Miracle-dz/UniFAR-FTUs huggingface dataset:
RETRACTION: Erlotinib, an Effective Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Induces p27KIP1 Up-Regulation and Nuclear Translocation in Association with Cell Growth Inhibition and G1/S Phase Arrest in Human Non-Small-Cell Lung Cancer Cell Lines

Erlotinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been shown to have potent antitumor effects against human non-small-cell lung cancer (NSCLC) cell growth; however, the mechanism of such an effect is not elucidated. Here, we demonstrate that erlotinib-induced cell growth inhibition in EGFR high-expressing human H322 NSCLC cells was accompanied by G1/S phase arrest, which was largely caused by a decrease in expression of G1/S-related cyclins, suppression of activities of cyclin-dependent kinase (CDK) 2 and CDK4, induction of CDK inhibitor p27KIP1, and retinoblastoma hypophosphorylation. To further understand the role of p27KIP1 in G1/S arrest and cell growth inhibition by erlotinib, we determined its effect on the expression of p27KIP1 at transcriptional and posttranscriptional levels. Studies using real-time reverse transcription-polymerase chain reaction analysis and p27 promoter-driven luciferase reporter showed that erlotinib treatment resulted in the promotion of p27 gene transcription. In addition, erlotinib treatment led to an increase in p27KIP1 half-life by inhibiting p27KIP1 phosphorylation at Thr187 and by down-regulating Skp2 expression. Furthermore, immunofluorescence staining and cell fractionation showed that erlotinib treatment led to p27KIP1 translocation to the nucleus. Knockdown of p27KIP1 expression with p27KIP1 small interfering RNA significantly abrogated erlotinib-induced G1 phase arrest and cell growth inhibition, suggesting that induction of p27KIP1 is required for G1 arrest and cell growth inhibition by erlotinib. It is noteworthy that we found that G1 arrest and p27KIP1 up-regulation by erlotinib occurred in the tested sensitive cell lines but to a lesser extent in the resistant cell lines. Taken together, these results suggest that erlotinib inhibits human NSCLC cell growth predominantly by inducing p27KIP1 expression and by suppressing cell-cycle events involved in the G1/S transition.
Volatility in Price of Rubber Crop in Kerala

Rubber is an important plantation crop cultivated in Kerala. The state holds a dominant position both in area and production. It is the main source of income for majority of farmers. Any volatility in the price of rubber put them in a miserable situation. Recent years witnessed unprecedented volatility in rubber price. Declining trend in the prices of rubber has pushed natural rubber production the lowest in the country. The study revealed that prices were so low so that the rubber cultivators cannot even pay workers wages and the recent unprecedented volatility in prices declined rubber production leads to the falling standard of living of the rubber farmers in Kerala.
[Birth asphyxia and hypoxic ischemic encephalopathy, incidence and obstetric risk factors].

