bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Brain Functional Network Topology in Lung Cancer Patients After Chemotherapy
Authors: You Jia , Zhang Juan , Shang Song'an , Gu Wei , Hu Lanyue , Zhang Yujie , Xiong Zhenyu , Chen Yu-Chen , Yin Xindao 
Published: August 2021

Purpose: This study aimed to explore the topological features of brain functional network in lung cancer patients before and after chemotherapy using graph theory.Methods: Resting-state functional magnetic resonance imaging scans were obtained from 44 post-chemotherapy and 46 non-chemotherapy patients as well as 49 healthy controls (HCs). All groups were age- and gender-matched. Then, the topological features of brain functional network were assessed using graph theory analysis.Results: At the global level, compared with the HCs, both the non-chemotherapy group and the post-chemotherapy group showed significantly increased values in sigma (p &lt; 0.05), gamma (p &lt; 0.05), and local efficiency, Eloc (p &lt; 0.05). The post-chemotherapy group and the non-chemotherapy group did not differ significantly in the above-mentioned parameters. At the nodal level, when non-chemotherapy or post-chemotherapy patients were compared with the HCs, abnormal nodal centralities were mainly observed in widespread brain regions. However, when the post-chemotherapy group was compared with the non-chemotherapy group, significantly decreased nodal centralities were observed primarily in the prefrontal–subcortical regions.Conclusions: These results indicate that lung cancer and chemotherapy can disrupt the topological features of functional networks, and chemotherapy may cause a pattern of prefrontal–subcortical brain network abnormality. As far as we know, this is the first study to report that altered functional brain networks are related to lung cancer and chemotherapy.
Variation in Neonatal Nutrition Practice and Implications: A Survey of Australia and New Zealand Neonatal Units
Authors: McLeod Gemma , Farrent Shelley , Gilroy Melissa , Page Denise , Oliver Colleen J. , Richmond Fiona , Cormack Barbara E. 
Published: August 2021

Background:Significant global variation exists in neonatal nutrition practice, including in assigned milk composition values, donor milk usage, fortification regimens, probiotic choice and in methods used to calculate and report nutrition and growth outcomes, making it difficult to synthesize data to inform evidence-based, standardized nutritional care that has potential to improve neonatal outcomes. The Australasian Neonatal Dietitians' Network (ANDiN) conducted a survey to determine the degree to which neonatal nutritional care varies across Australia and New Zealand (A&amp;NZ) and to highlight potential implications.Materials and Methods:A two-part electronic neonatal nutritional survey was emailed to each ANDiN member (n= 50). Part-One was designed to examine individual dietetic practice; Part-Two examined site-specific nutrition policies and practices. Descriptive statistics were used to examine the distribution of responses.Results:Survey response rate: 88%. Across 24 NICU sites, maximum fluid targets varied (150–180 mL.kg.d−1); macronutrient composition estimates for mothers' own(MOM) and donor (DM) milk varied (Energy (kcal.dL−1) MOM: 65–72; DM 69–72: Protein (g.dL−1): MOM: 1.0–1.5; DM: 0.8–1.3); pasteurized DM or unpasteurized peer-to-peer DM was not available in all units; milk fortification commenced at different rates and volumes; a range of energy values (kcal.g−1) for protein (3.8–4.0), fat (9.0–10.0), and carbohydrate (3.8–4.0) were used to calculate parenteral and enteral intakes; probiotic choice differed; and at least seven different preterm growth charts were employed to monitor growth.Discussion:Our survey identifies variation in preterm nutrition practice across A&amp;NZ of sufficient magnitude to impact nutrition interventions and neonatal outcomes. This presents an opportunity to use the unique skillset of neonatal dietitians to standardize practice, reduce uncertainty of neonatal care and improve the quality of neonatal research.
Inhibition of Renal Tubular Epithelial Mesenchymal Transition and Endoplasmic Reticulum Stress-Induced Apoptosis with Shenkang Injection Attenuates Diabetic Tubulopathy
Authors: Wang Wen-Wen , Liu Ying-Lu , Wang Mei-Zi , Li Huan , Liu Bu-Hui , Tu Yue , Yuan Can-Can , Fang Qi-Jun , Chen Jia-Xin , Wang Jie , Fu Yan , Wan Zi-Yue , Wan Yi-Gang , Wu Wei 
Published: August 2021

