bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implication of Vestibular Hair Cell Loss of Planar Polarity for the Canal and Otolith-Dependent Vestibulo-Ocular Reflexes in Celsr1–/– Mice
Authors: Simon François , Tissir Fadel , Michel Vincent , Lahlou Ghizlene , Deans Michael , Beraneck Mathieu 
Published: November 2021

Introduction: Vestibular sensory hair cells are precisely orientated according to planar cell polarity (PCP) and are key to enable mechanic-electrical transduction and normal vestibular function. PCP is found on different scales in the vestibular organs, ranging from correct hair bundle orientation, coordination of hair cell orientation with neighboring hair cells, and orientation around the striola in otolithic organs. Celsr1 is a PCP protein and a Celsr1 KO mouse model showed hair cell disorganization in all vestibular organs, especially in the canalar ampullae. The objective of this work was to assess to what extent the different vestibulo-ocular reflexes were impaired in Celsr1 KO mice.Methods: Vestibular function was analyzed using non-invasive video-oculography. Semicircular canal function was assessed during sinusoidal rotation and during angular velocity steps. Otolithic function (mainly utricular) was assessed during off-vertical axis rotation (OVAR) and during static and dynamic head tilts.Results: The vestibulo-ocular reflex of 10 Celsr1 KO and 10 control littermates was analyzed. All KO mice presented with spontaneous nystagmus or gaze instability in dark. Canalar function was reduced almost by half in KO mice. Compared to control mice, KO mice had reduced angular VOR gain in all tested frequencies (0.2–1.5 Hz), and abnormal phase at 0.2 and 0.5 Hz. Concerning horizontal steps, KO mice had reduced responses. Otolithic function was reduced by about a third in KO mice. Static ocular-counter roll gain and OVAR bias were both significantly reduced. These results demonstrate that canal- and otolith-dependent vestibulo-ocular reflexes are impaired in KO mice.Conclusion: The major ampullar disorganization led to an important reduction but not to a complete loss of angular coding capacities. Mildly disorganized otolithic hair cells were associated with a significant loss of otolith-dependent function. These results suggest that the highly organized polarization of otolithic hair cells is a critical factor for the accurate encoding of the head movement and that the loss of a small fraction of the otolithic hair cells in pathological conditions is likely to have major functional consequences. Altogether, these results shed light on how partial loss of vestibular information encoding, as often encountered in pathological situations, translates into functional deficits.
Long Chain Polyunsaturated Fatty Acids Docosahexaenoic Acid and Arachidonic Acid Supplementation in the Suckling and the Post-weaning Diet Influences the Immune System Development of T Helper Type-2 Bias Brown Norway Rat Offspring
Authors: Patel Dhruvesh , Newell Marnie , Goruk Susan , Richard Caroline , Field Catherine J. 
Published: November 2021

Background:Dietary long chain polyunsaturated fatty acids (LCPUFA) such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) play an important role in the development of the infant immune system. The role of LCPUFA in the T helper type 2 (Th2) biased immune system is unknown. We aimed to understand the effect of feeding LCPUFA during suckling and post-weaning on immune system development in Th2 bias Brown Norway rat offspring.Methods:Brown Norway dams were randomly assigned to nutritionally adequate maternal diet throughout the suckling period (0–3 weeks), namely, control diet (0% ARA, 0% DHA;n= 8) or ARA + DHA (0.45% ARA, 0.8% DHA;n= 10). At 3 weeks, offspring from each maternal diet group were randomized to either a control (0% ARA, 0% DHA;n= 19) or ARA+DHA post-weaning (0.5% ARA, 0.5% DHA;n= 18) diet. At 8 weeks, offspring were killed, and tissues were collected for immune cell function and fatty acid composition analyses.Results:ARA + DHA maternal diet resulted in higher (p&lt; 0.05) DHA composition in breast milk (4×) without changing ARA levels. This resulted in more mature adaptive immune cells in spleen [T regulatory (Treg) cells and B cells], mesenteric lymph nodes (MLN, lower CD45RA+), and Peyer's patches (PP; higher IgG+, B cells) in the ARA+DHA group offspring at 8 weeks. ARA+DHA post-weaning diet (3–8 weeks) resulted in 2 × higher DHA in splenocyte phospholipids compared to control. This also resulted in higher Th1 cytokines, ~50% higher TNF-α and IFNγ, by PMAi stimulated splenocytesex vivo, with no differences in Th2 cytokines (IL-4, IL-13, and IL-10) compared to controls.Conclusion:Feeding dams a diet higher in DHA during the suckling period resulted in adaptive immune cell maturation in offspring at 8 weeks. Providing ARA and DHA during the post-weaning period in a Th2 biased Brown Norway offspring model may support Th1 biased immune response development, which could be associated with a lower risk of developing atopic diseases.
The Ferroptosis-Related Noncoding RNA Signature as a Novel Prognostic Biomarker in the Tumor Microenvironment, Immunotherapy, and Drug Screening of Gastric Adenocarcinoma
Authors: Chen Xinming , Zhu Zheng , Li Xiaoling , Yao Xinyue , Luo Lianxiang 
Published: November 2021

