bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Brain Functional Network Connectivity in Infants With Prenatal Opioid Exposure
Authors: Radhakrishnan Rupa , Vishnubhotla Ramana V. , Zhao Yi , Yan Jingwen , He Bing , Steinhardt Nicole , Haas David M. , Sokol Gregory M. , Sadhasivam Senthilkumar 
Published: March 2022

BackgroundInfants with prenatal opioid and substance exposure are at higher risk of poor neurobehavioral outcomes in later childhood. Early brain imaging in infancy has the potential to identify early brain developmental alterations that may help predict behavioral outcomes in these children. In this study, using resting-state functional MRI in early infancy, we aim to identify differences in global brain network connectivity in infants with prenatal opioid and substance exposure compared to healthy control infants.Methods and MaterialsIn this prospective study, we recruited 23 infants with prenatal opioid exposure and 29 healthy opioid naïve infants. All subjects underwent brain resting-state functional MRI before 3 months postmenstrual age. Covariate Assisted Principal (CAP) regression was performed to identify brain networks within which functional connectivity was associated with opioid exposure after adjusting for sex and gestational age. Associations of these significant networks with maternal comorbidities were also evaluated. Additionally, graph network metrics were assessed in these CAP networks.ResultsThere were four CAP network components that were significantly different between the opioid exposed and healthy control infants. Two of these four networks were associated with maternal psychological factors. Intra-network graph metrics, namely average flow coefficient, clustering coefficient and transitivity were also significantly different in opioid exposed infants compared to healthy controls.ConclusionPrenatal opioid exposure is associated with alterations in global brain functional networks compared to non-opioid exposed infants, with intra-network alterations in graph network modeling. These network alterations were also associated with maternal comorbidity, especially mental health. Large-scale longitudinal studies can help in understanding the clinical implications of these early brain functional network alterations in infants with prenatal opioid exposure.
Peripheral Neuropathy During Concomitant Administration of Proteasome Inhibitors and Factor Xa Inhibitors: Identifying the Likelihood of Drug-Drug Interactions
Authors: Meng Long , Huang Jing , Qiu Feng , Shan Xuefeng , Chen Lin , Sun Shusen , Wang Yuwei , Yang Junqing 
Published: March 2022

Backgrounds: Proteasome inhibitors (PI) cause toxic peripheral neuropathy (PN), which is one of the dose-limiting adverse events of these treatments. Recent preclinical studies find that factor Xa inhibitor (FXaI), rivaroxaban, promotes PN in animals receiving oxaliplatin. Cancer patients can receive combined therapy of PI and FXaI. This study aimed to identify and characterize the interaction signals for the concomitant use of PI and FXaI resulting in PN.Methods: Reports from the United States FDA Adverse Event Reporting System (FAERS) were extracted from the first quarter of 2004 to the first quarter of 2020 for analysis. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) query was used to identify PN cases. We conducted an initial disproportionality investigation to detect PN adverse event signals associated with the combined use of PI and FXaI by estimating a reporting odds ratio (ROR) with a 95% confidence interval (CI). The adjusted RORs were then analyzed by logistic regression analysis (adjusting for age, gender, and reporting year), and additive/multiplicative models were performed to further confirm the findings. Additionally, subset data analysis was performed on the basis of a single drug of PI and FXaI.Results: A total of 159,317 adverse event reports (including 2,822 PN reports) were included. The combined use of PI and FXaI was associated with a higher reporting of PN (RORadj = 7.890, 95%CI, 5.321–11.698). The result remained significant based on additive/multiplicative methods. The observed association was consistent in the analysis restricted to all specific PI agents (bortezomib and ixazomib) and FXaI (rivaroxaban), except apixaban.Conclusion: Analysis of FAERS data identified reporting associations of PN in the combined use of PI and FXaI, suggesting the need for more robust preclinical and clinical studies to elucidate the relationship.
Mitochondrial Protein Akap1 Deletion Exacerbates Endoplasmic Reticulum Stress in Mice Exposed to Hyperoxia
Authors: Sidramagowda Patil Sahebgowda , Soundararajan Ramani , Fukumoto Jutaro , Breitzig Mason , Hernández-Cuervo Helena , Alleyn Matthew , Lin Muling , Narala Venkata Ramireddy , Lockey Richard , Kolliputi Narasaiah , Galam Lakshmi 
Published: March 2022

