Miracle-dz/UniFAR-FTUs huggingface dataset:
Thyroid cancer resistance to vitamin D receptor activation is associated with 24-hydroxylase levels but not the ff FokI polymorphism.

BACKGROUND The vitamin D receptor (VDR) has been studied as a novel target for cancer therapy in many tissue types as VDR ligands decrease cell proliferation in vitro and decrease tumor growth in vivo in sensitive cells. The objective of this study was to analyze the response to VDR agonist therapy in a panel of validated thyroid cancer cells and assess genetic markers predicting sensitivity and resistance to calcitriol and the noncalcemic analog DP006. METHODS Thyroid cancer cell lines were analyzed for VDR and RXR protein by Western blot. Cell growth after VDR agonist treatment (calcitriol or DP006) was assessed after 6 days of treatment by viable cell assay. To investigate calcitriol/DP006 resistance in VDR-expressing cells, the VDR was sequenced and 1-α and 24-hydroxylase mRNA expression was assessed. RESULTS VDR protein was variably expressed in the thyroid cancer cell lines and its presence was not sufficient for decreased viable cell count in response to calcitriol or DP006. The most sensitive cells (TPC1) have an ff FokI VDR polymorphism and the most resistant cells (HTh7 and 8505C) have an FF FokI VDR. This is a unique finding given that the balance of the literature of VDR polymorphisms describes an association of the ff FokI polymorphism with cancer risk and/or decreased VDR transactivation. 1-α and 24-hydroxylase mRNA expression before and after VDR agonist therapy was examined. 1-α-Hydroxylase levels did not change after calcitriol treatment. However, we found that higher baseline 24-hydroxylase levels and/or lower stimulation of 24-hydroxylase levels after calcitriol treatment were associated with relative resistance to calcitriol/DP006. CONCLUSIONS The VDR represents a novel therapeutic target in poorly differentiated thyroid cancer; however, the efficacy of VDR agonist therapy to decrease viable thyroid cancer cell count cannot be predicted solely on the presence of the VDR. The FF FokI VDR genotype and high baseline 24-hydroxylase levels were associated with relative resistance to calcitriol and DP006. Therefore, identifiable markers of sensitivity or resistance to VDR agonist therapy may allow for a personalized use of these agents in poorly differentiated thyroid cancer.
Cerebellar Malignant Fibrous Histiocytoma: Case Report and Literature Review

OBJECTIVE AND IMPORTANCEMalignant fibrous histiocytoma in the central nervous system is uncommon. Fewer than 70 cases have been documented and, to the best of our knowledge, this is the first case arising from the cerebellum. CLINICAL PRESENTATIONA 44-year-old woman presented with headaches, vomiting, and dizziness. A neurological examination revealed right cerebellar syndrome. Brain computed tomographic scans revealed an isodense tumor in the right cerebellar hemisphere. The breast ultrasonographic, bone scintigraphic, and thoracoabdominal computed tomographic findings were normal. INTERVENTIONThe patient was surgically treated. The tumor recurred 1.5 months later, demonstrating hemorrhagic characteristics on brain computed tomographic scans. The patient underwent a second operation, followed by radiotherapy. CONCLUSIONMalignant fibrous histiocytoma is still a controversial entity, and the lack of specific criteria means that it must be diagnosed via the process of elimination. With currently available therapy, our review can provide only a very poor prognosis. The median survival time was 27 months. In attempts to develop better therapeutic strategies, total excision and radiotherapy seem to represent the best treatment approach.
Pressure ulcer in patients with severe traumatic brain injury: significant factors and association with neurological outcome.

