bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Mutational Profile of Hypopharyngeal and Laryngeal Head and Neck Squamous Cell Carcinomas Identifies KMT2C as a Potential Tumor Suppressor
Authors: Machnicki Marcin M. , Rzepakowska Anna , Janowska Joanna I. , Pepek Monika , Krop Alicja , Pruszczyk Katarzyna , Stawinski Piotr , Rydzanicz Malgorzata , Grzybowski Jakub , Gornicka Barbara , Wnuk Maciej , Ploski Rafal , Osuch-Wojcikiewicz Ewa , Stoklosa Tomasz
Published: May 2022

Hypopharyngeal cancer is a poorly characterized type of head and neck squamous cell carcinoma (HNSCC) with bleak prognosis and only few studies focusing specifically on the genomic profile of this type of cancer. We performed molecular profiling of 48 HPV (Human Papilloma Virus)-negative tumor samples including 23 originating from the hypopharynx and 25 from the larynx using a targeted next-generation sequencing approach. Among genes previously described as significantly mutated, TP53, FAT1, NOTCH1, KMT2C, and CDKN2A were found to be most frequently mutated. We also found that more than three-quarters of our patients harbored candidate actionable or prognostic alterations in genes belonging to RTK/ERK/PI3K, cell-cycle, and DNA-damage repair pathways. Using previously published data we compared 67 hypopharyngeal cancers to 595 HNSCC from other sites and found no prominent differences in mutational frequency except for CASP8 and HRAS genes. Since we observed relatively frequent mutations of KTM2C (MLL3) in our dataset, we analyzed their role, in vitro, by generating a KMT2C-mutant hypopharyngeal cancer cell line FaDu with CRISPR-Cas9. We demonstrated that KMT2C loss-of-function mutations resulted in increased colony formation and proliferation, in concordance with previously published results. In summary, our results show that the mutational profile of hypopharyngeal cancers might be similar to the one observed for other head and neck cancers with respect to minor differences and includes multiple candidate actionable and prognostic genetic alterations. We also demonstrated, for the first time, that the KMT2C gene may play a role of tumor suppressor in HNSCC, which opens new possibilities in the search for new targeted treatment approaches.
Comprehensive Expression Profile Analysis of Neutrophil Extracellular Trap-Affected Genes in Gastric Cancer Cells and the Clinical Significance of lncRNA NEAT1-Related Signaling
Authors: Li Changjian , Zou Xiaoming , Cai Qingxin , Li Jiacheng , Yang Shifeng , Zhang Ange , Chen Chongyan , Zhu Lei
Published: May 2022

Background

Gastric cancer (GC) is the fifth most common malignant tumor and the third leading cause of cancer-related deaths worldwide. Neutrophil extracellular traps (NETs) can enhance the invasion of GC cells and are associated with poor prognosis in patients. However, its mechanism of action is not completely understood.

Methods

The content of NETs in the peripheral blood of patients with GC was detected by enzyme-linked immunosorbent assay. GC AGS cells were treated with or without NETs for 24 h. High-throughput RNA sequencing was performed to screen differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Real-time polymerase chain reaction (PCR) was used to verify gene expression. A competing endogenous RNA (ceRNA) regulatory network was constructed. Modules were screened using the molecular complex detection (MCODE) plug-in. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the genes in the network. The role and clinical significance of the lncRNA NEAT1-related signaling pathway were validated.

Results

The content of NETs in the patients with GC was significantly higher than that in healthy controls and was also higher in patients with high-grade (stages III and IV) GC. NETs promoted the invasion of AGS cells. A total of 1,340 lncRNAs, 315 miRNAs, and 1,083 mRNAs were differentially expressed after NET treatment. The expression of five genes was validated using real-time PCR, which were in accordance with the RNA sequencing results. A ceRNA regulatory network was constructed with 1,239 lncRNAs, 310 miRNAs, and 1,009 mRNAs. Four genes (RAB3B, EPB41L4B, ABCB11, and CCDC88A) in the ceRNA network were associated with patient prognosis, with RAB3B being the most prominent and with signaling among the lncRNA NEAT1, the miRNA miR-3158-5p, and RAB3B. NEAT1 was upregulated in AGS cells after NET treatment. RNA interference of NEAT1 inhibited the invasion of AGS cells induced by NETs, inhibited miR-3158-5p expression, and promoted RAB3B expression. NEAT1 and RAB3B expression were positively correlated in patients with GC. Furthermore, RAB3B was upregulated and miR-3158-5p was downregulated in GC tissues compared with adjacent normal tissues, which was also associated with cancer stage.

Conclusion

This study provides a comprehensive analysis of differentially expressed genes in NET-treated GC cells and validated the clinical significance of NEAT1-related signaling.
Treatment Response, Survival Benefit and Safety Profile of PD-1 Inhibitor Plus Apatinib Versus Apatinib Monotherapy in Advanced Colorectal Cancer Patients
Authors: Pan Dengdeng , Liu Dongliang , Liang Lichuan , Shen Tongyi , Shi Chenzhang , Qin Huanlong
Published: May 2022

Purpose

Programmed cell death protein 1 (PD-1) inhibitor plus apatinib is reported to be a promising strategy for advanced cancers. Moreover, a PD-1 inhibitor or apatinib exerts a certain efficacy in advanced colorectal cancer (CRC), whereas their synergistic effect is unclear. This study aimed to evaluate the treatment efficacy and safety of a PD-1 inhibitor plus apatinib in advanced CRC patients.

