Miracle-dz/UniFAR-FTUs huggingface dataset:
Isocitrate dehydrogenase 1–mutated human gliomas depend on lactate and glutamate to alleviate metabolic stress

Diffuse gliomas often carry point mutations in isocitrate dehydrogenase (IDH1mut), resulting in metabolic stress. Although IDHmut gliomas are difficult to culture in vitro, they thrive in the brain via diffuse infiltration, suggesting brain‐specific tumor–stroma interactions that can compensate for IDH‐1 deficits. To elucidate the metabolic adjustments in clinical IDHmut gliomas that contribute to their malignancy, we applied a recently developed method of targeted quantitative RNA next‐generation sequencing to 66 clinical gliomas and relevant orthotopic glioma xenografts, with and without the endogenous IDH‐1R132H mutation. Datasets were analyzed in R using Manhattan plots to calculate distance between expression profiles, Ward's method to perform unsupervised agglomerative clustering, and the Mann Whitney U test and Fisher's exact tests for supervised group analyses. The significance of transcriptome data was investigated by protein analysis, in situ enzymatic activity mapping, and in vivo magnetic resonance spectroscopy of orthotopic IDH1mut‐ and IDHwt‐glioma xenografts. Gene set enrichment analyses of clinical IDH1mut gliomas strongly suggest a role for catabolism of lactate and the neurotransmitter glutamate, whereas, in IDHwt gliomas, processing of glucose and glutamine are the predominant metabolic pathways. Further evidence of the differential metabolic activity in these cancers comes from in situ enzymatic mapping studies and preclinical in vivo magnetic resonance spectroscopy imaging. Our data support an evolutionary model in which IDHmut glioma cells exist in symbiosis with supportive neuronal cells and astrocytes as suppliers of glutamate and lactate, possibly explaining the diffuse nature of these cancers. The dependency on glutamate and lactate opens the way for novel approaches in the treatment of IDHmut gliomas. —Lenting, K. , Khurshed, M. , Peeters, T. H. , van den Heuvel, C. N. A. M. , van Lith, S. A. M. , de Bitter, T. , Hendriks, W. , Span, P. N. , Molenaar, R. J., Botman, D. , Verrijp, K. , Heerschap, A. , ter Laan, M. , Kusters, B. , van Ewijk, A. , Huynen, M. A. , van Noorden, C. J. F. , Leenders, W. P. J. Isocitrate dehydrogenase 1–mutated human gliomas depend on lactate and glutamate to alleviate metabolic stress. FASEB J. 33, 557–571 (2019). www.fasebj. org
Sudden Sensorineural Hearing Loss Predicts Ischemic Stroke: a Longitudinal Follow-Up Study.

OBJECTIVES To investigate the risk of stroke in SSNHL patients. STUDY DESIGN A longitudinal follow-up cohort study. SETTING The Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013. PATIENTS The 4,944 SSNHL participants were matched with 19,776 controls for age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia. The SSNHL subjects were diagnosed (International Classification of Disease [ICD]-10: H91.2), underwent an audiometry examination, and were treated with steroids. The history of hemorrhagic stroke, ischemic stroke, hypertension, diabetes, dyslipidemia, ischemic heart disease, and depression was investigated based on the ICD-10. MAIN OUTCOME MEASURES The hazard ratios (HRs) for hemorrhagic and ischemic stroke were analyzed using a Cox proportional hazard model. Subgroup analyses were conducted according to age (< 50 vs. ≥ 50 yr old) and sex. RESULTS Participants diagnosed with ischemic stroke included 4.2% of SSNHL subjects and 3.5% of control subjects (p = 0.013). The adjusted HR of SSNHL for ischemic stroke was 1.22 (95% confidence interval [95% CI] = 1.05 - 1.43, p = 0.012). The ≥ 50-year-old male SSNHL subgroup showed 1.40 adjusted HRs for ischemic stroke (95% CI = 1.10 - 1.78, p = 0.006). The rate of hemorrhagic stroke was 0.7% for SSNHL and 0.6% for control subjects. SSNHL did not elevate the risk of hemorrhagic stroke (p = 0.310). CONCLUSION SSNHL elevated the risk of ischemic stroke in the general population. Older males with SSNHL demonstrated a high risk for ischemic stroke; however, SSNHL did not increase the risk of hemorrhagic stroke.
Aberrant regulation of the GSK‐3β/NRF2 axis unveils a novel therapy for adrenoleukodystrophy

