bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerosol Delivery of Lung Surfactant and Nasal CPAP in the Treatment of Neonatal Respiratory Distress Syndrome
Authors: Walther Frans J. , Waring Alan J.
Published: June 2022

After shifting away from invasive mechanical ventilation and intratracheal instillation of surfactant toward non-invasive ventilation with nasal CPAP and less invasive surfactant administration in order to prevent bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome, fully non-invasive surfactant nebulization is the next Holy Grail in neonatology. Here we review the characteristics of animal-derived (clinical) and new advanced synthetic lung surfactants and improvements in nebulization technology required to secure optimal lung deposition and effectivity of non-invasive lung surfactant administration. Studies in surfactant-deficient animals and preterm infants have demonstrated the safety and potential of non-invasive surfactant administration, but also provide new directions for the development of synthetic lung surfactant destined for aerosol delivery, implementation of breath-actuated nebulization and optimization of nasal CPAP, nebulizer circuit and nasal interface. Surfactant nebulization may offer a truly non-invasive option for surfactant delivery to preterm infants in the near future.
Chinese Medicine, Succinum, Ameliorates Cognitive Impairment of Carotid Artery Ligation Rats and Inhibits Apoptosis of HT22 Hippocampal Cells via Regulation of the GSK3β/β-Catenin Pathway
Authors: Wei Chongqi , Zhu Ziqiang , Zheng Jia-ni , Lu Yunqing , Cao Cheng , Qu Suchen , Liu Mengqiu , Meng Xue-er , Lou Qianyin , Wang Qingqing , Duan Jin-ao , Shang Er-xin , Han Zhenxiang , Zhu Yue
Published: June 2022

Succinum is an organic mineral formed from the resin of ancient coniferous and leguminous plants, which is applied for tranquilizing mood, promoting blood circulation, and removing blood stasis in Chinese medicine. For quite a long time, the modern research of succinum mainly focuses on the study of physical and chemical properties and authenticity identification while few reports on its medicinal mechanism. In current study, we evaluated different solvent extracts of succinum on carotid artery ligation rats mimicking vascular dementia. It was found that ethyl acetate extracts of succinum significantly improved the learning and memory abilities of model rats and inhibited neuronal apoptosis in the hippocampus. On a mice hippocampal neuronal cell line (HT22), ethyl acetate extracts of succinum also exerted better action trend in inhibiting cell apoptosis induced by oxygen glucose deprivation (OGD). By using XAV-939 on both in vivo and in vitro studies, it was found that ethyl acetate extracts of succinum might exert these functions by regulating the GSK3β/β-catenin pathway. These studies revealed the neuronal function of succinum, which explained the traditional effects of succinum and provided more modern scientific basis for its clinical application.
Modulatory Impact of Lamiaceae Metabolites on Apoptosis of Human Leukemia Cells
Authors: Berdowska Izabela , Zieliński Bogdan , Matusiewicz Małgorzata , Fecka Izabela
Published: June 2022

Lamiaceae species are rich sources of biologically active compounds which have been applied in medicine since ancient times. Especially their antineoplastic properties have been thoroughly studied with respect to their putative application in chemoprevention and adjuvant therapy of cancer. However, the most known biological effects of Lamiaceae have been ascribed to their essential oil fractions, whereas their (poly)phenolic metabolites being also abundant in these plants, are much less recognized, nevertheless contributing to their beneficial properties, such as anti-cancer actions. The aim of this study was to evaluate the impact of dried aqueous extracts from common thyme (Thymus vulgaris L.) (ExTv), wild thyme (Thymus serpyllum L.) (ExTs), sweet marjoram (Origanum majorana L.) (ExOm), and peppermint (Mentha × piperita L.) (ExMp), as well as (poly)phenolic compounds: caffeic acid (CA), rosmarinic acid (RA), lithospermic acid (LA), luteolin-7-O-β-glucuronide (Lgr), luteolin-7-O-rutinoside (Lr), eriodictyol-7-O-rutinoside (Er), and arbutin (Ab), on unstimulated Jurkat cells, in comparison with their effect on staurosporine-stimulated Jurkat cells. Jurkat T cells were incubated with different concentrations of ExTv, ExTs, ExOm, ExMp, Lgr, LA, Er, Lr, RA, CA, or Ab. Subsequently, staurosporine was added to half of the samples and flow cytometry combined with fluorescence-activated cell sorting analysis was conducted, which allowed for the selection of early and late apoptotic cells. Both ExTs and ExOm stimulated apoptosis of Jurkat cells and enhanced the proapoptotic effect of staurosporine. Conversely, ExTv and ExMp demonstrated no clear effect on apoptosis. CA and RA raised the staurosporine-induced apoptotic effect. The impact of Er and Lgr on Jurkat cells showed fluctuations depending on the compound concentration. Neither Er nor Ab altered staurosporine-induced apoptosis in Jurkat cells, whereas Lgr seemed to weaken the proapoptotic action of staurosporine. The most evident observation in this study was the pro-apoptotic action of ExTs and ExOm observed both in staurosporine-unstimulated and stimulated Jurkat cells. Additionally, an enhancement of staurosporine-induced apoptosis by caffeic and rosmarinic acids was reported. Therefore, it might be concluded that these are the mixtures of biologically active polyphenols which often exert more pronounced beneficial effects than purified molecules.
Trends in Antihypertensive Medicine Utilization in the Republic of Srpska, Bosnia and Herzegovina: An Eleven-Year Follow-Up
Authors: Kalinić Dragan , Škrbić Ranko , Vulić Duško , Stojaković Nataša , Stoisavljević-Šatara Svjetlana , Stojiljković Miloš P. , Marković-Peković Vanda , Golić Jelić Ana , Pilipović-Broćeta Nataša , Wong Nathan D. , Godman Brian
Published: June 2022

Background: In last 2 decades, there have been substantial changes in the utilization patterns of antihypertensive medicines following new clinical trials and the introduction of new treatment guidelines. The aim of this study was to analyze utilization and prescribing patterns regarding antihypertensive medicines in the Republic of Srpska, Bosnia and Herzegovina during an 11-years follow-up according to national and European treatment guidelines.

