bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Potential Signatures and Their Functions for Acute Lymphoblastic Leukemia: A Study Based on the Cancer Genome Atlas
Authors: Wang Weimin , Lyu Chunhui , Wang Fei , Wang Congcong , Wu Feifei , Li Xue , Gan Silin 
Published: July 2021

ObjectiveAcute lymphoblastic leukemia (ALL) is a malignant disease most commonly diagnosed in adolescents and young adults. This study aimed to explore potential signatures and their functions for ALL.MethodsDifferentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified for ALL from The Cancer Genome Atlas (TCGA) and normal control from Genotype-Tissue Expression (GTEx). DElncRNA–microRNA (miRNA) and miRNA–DEmRNA pairs were predicted using online databases. Then, a competing endogenous RNA (ceRNA) network was constructed. Functional enrichment analysis of DEmRNAs in the ceRNA network was performed. Protein–protein interaction (PPI) network was then constructed. Hub genes were identified. DElncRNAs in the ceRNA network were validated using Real-time qPCR.ResultsA total of 2,903 up- and 3,228 downregulated mRNAs and 469 up- and 286 downregulated lncRNAs were identified for ALL. A ceRNA network was constructed for ALL, consisting of 845 lncRNA-miRNA and 395 miRNA–mRNA pairs. These DEmRNAs in the ceRNA network were mainly enriched in ALL-related biological processes and pathways. Ten hub genes were identified, including SMAD3, SMAD7, SMAD5, ZFYVE9, FKBP1A, FZD6, FZD7, LRP6, WNT1, and SFRP1. According to Real-time qPCR, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were significantly upregulated in ALL bone marrow samples compared to normal samples.ConclusionOur results showed the lncRNA expression profiles and constructed ceRNA network in ALL. Furthermore, eight lncRNAs including ATP11A-AS1, ITPK1-AS1, ANO1-AS2, CRNDE, MALAT1, CACNA1C-IT3, PWRN1, and WT1-AS were identified. These results could provide a novel insight into the study of ALL.
Cerebrospinal Fluid of Patients With Alzheimer’s Disease Contains Increased Percentages of Synaptophysin-Bearing Microvesicles
Authors: Utz Janine , Berner Judith , Muñoz Luis Enrique , Oberstein Timo Jan , Kornhuber Johannes , Herrmann Martin , Maler Juan Manuel , Spitzer Philipp 
Published: July 2021

IntroductionIn Alzheimer’s disease, the severity of symptoms is linked to a loss of synaptic density and the spread of pathologically hyperphosphorylated tau. The established cerebrospinal fluid markers Aβ, tau and phospho-tau reflect the histopathological hallmarks of Alzheimer’s disease but do not indicate disease progression. Such markers are of special interest, especially for trials of disease modifying drugs. Microvesicles are produced by stressed cells and reflect part of the metabolism of their cells of origin. Therefore, we investigated microvesicles of neuronal origin in cerebrospinal fluid.Materials and MethodsWe used flow cytometry to analyze microvesicles carrying tau, phospho-tau-Thr181, phospho-tau-Ser202Thr205, synaptophysin, and SNAP-25 in the cerebrospinal fluid of 19 patients with Alzheimer’s disease and 15 non-inflammatory neurological disease controls.ResultsThe percentages of synaptophysin-bearing microvesicles were significantly higher in the cerebrospinal fluid of patients with Alzheimer’s disease than in the CSF of non-inflammatory neurological disease controls. Tau, phospho-tau-Thr181, phospho-tau-Ser202Thr205, and SNAP-25 did not differ between the groups. The percentages of synaptophysin-bearing vesicles distinguished patients with Alzheimer’s disease from the controls (AUC = 0.81).ConclusionThe loss of synapses in Alzheimer’s disease may be reflected by synaptophysin-bearing microvesicles in the cerebrospinal fluid. Future studies are needed to investigate the possibility of using these MVs as a marker to determine the activity of Alzheimer’s disease.
Onset Symptom Clusters in Multiple Sclerosis: Characteristics, Comorbidities, and Risk Factors
Authors: Ajdacic-Gross Vladeta , Steinemann Nina , Horváth Gábor , Rodgers Stephanie , Kaufmann Marco , Xu Yanhua , Kamm Christian P. , Kesselring Jürg , Manjaly Zina-Mary , Zecca Chiara , Calabrese Pasquale , Puhan Milo A. , Wyl Viktor von 
Published: July 2021

