Miracle-dz/UniFAR-FTUs huggingface dataset:
Recent advances in connective tissue disease related interstitial lung disease

ABSTRACT Introduction: Interstitial lung disease (ILD) is a common manifestation of connective tissue disease (CTD). Although the majority of patients with CTD-ILD are stable or slowly progressive, a significant group exhibits a more severe and progressive decline. Interstitial pneumonia with autoimmune features (IPAF) describes the subset of patients with interstitial pneumonia who have features suggesting underlying autoimmunity, but whose features fall short of a clear diagnosis of CTD. Areas covered: In this focused review, we discuss recent advances in early detection, prognostic evaluation, and management of autoimmune forms of ILD. Expert commentary: Early detection of ILD and a better understanding of factors that impact prognostication may be helpful when making decisions regarding therapeutic interventions. The treatment of CTD-ILD should be comprehensive, is often fraught with challenges and can be complicated by comorbid conditions and extra-thoracic disease activities. Several large randomized studies have examined the impact of immunosuppressive therapy for CTD-ILD, however, additional studies are needed to determine the optimal treatment strategies. Future studies may provide additional information about the best treatments in patients with IPAF.
[Associations of the genetic polymorphisms in CYP11B2 gene with nonfamilial structural atrial fibrillation].

OBJECTIVE To investigate whether polymorphisms in CYP11B2 gene are associated with nonfamilial structural atrial fibrillation (AF) in Chinese Han population. METHODS A fine-designed pair-matched hospital based case-control study was performed in 297 cases and 297 controls. We investigated two tagging single nucleotide polymorphisms (tSNPs)-rs4545, rs3802228 in CYP11B2 gene by using GenomeLab SNPstream technique. RESULTS Two tSNPs were consistent with Hardy-Weinberg expectations in case and control groups. Compared with controls, the left atrial diameter of cases was significantly higher (P < 0.0001). No significant difference in genotype or allele frequencies of tSNPs in CYP11B2 gene was observed. However, at the site of rs3802228 in 3'UTR of the case group, the left atrial diameter in AF patients with GG genotype was significantly higher than others. After adjusted for covariates age, smoking, Body mass index and hypertension, we did not observe the association of rs4545, rs3802228 with AF. CONCLUSION Our result suggested that polymorphisms of rs4545 in CYP11B2 gene might not be associated with atrial fibrillation but polymorphism of 3'UTR rs3802228 locus in CYP11B2 gene might be associated with atrial structural remodeling.
[Detection of protein p53 in the stool of patients with colorectal cancer].

BACKGROUND AND AIMS Mutations of TP53, a tumor suppressor gene, are found in 60% to 70% of colorectal cancers. These mutations usually induce an overexpression caused by modification of the p53 protein conformation. The aim of this study was to investigate whether stool specimens of patients with colorectal cancer contain increased amounts of p53 protein. METHODS p53 protein was measured using a sandwich enzyme immunoassay in the stool specimens of 52 patients: 25 with colorectal cancer, 4 with colorectal adenomas and 23 apparently free of gastrointestinal disease. Results were expressed as pg/mg of total protein. The presence of fecal occult-blood was searched using Hemoccult II and Hemolex (an immunochemical assay for human hemoglobin). RESULTS Median concentrations of stool p53 protein were 16.6 pg/mg (range: 0-591 pg/mg) in patients with colorectal cancers, 39.1 pg/mg (range: 5-72 pg/mg) in patients with adenomas and 5.9 pg/mg (range: 0-65 pg/mg) in control subjects. Resection of colorectal cancers caused a marked decrease of stool p53 protein concentrations. When the cut-off value for stool p53 protein was set at 60 pg/mg of fecal protein (concentrations over the 95th percentile), the positivity of the assay was independent of tumor size and Astler-Coller stage, but weakly associated with rectal location of cancer. The sensitivity of stool p53 protein for colorectal cancer was 44%, and the specificity was 96%. In contrast, the sensitivity of Hemoccult II and Hemolex tests was 48% and 44%, whereas their specificity was 91% and 96%, respectively. CONCLUSION The detection of p53 protein is achievable in stool, but this assay is not more efficient than fecal occult blood tests for detection of colorectal cancer.
Simultaneous estimation of blood flow distribution and instrumentation noise from dynamic H/sub 2//sup 15/O PET study with stochastic block model

