Miracle-dz/UniFAR-FTUs huggingface dataset:
Oncotargets and Therapy Dovepress Dovepress a New Tumor Suppressor Lncrna Rp11-190d6.2 Inhibits the Proliferation, Migration, and Invasion of Epithelial Ovarian Cancer Cells

hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms Abstract: At present, a large number of long noncoding RNAs (lncRNAs) from the human genome have been discovered. Meanwhile, emerging evidence has indicated that lncRNAs could play a critical role in the regulation of cellular processes such as cancer progression and metastasis. However, the functions of some new lncRNAs in the complex transcriptional process are mostly unknown at present. Existing studies suggest that loss of WW domain-containing oxidoreductase (WWOX) expression is linked with poor prognosis in numerous cancers, including epithelial ovarian cancer (EOC). However, the functional role of its antisense transcript RP11-190D6.2 is not clear to date. In this study, WWOX antisense transcript RP11-190D6.2 was analyzed specifically in EOC cells using real-time polymerase chain reaction and gain-/ loss-of-function studies. We found that RP11-190D6.2 expression was positively correlated with WWOX expression. The RP11-190D6.2 expression was markedly downregulated in tumor tissues compared with normal tissues, but the RP11-190D6.2 expression was significantly downregu-lated in four EOC cell lines compared with human ovarian surface epithelial cell line. RP11-190D6.2 overexpression resulted in the increase of WWOX expression, whereas its knockdown led to the decrease of WWOX expression. We also found that RP11-190D6.2 was restored by 5-aza-2′-deoxycytidine treatment in EOC. In addition, the RP11-190D6.2 overexpression and knockdown experiments revealed that RP11-190D6.2 overexpression inhibited proliferation, migration, and invasion abilities in HO8910-PM cells, whereas RP11-190D6.2 knockdown in HEY-A8 cells had the opposite effect. The analyses in EOC implicate that RP11-190D6.2 may play a pivotal role in the regulation of tumor metastasis, suggesting that RP11-190D6.2 may serve as a potential biomarker and therapeutic target for EOC.
Risk prediction models for contrast induced nephropathy: systematic review

Objectives To look at the available literature on validated prediction models for contrast induced nephropathy and describe their characteristics. Design Systematic review. Data sources Medline, Embase, and CINAHL (cumulative index to nursing and allied health literature) databases. Review methods Databases searched from inception to 2015, and the retrieved reference lists hand searched. Dual reviews were conducted to identify studies published in the English language of prediction models tested with patients that included derivation and validation cohorts. Data were extracted on baseline patient characteristics, procedural characteristics, modelling methods, metrics of model performance, risk of bias, and clinical usefulness. Eligible studies evaluated characteristics of predictive models that identified patients at risk of contrast induced nephropathy among adults undergoing a diagnostic or interventional procedure using conventional radiocontrast media (media used for computed tomography or angiography, and not gadolinium based contrast). Results 16 studies were identified, describing 12 prediction models. Substantial interstudy heterogeneity was identified, as a result of different clinical settings, cointerventions, and the timing of creatinine measurement to define contrast induced nephropathy. Ten models were validated internally and six were validated externally. Discrimination varied in studies that were validated internally (C statistic 0.61-0.95) and externally (0.57-0.86). Only one study presented reclassification indices. The majority of higher performing models included measures of pre-existing chronic kidney disease, age, diabetes, heart failure or impaired ejection fraction, and hypotension or shock. No prediction model evaluated its effect on clinical decision making or patient outcomes. Conclusions Most predictive models for contrast induced nephropathy in clinical use have modest ability, and are only relevant to patients receiving contrast for coronary angiography. Further research is needed to develop models that can better inform patient centred decision making, as well as improve the use of prevention strategies for contrast induced nephropathy.
Socioeconomic Inequalities in Psychological Distress among Urban Adults: The Moderating Role of Neighborhood Social Cohesion