Background: Multiple sclerosis (MS) symptoms are expected to aggregate in specific patterns across different stages of the disease. Here, we studied the clustering of onset symptoms and examined their characteristics, comorbidity patterns and associations with potential risk factors.Methods: Data stem from the Swiss Multiple Sclerosis Registry, a prospective study including 2,063 participants by November 2019. MS onset symptoms were clustered using latent class analysis (LCA). The latent classes were further examined using information on socio-demographic characteristics, MS-related features, potential risk factors, and comorbid diseases.Results: The LCA model with six classes (frequencies ranging from 12 to 24%) was selected for further analyses. The latent classes comprised a multiple symptoms class with high probabilities across several symptoms, contrasting with two classes with solitary onset symptoms: vision problems and paresthesia. Two gait classes emerged between these extremes: the gait-balance class and the gait-paralysis class. The last class was the fatigue-weakness-class, also accompanied by depression symptoms, memory, and gastro-intestinal problems. There was a moderate variation by sex and by MS types. The multiple symptoms class yielded increased comorbidity with other autoimmune disorders. Similar to the fatigue-weakness class, the multiple symptoms class showed associations with angina, skin diseases, migraine, and lifetime prevalence of smoking. Mononucleosis was more frequently reported in the fatigue-weakness and the paresthesia class. Familial aggregation did not differ among the classes.Conclusions: Clustering of MS onset symptoms provides new perspectives on the heterogeneity of MS. The clusters comprise different potential risk factors and comorbidities. They point toward different risk mechanisms.
Hormone Receptor Status May Impact the Survival Benefit Between Medullary Breast Carcinoma and Atypical Medullary Carcinoma of the Breast: A Population-Based Study
Authors: Qin Wenxing , Qi Feng , Guo Mengzhou , Wang Liangzhe , Zang Yuan-Sheng 
Published: July 2021

BackgroundA rare subtype of breast cancer, atypical medullary carcinoma of the breast (AMCB), shows a highly adverse prognosis compared to medullary carcinoma of the breast (MBC). The current study aimed to establish a correlated nomogram for the identification of the prognostic factors of AMCB and MBC.MethodsKaplan–Meier and Cox regression analyses were applied to data acquired from the Surveillance, Epidemiology and End Results (SEER) database for 2004 to 2013 to analyse tumour characteristics and overall survival. Propensity score matching (PSM) analysis was performed to determine the overall survival (OS) among those with AMCB and MBC. A predictive nomogram was created, and the concordance index (C-index) was used to predict accuracy and discriminative ability.ResultsA total of 2,001 patients from the SEER database were diagnosed with MBC between 2004 and 2013, including 147 patients diagnosed with AMCB. The number of diagnoses gradually increased in both groups. Cox analysis of multivariate and Kaplan–Meier analysis showed that older age (HR = 3.005, 95% CI 1.906–4.739) and later stage were significantly associated with poor prognosis, while cancer-directed surgery was an independent protective factor (HR = 0.252, 95% CI 0.086–0.740). In the HR-negative stratification analysis, older age (HR = 2.476, 95% CI 1.398–4.385), later stage and histological type (HR=0.381, 95% CI 0.198-0.734) were found to be independent prognostic factors for low standard survival. The log-rank analysis demonstrated significantly worse prognostic factors for patients with AMCB than for those with MBC (P = 0.004). A nomogram (C-index for survival = 0.75; 95% CI 0.69–0.81) was established from four independent prognostic factors after complete identification.ConclusionsMBC is rare, and cancer-directed surgery, older age, and later stage are independently linked with prognosis. In the HR negative population, AMCB patients show a worse survival gain than those with MBC.
Improvement of Diabetes Mellitus After Colorectal Cancer Surgery: A Retrospective Study of Predictive Factors For Type 2 Diabetes Mellitus Remission and Overall Survival
Authors: Peng Dong , Liu Xiao-Yu , Cheng Yu-Xi , Tao Wei , Cheng Yong 
Published: July 2021

