bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric CIDP: Diagnosis and Management. A Single-Center Experience
Authors: Łukawska Małgorzata , Potulska-Chromik Anna , Lipowska Marta , Hoffman-Zacharska Dorota , Olchowik Beata , Figlerowicz Magdalena , Kanabus Karolina , Rosiak Edyta , Kostera-Pruszczyk Anna
Published: July 2021

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare acquired polyneuropathy that especially among youngest children should be differentiated with hereditary neuropathies. Even though upon diagnosis treatment options are similar in children and adults, diagnostic challenges are faced in the pediatric population.

Methods: We conducted a retrospective analysis of clinical symptoms, nerve conduction study results, modes of treatment, and final outcome in 37 children aged 3.5–17 years with a final diagnosis of CIDP (18 girls, 19 boys). We established three groups of patients based on age at onset of CIDP: 0–4, 4–13, and 13–18 years. Follow-up ranged from 10 to 222 months.

Results: In our analysis, 19/37 patients (51.4%) had an atypical presentation: distal variant of CIDP in 12/37 patients (32.4%) and pure motor variant of CIDP in 5/37 patients (13.5%), and one patient had a pure sensory variant (1/37, 2.7%). Furthermore, 3/37 patients (8.1%) had additional concurring symptoms, including involuntary movements of face muscles (1/37, 2.7%) or hand tremor (2/37, 5.4%). During the follow-up, 23/37 patients (62.2%) received intravenous immunoglobulin (IVIg); 22/37 patients (59.5%) received steroids, 6/37 patients (16.2%) received IVIg and steroids, and 12/37 patients (32.4%) received immunosuppressive drugs, mostly azathioprine, but also methotrexate and rituximab. One patient was treated with plasmapheresis. Complete remission was achieved in 19/37 patients (51.4%) with CIDP in its typical form. Remission with residual symptoms or minimal deficit was observed in 4/37 patients (10.8%), whereas 14/37 patients (37.8%) remain on treatment with gradual improvement.

Conclusion: Childhood CIDP may occur in its typical form, but even ~50% of children can present as an atypical variant including distal, pure motor, or pure sensory. Most children have a good prognosis; however, many of them may require long-term treatment. This highlights the importance of an early diagnosis and treatment for childhood CIDP.
Case Report: Coexistence of Anti-AMPA Receptor Encephalitis and Positive Biomarkers of Alzheimer's Disease
Authors: Song Yu , Chen Shanshan , Gao Ju , Lu Jie , Xu Wenwen , Lin Xingjian , Chen Jiu
Published: July 2021

Anti–α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is a rare autoimmune disease that is characterized by acute cognitive impairment, mental symptoms, and seizures. The high comorbidity rate between anti–AMPA receptor (AMPAR) encephalitis and other somatic diseases, such as malignancy, has revealed the possibility of potential copathogenesis. However, there have not yet been reports about anti-AMPAR encephalitis with concomitant cerebrospinal fluid (CSF) biomarkers consistent with Alzheimer disease (AD). Herein, we present the case of an elderly male patient with autoimmune encephalitis (AE) presenting with anti–AMPA1-R and anti–AMPA2-R antibodies, as well as CSF biomarkers of AD. The patient was hospitalized with acute memory decline for 1 week. Anti–AMPA1-R and anti–AMPA2-R antibodies were positively detected in CSF, and the anti–AMPA2-R antibody was also present in the serum. Additionally, the biomarkers of AD were concurrently present in CSF (Aβ1−42 = 245.70 pg/mL, t-Tau = 894.48 pg/mL, p-Tau = 78.66 pg/mL). After administering a combined treatment of intravenous immunoglobulin and glucocorticoids, the patient recovered significantly, and his cognitive function achieved a sustained remission during 2 months' follow-up. This case raises the awareness of a possible interaction between AE and changes of CSF biomarkers. We speculated that the existence of AMPAR antibodies can induce changes of CSF, and other pathological alterations. This present report highlights that a potential relationship exists among AE and provides a warning when making the diagnosis of AD.
The Effects of Brain Serotonin Deficiency on Responses to High Fat Diet in Female Mice
Authors: Huq Shama N. , Warner Allison K. , Buckhaults Kerry , Sachs Benjamin D.
Published: July 2021

Clinical studies have reported an increased risk of depression and anxiety disorders among individuals who are obese, and women are more likely than men to suffer from depression, anxiety, and obesity. However, the effects of obesity-promoting diets on depression- and anxiety-like behavior remain controversial. A recent study from our group used the tryptophan hydroxylase 2 (R439H) knock-in mouse line to evaluate the impact of genetic brain serotonin (5-HT) deficiency on behavioral responses to high fat diet (HFD) in male mice. That study indicated that chronic exposure to HFD induced pro-anxiety-like effects in the open field test and antidepressant-like effects in the forced swim test in wild-type males. Interestingly, the antidepressant-like effect of HFD, but not the anxiogenic effect, was blocked by brain 5-HT deficiency in males. The current work sought to repeat these studies in females. Our new data suggest that females are less susceptible than males to HFD-induced weight gain and HFD-induced alterations in behavior. In addition, the effects of chronic HFD on the expression of inflammation-related genes in the hippocampus were markedly different in females than we had previously reported in males, and HFD was shown to impact the expression of several inflammation-related genes in a genotype-dependent manner. Together, our findings highlight the importance of brain 5-HT and sex in regulating behavioral and molecular responses to HFD. Our results may have important implications for our understanding of the clinically observed sex differences in the consequences of obesity.
Optimization of Task Allocation for Collaborative Brain–Computer Interface Based on Motor Imagery
Authors: Gu Bin , Xu Minpeng , Xu Lichao , Chen Long , Ke Yufeng , Wang Kun , Tang Jiabei , Ming Dong
Published: July 2021