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are treated with high concentrations of supplementary oxygen. However, prolonged exposure to high oxygen concentrations stimulates the production of reactive oxygen species (ROS), which damages the mitochondria and accumulates misfolded proteins in the endoplasmic reticulum (ER). The mitochondrial protein A-kinase anchoring protein 1 (Akap1) is critical for mitochondrial homeostasis. It is known that Akap1 deficiency results in heart damage, neuronal development impairment, and mitochondrial malfunction in preclinical studies. Our laboratory recently revealed that deleting Akap1 increases the severity of hyperoxia-induced ALI in mice. To assess the role of Akap1 deletion in ER stress in lung injury, wild-type and Akap1−/− mice were exposed to hyperoxia for 48 h. This study indicates that Akap1−/− mice exposed to hyperoxia undergo ER stress, which is associated with an increased expression of BiP, JNK phosphorylation, eIF2α phosphorylation, ER stress-induced cell death, and autophagy. This work demonstrates that deleting Akap1 results in increased ER stress in the lungs of mice and that hyperoxia exacerbates ER stress-related consequences.
Deferoxamine Alleviates Osteoarthritis by Inhibiting Chondrocyte Ferroptosis and Activating the Nrf2 Pathway
Authors: Guo Zhou , Lin Jiamin , Sun Kai , Guo Jiayou , Yao Xudong , Wang Genchun , Hou Liangcai , Xu Jingting , Guo Jiachao , Guo Fengjing 
Published: March 2022

Objective: Osteoarthritis (OA) is a common disease with a complex pathology including mechanical load, inflammation, and metabolic factors. Chondrocyte ferroptosis contributes to OA progression. Because iron deposition is a major pathological event in ferroptosis, deferoxamine (DFO), an effective iron chelator, has been used to inhibit ferroptosis in various degenerative disease models. Nevertheless, its OA treatment efficacy remains unknown. We aimed to determine whether DFO alleviates chondrocyte ferroptosis and its effect on OA and to explore its possible mechanism.Methods: Interleukin-1β (IL-1β) was used to simulate inflammation, and chondrocyte ferroptosis was induced by erastin, a classic ferroptosis inducer. A surgical destabilized medial meniscus mouse model was also applied to simulate OA in vivo, and erastin was injected into the articular cavity to induce mouse knee chondrocyte ferroptosis. We determined the effects of DFO on ferroptosis and injury-related events: chondrocyte inflammation, extracellular matrix degradation, oxidative stress, and articular cartilage degradation.Results: IL-1β increased the levels of ROS, lipid ROS, and the lipid peroxidation end product malondialdehyde (MDA) and altered ferroptosis-related protein expression in chondrocytes. Moreover, ferrostatin-1 (Fer-1), a classic ferroptosis inhibitor, rescued the IL-1β–induced decrease in collagen type II (collagen II) expression and increase in matrix metalloproteinase 13 (MMP13) expression. Erastin promoted MMP13 expression in chondrocytes but inhibited collagen II expression. DFO alleviated IL-1β– and erastin-induced cytotoxicity in chondrocytes, abrogated ROS and lipid ROS accumulation and the increase in MDA, improved OA-like changes in chondrocytes, and promoted nuclear factor E2–related factor 2 (Nrf2) antioxidant system activation. Finally, intra-articular injection of DFO enhanced collagen II expression in OA model mice, inhibited erastin-induced articular chondrocyte death, and delayed articular cartilage degradation and OA progression.Conclusion: Our research confirms that ferroptosis occurs in chondrocytes under inflammatory conditions, and inhibition of chondrocyte ferroptosis can alleviate chondrocyte destruction. Erastin-induced chondrocyte ferroptosis can stimulate increased MMP13 expression and decreased collagen II expression in chondrocytes. DFO can suppress chondrocyte ferroptosis and promote activation of the Nrf2 antioxidant system, which is essential for protecting chondrocytes. In addition, ferroptosis inhibition by DFO injection into the articular cavity may be a new OA treatment.
Brief Maternal Separation Inoculates Against the Effects of Social Stress on Depression-Like Behavior and Cocaine Reward in Mice
Authors: Calpe-López C. , Martínez-Caballero M. A. , García-Pardo M. P. , Aguilar M. A. 
Published: March 2022