Methods

In total, 45 advanced CRC patients who received a PD-1 inhibitor plus apatinib (PD-1 inhibitor plus apatinib group, N=20) or apatinib monotherapy (apatinib group, N=25) as third-line therapies were enrolled in the current study.

Results

The objective response rate (20.0% vs. 8.0%) (P=0.383) and disease control rate (70.0% vs. 52.0%) (P=0.221) were numerically increased in the PD-1 inhibitor plus apatinib group, respectively, compared with the apatinib group, but no statistical significance was observed. The median progression-free survival (PFS) was 7.5 versus 4.8 months; the 1-year PFS rate was 32.5% versus 9.9%; the median overall survival (OS) was 12.3 versus 8.7 months; and the 1-year OS rate was 50.7% versus 27.0% in the PD-1 inhibitor plus apatinib group versus the apatinib group, respectively. PFS (P=0.038) and OS (P=0.048) were prolonged in the PD-1 inhibitor plus apatinib group compared with the apatinib group. PD-1 inhibitor plus apatinib (versus apatinib) was independently associated with longer PFS (P=0.012) and OS (P=0.009). The majority of the adverse events were of grade 1-2, wherein the incidence was similar between groups, except for the fact that the incidence of capillary proliferation was elevated in the PD-1 inhibitor plus apatinib group compared with the apatinib group (25.5% versus 0.0%) (P=0.013).

Conclusion

PD-1 inhibitor plus apatinib presents a potential improvement in efficacy and survival benefit compared with apatinib monotherapy, with tolerable safety in advanced CRC patients.
Survival of Patients Subjected to Hepatectomy After Spontaneous Rupture of Hepatocellular Carcinoma: A Meta-analysis of High-quality Propensity Score Matching Studies
Authors: Huang Xiaozhun , Jia Chenyang , Xu Lin , Bi Xinyu , Lai Fengyong , Huang Zhangkan , Li Xiaoqing , Yin Xin , Ni Yong , Che Xu
Published: May 2022

Background

The spontaneous rupture of hepatocellular carcinoma (HCC) is associated with high mortality rates, and liver resection can provide better outcomes than other available treatments. However, the survival length of patients subjected to hepatectomy after spontaneous rupture of hepatocellular carcinoma remains controversial.

Method

Articles reporting the comparison of the survival outcome between patients with rupture HCC (rHCC) and non-rupture HCC (nrHCC) from the inception until December 31, 2021 by PubMed, Web of Science, OVID, and the Cochrane Library databases were included. The high-quality propensity score matching analysis was used to investigate the impact of rupture on disease-free survival (DFS) and overall survival (OS) between the rHCC and nrHCC group with no heterogeneity.

Result

A total of 606 patients from six cohort studies were included. The major baseline characteristics of the eligible patients were well balanced between rHCC and nrHCC group. The 1-, 3-, and 5-year hazard ratios of DFS were 3.45 (95% confidence interval [CI] 2.54–4.68), 3.63 (95% CI 2.87–4.60), and 3.72 (95% CI 2.93–4.72), respectively. The 1-, 3-, and 5-year hazard ratios of OS were 5.01 (95% CI 3.26–7.69), 5.49 (95% CI 4.08–7.39), and 4.20 (95% CI 3.20–5.51), respectively.

Conclusion

The present meta-analysis demonstrated that the DSF and OS were significantly shorter in the rHCC group than in the nrHCC group, thus revealing that spontaneous HCC rupture was a predictor of poor survival.
Using Single Cell Transcriptomics to Elucidate the Myeloid Compartment in Pancreatic Cancer
Authors: Kadiyala Padma , Elhossiny Ahmed M. , Carpenter Eileen S.
Published: May 2022

Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a 5-year survival rate of 10%. A hallmark feature of this disease is its abundant microenvironment which creates a highly immunosuppressive milieu. This is, in large part, mediated by an abundant infiltration of myeloid cells in the PDAC tumor microenvironment. Consequently, therapies that modulate myeloid function may augment the efficacy of standard of care for PDAC. Unfortunately, there is limited understanding about the various subsets of myeloid cells in PDAC, particularly in human studies. This review highlights the application of single-cell RNA sequencing to define the myeloid compartment in human PDAC and elucidate the crosstalk between myeloid cells and the other components of the tumor immune microenvironment.
LncRNA-AL035458.2/hsa-miR-181a-5p Axis-Mediated High Expression of NCAPG2 Correlates With Tumor Immune Infiltration and Non-Small Cell Lung Cancer Progression
Authors: Chen Xi , Guo Jishu , Ren Wenjun , Zhou Fan , Niu Xiaoqun , Jiang Xiulin
Published: May 2022

