Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of reactive oxygen intermediates on the in vitro invasive capacity of tumor cells and liver metastasis in mice

We studied the role of reactive oxygen intermediates (ROls) in experimental liver metastasis induced in mice by the inoculation of COLON 26‐M5 murine colon cancer cells, a highly metastatic variant of COLON 26 cells, and the effect of ROIs on the invasive capacity of the cells in an in vitro chemo‐invasion assay model using reconstituted basement membrane matrigel. We also measured the release of ROIs from cells using electron spin resonance (ESR) spectrometry. Hydroxyl radicals (.OH) were constitutively released from the cells. This release was augmented by pre‐treatment with phorbol 12‐myristate 13‐acetate (PMA). In experimental liver metastasis in CDF1 mice, the administration of recombinant human superoxide dismu‐tase (r‐hSOD) significantly increased the number of metastatic nodules, while administration of catalase significantly inhibited metastasis formation. In vitro pre‐treatment of cells with PMA significantly increased the number of metastatic nodules. Invasive capacity of the cells was markedly augmented by pre‐treatment with PMA. PMA‐induced augmentation was significantly inhibited by the simultaneous addition of r‐hSOD to the assay. Catalase had no significant effect. Our findings suggest that ROIs play an important role in tumor invasion and metastasis, and that hydrogen peroxide (H2O2) may contribute to the retention or extravasation of circulating tumor cells. Furthermore, the superoxide anion (O2 ‐) released by tumor cells may play an important role in basement membrane degradation.
Gamma-interferon-inducible lysosomal thiol reductase is upregulated in human melanoma

T-cell-mediated immunity has the ability to produce durable antimelanoma responses, resulting in improved survival of patients with advanced melanoma. Antigen presentation is a key determinant of T-cell responses. Gamma-interferon-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentation of multiple melanoma antigens to CD4+ T cells. However, GILT expression in melanoma has not been defined. We evaluated GILT and MHC class II expression in human primary and metastatic melanomas and nevi using immunohistochemical analysis. GILT staining in melanocytes was observed in 70% of primary and 58% of metastatic melanomas versus 0% of nevi. When present, the GILT staining intensity in melanocytes was typically faint. Both GILT and MHC class II expression were increased in melanocytes of primary and metastatic melanomas compared with nevi. GILT staining in antigen-presenting cells (APCs) was detected in 100% of primary and metastatic melanomas versus 31% of nevi, and it was typically intense. GILT expression was increased in APCs of primary and metastatic melanomas compared with nevi, whereas MHC class II had equivalent high expression in APCs of all melanocytic lesions. GILT staining in keratinocytes was detected in 67% of primary melanomas versus 14% of nevi and 6% of metastatic melanomas. GILT, but not MHC class II, expression was increased in keratinocytes of primary melanomas compared with nevi and metastases. GILT expression is anticipated to result in improved presentation of melanoma antigens and more effective antimelanoma T-cell responses. GILT expression may be a biomarker of immune recognition of melanoma.
Association between maternal and fetal weight gain: cohort study

ABSTRACT CONTEXT AND OBJECTIVE: Excessive gestational weight gain is related to many complications (both maternal and fetal), such as macrosomia. The most common complications in macrosomic fetuses include: increased risk of intrauterine death, need for intensive care, fractures, neonatal hyperbilirubinemia, paralysis of the brachial plexus and obesity in childhood and adulthood. The aim of this study was to evaluate the association between gestational and fetal weight gain and the incidence of macrosomia in two maternity hospitals. DESIGN AND SETTING: Cohort study in two public maternity hospitals in Goiânia, Brazil. METHODS: This was a cohort study on 200 healthy pregnant women with normal body mass index, divided into two groups: one with normal weight gain and the other with excessive weight gain during pregnancy. RESULTS: The cohorts were similar regarding maternal age, per capita income, schooling level and reproductive behavior. The fetal weight was greater in the cohort with excessive maternal weight gain (3,388.83 g ± 514.44 g) than in the cohort with normal weight (3,175.86 g ± 413.70 g) (P < 0.01). The general incidence of macrosomia was 6.5%: 13.0% (13 cases) in the cohort with excessive maternal weight gain and 0.0% (0 cases) in the cohort with adequate weight gain. CONCLUSION: Excessive maternal weight gain was associated with increased fetal birth weight and incidence of macrosomia.
User-Generated Content in Pervasive Games