In order to model reasonably and flexibly the blood flow or perfusion in skeletal muscles with PET using H2 15O as tracer or radiopharmaceutical we introduce a new stochastic two-block - two-rate constants model with two new measurement equations. The stochastic two-block - two rate constants model utilizes the probability theory to describe the inherent variation of the muscle tissue with similarly distributed random rate constants realized uniquely for each volume element in tissue separately. The new measurement equations include both the uncertainty caused by the positron emission (Poisson noise) and the instrumentation or measurement noise (Gaussian) allowing an easy characterization of the radioactive decay and the deviation of the instrumentation noise. Applying maximum likelihood estimation procedure to the density function results in the volume-element-wise rate constant estimates providing the information about regional perfusion. In addition, we can calculate the estimator variation of the rate constant estimates and remove it resulting in the pure tissue heterogeneity, i.e. the variation of the volume-element-wise rate constants, the regional perfusion. We tested our model and methods by executing simulation runs. The simulations showed that we are able to estimate the unknown parameter values and their deviations the better the higher the time and spatial resolutions are. This is an expected phenomenon due to the consistency property of the maximum likelihood estimator
Matrix metalloproteinases, prostaglandins and endothelins: paracrine regulators of implantation.

IntroductionThe development of the hemochorial placenta in humans involves apposition and attachment of the blastocyst to the uterine wall, penetration of the epithelium and invasion through the decidua to the superficial layers of the myometrium. Implantation is a crucial process for the establishment of a normal pregnancy. Excessive invasion of the trophoblast may lead to adherence of the placenta deep in the myometrium. Inadequate trophoblast invasion may be implicated in the pathophysiology of miscarriage or placental abruption.
Effect of shear stress and a stable prostaglandin I2 analogue on adhesive interactions of colon cancer cells and endothelial cells

In the process of cancer metastasis, adhesion between cancer cells and endothelial cells is an important early step. In the present study, the effects of shear stress and the adhesion molecules responsible for cancer cell interactions with endothelial cells were investigated in a system similar to in vivo microcirculation. The effect of prostaglandin I2 (PGI2) also was determined. Human colon cancer cell line Colo 201 and human umbilical vein endothelial cells (HUVEC) were used. After HUVEC on a glass slide were incubated with IL‐1β for 4 h, cancer cells in suspension were perfused on HUVEC at wall shear stresses of 5–40 μN/cm2. Experiments were videotaped, and the number of adherent cells were counted. Additionally, the effects of anti‐sialyl Lewis a (SLea) MoAb, anti‐E‐selectin MoAb, and a PGI2 analogue were investigated. Expression of adhesion molecules on cancer cells and HUVEC was assessed using flow cytometry and enzyme immunoassay, respectively. Few cancer cells adhered to HUVEC without IL‐1β; however, many cancer cells adhered to IL‐1β‐stimulated HUVEC at low shear stress (5–20 μN/cm2). Cancer cells did not migrate beneath HUVEC. The increased adhesion was inhibited by anti‐E‐selectin MoAb, anti‐SLea MoAb, and a PGI2 analogue. In addition, the PGI2 analogue decreased the surface expression of SLea on Colo 201 cells. These results suggest that Colo 201 cells adhere to IL‐1β‐stimulated endothelial cells via SLea and E‐selectin under low flow conditions; PGI2 analogues may protect against metastasis by inhibiting cancer cell–endothelial cell interactions.
Theory of Mind Impairments in Youth at Clinical High Risk of Psychosis

