bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Prognosis of Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis Who Underwent Teratoma Removal: An Observational Study
Authors: Zhang Hesheng , Xiong Weixi , Liu Xu , Liu Wenyu , Zhou Dong , Wu Xintong
Published: April 2022

Objective

This study aimed to evaluate the clinical characteristics and long-term surgical outcomes of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with teratoma.

Methods

Patients who were admitted to West China Hospital from June 2012 to June 2019 and diagnosed with anti-NMDAR encephalitis were enrolled in the study. Medical records were reviewed prospectively to gather clinical characteristic data. Patients were followed up at long-term every 3 months.

Results

This study included 192 patients, among whom 21 (10.9%) were detected with having a teratoma. Patients included 20 women, with a mean age of 24.62 ± 7.61 years. Seizure and psychiatric symptoms were the most dominant symptoms in both groups, followed by memory deficits. Central hypoventilation (52.4 vs. 17%, p < 0.001) and decreased consciousness (71.4 vs. 31.3%, p = 0.002) were significantly more frequent in patients with teratoma than in those without. Moreover, the anti-NMDAR antibody titer was higher (p = 0.021) and the baseline modified Rankin scale score was lower (p = 0.004) in patients with teratoma than in those without. First-line immunotherapy was performed in 21 (100%) patients with teratoma and 167 (97.7%) patients without teratoma. All patients with teratoma had the tumor removed. During follow-up, two (9.5%) patients with teratoma and 11 (6.4%) patients without teratoma died, whereas 1 (4.8%) patient with teratoma and 37 (21.6%) patients without teratoma had relapses. Overall, 19 (90.5%) patients with teratoma and 151 (88.3%) patients without teratoma achieved favorable clinical outcomes at the final follow-up.

Conclusions

With early detection and removal of teratoma, most patients with anti-NMDAR encephalitis and teratoma achieved a favorable long-term prognosis.
Prepubertal Children With Metabolically Healthy Obesity or Overweight Are More Active Than Their Metabolically Unhealthy Peers Irrespective of Weight Status: GENOBOX Study
Authors: Llorente-Cantarero Francisco Jesús , Leis Rosaura , Rupérez Azahara I. , Anguita-Ruiz Augusto , Vázquez-Cobela Rocío , Flores-Rojas Katherine , González-Gil Esther M. , Aguilera Concepción M. , Moreno Luis A. , Gil-Campos Mercedes , Bueno Gloria
Published: April 2022

Background and Aim

The association of a metabolically healthy status with the practice of physical activity (PA) remains unclear. Sedentarism and low PA have been linked to increased cardiometabolic risk. The aim of this study was to evaluate the PA levels in metabolically healthy (MH) or unhealthy (MU) prepubertal children with or without overweight/obesity.

Methods

A total 275 children (144 boys) with 9 ± 2 years old were selected for the GENOBOX study. PA times and intensities were evaluated by accelerometry, and anthropometry, blood pressure, and blood biochemical markers were analyzed. Children were considered to have normal weight or obesity, and further classified as MH or MU upon fulfillment of the considered metabolic criteria.

Results

Classification resulted in 119 MH children (21% with overweight/obesity, referred to as MHO) and 156 MU children (47% with overweight/obesity, referred to as MUO). Regarding metabolic profile, MHO showed lower blood pressure levels, both systolic and diastolic and biochemical markers levels, such as glucose, Homeostatic Model Assessment of Insulin Resistance, triglycerides and higher HDL-c levels than MUO (P < 0.001). In addition, MHO children spent more time in PA of moderate intensity compared with MUO children. In relation to vigorous PA, MH normal weight (MHN) children showed higher levels than MUO children. Considering sex, boys spent more time engaged in moderate, vigorous, and moderate–vigorous (MV) PA than girls, and the number of boys in the MH group was also higher.

Conclusion

Prepubertal MHO children are less sedentary, more active, and have better metabolic profiles than their MUO peers. However, all children, especially girls, should increase their PA engagement, both in terms of time and intensity because PA appears to be beneficial for metabolic health status itself.
Fermentation With Pleurotus Ostreatus Enhances the Prebiotic Properties of Germinated Riceberry Rice
Authors: Soodpakdee Kanjana , Nacha Jutamat , Rattanachart Nattapol , Owatworakit Amorn , Chamyuang Sunita
Published: April 2022

Rice is the staple food for more than half of the world's population. In recent years, awareness of the health benefits of colored rice varieties and germinated rice has gradually increased. Riceberry rice (R), a black-purple variety, was germinated and subsequently fermented with Pleurotus ostreatus mycelium (M) to improve nutrient quality and prebiotic properties. The γ-aminobutyric acid (GABA) and β-glucan contents were measured daily for a total of 4 days. The prebiotic activities of R, germinated Riceberry rice (GR), and germinated Riceberry rice with mycelium (GRM) were evaluated on the probiotic bacteria Pediococcus sp., Lactobacillus acidophilus, and Streptococcus lactis. Results were compared with the M treatment and with the commercial prebiotic agents: inulin and β-glucan. The treatments were also used to evaluate growth of the pathogen Escherichia coli. The GABA content peaked after 3 days of germination. The GR sample fermented with M for 3 days had the optimal concentration of both β-glucan and GABA. Evaluation of the prebiotic properties of rice samples and the commercial standards (inulin and β-glucan) showed that these were enhanced on the GR and GRM treatments. Results also showed the improvement of prebiotic properties on GR as the R sample did not show any prebiotic properties in all probiotic bacteria, whereas the GR sample showed moderate prebiotic activity score of 0.40, 0.88, and 0.56 on Pediococcus sp., L. acidophilus, and S. lactis, respectively. Furthermore, the prebiotic activity of GR was improved when fermented with M. For further applications, the GRM could be used on rice-based products, such as rice flour, rice crackers, or other rice products to enhance nutritional value and improve digestive system health, especially in the elderly.
Fructose Induces Insulin Resistance of Gestational Diabetes Mellitus in Mice via the NLRP3 Inflammasome Pathway
Authors: Liu Yao , Wei Yuanhuan , Wu Lanlan , Lin Xiaoping , Sun Ruifang , Chen Hengying , Shen Siwen , Deng Guifang
Published: April 2022