User-generated content (UGC) is already incorporated in several computer game instances wherein the players may create, edit and release their own content to the game world, thus influencing the game's evolution as well as the experience of other players. Lately, pervasive games have emerged as an exciting new development in gaming extending the boundaries of play out in the real word. The effectiveness of pervasive games in creating immersive live-action game experiences principally depends on the correlation of the game content with actual physical elements. To address this issue, most pervasive game prototypes so far have been bound to specific locations, while game content has been manually edited by the developers; they have also been heavily dependent on the mediation of orchestration teams. Nevertheless, the capacity of pervasive games to be staged anywhere (i.e. their portability) is critical for their wider adoption and commercial success. Since the manual creation of game content is not feasible in portable games, UGC remains as the only practical option for content provision. Notably, the impact of UGC has not been studied so far in the pervasive games literature. This article introduces Barbarossa, a pervasive role-playing game based on UGC. Barbarossa serves as a testbed for investigating the effect of UGC under diverse technical, functional and game play characteristics. The user trials of Barbarossa confirmed that the effective use of UGC can enhance the quality of experience perceived by players and indirectly serve as a useful orchestration tool. We also document best practices with respect to the effective use of UGC in pervasive games, which could be useful to future developers.
Comparison between 68 Ga-bombesin ( 68 Ga-BZH 3 ) and the cRGD tetramer 68 Ga-RGD 4 studies in an experimental nude rat model with a neuroendocrine pancreatic tumor cell line

Objectives: Receptor scintigraphy gains more interest for diagnosis and treatment of tumors, in particular for neuroendocrine tumors (NET). We used a pan-Bombesin analog, the peptide DOTA-PEG2-[D-tyr , b-Ala, Thi, Nle] BN(6-14) amide (BZH3). BZH3 binds to at least three receptor subtypes: the BB1 (Neuromedin B), BB2 (Gastrin-releasing peptide, GRP), and BB3. Imaging of aνb3 integrin expression playing an important role in angiogenesis and metastasis was accomplished with a Ga-RGD tetramer. The purpose of this study was to investigate the kinetics and to compare both tracers in an experimental NET cell line. Methods: This study comprised nine nude rats inoculated with the pancreatic tumor cell line AR42J. Dynamic positron emission tomography (PET) scans using Ga-BZH3 and Ga-RGD tetramer were performed (Ga-RGD tetramer: n = 4, Ga-BZH3: n = 5). Standardized uptake values (SUVs) were calculated, and a two-tissue compartmental learning-machine model (calculation of K1 k4 vessel density (VB) and receptor binding potential (RBP)) as well as a non-compartmental model based on the fractal dimension was used for quantitative analysis of both tracers. Multivariate analysis was used to evaluate the kinetic data. Results: The PET kinetic parameters showed significant differences when individual parameters were compared between groups. Significant differences were found in FD, VB, K1, and RBP (p = 0.0275, 0.05, 0.05, and 0.0275 respectively). The 56to 60-min SUV for Ga-BZH3, with a range of 0.86 to 1.29 (median, 1.19) was higher than the corresponding value for the Ga-RGD tetramer, with a range of 0.78 to 1.31 (median, 0.99). Furthermore, FD, VB, K1, and RBP for Ga-BZH3 were generally higher than the corresponding values for the Ga-RGD tetramer, whereas k3 was slightly higher for Ga-RGD tetramer. Conclusions: As a parameter that reflects receptor binding, the increase of K1 for Ga-BZH3 indicated higher expression of bombesin receptors than that of the aνb3 integrin in neuroendocrine tumors. Ga-BZH3 seems better suited for diagnosis of NETs owing to higher global tracer uptake.
An Internal Signal Sequence Mediates the Targeting and Retention of the Human UDP-Glucuronosyltransferase 1A6 to the Endoplasmic Reticulum*