BackgroundFerroptosis is a new type of cell death different from apoptosis, necrosis, autophagy, and pyroptosis. This study aimed to explore the relationship between ferroptosis-related noncoding RNA (ncRNA) and gastric adenocarcinoma with regard to immunity and prognosis.MethodsFerroptosis-related ncRNA expression profiles and clinical pathology and overall survival information were collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database. The ferroptosis-related ncRNA signature was identified by Cox regression analysis and the least absolute shrinkage and selection operator analysis. The survival analysis, receiver operating characteristic (ROC) analysis, and decision curve analysis were adopted to evaluate the prognostic prediction performance of the signature. The correlation between risk and multiple clinical characteristics was analyzed using the chi-square test. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were used for mining functions and pathways. The CIBERSORT, ssGSEA, and ESTIMATE algorithms were used to assess immune infiltration and the tumor microenvironment. The response of immunotherapy was predicted using the Submap algorithm, and the Connectivity Map and the ridge regression model were used to screen and evaluate drugs.ResultsA carcinogenic risk signature was constructed using five ferroptosis-related ncRNAs. It showed an extraordinary ability to predict the prognoses of patients with gastric adenocarcinoma [area under the ROC curve (AUC) after 6 years = 0.689; GSE84426, AUC after 6 years = 0.747]. The lower ferroptosis potential level and lower tumor mutation burden were related to the poor prognoses of patients. The high-risk group had more immune cell recruitment, and the overall effect of the anti-immune checkpoint immunotherapy was not as good as that of the low-risk group. The high- and low-risk groups were enriched in tumor- and immune-related pathways, respectively. The screened antitumor drugs, such as genistein, guanabenz, and betulinic acid, improved the survival of the patients.ConclusionsThe ferroptosis-related ncRNA signature is a potential carcinogenic prognostic biomarker of gastric adenocarcinoma.
Axial Length Changes Following Surgical Intervention in Children With Primary Congenital Glaucoma
Authors: Al Dalgan Hind A. , Al Obaida Ibrahim A. , Al Owaifeer Adi M. , Ahmad Khabir , Malik Rizwan 
Published: November 2021

BackgroundPrimary congenital glaucoma (PCG) is a challenging condition to diagnose, treat and effectively monitor. Serial assessment of intraocular pressure (IOP), optic disc cupping, refraction, and axial length (AxL) after surgery are useful to assess disease control. This study aimed to evaluate AxL changes in relation to IOP changes following glaucoma surgery in children with PCG.MethodsWe retrospectively studied AxL changes in children with PCG undergoing surgery. Eyes of children aged ≤ 4 years that did not have prior ocular surgery and that underwent at least one glaucoma surgery during the course of follow-up between June 2014 and July 2018, were included. The effect of change in IOP on change in AxL was estimated using linear mixed effects models.ResultsA total of 105 eyes (of 72 children) with PCG underwent glaucoma surgery representing 26.4% (105/397) eyes. The mean ± SD age of children at baseline was 3.53 ± 4.04 months. At baseline, the mean IOP and AxL were 26.63 ± 9.57 mmHg and 21.67 ± 1.82 mm, respectively. During the course of follow-up post-surgery, the IOP decreased by a mean of 7.25 ± 12.08 mmHg while the AxL increased by a mean of 0.70 ± 1.40 mm. A multivariable mixed effects linear regression revealed that change in AxL was significantly associated with change in IOP (p=0.030) and time since first surgery (p&lt;0.001). A substantial reduction in IOP (≥35 mmHg) was needed at 3 months post-surgery, for AxL to regress.ConclusionIn children with PCG who undergo glaucoma surgery, change in IOP significantly influences change in AxL. For AxL to regress, a substantial reduction in IOP is needed post-surgery.
Myotonia Congenita: Clinical Characteristic and Mutation Spectrum of CLCN1 in Chinese Patients
Authors: Hu Chaoping , Shi Yiyun , Zhao Lei , Zhou Shuizhen , Li Xihua 
Published: November 2021

