Miracle-dz/UniFAR-FTUs huggingface dataset:
Fibroblastic reaction and vascular maturation in human colon cancers

Purpose: The objective of the present study was to provide evidence for the hypothesis of fibroblasts and the desmoplastic reaction, respectively, to impact the formation and maturation of the vascular network in human colon tumours via a retrospective in situ study. An in vivo xenograft model was evaluated to verify its potential for fibroblast-related functional studies. Materials and methods: In situ: Fiftytwo G2/G3 colon tumours were histomorphologically categorised into low (<50%), medium (50–75%) and high (>75%) grade desmoplasia based on hematoxylin/eosin and Elastica van Gieson stained paraffin sections. Low and high grade desmoplastic tumours were identified and stained for endothelial and pericyte markers to morphometrically analyse microvessel count (MVC), vascular surface area (VSA) and vascular maturation status. In vivo: One out of three established subcutaneous xenograft model in NMRI (nu/nu) mice was adapted to monitor the impact of primary human fibroblasts on xenograft formation and morphology. Results: Vascular structures in human colon tumours are predominantly located in the fibroblastic stromal regions. Highly desmoplastic tumours, however, have significantly lower MVC and VSA values at the invasion front with signs for augmented vascular maturation as compared with low grade desmoplastic colon cancers. Our in vivo approach verified that only high proportions of co-injected normal fibroblasts accelerate xenograft formation of HCT-116 colon cancer cells. Conclusions: The in situ data clearly support the hypothesis of fibroblasts to contribute to vascular maturation phenomena in colon cancers. The in vivo design of only 500 tumour cells co-injected with normal fibroblast is feasible, results in 100% engraftment and is the basis for further developments.
Metabolic Acidosis Stimulates RANKL RNA Expression in Bone Through a Cyclo‐oxygenase‐Dependent Mechanism

Metabolic acidosis inhibits osteoblastic bone formation and stimulates osteoclastic resorption. To determine whether acidosis alters expression of RNA for the osteoclastic differentiation factor RANKL, mouse calvariae were incubated in neutral or physiologically acidic media. Acidosis resulted in a significant cyclo‐oxygenase‐dependent increase in RANKL RNA levels, which would be expected to induce the associated increase in bone resorption.
DNS performance and the effectiveness of caching

This paper presents a detailed analysis of traces of domain name system (DNS) and associated TCP traffic collected on the Internet links of the MIT Laboratory for Computer Science and the Korea Advanced Institute of Science and Technology (KAIST). The first part of the analysis details how clients at these institutions interact with the wide-area domain name system, focusing on client-perceived performance and the prevalence of failures and errors. The second part evaluates the effectiveness of DNS caching.In the most recent MIT trace, 23% of lookups receive no answer; these lookups account for more than half of all traced DNS packets since query packets are retransmitted overly persistently. About 13% of all lookups result in an answer that indicates an error condition. Many of these errors appear to be caused by missing inverse (IP-to-name) mappings or NS records that point to nonexistent or inappropriate hosts. 27% of the queries sent to the root name servers result in such errors.The paper also presents the results of trace-driven simulations that explore the effect of varying TTLs and varying degrees of cache sharing on DNS cache hit rates. Due to the heavy-tailed nature of name accesses, reducing the TTLs of address (A) records to as low as a few hundred seconds has little adverse effect on hit rates, and little benefit is obtained from sharing a forwarding DNS cache among more than 10 or 20 clients. These results suggest that client latency is not as dependent on aggressive caching as is commonly believed, and that the widespread use of dynamic low-TTL A-record bindings should not greatly increase DNS related wide-area network traffic.
Fish full life‐cycle testing for androgen methyltestosterone on medaka (Oryzias latipes)