The nuclear factor erythroid 2‐like 2 (NRF2) is the master regulator of endogenous antioxidant responses. Oxidative damage is a shared and early‐appearing feature in X‐linked adrenoleukodystrophy (X‐ALD) patients and the mouse model (Abcd1 null mouse). This rare neurometabolic disease is caused by the loss of function of the peroxisomal transporter ABCD1, leading to an accumulation of very long‐chain fatty acids and the induction of reactive oxygen species of mitochondrial origin. Here, we identify an impaired NRF2 response caused by aberrant activity of GSK‐3β. We find that GSK‐3β inhibitors can significantly reactivate the blunted NRF2 response in patients’ fibroblasts. In the mouse models (Abcd1− and Abcd1−/Abcd2−/− mice), oral administration of dimethyl fumarate (DMF/BG12/Tecfidera), an NRF2 activator in use for multiple sclerosis, normalized (i) mitochondrial depletion, (ii) bioenergetic failure, (iii) oxidative damage, and (iv) inflammation, highlighting an intricate cross‐talk governing energetic and redox homeostasis in X‐ALD. Importantly, DMF halted axonal degeneration and locomotor disability suggesting that therapies activating NRF2 hold therapeutic potential for X‐ALD and other axonopathies with impaired GSK‐3β/NRF2 axis.
Facebook Addiction Disorder in Germany

This study explored the Facebook addiction disorder (FAD) in Germany. Of the 520 participants, 6.2 percent reached the critical polythetic cutoff score and 2.5 percent reached the critical monothetic cutoff score. FAD was significantly positively related to Facebook use frequency, the personality trait narcissism, as well as depression and anxiety symptoms, but also to subjective happiness. Its association with resilience was significantly negative. Furthermore, Facebook use frequency partly mediated the positive relationship between narcissism and FAD. Current results provide a first overview of FAD in Germany. They demonstrate that FAD is not only the consequence of excessive Facebook use. The positive relationship between FAD and happiness contributes to the understanding of the mechanisms that are involved in the development and maintenance of FAD, and partly explains earlier inconsistencies. Practical applications for future studies and limitations of present results are discussed.
Immunohistochemical expression profiles of MUC1 and MUC2 mucins in urothelial tumors of bladder

Background: Mucins may show aberrant expression, localization, and/or glycosylation in multiple malignancies. However, information regarding expression of these mucins is mostly unknown in urothelial tumors. Aim: This study was conducted for examining the expressions of membrane associated and secreted mucin (MUC1) and a secreted gel-forming mucin (MUC2) in urothelial tumors of the urinary bladder. Subjects and Methods: Archival transurethral resection materials of 97 urothelial carcinoma cases were reexamined light microscopically and graded according to the 2004 WHO Classification. Pathological stage was given as pTa, pT1, and pT2. Demonstrative sections were recut for immunohistochemistry for MUC1 and MUC2. The results were statistically analyzed, and P < 0.05 was considered statistically significant. Results: The positivity for MUC1 and MUC2 was 89.7% and 44.3%, respectively. Independent from pathological stage of the tumor, MUC1 expression showed statistically significant correlation with tumor grade (P < 0.05). We did not find any correlation between pathological stage and MUC1 and MUC2 expression (P > 0.05). MUC1 staining pattern in papillary urothelial neoplasm of low malignant potential cases was more commonly apical and superficial (luminal cell layer only). Intermediate cells ± basal cells or isolated cells or islands of tumor cells with cytoplasmic and/or circumferential membrane positivity for MUC1 and MUC2 were more commonly observed in both low- and high-grade carcinomas. The difference between groups in terms of MUC1 and MUC2 staining was statistically significant (P < 0.05). Conclusions: The staining patterns of both mucins are different between urothelial papillary tumors and may be used to make a differentiation, especially for low-grade papillary urothelial lesions. This difference may also be important in the carcinomatous transformation of urothelial neoplastic and preneoplastic lesions.
The procalcitonin/albumin ratio as an early diagnostic predictor in discriminating urosepsis from patients with febrile urinary tract infection