OBJECTIVE Modern medical practice has changed dramatically during the past decades because of improved technology. Still, fetal surveillance during labor is relatively unchanged since 1960 s when fetal heart rate monitoring (FHR) became standard practice. Newborn infants are still suffering from birth asphyxia and in severe cases leading to hypoxic ischemic encephalopathy (HIE) which sometimes results in permanent neurological damage. The incidence of birth asphyxia and HIE in Iceland is unknown and so are the risk factors for severe asphyxia. The objective of this study was to assess the incidence, obstetric risk factors and the sequela of severe asphyxia at Landspitali university hospital (LSH). MATERIAL AND METHODS All term infants born at LSH from 1.1. 1997- 31.12. 2001 with birth asphyxia, defined as five minute Apgar score %lt;6, were included in the study (n=127). Clinical information were collected retrospectively from maternal records on maternal diseases during pregnancy, cardiotocogram (CTG), type of birth, the presence of meconium and operative delivery rates. Information was also collected regarding birth asphyxia and HIE in the neonatal period. RESULTS The incidence of birth asphyxia was 9.4/1000 live term births during the study period, with increasing incidence during the three last years. The incidence of HIE was 1.4/ 1,000 live term births. Severe maternal diseases during pregnancy were not a significant risk factor for asphyxia. The amniotic fluid was meconium stained in fifty percent of cases and the umbilical cord was wrapped around the fetal neck in 41% of cases. Abnormal CTG tracing was observed in 66% of cases in the study group and in 79% of the HIE cases. Operative deliveries were significantly more common in the study cohort compared with other deliveries at LSH at the same time: ventouse delivery 22% vs 6.8% (p<0,001), forceps delivery 6.3% vs 1,03% (p<0,001), emergency cesarean section 19.7% vs 11.4% ( p=0,008). CONCLUSION The incidence of birth asphyxia is higher in LSH compared with the incidence found in other studies. Signs of fetal distress on CTG and delivery with operative interventions are common. With current available methods to detect intrapartum asphyxia there is a poor correlation with CTG and the development of HIE after severe asphyxia. The presence of severe maternal diseases does not correlate with increased incidence of asphyxia, presumably due to increased surveillance of these pregnancies and a lower treshold for intervention during delivery. In low risk pregnancies there is a lack of appropriate methods with high sensitivity and specificity to detect intrapartum asphyxia.
Elevated levels of free tissue factor pathway inhibitor antigen in cases of disseminated intravascular coagulation caused by various underlying diseases

Tissue factor pathway inhibitor (TFPI) is primarily synthesized by vascular endothelial cells and is foundin vivoin association with endothelial cells, lipoproteins, or in free form. Free TFPI is the most potent and important type, because it is released from endothelial cells following an injection of heparin, or as a result of pathological stimuli. In order to study the role of TFPI in disease, the concentration of free form TFPI was measured in the plasma of 114 patients suffering from disseminated intravascular coagulation (DIC), as the result of several underlying diseases. Plasma antigen levels of free TFPI were significantly higher even in those patients not exhibiting DIC than in normal healthy subjects. These levels were even higher among patients exhibiting DIC, especially those with acute promyelocytic leukemia or cancer, receiving continuous heparin drip infusions. A significant correlation was observed between the plasma antigen levels of free form TFPI and those of fibrin/fibrinogen degradation products, and free form TFPI and plasmin inhibitor complex (r= 0.428,P< 0.0001 andr= 0.329,P< 0.0001, respectively) among 114 DIC patients. There were no significant differences between the plasma levels of free TFPI in DIC patients with or without multiple organ failure. It has been suggested that the plasma levels of free TFPI are closely related to the levels of fibrinolysis occurring in DIC patients, although further study is required to clarify the degree to which TFPI is expressed by endothelial cells during DIC.
Metabolic profile and cardiovascular risk factors in adult patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Background: In congenital adrenal hyperplasia (CAH), long-term glucocorticoid treatment coupled with increased androgens may lead to undesirable metabolic effects. The aim of our report was to determine the prevalence of metabolic abnormalities and cardiovascular risk factors in a population of adult patients with CAH due to 21 hydroxylase deficiency. Materials and Methods: Twenty-six patients (11 males and 15 females, mean age ± SD=27.4±8.2 years) were recruited. Anthropometry, body composition, metabolic parameters and cardiovascular risk factors were studied. Results: Obesity (overweight included) was noted in 16 patients (61.5%), with android distribution in all cases. Bioelectrical impedance showed increased body fat mass in 12 patients (46.1%). Lipid profile alterations and carbohydrate metabolism disorders were detected in seven (26.9%) and five (19.2%) patients respectively. Moderate hepatic cytolysis, associated with hepatic steatosis, was found in one patient. Seven patients (27%) had insulin resistance. Ambulatory blood pressure monitoring showed abnormalities in six patients (23%). Increased carotid intima media thickness was found in 14 patients (53.8%). Conclusion: Adult CAH patients tend to have altered metabolic parameters and a higher prevalence of cardiovascular risk factors. Lifelong follow-up, lifestyle modifications, and attempts to adjust and reduce the glucocorticoid doses seem important.
The Effect of Aggregation of Accounting Information via Segment Reporting on Accounting Conservatism

