Miracle-dz/UniFAR-FTUs huggingface dataset:
Alternative splicing of the OCC-1 gene generates three splice variants and a novel exonic microRNA, which regulate the Wnt signaling pathway

The Wnt signaling pathway is hyperactivated in most colorectal cancers (CRC). Finding new regulators of this pathway represents the potential for cancer diagnosis or treatment. OCC-1 was initially reported as an up-regulated gene in colon carcinoma, without knowing its mechanism of action. Here, two novel transcript variants and an exonic microRNA that originated from the OCC-1 gene are reported, showing positive effects on Wnt activity. Up-regulation of the known OCC-1 variant (assigned as OCC-1A/B) was limited to CRC, and its overexpression increased survival of CRC-originated SW480 cells (Wnt+), while resulting in apoptosis of Wnt-suppressed SW480 cells or HeLa cells (Wnt–) detected by PI staining. Immunocytochemistry showed that the OCC-1A/B-encoded peptide was localized to the nucleus, where its overexpression resulted in Wnt signaling up-regulation, detected by TOP/FOPflash assay. The noncoding portion of the OCC-1A/B transcript had a suppressive effect on Wnt activity and had a negative correlation with APPL2 neighboring gene expression. Unlike OCC-1A/B, the novel OCC-1C splice variant had no expression alteration in CRC, and it seemed to encode a smaller peptide with cytoplasmic localization. A 60-nucleotide (nt) fragment containing an AUG start codon is spliced out to produce an OCC-1D noncoding RNA variant. The 60-nt RNA was validated as the precursor of a novel microRNA, which we named miR-ex1. Both OCC-1D and miR-ex1 were coordinately up-regulated in CRC. MiR-ex1 functional analysis revealed that it is targeting the APC2 tumor suppressor gene and is an activator of the Wnt signaling pathway. Overall, the OCC-1 gene is now introduced as a novel Wnt signaling regulator and as a potential therapeutic target.
The von Willebrand factor self‐association is modulated by a multiple domain interaction

Summary. Background: Platelet adhesion and aggregation at sites of vascular injury exposed to rapid blood flow require von Willebrand factor (VWF). VWF becomes immobilized by binding to subendothelial components or by a self‐association at the interface of soluble and surface‐bound VWF. Objectives: As this self‐association has been demonstrated only under shear conditions, our first goal was to determine whether the same interaction could be observed under static conditions. Furthermore, we wanted to identify VWF domain(s) important for this self‐association. Results: Biotinylated VWF (b‐VWF) interacted dose‐dependently and specifically with immobilized VWF in an enzyme‐linked immunosorbent assay (ELISA) assay, showing that shear is not necessary to induce the VWF self‐association. Whereas anti‐VWF monoclonal antibodies (mAbs) had no effect on the self‐association, the proteolytic VWF‐fragments SpII(1366–2050) and SpIII(1–1365) inhibited the b‐VWF–VWF interaction by 70 and 80%, respectively. Moreover, a specific binding of b‐VWF to immobilized Sp‐fragments was demonstrated. Finally, both biotinylated SpII and SpIII were able to bind specifically to both immobilized SpII and SpIII. Similar results were observed under flow conditions, which confirmed the functional relevance of our ELISA system. Conclusion: We have developed an ELISA binding assay in which a specific VWF self‐association under static conditions can be demonstrated. Our results suggest a multiple domain interaction between immobilized and soluble VWF.
IL-12 Produced by Dendritic Cells Augments CD8+ T Cell Activation through the Production of the Chemokines CCL1 and CCL171

IL-12 family members are an important link between innate and adaptive immunity. IL-12 drives Th1 responses by augmenting IFN-γ production, which is key for clearance of intracellular pathogens. IL-23 promotes the development of IL-17-producing CD4+ T cells that participate in the control of extracellular pathogens and the induction of autoimmunity. However, recent studies have shown that these cytokines can modulate lymphocyte migration and cellular interactions. Therefore, we sought to determine the individual roles of IL-12 and IL-23 in naive CD8+ T cell activation by addressing their ability to influence IFN-γ production and cellular interaction dynamics during priming by Listeria monocytogenes-infected dendritic cells (DC). We found that IL-12 was the major cytokine influencing the level of IFN-γ production by CD8+ T cells while IL-23 had little effect on this response. In addition, we observed that IL-12 promoted longer duration conjugation events between CD8+ T cells and DC. This enhanced cognate interaction time correlated with increased production of the chemokines CCL1 and CCL17 by WT but not IL-12-deficient DC. Neutralization of both chemokines resulted in reduced interaction time and IFN-γ production, demonstrating their importance in priming naive CD8+ T cells. Our study demonstrates a novel mechanism through which IL-12 augments naive CD8+ T cell activation by facilitating chemokine production, thus promoting more stable cognate interactions during priming.
Clinical and Histopathologic Features of Recurrent Vestibular Schwannoma (Acoustic Neuroma) after Stereotactic Radiosurgery