Abstract Discrimination between urosepsis and febrile urinary tract infections is important in therapeutic decision-making to indicate suitable treatments to avoid sepsis-related organ failure. Accurate diagnosis is time-consuming and susceptible to false-positive results. Moreover, patient responses to urosepsis are complex and varied. Therefore, this study aimed to develop a new, early diagnostic predictor that could discriminate between patients with urosepsis and those with febrile urinary tract infections using a combination of initial procalcitonin and albumin levels. We conducted a retrospective study involving 140 patients with febrile urinary tract infections from January 2013 to December 2017. Univariate and multivariate logistic analyses were performed to identify the independent risk factors for differentiating urosepsis from febrile urinary tract infection. A receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive accuracy of the procalcitonin/albumin ratio. Patients in the urosepsis group had higher procalcitonin/albumin ratios compared to those in the febrile urinary tract infection group [2.254 (0.978, 6.299) vs 0.021 (0.004, 0.095); P < . 001]. Based on multivariate logistic analysis, the procalcitonin/albumin ratio [adjusted odds ratio (OR) 1.029, 95% confidence interval (CI) 1.013–1.045, P < . 001] was an independent predictor of urosepsis, which allowed for differentiation from patients with febrile urinary tract infections. The area under the ROC curve (AUC) for the procalcitonin/albumin ratio was 0.937 (95% CI, 0.894–0.980); P < . 001. The sensitivity and specificity of the procalcitonin/albumin ratio cut-off values (>0.44) were 84.62% and 96.00%, respectively. Moreover, in the subset of 65 patients with urosepsis, the procalcitonin/albumin ratio in the uroseptic shock group was higher than in the group of patients without uroseptic shock [5.46 (1.43, 6.58) vs 1.24 (0.63, 4.38); P = . 009]. Our study demonstrates that the procalcitonin/albumin ratio is an early diagnostic predictor that can discriminate between urosepsis and febrile urinary tract infection. Additionally, in patients with urosepsis, those with higher procalcitonin/albumin ratios were more prone to uroseptic shock. Our findings suggest that the procalcitonin/albumin ratio is a rapid and relatively low-cost biomarker that can be used in clinical practice.
Germline pharmacogenomics of DPYD*9A (c.85T>C) variant in patients with gastrointestinal malignancies treated with fluoropyrimidines.

Background The correlation between DPYD*9A (c.85T>C) genotype and dihydropyrimidine dehydrogenase (DPD) deficiency clinical phenotype is controversial. Reference laboratories either did not perform DPYD*9A genotyping or have stopped DPYD*9A genotyping and limited genotyping to high-risk variants (DPYD*2A, DPYD*13 and DPYD*9B) only. This study explored DPYD*9A genotype and clinical phenotype correlation in patients with gastrointestinal (GI) malignancies treated with fluoropyrimidines. Methods Between 2011 and 2017, 67 patients with GI malignancies were genotyped for DPYD variants. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). Fisher's exact test was used for statistical analysis. Results DPYD variants were identified in 17 out of 67 (25%) patients. One patient was homozygous for DPYD*9A variant and one patient was double heterozygous for DPYD*9A and DPYD*9B variants. In patients with identified DPYD variants, 13/17 (76%) patients had DPYD*9A variant, 3/17 (18%) patients had DPYD*2A variant and 2/17 (12%) patient had DPYD*9B variant. Only patients genotyped prior to 2015 were genotyped for DPYD*9A variant (N=28). Of those, 13/28 patients (46%) had DPYD*9A variant. Grade 3-4 diarrhea was associated with DPYD*9A variant in patients treated with full dose fluoropyrimidines (P=0.0055). Conclusions In our cohort, DPYD*9A variant was the most common diagnosed variant. The correlation between DPYD*9A genotype and DPD deficiency in clinical phenotype was noticeable in patients who received full dose fluoropyrimidines as they all experienced grade 3-4 toxicities (diarrhea).
Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older Women: The Cardiovascular Health Study