Background:CLCN1-related myotonia congenita (MC) is one of the most common forms of non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked contraction. However, there is limited data of clinical and molecular spectrum of MC patients in China.Patients and Methods: Five patients with myotonia congenita due to mutations in CLCN1 gene were enrolled, which were identified through trio-whole-exome sequencing or panel-based next-generation sequencing test. The clinical presentation, laboratory data, electrophysiological tests, muscular pathology feature, and genetic results were collected and reviewed. We also searched all previously reported cases of MC patients with genetic diagnosis in Chinese populations, and their data were reviewed.Results: The median onset age of five patients was 3.0 years old, ranging from 1.0 to 5.0 years old, while the median age of admit was 5.0 years old, ranging from 3.5 to 8.8 years old. Five patients complained of muscle stiffness when rising from chairs or starting to climb stairs (5/5, 100.0%), four patients complained of delayed relaxation of their hands after forceful grip (4/5, 80.0%), all of which improved with exercise (warm-up phenomenon) (5/5, 100%). Electromyogram was conducted in five patients, which all revealed myotonic change (100%). Genetic tests revealed nine potential disease-causing variants in CLCN1 gene, including two novel variants: c.962T&gt;A (p.V321E) and c.1250A&gt;T (p.E417V). Literature review showed that 43 MC Chinese patients with genetic diagnosis have been reported till now (including our five patients). Forty-seven variants in CLCN1 gene were found, which consisted of 33 missense variants, 6 nonsense variants, 5 frame-shift variants, and 3 splicing variants. Variants in exon 8, 15, 12, and 16 were most prevalent, while the most common variants were c.892G&gt;A (p.A298T) (n = 9), c.139C&gt;T (p.R47W) (n = 3), c.1205C&gt;T(p.A402V) (n = 3), c.1657A&gt;T (p.I553F) (n = 3), c.1679T&gt;C (p.M560T) (n = 3), c.350A&gt;G (p.D117G) (n = 2), c.762C&gt;G (p.C254W) (n = 2), c.782A&gt;G (P.Y261C) (n = 2), and c.1277C&gt;A (p.T426N) (n = 2).Conclusion: Our results reported five CLCN1-related MC patients, which expanded the clinical and genetic spectrum of MC patients in China. Based on literature review, 43MC Chinese patients with genetic diagnosis have been reported till now, and variants in exon eight were most prevalent in Chinese MC patients while c.892G&gt;A (p.A298T) was probably a founder mutation.
Contribution of Character Strengths to Psychology Stress, Sleep Quality, and Subjective Health Status in a Sample of Chinese Nurses
Authors: Zhang Shu-e , Yang Li-bin , Zhao Chen-xi , Shi Yu , Wang Hong-ni , Zhao Xin , Wang Xiao-he , Sun Tao , Cao De-pin 
Published: November 2021

Objectives: The main objectives of this study were to describe the current state of character strengths (CSs) of nurses; explain how they affect stress, sleep quality, and subjective health status; and reveal the mediating role of stress for the subject matter on the association between CSs, sleep quality, and subjective health status.Methods: A cross-sectional online survey was conducted from September to October 2020 in China. A multistage stratified sampling method was used, and 1,221 valid questionnaires across 100 cities in 31 provinces were collected.Results: For the participants in this survey, the three dimensions of CSs ranging from high to low were caring (4.20 ± 0.640), self-control (3.53 ± 0.763), and inquisitiveness (3.37 ± 0.787). There was difference in CSs scores across age (F = 8.171, P &lt; 0.01), professional categories (F = 5.545, P &lt; 0.01), and job tenure (F = 9.470, P &lt; 0.01). The results showed that CSs significantly affected the psychological stress (β = −0.365, P&lt; 0.01), sleep quality (β = 0.312, P&lt; 0.01), and subjective health (β = 0.398, P&lt; 0.01) of nurses. Moreover, psychological stress partially mediated the association between CSs and both types of health outcomes.Conclusion: In China, the CSs of nurses are at high levels. We find that nurses with high-level CSs are likely to experience less psychological stress and exhibit healthy psycho–physiological responses, which contribute to positive health outcomes. Finally, our study argues that strength-based interventions of positive psychology in hospitals should be provided to minimize threats to the physical and psychological health of health professionals, which is a beneficial choice for future hospital reforms in the domain of occupational health management.
Proof of Concept: A Brief Psycho-Educational Training Program to Increase the Use of Positive Emotion Regulation Strategies in Individuals With Autism Spectrum Disorder
Authors: Zaharia Alexandra , Noir-Kahlo Katharina , Bressoud Nicolas , Sander David , Dukes Daniel , Samson Andrea C. 
Published: November 2021

