bluuebunny/crossref_metadata_2025_split huggingface dataset:
AQP9 Is a Prognostic Factor for Kidney Cancer and a Promising Indicator for M2 TAM Polarization and CD8+ T-Cell Recruitment
Authors: Jing Jibo , Sun Jin , Wu Yuqing , Zhang Nieke , Liu Chunhui , Chen Saisai , Li Wenchao , Hong Cheng , Xu Bin , Chen Ming 
Published: November 2021

BackgroundIt is undeniable that the tumor microenvironment (TME) plays an indispensable role in the progression of kidney renal clear cell carcinoma (KIRC). However, the precise mechanism of activities in TME is still unclear.Methods and ResultsUsing the CIBERSORT and ESTIMATE calculation methods, the scores of the two main fractions of tumor-infiltrating immune cells (TICs) from The Cancer Genome Atlas (TCGA) database of 537 KIRC patients were calculated. Subsequently, differentially expressed genes (DEGs) were drawn out by performing an overlap between Cox regression analysis and protein–protein interaction (PPI) network. Aquaporin 9 (AQP9) was identified as a latent predictor through the process. Following research revealed that AQP9 expression was positively correlated with the pathological characteristics (TNM stage) and negatively connected with survival time. Then, by performing gene set enrichment analysis (GSEA), it can be inferred that genes with high expression level of AQP9 were mainly enriched in immune-related activities, while low AQP9 group was associated with functions of cellular metabolism. Further studies have shown that regulatory T cells (Tregs), macrophages M2, macrophages M0, CD4+ T cells, and neutrophils were positively correlated with AQP9 expression. While the levels of mast cells, natural killer (NK) cells, and CD8+ T cells are negatively correlated with AQP9. The result of multiple immunohistochemistry (mIHC) suggests a negative relevance between AQP9 and CD8+ T cells and reveals a trend of consistent change on AQP9 and M2 macrophages.ConclusionThe expression level of AQP9 may be helpful in predicting the prognosis of patients with KIRC, especially to the TME state transition, the mechanism of which is possibly through lipid metabolism and P53, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways that affect M2 polarization. AQP9 was associated with the expression levels of M2, tumor-associated macrophages (TAMs), and the recruitment of CD8+ T cells in tumor environment. The research result indicates that AQP9 may be an obstacle to maintain the immune activity of TME.
Lack of Effects of the Presence of a Dog on Pain Perception in Healthy Participants—A Randomized Controlled Trial
Authors: Wagner Cora , Gaab Jens , Locher Cosima , Hediger Karin 
Published: November 2021

Animal-assisted interventions (AAIs) have been shown to be effective in the treatment of pain. Studies suggest that relationships with animals can have comparable qualities to relationships with humans and that this enables animals to provide social support. Further, the presence of an animal can strengthen the therapeutic alliance between patients and treatment providers. This suggests that the analgesic effects of AAI might be mediated by social support from an animal or by strengthening the alliance between the patient and the treatment provider. To test these assumptions, we examined the effects of the presence of a dog on experimentally induced pain in a pain assessment and a pain therapy context. Hundred thirty-two healthy participants were randomly assigned to the conditions “pain,” “pain + dog,” “pain + placebo,” or “pain + placebo + dog.” We collected baseline and posttreatment measurements of heat-pain tolerance and the heat-pain threshold and of the corresponding subjective ratings of heat-pain intensity and unpleasantness as well as of participants' perceptions of the study investigator. The primary outcome was heat-pain tolerance. The presence of the dog did not influence the primary outcome (“pain” vs. “pain + dog”: difference = 0.04, CI = −0.66 to 0.74, p = 0.905; “pain + placebo” vs. “pain + placebo + dog”: difference = 0.43, CI = −0.02 to 0.88, p = 0.059). Participants did also not perceive the study investigator to be more trustworthy in the presence of the dog (“pain” vs. “pain + dog”: difference = 0.10, CI = −0.67 to 0.87, p = 0.796; “pain + placebo” vs. “pain + placebo + dog”: difference = 0.11, CI = −0.43 to 0.64, p = 0.695). The results indicate that the mere presence of a dog does not contribute to pain reduction and that the analgesic effects of AAI that previous studies have found is not replicated in our study as AAI did not increase perceived social support and had no effect on the alliance between the participant and the treatment provider. We assume that the animal most likely needs to be an integrated and plausible part of the treatment rationale so that participants are able to form a treatment-response expectation toward AAI.Clinical Trial Registration: This study was preregistered as a clinical trial on www.clinicaltrials.gov (Identifier: NCT0389814).
Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain
Authors: Willits Adam B. , Grossi Victoria , Glidden Nicole C. , Hyams Jeffrey S. , Young Erin E. 
Published: November 2021