Objective Stereotactic radiosurgery for vestibular schwannoma entails uncertain long-term risk of tumor recurrence and delayed cranial neuropathies. In addition, the underlying histopathologic changes to the tumor bed are not fully characterized. We seek to understand the clinical and histologic features of recurrent vestibular schwannoma after stereotactic radiation therapy. Study Design Retrospective review. Setting Tertiary referral center. Patients Four patients who underwent microsurgical resection of vestibular schwannoma after primary stereotactic radiation therapy. Intervention Patients were treated primarily with gamma knife radiosurgery or fractionated stereotactic radiotherapy followed by salvage microsurgery. Retrosigmoid craniotomy was used in all cases. Main Outcome Measures Histopathologic review. Preoperative and postoperative facial nerve function was assessed with the House-Brackmann scale. Results We observed highly inconsistent radiation changes in the cerebellopontine angle and internal auditory canal. Fibrosis outside and within the tumor bed varied markedly, complicating microsurgical dissection. Light microscopy confirmed the presence of viable tumor in all cases. Histopathologic features were typical of vestibular schwannoma, and there was no significant scarring that could be attributed to radiation effect. Conclusions The variable fibrosis in the cerebellopontine angle and lack of radiation changes seen histopathologically in irradiated vestibular schwannoma suggest that a uniform treatment effect was not achieved in these cases. Although all four patients with preoperative cranial neuropathies were found intraoperatively to have fibrosis in the cerebellopontine angle, excellent preservation of facial nerve anatomy and function was possible with salvage microsurgical resection. Additional analyses are needed to clarify the histopathologic and molecular characteristics associated with vestibular schwannoma growth after stereotactic radiation.
Autogenic training and future oriented hypnotic imagery in the treatment of tension headache: outcome and process.

The aim of the present study was (a) to investigate the relative efficacy of autogenic training and future oriented hypnotic imagery in the treatment of tension headache and (b) to explore the extent to which therapy factors such as relaxation, imagery skills, and hypnotizability mediate therapy outcome. Patients were randomly assigned to the 2 therapy conditions and therapists. 55 patients (28 in the autogenic therapy condition and 27 in the future oriented hypnotic imagery condition) completed the 4 therapy sessions and 2 assessment sessions. No significant main effect or interaction effects for treatment condition or therapist was revealed. A significant effect for time in analyzing scores for headache pain, pain medication usage, depression, and state anxiety was found. In the self-hypnosis condition, pain reduction proved to be associated with depth of relaxation during home practice (as assessed with diaries) and capacity to involve in imagery (as assessed with the Dutch version [van der Velden & Spinhoven, 1984] of the Creative Imagination Scale [Barber & Wilson, 1978/79; Wilson & Barber, 1978]). After statistically controlling for relaxation and imagery, hypnotizability scores (as assessed with the Dutch version [Oyen & Spinhoven, 1983] of the Stanford Hypnotic Clinical Scale [Morgan & J.R. Hilgard, 1975, 1978/79]) were significantly correlated with ratings of pain reduction. Results are discussed in the context of the neo-dissociation and social-cognitive model of hypnoanalgesia. The clinical relevance and the methodological shortcomings of the present study are also critically assessed.
A REVIEW OF EXPERIMENTAL STUDIES ON DIESEL EXHAUST PARTICLES AND NASAL EPITHELIUM ALTERATIONS