The human UDP-glucuronosyltransferase isoform UGT1A6 is predicted to be a type I transmembrane protein anchored in the endoplasmic reticulum by a single C-terminal transmembrane domain, followed by a short cytoplasmic tail. This topology is thought to be established through the sequential action of a cleavable N-terminal signal peptide and of a C-terminal stop transfer/anchor sequence. We found that the deletion of the signal peptide did not prevent membrane targeting and insertion of this protein expressed in an in vitro transcription/translation system or in yeast Pichia pastoris. Interestingly, the same results were obtained when the protein was depleted of both the signal peptide and the C-terminal transmembrane domain/cytoplasmic tail sequences, suggesting the presence of an internal topogenic element able to translocate and retain UGT1A6 in the endoplasmic reticulum membrane in vitro and in yeast cells. To identify such a sequence, the insertion of several N-terminal deletion mutants of UGT1A6 into microsomal membranes was investigated in vitro. The data clearly showed that the deletion of the N-terminal end did not affect endoplasmic reticulum targeting and retention until residues 140–240 were deleted. The signal-like activity of the 140–240 region was demonstrated by the ability of this segment to confer endoplasmic reticulum residency to the cytosolic green fluorescent protein expressed in mammalian cells. Finally, we show that this novel topogenic sequence can posttranslationally mediate the translocation of UGT1A6. This study provides the first evidence that the membrane assembly of the human UGT1A6 involves an internal signal retention sequence.
Purification and identification of two antifungal cyclic dipeptides from Bacillus cereus subsp. thuringiensis associated with a rhabditid entomopathogenic nematode especially against Fusarium oxysporum

Abstract The cell-free culture filtrate of Bacillus cereus subsp. thuringiensis associated with an entomopathogenic nematode (EPN), Rhabditis (Oscheius) sp. , exhibited strong antimicrobial activity. The ethyl acetate extract of the bacterial culture filtrate was purified by silica gel column chromatography to obtain two cyclic dipeptides (CDPs). The structure and absolute stereochemistry of this compound were determined based on extensive spectroscopic analyses (FABMS, 1H NMR, 13C NMR, 1H--1H COSY, 1H--13C HMBC) and Marfey’s method. The compounds were identified as cyclo(D-Pro-L-Met) and cyclo(D-Pro-D-Tyr). CDPs showed significantly higher activity than the standard fungicide bavistin against agriculturally important fungi, viz., Fusarium oxysporum, Rhizoctonia solani and Penicillium expansum. The highest activity of 2 µg/ml by cyclo(D-Pro-D-Tyr) was recorded against F. oxysporum, a plant pathogen responsible for causing fusarium wilt followed by R. solani, a pathogen that causes root rot and P. expansum. To our knowledge, this is the first report on the isolation of these compounds from Rhabditis EPN bacterial strain Bacillus cereus subsp. thuringiensis.
Deep Breathing Exercises Performed 2 Months Following Cardiac Surgery: A RANDOMIZED CONTROLLED TRIAL

PURPOSE: Postoperative breathing exercises are recommended to cardiac surgery patients. Instructions concerning how long patients should continue exercises after discharge vary, and the significance of treatment needs to be determined. Our aim was to assess the effects of home-based deep breathing exercises performed with a positive expiratory pressure device for 2 months following cardiac surgery. METHODS: The study design was a prospective, single-blinded, parallel-group, randomized trial. Patients performing breathing exercises 2 months after cardiac surgery (n = 159) were compared with a control group (n = 154) performing no breathing exercises after discharge. The intervention consisted of 30 slow deep breaths performed with a positive expiratory pressure device (10-15 cm H2O), 5 times a day, during the first 2 months after surgery. The outcomes were lung function measurements, oxygen saturation, thoracic excursion mobility, subjective perception of breathing and pain, patient-perceived quality of recovery (40-Item Quality of Recovery score), health-related quality of life (36-Item Short Form Health Survey), and self-reported respiratory tract infection/pneumonia and antibiotic treatment. RESULTS: Two months postoperatively, the patients had significantly reduced lung function, with a mean decrease in forced expiratory volume in 1 second to 93 ± 12% (P< .001) of preoperative values. Oxygenation had returned to preoperative values, and 5 of 8 aspects in the 36-Item Short Form Health Survey were improved compared with preoperative values (P< .01). There were no significant differences between the groups in any of the measured outcomes. CONCLUSION: No significant differences in lung function, subjective perceptions, or quality of life were found between patients performing home-based deep breathing exercises and control patients 2 months after cardiac surgery.
Naftidrofuryl Inhibits Contractions to Serotonin in Intact and De‐endothelialized Cerebral Arteries in vitro