Background

Insulin resistance (IR), which is affected by dietary factors, is the main pathology underlying of gestational diabetes mellitus (GDM). Fructose (Fru), a sugar found in fruits, honey, and food sweeteners, has been reported to induce IR and inflammation. This study explored the effects and mechanisms of Fru on IR of GDM in pregnant and postpartum mice and their offspring.

Methods

The 6-week-old female C57BL/6J mice were randomly divided into control (Chow) and fructose (Fru) groups, with the latter receiving 20% (w/v) Fru in drinking water from 2 weeks before pregnancy to the end of pregnancy. The effects of Fru on IR and inflammation were determined using serum parameters, glucose metabolism tests, immunohistochemistry, and western blotting.

Results

Compared with the Chow group mice, pregnant mice treated with Fru exhibited greater gestational weight gain, higher fasting blood glucose and insulin concentrations, and a higher homeostasis model of assessment (HOMA) for IR index, but a lower HOMA for insulin sensitivity index. Treatment with Fru also increased the concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-17, and C-reactive protein in sera and the expression of IL-6, TNF-α, IL-17, and IL-1β mRNA in liver tissues of pregnant mice. Both CD68 and IL-1β positive cell were increased in Fru-treated mice compared with in Chow mice. Fru treatment also promoted IR and inflammation in mice at 4 weeks after delivery and in offspring mice. Mechanistically, Fru promoted the nuclear translocation of nuclear factor-kappa B (NF-κB) p65 to activate the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome.

Conclusions

Exposure to Fru before and during pregnancy induced IR in pregnant mice, which continued at 4 weeks postpartum and affected the offspring. The effects of Fru may be associated with activation of the NF-κB–NLRP3 pathway.
EVOO Promotes a Less Atherogenic Profile Than Sunflower Oil in Smooth Muscle Cells Through the Extracellular Vesicles Secreted by Endothelial Cells
Authors: Santiago-Fernandez Concepción , Rodríguez-Díaz Cristina , Ho-Plagaro Ailec , Gutierrez-Repiso Carolina , Oliva-Olivera Wilfredo , Martin-Reyes Flores , Mela Virginia , Bautista Rocío , Tome Mónicas , Gómez-Maldonado Josefa , Tinahones Francisco J. , Garcia-Fuentes Eduardo , Garrido-Sánchez Lourdes
Published: April 2022

Background

Little is known about the effect of extra virgin olive (EVOO) and sunflower oil (SO) on the composition of extracellular vesicles (EVs) secreted by endothelial cells and the effects of these EVs on smooth muscle cells (SMCs). These cells play an important role in the development of atherosclerosis.

Methods

We evaluated the effects of endothelial cells-derived EVs incubated with triglyceride-rich lipoproteins obtained after a high-fat meal with EVOO (EVOO-EVs) and SO (SO-EVs), on the transcriptomic profile of SMCs.

Results

We found 41 upregulated and 19 downregulated differentially expressed (DE)-miRNAs in EVOO-EVs. Afterwards, SMCs were incubated with EVOO-EVs and SO-EVs. SMCs incubated with SO-EVs showed a greater number of DE-mRNA involved in pathways related to cancer, focal adhesion, regulation of actin cytoskeleton, and MAPK, toll-like receptor, chemokine and Wnt signaling pathways than in SMCs incubated with EVOO-EVs. These DE-mRNAs were involved in biological processes related to the response to endogenous stimulus, cell motility, regulation of intracellular signal transduction and cell population proliferation.

Conclusion

EVOO and SO can differently modify the miRNA composition of HUVEC-derived EVs. These EVs can regulate the SMCs transcriptomic profile, with SO-EVs promoting a profile more closely linked to the development of atherosclerosis than EVOO-EVs.
Gadus morhua Eggs Sialoglycoprotein Prevent Estrogen Deficiency-Induced High Bone Turnover by Controlling OPG/RANKL/TRAF6 Pathway and Serum Metabolism
Authors: Zhao Meihui , Mei Fengfeng , Lu Jinfeng , Xiang Qingying , Xia Guanghua , Zhang Xueying , Liu Zhongyuan , Zhang Chenghui , Shen Xuanri , Zhong Qiuping
Published: April 2022