Objective

Collaborative brain–computer interfaces (cBCIs) can make the BCI output more credible by jointly decoding concurrent brain signals from multiple collaborators. Current cBCI systems usually require all collaborators to execute the same mental tasks (common-work strategy). However, it is still unclear whether the system performance will be improved by assigning different tasks to collaborators (division-of-work strategy) while keeping the total tasks unchanged. Therefore, we studied a task allocation scheme of division-of-work and compared the corresponding classification accuracies with common-work strategy’s.

Approach

This study developed an electroencephalograph (EEG)-based cBCI which had six instructions related to six different motor imagery tasks (MI-cBCI), respectively. For the common-work strategy, all five subjects as a group had the same whole instruction set and they were required to conduct the same instruction at a time. For the division-of-work strategy, every subject’s instruction set was a subset of the whole one and different from each other. However, their union set was equal to the whole set. Based on the number of instructions in a subset, we divided the division-of-work strategy into four types, called “2 Tasks” … “5 Tasks.” To verify the effectiveness of these strategies, we employed EEG data collected from 19 subjects who independently performed six types of MI tasks to conduct the pseudo-online classification of MI-cBCI.

Main results

Taking the number of tasks performed by one collaborator as the horizontal axis (two to six), the classification accuracy curve of MI-cBCI was mountain-like. The curve reached its peak at “4 Tasks,” which means each subset contained four instructions. It outperformed the common-work strategy (“6 Tasks”) in classification accuracy (72.29 ± 4.43 vs. 58.53 ± 4.36%).

Significance

The results demonstrate that our proposed task allocation strategy effectively enhanced the cBCI classification performance and reduced the individual workload.
The Role of the Gastrointestinal System in Neuroinvasion by SARS-CoV-2
Authors: Xu Jiali , Wu Zifeng , Zhang Mi , Liu Shijiang , Zhou Ling , Yang Chun , Liu Cunming
Published: July 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the most devastating pandemics in history. SARS-CoV-2 has infected more than 100 million people worldwide, leading to more than 3.5 million deaths. Initially, the clinical symptoms of SARS-CoV-2 infection were thought to be restricted to the respiratory system. However, further studies have revealed that SARS-CoV-2 can also afflict multiple other organs, including the gastrointestinal tract and central nervous system. The number of gastrointestinal and neurological manifestations after SARS-CoV-2 infection has been rapidly increasing. Most importantly, patients infected with SARS-CoV-2 often exhibit comorbid symptoms in the gastrointestinal and neurological systems. This review aims to explore the pathophysiological mechanisms of neuroinvasion by SARS-CoV-2. SARS-CoV-2 may affect the nervous system by invading the gastrointestinal system. We hope that this review can provide novel ideas for the clinical treatment of the neurological symptoms of SARS-CoV-2 infection and references for developing prevention and treatment strategies.
Differences in Comorbidities and Clinical Burden of Severe Bronchopulmonary Dysplasia Based on Disease Severity
Authors: Kim Hye-Rim , Jung Young Hwa , Kim Beyong Il , Kim So Young , Choi Chang Won
Published: July 2021

Background: The present study compared baseline characteristics, comorbidities and clinical burden of pre-term infants with type 1 and 2 severe bronchopulmonary dysplasia (BPD) Collaborative classification.

Methods: This study was a prospective cohort study of pre-term (<32 weeks) very-low-birth-weight infants. Severe BPD was divided into type 1 severe BPD requiring of ≥30% oxygen and/or non-invasive ventilation at 36 weeks post-menstrual age (PMA), and type 2 severe BPD requiring invasive mechanical ventilation at 36 weeks PMA. Baseline characteristics, comorbidities, and clinical burden were compared between these two types of severe BPD.

Results: Of the 1,328 infants included, 983 (74.0%) developed type 1 severe BPD, and 345 (26.0%) developed type 2 severe BPD. Lower birth weight, small for gestational age, lesser maternal pre-mature rupture of membrane, lower 5-min Apgar score, air leak, pulmonary hemorrhage, surgical ligation of patent ductus arteriosus, necrotizing enterocolitis, and late-onset sepsis were significantly associated with type 2 severe BPD. Compared with infants with type 1 severe BPD, infants with type 2 severe BPD had an increased risk of mortality (aOR 18.64, 95% CI 10.81–32.13), pulmonary hypertension (aOR 2.16, 95% CI 1.59–2.93), and tracheostomy (aOR 10.38, 95% CI 2.05–52.49).