The aim of the present review is to summarize biological events in nasal epithelium after short-term exposure to diesel exhaust particles (DEP). Therefore human, animal, and in vitro studies carried out since 1987 are reviewed. Short-term exposure results included qualitative alterations characterized by immediate nasal hyperresponsiveness, antioxidant responses, marked epithelial inflammation, and a specific humoral response. In addition, studies on combined DEP/allergen challenge reported that, besides their intrinsic deleterious properties, DEP produced adjuvant-like effects on the immediate and late-phase response to allergen challenge, since they are able to mimic effects occurring after allergen challenge. DEP act deeply in nasal epithelium by (1) directing cytokine gene expression toward a Th2 profile, (2) enhancing local antigen-specific immunoglobulin E (IgE) production, and (3) driving in vivo isotype switch to IgE. Furthermore, DEP can induce in allergic subjects sensitization to a neoallergen, sensitization that did not occur with exposure to the neoantigen alone. Particulate pollutants such as DEP, encountered in urban areas, are therefore thought to be contributing causal factors to the exaggerated sensitization to allergens in subjects with appropriate genetic predisposition, sensitization that they might not otherwise have experienced. These findings add weight to the hypothesis that DEP are involved in the increased prevalence of airway allergic diseases.
A dye-buoyant-density method for the detection and isolation of closed circular duplex DNA: the closed circular DNA in HeLa cells.

Covalently closed circular duplex DNA’s are now known to be widespread among living organisms. This DNA structure, originally identified in polyoma viral DNA,1’2 has been assigned to the mitochondrial DNA’s in ox3 and sheep heart,4 in mouse and chicken liver,3 and in unfertilized sea urchin egg.5 The animal viral DNA’s—polyoma, SV40,6 rabbit7 and human8 papilloma—the intracellular forms of the bacterial viral DNA’s—φX174,9, 10 lambda,11, 12 M13,13 and P2214—and a bacterial plasmid DNA, the colicinogenic factor E2,15 have all been shown to exist as closed circular duplexes. Other mitochondrial DNA’s16, 17 and a portion of the DNA from boar sperm18 have been reported to be circular, but as yet have not been shown to be covalently closed.
Screening techniques to identify people at high risk for diabetic foot ulceration: a prospective multicenter trial.

OBJECTIVE Diabetic foot ulceration is a preventable long-term complication of diabetes. A multicenter prospective follow-up study was conducted to determine which risk factors in foot screening have a high association with the development of foot ulceration. RESEARCH DESIGN AND METHODS A total of 248 patients from 3 large diabetic foot centers were enrolled in a prospective study. Neuropathy symptom score, neuropathy disability score (NDS), vibration perception threshold (VPT), Semmes-Weinstein monofilaments (SWFs), joint mobility, peak plantar foot pressures, and vascular status were evaluated in all patients at the beginning of the study. Patients were followed-up every 6 months for a mean period of 30 months (range 6-40), and all new foot ulcers were recorded. The sensitivity, specificity, and positive predictive value of each risk factor were evaluated. RESULTS Foot ulcers developed in 95 feet (19%) or 73 patients (29%) during the study. Patients who developed foot ulcers were more frequently men, had diabetes for a longer duration, had nonpalpable pedal pulses, had reduced joint mobility, had a high NDS, had a high VPT, and had an inability to feel a 5.07 SWE NDS alone had the best sensitivity, whereas the combination of the NDS and the inability to feel a 5.07 SWF reached a sensitivity of 99%. On the other hand, the best specificity for a single factor was offered by foot pressures, and the best combination was that of NDS and foot pressures. Univariate logistical regression analysis yielded a statistically significant odds ratio (OR) for sex, race, duration of diabetes, palpable pulses, history of foot ulceration, high NDSs, high VPTs, high SWFs, and high foot pressures. In addition, 94 (99%) of the 95 ulcerated feet had a high NDS and/or SWF which resulted in the highest OR of 26.2 (95% CI 3.6-190). Furthermore, in multivariate logistical regression analysis, the only significant factors were high NDSs, VPTs, SWFs, and foot pressures. CONCLUSIONS Clinical examination and a 5.07 SWF test are the two most sensitive tests in identifying patients at risk for foot ulceration, especially when the tests are used in conjunction with each other. VPT measurements are also helpful and can be used as an alternative. Finally, foot pressure measurements offer a substantially higher specificity and can be used as a postscreening test in conjunction with providing appropriate footwear.
A New Asymmetrical Half-Bridge Converter With Zero DC-Offset Current in Transformer