Objectives: Functional Abdominal Pain (FAP) and Irritable Bowel Syndrome (IBS) are common recurrent abdominal pain diagnoses with the hallmark, lack of inflammation. To identify a biological signature for IBS/FAP in the colon, this study used genetic profiling to uncover gene expression changes associated with IBS/FAP and abdominal pain.Methods: Patients (8 to 17 years) newly diagnosed with IBS or FAP were enrolled in the study. At diagnostic colonoscopy, three rectal biopsies were collected, and gene expression analysis was performed using a Qiagen PCR Array. Relative fold difference in gene expression for 84 pain-associated genes was calculated using the 2-ΔΔ Cq method compared with pain-free controls. Factors affecting pain burden (Pain Burden Interview; PBI) were analyzed, including age, sex, rectal inflammation, and gene expression. Data were analyzed using multiple stepwise linear regression and 2-tailed t tests (P ≤ 0.05).Results: Of the 22 total patients in the study, 19 were diagnosed with either IBS-Constipation (frequency of 5.26%), IBS-Diarrhea (47.37%), IBS-Mixed (10.53%), or FAP (36.84%). IBS/FAP patients reported significantly higher pain burden at the time of diagnosis compared to pain-free controls (p &lt; 0.001), as well as significantly higher abdominal pain (p = 0.01). Of the 84 genes, expression of GRIN1 (p = 0.02), MAPK3 (p = 0.04), P2X4 (p = 0.04), and PTGES3 (p = 0.02) were all significantly associated with PBI score.Discussion: Abdominal pain associated with IBS/FAP in pediatric patients may be linked to the expression of GRIN1, MAPK3, P2X4, and PTGES3, pointing to potential novel therapeutic targets for management of recurring abdominal pain.
Association Between Platelet-to-Lymphocyte Ratio and Preterm Necrotizing Enterocolitis
Authors: Zheng Juan , Wang Hua 
Published: November 2021

Introduction: Necrotizing enterocolitis (NEC) is a fatal condition for very-low-birth-weight infants. Necrotizing enterocolitis is a multi-factor phenomenon that results in intestinal mucosal damage and leads to intestinal necrosis. However, sensitive laboratory indicators for NEC are lacking, making early diagnosis difficult. This study aimed to explore the relationship between the platelet-to-lymphocyte ratio (PLR) and NEC in preterm neonates to enable an earlier diagnosis of the condition.Methods: This was a retrospective case–control study of preterm neonates diagnosed with NEC between January 2018 and December 2019 in the West China Second University Hospital. Controls were selected from preterm neonatal intensive care unit (NICU) graduates, and they were matched for gestation and year of birth to the preterms diagnosed without NEC. In total, 93 and 107 infants were included in the NEC and control groups, respectively. Empowerstats analysis was used to identify the association between PLR and preterm NEC.Results: The NEC group had significantly higher PLR levels than the control group. PLR &gt; 100 within 1 week before NEC diagnosis was a risk factor for NEC. There was a positive connection between PLR and preterm NEC. A PLR of &gt;100 was determined as the optimal cutoff for predicting preterm NEC, with patients with PLR &gt;100 having a higher risk of NEC [odds ratio (OR): 18.82 (95% confidence interval (CI): 2.93–120.98), p = 0.002].Conclusions: A PLR of &gt;100 within 1 week after clinical abnormalities is associated with a high risk of NEC in preterm neonates.
Outcomes of High-Flow Nasal Cannula Vs. Nasal Continuous Positive Airway Pressure in Young Children With Respiratory Distress: A Systematic Review and Meta-Analysis
Authors: Zhao Xueqin , Qin Qiaozhi , Zhang Xian 
Published: November 2021