Conclusions: Our data highlight the substantially greater mortality and clinical burden in infants with type 2 severe BPD than infants with type 1 severe BPD. A comprehensive and multidisciplinary approach is needed for infants with type 2 severe BPD.
Case Report: Rapid Recognition and Immune Modulation of Secondary HLH Due to Disseminated HSV Infection
Authors: McKeone Daniel J. , DeMartini Theodore K. M. , Kavanagh Robert P. , Halstead E. Scott
Published: July 2021

We describe the case of a newborn who presented with multiple organ dysfunction syndrome (MODS) and hyperferritinemia, who eventually met criteria for hemophagocytic lymphohistiocytosis (HLH) due to disseminated herpes simplex virus 1 (HSV-1). While the cytokine storm abated after administration of multiple immune modulatory therapies including dexamethasone, etoposide, intravenous immune globulin, anakinra, as well as the interferon gamma antagonist emapalumab, multiple organ dysfunction syndrome progressed. Care was withdrawn after 5 days. Subsequent genetic testing did not reveal any mutations associated with familial HLH. This case highlights that even with appropriate antiviral treatment and immune suppression, disseminated HSV is often fatal. Further study is warranted to determine whether early immune modulatory therapy including interferon gamma blockade can interrupt the HLH inflammatory cascade and prevent progression of MODS.
Outcome Measures Following Critical Illness in Children With Disabilities: A Scoping Review
Authors: Heneghan Julia A. , Sobotka Sarah A. , Hallman Madhura , Pinto Neethi , Killien Elizabeth Y. , Palumbo Kathryn , Murphy Salem Sinead , Mann Kilby , Smith Barbara , Steuart Rebecca , Akande Manzilat , Graham Robert J.
Published: July 2021

Children with disabilities compose a substantial portion of admissions and bed-days in the pediatric intensive care unit (PICU) and often experience readmissions over time. Impacts of a PICU admission on post-discharge health status may be difficult to distinguish from pre-existing disability in this population. Efforts to standardize outcome measures used for children with disabilities may help identify morbidities associated with PICU hospitalizations. Although a scoping review of outcome measures to assess children after episodes of critical illness has recently been published, it is not known to what extent these measures are appropriate for use in children with disabilities. This limits our ability to effectively measure long-term outcomes following critical illness in this important patient population. Through mixed methodology of scoping review and multi-stakeholder consensus, we aimed to identify and describe instruments previously utilized for this purpose and to explore additional tools for consideration. This yielded 51 measures across a variety of domains that have been utilized in the PICU setting and may be appropriate for use in children with disabilities. We describe characteristics of these instruments, including the type of developmental domains assessed, availability of population data, validation and considerations regarding administration in children with disabilities, and ease of availability of the instrument to researchers. Additionally, we suggest needed alterations or accommodations for these instruments to augment their utility in these populations, and highlight areas for future instrument development.
Naringin Chelates Excessive Iron and Prevents the Formation of Amyloid-Beta Plaques in the Hippocampus of Iron-Overloaded Mice
Authors: Jahanshahi Mehrdad , Khalili Masoumeh , Margedari Asra
Published: July 2021

Metal chelating agents are antioxidant agents, which decrease the reductive potential and stabilize the oxidized metal ion form. In this study, we evaluated the naringin capacity in chelating iron and preventing amyloid-beta plaque formation in the hippocampus of iron-overloaded mice. Thirty-five NMRI male mice (8–10 weeks old) were provided. The mice were classified into five groups. Iron dextran was administered as i.p. injection (100 mg/kg/day) four times a week for four subsequent weeks. The treated groups received 30 and 60 mg/kg/day naringin for a month. After histological processing, the brain sections were stained with Perls’ stain kit for iron spots, and Congo red was used to stain the brain and hippocampus for amyloid-beta plaques. 30 mg/kg/day of naringin was shown to decrease nonheme iron in an efficient manner; iron content in this group decreased to 16.83 ± 0.57 μg/g wet weight, a quantity as low as that observed in the normal saline-receiving group. The nonheme iron content in the mice receiving 60 mg/kg/day of naringin was 20.73 ± 0.65 μg/g wet weight. In addition, Aβ plaque numbers in CA1, CA3, and DG areas of the hippocampus decreased significantly following treatment with 30 or 60 mg/kg/day naringin. Naringin has a strong iron chelation capacity and is able to reduce the formation of amyloid plaques. So it can be useful for neuroprotection and prevention of Alzheimer’s disease.
Pericardial Toxicities Associated With Immune Checkpoint Inhibitors: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS) Database
Authors: Ma Zhuo , Pei Jie , Sun Ximu , Liu Lihong , Lu Wenchao , Guo Qixiang , Lyu Jiayou , Liu Yuwei , Zhang Yuhui , Zhao Zhixia
Published: July 2021

Introdution: Immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes for a wide range of cancers but can also lead to serious or fatal immune-related adverse events (irAEs). Although ICI-related pericardial toxicities have been reported, the clinical features are not well characterized in real-world studies.

Objective: To characterize the main features of ICI-related pericardial toxicities and identify factors associated with death.

Methods: Data from January 1, 2011 to March 31, 2020 in the FDA Adverse Event Reporting System database were retrieved for disproportionality analysis. We used the reporting odds ratio and the information component (IC) to evaluate the association between ICIs and pericardial adverse events. Clinical characteristics of patients with ICI-associated pericardial toxicities were collected and compared between fatal and non-fatal groups. The time to onset following different ICI regimens was further investigated.