Methods: In this retrospective, observational study, medicine utilization data were analyzed between 2009–2019 period using the ATC/DDD methodology and expressed as the number of DDD/1,000 inhabitants/day (DID/TID). The medicine utilization 90% (DU90%) method was used for determine the quality of prescribing.

Results: During the observed period, the use of antihypertensive medicines increased more than 3-times (125.97 DDD/TID in 2009 vs 414.95 DDD/TID in 2019), corresponding to a rise in the prevalence of hypertensive patients from 91.7/1,000 to 186.3/1,000 in the same period. This was mainly driven by increased use of angiotensin converting enzyme inhibitors with 241.69%, beta blockers with 146.87%, calcium channel blockers with 251.55%, and diuretics with 178.95%. Angiotensin receptor blockers were the fastest growing group of antihypertensive medicines in this period and their utilization increased nearly 40 times.

Conclusions: The overall antihypertensive medicines utilization was largely influenced by national and ESH/ESC guidelines and strongly corresponded to the positive medicine list of the national health insurance fund. Antihypertensive medicines utilization is comparable with medicine utilization trends in other countries.
Network Pharmacology and In Vitro Experimental Verification Reveal the Mechanism of the Hirudin in Suppressing Myocardial Hypertrophy
Authors: Liu Mengnan , Luo Gang , Dong Li , Mazhar Maryam , Wang Li , He Wenlu , Liu Yan , Wu Qibiao , Zhou Hua , Yang Sijin
Published: June 2022

Background: Myocardial hypertrophy is a complex pathological process, which is a common manifestation during the development of various cardiovascular diseases. Hirudin has been shown to have therapeutic effects on a variety of cardiovascular diseases, however, its therapeutic effect on myocardial hypertrophy is still unknown, and its chemical and pharmacological characteristics remain to be elucidated.

Methods: In this study, the network pharmacology method was used to characterize the mechanism of hirudin on myocardial hypertrophy. The potential protein targets of hirudin and myocardial hypertrophy were both obtained from the Genecards database, and potential pathways associated with genes were identified by Gene Ontology and pathway enrichment analysis, and the data were displayed in a visual manner. Subsequently, the potential mechanism of action of hirudin on myocardial hypertrophy predicted by network pharmacology analysis was verified by molecular docking, and finally, the main findings were further verified by in vitro experiments by molecular biology techniques. Based on the results obtained from the study of H9c2 cell line, the inhibitory effect of hirudin on myocardial hypertrophy was further proved in the primary rat cardiomyocytes.

Results: A total of 250 targets of hirudin, and 5,376 targets related to myocardial hypertrophy after deduplication were collected. The drug-disease network showed the relationship between hirudin, myocardial hypertrophy, and the targets. Further, systematic analysis from the PPI network indicated that blood coagulation, vesicle lumen, and signaling receptor activator activity may be the potential mechanisms of hirudin in the treatment of myocardial hypertrophy, and the PI3K/AKT signaling pathway may be the most relevant to the therapeutic effect of hirudin. Then, three therapeutic targets that were highly related to myocardial hypertrophy were extracted. Hirudin can be highly bound to STAT3, IL-6, and MAPK1 and found by molecular docking, which may be the basis for its inhibitory effect on myocardial hypertrophy. In addition, in vitro experiments showed that hirudin could inhibit AngII-induced hypertrophy and death of H9c2 cells, and significantly reduce the mRNA and protein expression levels of STAT3, MAPK1, and IL-6. The above conclusions were verified in primary rat cardiomyocytes.

Conclusion: Hirudin can be used to treat myocardial hypertrophy through a complex mechanism. The application of network pharmacology and experimental validation can promote the application of hirudin in cardiovascular diseases and the interpretation and understanding of molecular biological mechanisms.
Importance of Rare DPYD Genetic Polymorphisms for 5-Fluorouracil Therapy in the Japanese Population
Authors: Hishinuma Eiji , Narita Yoko , Obuchi Kai , Ueda Akiko , Saito Sakae , Tadaka Shu , Kinoshita Kengo , Maekawa Masamitsu , Mano Nariyasu , Hirasawa Noriyasu , Hiratsuka Masahiro
Published: June 2022

Dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is the rate-limiting enzyme in 5-fluorouracil (5-FU) degradation. In Caucasians, four DPYD risk variants are recognized to be responsible for interindividual variations in the development of 5-FU toxicity. However, these risk variants have not been identified in Asian populations. Recently, 41 DPYD allelic variants, including 15 novel single nucleotide variants, were identified in 3,554 Japanese individuals by analyzing their whole-genome sequences; however, the effects of these variants on DPD enzymatic activity remain unknown. In the present study, an in vitro analysis was performed on 41 DPD allelic variants and three DPD risk variants to elucidate the changes in enzymatic activity. Wild-type and 44 DPD-variant proteins were heterologously expressed in 293FT cells. DPD expression levels and dimerization of DPD were determined by immunoblotting after SDS-PAGE and blue native PAGE, respectively. The enzymatic activity of DPD was evaluated by quantification of dihydro-5-FU, a metabolite of 5-FU, using high-performance liquid chromatography-tandem mass spectrometry. Moreover, we used 3D simulation modeling to analyze the effect of amino acid substitutions on the conformation of DPD. Among the 41 DPD variants, seven exhibited drastically decreased intrinsic clearance (CLint) compared to the wild-type protein. Moreover, R353C and G926V exhibited no enzymatic activity, and the band patterns observed in the immunoblots after blue native PAGE indicated that DPD dimerization is required for its enzymatic activity. Our data suggest that these variants may contribute to the significant inter-individual variability observed in the pharmacokinetics and pharmacodynamics of 5-FU. In our study, nine DPD variants exhibited drastically decreased or no enzymatic activity due to dimerization inhibition or conformational changes in each domain. Especially, the rare DPYD variants, although at very low frequencies, may serve as important pharmacogenomic markers associated with the severe 5-FU toxicity in Japanese population.
Antiviral Efficacy and Safety of Molnupiravir Against Omicron Variant Infection: A Randomized Controlled Clinical Trial
Authors: Zou Rongrong , Peng Ling , Shu Dan , Zhao Lei , Lan Jianfeng , Tan Guoyu , Peng Jinghan , Yang Xiangyi , Liu Miaona , Zhang Chenhui , Yuan Jing , Wang Huxiang , Li Song , Lu Hongzhou , Zhong Wu , Liu Yingxia
Published: June 2022

Background: The rapid worldwide spread of the Omicron variant of SARS-CoV-2 has unleashed a new wave of COVID-19 outbreaks. The efficacy of molnupiravir, an approved drug, is still unknown in patients infected with the Omicron variant.

Objective: Evaluated the antiviral efficacy and safety of molnupiravir in patients infected with SARS-CoV-2 Omicron variant, with symptom duration within 5 days.

Methods: We conducted a randomized, controlled trial involving patients with mild or moderate COVID-19. Patients were randomized to orally receive molnupiravir (800 mg) plus basic treatment or only basic treatment for 5 days (BID). The antiviral efficacy of the drug was evaluated using reverse transcriptase polymerase chain reaction.

Results: Results showed that the time of viral RNA clearance (primary endpoint) was significantly decreased in the molnupiravir group (median, 9 days) compared to the control group (median, 10 days) (Log-Rank p = 0.0092). Of patients receiving molnupiravir, 18.42% achieved viral RNA clearance on day 5 of treatment, compared to the control group (0%) (p = 0.0092). On day 7, 40.79%, and 6.45% of patients in the molnupiravir and control groups, respectively, achieved viral RNA clearance (p = 0.0004). In addition, molnupiravir has a good safety profile, and no serious adverse events were reported.

Conclusion: Molnupiravir significantly accelerated the SARS-CoV-2 Omicron RNA clearance in patients with COVID-19.

Clinical Trial Registration: [chictr.org.cn], identifier [ChiCTR2200056817].
GNSS Spoofing Suppression Based on Multi-Satellite and Multi-Channel Array Processing
Authors: Ni Shaojie , Ren Binbin , Chen Feiqiang , Lu Zukun , Wang Jie , Ma Pengcheng , Sun Yifan
Published: June 2022

The endless spoofing interference affects the credibility of the navigation system seriously. In order to suppress the forward spoofing which is more threatening to military signals in GNSS, this paper proposes a spoofing suppression algorithm based on angle of arrival estimation and multi-satellite fusion. On the basis of successfully suppressing the spoofing signal, the algorithm improves the estimation accuracy of the angle of arrival of the forwarded spoofing and reduces the attenuation of the carrier to noise ratio of the real satellite signal. Finally, the effectiveness of the algorithm is verified by simulation, which has guiding significance for the anti-spoofing research of GNSS.
Wellness Forecasting by External and Internal Workloads in Elite Soccer Players: A Machine Learning Approach
Authors: Rossi Alessio , Perri Enrico , Pappalardo Luca , Cintia Paolo , Alberti Giampietro , Norman Darcy , Iaia F. Marcello
Published: June 2022

Training for success has increasingly become a balance between maintaining high performance standards and avoiding the negative consequences of accumulated fatigue. The aim of this study is to develop a big data analytics framework to predict players’ wellness according to the external and internal workloads performed in previous days. Such a framework is useful for coaches and staff to simulate the players’ response to scheduled training in order to adapt the training stimulus to the players’ fatigue response. 17 players competing in the Italian championship (Serie A) were recruited for this study. Players’ Global Position System (GPS) data was recorded during each training and match. Moreover, every morning each player has filled in a questionnaire about their perceived wellness (WI) that consists of a 7-point Likert scale for 4 items (fatigue, sleep, stress, and muscle soreness). Finally, the rate of perceived exertion (RPE) was used to assess the effort performed by the players after each training or match. The main findings of this study are that it is possible to accurately estimate players’ WI considering their workload history as input. The machine learning framework proposed in this study is useful for sports scientists, athletic trainers, and coaches to maximise the periodization of the training based on the physiological requests of a specific period of the season.
Pathophysiological Changes in Erythrocytes Contributing to Complications of Inflammation and Coagulation in COVID-19
Authors: Soma Prashilla , Bester Janette
Published: June 2022