AIMS AND OBJECTIVES To assess the factors associated with development of pressure ulcer in patients with severe traumatic brain injury (TBI) and study its prognostic significance with respect to neurological outcome at three months. BACKGROUND Patients with severe TBI are prone to develop pressure ulcer due to various factors, which have never been studied in detail. DESIGN Prospective longitudinal study. METHODS Eighty-nine patients of TBI in age group 20-60 years admitted with Glasgow Coma Scale (GCS) 4-8 without serious systemic disorder were enrolled for the study. Patient characteristics, haemoglobin, serum albumin levels at admission and their weekly changes till 21 days were noted along with daily assessment for presence of pressure ulcer. Mortality was assessed at 21 days and neurological outcome at three months through telephonic interview. RESULTS Of 89 patients studied, pressure ulcer was observed in 6 (7%) and 14 (16%) at the end of two and three weeks, respectively. Pressure ulcer in univariate analysis was significantly associated with poorer GCS (p = 0·05), delayed enteral feeding (p = 0·005) and fall in haemoglobin at two weeks (p = 0·005). Only the latter two were found significant in multivariate analysis. Age, gender, surgical intervention, tracheostomy, prolonged fever and change in albumin had no significant association with pressure ulcer development. Presence of pressure ulcer was significantly associated with mortality at 21 days (p = 0·006) and unfavourable neurological outcome at three months (p = 0·01). CONCLUSIONS The significant factors influencing pressure ulcer development in patients with TBI were delayed enteral feeding and fall in haemoglobin. Pressure ulcer had significant association with mortality at 21 days and recovery status at three months. RELEVANCE TO CLINICAL PRACTICE Early nutritional supplementation and monitoring of haemoglobin should be an important part of nursing care interventions for patients at increased risk of developing pressure ulcer.
Microvessel density, p53 overexpression, and apoptosis in invasive breast carcinoma.

AIM: To investigate the possibility of a correlation among microvessel density, p53 overexpression, and apoptosis in invasive breast carcinoma. METHODS: Microvessel density was analysed in 105 cases of invasive breast carcinoma by immunohistology using antifactor VIII related antibody. The results were correlated with the immunohistochemical expression of p53 and the apoptotic index, detected using the in situ end labelling of fragmented DNA method (TUNEL). Assessment was made with a CAS 200 image analyser. All these studies were performed on formalin fixed, paraffin wax embedded tissue sections of tumour samples. RESULTS: The mean (SD) microvessel count was 47.2 (51.1), with a range from 7 to 250. Thirty five (33%) carcinomas showed overexpression of p53 protein. The apoptotic index of tumours ranged from 0.0 to 28.0, with a mean (SD) of 1.7 (3.2). The results showed that there was a significant inverse correlation between microvessel density and p53 expression (p = 0.04; odds ratio, 0.37). In contrast, no correlation was identified between the microvessel density and apoptotic index. CONCLUSIONS: These results suggest that in invasive breast carcinoma the p53 overexpression phenotype downregulates tumour neoangiogenesis, as does the wild-type of p53 protein. In addition, they suggest that apoptosis and neoangiogenesis in these tumours are independent processes.
CUL1 regulates TOC1 protein stability in the Arabidopsis circadian clock.

SUMMARY The circadian clock is the endogenous timer that coordinates physiological processes with daily and seasonal environmental changes. In Arabidopsis thaliana, establishment of the circadian period relies on targeted degradation of TIMING OF CAB EXPRESSION 1 (TOC1) by the 26S proteasome. ZEITLUPE (ZTL) is the F-box protein that associates with the SCF (Skp/Cullin/F-box) E3 ubiquitin ligase that is responsible for marking TOC1 for turnover. CULLIN1 (CUL1) is a core component of SCF complexes and is involved in multiple signaling pathways. To assess the contribution of CUL1-containing SCF complexes to signaling within the plant oscillator, circadian rhythms were examined in the recessive, temperature-sensitive CUL1 allele axr6-3. The activity of CUL1 in this mutant declines progressively with increasing ambient temperature, resulting in more severe defects in CUL1-dependent activities at elevated temperature. Examination of circadian rhythms in axr6-3 revealed circadian phenotypes comparable to those observed in ztl null mutants; namely, lengthened circadian period, altered expression of core oscillator genes, and limited degradation of TOC1. In addition, treatment of seedlings with exogenous auxin did not alter TOC1 stability. These results demonstrate that CUL1 is required for TOC1 degradation and further suggest that this protein is the functional cullin for the SCF(ZTL) complex.
Serum ferritin levels as a useful diagnostic marker for the distinction of systemic juvenile idiopathic arthritis and Kawasaki disease