We studied the chronic effects of methyltestosterone (MT) on reproductive status of medaka (Oryzias latipes) over two generations under continuous exposure to verify the applicability of the fish full life‐cycle test (FFLC) for this androgen with this species. The exposure of parental (F0) medaka to MT was begun on embryos within 12 h postfertilization and continued for up to 101 d; assessment endpoints included embryological development, hatching, posthatch survival, growth, sexual differentiation, reproduction, and hepatic vitellogenin (VTG) levels under flow‐through exposure to MT at each mean measured concentration of 0.35, 1.09, 3.29, 9.98, and 27.75 ng/L. Eggs (F1) spawned from the F0 fish at 98, 99, and 100 d posthatch were examined for hatchability, survival after hatching, growth, sexual differentiation, and hepatic VTG level until 60 d posthatch. In the FFLC with medaka, MT induced masculinization of both secondary sex characteristics and gonads. We observed that all F0 fish in the 27.75‐ng/L treatment group showed male secondary sex characteristics in which no fish with ovary could be discerned. Several fish with ovaries in F0 and F1 generations treated with 9.98 ng/L showed male secondary sex characteristics. We also observed swollen abdomens in the F0 and F1 female fish in the 9.98‐ng/L treatment group. These swollen abdomens were induced by enlarged ovaries and were accompanied with declined fecundity and fertility in the F0 generation. These results indicate that MT reduces the reproductive potential of medaka and that the FFLC with this species is applicable to the evaluation of androgens.
The RARS–MAD1L1 Fusion Gene Induces Cancer Stem Cell–like Properties and Therapeutic Resistance in Nasopharyngeal Carcinoma

Purpose: Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC. Experimental Design: RNA sequencing (RNA-seq) was applied to look for interchromosome translocation in NPC. PCR, FISH, and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies. MTT assay, colony formation assay, sphere formation assay, co-immunoprecipitation, chromatin immunoprecipitation assay, and in vivo chemoresistance assay were applied to explore the function of RARS-MAD1L1 in NPC. Results: We demonstrated that RARS-MAD1L1 was present in 10.03% (35/349) primary NPC biopsies and 10.7% (9/84) in head and neck cancer (HNC) samples. RARS-MAD1L1 overexpression increased cell proliferation, colony formation, and tumorigenicity in vitro, and the silencing of endogenous RARS-MAD1L1 reduced cancer cell growth and colony formation in vitro. In addition, RARS-MAD1L1 increased the side population (SP) ratio and induced chemo- and radioresistance. Furthermore RARS-MAD1L1 interacted with AIMP2, which resulted in activation of FUBP1/c-Myc pathway. The silencing of FUBP1 or the administration of a c-Myc inhibitor abrogated the cancer stem cell (CSC)-like characteristics induced by RARS-MAD1L1. The expression of c-Myc and ABCG2 was higher in RARS-MAD1L1–positive HNC samples than in negative samples. Conclusions: Our findings indicate that RARS-MAD1L1 might contribute to tumorigenesis, CSC-like properties, and therapeutic resistance, at least in part, through the FUBP1/c-Myc axis, implying that RARS-MAD1L1 might serve as an attractive target for therapeutic intervention for NPC. Clin Cancer Res; 24(3); 659–73. ©2017 AACR.
Ensemble classifier with Random Forest algorithm to deal with imbalanced healthcare data

In day today life, data is generated in massive amount with rapid growth in health care environment. The medical industries have large amount of data sets, for diagnosis purpose and maintain patient's records. The medical researches come with new treatments and medicine every day. But availability of medical datasets is often not balanced in their class labels. The performance of some existing method is poor on imbalanced dataset. So the prediction of disease from imbalanced data becomes difficult to handle. In this proposal Classifier ensemble method (Random Forest algorithm) can be used to overcome existing classifier techniques. Multiple classifier system is more accurate and robust than an existing classifier technique. The ensemble method proves to be very efficient in classification of records from available imbalanced healthcare patient data, as it involves the process of considering opinion from multiple base classifiers, as opposed to the single classifier method. This method gives a very accurate and precise inference, as unrelated data's are removed because of multiple base classifiers. The problems of healthcare dataset especially with some uncertainty can be predicted.
Gangliosides for acute ischaemic stroke.