Exposure to intermittent repeated social defeat (IRSD) increases the vulnerability of mice to the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. According to the “inoculation of stress” hypothesis, a brief period of maternal separation (MS) can provide protection against the negative effects of IRSD. The aim of the present study was to assess whether exposure to a brief episode of MS prevents the subsequent short-term effects of IRSD on depression- and anxiety-like behaviors and to explore its long-term effects on cocaine CPP in mice. Four groups of male C57BL/6 mice were employed; two groups were separated from their mother [6 h on postnatal day (PND) 9], while the other two groups were not (controls). On PND 47, 50, 53 and 56, mice that had experienced MS were exposed to social defeat in the cage of an aggressive resident mouse (MS + IRSD group) or were allowed to explore an empty cage (MS + EXPL group). The same procedure was performed with control mice that had not experienced MS (CONTROL + IRSD and CONTROL + EXPL groups). On PND57-58, all the mice performed the elevated plus maze and the hole-board, social interaction and splash tests. Three weeks after the last episode of defeat, all the mice underwent the CPP procedure with cocaine (1 mg/kg). Irrespective of whether or not MS had taken place, a reduction in open arms measures, dips, and social interaction was observed in mice that experienced IRSD. A higher latency of grooming and acquisition of cocaine-induced CPP were observed only in mice exposed to IRSD alone (CONTROL + IRSD). These results suggest that exposure to a brief episode of stress early in life increases the subsequent resilience of animals to the effects of social stress on vulnerability to cocaine.
Discovery of Novel HPK1 Inhibitors Through Structure-Based Virtual Screening
Authors: Ge Huizhen , Peng Lizeng , Sun Zhou , Liu Huanxiang , Shen Yulin , Yao Xiaojun 
Published: March 2022

Hematopoietic progenitor kinase (HPK1) is a negative regulator of T-cell receptor and B-cell signaling, which has been recognized as a novel antitumor target for immunotherapy. In this work, Glide docking-based virtual screening and kinase inhibition assay were performed to identify novel HPK1 inhibitors. The kinase inhibition assay results demonstrated five compounds with IC50 values below 20 μM, and the most potent one (compound M074-2865) had an IC50 value of 2.93 ± 0.09 μM. Molecular dynamics (MD) simulations were performed to delve into the interaction of sunitinib and the identified compound M074-2865 with the kinase domain of HPK1. The five compounds identified in this work could be considered promising hit compounds for further development of HPK1 inhibitors for immunotherapy.
Continuous Activation of Dopamine Receptors Alleviates LPS-Induced Liver Injury in Mice via β-arrestin2 Dependent Akt/NF-κB Pathway
Authors: Li Mingan , Zhang Ce , Zhou Lin , Sun Xiaohui , Wang Tian , Fu Fenghua 
Published: March 2022

Many studies showed that dopamine receptors (DRs) agonists have anti-inflammatory effects. Rotigotine, a non-ergot dopamine receptor agonist, mainly actives DRD2/DRD3/DRD1. Rotigotine extended-release microspheres (RoMS) are a sustained-release formulation that can release sustainably rotigotine for more than 7 days after a single dose of RoMS. This study aimed to investigate whether RoMS can attenuate the lipopolysaccharide (LPS)-induced liver injury of mice. The liver injury was evaluated by assaying serum transaminase and observing histopathological changes. The levels of pro-inflammatory cytokines in serum were also detected. Western blot was employed to assay the expression of proteins in the Akt/NF-κB pathway. The results showed that pre-administration with a single dose of RoMS could inhibit the increase of serum transaminase induced by LPS, alleviate the pathological damage of liver tissue, and decrease the levels of tumor necrosis factor-α and interleukin-6. In addition, RoMS decreased Toll-like receptor 4 protein expression in liver tissue. RoMS mitigated liver injury by activating DRs and negatively regulating the β-arrestin2-dependent Akt/NF-κB signaling pathway. The effects of RoMS could be weakened or abolished by the specific DRD2 antagonist, R121. In conclusion, activation of DRs inhibited the releases of pro-inflammatory cytokines and alleviated the immune-mediated liver injury induced by LPS in mice. The anti-inflammatory mechanism of RoMS may be related to the regulation of the β-arrestin2-dependent Akt/NF-κB signaling pathway.
The Role of Different Afferent Systems in the Modulation of the Otolith-Ocular Reflex After Long-Term Space Flights
Authors: Glukhikh Dmitrii O. , Naumov Ivan A. , Schoenmaekers Catho , Kornilova Ludmila N. , Wuyts Floris L. 
Published: March 2022