PurposeThe purpose of the current study was to evaluate the impact of colorectal cancer (CRC) surgery on type 2 diabetes mellitus (T2DM) and to analyze the change in T2DM on overall survival after CRC surgery.MethodsPatients who underwent CRC surgery were retrospectively enrolled from January 2013 to December 2019. The status of T2DM pre- and 1-year after CRC surgery was recorded, and predictive factors for T2DM remission and overall survival were analyzed.ResultsA total of 296 patients were included in this study. Thirty-eight patients experienced remission of T2DM 1 year after CRC surgery, and the remission rate was 12.8%. Weight loss was significantly higher in the T2DM remission group (p = 0.038), and the T2DM duration was significantly shorter in the T2DM remission group (p = 0.015). In the multivariate logistic regression analysis, higher weight loss (p = 0.046, odds ratio = 1.060, 95% CI = 1.001–1.122) and shorter T2DM duration (p = 0.019, odds ratio = 1007, 95% CI = 1.001–1.014) were predictive factors for remission of T2DM. Furthermore, in multivariate Cox regression analysis, lower TNM stage (p = 0.000, odds ratio = 2.147, 95% CI = 1.474–3.128) and T2DM remission (p = 0.033, odds ratio = 2.999, 95% CI = 1.091–8.243) were the predictive factors for better overall survival.ConclusionPatients with concurrent CRC and T2DM had a 12.8% remission 1 year after CRC surgery. Higher weight loss and shorter T2DM duration contributed to T2DM remission, and patients with T2DM remission could improve in terms of their overall survival.
The Improved Prognosis of Hypoplastic Left Heart: A Population-Based Register Study of 343 Cases in England and Wales
Authors: Best Kate E. , Miller Nicola , Draper Elizabeth , Tucker David , Luyt Karen , Rankin Judith 
Published: July 2021

Background: Hypoplastic Left Heart Syndrome (HLHS) is a severe congenital heart defect (CHD) characterised by the underdevelopment of the left side of the heart with varying levels of hypoplasia of the left atrium, mitral valve, left ventricle, aortic valve and aortic arch. In the UK, age 12 survival for cases born between 1991 and 1993 was 21%. UK survival estimates corresponding to cases born between 2000 and 2015 were improved at 56%, but survival was examined up to age five only. Contemporary long-term survival estimates play a crucial role in counselling parents following diagnosis. The aim of this study was to report survival estimates up to age 15 for children born with HLHS or hypoplastic left ventricle with additional CHD in England and Wales between 1998 and 2012.Methods: Cases of HLHS notified to four congenital anomaly registers in England and Wales during 1998–2012, matched to Office for National Statistics mortality information, were included. Kaplan-Meier survival estimates to age 15 were reported. Cox regression models were fitted to examine risk factors for mortality.Results: There were 244 cases of HLHS and 99 cases of hypoplastic left ventricle co-occurring with other CHD, with traced survival status. Kaplan-Meier survival estimates for HLHS were 84.4% at age 1 week, 76.2% at 1 month, 63.5% at age 1 year, 58.6% at age 5 years, 54.6% at age 10 years, and 32.6% to age 15 years. The Kaplan-Meier survival estimates for cases of hypoplastic left ventricle co-occurring with additional CHD were 90.9% at age 1 week, 84.9% at 1 month, 73.7% at age 1 year, 67.7% to age 5 years, 59.2% to age 10 years, and 40.3% to age 15 years. Preterm birth (p = 0.007), low birth weight (p = 0.005), and female sex (p = 0.01) were associated with mortality.Conclusions: We have shown that prognosis associated with HLHS in the twenty first century exceeds that of many previous population-based studies, likely due to improvements in intensive care technologies and advances in surgical techniques over the last few decades.
Association Between Hyponatremia and Maintenance Intravenous Solutions in Critically Ill Children: A Retrospective Observational Study
Authors: Fernández-Sarmiento Jaime , Pérez Andrea , Echeverri Maria Alejandra , Jimenez Paola , Joachim Maria Alejandra , Andrés-Jagua  
Published: July 2021