Abstract In a sample of U.S. multiple-segment firms, we document a negative association between aggregation via segment reporting and timely loss recognition. A higher level of aggregation, as reflected in a firm’s reported organizational structure (the definition and characteristics of its segments), causes a multiple-segment firm to exhibit less cross-segment variation in profitability than a matched control portfolio of single-segment firms. We find that firms that engage in more aggregation report accounting numbers that provide less timely information about economic losses. We also observe that firms that provide more disaggregated segment data subsequent to adopting SFAS 131 experienced an increase in timely loss recognition. This result implies that higher quality segment reporting leads to an increase in timely loss recognition, which, per extant research, is associated with better governance. Our results complement results in Berger and Hann [2003. The impact of SFAS No. 131 on information and monitoring. Journal of Accounting Research, 41, 163–223] that show a decline in inefficient internal-capital-market transfers subsequent to the adoption of SFAS 131. Overall, we provide evidence supporting Beyer, Cohen, Lys, and Walther’s [2010. The financial reporting environment: Review of the recent literature. Journal of Accounting and Economics, 50, 296–343] contention that accounting conservatism is, in part, a function of managers’ aggregation choices.
The effects of the glutamate antagonist memantine on brain activation to an auditory perception task

Glutamate is critically involved in the regulation of cognitive functions in humans. There is, however, sparse evidence regarding how blocking glutamate action at the receptor site during a cognitive task affects brain activation. In the current study, the effects of the glutamate antagonist memantine were examined with functional magnetic resonance imaging (fMRI). Thirty‐one healthy adults were scanned twice in a counter‐balanced design, either in a no‐drug session or after administration of memantine for 21 days. The subjects performed a simple auditory perception task with consonant‐vowel stimuli. Group‐level spatial independent component analysis (ICA) was used to decompose the data and to extract task‐related activations. The focus was on four task‐related ICA components with frontotemporal localization. The results showed that glutamate‐blockage resulted in a significant enhancement in one component, with no significant effect in the other three components. The enhanced effect of memantine was in the middle temporal gyrus, superior frontal gyrus, and middle frontal gyrus. It is suggested that the results reflect effects of glutamatergic processes primarily through non‐N‐methyl‐D‐aspartate (NMDA) receptor pathways. Moreover, the results demonstrate that memantine can be used as a probe which allows for studying the effect of excitatory neurotransmission on neuronal activation. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Monocytes and dendritic cells are the primary sources of interleukin 37 in human immune cells

The interleukin (IL)‐1 family member IL‐37 is one of few anti‐inflammatory cytokines, and it is capable of countering a broad spectrum of proinflammatory assaults. Although it is known that leukocytes are a major source of IL‐37, knowledge on IL‐37 production and secretion in specific immune cell types remains limited. Thus, we investigated IL‐37 mRNA expression as well as protein production and secretion in human PBMCs. In PBMCs stimulated with agonists of Toll‐like receptors (TLRs) 1–6 and 9, IL1F7 (the IL‐37‐encoding gene) was induced up to 9‐fold, peaked at 6–8 h and returned to steady‐state at 72 h. LPS‐induced IL1F7 expression comprised isoforms b and c but not a and e. Flow cytometry revealed that among IL‐37+ PBMCs, monocytes predominated (81–91%), but T cells (6–8%) and myeloid dendritic cells (mDCs, 1–2%) also contributed to the IL‐37+ leukocyte pool. Monocytes and mDCs, but not T cells, were capable of secreting IL‐37. Whereas monocytes and mDCs secreted IL‐37 upon LPS stimulation, only mDCs also released IL‐37 at steady‐state. Among monocyte subsets, IL‐37 was LPS inducible and secreted only in classical and, although less pronounced, in intermediate monocytes; secretion was observed as early as 3 h after stimulation. Overall, our data suggest that constitutive IL‐37 secretion by mDCs may serve to maintain an anti‐inflammatory milieu at steady state, whereas IL‐37 is stored in monocytes to be available for rapid release upon inflammatory encounters, thus acting as a novel anti‐inflammatory alarmin. These insights may prove important to advancing towards clinical use the protective functions of one of the most powerful anti‐inflammatory mediators so far discovered.
Probiotics modulate inflammatory cytokine secretion from inflamed mucosa in active ulcerative colitis