Background Various studies have reported socioeconomic inequalities in mental health among urban residents. This study aimed at investigating whether neighborhood social cohesion influences the associations between socio-economic factors and psychological distress. Methods Cross-sectional questionnaire study on a random sample of 18,173 residents aged 16 years and older from 211 neighborhoods in the four largest cities in the Netherlands. Psychological distress was the dependent variable (scale range 10–50). Neighborhood social cohesion was measured by five statements and aggregated to the neighborhood level using ecometrics methodology. Multilevel linear regression analyses were used to investigate cross-level interactions, adjusted for neighborhood deprivation, between individual characteristics and social cohesion with psychological distress. Results The mean level of psychological distress among urban residents was 17.2. Recipients of disability, social assistance or unemployment benefits reported higher psychological distress (β = 5.6, 95%CI 5.2 to 5.9) than those in paid employment. Persons with some or great financial difficulties reported higher psychological distress (β = 3.4, 95%CI 3.2 to 3.6) than those with little or no financial problems. Socio-demographic factors were also associated with psychological distress, albeit with much lower influence. Living in a neighborhood with high social cohesion instead of low social cohesion was associated with a lower psychological distress of 22% among recipients of disability, social assistance or unemployment benefits and of 13% among citizens with financial difficulties. Conclusions Residing in socially cohesive neighborhoods may reduce the influence of lack of paid employment and financial difficulties on psychological distress among urban adults. Urban policies aimed at improving neighborhood social cohesion may contribute to decreasing socio-economic inequalities in mental health.
Multicentury Instability of the Atlantic Meridional Circulation in Rapid Warming Simulations With GISS ModelE2

In multimillennial global warming simulations with the GISS‐E2‐R climate model, we observe multicentennial shutdowns with restoration and fast overshooting in North Atlantic Deep Water production despite the absence of exogenous freshwater input. AMOC (Atlantic Meridional Overturning Circulation) cessation is associated with a sea surface salinity reduction, initiated by increases in precipitation over evaporation as the climate warms. These multicentury shutdowns are the direct result of cooling in the North Atlantic associated with an aerosol indirect effect on cloud cover. The local cooling reduces evaporation within the North Atlantic, while warming elsewhere provides moisture to maintain nearly unperturbed precipitation in this region. As global warming continues, warm temperature (low density) anomalies spread northward at depth in the North Atlantic eventually destabilizing the water column, even though precipitation input at the surface is initially unchanged. Internal ocean freshwater transports do not play an important role in initiating this behavior, as assumed by some standard metrics of AMOC stability. The importance of the aerosol indirect effect in these runs is due to its role in strengthening the sea surface temperature‐evaporation feedback; this suggests a renewed focus on surface flux observations to help assess overturning stability. The length of the AMOC reduction, and its rapid recovery, may be relevant to the onset and end of the Younger Dryas, which occurred within a warming climate during the last deglaciation.
Hypermedia and cognition: designing for comprehension

hypermedia, it is necessary to distinguish between two kinds of applications: “One encourages those who wish to wander through large clouds of information, gathering knowledge along the way. The other is more directly tied to specific problem-solving, and is quite structured and perhaps even constrained” [20, p. 119]. Applications of the first type appear as browsable databases—or hyperbases—that can be freely explored by a reader. In contrast, applications of the second type take the shape of electronic documents—or hyperdocuments—that intentionally guide readers through an information space, controlling their exploration along the lines of a predefined structure. Each type has its particular advantages and encourages different reading strategies. While the first one is better suited to support unconstrained search and information retrieval, the second one is more adequate for tasks requiring deep understanding and learning. As Hammond points out, it “may be fun and perhaps instructive, to open every door and peer inside, but there are many situations where learning is most effective when the freedom of the learner is restricted to a relevant and helpful subset of activities. ” It is this second type of task—reading a hyperdocument for learning—that we address in our discussion of “designing for comprehension. ”
Co-Saliency Detection via a Self-Paced Multiple-Instance Learning Framework