BACKGROUND Gangliosides may have a protective effect on the central and peripheral nervous systems. OBJECTIVES The objective of this review was to assess the effect of exogenous gangliosides in acute ischaemic stroke. SEARCH STRATEGY We searched the Cochrane Stroke Group trials register (last searched: March 1999) and contacted drug companies. SELECTION CRITERIA Randomised trials of gangliosides compared with placebo or standard treatment in people with definite or presumed ischaemic stroke. Trials were included if people were randomised within 15 days of symptom onset and if mortality data were available. DATA COLLECTION AND ANALYSIS One reviewer applied the inclusion criteria. Two reviewers independently extracted the data. Trial quality was assessed. MAIN RESULTS Eleven trials involving 2257 people were included. All the trials tested purified monosialoganglioside GM1. Only three trials described the randomisation procedure. Follow-up was between 15 to 180 days. Death at the end of follow-up showed no significant difference (odds ratio 0.91, 95% confidence interval 0.73 to 1.14). There was no difference shown between early (within 48 hours) and delayed treatment. For disability, two trials showed an improved Barthel index score with gangliosides (weighted mean difference 8.6, 95% confidence interval 1.2 to 16.0). In two trials, eight patients experienced adverse effects that led to discontinuation of ganglioside treatment, seven had skin reactions and one developed Guillain-Barré syndrome. REVIEWER'S CONCLUSIONS There is not enough evidence to conclude that gangliosides are beneficial in acute stroke. Caution is warranted because of reports of sporadic cases of Guillain-Barré syndrome after ganglioside therapy.
Video-Based People Fall Detection via Homography Mapping of Foreground Polygons from Overlapping Cameras

In this paper, we investigate a video-based method of detecting fall incidents from overlapping cameras. Our aim here is to propose a novel method, without any wearable device, to detect falls on the floor with a multiple cameras system by using homographic projection on aground plane (or on reference camera view plane). Two relatively orthogonal views are utilized, in turn, simplifying the estimation of the surface of the person which is in contact with the ground according of the foreground information of each camera. This information is computed in order to differentiate lying on floor posture which can be considered as fall to other position. The performance of our method is tested on a public multi-view fall dataset. The results show the accuracy of our proposed algorithm.
Impact of transmission constraints on supply-side bidding strategy using BLP approach

This paper presents an approach to develop an optimal bidding strategy for a generation company (GenCo) in the network constrained electricity markets. A bi-level programming (BLP) technique is formulated in which upper level problem represents an individual generating company (GenCo) payoff maximization and the lower level represents the independent system operator's (ISO) market clearing problem for minimizing consumers' payments. The objective function of BLP problem used for bidding strategy by economic withholding is highly nonlinear, and there are complementarity terms to represent the market clearing. This approach is applied to find the optimal bidding strategy of a GenCo competing with five GenCos in IEEE 30-bus test system. Opponents' bidding behavior is modeled with probabilistic estimation. The impact of network constraints and opponents bidding behavior on bidding strategy of a GenCo have been analyzed in four simulation cases to show the effectiveness and robustness of the proposed algorithm.
Linkage Analysis in a Dutch Population Isolate Shows No Major Gene for Left-Handedness or Atypical Language Lateralization

Cerebral dominance of language function and hand preference are suggested to be heritable traits with possible shared genetic background. However, joined genetic studies of these traits have never been conducted. We performed a genetic linkage study in 37 multigenerational human pedigrees of both sexes (consisting of 355 subjects) enriched with left-handedness in which we also measured language lateralization. Hand preference was measured with the Edinburgh Handedness Inventory, and language lateralization was measured with functional transcranial Doppler during language production. The estimated heritability of left-handedness and language lateralization in these pedigrees is 0.24 and 0.31, respectively. A parametric major gene model was tested for left-handedness. Nonparametric analyses were performed for left-handedness, atypical lateralization, and degree of language lateralization. We did not observe genome-wide evidence for linkage in the parametric or nonparametric analyses for any of the phenotypes tested. However, multiple regions showed suggestive evidence of linkage. The parametric model showed suggestive linkage for left-handedness in the 22q13 region [heterogeneity logarithm of odds (HLOD) = 2.18]. Nonparametric multipoint analysis of left-handedness showed suggestive linkage in the same region [logarithm of odds (LOD) = 2.80]. Atypical language lateralization showed suggestive linkage in the 7q34 region (LODMax = 2.35). For strength of language lateralization, we observed suggestive linkage in the 6p22 (LODMax = 2.54), 7q32 (LODMax = 1.93), and 9q33 (LODMax = 2.10) regions. We did not observe any overlap of suggestive genetic signal between handedness and the extent of language lateralization. The absence of significant linkage argues against the presence of a major gene coding for both traits; rather, our results are suggestive of these traits being two independent polygenic complex traits.
Chelation therapy for neurodegenerative diseases