Excised segments of rabbit middle cerebral artery were cannulated and perfused in vitro at constant flow (1 ml/min). In vessels with intact endothelium, integrity of the intima was checked by determining relaxations to acetylcholine. In another series of segments, the endothelium was destroyed mechanically. Serotonin (5-HT) was added to the perfusate in increasing concentrations (3 × 10−10 to 10−4 M). Perfusion pressure served as the index of vasomotor responses of the arterial segment. At therapeutic concentrations, the 5-HT2 antagonist naftidrofuryl did not change perfusion pressure of normal vessels in the absence of 5-HT. Addition of 5-HT to intact vessels had no effect on perfusion pressure, but potentiated the contraction induced by KCl. This reaction was greatly amplified after de-endothelialization. Addition of naftidrofuryl (107 M) to the perfusate strongly inhibited 5-HTs contracting effects on both intact and deendothelialized arterial segments. Naftidrofuryl at 10−6 M further displaced the dose-effect curve to the right in a competitive manner. These data confirm the potentiating effect of 5-HT on vascular smooth muscle (even in intact vessels) and the anticonstricting effects of naftidrofuryl when 5-HT2 receptors on smooth muscle cells are activated by serotonin.
Quality of life in patients attending a low‐risk gynaecological oncology follow‐up clinic

Objectives: (1) To assess the quality of life (QOL) of patients who had been treated for gynaecological malignancies and who were attending a low risk follow‐up clinic. (2) To determine the accuracy of the clinic physicians' assessment of patients' QOL compared with the Functional Living Index—Cancer (FLI‐C) [Schipper et al., 1984. Measuring the quality of life of cancer patients: the Functional Living Index—Cancer: development and validation. J Clin Oncol 2(5): 472–483]. (3) To examine a single subjective question about change in QOL. (4) To assess patient fear of cancer recurrence.
Scientific authority in policy contexts: Public attitudes about environmental scientists, medical researchers, and economists

This paper uses data from the US General Social Survey to examine public support for scientists in policy contexts and its link to scientific disciplines. An analysis of attitudes about the amount of influence that environmental scientists, two kinds of medical researchers, and economists should have over policy decisions reveals that in each discipline the extent to which scientists are thought to serve the nation’s best interests is the strongest determinant of attitudes about scientists as policy advisors. Perceptions of scientists’ technical knowledge and the level of consensus in the scientific community also have direct, albeit weaker effects on opinions about scientists’ appropriate roles in policy settings. Whereas previous research has stressed the importance of local variability in understanding the transfer of scientific authority across institutional boundaries, these results point to considerable homogeneity in the social bases of scientific authority in policy contexts.
Commutability and concordance of four hepatitis B virus DNA assays in an international multicenter study

Background HBV DNA is the most important molecular marker in hepatitis B, used to determine treatment indication and monitoring. Most patients require lifelong hepatitis B virus (HBV) management, thus viral load (VL) monitoring may be performed at different laboratories, with different HBV assays, which may result in different VL results. This multicenter study compares the commutability and concordance of results from four different HBV DNA assays: CAP/CTM HBVv2, HPS/CTM HBVv2 and the new cobas 6800/8800 HBV and cobas 4800 HBV assays. Methods Across all four assays, HBV limit of detection (LoD) and linearity at lower concentrations were assessed using panels traceable to the World Health Organization international standard, and concordance was investigated at the important medical decision cutoffs 2000 and 20,000 IU/ml, using specimens from HBV-positive patients. Results The calculated LoD via a probit curve was 2.7 IU/ml for cobas 6800/8800 HBV, 2.8 IU/ml for cobas 4800 HBV, 9.6 IU/ml for CAP/CTM HBVv2, and 6.2 IU/ml for HPS/CTM HBVv2. The average accuracy was comparable between cobas 6800/8800 HBV, cobas 4800 HBV and CAP/CTM HBVv2 (0.04–0.05 log10 IU/ml), while a slightly lower accuracy was documented for HPS/CTM HBVv2 (−0.16 log10 IU/ml). A total of 211–245 clinical samples were used for a pairwise comparison. Mean paired log differences ranged from −0.17 log10 IU/ml to −0.01 log10 IU/ml. Coefficient of determination was over 98% for all pairs with high overall percent agreement at the 2000 and 20,000 IU/ml cutoffs (from 91.7% to 96.3%). In a subset of samples with VL±0.5 log10 to the 2000 and 20,000 IU/ml thresholds, concordance was still 72% and 82%, respectively. Conclusions The new cobas 6800/8800 HBV and 4800 HBV assays show high accuracy in samples with low-level viremia and a high concordance with the established HBV tests, CAP/CTM HBVv2 and HPS/CTM HBVv2, at 2000 and 20,000 IU/ml. Thus, all four HBV assays have high commutability and may be used interchangeably in routine clinical practice.
The nested h refinement in 2D FETD via the hanging variable technique