Higher thrombotic burden in the acute phase of COVID-19 relies on a complex interplay between pro-inflammatory cytokine/chemokine release, increased endothelial dysfunction/damage, and potential sepsis-induced coagulopathy development in severe cases, all promoting coagulation activation. Plasma levels of cytokines and chemokines are known to be increased in COVID-19 however, are much higher in severe infections. Increased levels of IL-1β, IL-6, and IL-8 are known to play an important role in both acute and chronic inflammation, resulting in pathological clotting. However, little has been published on the effects of these interleukins on red blood cells (RBCs). Evidence shows that cytokines have a negative effect on the RBCs ultrastructure and introduce signs of eryptosis. Eryptosis can be described as a form of suicidal death of RBCs characterized by distinct findings of cell shrinkage, membrane blebbing, activation of proteases, and phosphatidylserine exposure at the outer membrane leaflet. Red blood cells from COVID-19 patients had increased levels of glycolytic intermediates, accompanied by oxidation and fragmentation of ankyrin, spectrin beta, and the N-terminal cytosolic domain of band 3 (AE1). Significantly altered lipid metabolism was also observed, in particular, short- and medium-chain saturated fatty acids, acyl-carnitines, and sphingolipids. Emerging research suggests that RBCs may contribute to a precision medicine approach to sepsis and have diagnostic value in monitoring complement dysregulation in COVID-19-sepsis and non-COVID sepsis as research indicates that complement activation products and viral antigens are present on RBCs in patients with COVID-19.
The Allelic Variant A391T of Metal Ion Transporter ZIP8 (SLC39A8) Leads to Hypotension and Enhanced Insulin Resistance
Authors: Verouti Sophia N. , Pujol-Giménez Jonai , Bermudez-Lekerika Paola , Scherler Laeticia , Bhardwaj Rajesh , Thomas Aurélien , Lenglet Sébastien , Siegrist Mark , Hofstetter Willy , Fuster Daniel G. , Hediger Matthias A. , Escher Geneviève , Vogt Bruno
Published: June 2022

The metal ion transporter ZIP8 (SLC39A8) mediates cellular uptake of vital divalent metal ions. Genome-wide association studies (GWAS) showed that the single-nucleotide polymorphism (SNP) variant A391T (rs13107325) is associated with numerous human traits, including reduced arterial blood pressure, increased body mass index and hyperlipidemia. We analyzed in vitro the transport properties of mutant ZIP8 A391T and investigated in vivo in mice the physiological effects of this polymorphism. In vitro, the intrinsic transport properties of mutant ZIP8 were similar to those of wild type ZIP8, but cellular uptake of zinc, cadmium and iron was attenuated due to reduced ZIP8 plasma membrane expression. We then generated the ZIP8 A393T mice (ZIP8KI) that carry the corresponding polymorphism and characterized their phenotype. We observed lower protein expression in lung and kidney membrane extracts in ZIP8KI mice. The ZIP8KI mice exhibited striking changes in metal ion composition of the tissues, including cobalt, palladium, mercury and platinum. In agreement with GWAS, ZIP8KI mice showed reduced arterial blood pressure. Body weight and plasma lipid composition remained unchanged, although these features were reported to be increased in GWAS. ZIP8KI mice also exhibited remarkable insulin resistance and were protected from elevated blood glucose when challenged by dietary sucrose supplementation. We showed that increased hepatic insulin receptor expression and decreased ZnT8 (slc30a8) metal ion transporter mRNA expression are associated with this phenotypic change. In conclusion, our data reveal that ZIP8 plays an important role in blood pressure regulation and glucose homeostasis.
Role of the Demethylase AlkB Homolog H5 in the Promotion of Dentinogenesis
Authors: Tian Cheng , Chai Jihua , Liu Weidong , Zhang Xinye , Li Yashu , Zuo Huanyan , Yuan Guohua , Zhang Haojian , Liu Huan , Chen Zhi
Published: June 2022

Dentinogenesis is a key process in tooth formation and is regulated by a series of pre- and post-transcriptional regulations. N6-methyl-adenosine (m6A), which is the most prevalent internal chemical modification that can be removed by the RNA demethylase AlkB homolog H5 (ALKBH5), has recently been reported to be involved in several biological processes. However, the exact function of ALKBH5-mediated m6A modification in tooth development remains unclear. Here, we showed that Alkbh5 was expressed in pre-odontoblasts, polarizing odontoblasts, and secretory odontoblasts. Alkbh5 overexpression in the mouse dental papilla cell line mDPC6T promoted odontoblastic differentiation. Conditional knockout of Alkbh5 in Dmp1-expressing odontoblasts led to a decrease in number of odontoblasts and increased pre-dentin formation. Mechanistically, RNA sequencing and m6A sequencing of Alkbh5-overexpressing mDPC6T cells revealed that Alkbh5 promoted odontoblast differentiation by prolonging the half-life of Runx2 transcripts in an m6A-dependent manner and by activating the phosphatidylinositol 3-kinase/protein kinase B pathway. Notably, the loss of Alkbh5 expression in odontoblasts impaired tertiary dentin formation in vivo. These results suggested that the RNA demethylase ALKBH5 plays a role in dentinogenesis.
Genetic Architecture of Heterophylly: Single and Multi-Leaf Genome-Wide Association Mapping in Populus euphratica
Authors: Zhu Xuli , Sun Fengshuo , Sang Mengmeng , Ye Meixia , Bo Wenhao , Dong Ang , Wu Rongling
Published: June 2022