Abstract Objectives: The clinical features and laboratory parameters of patients with Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (s-JIA) tend to overlap. Furthermore, there have been no definitive biomarkers for these diseases, making clinical diagnosis difficult. The purpose of this study was to investigate the diagnostic value of serum ferritin levels for differentiating KD from s-JIA and predicting the disease severity of KD. Methods: We analyzed 228 patients with KD and 81 patients with s-JIA. Serum ferritin levels were compared between patients with s-JIA and KD. Furthermore, serum ferritin levels in patients with KD were compared with respect to clinical features such as responsiveness to intravenous immunoglobulin (IVIG) therapy. Results: Serum ferritin levels in KD patients with no response to IVIG therapy were significantly higher than those in KD patients with a good response to IVIG therapy. Serum ferritin levels in patients with KD needing plasma exchange (PE) were significantly higher than those in patients not needing PE. However, serum ferritin levels overlapped between severe KD patients with nonresponsiveness to IVIG therapy or needing PE and other patients with mild KD. Furthermore, patients with s-JIA showed a distinct elevation of serum ferritin levels compared with KD patients. The cutoff value of serum ferritin levels for differentiating KD from s-JIA was 369.6 ng/ml. Conclusions: Serum ferritin levels were significantly elevated in s-JIA patients compared with KD patients. Measurement of serum ferritin levels can be useful for differentiating s-JIA from KD.
Reciprocal Control of Osteogenic and Adipogenic Differentiation by ERK/MAP Kinase Phosphorylation of Runx2 and PPARγ Transcription Factors

In many skeletal diseases, including osteoporosis and disuse osteopenia, defective osteoblast differentiation is associated with increased marrow adipogenesis. The relative activity of two transcription factors, RUNX2 and PPARγ, controls whether a mesenchymal cell will differentiate into an osteoblast or adipocyte. Herein we show that the ERK/MAP kinase pathway, an important mediator of mechanical and hormonal signals in bone, stimulates osteoblastogenesis and inhibits adipogenesis via phosphorylation of RUNX2 and PPARγ. Induction of osteoblastogenesis in ST2 mesenchymal cells was associated with increased MAPK activity and RUNX2 phosphorylation. Under these conditions PPARγ phosphorylation also increased, but adipogenesis was inhibited. In contrast, during adipogenesis MAPK activity and phosphorylation of both transcription factors was reduced. RUNX2 phosphorylation and transcriptional activity were directly stimulated by MAPK, a response requiring phosphorylation at S301 and S319. MAPK also inhibited PPARγ‐dependent transcription via S112 phosphorylation. Stimulation of MAPK increased osteoblastogenesis and inhibited adipogenesis, while dominant‐negative suppression of activity had the opposite effect. In rescue experiments using Runx2−/− mouse embryo fibroblasts (MEFs), wild type or, to a greater extent, phosphomimetic mutant RUNX2 (S301E,S319E) stimulated osteoblastogenesis while suppressing adipogenesis. In contrast, a phosphorylation‐deficient RUNX2 mutant (S301A,S319A) had reduced activity. Conversely, wild type or, to a greater extent, phosphorylation‐resistant S112A mutant PPARγ strongly stimulated adipogenesis and inhibited osteoblastogenesis in Pparg−/− MEFs, while S112E mutant PPARγ was less active. Competition between RUNX2 and PPARγ was also observed at the transcriptional level. Together, these studies highlight the importance of MAP kinase signaling and RUNX2/PPARγ phosphorylation in the control of osteoblast and adipocyte lineages. J. Cell. Physiol. 231: 587–596, 2016. © 2015 Wiley Periodicals, Inc.
The theatricality of accountability: The operation of governing bodies in schools

The shift from political leadership to new forms of governance has led to the establishment of locally appointed bodies in many public organizations including schools. From a dramaturgical perspective, this article focuses on the accountability of these new bodies, in particular on the codes of accountability. Using school governing bodies to illustrate, the article evaluates whether accountability in practice might be likened to a theatrical performance. The findings presented are relevant to school governing bodies and there may be wider application in public sector boards more generally.
MODELLING INVESTMENTS IN COTTON PRODUCTION IN THE MUNICIPAL AREAS OF KOUANDÃ‰ AND KÃ‰ROU IN THE NORTHERN PART OF REPUBLIC OF BENIN, WEST AFRICA