Mounting evidence suggests a central role for transition biometals in the etiopathogenesis of neurodegenerative diseases (ND). Indeed, while studying the molecular basis for this heterogeneous group of diseases, it has become increasingly evident that biometals and nonphysiological Al are often involved in pathology onset and progression, either by affecting the conformation of specific proteins or by exacerbating local oxidative stress. The apparently critical role played by metal dishomeostasis in ND makes chelation therapy an attractive pharmacological option. However, classical metal chelation approaches, relying on potent metal ligands, turned out to be successful only in those rare cases where exceptional brain metal accumulation occurs due to specific defects in metal metabolism. In contrast, metal‐targeted approaches using ligand of intermediate strength seem to be more appropriate in fighting the major ND, although their benefits are still questioned. We report here a survey of recent evidences supporting the use of a variety of metal ligands, and even functionalized nanoparticles, for the treatment of the most common ND. The beneficial neuropharmacological actions of metal‐targeted agents most likely arise from local metal redistribution rather than from massive metal removal. The perspectives for the development of new effective agents against ND are critically discussed. © 2009 Wiley Periodicals, Inc. Med Res Rev
Clinical correlation with failure of endovenous therapy for leg swelling

Background The development and use of minimally invasive procedures provide improved options for the management of symptoms of chronic venous insufficiency. While many patients with iliac venous occlusive disease and superficial venous insufficiency improve with combined iliac venous stenting and correction of superficial venous reflux, some patients have symptoms which persist. The goal of this study was to identify clinical factors related to persistent symptoms in patients with leg swelling after treatment of both iliac vein stenting and thermal ablation. Methods This observational study analyzed data for patients who underwent both iliac vein stent placement as well as endovenous ablation (either RFA or EVLT) as a management for chronic venous insufficiency between February 2012 and February 2014. Follow-up was performed after completion of both procedures and inquiring for improvement of swelling. Statistical analysis performed using Chi-square and student's t-test. Results Of the total 173 patients who underwent both endovenous closure and iliac vein stent placements, 55 (31.8%) patients were men; 29 (16%) patients stated they had no improvement after these procedures. The average age of patients who did not improve was 68.8 (±16.7 SD) years and 66.2 (±13.3 SD) years for patients who improved. Over all, the classification of the presenting symptoms by CEAP classification demonstrated 25.4%, 53.2%, 5.8%, and 15.6%, for C3–C6, respectively. There was no correlation with failure to improve the swelling with: age (P = .44), gender (P = .33), presenting symptom (P = .67), use of calcium channel blockers (P = .85), nitroglycerin (P = .86), Plavix (P = .07), aspirin (P = .55), Synthyroid (P = .55), Coumadin (P = .14), angiotensin receptor blocker (P = .81), β Blockers (P = .61), angiotensin converting enzyme inhibitors (P = .88), furosemide 40 mg (P = .74), hydrochlorothiazide 12.5 mg (P = .07), hydrochlorothiazide 25 mg (P = .48), and EVLT vs. RFA (P = .91). The use of furosemide (20 mg) was associated with continued swelling (P = .01). The use of dual diuretics (furosemide and hydrochlorothiazide) was associated with persistent swelling even after these combined endovenous procedures P = . 03). Conclusion These preliminary data suggest that the treatment with diuretics may be associated with failure to relieve lower extremity swelling despite combined endovascular therapy for chronic venous insufficiency.
Annual prevalence and economic burden of genital warts in Korea: Health Insurance Review and Assessment (HIRA) service data from 2007 to 2015