As an interesting and emerging topic, co-saliency detection aims at simultaneously extracting common salient objects from a group of images. On one hand, traditional co-saliency detection approaches rely heavily on human knowledge for designing hand-crafted metrics to possibly reflect the faithful properties of the co-salient regions. Such strategies, however, always suffer from poor generalization capability to flexibly adapt various scenarios in real applications. On the other hand, most current methods pursue co-saliency detection in unsupervised fashions. This, however, tends to weaken their performance in real complex scenarios because they are lack of robust learning mechanism to make full use of the weak labels of each image. To alleviate these two problems, this paper proposes a new SP-MIL framework for co-saliency detection, which integrates both multiple instance learning (MIL) and self-paced learning (SPL) into a unified learning framework. Specifically, for the first problem, we formulate the co-saliency detection problem as a MIL paradigm to learn the discriminative classifiers to detect the co-saliency object in the “instance-level”. The formulated MIL component facilitates our method capable of automatically producing the proper metrics to measure the intra-image contrast and the inter-image consistency for detecting co-saliency in a purely self-learning way. For the second problem, the embedded SPL paradigm is able to alleviate the data ambiguity under the weak supervision of co-saliency detection and guide a robust learning manner in complex scenarios. Experiments on benchmark datasets together with multiple extended computer vision applications demonstrate the superiority of the proposed framework beyond the state-of-the-arts.
Human Bocavirus in Korean Children with Gastroenteritis and Respiratory Tract Infections

Human bocaviruses (HBoVs) are suggested to be etiologic agents of childhood respiratory and gastrointestinal infections. There are four main recognized genotypes of HBoVs (HBoV1–4); the HBoV-1 genotype is considered to be the primary etiologic agent in respiratory infections, whereas the HBoV2–4 genotypes have been mainly associated with gastrointestinal infections. The aim of the present study was to determine the distribution of HBoV genotypes in children with respiratory or gastrointestinal infections in a hospital in Korea. A total of 662 nasopharyngeal swabs (NPSs) and 155 fecal specimens were collected from children aged 5 years or less. Polymerase chain reaction (PCR) was conducted to detect the NS1 HBoV gene. The VP1 gene of HBoV was further amplified in samples that were positive for the NS1 gene. The PCR products of VP1 gene amplification were genotyped by sequence analysis. HBoV was detected in 69 (14.5%) of 662 NPSs and in 10 (6.5%) of 155 fecal specimens. Thirty-three isolates from NPSs and five isolates from fecal specimens were genotyped, and all 38 sequenced isolates were identified as the HBoV-1 genotype. HBoV-1 is the most prevalent genotype in children with respiratory or gastrointestinal HBoV infections in a hospital in Korea.
Hypoxia-inducible Factor-1α Enhances Haptoglobin Gene Expression by Improving Binding of STAT3 to the Promoter*

Haptoglobin (Hp) is known to play a role in angiogenesis as well as in anti-inflammation. STAT3 is a major transcription factor for expression of human Hp. We investigated whether hypoxia-inducible factor-1α (HIF-1α), a key mediator of angiogenesis, participates in Hp gene expression. HIF-1α overexpression by gene transfection or hypoxia augmented Hp transcription in HepG2 human hepatoma cells. Conversely, knockdown of HIF-1α by specific siRNA transfection diminished Hp expression, although the level of STAT3 phosphorylation remained unchanged. A luciferase reporter assay using mutant Hp promoters demonstrated that two adjacent DNA elements, a STAT3-binding element (SBE) and a cAMP-response element (CRE)-like site in human Hp promoter −120/−97, were required for HIF-1α-stimulated transactivation of the Hp gene. HIF-1α, STAT3, and p300/CBP were simultaneously bound to the SBE/CRE as a complex form. When HIF-1α was knocked down, STAT3 binding to the SBE in the Hp promoter was attenuated. Our findings suggest that HIF-1α assists STAT3 in strong binding to the proximal SBE in the Hp promoter. The CRE-like site located near the SBE may contribute to the formation of a stable complex of STAT3, HIF-1α, and p300/CBP, which leads to maximum transcription of the Hp gene.
Chaperones increase association of tau protein with microtubules