Background: The proximal renal tubule plays a critical role in diabetic kidney disease (DKD) progression. Early glomerular disease in DKD triggers a cascade of injuries resulting in renal tubulointerstitial disease. These pathophysiological responses are collectively described as diabetic tubulopathy (DT). Thus, therapeutic strategies targeting DT hold significant promise for early DKD treatment. Shenkang injection (SKI) has been widely used to treat renal tubulointerstitial fibrosis in patients with chronic kidney disease in China. However, it is still unknown whether SKI can alleviate DT. We designed a series of experiments to investigate the beneficial effects of SKI in DT and the mechanisms that are responsible for its effect on epithelial-to-mesenchymal transition (EMT) and endoplasmic reticulum (ER) stress-induced apoptosis in DT.Methods: The modified DKD rat models were induced by uni-nephrectomy, streptozotocin intraperitoneal injection, and a high-fat diet. Following the induction of renal injury, these animals received either SKI, rosiglitazone (ROS), or vehicle, for 42 days. For in vitro research, we exposed NRK-52E cells to high glucose (HG) and 4-phenylbutyric acid (4-PBA) with or without SKI or ROS. Changes in parameters related to renal tubular injury and EMT were analyzed in vivo. Changes in the proportion of apoptotic renal tubular cells and ER stress, and the signaling pathways involved in these changes, were analyzed both in vivo and in vitro.Results: SKI and ROS improved the general condition, the renal morphological appearance and the key biochemical parameters, and attenuated renal injury and EMT in the rat model of DKD. In addition, SKI and ROS alleviated apoptosis, inhibited ER stress, and suppressed PERK-eIF2α-ATF4-CHOP signaling pathway activation both in vivo and in vitro. Notably, our data showed that the regulatory in vitro effects of SKI on PERK-eIF2α-ATF4-CHOP signaling were similar to those of 4-PBA, a specific inhibitor of ER stress.Conclusion: This study confirmed that SKI can alleviate DT in a similar manner as ROS, and SKI achieves this effect by inhibiting EMT and ER stress-induced apoptosis. Our findings thereby provide novel information relating to the clinical value of SKI in the treatment of DT.
Clinical Outcomes of Concomitant Use of Proton Pump Inhibitors and Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis
Authors: Guo Hongzhou , Ye Zhishuai , Huang Rongchong 
Published: August 2021

Background: The safety and efficacy associated with the use of proton pump inhibitors (PPIs) by patients with coronary artery disease receiving dual antiplatelet therapy (DAPT) remain unclear.Methods: The evaluated outcomes included combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), all-cause mortality, and gastrointestinal (GI) bleeding. A random effects meta-analysis, stratified by study design, was performed and heterogeneity was assessed using the I2 statistic.Results: In total, 6 randomized controlled trials (RCTs) (6930 patients) and 16 observational studies (183,546 patients) were included. Analysis of RCTs showed that there were no significant differences in the incidences of MACEs (risk ratio [RR] = 0.89 [95% confidence interval (CI) = 0.75–1.05]), MI (RR = 0.93 [95% CI = 0.76–1.15]), and all-cause mortality (RR = 0.79 [95% CI = 0.50–1.23]) in the PPI groups vs. the non-PPI groups. Pooled data from observational studies revealed an inconsistent association between the use of each PPI subtype and the increased risks of MACEs during clopidogrel treatment. There was no increased risk of MACEs or all-cause mortality associated with the use of PPIs (as a class) and other P2Y12 inhibitors. Both the RCTs and observational studies revealed that the use of PPIs significantly reduced the risks of GI bleeding.Conclusion: The use of PPIs was associated with a reduced risk of GI bleeding in patients treated with DAPT after percutaneous coronary intervention or acute coronary syndrome. There was no clear evidence of an association between the use of PPIs and adverse cardiovascular events.Clinical Trial Registration: identifier [CRD42020190315]
Chloroquine and Hydroxychloroquine Use During Pregnancy and the Risk of Adverse Pregnancy Outcomes Using Real-World Evidence
Authors: Bérard Anick , Sheehy Odile , Zhao Jin-Ping , Vinet Evelyne , Quach Caroline , Bernatsky Sasha 
Published: August 2021