Lung adenocarcinoma (LUAD) is the most common histological lung cancer, and it is the leading cause of cancer-related deaths worldwide. NCAPG2 (non-SMC condensin II complex subunit G2) has been shown to be upregulated in various human cancers. Nevertheless, the underlying biological function and potential mechanisms of NCAPG2 driving the progression of LUAD remain unclear. In this study, we investigated the role of NCAPG2 in LUAD and found that the expression of NCAPG2 in LUAD tissues was significantly higher than that of NCAPG2 expression in adjacent normal tissues. Kaplan–Meier survival analysis showed that patients with higher NCAPG2 expression correlated with unfavorable clinical outcomes. Receiver operating characteristic (ROC) curve analysis showed that the AUC value of NCAPG2 was 0.914. Correlation analysis showed that NCAPG2 expression was associated with immune infiltration in LUAD. Finally, we found that AL139385.1 was upregulated in LUAD cancer tissues and cell lines. Knockdown of NCAPG2 inhibited cell proliferation, cell migration, and cell invasion of LUAD in vitro. More importantly, we established the AL035458.2/hsa-miR-181a-5p axis as the most likely upstream ncRNA-related pathway of NCAPG2 in LUAD. In conclusion, our data demonstrated that ncRNA-mediated high expression of NCAPG2 was correlated with progression and immune infiltration, and could serve as a prognostic biomarker for LUAD.
BCG Moreau Polish Substrain Infections in Patients With Inborn Errors of Immunity: 40 Years of Experience in the Department of Immunology, Children's Memorial Health Institute, Warsaw
Authors: Bernatowska Ewa , Pac Małgorzata , Heropolitańska-Pliszka Edyta , Pietrucha Barbara , Dąbrowska-Leonik Nel , Skomska-Pawliszak Małgorzata , Bernat-Sitarz Katarzyna , Krzysztopa-Grzybowska Katarzyna , Wolska-Kuśnierz Beata , Bohynikova Nadia , Augustynowicz Ewa , Augustynowicz-Kopeć Ewa , Korzeniewska-Koseła Maria , Wieteska-Klimczak Anna , Książyk Janusz , Jackowska Teresa , van den Burg Mirjam , Casanova Jean-Laurent , Picard Capucine , Mikołuć Bożena
Published: May 2022

Objective

We aimed to assess BCG (Bacillus Calmette-Guérin) complications in patients with Inborn Errors of Immunity (IEI), according to the inherited disorders and associated immunological defects, as well as the different BCG substrains.

Material

We studied adverse reactions to the locally-produced BCG Moreau vaccine, analyzed in patients with IEI diagnosed between 1980 and 2020 in the Department of Immunology, Children's Memorial Health Institute (CMHI), Warsaw. These results were compared with previously published studies.

Results

Significantly fewer disseminated BCG infections (BCGosis) were found in 11 of 72 (15%) SCID (Severe Combined Immunodeficiency) NK (Natural Killer)-phenotype patients, when compared with the 119 out of 349 (34%) (p = 0.0012) patients with SCID with BCG in other countries. Significantly fewer deaths caused by BCGosis were observed (p = 0.0402). A significantly higher number of hematopoietic stem cell transplantations (HSCTs) were performed in the CMHI study (p = 0.00001). BCGosis was found in six patients with Mendelian susceptibility to mycobacterial diseases (MSMD). Other patients with IEI prone to BCG complications, such as CGD (Chronic Granulomatous Disease), showed no case of BCGosis.

Conclusion

The BCG Moreau substrain vaccine, produced in Poland since 1955, showed genetic differences with its parental Brazilian substrain together with a superior clinical safety profile in comparison with the other BCG substrains, with no BCGosis in patients with IEI other than SCID and MSMD. Our data also confirmed significantly fewer cases of BCGosis and deaths caused by BCG infection in patients with SCID with this vaccine substrain. Finally, they confirmed the protecting role of NK cells, probably via their production of IFN-γ.
Pediatric Surgical Care During the COVID-19 Lockdown: What Has Changed and Future Perspectives for Restarting in Italy. The Point of View of the Italian Society of Pediatric Surgery
Authors: Morini Francesco , Romeo Carmelo , Chiarenza Fabio , Esposito Ciro , Gamba Piergiorgio , Gennari Fabrizio , Inserra Alessandro , Cobellis Giovanni , Leva Ernesto , Angotti Rossella , Raffaele Alessandro , Cacciaguerra Sebastiano , Messina Mario , Lima Mario , Pelizzo Gloria
Published: May 2022

Background:

The coronavirus disease 2019 (COVID-19) time exacerbated some of the conditions already considered critical in pediatric health assistance before the pandemic. A new form of pediatric social abandonment has arisen leading to diagnostic delays in surgical disorders and a lack of support for the chronic ones. Health services were interrupted and ministerial appointments for pediatric surgical healthcare reprogramming were postponed. As a result, any determination to regulate the term “pediatric” specificity was lost. The aim is, while facing the critical issues exacerbated by the COVID-19 pandemic, to rebuild future perspectives of pediatric surgical care in Italy.

Methods

Each Pediatric Society, including the Italian Society of Pediatric Surgery (SICP), was asked by the Italian Federation of Pediatric Associations and Scientific Societies to fill a questionnaire, including the following the main issues: evaluation of pre-pandemic criticalities, pediatric care during the pandemic and recovery, and current criticalities. The future care model of our specialty was analyzed in the second part of the questionnaire.

Results

Children are seriously penalized both for surgical treatment as well as for the diagnostic component. In most centers, the pediatric surgical teams have been integrated with the adult ones and the specificity of training the pediatric operating nursing is in danger of survival. “Emotional” management of the child is not considered by the general management and the child has become again an adults patient of reduced size.