This paper proposes an asymmetrical half-bridge (AHB) converter with a new secondary rectifier. Due to the new rectifier stage, the proposed AHB converter has a zero dc-offset current in the transformer at any operating conditions so that the transformer core loss becomes very small compared to the conventional AHB converter. This results in higher efficiency. Besides, magnetic components can be optimally utilized because maximum flux density can be applied when designing the magnetic components. It also allows a flexible design to improve the efficiency or reduce the cost. This paper presents the operation principle and relevant analysis results of the proposed converter. A 300 W, 200-400-V input, and 50-V output laboratory prototype operating at 100 kHz is built and tested to verify the effectiveness of the proposed converter.
The Role of Social Skills and School Connectedness in Preadolescent Depressive Symptoms

In the current study, we tested whether school connectedness mediates more distal deficits in social skills in influencing depressive symptoms in a sample of 127 sixth- and seventh-grade students. Results demonstrated that school connectedness and social skills accounted for 44% and 26% of variance in depressive symptoms respectively and 49% in a combined model. Although the full mediation model hypothesis was not supported, follow-up analyses revealed that school connectedness partially mediated the link between social skills and preadolescent depressive symptoms. Thus, school connectedness appears to play as strong a role in depressive symptoms in this younger preadolescent age group.
Predicting herbivore faecal nitrogen using a multispecies near-infrared reflectance spectroscopy calibration

Optimal management of free-ranging herbivores requires the accurate assessment of an animal’s nutritional status. For this purpose ‘near-infrared reflectance spectroscopy’ (NIRS) is very useful, especially when nutritional assessment is done through faecal indicators such as faecal nitrogen (FN). In order to perform an NIRS calibration, the default protocol recommends starting by generating an initial equation based on at least 50–75 samples from the given species. Although this protocol optimises prediction accuracy, it limits the use of NIRS with rare or endangered species where sample sizes are often small. To overcome this limitation we tested a single NIRS equation (i.e., multispecies calibration) to predict FN in herbivores. Firstly, we used five herbivore species with highly contrasting digestive physiologies to build monospecies and multispecies calibrations, namely horse, sheep, Pyrenean chamois, red deer and European rabbit. Secondly, the equation accuracy was evaluated by two procedures using: (1) an external validation with samples from the same species, which were not used in the calibration process; and (2) samples from different ungulate species, specifically Alpine ibex, domestic goat, European mouflon, roe deer and cattle. The multispecies equation was highly accurate in terms of the coefficient of determination for calibration R2 = 0.98, standard error of validation SECV = 0.10, standard error of external validation SEP = 0.12, ratio of performance to deviation RPD = 5.3, and range error of prediction RER = 28.4. The accuracy of the multispecies equation to predict other herbivore species was also satisfactory (R2 > 0.86, SEP < 0.27, RPD > 2.6, and RER > 8.1). Lastly, the agreement between multi- and monospecies calibrations was also confirmed by the Bland-Altman method. In conclusion, our single multispecies equation can be used as a reliable, cost-effective, easy and powerful analytical method to assess FN in a wide range of herbivore species.
Gene expression abnormalities in histologically normal breast epithelium of breast cancer patients

Normal‐appearing epithelium of cancer patients can harbor occult genetic abnormalities. Data comprehensively comparing gene expression between histologically normal breast epithelium of breast cancer patients and cancer‐free controls are limited. The present study compares global gene expression between these groups. We performed microarrays using RNA from microdissected histologically normal terminal ductal‐lobular units (TDLU) from 2 groups: (i) cancer normal (CN) (TDLUs adjacent to untreated ER+ breast cancers (n = 14)) and (ii) reduction mammoplasty (RM) (TDLUs of age‐matched women without breast disease (n = 15)). Cyber‐T identified differentially expressed genes. Quantitative RT‐PCR (qRT‐PCR), immunohistochemistry (IHC), and comparison to independent microarray data including 6 carcinomas in situ (CIS), validated the results. Gene ontology (GO), UniProt and published literature evaluated gene function. About 127 probesets, corresponding to 105 genes, were differentially expressed between CN and RM (p < 0.0009, corresponding to FDR <0.10). 104/127 (82%) probesets were also differentially expressed between CIS and RM, nearly always (102/104 (98%)) in the same direction as in CN vs. RM. Two‐thirds of the 105 genes were implicated previously in carcinogenesis. Overrepresented functional groups included transcription, G‐protein coupled and chemokine receptor activity, the MAPK cascade and immediate early genes. Most genes in these categories were under‐expressed in CN vs. RM. We conclude that global gene expression abnormalities exist in normal epithelium of breast cancer patients and are also present in early cancers. Thus, cancer‐related pathways may be perturbed in normal epithelium. These abnormalities could be markers of disease risk, occult disease, or the tissue's response to an existing tumor. © 2007 Wiley‐Liss, Inc.
Expression of thyrotropin‐releasing hormone receptor 2 (TRH‐R2) in the central nervous system of rats