In recent years, the development of safe and effective anti-osteoporosis factors has attracted extensive attention. In this study, an estrogen-deficient osteoporosis rat model was employed to study the improving mechanism of sialoglycoprotein isolated from Gadus morhua eggs (Gds) against osteoporosis. The results showed that compared with OVX, Gds ameliorated the trabecular microstructure, especially the increased trabecular thickness, decreased trabecular separation, and enhanced the trabecular number. The analysis of qRT-PCR and western blotting found that Gds reduced bone resorption by inhibiting RANKL-induced osteoclastogenesis. The LC-MS/MS was used to investigate serum metabolism, and the enrichment metabolites were analyzed by the KEGG pathway. The results revealed that the Gds significantly altered the fat anabolism pathway, which includes ovarian steroidogenesis pathway and arachidonic acid metabolism pathway. Altogether, Gds could improve osteoporosis by suppressing high bone turnover via controlling OPG/RANKL/TRAF6 pathway, which is implicated with ovarian steroidogenesis pathway and arachidonic acid metabolism pathway. These findings indicated that Gds could be a candidate factor for anti-osteoporosis.
Quantifying Societal Burden of Radiation-Induced Cardiovascular Events in Breast Cancer Survivors
Authors: Kimpe Eva , Werbrouck Amber , De Ridder Mark , Putman Koen
Published: April 2022

Background and Purpose

Radiation-induced cardiotoxicity is an important health concern for clinicians during treatment of breast cancer (BC) patients. Underlying mechanisms are well-documented, whereas little is known about the societal impact of this long-term effect. This study aimed to quantify the additional burden of radiation-induced cardiovascular (CV) diseases in BC survivors.

Materials and Methods

Conventional health economic modelling techniques were applied to estimate attributed CV-related costs and disutility in a hypothetical cohort of BC survivors. A situation in which radiotherapy caused an additional CV risk was compared with a situation in which this risk was not taken into account. Uncertainty was assessedviadeterministic and probabilistic sensitivity analyses. Analyses were performed from a broad societal perspective up until 20 years after BC treatment.

Results

Radiation-induced cardiotoxicity evokes a mean incremental cost of €275.10 per woman over a time horizon of 20 years after BC treatment. An additional decrement of 0.017 QALYs (per woman) might be expected when taking the radiation-induced cardiotoxic risk into account in BC survivors. Incremental costs and disutility increased with age. A scenario analysis showed that these results were more profound in women with more advanced staging.

Conclusion

Our analyses suggest that with current radiation techniques, rather minor costs and disutility are to be expected from radiation-induced cardiotoxicity in BC survivors. The cost of past investments in order to achieve current mean heart dose (MHD) seems justified when considering the gains from cost and disutility reduction resulting from radiation-induced cardiovascular events. The question we might consider is whether future opportunity costs associated with investments on further technological advancements offset the expected marginal benefit from further reducing the MHD.
Single-Cell RNA Sequencing of Metastatic Testicular Seminoma Reveals the Cellular and Molecular Characteristics of Metastatic Cell Lineage
Authors: Mo Linjian , Yu Zhenyuan , Lv Yufang , Cheng Jiwen , Yan Haibiao , Lu Wenhao , Su Cheng , Ling Qiang , Mo Zengnan
Published: April 2022

Background

Testicular cancer is the most common solid malignancy in young men. Given the many histological classifications of testicular tumors, seminoma is one of the most treatable cancers. The survival rate in early-stage disease was more than 90%. Thus, seminoma at the cellular and molecular levels, especially at the single-cell level, is worth studying.

Methods

We performed a single-cell RNA sequencing (scRNA-seq) study on a patient who was diagnosed with testicular seminoma with lymph node metastasis. This study presented tumor tissue, PBMC, pelvic and renal hilus lymph node in a total of 18,206 high-quality single-cell transcriptome information. The characteristics of metastatic cell lineage were revealed by the comparison between different tumor cell subtypes at the scRNA level.

Results

A single-cell map of testicular seminoma with lymph node metastasis was constructed by scRNA-seq. We discovered the gene expression characteristics of the tumor cells in testicular seminoma, especially metastatic tumor cells. KRT8 and KRT18 were commonly expressed in the three tumor cell subtypes. However, TCF7L1, SCG3 and SV2C were the specifically expressed genes of tumor cell subtypes in primary tumor sites. Some molecular markers specifically expressed by the metastatic cell lineage, such as POU5F1, were identified.

Conclusions

We revealed the molecular characteristics of testicular seminoma at the single-cell level, especially the metastatic tumor cells. This study could provide new insights into the diagnosis and treatment of testicular seminoma.
Atypical Rearrangements in APL-Like Acute Myeloid Leukemias: Molecular Characterization and Prognosis
Authors: Guarnera Luca , Ottone Tiziana , Fabiani Emiliano , Divona Mariadomenica , Savi Arianna , Travaglini Serena , Falconi Giulia , Panetta Paola , Rapanotti Maria Cristina , Voso Maria Teresa
Published: April 2022

Acute promyelocytic leukemia (APL) accounts for 10–15% of newly diagnosed acute myeloid leukemias (AML) and is typically caused by the fusion of promyelocytic leukemia with retinoic acid receptor α (RARA) gene. The prognosis is excellent, thanks to the all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combination therapy. A small percentage of APLs (around 2%) is caused by atypical transcripts, most of which involve RARA or other members of retinoic acid receptors (RARB or RARG). The diagnosis of these forms is difficult, and clinical management is still a challenge for the physician due to variable response rates to ATRA and ATO. Herein we review variant APL cases reported in literature, including genetic landscape, incidence of coagulopathy and differentiation syndrome, frequent causes of morbidity and mortality in these patients, sensitivity to ATRA, ATO, and chemotherapy, and outcome. We also focus on non-RAR rearrangements, complex rearrangements (involving more than two chromosomes), and NPM1-mutated AML, an entity that can, in some cases, morphologically mimic APL.
Epidemiology and Clinical Characteristics of Human Coronaviruses-Associated Infections in Children: A Multi-Center Study
Authors: Jo Kyo Jin , Choi Soo-Han , Oh Chi Eun , Kim HyeonA , Choi Bong Seok , Jo Dae Sun , Park Su Eun
Published: April 2022

Background

Human coronaviruses (HCoVs) are associated with upper respiratory tract infections. Although studies have analyzed the clinical and epidemiological characteristics of HCoV-associated infections, no multi-center studies have been conducted in Korean children. We aimed to describe the epidemiology and clinical characteristics of HCoV-associated infection in children.

