bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of RNA Modification in Mouse Germ Cell-2 Spermatids Under Hypoxic Stress
Authors: He Tong , Guo Huanping , Xia Lin , Shen Xipeng , Huang Yun , Wu Xiao , Jiang Xuelin , Xu Yinying , Tan Yi , Zhang Yunfang , Tan Dongmei 
Published: June 2022

Hypoxia is a known stress factor in mammals and has been shown to potentially impair male fertility, which manifests as spermatogenic dysfunction and decreased semen quality. Studies have shown that RNA modifications, the novel post-transcriptional regulators, are involved in spermatogenesis, and hypoxia-induced alterations in RNA modification in testes and sperm cells may be associated with impaired spermatogenesis in mice. However, the molecular mechanisms via which RNA modifications influence spermatogenesis under hypoxic stress conditions are unclear. In this study, we generated a mouse Germ Cell-2 spermatid (GC-2spd) hypoxia model by culturing cells in a 1% O2 incubator for 48 h or treating them with CoCl2 for 24 h. The hypoxia treatment significantly inhibited proliferation and induced apoptosis in GC-2spd cells. The RNA modification signatures of total RNAs (2 types) and differentially sized RNA fragments (7 types of approximately 80 nt-sized tRNAs; 9 types of 17–50 nt-sized sncRNAs) were altered, and tRNA stability was partially affected. Moreover, the expression profiles of sncRNAs, such as microRNAs, tsRNAs, rsRNAs, and ysRNAs, were significantly regulated, and this might be related to the alterations in RNA modification and subsequent transcriptomic changes. We comprehensively analyzed alterations in RNA modification signatures in total RNAs, tRNAs (approximately 80 nt), and small RNAs (17–50 nt) as well as the expression profiles of sncRNAs and transcriptomes in hypoxia-treated GC-2spd cells; our data suggested that RNA modifications may be involved in cellular responses under hypoxic stress conditions and could provide a basis for a better understanding of the molecular mechanisms underlying male infertility.
A Method to Combine Neurofilament Light Measurements From Blood Serum and Plasma in Clinical and Population-Based Studies
Authors: Rübsamen Nicole , Willemse Eline A. J. , Leppert David , Wiendl Heinz , Nauck Matthias , Karch André , Kuhle Jens , Berger Klaus 
Published: June 2022

IntroductionNeurofilament light (NfL) can be detected in blood of healthy individuals and at elevated levels in those with different neurological diseases. We investigated if the choice of biological matrix can affect results when using NfL as biomarker in epidemiological studies.MethodWe obtained paired serum and EDTA-plasma samples of 299 individuals aged 37–67 years (BiDirect study) and serum samples of 373 individuals aged 65–83 years (MEMO study). In BiDirect, Passing–Bablok analyses were performed to assess proportional and systematic differences between biological matrices. Associations between serum or EDTA-plasma NfL and renal function (serum creatinine, serum cystatin C, glomerular filtration rate, and kidney disease) were investigated using linear or logistic regression, respectively. All regression coefficients were estimated (1) per one ng/L increase and (2) per one standard deviation increase (standardization using z-scores). In MEMO, regression coefficients were estimated (1) per one ng/L increase of serum or calculated EDTA-plasma NfL and (2) per one standard deviation increase providing a comparison to the results from BiDirect.ResultsWe found proportional and systematic differences between paired NfL measurements in BiDirect, i.e., serum NfL [ng/L] = −0.33 [ng/L] + 1.11 × EDTA-plasma NfL [ng/L]. Linear regression coefficients for the associations between NfL and renal function did not vary between the different NfL measurements. In MEMO, one standard deviation increase in serum NfL was associated with greater changes in the outcomes than in BiDirect.ConclusionAlthough there are differences between serum and EDTA-plasma NfL, results can be used interchangeably if standardized values are used.
Intestinal Microbiota Regulate Certain Meat Quality Parameters in Chicken
Authors: Lei Jiaqi , Dong Yuanyang , Hou Qihang , He Yang , Lai Yujiao , Liao Chaoyong , Kawamura Yoichiro , Li Junyou , Zhang Bingkun 
Published: June 2022

