Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of LFA‐1 in the activation and trafficking of T cells: Implications in the induction of chronic colitis

Introduction: We have previously demonstrated that adoptive transfer of naïve CD4+ T cells devoid of lymphocyte function‐associated antigen‐1‐deficient (LFA‐1; CD11a/CD18) into recombination activating gene‐1 (RAG‐1) deficient (RAG−/−) mice fails to induce chronic colitis whereas transfer of wild type (WT) T‐cells induces unrelenting and chronic disease. Methods: The objectives of this study were to assess the role of lymphocyte function‐associated antigen‐1 (LFA‐1) in enteric antigen (EAg)‐induced activation of T cells in vitro and in vivo and to define the importance of this integrin in promoting trafficking of T cells to the mesenteric lymph nodes (MLNs) and colon. Results: We found that EAg‐pulsed dendritic cells (DCs) induced proliferation of LFA‐1‐deficient (CD11a−/−) CD4+ T cells that was very similar to that induced using WT T cells, suggesting that LFA‐1 is not required for activation/proliferation of T cells in vitro. Coculture of WT or CD11a−/− T cells with EAg‐pulsed DCs induced the generation of similar amounts of interferon‐gamma, interleukin (IL)‐4, and IL‐10, whereas IL‐17A production was reduced ≈2‐fold in cocultures with CD11a−/− T cells. Short‐term (20–22 hours) trafficking studies demonstrated that while both WT and CD11a−/− T cells migrated equally well into the spleen, liver, lungs, small intestine, cecum, and colon, trafficking of CD11a−/− T cells to the MLNs was reduced by 50% when compared to WT T cells. When the observation period was extended to 3–7 days posttransfer, we observed ≈2–3‐fold more WT T cells within the MLNs and colon than CD11a−/− T cells, whereas T‐cell proliferation (as measured by CFSE dilution) was comparable in both populations. Conclusions: Taken together, our data suggest that LFA‐1 is not required for EAg‐induced activation of CD4+ T cells in vitro or in vivo but is required for trafficking of T cells to the MLNs and homing of colitogenic effector cells to the colon where they initiate chronic gut inflammation. (Inflamm Bowel Dis 2012;)
A Novel COLD-PCR/FMCA Assay Enhances the Detection of Low-abundance IDH1 Mutations in Gliomas

Point mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in many gliomas. The detection of IDH1 mutations becomes challenging on suboptimal glioma biopsies when a limited number of tumor cells is available for analysis. Coamplification at lower denaturing-polymerase chain reaction (COLD-PCR) is a PCR technique that deliberately lowers the denaturing cycle temperature to selectively favor amplification of mutant alleles, allowing for the sensitive detection of low-abundance mutations. We developed a novel COLD-PCR assay on the LightCycler platform (Roche, Applied Science, Indianapolis, IN), using post-PCR fluorescent melting curve analysis (FMCA) for the detection of mutant IDH1 with a detection limit of 1%. Thirty-five WHO grade I to IV gliomas and 9 non-neoplastic brain and spinal cord biopsies were analyzed with this technique and the results were compared with the conventional real-time PCR and the Sanger sequencing analysis. COLD-PCR/FMCA was able to detect the most common IDH1 R132H mutation and rare mutation types including R132H, R132C, R132L, R132S, and R132G mutations. Twenty-five glioma cases were positive for IDH1 mutations by COLD-PCR/FMCA, and 23 gliomas were positive by the conventional real-time PCR and Sanger sequencing. A pilocytic astrocytoma (PA I) and a glioblastoma multiforme (GBM IV) showed low-abundance IDH1 mutations detected by COLD-PCR/FMCA. The remaining 10 glioma and 9 non-neoplastic samples were negative by all the 3 methods. In summary, we report a novel COLD-PCR/FMCA method that provides rapid and sensitive detection of IDH1 mutations in formalin-fixed paraffin-embedded tissue and can be used in the clinical setting to assess the small brain biopsies.
Repetition of attempted suicide: The performance of the Edinburgh predictive scales in patients in Oxford