Methods

We retrospectively reviewed medical records of children in whom HCoVs were detected using multiplex reverse transcriptase-polymerase chain reaction amplification in five centers from January 2015 to December 2019.

Results

Overall, 1,096 patients were enrolled. Among them, 654 (59.7%) patients were male. The median age was 1 year [interquartile range (IQR), 0–2 years]. HCoVs were identified mainly in winter (55.9%). HCoV-229E, HCoV-OC43, and HCoOV-NL63 were detected mainly in winter (70.9, 55.8, and 57.4%, respectively), but HCoV-HKU1 was mainly identified in spring (69.7%). HCoV-OC43 (66.0%) was detected most frequently, followed by HCoV-NL63 (33.3%), and HCoV-229E (7.7%). Two different types of HCoVs were co-detected in 18 samples, namely. Alphacoronavirus-betacoronavirus co-infection (n = 13) and, alphacoronavirus-alphacoronavirus co-infection (n = 5). No betacoronavirus-betacoronavirus co-infection was detected. Patients were diagnosed with upper respiratory tract infection (41.4%), pneumonia (16.6%), acute bronchiolitis (15.5%), non-specific febrile illness (13.1%), croup (7.3%), and acute gastroenteritis (5.1%). There were 832 (75.9%) hospitalized patients with a median duration of hospitalization of 4 days (IQR, 3–5 days); 108 (9.9%) patients needed supplemental oxygen with 37 (3.4%) needing high-flow nasal cannula or mechanical ventilation. There were no deaths.

Conclusion

HCoV-associated infections exhibit marked seasonality with peaks in winter. Patients with lower respiratory tract infection, a history of prematurity, or underlying chronic diseases may progress to a severe course and may need oxygen therapy.
Maslinic Acid Attenuates Ischemia/Reperfusion-Induced Acute Kidney Injury by Suppressing Inflammation and Apoptosis Through Inhibiting NF-κB and MAPK Signaling Pathway
Authors: Sun Wenjuan , Choi Hong Sang , Kim Chang Seong , Bae Eun Hui , Ma Seong Kwon , Kim Soo Wan
Published: April 2022

Inflammation and apoptosis are the major contributors to the mechanisms of acute kidney injury (AKI) due to renal ischemia-reperfusion injury (IRI). Maslinic acid (MA), a pentacyclic triterpene acid mostly found in dietary plants, the current study was to demonstrate the renoprotective effect of MA on IRI-induced AKI, and to investigate the role of inflammation and apoptosis-related signaling pathways as a molecular mechanism. C57BL/6J mice were subjected to IRI for 72 h, and MA was daily administered by intraperitoneal injection during this period. In parallel, rat renal proximal tubule cells (NRK52E) were prophylactically treated with MA and then exposed to hydrogen peroxide (H2O2). MA treatment significantly inhibited the mRNA expression of interleukin (IL-1β), tumor necrosis factor-α (TGF-α), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1(ICAM-1). Also, MA reduced the expression of Bax/Bcl2 ratio and cleaved caspase-3. In NRK52 cells, MA inhibited the IκBα degradation, blocked NF-κB/p65 phosphorylation, and nuclear translocation. The phosphorylation of ERK, JNK, and p38 was attenuated by MA in IRI-induced kidney injury and H2O2-stimulated NRK52 cells. The expression levels of IL-1β, MCP-1, and ICAM-1 were upregulated in H2O2-stimulated NRK52E cells, which was attenuated by NF-κB inhibitor. H2O2 treatment increased the Bax/Bcl2 ratio and cleaved caspase-3 in NRK52E cells, which was counteracted by MAPK inhibitors. Together, our data demonstrate that MA suppresses IR-induced AKI injury through NF-κB and MAPK signaling pathways and that MA is a promising agent in the treatment of kidney diseases.
Safety of Off-Label Pharmacological Treatment in Pediatric Neuropsychiatric Disorders: A Global Perspective From an Observational Study at an Italian Third Level Children’s Hospital
Authors: Giurin Maria Sole , Trojniak Marta Paulina , Arbo Anna , Carrozzi Marco , Abbracciavento Giuseppe , Monasta Lorenzo , Zanus Caterina
Published: April 2022

Background: The acquisition of proper and relevant pediatric clinical data is essential to ensure tolerable and effective pediatric drug therapies. In the field of pharmacological treatment of neuropsychiatric disorders, the lack of sufficient high quality scientific evidence for pediatric age results in the frequent need to prescribe off-label drugs. With the aim of improving knowledge about safety profile of off-label drug prescription in children and adolescent with neurological and/or psychiatric disorders, we realized a multidisciplinary pharmacovigilance study.

Materials and methods: An observational retrospective study was conducted to assess the safety of off-label pharmacological therapies in patients aged 0–18 years, admitted to the Neuropsychiatry Unit of the Institute for Maternal and Child Health - IRCCS “Burlo Garofolo” between January 2016 and December 2018. Prescription patterns and adverse drug reactions were evaluated by a multidisciplinary team.