Introduction: Chloroquine (CQ) and hydroxychloroquine (HCQ) are currently used for the prevention/treatment of malaria, and treatment of systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Although present data do not show their efficacy to treat COVID-19, they have been used as potential treatments for COVID-19. Given that pregnant women are excluded from randomized controlled trials, and present evidence are inconsistent and inconclusive, we aimed to investigate the safety of CQ or HCQ use in a large pregnancy cohort using real-world evidence.Methods: Using Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn, 1998–2015, (n = 233,748). The exposure time window for analyses on prematurity and low birth weight (LBW) was the second/third trimesters; was any time during pregnancy; only first trimester exposure was considered for analyses on major congenital malformations (MCM). The risk of prematurity, LBW, and MCM (overall and organ-specific) were quantified using generalized estimation equations.Results: We identified 288 pregnancies (0.12%) exposed to CQ (183, 63.5%) or HCQ (105, 36.5%) that resulted in liveborn singletons; CQ/HCQ was used for RA (17.4%), SLE (16.3%) or malaria (0.7%). CQ/HCQ was used for 71.8 days on average [standard-deviation (SD) 70.5], at a dose of 204.3 mg/d (SD, 155.6). We did not observe any increased risk related to CQ/HCQ exposure for prematurity (adjusted odds ratio [aOR] 1.39, 95%CI 0.84–2.30), LBW (aOR 1.11, 95%CI 0.59–2.06), or MCM (aOR 1.01, 95%CI 0.67–1.52).Conclusion: in this large CQ/HCQ exposed pregnancy cohort, we saw no clear increased risk of prematurity, LBW, or MCM, although number of exposed cases remained low.
Peak Fat Oxidation Rate Is Closely Associated With Plasma Free Fatty Acid Concentrations in Women; Similar to Men
Authors: Frandsen Jacob , Poggi Axel Illeris , Ritz Christian , Larsen Steen , Dela Flemming , Helge Jørn W. 
Published: August 2021

Introduction: In men, whole body peak fat oxidation (PFO) determined by a graded exercise test is closely tied to plasma free fatty acid (FFA) availability. Men and women exhibit divergent metabolic responses to fasting and exercise, and it remains unknown how the combined fasting and exercise affect substrate utilization in women. We aimed to investigate this, hypothesizing that increased plasma FFA concentrations in women caused by fasting and repeated exercise will increase PFO during exercise. Then, that PFO would be higher in women compared with men (data from a previous study).Methods: On two separate days, 11 young endurance-trained women were investigated, either after an overnight fast (Fast) or 3.5 h after a standardized meal (Fed). On each day, a validated graded exercise protocol (GXT), used to establish PFO by indirect calorimetry, was performed four times separated by 3.5 h of bed rest both in the fasted (Fast) or fed (Fed) state.Results: Peak fat oxidation increased in the fasted state from 11 ± 3 (after an overnight fast, Fast 1) to 16 ± 3 (mean ± SD) mg/min/kg lean body mass (LBM) (after ~22 h fast, Fast 4), and this was highly associated with plasma FFA concentrations, which increased from 404 ± 203 (Fast 1) to 865 ± 210 μmol/L (Fast 4). No increase in PFO was found during the fed condition with repeated exercise. Compared with trained men from a former identical study, we found no sex differences in relative PFO (mg/min/kg LBM) between men and women, in spite of significant differences in plasma FFA concentrations during exercise after fasting.Conclusion: Peak fat oxidation increased with fasting and repeated exercise in trained women, but the relative PFO was similar in young trained men and women, despite major differences in plasma lipid concentrations during graded exercise.
Maternal Parenting Stress in the Face of Early Regulatory Disorders in Infancy: A Machine Learning Approach to Identify What Matters Most
Authors: Georg Anna K. , Schröder-Pfeifer Paul , Cierpka Manfred , Taubner Svenja 
Published: August 2021