Abstract Non-fatal suicidal behaviour is often repeated especially in the first few months after an attempt. Repetition increases the risk of eventual completed suicide. Scales have been developed to predict the risk of repetition, particularly in the short-term. We have tested a recently developed scale from Edinburgh in two one-year cohorts of patients assessed in routine clinical practice following attempts that resulted in referral to the general hospital in Oxford. The scale was tested in both its clinical and research (weighted item) versions, first, as originally evaluated by its originators and, second, using only first attempts by individual persons rather than any episode (i.e., including repeat episodes) during the study periods as the index events and a standard one year follow-up period, rather than within a calendar year period. We also compared the performance of the scale with a short scale, again from Edinburgh, which was developed in the 1970s. The new Edinburgh Risk of Repetition Scale .
Serial Maternal Serum α1‐Fetoprotein Concentration During Induced Abortions

Abstract. Serial maternal serum α1‐fetoprotein (AFP) quantitations were carried out in legal induced first and second trimester abortions by both a double antibody radioimmunoassay (RIA) and by a simple radioimmunoelectrophoretical (RIEP) technique. in seven cases of first trimester abortions carried out by suction curettage a marked immediate increase in maternal AFP was found in four cases. No change was observed in the remaining three. in six cases of legal second trimester abortions induced by instillation of 20 per cent sodium chloride solution a marked increase in maternal serum AFP was found in all cases. the increased AFP concentration found in induced second trimester abortions took place before death of the fetus and reached a maximum value a few hours after delivery of the fetus. As expected a rapid fall in the serum concentration of HPL and progesterone is seen when suction curettage is used. However, by instillation of a 20 per cent sodium chloride solution only a slight initial decrease is found for both HPL and progesterone.
Effects of Context on Electrophysiological Response to Musical Accents

Listeners’ aesthetic and emotional responses to music typically occur in the context of long musical passages that contain structures defined in terms of the events that precede them. We describe an electrophysiological study of listeners’ brain responses to musical accents that coincided in longer musical sequences. Musically trained listeners performed a timbre‐change detection task in which a single‐tone timbre change was positioned within 4‐bar melodies composed of 350‐ms tones to coincide or not with melodic contour accents and temporal accents (induced with temporal gaps). Event‐related potential responses to (task‐relevant) attended timbre changes elicited an early negativity (MMN/N2b) around 200 ms and a late positive component around 350 ms (P300), reflecting updating of the timbre change in working memory. The amplitudes of both components changed systematically across the sequence, consistent with expectancy‐based context effects. Furthermore, melodic contour changes modulated the MMN/N2b response (but not the P300) to timbre changes in later sequence positions. In contrast, task‐irrelevant temporal gaps elicited an MMN that was not modulated by position within the context; absence of a P300 indicated that temporal‐gap accents were not updated in working memory. Listeners’ neural responses to musical structure changed systematically as sequential predictability and listeners’ expectations changed across the melodic context.
Competitive exclusion in a multi-strain immuno-epidemiological influenza model with environmental transmission

ABSTRACT In this paper, a multi-strain model that links immunological and epidemiological dynamics across scales is formulated. On the within-host scale, the n strains eliminate each other with the strain having the largest immunological reproduction number persisting. However, on the population scale, we extend the competitive exclusion principle to a multi-strain model of SI-type for the dynamics of highly pathogenic flu in poultry that incorporates both the infection age of infectious individuals and biological age of pathogen in the environment. The two models are linked through the age-since-infection structure of the epidemiological variables. In addition the between-host transmission rate, the shedding rate of individuals infected by strain j and the disease-induced death rate depend on the within-host viral load. The immunological reproduction numbers and the epidemiological reproduction numbers are computed. By constructing a suitable Lyapunov function, the global stability of the infection-free equilibrium in the system is obtained if all reproduction numbers are smaller or equal to one. If , the reproduction number of strain j is larger than one, then a single-strain equilibrium, corresponding to strain j exists. This single-strain equilibrium is globally stable whenever and is the unique maximal reproduction number and all of the reproduction numbers are distinct. That is, the strain with the maximal basic reproduction number competitively excludes all other strains.
Risk Factors for Apnea in Children Presenting With Out-of-Hospital Seizure