Results: We identified a total of 705 ICI-associated pericardial toxicities which appeared to influence more men (53.90%) than women (36.03%), with a median age of 63 (interquartile range [IQR] 54–69) years. Patients with lung cancer accounted for the largest proportion (55.6%). ICI therapies were detected with pharmacovigilance signals of pericardial toxicities, corresponding to IC025 = 2.11 and ROR 4.87 [4.51–5.25]. Nevertheless, there was a lack of association between anti-CTLA-4 and pericardial toxicities. There was no difference in onset time among all ICI regimens. However, TTO of fatal cases (25 days (interquartile range [IQR] 6–70)) occurred statistically earlier than non-fatal cases (42 days (IQR 12–114), p = 0.003).

Conclusion: ICI monotherapy (PD-1/PD-L1 therapy) and combination therapy can lead to pericardial toxicities that can result in serious outcomes and tend to occur early. Early recognition and management of ICI-related pericardial disorders should attract clinical attention. The findings require further clinical surveillance for the quantification.
Extract of Seaweed Codium fragile Inhibits Integrin αIIbβ3-Induced Outside-in Signaling and Arterial Thrombosis
Authors: Kim Tae In , Kim Yeon-Ji , Kim Kyungho
Published: July 2021

Seaweeds are thought to be promising candidates for functional foods and to help prevent thrombotic and related cardiovascular diseases. Codium fragile (Suringer) Hariot has been traditionally used as a culinary ingredient, and it possesses a range of biological activities, including the inhibition of platelet function. However, the mechanism of this inhibition is unclear. The aim of this study was to examine the inhibitory effect of C. fragile in platelet function. The antiplatelet activity of C. fragile on agonist-activated platelet aggregation, granule secretion, calcium mobilization, platelet spreading, and clot retraction was assessed. The phosphorylation of c-Src, Syk, PLCγ2, and several proteins involving in the αIIbβ3 integrin outside-in signaling pathway were also studied in thrombin and CRP-stimulated platelets. The antithrombotic effect was investigated in mice using ferric chloride-induced arterial thrombus formation in vivo. Transection tail bleeding time was used to evaluate whether C. fragile inhibited primary hemostasis. The main components and contents of C. fragile ethanol extract were confirmed by GC-MS analysis. C. fragile significantly impaired agonist-induced platelet aggregation granule secretion, calcium mobilization, platelet spreading, and clot retraction. Biochemical analysis revealed that C. fragile inhibited the agonist-induced activation of c-Src, Syk, and PLCγ2, as well as the phosphorylation of PI3K, AKT, and mitogen-activated protein kinases (MAPKs). The inhibitory effect of C. fragile resulted from an inhibition of platelet αIIbβ3 integrin outside-in signal transduction during cell activation. Oral administration of C. fragile efficiently blocked FeCl3-induced arterial thrombus formation in vivo without prolonging bleeding time. GC-MS analysis revealed that phytol was the main constituent and the total content of isomers was 160.8 mg/kg. Our results demonstrated that C. fragile suppresses not only the inside-out signaling of αIIbβ3 integrin but also outside-in signal transmission. Therefore, C. fragile could be an effective antiplatelet therapeutic candidate.
Emerging Biological Functions of IL-17A: A New Target in Chronic Obstructive Pulmonary Disease?
Authors: Liu Meiling , Wu Kang , Lin Jinduan , Xie Qingqiang , Liu Yuan , Huang Yin , Zeng Jun , Yang Zhaogang , Wang Yifan , Dong Shiyan , Deng Weiye , Yang Mingming , Wu Song , Jiang Wen , Li Xuefeng
Published: July 2021

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that causes high rates of disability and mortality worldwide because of severe progressive and irreversible symptoms. During the period of COPD initiation and progression, the immune system triggers the activation of various immune cells, including Regulatory T cells (Tregs), dendritic cells (DCs) and Th17 cells, and also the release of many different cytokines and chemokines, such as IL-17A and TGF-β. In recent years, studies have focused on the role of IL-17A in chronic inflammation process, which was found to play a highly critical role in facilitating COPD. Specially, IL-17A and its downstream regulators are potential therapeutic targets for COPD. We mainly focused on the possibility of IL-17A signaling pathways that involved in the progression of COPD; for instance, how IL-17A promotes airway remodeling in COPD? How IL-17A facilitates neutrophil inflammation in COPD? How IL-17A induces the expression of TSLP to promote the progression of COPD? Whether the mature DCs and Tregs participate in this process and how they cooperate with IL-17A to accelerate the development of COPD? And above associated studies could benefit clinical application of therapeutic targets of the disease. Moreover, four novel efficient therapies targeting IL-17A and other molecules for COPD are also concluded, such as Bufei Yishen formula (BYF), a Traditional Chinese Medicine (TCM), and curcumin, a natural polyphenol extracted from the root ofCurcuma longa.
Potential Role of Protein Kinase C in the Pathophysiology of Diabetes-Associated Atherosclerosis
Authors: Lien Chih-Feng , Chen Sy-Jou , Tsai Min-Chien , Lin Chin-Sheng
Published: July 2021