Objective: The normal maturational processes of theory of mind (ToM) capacity are ongoing during adolescence and even early adulthood. However, research has shown that ToM ability also declines among adults suffering from prodromal psychotic experiences. The goal of this study was to investigate the characteristics of ToM performance in youth with clinical high risk (CHR) of psychosis. Methods: The Reading Mind in Eyes Task (RMET), including own-race and other-race eyes, was administered to 40 CHR youth; 42 age-, gender-, and education-matched healthy controls (HCs); and 62 adult patients with schizophrenia (SZ). Nine-month follow-up data were collected from 31 CHR subjects, of whom 7 (22.6%) had made the transition to psychosis. Results: CHR youth showed significant impairment in RMET performance compared to HC youth but performed better than did SZ patients. Moreover, they were significantly slower than were HC youth in responding to the RMET, with a response time similar to that of SZ patients. In particular, they had significantly poorer accuracy in interpreting positive and neutral eye expressions compared to the HC group, but not in interpreting negative eye expressions. Preliminary follow-up data showed a trend toward significance (p = 0.079) for RMET performance between those who transitioned to psychosis and those who did not. Conclusions: Our findings illustrate that deficits in ToM capacity, specifically the ability to interpret people’s mental state from eye expressions, occur early on in prodromal psychosis in youth. Early interventions for CHR youth focusing on ToM enhancement may halt progress toward psychosis.
Periprosthetic bone loss in total hip arthroplasty. Polyethylene wear debris and the concept of the effective joint space.

Thirty-four hips in which there had been prosthetic replacement were selected for study because of the presence of linear (diffuse) or lytic (localized) areas of periprosthetic bone loss. In all hips, there was careful documentation of the anatomical location of the material that had been obtained for histological analysis, and the specific purpose of the removal of the tissue was for examination to determine the cause of the resorption of bone. Specimens from twenty-three hips were retrieved during an operation and from eleven hips, at autopsy. The area of bone loss was linear only in sixteen hips, lytic only in thirteen, and both linear and lytic in five. In all thirty-four hips, intracellular particulate debris was found in the macrophages that were present in the area of bone resorption. All thirty-four had intracellular particles of polyethylene, many of which were less than one micrometer in size. Thirty-one hips had extracellular particles of polyethylene as well. Twenty-two of the thirty-four hips had intracellular metallic debris; in ten, metallic debris was found extracellularly as well. Ten of the sixteen cemented specimens had intracellular and extracellular polymethylmethacrylate debris. In the mechanically stable prostheses--cemented and uncemented--polyethylene wear debris was identified in areas of bone resorption far from the articular surfaces. The number of macrophages in a microscopic field was directly related to the amount of particulate polyethylene debris that was visible by light microscopy. Although the gross radiographic appearances of linear bone loss and lytic bone loss were different, the histological appearance of the regions in which there was active bone resorption was similar. Regardless of the radiographic appearance and anatomical origin of the specimen, bone resorption was found to occur in association with macrophages that were laden with polyethylene debris. In general, the number of macrophages present had a direct relationship to the degree of bone resorption that was seen. We believe that these findings indicate that joint fluid penetrates far more extensively than previously thought, even in a well fixed component, along the interface between the prosthesis and bone and in the periprosthetic tissues; it is often more extensive than is shown by arthrography. We therefore suggest the concept of the effective joint space to include all periprosthetic regions that are accessible to joint fluid and thus accessible to particulate debris. (ABSTRACT TRUNCATED AT 400 WORDS)
Cataloguing/analogizing: A nonmonotonic view

Reasoning deductively under incomplete information is nonmonotonic in nature since the arrival of additional information may invalidate or reverse previously obtained conclusions. It amounts to apply generic default rules in an appropriate way to a particular (partially described) situation. This type of nonmonotonic reasoning can only provide plausible conclusions. Analogical reasoning is another form of commonly used reasoning that yields brittle conclusions. It is nondeductive in nature and proceeds by putting particular situations in parallel. Analogical reasoning also exhibits nonmonotonic features, as investigated in this paper when particular situations may be incompletely stated. The paper reconsiders the pattern of plausible reasoning proposed by Polya, “a and b are analogous, a is true, then b true is more credible,'' from a nonmonotonic reasoning point of view. A representation of the statement “a and b are analogous” in terms of nonmonotonic consequences relations is presented. This representation is then related to a logical definition of analogical proportions, i.e. statements of the form “a is to b as c is to d” that has been recently proposed and extended to other types of proportions. Remarkably enough, semantic equivalence between conditional objects of the form “b given a,” which have been shown as being at the root of nonmonotonic reasoning, constitutes another type of noticeable proportions. By offering a parallel between two important forms of commonsense reasoning, this paper enriches the comparison between nonmonotonic reasoning and analogical reasoning that is not often made. © 2011 Wiley Periodicals, Inc.
Does EU support contribute to economically successful Public-Private Partnerships (PPPs)? A panel data analysis of road PPP projects in Spain