Objective: Early regulatory disorders (ERD) in infancy are typically associated with high parenting stress (PS). Theoretical and empirical literature suggests a wide range of factors that may contribute to PS related to ERD. The aim of this study was to identify key predictors of maternal PS within a large predictor data set in a sample of N = 135 mothers of infants diagnosed with ERD.Methods: We used machine learning to identify relevant predictors. Maternal PS was assessed with the Parenting Stress Index. The multivariate dataset assessed cross-sectionally consisted of 464 self-reported and clinically rated variables covering mother-reported psychological distress, maternal self-efficacy, parental reflective functioning, socio-demographics, each parent's history of illness, recent significant life events, former miscarriage/abortion, pregnancy, obstetric history, infants' medical history, development, and social environment. Variables were drawn from behavioral diaries on regulatory symptoms and parental co-regulative behavior as well as a clinical interview which was utilized to diagnose ERD and to assess clinically rated regulatory symptoms, quality of parent–infant relationship, organic/biological and psychosocial risks, and social–emotional functioning.Results: The final prediction model identified 11 important variables summing up to the areas maternal self-efficacy, psychological distress (particularly depression and anger-hostility), infant regulatory symptoms (particularly duration of fussing/crying), and age-appropriate physical development. The RMSE (i.e., prediction accuracy) of the final model applied to the test set was 21.72 (R2 = 0.58).Conclusions: This study suggests that among behavioral, environmental, developmental, parent–infant relationship, and mental health variables, a mother's higher self-efficacy, psychological distress symptoms particularly depression and anger symptoms, symptoms in the child particularly fussing/crying symptoms, and age-inappropriate physical development are associated with higher maternal PS. With these factors identified, clinicians may more efficiently assess a mother's PS related to ERD in a low-risk help-seeking sample.
Meaning in Life in Long-Term Recovery in First-Episode Psychosis: An Interpretative Phenomenological Analysis
Authors: O'Keeffe Donal , Keogh Brian , Higgins Agnes 
Published: August 2021

Background: Meaning in Life (MIL) is a central aspect of service user defined personal recovery in mental health. It is unclear whether current knowledge regarding MIL is applicable to the lives of those who have experienced psychosis. As it was not possible to locate any study examining service user perspectives on MIL in first-episode psychosis (FEP), conducting in-depth qualitative research in this area offers an opportunity to develop a conceptualisation of MIL that may be transferable to the broad psychosis spectrum.Aim: The aim of the study was to explore how people find, develop, and maintain MIL approximately 21 years after their FEP diagnosis.Materials and Methods: The study aim was addressed using Interpretative Phenomenological Analysis (IPA). Participants were members of an epidemiologically complete FEP incidence cohort in Ireland. Purposive maximum variation sampling enabled the recruitment of a sample balanced across remission status, age at time of FEP onset, and gender. Semi-structured interviews were conducted circa 21 years post FEP with 16 participants. Data analysis was guided by IPA procedures.Results: Participants experienced MIL as awareness of connectedness to context – the interrelated conditions they existed in (their relationships with the self, others, systems, the environment, and time). Awareness of connectedness to context occurred in five main ways: Being myself — de-othering and authenticity (Enacting identity); Becoming significant where the self is witnessed (Belonging in life); Generating meaning within and beyond systems (Independence); Shaping and being shaped by life (Agency and patiency); and Integrating different perspectives of time (Reconciling temporality).Conclusions: Findings offer the first in-depth understanding of how people diagnosed with a FEP experience MIL in mid-later life recovery. Current tripartite MIL theories do not fully represent the array of MIL perspectives articulated by our participants. MIL concepts developed are potential areas for intervention for mental health services seeking to implement the recovery approach. Findings can be used to foster optimism among service users and their supporters for MIL attainment in psychosis and offer guidance for education, clinical practice, policy, and future research.
Psychometric Properties of the Impact of Events Scale-Revised (IES-R) Among General Iranian Population During the COVID-19 Pandemic
Authors: Sharif Nia Hamid , Kaur Harpaljit , Fomani Fatemeh Khoshnavay , Rahmatpour Pardis , Kaveh Omolhoda , Pahlevan Sharif Saeed , Venugopal A. Vijayalakshmi , Hosseini Lida 
Published: August 2021