Diabetes mellitus is a metabolic syndrome that affects millions of people worldwide. Recent studies have demonstrated that protein kinase C (PKC) activation plays an important role in hyperglycemia-induced atherosclerosis. PKC activation is involved in several cellular responses such as the expression of various growth factors, activation of signaling pathways, and enhancement of oxidative stress in hyperglycemia. However, the role of PKC activation in pro-atherogenic and anti-atherogenic mechanisms remains controversial, especially under hyperglycemic condition. In this review, we discuss the role of different PKC isoforms in lipid regulation, oxidative stress, inflammatory response, and apoptosis. These intracellular events are linked to the pathogenesis of atherosclerosis in diabetes. PKC deletion or treatment with PKC inhibitors has been studied in the regulation of atherosclerotic plaque formation and evolution. Furthermore, some preclinical and clinical studies have indicated that PKCβ and PKCδ are potential targets for the treatment of diabetic vascular complications. The current review summarizes these multiple signaling pathways and cellular responses regulated by PKC activation and the potential therapeutic targets of PKC in diabetic complications.
Left Atrial Wall Stress and the Long-Term Outcome of Catheter Ablation of Atrial Fibrillation: An Artificial Intelligence-Based Prediction of Atrial Wall Stress
Authors: Lee Jae-Hyuk , Kwon Oh-Seok , Shim Jaemin , Lee Jisu , Han Hee-Jin , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung , Kim Young-Hoon , Pak Hui-Nam
Published: July 2021

Atrial stretch may contribute to the mechanism of atrial fibrillation (AF) recurrence after atrial fibrillation catheter ablation (AFCA). We tested whether the left atrial (LA) wall stress (LAW-stress[measured]) could be predicted by artificial intelligence (AI) using non-invasive parameters (LAW-stress[AI]) and whether rhythm outcome after AFCA could be predicted by LAW-stress[AI] in an independent cohort. Cohort 1 included 2223 patients, and cohort 2 included 658 patients who underwent AFCA. LAW-stress[measured] was calculated using the Law of Laplace using LA diameter by echocardiography, peak LA pressure measured during procedure, and LA wall thickness measured by customized software (AMBER) using computed tomography. The highest quartile (Q4) LAW-stress[measured] was predicted and validated by AI using non-invasive clinical parameters, including non-paroxysmal type of AF, age, presence of hypertension, diabetes, vascular disease, and heart failure, left ventricular ejection fraction, and the ratio of the peak mitral flow velocity of the early rapid filling to the early diastolic velocity of the mitral annulus (E/Em). We tested the AF/atrial tachycardia recurrence 3 months after the blanking period after AFCA using the LAW-stress[measured] and LAW-stress[AI] in cohort 1 and LAW-stress[AI] in cohort 2. LAW-stress[measured] was independently associated with non-paroxysmal AF (p < 0.001), diabetes (p = 0.012), vascular disease (p = 0.002), body mass index (p < 0.001), E/Em (p < 0.001), and mean LA voltage measured by electrogram voltage mapping (p < 0.001). The best-performing AI model had acceptable prediction power for predicting Q4-LAW-stress[measured] (area under the receiver operating characteristic curve 0.734). During 26.0 (12.0–52.0) months of follow-up, AF recurrence was significantly higher in the Q4-LAW-stress[measured] group [log-rank p = 0.001, hazard ratio 2.43 (1.21–4.90), p = 0.013] and Q4-LAW-stress[AI] group (log-rank p = 0.039) in cohort 1. In cohort 2, the Q4-LAW-stress[AI] group consistently showed worse rhythm outcomes (log-rank p < 0.001). A higher LAW-stress was associated with poorer rhythm outcomes after AFCA. AI was able to predict this complex but useful prognostic parameter using non-invasive parameters with moderate accuracy.
Leptin Receptor Blockade Attenuates Hypertension, but Does Not Affect Ventilatory Response to Hypoxia in a Model of Polygenic Obesity
Authors: Kim Lenise J. , Shin Mi-Kyung , Pho Huy , Otvos Laszlo , Tufik Sergio , Andersen Monica L. , Pham Luu V. , Polotsky Vsevolod Y.
Published: July 2021

Background

Obesity can cause hypertension and exacerbates sleep-disordered breathing (SDB). Leptin is an adipocyte-produced hormone, which increases metabolic rate, suppresses appetite, modulates control of breathing, and increases blood pressure. Obese individuals with high circulating levels of leptin are resistant to metabolic and respiratory effects of leptin, but they appear to be sensitive to hypertensive effects of this hormone. Obesity-induced hypertension has been associated with hyperleptinemia. New Zealand obese (NZO) mice, a model of polygenic obesity, have high levels of circulating leptin and hypertension, and are prone to develop SDB, similarly to human obesity. We hypothesize that systemic leptin receptor blocker Allo-aca will treat hypertension in NZO mice without any effect on body weight, food intake, or breathing.

Methods

Male NZO mice, 12–13 weeks of age, were treated with Allo-aca (n = 6) or a control peptide Gly11 (n = 12) for 8 consecutive days. Doses of 0.2 mg/kg were administered subcutaneously 2×/day, at 10 AM and 6 PM. Blood pressure was measured by telemetry for 48 h before and during peptide infusion. Ventilation was assessed by whole-body barometric plethysmography, control of breathing was examined by assessing the hypoxic ventilatory response (HVR), and polysomnography was performed during light-phase at baseline and during treatment. Heart rate variability analyses were performed to estimate the cardiac autonomic balance.

Results

Systemic leptin receptor blockade with Allo-aca did not affect body weight, body temperature, and food intake in NZO mice. Plasma levels of leptin did not change after the treatment with either Allo-aca or the control peptide Gy11. NZO mice were hypertensive at baseline and leptin receptor blocker Allo-aca significantly reduced the mean arterial pressure from 134.9 ± 3.1 to 124.9 ± 5.7 mmHg during the light phase (P < 0.05), whereas the control peptide had no effect. Leptin receptor blockade did not change the heart rate or cardiac autonomic balance. Allo-aca did not affect minute ventilation under normoxic or hypoxic conditions and HVR. Ventilation, apnea index, and oxygen desaturation during NREM and REM sleep did not change with leptin receptor blockade.