Attenuated positive emotions and difficulties in regulating emotions are frequently observed in individuals with autism spectrum disorders (ASD) and are linked to increased risk of affective disorders, problematic behaviors, and impaired socio-emotional functioning. As such, interventions specifically focused on positive emotion regulation (ER) skills could be very valuable for individuals with ASD, their caregivers, and therapists. However, the field of positive ER in ASD is under-researched. The present study aimed at testing the practical potential and the preliminary effects of a brief novel psycho-educational training program on positive ER for individuals with ASD. Thirty male participants with ASD (aged 10–35years; Ntraining=14, Nwaitlist=16) underwent a three-session program on the use of adaptive positive ER strategies (i.e., attentional deployment, cognitive change, and response modulation). Participants rated the program as easy to understand, interesting, pleasant, and likable. No dropouts or adverse effects were observed. The training group showed a significant increase in the self-reported use of the ER strategies compared to the waitlist group. The increase in the use of ER strategies maintained up to 7 weeks in the overall sample. Having reached high satisfaction rates and the intended effects in this proof of concept study, this novel program represents a promising tool to support ER. Future research should next investigate the efficacy of the intervention on day-to-day emotional experience and wellbeing.Clinical Trial Registration:ClinicalTrials.gov # NCT02898298
Post-Traumatic Stress Disorder, Mobile Phone Dependence, and Academic Boredom in Adolescents During the COVID-19 Pandemic
Authors: Shen Lingyan , Wu Xinyue , Zhen Rui , Zhou Xiao 
Published: November 2021

Background: The coronavirus disease (COVID-19) pandemic has threatened adolescents’ mental health and even elicited their academic problems. Post-traumatic stress disorder (PTSD) is one of the most common negative psychological reactions, and academic boredom is a typical academic problem to the pandemic. PTSD might be related to academic boredom, but the underlying mechanism of this potential relation in the context of the COVID-19 pandemic remains unclear.Aims: Under the framework of the job demands–resources model and the model of compensatory internet use, this study aims to examine the mediating role of mobile phone dependency in the relation between PTSD and academic boredom.Methods: Six hundred and thirty-one middle school students in Hubei Province were investigated using self-report questionnaires. SPSS19.0 and Mplus7.0 were used for data analysis.Results: PTSD symptoms were associated positively with academic boredom, and mobile phone dependence played a mediating role in the relation between PTSD and academic boredom. Specifically, adolescents with severe PTSD symptoms tended to report greater dependency on mobile phones, and hence show higher levels of boredom in learning.Conclusion: PTSD symptoms of adolescents directly aggravated their academic boredom, and indirectly affected academic boredom by increasing their dependence on mobile phones.
Fear of COVID-19 and Life Satisfaction: The Role of the Health-Related Hardiness and Sense of Coherence
Authors: Dymecka Joanna , Gerymski Rafał , Machnik-Czerwik Anna , Derbis Romuald , Bidzan Mariola 
Published: November 2021