Background: Continuous positive airway pressure (CPAP) has been associated with a lower risk of treatment failure than high-flow nasal cannula (HFNC) in pediatric patients with respiratory distress and severe hypoxemia. However, the publication of new trials on children younger than 2 years warrants a review and updated meta-analysis of the evidence.Methods: We conducted a systematic search in the PubMed, Scopus, and Google scholar databases for randomized controlled trials (RCTs) in pediatric patients with acute respiratory distress that examined outcomes of interest by the two usual management modalities (CPAP and HFNC). We used pooled adjusted relative risks (RRs) to present the strength of association for categorical outcomes and weighted mean differences (WMDs) for continuous outcomes.Results: We included data from six articles in the meta-analysis. The quality of the studies was deemed good. Included studies had infants with either acute viral bronchiolitis or pneumonia. Compared to CPAP, HFNC treatment carried a significantly higher risk of treatment failure [RR, 1.45; 95% CI, 1.06 to 1.99; I2 = 0.0%, n = 6]. Patients receiving HFNC had a lower risk of adverse events, mainly nasal trauma [RR, 0.30; 95% CI, 0.14 to 0.62; I2 = 0.0%, n = 2] than the others. The risk of mortality [RR, 3.33; 95% CI, 0.95, 11.67; n = 1] and need for intubation [RR, 1.69; 95% CI, 0.97, 2.94; I2 = 0.0%, n = 5] were statistically similar between the two management strategies; however, the direction of the pooled effect sizes is indicative of a nearly three times higher mortality and two times higher risk of intubation in those receiving HFNC. We found no statistically significant differences between the two management modalities in terms of modified woods clinical asthma score (M-WCAS; denoting severity of respiratory distress) and hospitalization length (days). Patients receiving HFNC had the time to treatment failure reduced by approximately 3 h [WMD, −3.35; 95% CI, −4.93 to −1.76; I2 = 0.0%, n = 2] compared to those on CPAP.Conclusions: Among children with respiratory distress younger than 2 years, HFNC appears to be associated with higher risk of treatment failure and possibly, an increased risk of need for intubation and mortality. Adequately powered trials are needed to confirm which management strategy is better.
Transgenic Overexpression of Galectin-3 in Pancreatic β Cells Attenuates Hyperglycemia in Mice: Synergistic Antidiabetic Effect With Exogenous IL-33
Authors: Jovicic Nemanja , Petrovic Ivica , Pejnovic Nada , Ljujic Biljana , Miletic Kovacevic Marina , Pavlovic Sladjana , Jeftic Ilija , Djukic Aleksandar , Srejovic Ivan , Jakovljevic Vladimir , Lukic Miodrag L 
Published: November 2021

Galectin-3 (Gal-3) has diverse roles in inflammatory and autoimmune diseases. There is evidence that Gal-3 plays a role in both type 1 and type 2 diabetes. While the role of Gal-3 expression in immune cells invading the pancreatic islets in the experimental model of type 1 diabetes mellitus has been already studied, the importance of the overexpression of Gal-3 in the target β cells is not defined. Therefore, we used multiple low doses of streptozotocin (MLD–STZ)–induced diabetes in C57Bl/6 mice to analyze the effect of transgenic (TG) overexpression of Gal-3 in β cells. Our results demonstrated that the overexpression of Gal-3 protected β cells from apoptosis and attenuated MLD–STZ–induced hyperglycemia, glycosuria, and ketonuria. The cellular analysis of pancreata and draining lymph nodes showed that Gal-3 overexpression significantly decreased the number of pro-inflammatory cells without affecting the presence of T-regulatory cells. As the application of exogenous interleukin 33 (IL-33) given from the beginning of MLD–STZ diabetes induction attenuates the development of disease, by increasing the presence of regulatory FoxP3+ST2+cells, we evaluated the potential synergistic effect of the exogenous IL-33 and TG overexpression of Gal-3 in β cells at the later stage of diabetogenesis. The addition of IL-33 potentiated the survival of β cells and attenuated diabetes even when administered later, after the onset of hyperglycemia (12–18 days), suggesting that protection from apoptosis and immunoregulation by IL-33 may attenuate type 1 diabetes.
Identification of Hypoxia Induced Metabolism Associated Genes in Pulmonary Hypertension
Authors: He Yang-Yang , Xie Xin-Mei , Zhang Hong-Da , Ye Jue , Gencer Selin , van der Vorst Emiel P. C. , Döring Yvonne , Weber Christian , Pang Xiao-Bin , Jing Zhi-Cheng , Yan Yi , Han Zhi-Yan 
Published: November 2021