This study aims at analysing the effects of the investments in cotton production on the output elasticity in KouandA© and KA©rou, Republic of Benin, West Africa. Data were collected from June to September 2012 by surveying one hundred and forty (140) cotton farmers, randomly selected in the study area. The Cobb-Douglas and Translog models were estimated by considering six (06) inputs, namely:Â acreage of cotton, quantities of mineral fertilisers used, insecticides, herbicides, capital and family labour. The results revealed that the average acreage of cotton per farmer was 3.05 ha. Per hectare, farmers used on average 145.01 Man-Day of family labour, 305.15 kg of fertilisers (NPK and Urea), 1826.30 ml of insecticides (Thian, Serfox, Tunder, and Miticide), 3692.70 ml of herbicides (Calah and Califor G), and Francs CFA 42411 as capital. The Cobb-Douglas model showed that investing in land, mineral fertilisers, insecticides, and herbicides was technically efficient. In contrast, the Translog model revealed that the cotton productivity was rather determined by the interactions between â€œlabour and herbicidesâ€, â€œlabour and capitalâ€, and â€œcapital and herbicidesâ€; which have significantly impacts on the cotton output elasticity. Among these options, only the combination â€œlabour and herbicidesâ€ ensure a positive and significant output elasticity and therefore, appears to be the best investment alternative.
The Predicted Coiled-coil Domain of Myosin 10 Forms a Novel Elongated Domain That Lengthens the Head*

Myosin 10 contains a region of predicted coiled coil 120 residues long. However, the highly charged nature and pattern of charges in the proximal 36 residues appear incompatible with coiled-coil formation. Circular dichroism, NMR, and analytical ultracentrifugation show that a synthesized peptide containing this region forms a stable single α-helix (SAH) domain in solution and does not dimerize to form a coiled coil even at millimolar concentrations. Additionally, electron microscopy of a recombinant myosin 10 containing the motor, the three calmodulin binding domains, and the full-length predicted coiled coil showed that it was mostly monomeric at physiological protein concentration. In dimers the molecules were joined only at their extreme distal ends, and no coiled-coil tail was visible. Furthermore, the neck lengths of both monomers and dimers were much longer than expected from the number of calmodulin binding domains. In contrast, micrographs of myosin 5 heavy meromyosin obtained under the same conditions clearly showed a coiled-coil tail, and the necks were the predicted length. Thus the predicted coiled coil of myosin 10 forms a novel elongated structure in which the proximal region is a SAH domain and the distal region is a SAH domain (or has an unknown extended structure) that dimerizes only at its end. Sequence comparisons show that similar structures may exist in the predicted coiled-coil domains of myosins 6 and 7a and MyoM and could function to increase the size of the working stroke.
Structural Analysis of a Complex between Small Ubiquitin-like Modifier 1 (SUMO1) and the ZZ Domain of CREB-binding Protein (CBP/p300) Reveals a New Interaction Surface on SUMO*

We have recently discovered that the ZZ zinc finger domain represents a novel small ubiquitin-like modifier (SUMO) binding motif. In this study we identify the binding epitopes in the ZZ domain of CBP (CREB-binding protein) and SUMO1 using NMR spectroscopy. The binding site on SUMO1 represents a unique epitope for SUMO interaction spatially opposite to that observed for canonical SUMO interaction motifs (SIMs). HADDOCK docking simulations using chemical shift perturbations and residual dipolar couplings was employed to obtain a structural model for the ZZ domain-SUMO1 complex. Isothermal titration calorimetry experiments support this model by showing that the mutation of key residues in the binding site abolishes binding and that SUMO1 can simultaneously and non-cooperatively bind both the ZZ domain and a canonical SIM motif. The binding dynamics of SUMO1 was further characterized using 15N Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersions, which define the off rates for the ZZ domain and SIM motif and show that the dynamic binding process has different characteristics for the two cases. Furthermore, in the absence of bound ligands SUMO1 transiently samples a high energy conformation, which might be involved in ligand binding.
A Comparison of Anterior Cervical Corpectomy and Fusion Combined With Artificial Disc Replacement and Cage Fusion in Patients With Multilevel Cervical Spondylotic Myelopathy