Conclusion

A new functional pediatric surgical model needs to be established in general hospitals, including activities for day surgery and outpatient surgery. To support the care of the fragile child, a national health plan for the pediatric surgery is required.
Short-Term Nutritional Support for Infants With Unrestricted Ventricular Septal Defects to Promote Postoperative Recovery
Authors: Zhang Qi-Liang , Lin Shi-Hao , Lin Wen-Hao , Cao Hua , Chen Qiang
Published: May 2022

Objective

This study is aimed to explore the effect of short-term nutritional support for infants with unrestricted ventricular septal defects on improving preoperative nutritional status and promoting postoperative recovery.

Methods

The clinical data of 35 infants with unrestricted ventricular septal defects who were treated with 2 weeks of nutritional support in our hospital from December 2020 to March 2021 were analyzed retrospectively. The clinical data of 38 infants with unrestricted ventricular septal defects who were treated in our hospital from May 2020 to October 2020 were selected as controls.

Results

The preoperative body weight, preoperative albumin, preoperative prealbumin, and preoperative hemoglobin in the intervention group were significantly higher than those in the control group (P < 0.05). The postoperative ventilator time, intensive care time, and discharge time in the intervention group were significantly shorter than those in the control group (P < 0.05).

Conclusion

Performing 2 weeks of nutritional support for infants with unrestricted ventricular septal defects can improve their preoperative nutritional status and promote postoperative recovery.
Effects of Bisphosphonates Treatments in Osteopenic Older Women: A Systematic Review and Meta-Analysis
Authors: Li Jiangbi , Sun Yang , Chen Zhuo , Xie Xiaoping , Gu Feng , Bi Songqi , Yu Tiecheng
Published: May 2022

Aims: To review the effects of bisphosphonates on bone density, fractures, and bone markers in osteopenic older women.

Methods: Relevant articles published before February 2022 were searched in PubMed, EMBASE, and the Cochrane Library. All randomized controlled trials that reported incident fractures, bone mineral density (BMD), bone markers, or adverse events with bisphosphonates in osteopenic older women were included. The quality of included studies was assessed using the Cochrane Risk of Bias tool. The risk ratios (RRs) for fractures, net percent change in bone mineral density and differences in bone markers were calculated using a meta-analysis.

Results: A total of 11 studies were included in our meta-analysis. Bisphosphonates significantly increased the percent changes in the lumbar spine BMD (WMD, 5.60; 95% CI, 4.16–7.03; I2 = 93.6%), hip BMD (WMD, 4.80; 95% CI, 2.93 to 6.66; I2 = 97.1%), total body BMD (WMD, 3.24; 95% CI, 2.12–4.35; I2 = 90.9%), femoral neck BMD (WMD, 4.02; 95% CI, 1.70–6.35; I2 = 91.8%) and trochanter BMD (WMD, 5.22; 95% CI, 3.51–6.93; I2 = 83.6%) when compared to placebo. Zoledronate was associated with a great treatment effect on fragility fracture (RR, 0.63; 95% CI, 0.50–0.79), clinical vertebral fracture (RR, 0.41; 95% CI, 0.22–0.76), and radiographic vertebral fracture (RR, 0.60; 95% CI, 0.27–1.35) compared to placebo. Meanwhile, alendronate was also associated with beneficial effects on fragility fracture (RR, 0.40; 95% CI, 0.15–1.07), clinical vertebral fracture (RR, 0.46; 95% CI, 0.17–1.24), and radiographic vertebral fracture (RR, 0.64; 95% CI, 0.38–1.09). In addition, the use of bisphosphonates reduced the concentration of procollagen type I N-terminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX) over placebo by 15.79 (95% CI, −18.92 to −12.66; I2 = 28.4%), −0.23 (95% CI, −0.35 to −0.10; I2 = 91.3%), respectively. Although there was insufficient evidence to determine their safety, these bisphosphonates may have an effect on cancer, cardiac events, and mortality in osteopenic older women.

Conclusion: All bisphosphonates examined were associated with beneficial effects on fractures, BMD, and bone markers in women with osteopenia. Further randomized controlled trials are necessary to clarify the safety of bisphosphonates in women with osteopenia.
Analysis of Actomyosin Oscillatory Dynamics Using a Coarse-Grained Model
Authors: Hernández-Del-Valle Miguel , Valencia-Expósito Andrea , Gorfinkiel Nicole , Martín-Bermudo Maria D. , Míguez David G.
Published: May 2022

Autonomous oscillatory dynamics are ubiquitous at every level in Biology. At the cellular level, one of the most relevant and well characterized examples of periodic behavior is the cyclic assembly and disassembly of actomyosin networks. In Drosophila, these oscillations induce the robust contraction and expansion of individual cells required for correct dorsal closure, while in the follicular epithelium that surrounds the germline, periodic contractions of the basal actomyosin network are required for proper elongation of the egg chamber. While some studies suggest that actomyosin oscillations are driven by upstream signaling or mechanochemical features, we have recently proposed that they arise as a systems property from the competition between two well characterized features of the actomyosin machinery: 1) cooperative assembly of actin networks mediated by Actin crosslinker proteins and 2) tension-induced disassembly of actin networks mediated by myosin motors. Here, we perform experiments in amnioserosa and in the follicle cells of drosophila and simulations using a coarse-grained model of the actomyosin cortex to characterize the properties of the oscillations and how they depend on different features of the system. We also compare model and experiments to study the dynamics of actomyosin flows and the effect of mechanical coupling between cells in the tissue. In conclusion, our model is a powerful tool to study key features of actomyosin oscillations, from the effect of the individual components to network properties and finally supra-cellular organization of the oscillations at the tissue level.
CRISRP/Cas9-Mediated Targeted Mutagenesis of Tomato Polygalacturonase Gene (SlPG) Delays Fruit Softening
Authors: Nie Hongmei , Shi Yu , Geng Xueqing , Xing Guoming
Published: May 2022