Results: Overall, 230 patients were enrolled, 48% boys (N = 111), 52% girls (N = 119), average age of 10 years, and a total of 534 prescriptions was analyzed. 54.5% (N = 125) of patients had epilepsy, 37.5% (N = 86) suffered from psychiatric disorders, 8% (N = 19) had other neurological disorders. The prevalence of off-label prescriptions was 32% and 50% of the study population received at least one off-label drug. A total of 106 ADRs was detected: 57% of ADRs were due to drug-drug interactions, 30% were due to off-label prescriptions, 10% were due to overdose and 3% were due to improper use. No significant association between emerged ADRs and off label prescriptions was found (Fisher’s exact two-tailed test, p = 1.000). There was significant association between increasing number of administrated drugs and risk of ADRs (OR 1.99; IC95% 1.58–2.5; p = 0.000). Psychiatric disorders were associated with at least three times higher risk to be treated with an off-label drug (OR 3.30; IC95% 2.26–4.83; p = 0.000).

Conclusions: This study shows that off-label prescribing in neuropsychiatric disorders does not pose a greater risk of ADRs than on-label prescribing and highlights unmet clinical needs in pediatric neuropsychopharmacology. The multidisciplinary approach can provide important contributions to improve therapeutic path of these already complex pathologies by careful monitoring of therapeutic appropriateness and drug interactions.
The Musculoskeletal Involvement After Mild to Moderate COVID-19 Infection
Authors: dos Santos Patty K. , Sigoli Emilly , Bragança Lorenna J.G. , Cornachione Anabelle S.
Published: April 2022

COVID-19, a disease caused by the novel coronavirus SARS-CoV-2, has been drastically affecting the daily lives of millions of people. COVID-19 is described as a multiorgan disease that affects not only the respiratory tract of infected individuals, but it has considerable effects on the musculoskeletal system, causing excessive fatigue, myalgia, arthralgia, muscle weakness and skeletal muscle damage. These symptoms can persist for months, decreasing the quality of life of numerous individuals. Curiously, most studies in the scientific literature focus on patients who were hospitalized due to SARS-CoV-2 infection and little is known about the mechanism of action of COVID-19 on skeletal muscles, especially of individuals who had the mild to moderate forms of the disease (non-hospitalized patients). In this review, we focus on the current knowledge about the musculoskeletal system in COVID-19, highlighting the lack of researches investigating the mild to moderate cases of infection and pointing out why it is essential to care for these patients. Also, we will comment about the need of more experimental data to assess the musculoskeletal manifestations on COVID-19-positive individuals.
Potential Role of the Retrotrapezoid Nucleus in Mediating Cardio-Respiratory Dysfunction in Heart Failure With Preserved Ejection Fraction
Authors: Toledo Camilo , Ortolani Domiziana , Ortiz Fernando C. , Marcus Noah J. , Del Rio Rodrigo
Published: April 2022

A strong association between chemoreflex hypersensitivity, disordered breathing, and elevated sympathetic activity has been shown in experimental and human heart failure (HF). The contribution of chemoreflex hypersensitivity in HF pathophysiology is incompletely understood. There is ample evidence that increased peripheral chemoreflex drive in HF with reduced ejection fraction (HFrEF; EF<40%) leads to pathophysiological changes in autonomic and cardio-respiratory control, but less is known about the neural mechanisms mediating cardio-respiratory disturbances in HF with preserved EF (HFpEF; EF>50%). Importantly, it has been shown that activation of the central chemoreflex worsens autonomic dysfunction in experimental HFpEF, an effect mediated in part by the activation of C1 catecholaminergic neurons neighboring the retrotrapezoid nucleus (RTN), an important region for central chemoreflex control of respiratory and autonomic function. Accordingly, the main purpose of this brief review is to discuss the possible role played by activation of central chemoreflex pathways on autonomic function and its potential role in precipitating disordered breathing in HFpEF. Improving understanding of the contribution of the central chemoreflex to the pathophysiology of HFpEF may help in development of novel interventions intended to improve cardio-respiratory outcomes in HFpEF.
The Role of the Melatoninergic System in Circadian and Seasonal Rhythms—Insights From Different Mouse Strains
Authors: Pfeffer Martina , von Gall Charlotte , Wicht Helmut , Korf Horst-Werner
Published: April 2022

The melatoninergic system comprises the neurohormone melatonin and its molecular targets. The major source of melatonin is the pineal organ where melatonin is rhythmically produced during darkness. In mammals, melatonin biosynthesis is controlled by the central circadian rhythm generator in the suprachiasmatic nucleus (SCN) and photoreceptors in the retina. Melatonin elicits its function principally through two specific receptors called MT1 and MT2. MT1 is highly expressed in the SCN and the hypophysial pars tuberalis (PT), an important interface for control of seasonal functions. The expression of the MT2 is more widespread. The role of the melatoninergic system in the control of seasonal functions, such as reproduction, has been known for more than 4 decades, but investigations on its impact on the circadian system under normal (entrained) conditions started 2 decades later by comparing mouse strains with a fully functional melatoninergic system with mouse strains which either produce insufficient amounts of melatonin or lack the melatonin receptors MT1 and MT2. These studies revealed that an intact melatoninergic system is not required for the generation or maintenance of rhythmic behavior under physiological entrained conditions. As shown by jet lag experiments, the melatoninergic system facilitated faster re-entrainment of locomotor activity accompanied by a more rapid adaptation of the molecular clock work in the SCN. This action depended on MT2. Further studies indicated that the endogenous melatoninergic system stabilizes the locomotor activity under entrained conditions. Notably, these effects of the endogenous melatoninergic system are subtle, suggesting that other signals such as corticosterone or temperature contribute to the synchronization of locomotor activity. Outdoor experiments lasting for a whole year indicate a seasonal plasticity of the chronotype which depends on the melatoninergic system. The comparison between mice with an intact or a compromised melatoninergic system also points toward an impact of this system on sleep, memory and metabolism.
Arabidopsis Novel Microgametophyte Defective Mutant 1 Is Required for Pollen Viability via Influencing Intine Development in Arabidopsis
Authors: Mi Limin , Mo Aowei , Yang Jiange , Liu Hui , Ren Ding , Chen Wanli , Long Haifei , Jiang Ning , Zhang Tian , Lu Pingli
Published: April 2022