Molecular chaperones and their functions in protein folding have been implicated in several neurodegenerative diseases, including Parkinson's disease and Huntington's disease, which are characterized by accumulation of protein aggregates (e.g., α-synuclein and huntingtin, respectively). These aggregates have been shown in various experimental systems to respond to changes in levels of molecular chaperones suggesting the possibility of therapeutic intervention and a role for chaperones in disease pathogenesis. It remains unclear whether chaperones also play a role in Alzheimer's disease, a neurodegenerative disorder characterized by β-amyloid and tau protein aggregates. Here, we report an inverse relationship between aggregated tau and the levels of heat shock protein (Hsp)70/90 in tau transgenic mouse and Alzheimer's disease brains. In various cellular models, increased levels of Hsp70 and Hsp90 promote tau solubility and tau binding to microtubules, reduce insoluble tau and cause reduced tau phosphorylation. Conversely, lowered levels of Hsp70 and Hsp90 result in the opposite effects. We have also demonstrated a direct association of the chaperones with tau proteins. Our results suggest that up-regulation of molecular chaperones may suppress formation of neurofibrillary tangles by partitioning tau into a productive folding pathway and thereby preventing tau aggregation.
Cashmere-VLM: Remote memory paging for software distributed shared memory

Software distributed shared memory (DSM) systems have successfully provided the illusion of shared memory on distributed memory machines. However most software DSM systems use the main memory of each machine as a level in a cache hierarchy, replicating copies of shared data in local memory. Since computer memories tend to be much larger than caches, DSM systems have largely ignored memory capacity issues, assuming there is always enough space in main memory in which to replicate data. Applications that access data that exceeds the capacity available in local memory will page to disk, resulting in reduced performance. We have developed a software DSM system based on Cashmere that takes advantage of system-wide memory resources in order to reduce or eliminate paging overhead. Experimental results on a 4-node, 16-processor AlphaServer system demonstrate the improvement in performance using the enhanced software DSM system for applications with large data sets.
Therapy of hypoparathyroidism with PTH(1-84): a prospective four-year investigation of efficacy and safety.

CONTEXT PTH may be an effective treatment option for hypoparathyroidism, but long-term data are not available. OBJECTIVE We studied the effect of 4 yr of PTH(1-84) treatment in hypoparathyroidism. DESIGN Twenty-seven subjects were treated with PTH(1-84) for 4 yr, with prospective monitoring of calcium and vitamin D requirements, serum and urinary calcium, serum phosphorus, bone turnover markers, and bone mineral density (BMD). RESULTS Treatment with PTH(1-84) reduced supplemental calcium requirements by 37% (P = 0.006) and 1,25-dihydroxyvitamin D requirements by 45% (P = 0.008). Seven subjects (26%) were able to stop 1,25-dihydroxyvitamin D completely. Serum calcium concentration remained stable, and urinary calcium and phosphorus excretion fell. Lumbar spine BMD increased by 5.5 ± 9% at 4 yr (P < 0.0001). Femoral neck and total hip BMD remained stable. At 4 yr, distal radius BMD was not different from baseline. Bone turnover markers increased significantly, reaching a 3-fold peak from baseline values at 6-12 months (P < 0.05 for all), subsequently declining to steady-state levels at 30 months. Hypercalcemia was uncommon (11 episodes in eight subjects over 4 yr; 1.9% of all values), with most episodes occurring within the first 6 months and resolving with adjustment of supplemental calcium and vitamin D. CONCLUSIONS PTH(1-84) treatment of hypoparathyroidism for up to 4 yr maintains the serum calcium concentration, while significantly reducing supplemental calcium and 1,25-dihydroxyvitamin D requirements. Lumbar spine BMD increases without significant changes at other sites. These data provide support for the safety and efficacy of PTH(1-84) therapy in hypoparathyroidism for up to 4 yr.
Comparison of synovial tissues from the knee joints and the small joints of rheumatoid arthritis patients: Implications for pathogenesis and evaluation of treatment.