Growing evidence of intestinal microbiota-muscle axis provides a possibility to improve meat quality of broilers through regulating intestinal microbiota. Water-holding capacity is a crucial factor to evaluate the meat quality. High quality of water-holding capacity is usually described as a low drip-losing rate. This study aimed to explore the relationship between intestinal microbiota and water-holding capacity of muscle in broilers. According to our results, two native breeds of broilers (the Arbor Acres broilers and the Beijing-You broilers) exhibited remarkable differences in microbiota composition. However, the regular of gut bacteria compositions gradually became similar when the two breeds of broiler were raised in a same feeding environment. Therefore, this similar regular of intestinal microbiota induced similar water-holding capacity of the muscle from the two breeds. In subsequent fecal microbiota transplantation (FMT) experiments, the intestinal microbiota community of the Arbor Acres broilers was remodeling by oral gavage of bacterial suspension that was derived from the Beijing-You broilers. Then, not only body weight and abdominal fat rate were increased, but also drip loss of muscle was decreased in the Arbor Acres broilers. Additionally, muscle fiber diameter of biceps femoris muscle and expression of MyoD1 were notably enlarged. Muscle fiber diameter and related genes were deemed as important elements for water-holding capacity of muscle. Simultaneously, we screened typical intestinal bacteria in both the two native breeds of broilers by 16S rDNA sequencing. Lachnoclostridium was the only bacteria genus associated with drip-losing rate, meat fiber diameter, body weight, and abdominal fat rate.ImportanceHigher body weight and superior meat quality in livestock imply an adequate source of protein and substantial commercial value. Regulating the intestinal microbiota of broilers is a promising approach to optimize commercial phenotypes. Our results indicate that the intestinal microbiota profile could be reconstructed by external factors, leading to advantageous changes in muscle characteristics. The cecum microbiota of native broilers have the ability to improve certain meat quality and production performance. The population of Lachnoclostridium spp. could be used to regulate body weight and drip-losing rate in broilers, but more study is needed.
Long Non-Coding RNA-TMPO-AS1 as ceRNA Binding to let-7c-5p Upregulates STRIP2 Expression and Predicts Poor Prognosis in Lung Adenocarcinoma
Authors: Wang Juan , Yuan Yixiao , Tang Lin , Zhai Haoqing , Zhang Dahang , Duan Lincan , Jiang Xiulin , Li Chen 
Published: June 2022

BackgroundStriatin-interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth. But the role of STRIP2 in lung adenocarcinoma (LUAD) has not been discovered clearly. Thus, the aim of our study is to explore the function and underlying mechanism of STRIP2 in LUAD.MethodsExpression of STRIP2 was determined using the Cancer Genome Atlas (TCGA), GTEx, Ualcan, and the Human Protein Altas databases. The Correlation of STRIP2 and survival was detected by PrognoScan and Kaplan–Meier plotter databases. Besides, the correlation between STRIP2 expression and tumor immune infiltration as well as immune checkpoints were analyzed by the ssGSEA method. The biological function of STRIP2 and its co-expression genes was determined by gene ontology (GO) and Genes and Genomes (KEGG), respectively. Finally, the expression level and biological function of STRIP2 in LUAD were determined by qPCR, CCK8, transwell, and wound healing assays.ResultsThis manuscript revealed a significantly increased expression of mRNA and protein of STRIP2 in lung adenocarcinoma compared with the adjacent normal tissues. GEO and Kaplan–Meier plotter databases showed higher STRIP2 expression levels were correlated with poor prognosis survival of LUAD. Moreover, Cox regression analysis suggested that a higher STRIP2 level served as an independent risk factor in predicting deteriorative overall survival (OS) for LUAD patients. SsGSEA results showed STRIP2 expression level was positively correlated with infiltrating levels of Th2 cells in LUAD. Lastly, GO analysis indicated the biological processes were enriched in nuclear division and positive regulation of the cell cycle. KEGG signaling pathway analysis showed STRIP2 was correlated with the MAPK signaling pathway and the TNF signaling pathway. The GSEA database showed that STRIP2 was positively associated with the epithelial–mesenchymal transition, cell cycle, and TNF signaling pathway. The QRT-PCR assay showed that STRIP2 was upregulated in LUAD cell lines. Cell proliferation and migration were inhibited in LUAD by knockdown of STRIP2. Moreover, we confirmed that the TMPO-AS1/let-7c-5p/STRIP2 network regulates STRIP2 overexpression in LUAD and is associated with poor prognosis.ConclusionOur findings indicated that STRIP2 acted as a crucial oncogene in LUAD and was correlated with unfavorable survival and tumor infiltration inflation.
Reliability of Cell-Free DNA and Targeted NGS in Predicting Chromosomal Abnormalities of Patients With Myeloid Neoplasms
Authors: Ip Andrew , Della Pia Alexandra , Kim Gee Youn (Geeny) , Lofters Jason , Behrmann James , Patel Dylon , Kats Simone , Estella Jeffrey Justin , De Dios Ivan , Ma Wanlong , Pecora Andrew L. , Goy Andre H. , Koprivnikar Jamie , McCloskey James K. , Albitar Maher 
Published: June 2022