Heterophylly is an adaptive strategy used by some plants in response to environmental changes. Due to the lack of representative plants with typical heteromorphic leaves, little is known about the genetic architecture of heterophylly in plants and the genes underlying its control. Here, we investigated the genetic characteristics underlying changes in leaf shape based on the model species, Populus euphratica, which exhibits typical heterophylly. A set of 401,571 single-nucleotide polymorphisms (SNPs) derived from whole-genome sequencing of 860 genotypes were associated with nine leaf traits, which were related to descriptive and shape data using single- and multi-leaf genome-wide association studies (GWAS). Multi-leaf GWAS allows for a more comprehensive understanding of the genetic architecture of heterophylly by considering multiple leaves simultaneously. The single-leaf GWAS detected 140 significant SNPs, whereas the multi-leaf GWAS detected 200 SNP-trait associations. Markers were found across 19 chromosomes, and 21 unique genes were implicated in traits and serve as potential targets for selection. Our results provide novel insights into the genomic architecture of heterophylly, and provide candidate genes for breeding or engineering P. euphratica. Our observations also improve understanding of the intrinsic mechanisms of plant growth, evolution, and adaptation in response to climate change.
Desorption Electrospray Ionization Mass Spectrometry Imaging Illustrates the Quality Characters of Isatidis Radix
Authors: Nie Li-Xing , Huang Lie-Yan , Wang Xin-Ping , Lv Lin-Feng , Yang Xue-Xin , Jia Xiao-Fei , Kang Shuai , Yao Ling-Wen , Dai Zhong , Ma Shuang-Cheng
Published: June 2022

For a long history, herbal medicines have made significant contributions to human health all around the world. However, the exploration of an effective approach to illustrate their inner quality remains a challenge. So, it is imperative to develop new methods and technologies to characterize and identify quality markers of herbal medicines. Taking Isatidis Radix, the dried root of Isatis indigotica as an example, desorption electrospray ionization (DESI), in combination with quadrupole-time-of-flight mass spectrometry (Q-TOF/MS), was applied in this work for the first time to reveal the comprehensive spatial distribution of metabolites and, further, to illustrate quality characters of this herbal medicine. After simple pretreatment, 102 metabolites including alkaloids, sulfur-containing compounds, phenylpropanoids, nucleosides, amino acids, organic acids, flavonoids, phenols, terpenes, saccharides, peptides, and sphingolipids were characterized, some of which were successfully localized and visualized in the transverse section of the root. Based on the ion images, samples with different quality characters were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 11 major influencing components exerting higher ion intensities in superior samples were identified as the potential quality markers of Isatidis Radix. Desorption electrospray ionization (DESI) mass spectrometry imaging (MSI), together with chemometric analysis could not only improve the understanding of the plant biology of herbal medicines but also be beneficial in the identification of quality markers, so as to carry out better quality control of herbal medicines.
Karyology and Genome Size Analyses of Iranian Endemic Pimpinella (Apiaceae) Species
Authors: Mehravi Shaghayegh , Ranjbar Gholam Ali , Najafi-Zarrini Hamid , Mirzaghaderi Ghader , Hanifei Mehrdad , Severn-Ellis Anita Alice , Edwards David , Batley Jacqueline
Published: June 2022

Pimpinella species are annual, biennial, and perennial semibushy aromatic plants cultivated for folk medicine, pharmaceuticals, food, and spices. The karyology and genome size of 17 populations of 16 different Pimpinella species collected from different locations in Iran were analyzed for inter-specific karyotypic and genome size variations. For karyological studies, root tips were squashed and painted with a DAPI solution (1 mg/ml). For flow cytometric measurements, fresh leaves of the standard reference (Solanum lycopersicum cv. Stupick, 2C DNA = 1.96 pg) and the Pimpinella samples were stained with propidium iodide. We identified two ploidy levels: diploid (2x) and tetraploid (4x), as well as five metaphase chromosomal counts of 18, 20, 22, 24, and 40. 2n = 24 is reported for the first time in the Pimpinella genus, and the presence of a B-chromosome is reported for one species. The nuclear DNA content ranged from 2C = 2.48 to 2C = 5.50 pg, along with a wide range of genome sizes between 1212.72 and 2689.50 Mbp. The average monoploid genome size and the average value of 2C DNA/chromosome were not proportional to ploidy. There were considerable positive correlations between 2C DNA and total chromatin length and total chromosomal volume. The present study results enable us to classify the genus Pimpinella with a high degree of morphological variation in Iran. In addition, cytological studies demonstrate karyotypic differences between P. anthriscoides and other species of Pimpinella, which may be utilized as a novel identification key to affiliate into a distinct, new genus – Pseudopimpinella.
Deciphering the Multi-Chromosomal Mitochondrial Genome of Populus simonii
Authors: Bi Changwei , Qu Yanshu , Hou Jing , Wu Kai , Ye Ning , Yin Tongming
Published: June 2022

Mitochondria, inherited maternally, are energy metabolism organelles that generate most of the chemical energy needed to power cellular various biochemical reactions. Deciphering mitochondrial genome (mitogenome) is important for elucidating vital activities of species. The complete chloroplast (cp) and nuclear genome sequences of Populus simonii (P. simonii) have been reported, but there has been little progress in its mitogenome. Here, we assemble the complete P. simonii mitogenome into three circular-mapping molecules (lengths 312.5, 283, and 186 kb) with the total length of 781.5 kb. All three molecules of the P. simonii mitogenome had protein-coding capability. Whole-genome alignment analyses of four Populus species revealed the fission of poplar mitogenome in P. simonii. Comparative repeat analyses of four Populus mitogenomes showed that there were no repeats longer than 350 bp in Populus mitogenomes, contributing to the stability of genome sizes and gene contents in the genus Populus. As the first reported multi-circular mitogenome in Populus, this study of P. simonii mitogenome are imperative for better elucidating their biological functions, replication and recombination mechanisms, and their unique evolutionary trajectories in Populus.
Raman Spectroscopy Enables Confirmatory Diagnostics of Fusarium Wilt in Asymptomatic Banana
Authors: Parlamas Stephen , Goetze Paul K. , Humpal Dillon , Kurouski Dmitry , Jo Young-Ki
Published: June 2022