OBJECTIVE Serial synovial biopsy samples are increasingly being used for the evaluation of novel therapies for rheumatoid arthritis (RA). Most studies have used tissues from knee biopsies, but technical improvements have made serial small joint arthroscopy feasible as well. Theoretically, there could be differences in the features of synovial inflammation between various joints as a result of mechanical factors, differences in innervation, and other factors. We therefore undertook this study to compare the cell infiltrate in paired synovial biopsy samples from inflamed knee joints and paired inflamed small joints of patients with RA. METHODS Nine RA patients with both an inflamed knee joint and an inflamed small joint (wrist or metacarpophalangeal joint) underwent an arthroscopic synovial biopsy of both joints on the same day. Multiple biopsy specimens were collected and stained for macrophages, T cells, plasma cells, fibroblast-like synoviocytes, and interleukin-6 (IL-6) by immunohistochemistry. Sections were evaluated by digital image analysis. RESULTS There were no significant differences in mean cell numbers for all markers investigated in samples from the knee joint compared with samples from the small joints. We detected statistically significant correlations for the numbers of sublining macrophages, T cells, and plasma cells, as well as for IL-6 expression, between the knee joint and the small joints. However, there was no significant correlation between different joints for the numbers of intimal macrophages or fibroblast-like synoviocytes. CONCLUSION The results of this study show that the inflammation in one inflamed joint is generally representative of that in other inflamed joints. Therefore, it is possible to use serial samples from the same joint, selecting either large or small joints, for the evaluation of antirheumatic therapies.
Early Neolithic wine of Georgia in the South Caucasus

Significance The earliest biomolecular archaeological and archaeobotanical evidence for grape wine and viniculture from the Near East, ca. 6,000–5,800 BC during the early Neolithic Period, was obtained by applying state-of-the-art archaeological, archaeobotanical, climatic, and chemical methods to newly excavated materials from two sites in Georgia in the South Caucasus. Wine is central to civilization as we know it in the West. As a medicine, social lubricant, mind-altering substance, and highly valued commodity, wine became the focus of religious cults, pharmacopoeias, cuisines, economies, and society in the ancient Near East. This wine culture subsequently spread around the globe. Viniculture illustrates human ingenuity in developing horticultural and winemaking techniques, such as domestication, propagation, selection of desirable traits, wine presses, suitable containers and closures, and so on. Chemical analyses of ancient organic compounds absorbed into the pottery fabrics from sites in Georgia in the South Caucasus region, dating to the early Neolithic period (ca. 6,000–5,000 BC), provide the earliest biomolecular archaeological evidence for grape wine and viniculture from the Near East, at ca. 6,000–5,800 BC. The chemical findings are corroborated by climatic and environmental reconstruction, together with archaeobotanical evidence, including grape pollen, starch, and epidermal remains associated with a jar of similar type and date. The very large-capacity jars, some of the earliest pottery made in the Near East, probably served as combination fermentation, aging, and serving vessels. They are the most numerous pottery type at many sites comprising the so-called “Shulaveri-Shomutepe Culture” of the Neolithic period, which extends into western Azerbaijan and northern Armenia. The discovery of early sixth millennium BC grape wine in this region is crucial to the later history of wine in Europe and the rest of the world.
Unusual sequence effects on nucleotide excision repair of arylamine lesions: DNA bending/distortion as a primary recognition factor

The environmental arylamine mutagens are implicated in the etiology of various sporadic human cancers. Arylamine-modified dG lesions were studied in two fully paired 11-mer duplexes with a -G*CN- sequence context, in which G* is a C8-substituted dG adduct derived from fluorinated analogs of 4-aminobiphenyl (FABP), 2-aminofluorene (FAF) or 2-acetylaminofluorene (FAAF), and N is either dA or dT. The FABP and FAF lesions exist in a simple mixture of 'stacked' (S) and 'B-type' (B) conformers, whereas the N-acetylated FAAF also samples a 'wedge' (W) conformer. FAAF is repaired three to four times more efficiently than FABP and FAF. A simple A- to -T polarity swap in the G*CA/G*CT transition produced a dramatic increase in syn-conformation and resulted in 2- to 3-fold lower nucleotide excision repair (NER) efficiencies in Escherichia coli. These results indicate that lesion-induced DNA bending/thermodynamic destabilization is an important DNA damage recognition factor, more so than the local S/B-conformational heterogeneity that was observed previously for FAF and FAAF in certain sequence contexts. This work represents a novel 3'-next flanking sequence effect as a unique NER factor for bulky arylamine lesions in E. coli.