IntroductionCytogenetic analysis is important for stratifying patients with various neoplasms. We explored the use of targeted next generation sequencing (NGS) in detecting chromosomal structural abnormalities or copy number variations (CNVs) in patients with myeloid neoplasms.MethodsPlasma cell-free DNA (cfDNA) from 2821 myeloid or lymphoid neoplasm patients were collected. cfDNA was sequenced using a 275 gene panel. CNVkit software was used for analyzing and visualizing CNVs. Cytogenetic data from corresponding bone marrow (BM) samples was available on 89 myeloid samples.ResultsOf the 2821 samples, 1539 (54.5%) showed evidence of mutations consistent with the presence of neoplastic clones in circulation. Of these 1539 samples, 906 (59%) showed abnormalities associated with myeloid neoplasms and 633 (41%) with lymphoid neoplasms. Chromosomal structural abnormalities in cfDNA were detected in 146 (16%) myeloid samples and 76 (12%) lymphoid samples. Upon comparison of the myeloid samples with 89 BM patients, NGS testing was able to reliably detect chromosomal gain or loss, except for fusion abnormalities. When cytogenetic abnormalities were classified according to prognostic classes, there was a complete (100%) concordance between cfDNA NGS data and cytogenetic data.ConclusionsThis data shows that liquid biopsy using targeted NGS is reliable in detecting chromosomal structural abnormalities in myeloid neoplasms. In specific circumstances, targeted NGS may be reliable and efficient to provide adequate information without the need for BM biopsy considering broad mutation profiling can be obtained through adequate sequencing within the same test. Overall, this study supports the use of liquid biopsy for early diagnosis and monitoring of patients with myeloid neoplasms.
Characteristics of People Seeking Prescribed Cannabinoids for the Treatment of Chronic Pain: Evidence From Project Twenty 21
Authors: Schlag Anne Katrin , Lynskey Michael , Fayaz Alan , Athanasiou-Fragkouli Alkyoni , Brandner Brigitta , Haja Barbara , Iveson Elizabeth , Nutt David J. 
Published: June 2022

BackgroundPrescribed cannabinoids are now legal in the UK and increasingly being used for a variety of conditions, with one of the most frequent conditions being chronic pain. This paper describes the characteristics of individuals seeking prescribed cannabinoids for the treatment of chronic pain in Project Twenty 21, a UK based real world data registry of prescribed cannabis patients.MethodBy 1st November 2021 data were available for 1,782 people who had sought treatment with medical cannabis as part of Project Twenty 21. The most common diagnosis among this cohort was chronic pain with 949 (53.5%) of the cohort reporting a primary condition related to chronic pain. Medical and self-report data on the characteristics of these patients, their health status and type/s of cannabinoid/s prescribed are summarized in this report.ResultsOf the 949 people reporting chronic pain as a primary condition 54.7% were male and their average age was 42.0 years (range = 18–84). Patients reported a low quality of life and high levels of comorbidity: people reported an average of 4.6 comorbid conditions with the most common comorbid conditions including anxiety, depression, insomnia and stress. A range of cannabinoid products were prescribed with the most common products being classified as high THC flower (48.5%). The majority of patients also reported using at least one other prescribed medication (68.7%).ConclusionsConsistent with findings in other national and international databases, chronic pain was the most common primary condition in this real world study of prescribed cannabinoids. There was considerable variation in the types of chronic pain, comorbid pathology and in the characteristics of products being prescribed to treat these conditions. Together, this evidence supports the utility of real world evidence, as opposed to clinical trial approaches to studying the potential benefits of prescribed cannabinoids in treating chronic pain.
Investigational Drugs for the Treatment of Depression (Part 1): Monoaminergic, Orexinergic, GABA-Ergic, and Anti-Inflammatory Agents
Authors: Vasiliu Octavian 
Published: June 2022