Objetive: We sought to determine the association between maintenance intravenous solutions and the presence of hyponatremia in children in pediatric intensive care (PICU).Materials and Methods: An analytical observational study in children hospitalized in the PICU between January 2015 and December 2018. Patients who received maintenance fluids within the first 48 h after admission and who had at least two serum sodium levels drawn during this time were included.Measurements and Main Results: A total of 1,668 patients were admitted to the PICU during the study period, 503 of whom met the inclusion criteria. The median age was 24 months (IQR 8–96) and 50.9% were female. Altogether, 24.1% of the children developed hyponatremia; it was more frequent in those who received hypotonic solutions (63 vs. 37%; OR 1.41 95% CI 0.92, 2.15 p = 0.106), who also had a longer hospital stay (20 vs. 14 days, difference in means 8 days, 95% CI 2.67, 13.3, p = 0.001). Children who received loop diuretics and those who were post-operative had a greater risk of developing hyponatremia if they received hypotonic solutions (aOR 2.1 95% CI 1.41, 3.0, p = 0.000). Those with balanced isotonic solutions had a lower risk of developing hyponatremia (aOR 0.59 95% CI 0.35, 0.99, p = 0.004) and hyperchloremia (aOR 0.51 95% CI 0.34, 0.77, p = 0.000), adjusted for disease severity. A greater risk of death was found in the group with severe hyponatremia &lt;130 mEq/L (aOR 9.75 95% CI 1.64–58.15; p = 0.01).Conclusions: Hyponatremia associated with the use of hypotonic maintenance solutions occurs in one out of four children in intensive care. The use of these solutions is associated with a longer hospital stay, and the main risk groups are post-operative patients and those who receive loop diuretics. Clinical studies are needed to determine which maintenance solutions have the greatest efficacy and safety in critically ill children.
Developmental Pharmacogenetics of CYP2D6 in Chinese Children: Loratadine as a Substrate Drug
Authors: Li Qian , Wu Yue-E , Wang Kai , Shi Hai-Yan , Zhou Yue , Zheng Yi , Hao Guo-Xiang , Yang Yi-Lei , Su Le-Qun , Wang Wen-Qi , Yang Xin-Mei , Zhao Wei 
Published: July 2021

Objective: The elucidation of CYP2D6 developmental pharmacogenetics in children has improved, however, these findings have been largely limited to studies of Caucasian children. Given the clear differences in CYP2D6 pharmacogenetic profiles in people of different ancestries, there remains an unmet need to better understand the developmental pharmacogenetics in populations of different ancestries. We sought to use loratadine as a substrate drug to evaluate the effects of ontogeny and pharmacogenetics on the developmental pattern of CYP2D6 in Chinese pediatric patients.Methods: Chinese children receiving loratadine treatment were enrolled in the present study. The metabolite-to-parent ratio (M/P ratio), defined as the molar ratio of desloratadine to loratadine of trough concentrations samples at steady-state condition, was used as a surrogate of CYP2D6 activity. Loratadine and desloratadine were determined by LC/MS/MS method. Variants of CYP2D6 were genotyped by polymerase chain reaction for CYP2D6 *4, *10, *41 and long polymerase chain reaction for CYP2D6 *5.Results: A total of 40 patients were available for final analysis. The mean age was 4.50 (range 0.50–9.00) years and the mean weight was 19.64 (range 7.00–42.00) kg. The M/P ratio was significantly lower in intermediate metabolizers (IMs) compared to normal metabolizers (NMs) (10.18 ± 7.97 vs. 18.80 ± 15.83, p = 0.03). Weight was also found to be significantly associated with M/P ratio (p = 0.03).Conclusion: The developmental pharmacogenetics of CYP2D6 in Chinese children was evaluated using loratadine as a substrate drug. This study emphasizes the importance of evaluating the developmental pharmacogenetics in populations of different ancestries.
Gallic Acid Prevents the Oxidative and Endoplasmic Reticulum Stresses in the Hippocampus of Adult-Onset Hypothyroid Rats
Authors: Blas-Valdivia Vanessa , Franco-Colín Margarita , Rojas-Franco Placido , Chao-Vazquez Alberto , Cano-Europa Edgar 
Published: July 2021

Thyroid hormone is essential for hippocampal redox environment and neuronal viability in adulthood, where its deficiency causes hypothyroidism related to oxidative and endoplasmic reticulum stresses in the hippocampus, resulting in neuronal death. One option of treatment is antioxidants; however, they must be transported across the blood-brain barrier. Gallic acid is a polyphenol that meets these criteria. Thus, this study aimed to prove that the neuroprotective mechanism of GA is associated with the prevention of oxidative and endoplasmic reticulum stresses in the hippocampus of adult-onset hypothyroid rats. Male Wistar rats were divided into euthyroid (n = 20) and hypothyroid groups (n = 20). Thyroidectomy with parathyroid gland reimplementation caused hypothyroidism. Each group was subdivided into two: vehicle and 50 mg/kg/d of gallic acid. 3 weeks after thyroidectomy, six animals of each group were euthanized, and the hippocampus was dissected to evaluate oxidative and endoplasmic reticulum stress markers. The rest of the animals were euthanized after 4 weeks of treatment for histological analysis of the hippocampus. The results showed that hypothyroidism increased lipid peroxidation, reactive oxygen species, and nitrites; it also increased endoplasmic reticulum stress by activating the inositol-requiring enzyme-1α (IRE1α) pathway, the protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activated transcription factor 6α (ATF6α) pathways associated with a proapoptotic state that culminates in hippocampal neuronal damage. Meanwhile, the hypothyroid rat treated with gallic acid reduced oxidative stress and increased endoplasmic reticulum-associated degradation (ERAD) through IRE1α and ATF6. Also, the gallic acid treatment prevented the Bax/BCl2 ratio from increasing and the overexpression of p53 and caspase 12. This treatment in hypothyroid animals was associated with the neuronal protection observed in the hippocampus. In conclusion, gallic acid prevents hypothyroidism-induced hippocampal damage associated with oxidative and endoplasmic reticulum stresses.
Heart Rate Methods Can Be Valid for Estimating Intensity Spectrums of Oxygen Uptake in Field Exercise
Authors: Salier Eriksson Jane , Olsson Karin S. E. , Rosdahl Hans , Schantz Peter 
Published: July 2021