BackgroundThe vestibular (otolith) function is highly suppressed during space flight (SF) and the study of these changes is very important for the safety of the space crew during SF missions. The vestibular function (particularly, otolith-ocular reflex–OOcR) in clinical and space medicine is studied using different methodologies. However, different methods and methodologies can influence the outcome results.ObjectiveThe current study addresses the question of whether the OOcR results obtained by different methods are different, and what the role is of the different afferent systems in the modulation of the OOcR.MethodsA total of 25 Russian cosmonauts voluntarily took part in our study. They are crewmembers of long duration space missions on the International Space Station (ISS). Cosmonauts were examined in pre- and post-flight “Sensory Adaptation” and “Gaze Spin” experiments, twice before (preflight) and three times after SF (post-flight). We used two different video oculography (VOG) systems for the recording of the OOcR obtained in each experiment.ResultsComparison of the two VOG systems didn’t result into significant and systematic differences in the OOcR measurements. Analysis of the static torsion otolith–ocular reflex (OOR), static torsion otolith–cervical–ocular reflex (OCOR) and static torsion otolith–ocular reflex during eccentric centrifugation (OOREC) shows that the OOREC results in a lower OOcR response compared to the OOR and OCOR (before flight and late post-flight). However, all OOcRs were significantly decreased in all cosmonauts early post-flight.ConclusionAnalysis of the results of ocular counter rolling (OCR) obtained by different methods (OOR, OCOR, and OOREC) showed that different afferent systems (tactile-proprioception, neck-cervical, visual and vestibular afferent input) have an impact on the OOcR.
Examining the Prevalence and Risk Factors of School Bullying Perpetration Among Chinese Children and Adolescents
Authors: Xue Jia , Hu Ran , Chai Lei , Han Ziqiang , Sun Ivan Y. 
Published: March 2022

Background and ObjectivesSchool bullying threatens the health of children and adolescents, such as mental health disorders, social deviant behaviors, suicidal behaviors, and coping difficulties. The present study aims to address (1) prevalence rates of both traditional and cyber school bullying perpetration, and (2) the associations between self-control, parental involvement, experiencing conflicts with parents, experiencing interparental conflict, and risk behaviors, and school bullying perpetration among Chinese children and adolescents.MethodThis study used data from a national representative school bullying survey (n= 3,675) among children and adolescents from all grades (primary school 4th grade to high school 12th grade) in seven cities in China. Negative binomial regression was used to estimate the effects of these predictive factors on traditional and cyber school bullying perpetration, respectively. Seven control variables were included, such as gender, boarding school, family socioeconomic status, and parents’ education levels.ResultsThe sample comprised 52% female, 18% at boarding school, 70% of the participants’ academic performance was average or above. Approximately 17.3% of the participants reported participating in traditional school bullying against their peers, and 7.8% perpetrated cyberbullying behaviors. Also, after controlling sociodemographic characteristics and high self-control, parental involvement reduced the likelihood of traditional and cyberbullying perpetrating. Experiencing interparental conflict and risk behavior was significantly associated with increased perpetration of traditional and cyber school bullying. We found that having a conflict with parents was significantly associated with cyberbullying perpetration.ImplicationsFindings have implications for practice. Anti-bullying intervention programs targeting this population should consider these factors. For example, school administrators may develop school programs involving parents in the efforts and interventions workshops improving children and adolescents’ levels of self-control. Limitations are also discussed.
A Study on the Correlation Between Quality of Life and Unhealthy Emotion Among Patients With Endometriosis
Authors: He Guimei , Chen Jiebing , Peng Zhangqing , Feng Kai , Luo Chunqi , Zeng Xun 
Published: March 2022

ObjectiveTo investigate the influence of quality of life (QOL) on unhealthy emotions as well as relevant factors among patients with endometriosis for supporting relevant clinical care.MethodsA convenience sampling method was used to administer questionnaires to 139 patients with endometriosis, using the Hamilton Anxiety Inventory (HAMA), the Depression Anxiety Scale (SDS), and the SF-12 Health Survey Short Form, and the results were analyzed. The SPSS20.0 software was used for statistical analysis on relevant data. If P &lt; 0.05, there was statistical significance.ResultsTwelve-Item Short Form (SF-12) for health survey covered two comprehensive indexes, i.e., physical component summary (PCS) and mental component summary (MCS) scores. MCS score was the main factor influencing anxiety and depression in patients with endometriosis; the higher the MCS score, the lower the anxiety and depression degrees in patients with endometriosis (OR = 0.912, 95% CI: 0.877–0.949; OR = 0.899, 95% CI: 0.866–0.933). PCS score was a factor influencing anxiety degree; the higher the PCS score, the lower the anxiety degree (OR = 0.936, 95% CI: 0.891–0.983).ConclusionThe QOL of patients with endometriosis is negatively correlated with anxiety and depression. Therefore, improvement in QOL may help relevant patients to relieve their unhealthy emotions.
Bullying, Psychological, and Physical Trauma During Early Life Increase Risk of Major Depressive Disorder in Adulthood: A Nationwide Community Sample of Korean Adults
Authors: Kim Hyun Soo , Pyo Hong Jin , Fava Maurizio , Mischoulon David , Park Mi Jin , Jeon Hong Jin 
Published: March 2022