Therapeutic management of depression has currently important limitations, and its low efficacy is reflected in high rates of non-response even after multiple trials of antidepressants. Almost two-thirds of the patients diagnosed with major depression who received a 4–6 weeks trial of antidepressant could not reach remission, and more than 30% of these patients are considered treatment-resistant. In bipolar depression, the situation is also discouraging if we analyze the high suicide rate, the risk for the treatment-emergent affective switch when antidepressants are added, the high rate of treatment resistance (up to 25%), and the severe functional impairments associated with these episodes. Therefore, new therapeutic agents are needed, as well as new pathogenetic models for depression. The vast majority of the currently approved antidepressants are based on the monoamine hypothesis, although new drugs exploiting different neurotransmitter pathways have been recently approved by FDA. Brexanolone, an allopregnanolone analog, is an example of such new antidepressants, and its approval for post-partum depression inspired the search for a new generation of neurosteroids and GABA-ergic modulators, with an easier way of administration and superior tolerability profile. Orexin receptors antagonists are also extensively studied for different psychiatric disorders, depression included, in phase II trials. Antiinflammatory drugs, both cyclo-oxygenase 2 inhibitors and biological therapy, are investigated in patients with depressive disorders based on the proven correlation between inflammation and mood disorders in preclinical and clinical studies. Also, a new generation of monoamine-based investigational drugs is explored, ranging from triple reuptake inhibitors to atypical antipsychotics, in patients with major depression. In conclusion, there is hope for new treatments in uni- and bipolar depression, as it became clear, after almost seven decades, that new pathogenetic pathways should be targeted to increase these patients’ response rate.
The Anti-Glioma Effect of Juglone Derivatives through ROS Generation
Authors: Zhang Jinsen , Fu Minjie , Wu Jinfeng , Fan Fengfeng , Zhang Xin , Li Chunjie , Yang Hui , Wu Yonghe , Yin Yiming , Hua Wei 
Published: June 2022

Juglone has been extensively reported as a natural antitumor pigment. However, it is easy to be oxidized due to active hydroxy in the quinone. Here, we designed some new juglone derivatives, as the hydroxy was replaced by methyl (D1), allyl (D2), butyl (D3), and benzyl (D4) groups. Nuclear magnetic resonance spectra and mass spectrometry were applied to confirm the derivatives and oxidative products of juglone. U87 and U251 cell lines were used for tests in vitro, and primary human glioblastoma cells were applied for in vivo experiments. The CCK8 and EdU assay demonstrated the anti-tumor effect of the four derivatives, and IC50 for U87 was 3.99, 3.28, 7.60, and 11.84 μM, respectively. In U251, IC50 was 7.00, 5.43, 8.64, and 18.05 μM, respectively. D2 and D3 were further selected, and flow cytometry showed that apoptosis rates were increased after D2 or D3 treatment via ROS generation. Potential targets were predicted by network pharmacology analysis, most of which were associated with apoptosis, cell cycle, and metabolism pathway. CDC25B and DUSP1 were two of the most likely candidates for targets. The orthotopic glioblastoma model was established to evaluate the anti-glioma effect and side-effect of juglone derivatives, and the in vivo experiments confirmed the anti-glioma effects of juglone derivatives. In conclusion, new derivatives of juglone were created via chemical group substitution and could inhibit glioma cell viability and proliferation and induce apoptosis rate via ROS generation.
Fluid-Structure Interaction Simulations of Repaired Type A Aortic Dissection: a Comprehensive Comparison With Rigid Wall Models
Authors: Zhu Yu , Mirsadraee Saeed , Rosendahl Ulrich , Pepper John , Xu Xiao Yun 
Published: June 2022