Objective: Pulmonary hypertension (PH) associated with hypoxia and lung disease (Group 3) is the second most common form of PH and associated with increased morbidity and mortality. This study was aimed to identify hypoxia induced metabolism associated genes (MAGs) for better understanding of hypoxic PH.Methods: Rat pulmonary arterial smooth muscle cells (PASMCs) were isolated and cultured in normoxic or hypoxic condition for 24 h. Cells were harvested for liquid chromatography-mass spectrometry analysis. Functional annotation of distinguishing metabolites was performed using Metaboanalyst. Top 10 enriched metabolite sets were selected for the identification of metabolism associated genes (MAGs) with a relevance score &gt;8 in Genecards. Transcriptomic data from lungs of hypoxic PH in mice/rats or of PH patients were accessed from Gene Expression Omnibus (GEO) database or open-access online platform. Connectivity Map analysis was performed to identify potential compounds to reverse the metabolism associated gene profile under hypoxia stress. The construction and module analysis of the protein-protein interaction (PPI) network was performed. Hub genes were then identified and used to generate LASSO model to determine its accuracy to predict occurrence of PH.Results: A total of 36 altered metabolites and 1,259 unique MAGs were identified in rat PASMCs under hypoxia. 38 differentially expressed MAGs in mouse lungs of hypoxic PH were revealed, with enrichment in multi-pathways including regulation of glucose metabolic process, which might be reversed by drugs such as blebbistatin. 5 differentially expressed MAGs were displayed in SMCs of Sugen 5416/hypoxia induced PH rats at the single cell resolution. Furthermore, 6 hub genes (Cat, Ephx1, Gpx3, Gstm4, Gstm5, and Gsto1) out of 42 unique hypoxia induced MAGs were identified. Higher Cat, Ephx1 and lower Gsto1 were displayed in mouse lungs under hypoxia (all p &lt; 0.05), in consistent with the alteration in lungs of PH patients. The hub gene-based LASSO model can predict the occurrence of PH (AUC = 0.90).Conclusion: Our findings revealed six hypoxia-induced metabolism associated hub genes, and shed some light on the molecular mechanism and therapeutic targets in hypoxic PH.
Emotional Distress in Cancer Patients During the First Wave of the COVID-19 Pandemic
Authors: Toquero Patricia , Blanco Fernández Carmen , López Martí María Pilar , Hernández Marín Berta , Vera Cea E. Beatriz , Garrido García Ana , Méndez Carrascosa Elena , Bañón Torres Dulce , Donnay Candil Olga , Ballesteros García Ana Isabel , Sánchez-Torres José Miguel , Costas Rojo Pablo , Mondéjar Rebeca , Colomer Ramon , Romero-Laorden Nuria 
Published: November 2021

Background: The COVID-19 pandemic has caused mental health problems worldwide. The psychopathological implications of COVID-19 in cancer patients have rarely been addressed. Considering the increased vulnerability of oncology patients, this issue needs to be addressed to improve the long-term mental health status of these patients.Methods: We conducted a prospective study in outpatients under active cancer treatment during the first wave of the COVID-19 pandemic. A semi-structured 24-question survey was designed to measure baseline sociodemographic, psychosocial and COVID-19 exposure characteristics. The Hospital Anxiety and Depression Scale was used to measure psychological symptoms. A descriptive and analytical univariate analysis of the variables studied was performed. We used the Z-score to compare different populations (experimental and historical control cohort).Results: 104 patients were included, the majority of which were women (64.4%), were above 65 years of age (57.7%), had either lung and breast cancer (56.7%), had advanced disease (64%) and were undergoing chemotherapy (63.5%). 51% of them expressed greater fear of cancer than of COVID-19 infection or both.In relation to HADS, 52.8% of emotional distress, 42.3% of anxiety and 58.6% of depression rates were detected. The main factors related with higher rates of psychological symptomatology were history of previous psychotropic drug consumption and the adoption of additional infection prevention measures because they considered themselves at risk of severe COVID-19 infection (p = 0.008; p = 0.003 for emotional distress, p = 0.026; p = 0.004 for anxiety, and p = 0.013; p = 0.008 for depression). Tumor type, stage, oncologic treatment or rescheduling of cancer treatments were not related to higher levels of psychological symptomatology.Comparison of our results with another population of similar characteristics was not significant (Z score = −1.88; p = 0.060).Conclusions: We detected high rates of emotional distress during the first wave of the COVID-19 pandemic among cancer patients in active treatment (52.8%). This was higher and clinically relevant than observed in a comparable population (42.5%), although not significant. Cancer itself is the main factor of concern for cancer patients, above and beyond the emotional distress generated by COVID-19 pandemic.
Cannabidiol Cigarettes as Adjunctive Treatment for Psychotic Disorders – A Randomized, Open-Label Pilot-Study
Authors: Köck Patrick , Lang Elisabeth , Trulley Valerie-Noelle , Dechent Frieder , Mercer-Chalmers-Bender Katja , Frei Priska , Huber Christian , Borgwardt Stefan 
Published: November 2021