Enteric microflora of ulcerative colitis patients becomes aberrant. The abnormal interaction between microflora and intestinal mucosal immune system leads the mucosal inflammation. Probiotic administration may recover the commensal microflora and normalise the host–microbial interaction. In this experiment, we cocultured colonic biopsies from active ulcerative colitis patients with bifidobacterium to investigate the modulation effect of probiotics on inflamed colonic tissues and its possible mechanism.
Magnetic resonance imaging and electromyography as indexes of muscle function.

Electromyography (EMG) is commonly used to determine the electrical activity of skeletal muscle during contraction. To date, independent verification of the relationship between muscle use and EMG has not been provided. It has recently been shown that relaxation- (e.g., T2) weighted magnetic resonance images (MRI) of skeletal muscle demonstrate exercise-induced contrast enhancement that is graded with exercise intensity. This study was conducted to test the hypothesis that exercise-induced magnetic resonance (MR) contrast shifts would relate to EMG amplitude if both measures reflect muscle use during exercise. Both MRI and EMG data were collected for separate eccentric (ECC) and concentric (CON) exercise of increasing intensity to take advantage of the fact that the rate of increase and amplitude of EMG activity are markedly greater for CON muscle actions. Seven subjects 30 +/- 2 (SE) yr old performed five sets of 10 CON or ECC arm curls with each of four resistances representing 40, 60, 80, and 100% of their 10 repetition maximum for CON curls. There was 1.5 min between sets and 30 min between bouts (5 sets of 10 actions at each relative resistance). Multiple echo, transaxial T2-weighted MR images (1.5 T, TR/TE 2,000/30) were collected from a 7-cm region in the middle of the arm before exercise and immediately after each bout. Surface EMG signals were collected from both heads of the biceps brachii and the long head of the triceps brachii muscles. CON and ECC actions resulted in increased integrated EMG (IEMG) and T2 values that were strongly related (r = 0.99, P < 0.05) with relative resistance. (ABSTRACT TRUNCATED AT 250 WORDS)
Automated curved planar reformation of 3D spine images

Traditional techniques for visualizing anatomical structures are based on planar cross-sections from volume images, such as images obtained by computed tomography (CT) or magnetic resonance imaging (MRI). However, planar cross-sections taken in the coordinate system of the 3D image often do not provide sufficient or qualitative enough diagnostic information, because planar cross-sections cannot follow curved anatomical structures (e.g. arteries, colon, spine, etc). Therefore, not all of the important details can be shown simultaneously in any planar cross-section. To overcome this problem, reformatted images in the coordinate system of the inspected structure must be created. This operation is usually referred to as curved planar reformation (CPR). In this paper we propose an automated method for CPR of 3D spine images, which is based on the image transformation from the standard image-based to a novel spine-based coordinate system. The axes of the proposed spine-based coordinate system are determined on the curve that represents the vertebral column, and the rotation of the vertebrae around the spine curve, both of which are described by polynomial models. The optimal polynomial parameters are obtained in an image analysis based optimization framework. The proposed method was qualitatively and quantitatively evaluated on five CT spine images. The method performed well on both normal and pathological cases and was consistent with manually obtained ground truth data. The proposed spine-based CPR benefits from reduced structural complexity in favour of improved feature perception of the spine. The reformatted images are diagnostically valuable and enable easier navigation, manipulation and orientation in 3D space. Moreover, reformatted images may prove useful for segmentation and other image analysis tasks.
Adenovirus type 5 with modified hexons induces robust transgene‐specific immune responses in mice with pre‐existing immunity against adenovirus type 5