This study aimed to evaluate the effect of aortic wall compliance on intraluminal hemodynamics within surgically repaired type A aortic dissection (TAAD). Fully coupled two-way fluid-structure interaction (FSI) simulations were performed on two patient-specific post-surgery TAAD models reconstructed from computed tomography angiography images. Our FSI model incorporated prestress and different material properties for the aorta and graft. Computational results, including velocity, wall shear stress (WSS) and pressure difference between the true and false lumen, were compared between the FSI and rigid wall simulations. It was found that the FSI model predicted lower blood velocities and WSS along the dissected aorta. In particular, the area exposed to low time-averaged WSS (≤0.2 Pa) was increased from 21 cm2 (rigid) to 38 cm2 (FSI) in patient 1 and from 35 cm2 (rigid) to 144 cm2 (FSI) in patient 2. FSI models also produced more disturbed flow where much larger regions presented with higher turbulence intensity as compared to the rigid wall models. The effect of wall compliance on pressure difference between the true and false lumen was insignificant, with the maximum difference between FSI and rigid models being less than 0.25 mmHg for the two patient-specific models. Comparisons of simulation results for models with different Young’s moduli revealed that a more compliant wall resulted in further reduction in velocity and WSS magnitudes because of increased displacements. This study demonstrated the importance of FSI simulation for accurate prediction of low WSS regions in surgically repaired TAAD, but a rigid wall computational fluid dynamics simulation would be sufficient for prediction of luminal pressure difference.
Self-Stigma Among People With Mental Health Problems in Terms of Warmth and Competence
Authors: Gärtner Laura , Asbrock Frank , Euteneuer Frank , Rief Winfried , Salzmann Stefan 
Published: June 2022

IntroductionSelf-stigma arising from public stigma is a heavy burden for people suffering from mental health problems. Both public stigma and self-stigma encompass the same three elements: stereotype, prejudice, and discrimination. Public stigma has already been successfully explored by the Stereotype Content Model (SCM) and the Behaviors from Intergroup Affect and Stereotypes (BIAS) map. However, this is not the case for self-stigma. Therefore, this is the first study that applies SCM and the BIAS map to self-stigma by examining whether the effects of self-stereotypes on self-directed discrimination would be mediated by self-directed prejudices in people with mental health problems.MethodWithin a total sample of N = 823 participants, who took part in an online survey, n = 336 people reported mental health problems. Mental health and self-stereotypes (warmth, competence), self-directed prejudice (negative emotions), and self-directed discrimination (active/passive self-harm) were assessed.ResultsStructural equation modeling supported the hypothesis that the stereotype dimensions warmth and competence negatively related to prejudice, while stronger prejudice was associated with more discrimination (active/passive self-harm). Prejudice fully mediated the relationship between stereotypes and discrimination. The indirect effects of warmth and competence on active and passive self-harm were moderated by competence and warmth.DiscussionImplications for further research on self-stigma and the usage of SCM and BIAS map are discussed.
Key Informant Interviews to Inform Nutrition and Physical Activity Recovery Efforts in Child Care Settings amid the COVID-19 Pandemic in the United States
Authors: Nitto Allison M. , Berrigan David , Bremer Andrew A. , Kersten Sarah K. , Carpenter Leah R. , Yaroch Amy L. 
Published: June 2022

PurposeThe COVID-19 pandemic created a series of challenges for children's health, including several challenges related to nutrition and physical activity in child care settings. Thus, this study explored: 1) how COVID-19 impacted nutrition and physical activity in child care settings and how to address these challenges moving forward; 2) potential best practices in child care that emerged during the COVID-19 pandemic worth continuing; and 3) future directions for accessing, implementing, and evaluating COVID-19 federal investments in child care settings.MethodsThe study utilized a qualitative content analysis approach. In June 2021, the investigators conducted 17 qualitative interviews with federal representatives (n = 4), practitioners (n = 7), and researchers (n = 6). Recruitment continued until saturation was achieved. Virtual interviews lasted approximately 45 to 60 minutes and were recorded, transcribed, and coded for themes and subthemes using thematic content analysis.ResultsPrimary findings included: 1) COVID-19 likely increased stress and exacerbated prevalence of food insecurity for child care staff and participating families, and decreased diet quality among children both while in and outside of child care; 2) flexibilities to federal child care requirements, outdoor learning opportunities, and meal provision strategies implemented during the pandemic were perceived as positive and could continue post-pandemic; and 3) future efforts could utilize the recovery funds to make changes that are equitable and sustainable, such as conducting equity assessments and collaborating with community organizations, along with evaluating impacts of these efforts on food insecurity and health of child care staff and participating children.ConclusionOverall, recommendations focused on several social determinants of health, including addressing food insecurity among both children and staff, and infrastructure for nutrition and physical activity. Continued programmatic and public health recovery efforts aimed to mitigate the negative impacts of COVID-19 are critical to fostering health and wellbeing in child care settings.