Conclusion

Systemic leptin receptor blockade attenuates hypertension in NZO mice, but does not exacerbate obesity and SDB. Thus, leptin receptor blockade represents a potential pharmacotherapy for obesity-associated hypertension.
Comparative Analysis of Skeletal Muscle DNA Methylation and Transcriptome of the Chicken Embryo at Different Developmental Stages
Authors: Ran Jinshan , Li Jingjing , Yin Lingqian , Zhang Donghao , Yu Chunlin , Du Huarui , Jiang Xiaosong , Yang Chaowu , Liu Yiping
Published: July 2021

DNA methylation is a key epigenetic mechanism involved in embryonic muscle development and plays an important role in early muscle development. In this study, we sought to investigate the effects of genome-wide DNA methylation by combining the expression profiles of the chicken embryonic muscle. Genome-wide DNA methylation maps and transcriptomes of muscle tissues collected from different embryonic development points (E7, E11, E17, and D1) were used for whole-genome bisulfite sequencing (WGBS) and RNA sequencing, respectively. We found that the differentially methylated genes (DMGs) were significantly associated with muscle organ development, regulation of skeletal muscle satellite cell proliferation, and actin filament depolymerization. Furthermore, genes TBX1, MEF2D, SPEG, CFL2, and TWF2 were strongly correlated with the methylation-caused expression switch. Therefore, we chose the CFL2 gene to explore its function in skeletal muscle satellite cells, and the in vitro experiments showed that CFL2 acts as a negative regulator of chicken skeletal muscle satellite cell proliferation and can induce cell apoptosis. These results provide valuable data for future genome and epigenome studies of chicken skeletal muscle and may help reveal the molecular mechanisms of potential economic traits.
Physiological Alterations in Deletion Mutants of Two Insulin-Like Peptides Encoded in Maruca vitrata Using CRISPR/Cas9
Authors: Al Baki Md. Abdullah , Kyo Jung Jin , Kim Yonggyun
Published: July 2021

Most insect species encode multiple insulin-like peptides (ILPs) that exhibit functional overlaps in mediating physiological processes such as development and reproduction. Why do they need multiple ILPs? To address this question, we tested a hypothesis of the requirement of multiple ILPs by generating mutants lacking individual ILP genes using the CRISPR/Cas9 technology. Two ILPs (ILP1 and ILP2) in the legume pod borer, Maruca vitrata, mediate similar physiological processes such as hemolymph sugar level, larval development, and adult reproduction. Individual knock-out mutants (ΔILP1 and ΔILP2) were generated. They showed successful development from larvae to adults. However, they suffered from high hemolymph sugar levels by enhancing trehalose titers in the hemolymph. The hyperglycemic effect was more evident in ΔILP2 mutants than in ΔILP1 mutants. Both mutants showed increased expression of trehalose-6-phosphate synthase but suppressed expression of trehalase. These mutants also showed altered expression patterns of insulin signaling components. Expression levels of insulin receptor and Akt genes were upregulated, while those of FOXO and Target of rapamycin genes were downregulated in these mutants. These alterations of signal components resulted in significant retardation of immature development and reduced body sizes. ΔILP1 or ΔILP2 females exhibited poor oocyte development. Bromo-uridine incorporation was much reduced at the germarium of ovarioles of these mutants compared with wild females. Expression of the vitellogenin gene was also reduced in these mutants. Furthermore, males of these deletion mutants showed impaired reproductive activities when they mated with wild-type females. These results suggest that both ILPs are required for mediating larval development and adult reproduction in M. vitrata.
All Plant Breeding Technologies Are Equal, but Some Are More Equal Than Others: The Case of GM and Mutagenesis
Authors: Batalha Luisa , Foroni Francesco , Jones Brian Joseph
Published: July 2021

A pervasive opposition to genetically modified (GM) foods has developed from the notion that they pose a risk to human and environmental health. Other techniques for the genetic modification of plants, such as sexual crossing and mutagenesis breeding, have mostly remained unchallenged. This research aims to investigate public perception of plant breeding technologies. Specifically, sexual crossing, mutagenesis, transgenics (GM) and gene editing. It was expected that attitudes and intentions would be most positive and the perception of risk lowest for plant genetic modification through sexual crosses. Scores on these variables were expected to be similar between mutagenesis, GM and gene editing. It was also expected that attitudes, intentions and risk perception would change (becoming more positive) once participants learned about foods developed through these technologies. Participants reported their attitudes, intentions and risk perception at two points in time. At Time 2, they were presented with pictures of food items developed through sexual crossing, GM and mutagenesis. The results showed that mutagenesis stood out as the most negatively perceived technology, whereas genetic development via sexual crosses was generally perceived as positive. The results highlight the importance of messaging, framing in consumer attitudes.
The Role of Nitric Oxide-Induced ATILL6 in Growth and Disease Resistance in Arabidopsis thaliana
Authors: Khan Murtaza , Al Azawi Tiba Nazar Ibrahim , Pande Anjali , Mun Bong-Gyu , Lee Da-Sol , Hussain Adil , Lee Byung-Hyun , Yun Byung-Wook
Published: July 2021