OBJECTIVE To investigate the relationship of osteocalcin (OC), a marker of bone formation, and C-terminal cross-linked telopeptide of type I collagen (CTX), a marker of bone resorption, with incident diabetes in older women. RESEARCH DESIGN AND METHODS The analysis included 1,455 female participants from the population-based Cardiovascular Health Study (CHS) (mean [SD] age 74.6 [5.0] years). The cross-sectional association of serum total OC and CTX levels with insulin resistance (HOMA-IR) was examined using multiple linear regression. The longitudinal association of both markers with incident diabetes, defined by follow-up glucose measurements, medications, and ICD-9 codes, was examined using multivariable Cox proportional hazards models. RESULTS OC and CTX were strongly correlated (r = 0.80). In cross-sectional analyses, significant or near-significant inverse associations with HOMA-IR were observed for continuous levels of OC (β = −0.12 per SD increment; P = 0.004) and CTX (β = −0.08 per SD; P = 0.051) after full adjustment for demographic, lifestyle, and clinical covariates. During a median follow-up of 11.5 years, 196 cases of incident diabetes occurred. After full adjustment, both biomarkers exhibited inverse associations with incident diabetes (OC: hazard ratio 0.85 per SD [95% CI 0.71–1.02; P = 0.075]; CTX: 0.82 per SD [0.69–0.98; P = 0.031]), associations that were comparable in magnitude and approached or achieved statistical significance. CONCLUSIONS In late postmenopausal women, lower OC and CTX levels were associated with similarly increased risks of insulin resistance at baseline and incident diabetes over long-term follow-up. Further research to delineate the mechanisms linking abnormal bone homeostasis and energy metabolism could uncover new approaches for the prevention of these age-related disorders.
Intimate Partner Violence Victimization and Perpetration in a Turkish Female Sample: Rejection Sensitivity and Hostility

Intimate partner violence (IPV) against women is one of the most alarming social problems all over the world. Recently, IPV research focuses on the bidirectional nature of the phenomenon, which underlines that both women and men can equally be victims and perpetrators of IPV, especially in community samples. The cycle of violence theory asserts that child abuse and neglect (CAN) is a vulnerability factor for being both a victim and perpetrator of IPV while developmental mechanisms perspective assesses mediators explaining this association. The purpose of the current study was to investigate whether CAN and each type of CAN (emotional maltreatment, physical abuse and neglect, and sexual abuse) would be associated with victimization of and perpetration by women via the multiple mediator roles of rejection sensitivity and hostility after controlling for co-occurring CAN types. The sample (N = 288) included Turkish women who were currently married or in a romantic relationship or in one of these statutes in the past year. Participants were recruited via online survey to fill out the related questionnaires. The results of Bootstrap analyses showed that the total CAN scores were associated with being a victim and perpetrator of IPV in the past year. Rejection sensitivity mediated the association between CAN and being a victim of IPV while hostility was a mediator between CAN and perpetration of IPV. Childhood emotional maltreatment (CEM) was the only trauma type which predicted victimization by rejection sensitivity and perpetration by hostility above and beyond the effects of co-occurring trauma types. The present study findings contributed to the growing literature that women exposed to childhood traumas can also be perpetrators of violence that was a demonstrated risk factor for the repeated victimization. Results implied that developmental and process variables should be taken into account rather than a strict gendered analysis of IPV in research and clinical practice.
Fetus delivery time in extraperitoneal versus transperitoneal cesarean section: a randomized trial

Abstract Objective: We compared the extraperitoneal cesarean section to transperitoneal cesarean on fetal delivery time. Material and methods: This randomized study included 210 pregnant women undergoing cesarean section for elective reasons, repeat cesarean (< four), or dystocia. Patients who required an urgent cesarean section, who were at high risk for obstetric or maternal bleeding, who had a uterine or adnexal mass, or who requested tubal ligation were excluded from the study. The primary outcome of the study was the skin incision-to-delivery time. The sample size was set to detect of 1-minute difference in fetal delivery time between groups (two-tailed hypothesis, α = 0.05, β = 0.10). Secondary outcome measures were total operation time, intraoperative nausea, gag reflex, vomiting, pain and anxiety for those receiving regional anesthesia, postoperative pain, change in hemoglobin, postoperative analgesic requirements, nausea, vomiting and shoulder pain, urogenital distress, time until gas passage, and neonatal outcome. Results: No significant difference occurred between the two groups for skin incision-to- delivery time (extraperitoneal cesarean 3.9 minutes [2.1–7.3] versus transperitoneal cesarean 4.2 minutes [1.9–8.2], p = .065). Significant differences regarding intraoperative pain, total operation time, postoperative pain at the surgical site and shoulder pain, analgesic requirements, time until gas passage, and oral tolerability favored the extraperitoneal group. No significant differences between groups occurred regarding other seconder outcome parameters. Conclusions: There is no clinically significant difference between extraperitoneal cesarean section and transperitoneal cesarean on fetal delivery time. Extraperitoneal cesarean reduces postoperative pain, analgesic requirements, and improves oral tolerability.
A Comparative Study of Students Attitudes towards Mathematics in Two Different School Systems