Objective: The aim of this study was to translate and evaluate the validity and reliability of the Impact of Events Scale-Revised (IES-R) among the Iranian general population during the coronavirus disease 2019 (COVID-19) pandemic.Method: This study was methodological cross-sectional. It was conducted on an Iranian public population from April to July 2020 which was during the COVID-19 pandemic. Construct validity was determined through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) with a total of 500 adults recruited via online data gathering. Reliability was checked through the average inter-item correlation (AIC), Cronbach's alpha, and McDonald's omega. Convergent and divergent validity was determined using Fornell and Larcker's approach.Results: The results showed that the Persian version of IES-R had three factors, including intrusion (six items), avoidance (seven items), and hyperarousal (five items), that explained 59.22% of the total variance of the IES-R. The CFA findings indicated that all goodness-of-fit indices confirmed the model fit. The Cronbach's alpha, McDonald's omega, composite reliability (CR), and maximal reliability were excellent, and the three factors have good convergent validity.Conclusion: The findings of this study indicated that the Persian version of the IES-R scale is efficient and useful to assess post-traumatic stress disorder among Iran general population in the COVID-19 outbreak.
Comprehensive Analysis of Metabolic Genes in Breast Cancer Based on Multi-Omics Data
Authors: Hua Yu , Gao Lihong , Li Xiaobo 
Published: August 2021

Background: Reprogramming of cell metabolism is one of the most important hallmarks of breast cancer. This study aimed to comprehensively analyze metabolic genes in the initiation, progression, and prognosis of breast cancer.Materials and Methods: Data from The Cancer Genome Atlas (TCGA) in breast cancer were downloaded including RNA-seq, copy number variation, mutation, and DNA methylation. A gene co-expression network was constructed by the weighted correlation network analysis (WGCNA) package in R. Association of metabolic genes with tumor-related immune cells and clinical parameters were also investigated.Results: We summarized 3,620 metabolic genes and observed mutations in 2,964 genes, of which the most frequently mutated were PIK3CA (51%), TNN (26%), and KMT2C (15%). Four genes (AKT1, ERBB2, KMT2C, and USP34) were associated with survival of breast cancer. Significant association was detected in the tumor mutation burden (TMB) of metabolic genes with T stage (p = 0.045) and N stage (p = 0.004). Copy number variations were significantly associated with recurrence and prognosis of breast cancer. The co-expression network for differentially expressed metabolic genes by WGCNA suggested that the modules were associated with glycerophospholipid, arachidonic acid, carbon, glycolysis/gluconeogenesis, and pyrimidine/purine metabolism. Glycerophospholipid metabolism correlated with most of the immune cells, while arachidonic acid metabolism demonstrated a significant correlation with endothelial cells. Methylation and miRNA jointly regulated 14 metabolic genes while mutation and methylation jointly regulated PIK3R1.Conclusion: Based on multi-omics data of somatic mutation, copy number variation, mRNA expression, miRNA expression, and DNA methylation, we identified a series of differentially expressed metabolic genes. Metabolic genes are associated with tumor-related immune cells and clinical parameters, which might be therapy targets in future clinical application.
Cell-Extrinsic Differentiation Block Mediated by EphA3 in Pre-Leukaemic Thymus Contributes to Disease Progression
Authors: Pliego Zamora Adriana C. , Ranasinghe Hansini , Lisle Jessica E. , Ng Chun Ki , Huang Stephen , Wadlow Racheal , Scott Andrew M. , Boyd Andrew W. , Slape Christopher I. 
Published: August 2021

We recently characterised the NUP98-HOXD13 (NHD13) mouse as a model of T-cell pre-leukaemia, featuring thymocytes that can engraft in recipient animals and progress to T-cell acute lymphoblastic leukaemia (T-ALL). However, loss of this engraftment ability by deletion of Lyl1 did not result in any loss of leukemogenesis activity. In the present study, we observe that NHD13 thymocytes overexpress EPHA3, and we characterise thymocyte behaviour in NHD13 mice with deletion of EphA3, which show a markedly reduced incidence of T-ALL. Deletion of EphA3 from the NHD13 mice does not prevent the abnormal accumulation or transplantation ability of these thymocytes. However, upon transplantation, these cells are unable to block the normal progression of recipient wild type (WT) progenitor cells through the normal developmental pathway. This is in contrast to the EphA3+/+ NHD13 thymocytes, which block the progression of incoming WT progenitors past the DN1 stage. Therefore, EphA3 is not critical for classical self-renewal, but is essential for mediating an interaction between the abnormally self-renewing cells and healthy progenitors—an interaction that results in a failure of the healthy cells to differentiate normally. We speculate that this may orchestrate a loss of healthy cell competition, which in itself has been demonstrated to be oncogenic, and that this may explain the decrease in T-ALL incidence in the absence of EphA3. We suggest that pre-leukaemic self-renewal in this model is a complex interplay of cell-intrinsic and -extrinsic factors, and that multiple redundant pathways to leukaemogenesis are active.