The pollen intine layer is necessary for male fertility in flowering plants. However, the mechanisms behind the developmental regulation of intine formation still remain largely unknown. Here, we identified a positive regulator, Arabidopsis novel microgametophyte defective mutant 1 (AtNMDM1), which influences male fertility by regulating intine formation. The AtNMDM1, encoding a pollen nuclei-localized protein, was highly expressed in the pollens at the late anther stages, 10–12. Both the mutations and the knock-down of AtNMDM1 resulted in pollen defects and significantly lowered the seed-setting rates. Genetic transmission analysis indicated that AtNMDM1 is a microgametophyte lethal gene. Calcofluor white staining revealed that abnormal cellulose distribution was present in the aborted pollen. Ultrastructural analyses showed that the abnormal intine rather than the exine led to pollen abortion. We further found, using transcriptome analysis, that cell wall modification was the most highly enriched gene ontology (GO) term used in the category of biological processes. Notably, two categories of genes, Arabinogalactan proteins (AGPs) and pectin methylesterases (PMEs) were greatly reduced, which were associated with pollen intine formation. In addition, we also identified another regulator, AtNMDM2, which interacted with AtNMDM1 in the pollen nuclei. Taken together, we identified a novel regulator, AtNMDM1 that affected cellulose distribution in the intine by regulating intine-related gene expression; furthermore, these results provide insights into the molecular mechanisms of pollen intine development.
S-Nitrosoglutathione Reductase Contributes to Thermotolerance by Modulating High Temperature-Induced Apoplastic H2O2 in Solanum lycopersicum
Authors: Song Xuewei , Wang Ting , Zhang Yang , Yu Jing-Quan , Xia Xiao-Jian
Published: April 2022

S-nitrosoglutathione reductase (GSNOR) is considered as a critical regulator of plant stress tolerance for its impacts on protein S-nitrosylation through regulation of the S-nitrosothiol (SNO) level. However, the mechanism of GSNOR-mediated stress tolerance is still obscure. Here, we found that GSNOR activity was induced by high temperature in tomato (Solanum lycopersicum) plants, whereas mRNA level of SlGSNOR1 exhibited little response. Suppressing SlGSNOR1 expression by virus-induced gene silencing (VIGS) increased accumulation of SNO and nitrites under high temperature and reduced thermotolerance. The compromised thermotolerance was associated with less accumulation of abscisic acid (ABA) and salicylic acid (SA), attenuated activation of mitogen-activated protein kinase (MAPK) and reduced expression of heat shock protein. Intriguingly, SlGSNOR1 silencing impaired upregulation of RESPIRATORY BURST OXIDASE HOMOLOG1 (SlRBOH1) and apoplastic H2O2 accumulation in response to high temperature, whereas SlRBOH1 silencing abolished activation of GSNOR and led to a similar decline in thermotolerance as in SlGSNOR1-silenced plants. Importantly, H2O2 treatment recovered the thermotolerance and improved antioxidant capacity in SlGSNOR1-silenced plants. Our results suggest that GSNOR plays a role in regulating the SlRBOH1-dependent apoplastic H2O2 production in response to high temperature, while a balanced interaction between SNO and H2O2 is critical for maintaining the cellular redox homeostasis and thermotolerance.
Relationships Between Basic Psychological Need Satisfaction, Regulations, and Behavioral Engagement in Mathematics
Authors: Hofverberg Anders , Winberg Mikael , Palmberg Björn , Andersson Catarina , Palm Torulf
Published: April 2022

Behavioral engagement is a key determinant of students’ learning. Hence, knowledge about mechanisms affecting engagement is crucial for educators and stakeholders. Self-determination theory (SDT) offers a framework to understand one of these mechanisms. However, extant studies mostly consider only parts of SDT’s theoretical paths from basic psychological need satisfaction via regulations to student engagement. Studies that investigate the full model are rare, especially in mathematics, and results are inconclusive. Moreover, constructs are often merged in ways that may preclude detailed understanding. In this study, we used structural equation modeling to test several hypothesized paths between the individual variables that make up higher-order constructs of need satisfaction, regulations, and behavioral engagement. Satisfaction of the need for competence had a dominating effect on engagement, both directly and via identified regulation. Similarly, satisfaction of the need for relatedness predicted identified regulation, that in turn predicted engagement. Satisfaction of the need for autonomy predicted intrinsic regulation as expected but, in contrast to theory, was also positively associated with controlled motivation (external and introjected regulation). Neither intrinsic nor controlled regulation predicted engagement. Theoretical and method-related reasons for this unexpected pattern are discussed, as well as implications for research and teaching.
From Entrepreneurship Education, Government Support, and Global Competence to Entrepreneurial Behavior: The Serial Double Mediating Effect of the Self-Efficacy and Entrepreneurial Intention
Authors: Zhang Jinzi , Li Bing , Zhang Yanning , Gong Chi , Liu Ziyang
Published: April 2022