Objective This study aimed to quantify risk factors for apnea in children 0 to 5 years of age with out-of-hospital seizure. Methods This is a retrospective study of pediatric patients with seizure transported by paramedics to the pediatric emergency department (PED) of a tertiary center from July 2008 to June 2009. Patients with traumatic injury and those with another diagnosis after PED evaluation were excluded. We evaluated the effect of field diazepam and other potential risk factors on the occurrence of apnea, defined as the need for airway management, that is, bag-mask ventilation by paramedics or bag-mask ventilation or intubation by PED staff within 30 minutes of arrival. Results There were 336 pediatric patients meeting inclusion criteria. The median age was 1.9 years (interquartile range,1.3–3.0 years); 193 patients (57%) were male. Fifty-four patients (16%) were treated with diazepam before PED arrival. There were 28 apneic events (8.3%). The adjusted relative risk for apnea given diazepam in the field by any route was 10.2 (95% confidence interval, 3.9–21.8; P < 0.0001), adjusted for age and seizure on arrival. Persistent seizure on PED arrival was also highly associated with apnea, with an adjusted relative risk of 15.8 (95% confidence interval, 6.5–28.9; P < 0.0001). Conclusions Field treatment with diazepam and seizing at the time of PED arrival are associated with the occurrence of apnea in children 0 to 5 years of age with out-of-hospital seizure. Larger studies are needed to determine what other factors may contribute to this risk.
A Novel Text Sample Selection Model for Scene Text Detection via Bootstrap Learning

Text detection has been a popular research topic in the field of computer vision. It is difficult for prevalent text detection algorithms to avoid the dependence on datasets. To overcome this problem, we proposed a novel unsupervised text detection algorithm inspired by bootstrap learning. Firstly, the text candidate in a novel form of superpixel is proposed to improve the text recall rate by image segmentation. Secondly, we propose a unique text sample selection model (TSSM) to extract text samples from the current image and eliminate database dependency. Specifically, to improve the precision of samples, we combine maximally stable extremal regions (MSERs) and the saliency map to generate sample reference maps with a double threshold scheme. Finally, a multiple kernel boosting method is developed to generate a strong text classifier by combining multiple single kernel SVMs based on the samples selected from TSSM. Experimental results on standard datasets demonstrate that our text detection method is robust to complex backgrounds and multilingual text and shows stable performance on different standard datasets.
Adverse stroke outcomes among patients with bipolar disorder

Failure to deliver the standard stroke care is suspected to be a potential reason for disproportionately high mortality among patients with co-morbid bipolar disorder (BD). Few studies have explored adverse outcomes and medical care costs concurrently (as a proxy for care intensity) among patients with BD admitted for stroke. Data for this nationwide population-based study were extracted from the Taiwan National Health Insurance Research Database, on 580 patients with BD hospitalized for stroke (the study group) and a comparison group consisting of randomly selected 1740 stroke patients without BD matched by propensity scores. Conditional logistic regression was used to estimate odds ratios (OR) for adverse in-hospital outcomes between study group and comparison group. We found that stroke patients with BD had significantly lower in-hospital mortality (3.28% vs. 5.63%), acute respiratory failure (2.59% vs. 5.57%), and use of mechanical ventilation (6.55% vs. 10.23%) than the comparison group. After adjusting for geographical location, urbanization level, monthly income, hypertension, diabetes, hyperlipidemia, and coronary heart disease, the odds of in-hospital mortality, acute respiratory failure, and use of mechanical ventilation in the BD group were 0.56 (95% CI: 0.34–0.92), 0.46 (95% CI: 0.26–0.80), and 0.63 (95% CI: 0.44–0.91), respectively. No differences were found in hospitalization costs and the length of hospital stay. With comparable hospitalization costs and length of hospital stay, we concluded that stroke patients with BD had lower in-hospital mortality and serious adverse events compared to stroke patients without BD.
Voxel based comparison and texture analysis of 18F-FDG and 18F-FMISO PET of patients with head-and-neck cancer