Fusarium oxysporum f. sp. cubense (FOC) causes Fusarium wilt, one of the most concerning diseases in banana (Musa spp.), compromising global banana production. There are limited curative management options after FOC infections, and early Fusarium wilt symptoms are similar with other abiotic stress factors such as drought. Therefore, finding a reliable and timely form of early detection and proper diagnostics is critical for disease management for FOC. In this study, Portable Raman spectroscopy (handheld Raman spectrometer equipped with 830 nm laser source) was applied for developing a confirmatory diagnostic tool for early infection of FOC on asymptomatic banana. Banana plantlets were inoculated with FOC; uninoculated plants exposed to a drier condition were also prepared compared to well-watered uninoculated control plants. Subsequent Raman readings from the plant leaves, without damaging or destroying them, were performed weekly. The conditions of biotic and abiotic stresses on banana were modeled to examine and identify specific Raman spectra suitable for diagnosing FOC infection. Our results showed that Raman spectroscopy could be used to make highly accurate diagnostics of FOC at the asymptomatic stage. Based on specific Raman spectra at vibrational bands 1,155, 1,184, and 1,525 cm−1, Raman spectroscopy demonstrated nearly 100% accuracy of FOC diagnosis at 40 days after inoculation, differentiating FOC-infected plants from uninoculated plants that were well-watered or exposed to water deficit condition. This study first reported that Raman spectroscopy can be used as a rapid and non-destructive tool for banana Fusarium wilt diagnostics.
The Spatial Distribution and Genetic Diversity of the Soybean Cyst Nematode, Heterodera glycines, in China: It Is Time to Take Measures to Control Soybean Cyst Nematode
Authors: Lian Yun , Koch Georg , Bo Dexin , Wang Jinshe , Nguyen Henry T. , Li Chun , Lu Weiguo
Published: June 2022

The continuous evolution and spread of virulent forms of the soybean cyst nematode (SCN) driven by the environment and anthropogenic intervention is a serious threat to the soybean production worldwide, including China. Especially in China, the implemented measures to control SCN are insufficient for sustainable agricultural development yet. We summarized our knowledge about the spread and spatial distribution of SCN in China and the virulence diversity in the main soybean growing areas. To reveal the genetic relatedness and diversity of SCN populations, we re-sequenced 53 SCN genomes from the Huang-Huai Valleys, one of the two main soybean growing areas in China. We identified spreading patterns linked to the local agroecosystems and topographies. Moreover, we disclosed the first evidence for the selection of complex virulence in the field even under low selection pressure in an example from North Shanxi. SCN is present in all soybean growing areas in China but SCN susceptible cultivars are still largely grown indicating that SCN-related damage and financial loss have not received the attention they deserve yet. To prevent increasing yield losses and to improve the acceptance of resistant cultivars by the growers, we emphasized that it is time to accelerate SCN resistance breeding, planting resistant cultivars to a larger extent, and to support farmers to implement a wider crop rotation for sustainable development of the soybean production in China.
The Noetic Signature Inventory: Development, Exploration, and Initial Validation
Authors: Wahbeh Helané , Fry Nina , Speirn Paolo
Published: June 2022

Noetic comes from the Greek word noēsis, meaning inner wisdom or direct knowing. Noetic experiences often transcend the perception of our five senses and are ubiquitous worldwide, although no instrument exists to evaluate noetic characteristics both within and between individuals. We developed the Noetic Signature Inventory (NSI) through an iterative qualitative and statistical process as a tool to subjectively assess noetic characteristics. Study 1 developed and evaluated a 175-item NSI using 521 self-selected research participants, resulting in a 46-item NSI with an 11-factor model solution. Study 2 examined the 11-factor solution, construct validity, and test–retest reliability, resulting in a 44-item NSI with a 12-factor model solution. Study 3 confirmed the final 44-item NSI in a diverse population. The 12-factors were: (1) Inner Knowing, (2) Embodied Sensations, (3) Visualizing to Access or Affect, (4) Inner Knowing Through Touch, (5) Healing, (6) Knowing the Future, (7) Physical Sensations from Other People, (8) Knowing Yourself, (9) Knowing Other’s Minds, (10) Apparent Communication with Non-physical Beings, (11) Knowing Through Dreams, and (12) Inner Voice. The NSI demonstrated internal consistency, convergent and divergent content validity, and test–retest reliability. The NSI can be used for the future studies to evaluate intra- and inter-individual variation of noetic experiences.
Understanding Zhongyong Using a Zhongyong Approach: Re-examining the Non-linear Relationship Between Creativity and the Confucian Doctrine of the Mean
Authors: Gao Ruixiang , Huang Shiqi , Yao Yujie , Liu Xiaoqin , Zhou Yujun , Zhang Shijia , Cai Shaohua , Zuo Huang , Zhan Zehui , Mo Lei
Published: June 2022