SUMMARY This study evaluated the annual prevalence of anogenital warts (AGW) caused by human papillomavirus (HPV) and analysed the trend in annual per cent changes (APC) by using national claims data from the Health Insurance Review and Assessment of Korea, 2007–2015. We also estimated the socio-economic burden and co-morbidities of AGW. All analyses were performed based on data for primary A63.0, the specific diagnosis code for AGW. The socio-economic cost of AGW was calculated based on the direct medical cost, direct non-medical cost and indirect cost. The overall AGW prevalence and socio-economic burden has increased during the last 9 years. However, the prevalence of AGW differed significantly by sex. The female prevalence increased until 2012, and decreased thereafter (APC + 3·6%). It would fall after the introduction of routine HPV vaccination, principally for females, in Korea. The male prevalence increased continuously over time (APC + 11·6%), especially in those aged 20–49 years. Referring to the increasing AGW prevalence and its disease burden, active HPV infection control surveillance and prevention in males are worth consideration.
The relationship between elastase and lactoferrin in healthy, gingivitis and periodontitis sites.

OBJECTIVES To compare the relative amounts of elastase (primary polymorphonuclear leucocyte granule constituent) and lactoferrin (secondary PMN granule constituent) in the gingival crevicular fluid (GCF) of healthy, gingivitis and periodontitis sites. DESIGN This cross-sectional study looked at the two GCF constituents in three categories of disease status within the same subject. MATERIALS AND METHODS Patients with chronic adult periodontitis were screened and those exhibiting all three types of sites ie periodontally healthy, gingivitis and periodontitis sites were recruited (n=10) and had GCF collected from the three sites. Lactoferrin and elastase were measured in eluates of GCF by enzyme-linked immunosorbent assay. RESULTS The absolute amount of lactoferrin measured in ng per 30 s samples was significantly lower in healthy and gingivitis sites as compared to periodontitis sites; however this difference failed to reach significance when the concentration of lactoferrin in GCF was used as the analytical unit. No significant differences were found for elastase levels at any sites when expressed as either absolute amounts or concentrations. Secondary granule release, as evidenced by lactoferrin levels, occurs during cell migration and the process is independent of primary granule release, which is thought to correlate with PMN activation. The relationship between granule constituents in the samples showed significant differences, the highest lactoferrin/elastase ratio being at periodontitis sites (P<0.001). CONCLUSIONS These findings imply a change in the relative amounts of elastase and lactoferrin released at different disease level sites, wth an almost 10-fold increase in the proportion of lactoferrin to elastase in periodontitis sites over healthy and gingivitis sites. This variation in the release by PMNs of primary and secondary granule constituents may indicate alterations in PMN function in different disease environments.
Modulation of Hexa-Acyl Pyrophosphate Lipid A Population under Escherichia coli Phosphate (Pho) Regulon Activation

ABSTRACT Environmental phosphate is an important signal for microorganism gene regulation, and it has recently been shown to trigger some key bacterial virulence mechanisms. In many bacteria, the Pho regulon is the major circuit involved in adaptation to phosphate limitation. The Pho regulon is controlled jointly by the two-component regulatory system PhoR/PhoB and by the phosphate-specific transport (Pst) system, which both belong to the Pho regulon. We showed that a pst mutation results in virulence attenuation in extraintestinal pathogenic Escherichia coli (ExPEC) strains. Our results indicate that the bacterial cell surface of the pst mutants is altered. In this study, we show that pst mutants of ExPEC strains display an increased sensitivity to different cationic antimicrobial peptides and vancomycin. Remarkably, the hexa-acylated 1-pyrophosphate form of lipid A is significantly less abundant in pst mutants. Among differentially expressed genes in the pst mutant, lpxT coding for an enzyme that transfers a phosphoryl group to lipid A, forming the 1-diphosphate species, was found to be downregulated. Our results strongly suggest that the Pho regulon is involved in lipid A modifications, which could contribute to bacterial surface perturbations. Since the Pho regulon and the Pst system are conserved in many bacteria, such a lipid A modification mechanism could be widely distributed among gram-negative bacterial species.