BackgroundThere is an association between early life traumas and the development of depression in adults. Few studies have used nationwide population-based samples to investigate whether the type of early life trauma differentially influences the risk of developing depression.MethodsMajor depressive disorder and early life trauma were assessed using the Korean version of the Composite International Diagnostic Interview (K-CIDI) for DSM-IV psychiatric disorder and a questionnaire for early life trauma in the Korean Epidemiological Catchment Area Study in 2016. A total of 4,652 participants were included in the final analysis. This study evaluated the effect of the type and frequency of reported early life trauma on the risk of developing MDD and the association between reported early life trauma and differential symptoms of MDD.ResultsIndividuals with reported early life trauma had a 3.7-fold increased risk of MDD. The risk of MDD was associated with bullying trauma (odds ratio (OR) = 1.847, p = 0.005) after adjusting for age, gender, marriage, job, and education years. The risk of MDD was increased as the types of reported early life traumas increased.ConclusionBullying trauma during early life represents a risk factor for MDD, especially in individuals exposed to multiple traumas in early life.
Contributions of COVID-19 Pandemic-Related Stressors to Racial and Ethnic Disparities in Mental Health During Pregnancy
Authors: Avalos Lyndsay A. , Nance Nerissa , Zhu Yeyi , Croen Lisa A. , Young-Wolff Kelly C. , Zerbo Ousseny , Hedderson Monique M. , Ferrara Assiamira , Ames Jennifer L. , Badon Sylvia E. 
Published: March 2022

BackgroundThis study aimed to identify racial and ethnic disparities in prenatal mental health and identify COVID-19 pandemic-related health/healthcare and economic contributors to these disparities, using an established framework for disparity investigation.MethodsThis cross-sectional study includes 10,930 pregnant people at Kaiser Permanente Northern California who completed an online survey between June 22, 2020 and April 28, 2021 on COVID-19 pandemic-related health/healthcare and economic stressors, depression, and anxiety. Self-reported race and ethnicity were extracted from electronic health records. Weighted analyses were used to evaluate the association between racial and ethnic category and prenatal depression and anxiety; the prevalence of each stressor by race and ethnicity; and the relationship between each stressor and prenatal depression and anxiety in each racial and ethnic category.ResultsThe sample was 22% Asian, 3% Black, 20% Hispanic, 5% Other/Multiracial/Unknown, and 49% White. Compared to White people, Black and Hispanic people had a higher prevalence of prenatal depression (aPR: 1.85, 95% CI: 1.45, 2.35 and aPR: 1.17, 95% CI: 1.00, 1.37, respectively) and anxiety (aPR: 1.71, 95% CI: 1.34, 2.18 and aPR: 1.10, 95% CI: 0.94, 1.29, respectively). Compared to White people, Black and Hispanic people had a higher prevalence of moderate/severe distress due to changes in prenatal care (24 vs. 34 and 31%), and food insecurity (9 vs. 31 and 24%). Among Black and Hispanic people, distress due to changes in prenatal care was associated with a greater prevalence of prenatal depression (aPR: 2.27, 95% CI: 1.41, 3.64 and aPR: 2.76, 95% CI: 2.12, 3.58, respectively) and prenatal anxiety (aPR: 3.00, 95% CI: 1.85, 4.84 and aPR: 2.82, 95% CI: 2.15, 3.71, respectively). Additionally, among Hispanic people, high-risk employment and food insecurity were associated with a greater prevalence of prenatal depression and anxiety.ConclusionsThis study identified racial and ethnic disparities in mental health for pregnant Black and Hispanic people. Distress due to prenatal care changes contributed to the observed disparities in prenatal depression and anxiety for Black and Hispanic people and food insecurity additionally contributed to the observed disparities for Hispanic people. Addressing distress due to changes to prenatal care and food insecurity specifically in Black and Hispanic people may help reduce the high burden of poor mental health and reduce observed disparities in these communities.