYs) over a time horizon of 5 and 60 years for two strategies: (1) NBS for SCID and treat with early hematopoietic stem cell transplantation (HSCT); (2) no NBS for SCID and treat with late HSCT. Incremental costs were compared to incremental QALYs to calculate the incremental cost-effectiveness ratios (ICER). Sensitivity analyses were performed to assess the model uncertainty and identify key parameters impacting on the ICER. In the long-term over 60 years, universal NBS for SCID would gain 10 QALYs at a cost of US $0.3 million, resulting in an ICER of US$33,600/QALY. Probabilistic sensitivity analysis showed that more than half of the simulated ICERs were considered cost-effective against the common willingness-to-pay threshold of A$50,000/QALY (US$35,000/QALY). In the Australian context, screening for SCID should be introduced into the current NBS program from both clinical and economic perspectives.