Entrepreneurship plays a significant role in promoting the social and economic development of a country. At present, entrepreneurship education is widely carried out in universities and colleges in order to improve students’ entrepreneurial ability, and then to provide support for the formation of a comprehensive entrepreneurial situation. As entrepreneurship education has gradually become a hot topic of teaching for innovation and entrepreneurship education of international students, studies on the influencing mechanism of entrepreneurship education of international students in relation to their entrepreneurial behavior are conducive to providing theoretical basis and empirical evidence for international students’ entrepreneurship education, so as to pertinently guide international students’ innovation and entrepreneurship practice. This study aims to explore the influence of entrepreneurship education, government support for entrepreneurship, global competence, entrepreneurial self-efficacy, and entrepreneurial intention on the entrepreneurial behavior of international students in the Republic of Korea (“Korea”). It summarized and drew on the results of the existing literature research. According to the contents and points of research, this study takes the international students studying in Korea as the sample and uses statistical analysis software, SPSS 22.0 and AMOS 24.0, to establish a structural equation model to conduct empirical study on the influencing mechanism of entrepreneurial behavior of international students in Korea, so as to better understand the influence of entrepreneurship education in Korean universities and colleges on entrepreneurial behavior of international students in Korea. Based on the analysis results, this study puts forward the theoretical basis for the policies related to effective management of entrepreneurship, which will help alleviate the unemployment of young people studying in Korea and the tight labor market supply and demand.
Scaling Up of Nature-Based Solutions to Guide Climate Adaptation Planning: Evidence From Two Case Studies
Authors: Cilliers Elizelle Juanee , Timmermans Wim , Rohr Hildegard , Goosen Hasse
Published: April 2022

Nature-based solutions are gaining importance within the notion of urban sustainability problems and associated global goals. This paper argues that nature-based solutions could guide climate adaptation planning, but it would need to be scaled-up across the globe to have an effective impact on climate adaptation. Literature poses various proposals of how to include nature-based solutions to guide adaptation planning, but practical examples and evidence of such are more limited. This paper addresses this lack by providing examples of two case studies, one in the Netherlands (Amersfoort) and one in South Africa (Lephalale). These two case studies were purposefully selected based on the nature-based approaches they employed in response to climate change challenges. The cases were accordingly considered in terms of their socio-ecological and environmental context, the scale of implementation of the nature-based solutions, the flexibility of these responses employed, and the overall benefits provided through the nature-based approaches. A comparative analysis was conducted between the two cases and highlighted that nature-based approaches could not be limited to a singular ad-hoc approach, but should rather be scaled up and more comprehensive, in order to align with the objectives of climate adaptation planning. The cases evidenced how the broader environment could benefit when nature-based solutions are scaled up to guide climate adaptation.
Let's Get Back to Normal? COVID-19 and the Logic of Cure
Authors: Berghs Maria
Published: April 2022

The COVID-19 pandemic has inversed certainties of absolutes of cure in everyday life but paradoxically this has occurred during a time when novel scientific advancements seem to herald a new frontier of cures for rare diseases, chronic conditions, disabilities and viruses that were previously incurable. In this paper, I illustrate the development of a logic of cure by first of all noting a lacuna in the medical sociological and anthropological literature, where although a lot of empirical research and theoretical work to understand cure has been undertaken, there has been no sociology or anthropology of cure. Using three case studies, I examine what they reveal about the logic of cure. Firstly, I argue that there is a development of a bioethics of cure in reactions of disability community and disabled people to care as cure during the COVID-19 pandemic. The second case-study focuses on understanding limitations of vaccines and how people react against such indeterminancies of loss of absolutes of cure. Lastly, the final case study describes how while there are cures, for example, for rare genetic conditions, they are often initially curated with long-term cost-benefit analysis for the Global North. In conclusion, it is found that many of the developments within sociology and anthropology are missing from a logic of cure and that a new theory of cure has to develop.
Neighborhood Walking and Social Connectedness
Authors: Glover Troy D. , Todd Joe , Moyer Luke
Published: April 2022

Neighborhood social ties matter crucially, especially during stressful life events like a global pandemic, for they represent vital sources of wellbeing and community capacity. Activities that enable community members to engage in incidental sociability and acts of “neighboring”—that is, authentic social interactions with their neighbors—warrant attention from sport and active living researchers because of their potential to bolster the social fabric of our neighborhoods and facilitate neighbors' access to important resources, such as information, material resources, and social support. Though perhaps dismissed as trivial, neighborhood walking represents a valuable and underappreciated everyday activity that fits this description, especially in an age characterized by an epidemic of social isolation and loneliness. Despite its vast potential to address the quasi-anonymity of urban life, neighborhood walking remains surprisingly underexamined as a facilitator for fostering social connectedness, the sense of connection and social bond people feel toward others. The goal of this manuscript, therefore, is to establish the conceptual grounding for how neighborhood walking strengthens social ties among neighbors to facilitate access to important coping resources. In doing so, it aims to advance a research agenda on walking that moves beyond the benefits of physical activity.
Insights Into Long Non-Coding RNA and mRNA Expression in the Jejunum of Lambs Challenged With Escherichia coli F17
Authors: Chen Weihao , Lv Xiaoyang , Zhang Weibo , Hu Tingyan , Cao Xiukai , Ren Ziming , Getachew Tesfaye , Mwacharo Joram M. , Haile Aynalem , Sun Wei
Published: April 2022