Polygalacturonase (PG) gene has been documented as a key candidate for the improvement of fruit firmness, which is a target trait for tomato production because it facilitates transportation and storage. To reduce the expression of the PG gene, most of the elite commercial tomato varieties were obtained by RNA interference technology. However, this approach of producing commercialized tomatoes by integration of the exogenous gene is controversial. In this work, CRISPR/Cas9 technology was used to induce the targeted mutagenesis of the SlPG gene to delay the softening of tomato fruit. Results showed that the SlPG gene was frameshift mutated by 4 bp deletion, 10 bp deletion, and 1 bp insertion, which generated premature translation termination codons. Compared with wild-type (WT), homozygous T1-generation tomato plants exhibited late fruit softening under natural conditions. Consistent with this phenomenon, the firmness value of WT fruit was lower in slpg mutant fruit, and the physiological loss of water was higher. Collectively, these data demonstrate that the mutation of the SlPG gene delays tomato fruit softening. More importantly, 8 out of 20 transgene-free tomato plants, which were homozygous for null alleles of SlPG, were separated in the T3-generation of line slpgT2-#2. This transgene-free slpg may provide materials for more in-depth research of SlPG functions and the molecular mechanism of fruit softening in tomatoes.
Population and Landscape Genetics Provide Insights Into Species Conservation of Two Evergreen Oaks in Qinghai–Tibet Plateau and Adjacent Regions
Authors: Liu Keke , Qi Min , Du Fang K.
Published: May 2022

The combination of population and landscape genetics can facilitate the understanding of conservation strategy under the changing climate. Here, we focused on the two most diverse and ecologically important evergreen oaks: Quercus aquifolioides and Quercus spinosa in Qinghai–Tibetan Plateau (QTP), which is considered as world’s biodiversity hotspot. We genotyped 1,657 individuals of 106 populations at 15 nuclear microsatellite loci throughout the species distribution range. Spatial patterns of genetic diversity were identified by mapping the allelic richness (AR) and locally common alleles (LCA) according to the circular neighborhood methodology. Migration routes from QTP were detected by historical gene flow estimation. The response pattern of genetic variation to environmental gradient was assessed by the genotype–environment association (GEA) analysis. The overall genetic structure showed a high level of intra-species genetic divergence of a strong west-east pattern. The West-to-East migration route indicated the complex demographic history of two oak species. We found evidence of isolation by the environment in Q. aqu-East and Q. spi-West lineage but not in Q. aqu-West and Q. spi-East lineage. Furthermore, priority for conservation should be given to populations that retain higher spatial genetic diversity or isolated at the edge of the distribution range. Our findings indicate that knowledge of spatial diversity and migration route can provide valuable information for the conservation of existing populations. This study provides an important guide for species conservation for two oak species by the integration of population and landscape genetic methods.
Evaluating Decision Support Tools for Precision Nitrogen Management on Creeping Bentgrass Putting Greens
Authors: Zhou Qiyu , Soldat Douglas J.
Published: May 2022

Nitrogen (N) is the most limiting nutrient for turfgrass growth. Few tools or soil tests exist to help managers guide N fertilizer decisions. Turf growth prediction models have the potential to be useful, but the lone turfgrass growth prediction model only takes into account temperature, limiting its accuracy. This study investigated the ability of a machine learning (ML)-based turf growth model using the random forest (RF) algorithm (ML-RF model) to improve creeping bentgrass (Agrostis stolonifera) putting green management by estimating short-term clipping yield. This method was compared against three alternative N application strategies including (1) PACE Turf growth potential (GP) model, (2) an experience-based method for applying N fertilizer (experience-based method), and (3) the experience-based method guided by a vegetative index, normalized difference red edge (NDRE)-based method. The ML-RF model was built based on a set of variables including 7-day weather, evapotranspiration (ET), traffic intensity, soil moisture content, N fertilization rate, NDRE, and root zone type. The field experiment was conducted on two sand-based research greens in 2020 and 2021. The cumulative applied N fertilizer was 281 kg ha−1 for the PACE Turf GP model, 190 kg ha−1 for the experience-based method, 140 kg ha−1 for the ML-RF model, and around 75 kg ha−1 NDRE-based method. ML-RF model and NDRE-based method were able to provide customized N fertilization recommendations on different root zones. The methods resulted in different mean turfgrass qualities and NDRE. From highest to lowest, they were PACE Turf GP model, experience-based, ML-RF model, and NDRE-based method, and the first three methods produced turfgrass quality over 7 (on a scale from 1 to 9) and NDRE value over 0.30. N fertilization guided by the ML-RF model resulted in a moderate amount of fertilizer applied and acceptable turfgrass performance characteristics. This application strategy is based on the N cycle and has the potential to assist turfgrass managers in making N fertilization decisions for creeping bentgrass putting greens.
An Integrated Metabolome and Transcriptome Analysis Reveal the Regulation Mechanisms of Flavonoid Biosynthesis in a Purple Tea Plant Cultivar
Authors: Song SaSa , Tao Yu , Gao LongHan , Liang HuiLing , Tang DeSong , Lin Jie , Wang YuChun , Gmitter Frederick G. , Li ChunFang
Published: May 2022