Adenovirus type 5 (Ad5) is widely used as a vehicle for vaccine delivery in the treatment of infectious disease and cancer. However, the efficacy of Ad5 vectors has been limited in humans because exposure to Ad5 infections results in most adults having neutralizing antibodies against Ad5. To overcome this limitation, the hexon epitope present in the fifth hypervariable region of Ad5 was modified.
Site and Tumor Type Predicts DNA Mismatch Repair Status in Cutaneous Sebaceous Neoplasia

Cutaneous sebaceous neoplasia is known to exhibit a high degree of DNA mismatch repair (MMR) deficiency leading to microsatellite instability and these tumors can be markers of the Muir-Torre syndrome and internal malignancy. Other tumors, such as colonic carcinoma, show tendencies toward particular histologic features and sites of involvement correlating with MMR deficiency. There are few comprehensive studies of unselected cutaneous sebaceous neoplasms. To address this gap in knowledge, we examined 94 sebaceous neoplasms from 92 patients and 17 sebaceous hyperplasia controls using immunohistochemistry for MLH1, MSH2, and MSH6. Our results indicate that MMR deficiency is significantly associated with anatomic location (more frequently in the trunk and extremities as compared with head and neck), tumor type (more often in adenoma compared with carcinoma within the head and neck region), and architecture (keratoacanthomalike). No correlation between cystic change and MMR deficiency was noted. Cutaneous sebaceous neoplasia has tendencies toward certain tumor types and anatomic distribution based on MMR status analogous to that seen in colonic carcinomas and other tumors. These may be helpful indicators for further workup for the Muir-Torre syndrome.
Developing leadership skills among adolescents and young adults: a review of leadership programmes

Abstract Our understanding of leadership is skewed towards the adult experience of leadership. There is a gap in the literature with regard to the experience of leadership among school children and young adults. Young people experience their first formal organization at school and models of leadership are developed from this critical period. The present review identified studies on leadership development programmes for young adults from 2003 to 2015 via electronic databases: Scopus, PubMed and Science direct. Nine studies met all the inclusion criteria and were analysed with regard to; selection, content, outcomes and theoretical background. Considerable heterogeneity in the methods used was observed. The review presents key research questions that need to be addressed in future studies.
Peer review for improving the quality of grant applications.

BACKGROUND Grant giving relies heavily on peer review for the assessment of the quality of proposals but the evidence of effects of these procedures is scarce. OBJECTIVES To estimate the effect of grant giving peer review processes on importance, relevance, usefulness, soundness of methods, soundness of ethics, completeness and accuracy of funded research. SEARCH STRATEGY Electronic database searches and citation searches; researchers in the field were contacted. SELECTION CRITERIA Prospective or retrospective comparative studies with two or more comparison groups assessing different interventions or one intervention against doing nothing. Interventions may regard different ways of screening, assigning or masking submissions, different ways of eliciting opinions or different decision making procedures. Only original research proposals and quality outcome measures were considered. DATA COLLECTION AND ANALYSIS Studies were read, classified and described according to their design and study question. No quantitative analysis was performed. MAIN RESULTS Ten studies were included. Two studies assessed the effect of different ways of screening submissions, one study compared open versus blinded peer review and three studies assessed the effect of different decision making procedures. Four studies considered agreement of the results of peer review processes as the outcome measure. Screening procedures appear to have little effect on the result of the peer review process. Open peer reviewers behave differently from blinded ones. Studies on decision-making procedures gave conflicting results. Agreement among reviewers and between different ways of assigning proposals or eliciting opinions was usually high. AUTHORS' CONCLUSIONS There is little empirical evidence on the effects of grant giving peer review. No studies assessing the impact of peer review on the quality of funded research are presently available. Experimental studies assessing the effects of grant giving peer review on importance, relevance, usefulness, soundness of methods, soundness of ethics, completeness and accuracy of funded research are urgently needed. Practices aimed to control and evaluate the potentially negative effects of peer review should be implemented meanwhile.