Background: Psychotic disorders are associated with high rates of comorbid substance use disorders. Use of cannabis rich in tetrahydrocannabinol (THC) is linked to an increased risk of psychosis, worsening of psychotic symptoms, and an adverse course of psychotic disorders. Previous studies suggest oral cannabidiol (CBD) as possible novel antipsychotic agent; however, no studies evaluated the effects of smoked CBD.Objective: The main aim of the study was to clarify the antipsychotic potential of CBD used as adjunctive therapy simulating a naturalistic setting. Our trial is the first study evaluating the effects of smoked CBD-cigarettes as adjunctive therapy for psychotic symptoms.Methods: A randomized, placebo-controlled open-label trial of cigarettes containing CBD-rich cannabis (THC &lt; 1%) as adjunctive therapy to standard psychiatric treatment was conducted (ClinicalTrials.gov identifier NCT04700930). Primary outcomes were mean scores of Positive and Negative Syndrome Scale (PANSS), Brøset Violence Checklist, the Beck's Depression Inventory (BDI), the Subjective Well-Being Under Neuroleptics Scale short form (SWN-K), and antipsychotic medication equivalent doses. Outcomes were assessed after 4 weeks of acute treatment and long-term follow-up after discontinuation of CBD-cigarettes after 25 weeks. Participants were 31 acutely psychotic patients with tobacco use disorder and a mean age of 35.1 ± 10.58 years (71% male). Comorbid cannabis use was diagnosed in 51.6%.Results: A discontinuous multilevel model revealed no significant group differences for primary outcomes. After 4 weeks of acute treatment, mean PANSS and BDI decreased in both groups, while an increase of antipsychotic medication equivalent was observed in the placebo group.Conclusions: The presented findings might suggest an antipsychotic medication sparing effect of CBD-cigarettes as adjunctive treatment of acute psychosis. However, the low number of participants did not allow for further statistical analysis. Hence, a larger study sample and a more rigorous study design (blinding of the interventional product, fixed dosing regimen) may reveal different results.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT04700930
Impact of Adverse Childhood Experiences on Older Adult Poverty: Mediating Role of Depression
Authors: Liao Hui , Yan Chaoyang , Ma Ying , Wang Jing 
Published: November 2021

Background: Adverse childhood experiences (ACEs) refer to traumatic events experienced by children in early life, including abuse, neglect, and family dysfunction, which are common worldwide. ACEs are harmful to mental health, and psychological problems can influence personal economic poverty in adulthood. We focused on family dysfunction and discussed the effect of different types of ACEs on poverty and the corresponding mediating effect of depression.Materials and Methods: A total of 9,910 individuals who were 60 years or older from the China Health and Retirement Longitudinal Study in 2014 and 2015 were analysed. The chi-square test was used to compare poverty incidence among subgroups of independent or control variables. Binary logistic regression analysis was used to test the effect of different types of ACEs on depression, and four logistic regression models were established to observe the association between ACEs on older adult poverty and the mediating effect of depression. The path diagram of the direct effect and indirect effect was drawn to test the mediating effect of depression.Results: Early death of father, the male guardian getting upset and witnessing violence of father to mother are the risk factors for older adult poverty, whereas female guardian getting upset, relationship with female guardians and parental quarrel are protective factors for older adult poverty. Furthermore, depression has a partial mediating effect on some factors including early death of father, male guardian getting upset, relationship with female guardian, parental quarrel, and witnessing violence of father to mother.Conclusions: Paternal ACE factors can directly make children more likely to fall into poverty as older adults and can indirectly influence older adult poverty through the partial mediating effect of depression. Assisting poor families, providing psychological counselling, formulating family visit plans, nurturing orphan children under state supervision, and other policies that focus on groups that have experienced paternal ACE events are essential to eliminating the risk factors that influence older adult poverty.