Purple tea plant cultivars, enrich with flavonoids and anthocyanins, are valuable materials for manufacturing tea with unique color and flavor. Researchers found that ‘Zijuan’ leaves changed from purple to green mainly caused by the decreased flavonoids and anthocyanins concentrations. The mechanism of flavonoids and anthocyanin biosynthesis has been studied in many purple tea plant cultivars and the key genes which regulated the biosynthesis of flavonoid and anthocyanins in different purple tea plant cultivars were quite different. Also, the molecular regulation mechanism underlying the flavonoids and anthocyanins biosynthesis during leaves development and color changes is less-thoroughly understood. In this study, an integrative analysis of transcriptome and metabolome was performed on the purple leaves and green leaves of ‘Zijuan’ tea plant to reveal the regulatory networks correlated to flavonoid biosynthesis and to identify key regulatory genes. Our results indicated that the ‘Zijuan’ new shoots leaves were purple might be due to the copigmentation of quercetin and kaempferol derivatives. In ‘Zijuan’ tea plant cultivar, flavonoids metabolites concentrations in purple leaves and green leaves were significantly influenced by the genes involved in flavonoid biosynthesis, transcriptional regulation, transport, and hormone response. Transcription factors including NAC008, MYB23, and bHLH96 and transporters such as ABC transporter I might be responsible for the flavonoid and anthocyanins accumulation in purple leaves. This study provides a new insight into the metabolism and molecular mechanisms underlying flavonoid and anthocyanin biosynthesis in tea plant.
Evolutionary and Regulatory Pattern Analysis of Soybean Ca2+ ATPases for Abiotic Stress Tolerance
Authors: Wang Jian , Fu Xujun , Zhang Sheng , Chen Guang , Li Sujuan , Shangguan Tengwei , Zheng Yuanting , Xu Fei , Chen Zhong-Hua , Xu Shengchun
Published: May 2022

P2-type Ca2+ ATPases are responsible for cellular Ca2+ transport, which plays an important role in plant development and tolerance to biotic and abiotic stresses. However, the role of P2-type Ca2+ ATPases in stress response and stomatal regulation is still elusive in soybean. In this study, a total of 12 P2-type Ca2+ ATPases genes (GmACAs and GmECAs) were identified from the genome of Glycine max. We analyzed the evolutionary relationship, conserved motif, functional domain, gene structure and location, and promoter elements of the family. Chlorophyll fluorescence imaging analysis showed that vegetable soybean leaves are damaged to different extents under salt, drought, cold, and shade stresses. Real-time quantitative PCR (RT-qPCR) analysis demonstrated that most of the GmACAs and GmECAs are up-regulated after drought, cold, and NaCl treatment, but are down-regulated after shading stress. Microscopic observation showed that different stresses caused significant stomatal closure. Spatial location and temporal expression analysis suggested that GmACA8, GmACA9, GmACA10, GmACA12, GmACA13, and GmACA11 might promote stomatal closure under drought, cold, and salt stress. GmECA1 might regulate stomatal closure in shading stress. GmACA1 and GmECA3 might have a negative function on cold stress. The results laid an important foundation for further study on the function of P2-type Ca2+ ATPase genes GmACAs and GmECAs for breeding abiotic stress-tolerant vegetable soybean.
Patterns of Children’s Relationships With Parents and Teachers in Grade 1: Links to Task Persistence and Performance
Authors: Silinskas Gintautas , Kikas Eve
Published: May 2022

Our study aimed to investigate the patterns of children’s relationships with their parents and teachers, the development of these relationships during Grade 1, and respective links to children’s learning (in task persistence and performance). Parents of 350 children answered questionnaires about the quality of their relationships with their children; 25 teachers answered questions about children’s task persistence at school and the quality of their relationships with their students; 350 children completed literacy and math performance tests; and six testers evaluated children’s task persistence when completing those tests. All measures were administered twice: at the start and end of Grade 1. Latent profile analyses found two meaningful child profiles that were similar at the beginning and end of Grade 1: average relationship (89% at T1, 85% at T2) and conflictual relationship (11% at T1, 15% at T2) with parents and teachers. These profiles were highly stable throughout Grade 1, except for 15 children who moved from an average relationship to a conflictual relationship profile. This declining trajectory can be characterized by poor relationships with teachers and low task persistence at the end of Grade 1, although they did not perform any worse than other children. Finally, children exhibiting conflictual relationships with their parents and teachers at the beginning of Grade 1 performed worse on spelling and subtraction tasks and demonstrated lower task-persistent behavior at the end of Grade 1 than those with average (good) relationships with parents and teachers.
Born to Be a Risky Driver? The Relationship Between Cloninger’s Temperament and Character Traits and Risky Driving
Authors: Lajunen Timo , Gaygısız Esma
Published: May 2022