Study Design. A retrospective study. Objective. The aim of this study was to compare clinical and radiological outcomes of anterior cervical corpectomy and fusion (ACCF) combined with artificial disc replacement (C-ADR) and ACCF combined with anterior cervical discectomy and fusion (ACDF) in patients with consecutive 3-level cervical spondylotic myelopathy (CSM). Summary of Background Data. The optimal surgical strategy for multilevel CSM (MCSM) remains undefined. C-ADR maintains motion at the level of the surgical procedure and decreases strain on the adjacent segments. The clinical results of multilevel C-ADR have not yet been elucidated. ACCF combined with 1-level C-ADR for the treatment of consecutive 3-level CSM may be a reasonable alternative to 3-level fusion. Methods. We retrospectively reviewed the histories of patients who underwent surgery for consecutive 3-level CSM between C3–4 and C6–7 from June 2007 to August 2011. A total of 42 patients were divided into 2 groups. Group A (n = 19) underwent ACCF combined with 1-level C-ADR; group B (n = 23) underwent ACCF combined with 1-level ACDF. We compared perioperative parameters, clinical parameters, and radiological parameters. Results. There were no significant differences in the average age, sex ratio, the preoperative heights of the disc space or average blood loss between the 2 groups. Group A had longer operation times than group B (P < 0.05). During the follow-up period, group A showed a better Neck Dysfunction Index recovery (P < 0.05) at 24 months postoperatively, and less visual analogue scale scores at 12 and 24 months postoperatively (P < 0.05 and P < 0.001, respectively). Moreover, group A exhibited better C2–C7 range of motion recovery at 6, 12, and 24 months postoperatively (P < 0.05, respectively). Conclusion. Group A was superior to Group B in terms of better Neck Dysfunction Index recovery, less intermediate term pain, and better C2–C7 ROM recovery. ACCF hybrid 1-level C-ADR may be a suitable choice for the management of 3-level CSM in appropriate patients. Level of Evidence: 3
Estimating the Risk of Future Reading Difficulties in Kindergarten Children: A Research-Based Model and Its Clinical Implementation.

PURPOSE Speech-language pathologists have the skills and knowledge needed to play an important role in the early identification of children who are at risk for reading difficulties. Whereas research has identified language and other factors that may be predictive of future reading problems, studies have not provided the statistical models and classification data needed for the implementation of early identification programs. In this paper, we report the results of a longitudinal study that examined kindergarten predictors of second-grade reading outcome. METHOD Six hundred and four children were given a battery of language, early literacy, and nonverbal cognitive measures in kindergarten as part of an epidemiologic study of language impairments in children. Follow-up testing of reading achievement was completed in second grade. Participants were divided into those children with and without reading difficulties. RESULTS Findings indicated that five kindergarten variables (letter identification, sentence imitation, phonological awareness, rapid naming, and mother's education) uniquely predicted reading outcome in second grade. CLINICAL IMPLICATIONS A logistic regression formula and classification data based on these results are provided. Suggestions are offered concerning how this information could be used in an early identification and intervention program for children who are at risk for reading difficulties.
No differences in mucosal adaptive growth one week after intestinal resection in rats given enteral glutamine supplementation or deprived of glutamine.

OBJECTIVE To evaluate the effects of intraluminal glutamine on the adaptation of intestinal mucosa after resection compared with transsection and un-operated on control animals. DESIGN Open, controlled, experimental study. SETTING University hospital, Sweden. SUBJECTS 123 Sprague-Dawley rats. INTERVENTION Daily isonitrogenous oral diet was given either free of glutamine or supplemented with 4% glutamine for 2 or 7 days to rats subjected to intestinal resection, transection or no operation. MAIN OUTCOME MEASURES Body weight and protein content, DNA content, and thymidine incorporation in jejunal and ileal mucosa. RESULTS Resection resulted in a significant growth stimulation evaluated by weight/body weight, protein, and DNA content (p < 0.05-0.001). Glutamine supplementation did not significantly influence this growth response. Thymidine incorporation in jejunum was stimulated by glutamine on day 3 (p < 0.05-0.001). CONCLUSION The glutamine fortified diet had no growth stimulating effects compared with a glutamine free diet one week after 60% intestinal resection. An early increase in thymidine incorporation indicated that glutamine had a transient proliferative effect.