Much research has been carried out in the history of mathematics education to find the factors that influence student achievement in the subject. Among these factors, student attitude towards mathematics has been consistently studied. There has often been a correlation found between students' attitudes and their achievement. In recent years Chinese students have consistently scored in the top band in mathematics international comparison tests while Irish students have been ranked at either side of the average mark. This study is in part motivated to explain why Chinese students appear to do so well in these international comparisons and whether differences in students' attitudes may play a key role. The attitudes towards mathematics of a cohort of 15 to 16 year old students in two selected schools in Ireland and China will be compared. This is a sample of students from one school in each country and so caution should be applied and the results should not be generalised. However there are some noteworthy findings which upon further investigation may have implications for policy makers and mathematics educators in both countries.
Postoperative functional exercise for patients who underwent percutaneous transforaminal endoscopic discectomy for lumbar disc herniation.

OBJECTIVE To explore the effects of postoperative functional exercise on patients who underwent percutaneous transforaminal endoscopic discectomy for lumbar disc herniation. PATIENTS AND METHODS From January to May 2011, patients who had a lumbar disc herniation and then underwent percutaneous transforaminal endoscopic discectomy were divided randomly into two groups: the intervention group (n=46) and the control group (n=46). The intervention group conducted early functional exercises of passive and autonomic activities after their operations, while the control group conducted routine functional exercises after their operations. Short-term and long-term curative effects and quality of life were compared; risk factors that might affect the rehabilitation effects on the patients were analyzed using logistic regression. RESULTS The lumbar curvature, lumbar lordosis index and sacral inclination angle of the intervention group were better than that those same spinal stability factors in the control group six months after their operations (p<0.05). Scores for residual lumbocrural pain, straight leg raising, muscle strength (skin) sensory, nerve reflex and lumbar function of patients in the intervention group were better than those scores of the control group (p<0.05). The scores for physiological function, emotional function, activity and social function, mental health and quality of life of the intervention group were better than those of the control group (p<0.05). After 1 year of follow-up, the total effective rate for the intervention group was 82.6%, significantly higher than the control group, which had a total effective rate of 71.7% (p<0.05). After 3 years of follow-up, the score for the intervention group was 97.8%, significantly higher than the control group, which had an overall average score of 89.1% (p<0.05). Logistic regression analysis showed that the type of disc herniation, whether patients abided by their doctors' advice during treatment and protected their lumbar vertebra during treatment, and their age were all influential factors on patient rehabilitation. CONCLUSIONS Early functional exercises of passive and autonomic activities can improve the postoperative quality of life of patients with lumbar disc herniation and provides a basis for inclusion in postoperative treatment of lumbar disc herniation. Importance should be placed on factors, such as postoperative exercise, that can improve the curative effect of rehabilitation.
Extracellular reduction of solid electron acceptors by Shewanella oneidensis

Shewanella oneidensis is the best understood model organism for the study of dissimilatory iron reduction. This review focuses on the current state of our knowledge regarding this extracellular respiratory process and highlights its physiologic, regulatory and biochemical requirements. It seems that we have widely understood how respiratory electrons can reach the cell surface and what the minimal set of electron transport proteins to the cell surface is. Nevertheless, even after decades of work in different research groups around the globe there are still several important questions that were not answered yet. In particular, the physiology of this organism, the possible evolutionary benefit of some responses to anoxic conditions, as well as the exact mechanism of electron transfer onto solid electron acceptors are yet to be addressed. The elucidation of these questions will be a great challenge for future work and important for the application of extracellular respiration in biotechnological processes.