Nitric oxide (NO) is a signaling molecule that regulates various processes, including plant growth and development, immunity, and environmental interactions. Using high throughput RNA-seq data, we explored the role of the NO-induced ATILL6 gene in plant growth and defense using functional genomics. The atill6 mutant and wild-types were challenged with either oxidative (H2O2, MV) or nitro-oxidative (CySNO, GSNO) stress conditions, and the phenotypic results showed that ATILL6 gene differentially regulates cotyledon development frequency (CDF) as well as the root and shoot lengths of the plants. To investigate whether ATILL6 plays a role in plant basal or resistance (R)-gene-mediated defense, the plants were challenged with either virulent or avirulent strains of Pseudomonas syringae pathovar tomato (Pst) DC3000. The atill6 line showed a susceptible phenotype, higher pathogen growth, and highly reduced transcript accumulation of PR1 and PR2 genes. These results suggested that ATILL6 positively regulates plant basal defense. Furthermore, after the inoculation of atill6 with avirulent Pst (DC3000), the expressions of the PR1 and PR2 genes decreased, suggesting a positive role in R-gene-mediated resistance in protecting the plant from further spread of disease. We also investigated the role of ATILL6 in systemic acquired resistance (SAR), and the results showed that ATILL6 positively regulates SAR, as the mutant line atill6 has significantly (p ≤ 0.05) lower transcript accumulation of PR, G3DPH, and AZI genes. Overall, these results indicate that the NO-induced ATILL6 gene differentially regulates plant growth and positively regulates plant basal defense, R-gene-mediated resistance, and SAR.
Genetic Dissection of Quantitative Resistance to Common Rust (Puccinia sorghi) in Tropical Maize (Zea mays L.) by Combined Genome-Wide Association Study, Linkage Mapping, and Genomic Prediction
Authors: Ren Jiaojiao , Li Zhimin , Wu Penghao , Zhang Ao , Liu Yubo , Hu Guanghui , Cao Shiliang , Qu Jingtao , Dhliwayo Thanda , Zheng Hongjian , Olsen Michael , Prasanna Boddupalli M. , San Vicente Felix , Zhang Xuecai
Published: July 2021

Common rust is one of the major foliar diseases in maize, leading to significant grain yield losses and poor grain quality. To dissect the genetic architecture of common rust resistance, a genome-wide association study (GWAS) panel and a bi-parental doubled haploid (DH) population, DH1, were used to perform GWAS and linkage mapping analyses. The GWAS results revealed six single-nucleotide polymorphisms (SNPs) significantly associated with quantitative resistance of common rust at a very stringent threshold of P-value 3.70 × 10–6 at bins 1.05, 1.10, 3.04, 3.05, 4.08, and 10.04. Linkage mapping identified five quantitative trait loci (QTL) at bins 1.03, 2.06, 4.08, 7.03, and 9.00. The phenotypic variation explained (PVE) value of each QTL ranged from 5.40 to 12.45%, accounting for the total PVE value of 40.67%. Joint GWAS and linkage mapping analyses identified a stable genomic region located at bin 4.08. Five significant SNPs were only identified by GWAS, and four QTL were only detected by linkage mapping. The significantly associated SNP of S10_95231291 detected in the GWAS analysis was first reported. The linkage mapping analysis detected two new QTL on chromosomes 7 and 10. The major QTL on chromosome 7 in the region between 144,567,253 and 149,717,562 bp had the largest PVE value of 12.45%. Four candidate genes of GRMZM2G328500, GRMZM2G162250, GRMZM2G114893, and GRMZM2G138949 were identified, which played important roles in the response of stress resilience and the regulation of plant growth and development. Genomic prediction (GP) accuracies observed in the GWAS panel and DH1 population were 0.61 and 0.51, respectively. This study provided new insight into the genetic architecture of quantitative resistance of common rust. In tropical maize, common rust could be improved by pyramiding the new sources of quantitative resistance through marker-assisted selection (MAS) or genomic selection (GS), rather than the implementation of MAS for the single dominant race-specific resistance gene.
The Personalization of Politics in Anglo-American Democracies
Authors: Bittner Amanda
Published: July 2021

In American politics, few argue with the idea that leaders matter: in the 2020 American election, the media closely tracked the performance and activities of Joe Biden and Donald Trump, for example, suggesting to us that who they are matters. Voters indicate on their ballot which presidential candidate they prefer, marking an x next to the person’s name, giving further credence to the idea that the individual matters in the process. Contemporary Anglo-Westminster-style democracies have many things in common with the United States, but operate with completely different political systems, and without a direct vote for a specific party leader. What is the relationship between voters and party leaders in these contexts? Do party leaders matter the same way in these countries? Has this relationship changed over time? Are we really seeing the personalization of parliamentary elections, as some scholars have suggested? The personalization literature provides us with mixed evidence of the increasing importance of leaders, and part of the reason for that maybe linked to the lack of comparable data. This paper assesses the role of leaders in the United States as well as four parliamentary democracies (Britain, Canada, New Zealand, and Australia) over time. Combining data from the election studies of these five countries from the 1960 s to the present, the analyses presented here suggest that leaders are not increasingly important to voters over time, but that leaders have always been important to election outcomes. What has changed over time, however, is the way partisans see the leaders of other parties. Partisans are increasingly polarized in their views of opposing party leaders, and this has the potential to change the impact of leaders in the electoral process.
Proactive Personality and Social Support With Pre-retirement Anxiety: Mediating Role of Subjective Career Success
Authors: Ugwu Lawrence Ejike , Enwereuzor Ibeawuchi K. , Nwankwo Barnabas E. , Ugwueze Stella , Ogba Franscisca N. , Nnadozie Evelyn E. , Elom Chinyere O. , Eze Angela , Ezeh Michael A.
Published: July 2021