Background Hypoxia can induce radiation resistance and is an independent prognostic marker for outcome in head and neck cancer. As 18F-FMISO (FMISO), a hypoxia tracer for PET, is far less common than 18F-FDG (FDG) and two separate PET scans result in doubled cost and radiation exposure to the patient, we aimed to predict hypoxia from FDG PET with new techniques of voxel based analysis and texture analysis. Methods Thirty-eight patients with head-and-neck cancer underwent consecutive FDG and FMISO PET scans before any treatment. ROIs enclosing the primary cancer were compared in a voxel-by-voxel manner between FDG and FMISO PET. Tumour hypoxia was defined as the volume with a tumour-to-muscle ratio (TMR) > 1.25 in the FMISO PET and hypermetabolic volume was defined as >50% SUVmax in the FDG PET. The concordance rate was defined as percentage of voxels within the tumour which were both hypermetabolic and hypoxic. 38 different texture analysis (TA) parameters were computed based on the ROIs and correlated with presence of hypoxia. Results Within the hypoxic tumour regions, the FDG uptake was twice as high as in the non-hypoxic tumour regions (SUVmean 10.9 vs. 5.4; p<0.001). A moderate correlation between FDG and FMISO uptake was found by a voxel-by-voxel comparison (r = 0.664 p<0.001). The average concordance rate was 25% (± 22%). Entropy was the TA parameter showing the highest correlation with hypoxia (r = 0.524 p<0.001). Conclusion FDG uptake was higher in hypoxic tumour regions than in non-hypoxic regions as expected by tumour biology. A moderate correlation between FDG and FMISO PET was found by voxel-based analysis. TA yielded similar results in FDG and FMISO PET. However, it may not be possible to predict tumour hypoxia even with the help of texture analysis.
Developing a Pipeline for Multiparametric MRI-Guided Radiation Therapy: Initial Results from a Phase II Clinical Trial in Newly Diagnosed Glioblastoma

Quantitative mapping of hyperperfused and hypercellular regions of glioblastoma has been proposed to improve definition of tumor regions at risk for local recurrence following conventional radiation therapy. As the processing of the multiparametric dynamic contrast-enhanced (DCE-) and diffusion-weighted (DW-) magnetic resonance imaging (MRI) data for delineation of these subvolumes requires additional steps that go beyond the standard practices of target definition, we sought to devise a workflow to support the timely planning and treatment of patients. A phase II study implementing a multiparametric imaging biomarker for tumor hyperperfusion and hypercellularity consisting of DCE-MRI and high b-value DW-MRI to guide intensified (75 Gy/30 fractions) radiation therapy (RT) in patients with newly diagnosed glioblastoma was launched. In this report, the workflow and the initial imaging outcomes of the first 12 patients are described. Among all the first 12 patients, treatment was initiated within 6 weeks of surgery and within 2 weeks of simulation. On average, the combined hypercellular volume and high cerebral blood volume/tumor perfusion volume were 1.8 times smaller than the T1 gadolinium abnormality and 10 times smaller than the FLAIR abnormality. Hypercellular volume and high cerebral blood volume/tumor perfusion volume each identified largely distinct regions and showed 57% overlap with the enhancing abnormality, and minimal-to-no extension outside of the FLAIR. These results show the feasibility of implementing a workflow for multiparametric magnetic resonance-guided radiation therapy into clinical trials with a coordinated multidisciplinary team, and the unique and complementary tumor subregions identified by the combination of high b-value DW-MRI and DCE-MRI.
Allosteric mechanism of the circadian protein Vivid resolved through Markov state model and machine learning analysis

The fungal circadian clock photoreceptor Vivid (VVD) contains a photosensitive allosteric light, oxygen, voltage (LOV) domain that undergoes a large N-terminal conformational change. The mechanism by which a blue-light driven covalent bond formation leads to a global conformational change remains unclear, which hinders the further development of VVD as an optogenetic tool. We answered this question through a novel computational platform integrating Markov state models, machine learning methods, and newly developed community analysis algorithms. Applying this new integrative approach, we provided a quantitative evaluation of the contribution from the covalent bond to the protein global conformational change, and proposed an atomistic allosteric mechanism leading to the discovery of the unexpected importance of A’α/Aβ and previously overlooked Eα/Fα loops in the conformational change. This approach could be applicable to other allosteric proteins in general to provide interpretable atomistic representations of their otherwise elusive allosteric mechanisms.
Magic roundabout is an endothelial-specific ohnolog of ROBO1 which neo-functionalized to an essential new role in angiogenesis