Abstract The EU infrastructure policy has relied on Public-Private Partnerships (PPPs) as a means to successfully deliver infrastructure of benefit for the EU. To reach its infrastructure policy objectives, the EU has implemented support mechanisms aimed at facilitating the delivery of PPPs. This article is aimed at evaluating to what extent these mechanisms have actually contributed to improving the economic performance of PPPs. To that end, we have selected the case of Spanish road PPPs for empirical analysis. The main result shows that EU support positively influences the economic performance of PPP projects. This is caused by the fact that the EU conditions its financial support on a project’s meeting a set of requirements that help assure the success of the project. From this result, we obtain a set of conclusions that may be generalised to other cases, and provide a contribution to the body of knowledge on PPPs.
Endometrial Endometrioid Adenocarcinoma With a Deceptive Pattern of Spread to the Uterine Cervix: A Manifestation of Stage IIB Endometrial Carcinoma Liable to Be Misinterpreted as an Independent Carcinoma or a Benign Lesion

The prognosis of endometrial endometrioid adenocarcinoma is determined in part by stage; endocervical stromal involvement (stage IIB) imparts a worsened prognosis. We describe a deceptive pattern of stage IIB disease that mimics a primary endocervical glandular proliferation and may lead to understaging of endometrial endometrioid adenocarcinoma. Fifteen cases of endometrial endometrioid adenocarcinoma with a peculiar pattern of cervical involvement were identified from our consultation files. All cases were referred in consultation because of doubt about the nature of the cervical process and its relation to the corpus tumor; in a few instances, the cervical proliferation was considered possibly benign and in one case was misinterpreted as mesonephric hyperplasia. The patients ranged from 49 to 84 years in age (mean age 64.9 years). There was usually a grossly evident endometrial tumor. The cervix was unremarkable grossly in at least 11 patients. The cervical tumors were composed of variably shaped, often tubular glands with little or no stromal response and mainly invaded as widely spaced glands that often appeared deceptively benign. In 14 cases luminal secretions, mainly eosinophilic, were identified, often leading to consideration of a mesonephric lesion. Ten of the endometrial tumors were grade 1, four grade 2, and one grade 3. One was noninvasive, nine superficially invasive, and five deeply invasive. In four cases myoinvasion had, at least in part, a diffusely infiltrative pattern. The tumors in the cervix showed no in situ component and no definite surface involvement. Continuity with the corpus tumor could be demonstrated in 12 cases. Ten of the cervical tumors invaded more deeply than the endometrial tumor, four invaded to a similar depth, and only one was more superficial than its endometrial counterpart. The cervical and corpus tumors had a similar immunoprofile in nine cases: all were vimentin positive, eight estrogen positive and one negative, four carcinoembryonic antigen negative, and five with focal apical or rare cytoplasmic staining. This immunoprofile in conjunction with routine morphologic similarity between the two tumors and the usual documented continuity between them indicate that the cervical process represents spread from the endometrial endometrioid adenocarcinoma. It is important for both therapeutic and prognostic reasons that the cervical abnormality is not misinterpreted as a benign or malignant primary endocervical glandular process.
Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression

Protein arginine methyltransferases (PRMTs) catalyze protein arginine methylation and are linked to carcinogenesis and metastasis. Some members of PRMTs have been found to undergo automethylation; however, the biologic significance of this self‐modification is not entirely clear. In this report, we demonstrate that R531 of PRMT7 is self‐methylated, both in vitro and in vivo. Automethylation of PRMT7 plays a key role in inducing the epithelial–mesenchymal transition (EMT) program and in promoting the migratory and invasive behavior of breast cancer cells. We also prove in a nude mouse model that expression of wild‐type PRMT7 in MCF7 breast cancer cells promotes metastasis in vivo, in contrast to the PRMT7 R531K mutant (a mimic of the unmethylated status). Moreover, our immunohistochemical data unravel a close link between PRMT7 automethylation and the clinical outcome of breast carcinomas. Mechanistically, we determine that loss of PRMT7 automethylation leads to the reduction of its recruitment to the E‐cadherin promoter by YY1, which consequently derepresses the E‐cadherin expression through decreasing the H4R3me2s level. The findings in this work define a novel post‐translational modification of PRMT7 that has a promoting impact on breast cancer metastasis. —Geng, P., Zhang, Y. , Liu, X. , Zhang, N. , Liu, Y. , Liu, X. , Lin, C. , Yan, X. , Li, Z. , Wang, G. , Li, Y. , Tan, J., Liu, D. ‐X. , Huang, B. , Lu, J. Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression. FASEB J. 31, 2287–2300 (2017). www.fasebj. org
Investigation of Nanowire Line-Edge Roughness in Gate-All-Around Silicon Nanowire MOSFETs

In this paper, the effects of nanowire line-edge roughness (LER) in gate-all-around silicon nanowire MOSFETs (SNWTs) are comprehensively investigated through 3-D statistical simulation. The LER impacts on both the device performance variation and mean value degradation are discussed in detail. Due to the unique nature of a nanowire structure, the LER in SNWTs contains two degrees of freedom, which allows the nanowire edges to vary in arbitrary transverse direction and which is different from the LER in traditional devices with one degree of freedom. In order to identify the relative importance of the diameter and center position variations, the nanowire LER can be considered as the combination of two basic types: One has a varied diameter with a fixed center (type A), and the other has a varied center position with a fixed diameter (type B). The results indicate the tradeoff between these two types of LER, with type A of a larger performance variation and type B of a larger performance degradation. Furthermore, as the gate length Lg shrinks below the correlation length Λ of the nanowire LER, the impacts from the source/drain extension region will dominate the variation. The impact of the main LER parameters is discussed for the scaled case with a non-Gaussian distribution in the device electrical parameters observed, and a new statistical method is proposed for better evaluation. On the other hand, the performance variation becomes insensitive to the correlation length in the case of Λ > Lg, which indicates a higher tolerance for the nanowire LER design in ultrascaled SNWTs. The optimized LER parameters are also given for the nanowire LER design with acceptable performance variation and suppressed mean value degradation in SNWTs.
Anticonvulsant activity of a nonpeptide galanin receptor agonist

Galanin is a neuropeptide with a wide variety of biological functions, including that of a strong endogenous anticonvulsant. No nonpeptide ligands, capable of activating galanin receptors, are available today. Based on known pharmacophores of galanin, a combinatorial library was designed, synthesized, and screened at the rat hippocampal galanin receptor. A low molecular weight galanin receptor agonist, 7-((9-fluorenylmethoxycarbonyl)cyclohexylalanyllysyl)amino-4-methylcoumarin (galnon) was found to displace 125I-galanin with micromolar affinity at Bowes cellular and rat hippocampal membranes. Autoradiographic binding assay on rat spinal cord sections confirmed the ability of galnon to displace 125I-galanin from its binding sites. Galnon inhibited adenylate cyclase activity, suggesting an agonist action at galanin receptors. When injected i.p. galnon reduced the severity and increased the latency of pentylenetetrazole-induced seizures in mice and reversed the proconvulsant effects of the galanin receptor antagonist M35, injected into a lateral ventricle. Intrahippocampal injection of galnon also shortened the duration of self-sustaining status epilepticus in rats, confirming its agonist properties in vivo. Pretreatment of rats with antisense peptide nucleic acid targeted to galanin receptor type 1 mRNA abolished the effect of galnon, suggesting mediation of its anticonvulsant properties through this receptor subtype. These findings introduce a systemically active nonpeptide galanin agonist anticonvulsant.