In this study, an initial concept of the h refinement in the FETD method with the hanging variable technique is presented. With the hanging variable method, intermediate elements are created to connect the refined and non-refined regions. With this approach, remeshing can be avoided and the refined mesh can have the same quality as the initial mesh. The numerical experiment in 2D indicates the initial success of our approach which leads to further study in the three dimensional h refinement for the FETD method with the hanging variable technique
Quality-of-life assessment after supradose selective intra-arterial cisplatin and concomitant radiation (RADPLAT) for inoperable stage IV head and neck squamous cell carcinoma.

OBJECTIVE To evaluate quality-of-life (QOL) aspects of an organ preservation intra-arterial chemotherapy and concomitant radiation protocol, RADPLAT. DESIGN Nonrandomized phase 2B feasibility trial. PATIENTS Fifty consecutive patients with inoperable stage IV head and neck cancer. INTERVENTION Supradose selective intra-arterial cisplatin and concomitant standard radiation (RADPLAT). MEASURES Assessment with structured questionnaires before treatment and at 3, 6, and 12 months. RESULTS Twenty-six patients were available for QOL assessment at 1 year (the "1-year QOL" group), as 16 patients died, 5 needed salvage surgery, and 3 were not available for interview (the "failure" group). Twelve-month results were mainly based on the first group. The functional well-being and head and neck scales showed a statistically significant improvement over time (P<.001). After 12 months, 21 patients (81%) returned to an oral diet, while 5 patients still needed tube feeding. For 23 patients (88%), the quality and strength of the voice was more or less normal. Of the 18 patients who were employed before their treatment, 10 were able to return to their job within 12 months. Xerostomia was reported by 17 patients (65%). Further detailed analysis showed statistically significant differences in pretreatment scores between the 1-year QOL group and the failure group, ie, physical well-being, functional well-being, and the head and neck scales (P<.05). Differences in these groups with respect to sex, age, tumor site, or stage could not be found. CONCLUSION Given that only patients with locally (anatomic or functional) inoperable stage IV disease were treated, the results are promising, underlining the feasibility of the RADPLAT protocol.
Fluid balance, thermoregulation and sprint and passing skill performance in female soccer players

Ten females performed 90 min of the Loughborough Intermittent Shuttle Test (LIST) on two occasions separated by 7 days. Water [3 mL/kg body mass (BM)] was provided every 15 min during exercise (FL); no fluid was given in the other trial (NF). Participants performed the Loughborough Soccer Passing Test (LSPT) before and every 15 min during the LIST. Core temperature (Tc) was measured throughout using ingestible temperature sensors. Heart rate (HR), blood lactate ([La−]) and ratings of perceived exertion (RPE) were collected at regular intervals during exercise. Participants experienced greater BM loss in NF (2.2 ± 0.4%) than FL (1.0 ± 0.4%; P<0.001). Sprint performance deteriorated by 2.7% during exercise (P<0.001) but there was no difference between trials (P=0.294). No significant differences in LSPT performance were detected between trials (P=0.31). Tc was higher during exercise in NF and was 38.6 ± 0.3 °C (NF) and 38.3 ± 0.3 °C (FL; P<0.01) after 90 min. HR (P<0.001), [La−] (P<0.01) and RPE (P=0.009) were higher during exercise in NF. Ingesting water during a 90‐min match simulation reduces the mild dehydration seen in female soccer players when no fluid is consumed. However, there was no effect of fluid ingestion on soccer passing skill or sprint performance.