Temperament refers to basic, largely inherited, relatively stable personality traits which have been present since early childhood. Considering the very fundamental role of temperament in human development and behaviour, it is reasonable to assume that temperament is also related to risky driving and drivers’ view of themselves as drivers. The aim of the present study was to investigate the relationships between Cloninger’s temperament dimensions, risky driving and drivers’ view of their perceptual motor and safety skills. The sample consisted of 335 Turkish drivers (aged 19–57; 53.7% men) who completed an Internet-based survey including Temperament and Character Inventory (TCI), Driver Behaviour Questionnaire (DBQ) and Driver Skill Inventory (DSI). Correlation analyses showed that TCI scale Cooperativeness correlated negatively with all DBQ scales indicating risky driving and positively with safety skills. In regression analyses after controlling age, gender and lifetime mileage, cooperativeness still was significantly related to all DBQ scales and safety skills. Persistence correlated negatively with ordinary violations, lapses and errors and positively with perceptual motor skills. In regression analyses, persistence was related to errors and lapses. Reward dependence was positively related to lapses and harm avoidance negatively to perceptual motor skills. The results of the present study indicate that largely innate temperament character traits may influence an individual’s predisposition to risky driving. Future studies about temperament and risky driving with larger samples allowing sub-group analyses are needed.
Modeling the Significance of Sustainability Orientation on the Sustainability Performance of Micro-Enterprises in an Emerging Economy
Authors: Wan Mustapa Wan Nurulasiah binti , Hayat Naeem , Fazal Syed Ali , Al Mamun Abdullah , Salameh Anas A. , Zainol Noor Raihani
Published: May 2022

Sustainable enterprises are essential for developing economies’ progress and prosperity. Micro-enterprises (MEs) play an important role in creating jobs and actively participating in socioeconomic activities. However, little is known about how MEs use internal capabilities to achieve long-term success. This study explores the influence of the strategic orientations (i.e., sales, consumer, competitive, emotional, business, and networking) instigating the sustainability orientation. The sustainability orientation nurtures the sustainable performance of the MEs. The cross-sectional data collected from the 450 MEs with the structured interviews and samples were randomly selected from the list of MEs registered in seven districts of Kelantan, Malaysia. The collected data were analyzed with partial least square structural equation modeling (PLS-SEM). The data analysis discovered that the sale, consumer, competitive, and emotional orientation significantly impact the MEs’ sustainable orientation. The business and networking orientations insignificantly facilitate the sustainable orientation among the samples. The MEs’ sustainable orientation suggestively influences the sustainable performance among the MEs. Furthermore, the study analysis postulated a significant mediating effect of sustainable orientation among the orientations (sale, consumer, competitive, and emotional) on the MEs’ sustainable performance. Our study offers a better understanding of the RBV in the MEs and brings significant empirical evidence to attain sustainable performance with the firm’s level orientation for the MEs. The study brings forward the practical implication for business and policymakers that the MEs require internal and external support to align the business and networking orientation to harness the sustainable performance among the MEs. In the end, the study limitations and future research options are highlighted.
Neural Correlates of Reactive Aggression in Adult Attention-Deficit/Hyperactivity Disorder
Authors: Jakobi Babette , Arias-Vasquez Alejandro , Hermans Erno , Vlaming Priscilla , Buitelaar Jan , Franke Barbara , Hoogman Martine , van Rooij Daan
Published: May 2022

Despite not being part of the core diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD), emotion dysregulation is a highly prevalent and clinically important component of (adult) ADHD. Emotionally dysregulated behaviors such as reactive aggression have a significant impact on the functional outcome in ADHD. However, little is known about the mechanisms underlying reactive aggression in ADHD. In this study, we aimed to identify the neural correlates of reactive aggression as a measure of emotionally dysregulated behavior in adults with persistent ADHD during implicit emotion regulation processes. We analyzed associations of magnetic resonance imaging-based whole-brain activity during a dynamic facial expression task with levels of reactive aggression in 78 adults with and 78 adults without ADHD, and also investigated relationships of reactive aggression with symptoms and impairments. While participants with ADHD had higher reactive aggression scores than controls, the neural activation patterns of both groups to processing of emotional faces were similar. However, investigating the brain activities associated with reactive aggression in individuals with and without ADHD showed an interaction of diagnosis and reactive aggression scores. We found high levels of activity in the right insula, the hippocampus, and middle and superior frontal areas to be particularly associated with high reactive aggression scores within the ADHD group. Furthermore, the limbic activity was associated with more hyperactivity/impulsivity symptoms. These results suggest a partly differential mechanism associated with reactive aggression in ADHD as compared to controls. Emotional hyper-reactivity in the salience network as well as more effortful top–down regulation from the self-regulation network might contribute to emotionally dysregulated behavior as measured by reactive aggression.
Sirtuin Type 1 Mediates the Antidepressant Effect of S-Ketamine in a Chronic Unpredictable Stress Model
Authors: Hou Lanwei , Miao Jingyu , Meng Haiwei , Liu Xiao , Wang Di , Tan Yawen , Li Chuangang
Published: May 2022

Background

Major depressive disorder (MDD) refers to a mental disease with complex pathogenesis and treatment mechanism. S-ketamine exhibited high effectiveness in treating MDD. However, the pharmacological activity of S-ketamine has not been reported yet.

Materials and Methods

In this study, depression-like characteristics were induced by chronic unpredictable stress (CUS). After S-ketamine (15 mg/kg) was intraperitoneally injected, the behaviors of mice were tested by conducting open-field test, elevated plus maze test, tail suspension test, and forced swimming test. Bilateral injection of sirtuin type 1 (SIRT1) inhibitor EX-527 was injected into the medial prefrontal cortex (mPFC) to upregulate the SIRT1 expression. The expression of SIRT1 and brain-derived neurotrophic factor (BDNF) was detected by conducting Western blot and immunofluorescence assays. Meanwhile, the synaptic ultrastructure was detected by transmission electron microscopy.