PurposeQuantifying intensities of physical activities through measuring oxygen uptake (V̇O2) is of importance for understanding the relation between human movement, health and performance. This can in principle be estimated by the heart rate (HR) method, based on the linear relationship between HR and V̇O2established in the laboratory. It needs, however, to be explored whether HR methods, based on HR-V̇O2relationships determined in the laboratory, are valid for estimating spectrums of V̇O2in field exercise. We hereby initiate such studies, and use cycle commuting as the form of exercise.MethodsTen male and ten female commuter cyclists underwent measurements of HR and V̇O2while performing ergometer cycling in a laboratory and a normal cycle commute in the metropolitan area of Stockholm County, Sweden. Two models of individual HR-V̇O2relationships were established in the laboratory through linear regression equations. Model 1 included three submaximal work rates, whereas model 2 also involved a maximal work rate. The HR-V̇O2regression equations of the two models were then used to estimate V̇O2at six positions of field HR: five means of quintiles and the mean of the whole commute. The estimations obtained were for both models compared with the measured V̇O2.ResultsThe measured quintile range during commuting cycling was about 45–80% of V̇O2max. Overall, there was a high resemblance between the estimated and measured V̇O2, without any significant absolute differences in either males or females (range of all differences: −0.03–0.20 L⋅min–1). Simultaneously, rather large individual differences were noted.ConclusionThe present HR methods are valid at group level for estimating V̇O2of cycle commuting characterized by relatively wide spectrums of exercise intensities. To further the understanding of the external validity of the HR method, there is a need for studying other forms of field exercises.
Negative Childbirth Experience and Post-traumatic Stress Disorder - A Study Among Postpartum Women in South India
Authors: Shiva Lakshmi , Desai Geetha , Satyanarayana Veena A. , Venkataram Padmalatha , Chandra Prabha S. 
Published: July 2021

Purpose: Negative childbirth experience has been associated with post-traumatic stress disorder (PTSD) and depression in the postpartum period with a significant impact on the mother as well as the infant.Methods: The current study aimed at studying the association of negative child birth experience with PTSD and depressive symptoms among primiparous mothers within 6 weeks of child birth. The Childbirth Experience Questionnaire (CEQ), PTSD checklist (PCL), and Edinburgh Postnatal Depression scale (EPDS) were used to assess negative childbirth experience, symptoms of PTSD, and depression respectively.Results: Of the 95 women in the study, fifty women (52.6%) had a score below the median of CEQ score (score of 72) indicating a negative childbirth experience. Lower Scores on CEQ indicating negative childbirth experience correlated with PTSD scores on the PCL (r = −0.560, p = 0.001) and depression scores on the EPDS (r = −0.536, p = 0.001). Of the sample of 95 women, 7.36% (N = 7) met the criteria for probable PTSD and 3.16% (N = 3) met criteria for partial PTSD. Twelve women (12.6%) had EPDS scores above 13 indicating probable clinical depression. Median CEQ scores were lower among the women who had PTSD or partial PTSD (N = 10) and among the women who had probable depression (N = 12) than those who did not. Childbirth experience emerged as the only predictor of PTSD on logistic regression (p = 0.03) (95% CI 1.17–79.61).Conclusions: Negative childbirth experiences are common and appear to be associated with depressive and PTSD symptoms. These findings emphasize the need to provide good intrapartum care including respectful maternity care for a positive childbirth experience.