The main objective of this paper is to investigate the mediating role of subjective career success (SCS) in the relationship between proactive personality, social support (SS), and pre-retirement anxiety. Using a two-wave longitudinal design, 624 pre-retirees were sampled (M = 56.49 years; SD = 4.56); of these, 237 (37.98%) were males and 387 (62.02%) were females. Measurement model and mediation test were performed using the SmartPLS and IBM SPSS Amos software. The result indicated that proactive personality, SS, and SCS showed negative relationships with the dimensions of pre-retirement anxiety (financial preparedness, social obligation, and social alienation). Subjective career success mediated the relationship between proactive personality and pre-retirement anxiety.
Component Processes of Decision Making in a Community Sample of Precariously Housed Persons: Associations With Learning and Memory, and Health-Risk Behaviors
Authors: Baitz Heather A. , Jones Paul W. , Campbell David A. , Jones Andrea A. , Gicas Kristina M. , Giesbrecht Chantelle J. , Loken Thornton Wendy , Barone Carmelina C. , Wang Nena Y. , Panenka William J. , Lang Donna J. , Vila-Rodriguez Fidel , Leonova Olga , Barr Alasdair M. , Procyshyn Ric M. , Buchanan Tari , Rauscher Alexander , MacEwan G. William , Honer William G. , Thornton Allen E.
Published: July 2021

The Iowa Gambling Task (IGT) is a widely used measure of decision making, but its value in signifying behaviors associated with adverse, “real-world” consequences has not been consistently demonstrated in persons who are precariously housed or homeless. Studies evaluating the ecological validity of the IGT have primarily relied on traditional IGT scores. However, computational modeling derives underlying component processes of the IGT, which capture specific facets of decision making that may be more closely related to engagement in behaviors associated with negative consequences. This study employed the Prospect Valence Learning (PVL) model to decompose IGT performance into component processes in 294 precariously housed community residents with substance use disorders. Results revealed a predominant focus on gains and a lack of sensitivity to losses in these vulnerable community residents. Hypothesized associations were not detected between component processes and self-reported health-risk behaviors. These findings provide insight into the processes underlying decision making in a vulnerable substance-using population and highlight the challenge of linking specific decision making processes to “real-world” behaviors.
Who Is Next? A Study on Victims of Financial Fraud in Japan
Authors: Kadoya Yoshihiko , Khan Mostafa Saidur Rahim , Narumoto Jin , Watanabe Satoshi
Published: July 2021

Japan has seen an increase in the incidents of financial frauds over the last couple of decades. Although authorities are aware of the problem, an effective solution eludes them as fraudsters use innovative swindling methods and continually change the target group. Using a nationwide survey conducted by Hiroshima University, Japan, in 2020, this study investigated the socioeconomic and psychological profiles of victims of trending and special financial fraud such as fictitious billing fraud, loan guarantee fraud, and refund fraud. It was found that financial fraud victims' profiles are dissimilar at the aggregate and specific levels. At the specific level, victim profiles were diverse, that is, in fictitious billing fraud, loan guarantee fraud, and refund fraud cases. Males, married, and financially less satisfied people were more often victims of fictitious billing fraud; less anxious people were more likely victims of loan guarantee fraud; and older, asset-holding, and less-income-generating respondents were found to be victims of refund fraud. Our results also show some commonalities in the victims' profiles. For example, financially less-literate people were found to be more likely victims of fictitious billing fraud and loan guarantee fraud. Finally, respondents who lived with their family, those who did not have careful buying habits, and those who suffer from bouts of loneliness were found to be common victims of all types of special financial fraud. The results of our study suggest that a one-size-fits-all policy cannot effectively combat financial fraud.
“I Wish I Had Help Earlier. We Could Have Been Happier Sooner.” Overcoming the Bystander Effect in the Care for Alcohol-Dependent Parents
Authors: Snoek Anke , Dijkstra Boukje A. G. , Markus Wiebren , Van der Meer Margreet , De Wert Guido , Horstkötter Dorothee
Published: July 2021

Parental alcohol dependency is associated with risks for the well-being of their children. However, guiding these families to support is often complicated. We interviewed 10 alcohol dependent parents, and held 3 focus group interviews with child welfare social workers, and alcohol and other drug workers. We identified a reluctance to act among professional and non-professional bystanders. Family members, neighbours, teachers, and general practitioners are often aware of parental drinking problems, but are reluctant to discuss them with the parents or to alert services designed to support families. The aim of this paper is to share the experiences of parents and show that parents appreciate interventions if done in a certain manner. Although parents were reluctant to discuss their drinking problem, they considered these problems as symptoms of underlying severe distress. They were highly motivated to get help for these underlying problems and wondered why they were not questioned about their distress by those around them. The silence of others reinforced pre-existing feelings of worthlessness and hopelessness. In this paper we analyse other's hesitation to intervene as a form of the bystander effect, and make suggestions on how this bystander effect can be overcome.