Zhongyong, a central theme of Confucian thought, refers to the “doctrine of the mean,” or the idea that moderation in all things is the optimal path. Despite considerable interest in the relationship between zhongyong and creativity, especially in China, studies of this relationship have not yielded consistent results. Based on a review of the literature, we hypothesized that this inconsistency arises from the dual nature of zhongyong itself, which has both a positive side, promoting creativity, and a negative side, inhibiting creativity. We also hypothesized that the negative side of zhongyong takes the form of excessive zhongyong. Indeed, the observations that every coin has two sides and that too much of a good thing is as bad as too little are core principles of zhongyong in traditional Chinese culture. To test these hypotheses, we conducted two empirical studies (measuring explicit and implicit zhongyong personality, respectively) to examine the relationships between positive and negative zhongyong and creativity (measured in terms of creative personality, divergent thinking, and convergent thinking). The results of both studies revealed an interaction between positive zhongyong and negative zhongyong, indicating that only a moderate level of zhongyong is conducive to creativity; both deficiency and excess are harmful. We discuss the implications of these results, suggesting that a zhongyong approach can help to clarify non-linear relationships between things, and recommending to re-assess the creativity of Chinese culture from a neutral and objective outlook. This paper deepens understanding of zhongyong and offers clear insights into creativity from an in-depth cultural perspective.
An Open-Source Relational Network Derivation Script in R for Modeling and Visualizing Complex Behavior for Scientists and Practitioners
Authors: Smith Patrick , Hayes Steven C.
Published: June 2022

Relational models of cognition provide parsimonious and actionable models of generative behavior witnessed in humans. They also inform many current computational analogs of cognition including Deep Neural Networks, Reinforcement Learning algorithms, Self-Organizing Maps, as well as blended architectures that are outperforming traditional semantic models. The black box nature of these computer models artificially limits scientific and applied progress and human computer interaction. This paper presents a first in the field attempt to model relational processes using logical derivation scripts and network graph visualizations written in the open-source R language. These tools are presented as a way for researchers and practitioners to begin to explore more complex relational models in a manner that can advance the theory and empirical science, as well as prepare the field for future collaborations with advanced computational models of cognition.
Virtual Community Engagement Studio (V-CES): Engaging Mothers With Mental Health and Substance Use Conditions in Research
Authors: Zisman-Ilani Yaara , Buell Jennifer , Mazel Shayna , Hennig Shannon , Nicholson Joanne
Published: June 2022

Active engagement of community stakeholders is increasingly encouraged in behavioral health research, often described as a co-production approach. Community stakeholders (e.g., patients, providers, policy makers, advocates) play a leading role together with research investigators in conducting the various phases of research, including conceptualization, design, implementation, and the interpretation and dissemination of findings. The concept of co-production has promising benefits for both the target population and the research outcomes, such as producing person-centered interventions with greater acceptability and usability potential. However, it is often the case that neither researchers nor community members are trained or skilled in co-production methods. The field of behavioral health research lacks tools and methods to guide and promote the engagement of diverse stakeholders in the research process. The purpose of this methods paper is to describe the Virtual Community Engagement Studio (V-CES) as a new method for engaging vulnerable populations like mothers with mental health and substance use conditions in research. We piloted the method in collaboration with the Maternal Mental Health Research Collaborative (MMHRC), focusing on one of the most vulnerable, under-researched populations, mothers coping with mental health and/or substance abuse disorders. Our pilot included mothers and providers who work with them as Community Experts to inform all phases of research design and implementation, and the interpretation and application of findings. The aim of this article is to describe the V-CES as a powerful tool that supports the engagement of mothers with mental health and/or substance use disorders and other community stakeholders in research, to provide examples of its use, and to make recommendations for future use, based on lessons learned. The V-CES toolkit is available for use with this target population as well as others.
Bipolar Disorder and Polysubstance Use Disorder: Sociodemographic and Clinical Correlates
Authors: Aguglia Andrea , Natale Antimo , Fusar-Poli Laura , Amerio Andrea , Bruno Edoardo , Placenti Valeria , Vai Eleonora , Costanza Alessandra , Serafini Gianluca , Aguglia Eugenio , Amore Mario
Published: June 2022

Introduction

Patients with bipolar disorder (BD) often show comorbidity with substance use disorder (SUD) with a negative impact on clinical course, prognosis, and functioning. The role of polysubstance use disorder (polySUD) is understudied. The aim of the present paper is to evaluate the sociodemographic and clinical characteristics associated with BD and comorbid SUD, focusing on polySUD, in order to phenotype this specific group of patients and implement adequate treatment and prevention strategies.

Methods

A cross-sectional study was conducted involving 556 patients with a primary diagnosis of BD (376 without SUD, 101 with SUD, and 79 with polySUD). A semi-structured interview was administered to collect sociodemographic variables, clinical characteristics, and pharmacological treatment. ANOVA and chi-square tests were used to compare the three groups. Significantly different variables were then inserted in multivariate logistic regression.

Results

Patients affected by BD and polySUD were younger, and more frequently males and single, than patients with SUD or without SUD. Indeed, the prevalence of patients affected by BD and polySUD living in residential facilities was higher than in the other groups. Moreover, earlier age at onset, higher prevalence of psychotic and residual symptoms, involuntary hospitalization, and a family history of psychiatric disorders were associated with polySUD in patients suffering from BD. Lastly, patients with BD and polySUD were more likely to take four or more medications, particularly benzodiazepines and other drugs. At the multinomial regression, younger age, male gender, early age at onset, psychotic and residual symptoms, positive family history of psychiatric disorders, and use of benzodiazepines remained significantly associated with polySUD in patients with BD.