Background Magic roundabout (ROBO4) is an unusual endothelial-specific paralog of the family of neuronally-expressed axon guidance receptors called roundabouts. Endothelial cells (ECs), whose uninterrupted sheet delimits the lumen of all vertebrate blood vessels and which are absent from invertebrate species, are a vertebrate-specific evolutionary novelty. Results Herein, the evolutionary mechanism of the duplication, retention and divergence of ROBO4 was investigated for the first time. Phylogenetic analyses carried out suggested that ROBO4 is a fast-evolving paralog of ROBO1 formed at the base of vertebrates. The ancestral expression pattern was neuronal. ROBO4 dramatically shifted its expression and became exceptionally specific to ECs. The data-mining of FANTOM5 and ENCODE reveals that ROBO4’s endothelial expression arises from a single transcription start site (TSS), conserved in mouse, controlled by a proximal promoter with a complex architecture suggestive of regulatory neo-functionalization. (An analysis of promoter probabilities suggested the architecture was not due to a chance arrangement of TFBSes). Further evidence for the neo-functionalization of ROBO4 comes from the analysis of its protein interactions, the rates of protein evolution, and of positively selected sites. Conclusions The neo-functionalization model explains why ROBO4 protein acquired new context-specific biological functions in the control of angiogenesis. This endothelial-specific roundabout receptor is an illustrative example of the emergence of an essential vertebrate molecular novelty and an endothelial-specific signaling sub-network through 2R-WGD. The emergence of novel cell types, such as ECs, might be a neglected evolutionary force contributing to the high rate of retention of duplicates post-2R-WGD. Crucially, expression neo-functionalization to evolutionarily novel sites of expression conceptually extends the classical model of neo-functionalization.
BMP signaling is required for nkx2.3-positive pharyngeal pouch progenitor specification in zebrafish

Pharyngeal pouches, a series of outpocketings that bud from the foregut endoderm, are essential to the formation of craniofacial skeleton as well as several important structures like parathyroid and thymus. However, whether pharyngeal pouch progenitors exist in the developing gut tube remains unknown. Here, taking advantage of cell lineage tracing and transgenic ablation technologies, we identified a population of nkx2.3+ pouch progenitors in zebrafish embryos and demonstrated an essential requirement of ectodermal BMP2b for their specification. At early somite stages, nkx2.3+ cells located at lateral region of pharyngeal endoderm give rise to the pouch epithelium except a subpopulation expressing pdgfαa rather than nkx2.3. A small-scale screen of chemical inhibitors reveals that BMP signaling is necessary to specify these progenitors. Loss-of-function analyses show that BMP2b, expressed in the pharyngeal ectoderm, actives Smad effectors in endodermal cells to induce nkx2.3+ progenitors. Collectively, our study provides in vivo evidence for the existence of pouch progenitors and highlights the importance of BMP2b signaling in progenitor specification.
A site‐specific ecological risk assessment for corn‐associated insecticides

A site‐specific ecological risk assessment (ERA) was conducted to examine the simultaneous use of genetically modified corn (Bt corn) with a neonicotinoid seed coating, clothianidin, and use of a granular insecticide, tefluthrin, to protect crops from pest damage. A field study was conducted on site, and exposure data from the literature were summarized to determine the matrices and exposure concentrations that nontarget species could typically experience within an agricultural ecosystem. To determine ecological effects on nontarget species, acute toxicity bioassays were conducted on earthworms (Eisenia fetida), amphipods (Hyalella azteca), and Elmid riffle beetle larvae (Ancyronyx spp.) in which the test species were exposed to single insecticides as well as the mixture of the 3 insecticides. In the risk characterization section of the ERA, stressor–response profiles for each species tested were compared with field distributions of the insecticides, and a margin of safety at the 10th percentile (MOS10) was calculated to estimate risk. No acute toxicity was observed in any of the 3 nontarget species after exposure to senescent Bt corn leaf tissue. Large MOS10 values were calculated for clothianidin to the nontarget species. When bioassays were compared with tefluthrin field distributions, very low MOS10 values were calculated for earthworms (0.06) and H. azteca (0.08) because the environmental concentrations often exceeded the stressor–response profile. No increased toxicity was observed when nontarget species were exposed to a mixture of the 3 insecticides. In summary, the genetically modified corn insecticidal proteins and clothianidin were not found at environmental concentrations exceeding benchmark values for ecological effects, but tefluthrin was consistently detected in the environment at levels that could be causing toxicity to nontarget species, especially if this pyrethroid is able to travel off site. Integr Environ Assess Manag 2015;11:445–458. © 2015 SETAC