Results

In this study, the mice showed depression-like behavior in a series of behavioral tests. After the treatment with S-ketamine, the depression-like behavior stopped. Further, the synaptic ultrastructure in mPFC, including the decreased curvature of the post synaptic density and thinning of the postsynaptic density, improved after the S-ketamine treatment. Moreover, we found that S-ketamine had the possibility of spontaneous binding with SIRT1 at the molecular level and reversed CUS-induced SIRT1 reduction. Meanwhile, a positive relationship between SIRT1 and BDNF expression in mPFC and SIRT1 inhibitor limited the role of S-ketamine in reducing the depression-like behavior and increasing the BDNF level.

Conclusion

S-ketamine upregulated the SIRT1-mediated BDNF in mPFC and reversed the synaptic structural defects caused by CUS. SIRT1 is a mediator of S-ketamine in alleviating depression-like behavior.
Predicting Managers' Mental Health Across Countries: Using Country-Level COVID-19 Statistics
Authors: Li Lun , Zhang Stephen X. , Graf-Vlachy Lorenz
Published: May 2022

Background

There is limited research focusing on publicly available statistics on the Coronavirus disease 2019 (COVID-19) pandemic as predictors of mental health across countries. Managers are at risk of suffering from mental disorders during the pandemic because they face particular hardship.

Objective

We aim to predict mental disorder (anxiety and depression) symptoms of managers across countries using country-level COVID-19 statistics.

Methods

A two-wave online survey of 406 managers from 26 countries was performed in May and July 2020. We used logistic panel regression models for our main analyses and performed robustness checks using ordinary least squares regressions. In the sample, 26.5% of managers reached the cut-off levels for anxiety (General Anxiety Disorder-7; GAD-7) and 43.5% did so for depression (Patient Health Questionnaire-9; PHQ-9) symptoms.

Findings

We found that cumulative COVID-19 statistics (e.g., cumulative cases, cumulative cases per million, cumulative deaths, and cumulative deaths per million) predicted managers' anxiety and depression symptoms positively, whereas daily COVID-19 statistics (daily new cases, smoothed daily new cases, daily new deaths, smoothed daily new deaths, daily new cases per million, and smoothed daily new cases per million) predicted anxiety and depression symptoms negatively. In addition, the reproduction rate was a positive predictor, while stringency of governmental lockdown measures was a negative predictor. Individually, we found that the cumulative count of deaths is the most suitable single predictor of both anxiety and depression symptoms.

Conclusions

Cumulative COVID-19 statistics predicted managers' anxiety and depression symptoms positively, while non-cumulative daily COVID-19 statistics predicted anxiety and depression symptoms negatively. Cumulative count of deaths is the most suitable single predictor of both anxiety and depression symptoms. Reproduction rate was a positive predictor, while stringency of governmental lockdown measures was a negative predictor.
Association Between Residence Status Regularization and Access to Healthcare for Undocumented Migrants in Switzerland: A Panel Study
Authors: Fakhoury Julien , Burton-Jeangros Claudine , Consoli Liala , Duvoisin Aline , Jackson Yves
Published: May 2022

Background

Switzerland has a universal healthcare system. Yet, undocumented migrants face barriers at different levels that hinder their access to healthcare services. The aim of this study is to assess whether undocumented migrants' healthcare utilization improves with residence status regularization.

Methods

We used two-wave panel data from the Parchemins study, a study exploring the impact of regularization on undocumented migrants' health in Geneva, Switzerland. First wave data were collected between 2017 and 2018, second wave data between 2019 and 2020. At baseline, the sample consisted of 309 undocumented migrants, recruited after the implementation of a temporary regularization policy in Geneva. We distributed them into two groups according to their residence status 12 months before the second data collection [regularized vs. undocumented (controls)]. Using as dependent variable the number of medical consultations within two distinct 12-months periods (the first before regularization, the second after regularization), we conducted multivariable regression analyses applying hurdle specification to identify factors enhancing healthcare utilization. Then, we estimated first-difference panel models to assess change in healthcare utilization along regularization. Models were adjusted for demographic, economic and health-related factors.

Results

Of the 309 participants, 68 (22%) were regularized. For the 12 months before regularization, these migrants did not significantly differ in their healthcare utilization from the controls. At this stage, factors increasing the odds of having consulted at least once included being a female (aOR: 2.70; 95% CI: 1.37–5.30) and having access to a general practitioner (aOR: 3.15; 95% CI: 1.62–6.13). The factors associated with the number of consultations apart from underlying health conditions were the equivalent disposable income (aIRR per additional CHF 100.-: 0.98; 95% CI: 0.97–1.00) and having access to a general practitioner (aIRR: 1.45; 95% CI: 1.09–1.92). For the 12 months after regularization, being regularized was not associated with higher odds of having consulted at least once. However, among participants who consulted at least once, regularized ones reported higher counts of medical consultations than controls (3.7 vs. 2.6, p = 0.02), suggesting a positive impact of regularization. Results from the first-difference panel models confirmed that residence status regularization might have driven migrants' healthcare utilization (aβ: 0.90; 95% CI: 0.31-1.77).

Conclusions

This study supports the hypothesis that residence status regularization is associated with improved healthcare utilization among undocumented migrants. Future research is needed to understand the mechanisms through which regularization improves undocumented migrants' use of healthcare services.