Conclusion

Our findings show a specific profile of patients with BD and polySUD. It is important to conduct research on this topic in order to adopt specific therapeutic strategies, minimize the use of polypharmacy, and aim at full remission and mood stabilization.
Practice Level and Associated Factors Towards the Preventive Measures of COVID-19 Among the General Population; A Systematic Review and Meta-Analysis
Authors: Tadesse Abay Woday , Aychiluhm Setognal Birara , Mare Kusse Urmale , Tarekegn Setegn Mihret , Biset Gebeyaw
Published: June 2022

Background

Studies conducted on the practice of COVID-19 preventive methods across the world are highly inconsistent and inconclusive. Hence, this study intended to estimate the pooled preventive practice and its determinants among the general population.

Methods

This study was conducted using online databases (PubMed, HINARI, Scopus, EMBASE, Science Direct, and Cochrane library database), African Journals online, Google Scholar, open gray and online repository accessed studies. The quality of the included studies was assessed using Newcastle-Ottawa Quality Assessment Scale (NOS). STATA 14.0 software for analysis. The existence of heterogeneity between studies was checked using Cochran Q test and I2 test statistics and then, the presence of publication bias was detected using both funnel plot and Egger's test.

Results

51 studies were included and the pooled level of practice toward the preventive measures of COVID-19 was 74.4% (95% CI: 70.2–78.6%, I2 = 99.7%, P < 0.001] using a random effects model. Being female [OR = 1.97: 95% CI 1.75, 2.23; I2 = 0.0%, P < 0.698], rural residence [OR = 0.53: 95% CI 0.44, 0.65; I2 = 73.5%, P < 0.013], attending higher education level [OR = 1.47: 95% CI 1.18, 1.83; I2 = 75.4%, P < 0.001], being employed [OR = 2.12: 95% CI 1.44, 3.12; I2 = 91.8%, P < 0.001], age < 30 [OR = 0.73: 95% CI 0.60, 0.89; I2 = 73.9%, P < 0.001], and knowledgeable [OR = 1.22: 95% CI 1.09, 1.36; I2 = 47.3%, P < 0.077] were the independent predictors of adequate practice level.

Conclusions

nearly three-fourths of the general population has an adequate preventive practice level toward COVID-19. Thus, the global, regional, national, and local governments need to establish policies and strategies to address the identified factors.
Health Promoting Lifestyle Behaviors and Sleep Quality Among Saudi Postmenopausal Women
Authors: Abdelaziz Enas Mahrous , Elsharkawy Nadia Bassuoni , Mohamed Sayeda Mohamed
Published: June 2022

Background

One of the most effective measures regarding improving women's health is to promote healthy lifestyle behaviors. This study aimed to investigate the relationship between health-promoting behaviors and sleep quality among a sample of Saudi menopausal women.

Methods

A descriptive cross-sectional study was used to collect data from 410 Saudi postmenopausal women visiting primary healthcare care centers located in Sakaka, Jouf, Saudi Arabia, using the Menopause Rating Scale (MRS), Health-Promoting Lifestyle Profile II (HPLPII) and Pittsburgh Sleep Quality Index (PSQI).

Results

The mean age of the study participants was 52.60 ± 4.65 years, the study findings highlighted that among all the HPLP domains, the highest mean score was observed for spiritual growth (24.00 ± 6.60) whereas the lowest score was observed for physical activity (16.18 ± 1.8). Statistically significant negative relations between the total score of HPLP and sleep quality score and menopausal symptoms (p< 0.001,p< 0.005), respectively. Total scores of lifestyle, health responsibility, and stress management were significant differences between participants with good and poor sleep quality. Being overweight/obese, physically inactive, having a chronic illness and poor sleep quality were predictors influencing health-promoting behavior.

Conclusion

Health-Promoting Lifestyle Profile II was more obvious in the good sleeper in form of health responsibility and stress management. Being overweight and or obese, having a chronic illness, and having poor sleep quality were the significant factors influencing health-promoting behaviors. Designing and performing educational interventional plans are crucial to create motivation toward a healthy lifestyle and improve the quality of their sleep.
Principles and Design Scenarios for Sustainable Urban Food Logistics
Authors: Tochtrop Christoph , Bickel Manuel W. , Hennes Lena , Speck Melanie , Liedtke Christa
Published: June 2022

Food and nutrition systems are linked to all Sustainable Development Goals (SDGs), which makes their transition toward social-ecological behavior patterns crucial for an overarching sustainability transformation. The perspective of (urban) logistics is of special interest. It couples the production and consumption physically and virtually. In this context, we shed light on the design of the turnover point of food in urban areas from the supply chain toward consumers and contribute to an overarching systemic perspective toward establishing a sustainable multilevel food system. We describe current patterns in urban food systems and propose several principles for sustainable design of (urban) food systems based on concepts such as (regional) collaboration and food literacy. Using these principles, we provide four design scenarios that concretely imagine future urban food consumption and production patterns titled “slow stock supply service, ” “deliver into the daily walk, ” “central district food depot, ” “super food action place.” With this work we provide a starting for reflecting whether certain combinations of principles actually lead to patterns of daily life that are feasible, acceptable, or desirable. Moreover, we provide an initial qualitative assessment to stimulate further research that explores scenario pathways and incorporates additional indicators regarding the impact on social-ecological. We open up various research questions with regard to the overarching question of how urban food logistics should be designed to be consistent with the SDGs.