It has long been recognized that enterotoxigenic Escherichia coli (ETEC) is the major pathogen responsible for vomiting and diarrhea. E. coli F17, a main subtype of ETEC, is characterized by high morbidity and mortality in young livestock. However, the transcriptomic basis underlying E. coli F17 infection has not been fully understood. In the present study, RNA sequencing was conducted to explore the expression profiles of mRNAs and long non-coding RNAs (lncRNAs) in the jejunum of lambs who were identified as resistant or sensitive to E. coli F17 that was obtained in a challenge experiment. A total of 772 differentially expressed (DE) mRNAs and 190 DE lncRNAs were detected between the E. coli F17—resistance and E. coli F17-sensitive lambs (i.e., TFF2, LOC105606142, OLFM4, LYPD8, REG4, APOA4, TCONS_00223467, and TCONS_00241897). Then, a two-step machine learning approach (RX) combination Random Forest and Extreme Gradient Boosting were performed, which identified 16 mRNAs and 17 lncRNAs as potential biomarkers, within which PPP2R3A and TCONS_00182693 were prioritized as key biomarkers involved in E. coli F17 infection. Furthermore, functional enrichment analysis showed that peroxisome proliferator-activated receptor (PPAR) pathway was significantly enriched in response to E. coli F17 infection. Our finding will help to improve the knowledge of the mechanisms underlying E. coli F17 infection and may provide novel targets for future treatment of E. coli F17 infection.
C-Type Natriuretic Peptide Regulates the Expression and Secretion of Antibacterial Peptide S100A7 in Goat Mammary Gland Through PKG/JNK/c-Jun Signaling Pathway
Authors: Fan Mingzhen , Miao Yuyang , Yan Yutong , Zhu Kunyuan , Zhao Xiaoe , Pan Menghao , Ma Baohua , Wei Qiang
Published: April 2022

During infection, the infected tissue secretes a variety of endogenous peptides to resist further invasion of pathogens. Among these endogenous peptides, the natriuretic peptides and the antimicrobial peptides attracted the most attention. C-type natriuretic peptide (CNP) and its receptor natriuretic peptide receptor B (NPR-B) were members of the natriuretic peptide system. The antimicrobial peptide S100A7 plays an important role to resist infection of bacteria in mastitis. It is reported that the expression of S100A7 is regulated by an activator protein-1 (AP-1)-responsive promoter. As a subunit of AP-1, c-Jun is a downstream target of CNP/NPR-B signaling pathway. Therefore, it is a hypothesis that the CNP/NPR-B signaling pathway induces the expression and secretion of S100A7 in mammary glands to take part in local mammary gland innate immunity. To verify this hypothesis, goat mammary gland and isolated mammary epithelial cells (MECs) were used to explore the expression of CNP/NPR-B and their physiological roles in goat mammary gland. The results showed that goat mammary gland expressed NPR-B, but not CNP. The expression and secretion of S100A7 in goat MECs were obviously induced by CNP/NPR-B signaling pathway. After treatment with CNP, the cyclic guanosine monophosphate (cGMP) level in goat MECs was significantly upregulated. Along with the upregulation of cGMP level, the phosphorylation levels of c-Jun N-terminal kinase (JNK) and its target c-Jun were also increased gradually. KT5823 is a specific inhibitor for protein kinase G (PKG). KT5823 remarkably inhibited the phosphorylation of JNK and c-Jun induced by CNP. Correspondingly, KT5823 evidently inhibited the expression and secretion of S100A7 induced by CNP. On the other hand, the expression of NPR-B and S100A7 was upregulated in the mastitis goat mammary gland. But, there was no significant difference in expression of CNP between healthy and mastitis goat mammary gland tissues. The goat mastitis model was established in vitro using goat MECs treated by lipopolysaccharide (LPS). LPS treatment also could increase the expression of NPR-B and S100A7. In conclusion, goat mammary gland expressed NPR-B, indicating mammary gland was the target organ for natriuretic peptide system. Moreover, CNP, through NPR-B/JNK/c-Jun signaling pathway to regulate the expression and secretion of S100A7 in MECs, played an important role in mammary gland innate immunity.
Investigation of Alberich Coating to Optimise Acoustic Stealth of Submarines
Authors: Daniels Callum , Perera Noel
Published: April 2022

Due to the nature of their deployment, very few people know the location and course of a submarine during its time at sea, including only a handful of the ship’s crew. The possibility of immediate retaliation by the UK and her allies is aided by the submarine’s ability to remain undetected by SONAR at all times. To investigate one method for improving acoustic stealth, a finite element model (FEM) was created on ANSYS to model a unit-cell of an Alberich coating and impeding sound wave representative of SONAR. A simplification of a widely used acoustic impedance equation was adopted into MATLAB code to attain values of impedance that were applied to the model in place of a water loading boundary. Using the results given by five sets of simulations, an optimised Alberich coating was modelled, containing a 26 mm spherical cavity, 40 mm anechoic layer and 30 mm long steel backplate. This optimised model improved the acoustic stealth of submarines by displaying greater acoustic absorption at both ends of the frequency range, compared with other models used, showing that Alberich-style coatings can be used to improve acoustic stealth, to combat new low-frequency SONAR.