Introduction: The COVID-19 pandemic is contributing to increased fear and anxiety throughout society, which may affect life satisfaction. Health-related hardiness and sense of coherence (SOC) are personal resources that help people adapt to difficult circumstances. The purpose of this study was to investigate the relationship between fear of COVID-19, SOC, health-related hardiness, and life satisfaction.Methods: A total of 907 Polish people (522 women and 385 men) participated in this study. The Fear of COVID-19 Scale (FOC-6), the Health-Related Hardiness Scale, the Sense of Coherence Scale (SOC-29), and the Satisfaction with Life Scale were used.Results: Correlation showed that fear of COVID-19 was negatively related to health-related hardiness, SOC, and life satisfaction. Health-related hardiness and SOC were positively related to life satisfaction. Both SOC and hardiness were mediators between fear of COVID-19 and life satisfaction during the current pandemic.Conclusion: SOC and health-related hardiness are personal resources that are important for dealing with the effects of the COVID-19 pandemic. According to our study, SOC and hardiness can mediate between fear of COVID-19 and life satisfaction. Presented cross-sectional results have to be verified in future longitudinal studies in order to strengthen the conclusions presented in this manuscript. This study verified the role of only two personal resources, so more research is needed on the role of other personal resources during COVID-19 pandemic.
Brain Functional and Structural Changes in Alzheimer's Disease With Sleep Disorders: A Systematic Review
Authors: Liu Yong-shou , Wang Yong-ming , Zha Ding-jun 
Published: November 2021

Introduction: Sleep disorders (SLD) are supposed to be associated with increased risk and development of Alzheimer's disease (AD), and patients with AD are more likely to show SLD. However, neurobiological performance of patients with both AD and SLD in previous studies is inconsistent, and identifying specific patterns of the brain functional network and structural characteristics in this kind of comorbidity is warranted for understanding how AD and SLD symptoms interact with each other as well as finding effective clinical intervention. Thus, the aims of this systematic review were to summarize the relevant findings and their limitations and provide future research directions.Methods: A systematic search on brain functional and structural changes in patients with both AD and SLD was conducted from PubMed, Web of Science, and EMBASE databases.Results: Nine original articles published between 2009 and 2021 were included with a total of 328 patients with comorbid AD and SLD, 367 patients with only AD, and 294 healthy controls. One single-photon emission computed tomography study and one multislice spiral computed tomography perfusion imaging study investigated changes of cerebral blood flow; four structural magnetic resonance imaging (MRI) studies investigated brain structural changes, two of them used whole brain analysis, and another two used regions of interest; two resting-state functional MRI studies investigated brain functional changes, and one 2-deoxy-2-(18F)fluoro-d-glucose positron emission tomography (18F-FDG-PET) investigated 18F-FDG-PET uptake in patients with comorbid AD and SLD. Findings were inconsistent, ranging from default mode network to sensorimotor cortex, hippocampus, brain stem, and pineal gland, which may be due to different imaging techniques, measurements of sleep disorder and subtypes of AD and SLD.Conclusions: Our review provides a systematic summary and promising implication of specific neuroimaging dysfunction underlying co-occurrence of AD and SLD. However, limited and inconsistent findings still restrict its neurobiological explanation. Further studies should use unified standards and comprehensive brain indices to investigate the pathophysiological basis of interaction between AD and SLD symptoms in the development of the disease spectrums.
Effect of Limonene on Cancer Development in Rodent Models: A Systematic Review
Authors: Zhou Jingyi , Azrad Maria , Kong Lingyan 
Published: November 2021

Cancer is a major health issue and one of the leading causes of death worldwide. Many natural compounds, e.g., lycopene, curcumin, resveratrol, etc., have been shown to inhibit the growth of cancer cells. Similarly, limonene, a major active component in citrus essential oils and widely used flavoring additive, has demonstrated anticarcinogenic effects in both cell and animal studies. This systematic review aimed to evaluate the anticarcinogenic effects of limonene and its potential underlying mechanisms. Eight peer-reviewed articles published in English between 2000 and 2020 were identified after screening using MEDLINE, Academic Search Premier, and CINAHL plus. All 8 studies showed an effect of limonene on reducing tumor burden, resulting in either decreased size, number, weight, or multiplicities of tumors. Limonene treatment extended the latency and survival periods in 2 studies yet did not reduce tumor incidence rate in another study. Limonene was shown to promote cell apoptosis in 4 studies that examined either the apoptosis index or apoptosis related gene/protein expressions. Two studies tried to explain the cancer preventive mechanisms of limonene and found limonene could restore the antioxidant capacity or immune functions that were impaired by cancer. These results supported the potential applicability of limonene on inhibiting cancer development, yet the real-world applicability on human requires more research and evaluation through clinical studies.Systematic Review Registration: PROSPERO, identifier: CRD42020168387.