The distribution of the recently discovered thyrotropin‐releasing hormone (TRH) receptor subtype TRH‐R2 was studied in rat brain, pituitary, and spinal cord by in situ hybridization histochemistry and compared with the distribution patterns of the other elements of TRH signaling, namely TRH, TRH‐R1, and the TRH‐degrading ectoenzyme (TRH‐DE). In contrast to the very restricted mRNA expression of TRH‐R1 in the central nervous system, TRH‐R2 mRNA was widely distributed with highest transcript levels throughout the thalamus, in the cerebral and cerebellar cortex, medial habenulae, medial geniculate nucleus, pontine nuclei, and throughout the reticular formation. In accordance with the well‐known endocrine function of TRH, TRH‐R1 is found predominantly expressed in hypothalamic regions. Expression of TRH‐R1 in various brainstem nuclei and spinal cord motoneurons seems to be associated with the described effects of TRH on the vegetative and autonomic system as well as on the somatomotor system. Furthermore, the fully complementary expression of both receptor subtypes, even in regions where transcripts for both receptors were found (e.g., medial septum, lateral hypothalamus superior colliculi, substantia nigra, etc.), indicates that in discrete neuroanatomical pathways the two receptors serve highly specific functions for the transmission of TRH signals. Together with TRH‐DE, the putative terminator of TRH actions that shows in various, but not all, brain areas, an overlapping mRNA distribution pattern with both receptors, the distribution of TRH‐R2 mRNA seems to provide the anatomical basis for the described effects of TRH on higher cognitive functions as well as its effect on arousal, locomotor activity, and pain perception. J. Comp. Neurol. 428:319–336, 2000. © 2000 Wiley‐Liss, Inc.
The role of blood lactate clearance as a predictor of mortality in children undergoing surgery for tetralogy of Fallot

Background: The identification of biomarkers for predicting morbidity and mortality, particularly in pediatric population undergoing cardiac surgery will contribute toward improving the patient outcome. There is an increasing body of literature establishing the clinical utility of hyperlactatemia and lactate clearance as prognostic indicator in adult cardiac surgical patients. However, the relationship between lactate clearance and mortality risk in the pediatric population remains to be established. Objective: To assess the role of lactate clearance in determining the outcome in children undergoing corrective surgery for tetralogy of Fallot (TOF). Methods and Study Design: A prospective, observational study. Setting: A tertiary care center. Study Population: Two hundred children undergoing elective surgery for TOF. Study Method: Blood lactate levels were obtained as baseline before operation (T0), postoperatively at admission to the cardiac intensive care unit after surgery (T1), and then at every 6 h for the first 24 h of Intensive Care Unit (ICU) stay (T6, T12, T18, and T24, respectively). The lactate clearance in the study is defined by the equation ([lactate initial - lactate delayed]/lactate initial) ×100%. Lactate clearance was determined at T1-T6, T1-T12, T1-T18, and T1-T24 time interval, respectively. The primary outcome measured was mortality. Secondary outcomes measured were the duration of mechanical ventilation, duration of inotropic requirement, and duration of ICU stay. Results: Eleven out of the two hundred patients enrolled in the study died. Nonsurvivors had higher postoperative lactate concentration (P < 0.05) and low-blood lactate clearance rate during 24 h (P < 0.05) in comparison to the survivors. Lactate clearance was significantly higher in survivors than in nonsurvivors for the T1-T6 period (19.55 ± 14.28 vs. 5.24 ± 27.79%, P = 0.009) and remained significantly higher for each studied interval in first 24 h. Multivariate logistic regression analysis of statistically significant univariate variables showed early lactate clearance to have a significant relationship with mortality. Patients with a lactate clearance >10%, relative to patients with a lactate clearance <10%, in the early postoperative period, had improved outcome and lower mortality. Conclusion: Lactate clearance in the early postoperative period (6 h) is associated with decreased mortality rate. Patients with higher lactate clearance (>10%) after 6 h have improved outcome compared with those with lower lactate clearance.