Miracle-dz/UniFAR-FTUs huggingface dataset:
Control of Proliferation, Migration, and Invasiveness of Human Extravillous Trophoblast by Decorin, a Decidual Product1

Abstract Extravillous trophoblast (EVT) cells of the human placenta progressively lose their proliferative activity in situ as EVT cell columns migrate into and invade the decidua. It remains unclear whether this is due to a terminal differentiation of EVT cells along the invasive pathway with concomitant loss of proliferative ability, or a negative regulation by decidua-derived factors, or both mechanisms. Our earlier studies provided evidence for a negative regulation by a decidua-derived factor, transforming growth factor (TGF)-β, which inhibited proliferation, migration, and invasiveness of first-trimester EVT cells in vitro. We further discovered that decidua also produces decorin, a proteoglycan that binds TGF-β (and in some cases, inactivates TGF-β), which is colocalized with TGF-β in the decidual extracellular matrix. The present study used in vitro-propagated EVT cell lines to examine whether EVT cells retain their capacity for proliferation after the process of invasion; and whether decorin exerts any effect on EVT cell proliferation, migration, or invasiveness in a TGF-β-dependent or TGF-β-independent manner. We also examined whether trophoblastic cancer (choriocarcinoma) JAR and JEG-3 cells responded to decorin in a similar manner. Proliferation was measured using a colorimetric (MTT) cellularity assay and immunolabeling for the Ki-67 proliferation marker. Migration and invasiveness were measured in transwells by the ability of cells to cross 8-μm pores of polycarbonate membranes in the absence or presence of an additional matrigel barrier. These experiments revealed three points. First, EVT cells retained limited but significant proliferative ability in vitro after invading matrigel. Second, that decorin alone blocked EVT cell proliferation in a dose-dependent manner. This effect remained unaffected in an additional presence of TGF-β, which exerted antiproliferative effects on its own. The antiproliferative effect of decorin was explained by an up-regulation of the p21 protein. Third, that decorin alone or TGF-β alone exerted antimigratory and anti-invasive effects on EVT cells, but the addition of TGF-β to decorin did not alter decorin action. And fourth, that choriocarcinoma cells were resistant to antiproliferative, antimigratory, and anti-invasive effects of decorin. These results suggest 1) that the invasive function of EVT cells is not associated with a terminal differentiation into a noncycling state; 2) that proliferation, migration, and invasiveness of EVT cells within the decidua are independently controlled by two decidual products, TGF-β and decorin (decorin in the decidual extracellular matrix may serve as a storage mechanism for TGF-β in an inactive state and may be activated by EVT cell proteolytic mechanisms, thus preventing overinvasion); and 3) that choriocarcinoma cells are refractory to negative regulation by both decidua-derived factors.
Selective radiosensitization of p53 mutant pancreatic cancer cells by combined inhibition of Chk1 and PARP1

We have recently shown that inhibition of HRR (homologous recombination repair) by Chk1 (checkpoint kinase 1) inhibition radiosensitizes pancreatic cancer cells and others have demonstrated that Chk1 inhibition selectively sensitizes p53 mutant tumor cells. Furthermore, PARP1 [poly (ADP-ribose) polymerase-1] inhibitors dramatically radiosensitize cells with DNA double strand break repair defects. Thus, we hypothesized that inhibition of HRR (mediated by Chk1 via AZD7762) and PARP1 [via olaparib (AZD2281)] would selectively sensitize p53 mutant pancreatic cancer cells to radiation. We also used 2 isogenic p53 cell models to assess the role of p53 status in cancer cells and intestinal epithelial cells to assess overall cancer specificity. DNA damage response and repair were assessed by flow cytometry, γH2AX, and an HRR reporter assay. We found that the combination of AZD7762 and olaparib produced significant radiosensitization in p53 mutant pancreatic cancer cells and in all of the isogenic cancer cell lines. The magnitude of radiosensitization by AZD7762 and olaparib was greater in p53 mutant cells compared with p53 wild type cells. Importantly, normal intestinal epithelial cells were not radiosensitized. The combination of AZD7762 and olaparib caused G2 checkpoint abrogation, inhibition of HRR, and persistent DNA damage responses. These findings demonstrate that the combination of Chk1 and PARP1 inhibition selectively radiosensitizes p53 mutant pancreatic cancer cells. Furthermore, these studies suggest that inhibition of HRR by Chk1 inhibitors may be a useful strategy for selectively inducing a BRCA1/2 ‘deficient-like’ phenotype in p53 mutant tumor cells, while sparing normal tissue.
Sources of Measurement Variation in Blood Pressure in Large-scale Epidemiological Surveys with Follow-up

The Copenhagen City Heart Study (CCHS) is a longitudinal epidemiological study of 19698 subjects followed up since 1976. Variation in blood pressure (BP) measurement in the first three CCHS surveys is evaluated by assessing two components, systematic variation and random variation [daytime and seasonally variation, observer bias, non-response bias, variation with explanatory variables, such as diabetes, hypertension, body mass index (BMI), height, plasma cholesterol and smoking] for the purpose of identifying relevant errors in population surveys. BP was measured in the seated position after a 5 min rest, with the cuff around the non-dominating arm, in accordance with recommended guidelines. The participation rate fell from 74% in survey 1 to 63% in survey 3. Significant non-response bias with respect to BP values was not found. No daytime variability was noted either in systolic (SBP) or diastolic (DBP) BPs. A trend towards a lower BP was seen during the summertime. Random variation, expressed as the standard deviation of the measured values, increased with increasing BP values (SBP: 11.9-13.4 to 21.2- 25.1 mmHg; DBP: 10.6-11.2 to 11.9-13.4 mmHg). SBP was positively correlated to BMI and plasma cholesterol. SBP was 5-10 mmHg higher in diabetics ( p = 0.000-0.04) than in age- and sex-matched nondiabetics. DBP did not differ between the two groups. Smokers from the age of 50 years had a 2-4 mmHg lower SBP ( p = 0.000-0.01) and 1-3 mmHg lower DBP ( p = 0.000-0.005) than had non-smokers. In addition, significantly fewer smokers took antihypertensive medication than did non-smokers ( p = 0.000). In conclusion, judging from the degree of association with BP and/or differences between the three surveys, the most important factors to consider were seasonal variation, BMI, the use of antihypertensive drug therapy, plasma cholesterol, smoking status and diabetes. An inter-survey comparison of BP in population cohorts requires controlling for these factors.
Technical reliability of the CSA activity monitor: The EarlyBird Study.

PURPOSE To evaluate the technical performance of the CSA accelerometer-based activity monitor. METHODS Twenty-three CSA monitors were subjected to intra- and inter-instrument variability tests by controlled trials using a motorized turntable. The CSA monitor measures change in acceleration, and precision was tested by producing sinusoidal variations in speed around two fixed baseline speeds (fast and medium). The angle of the monitor to the line of force along the radius of the turntable was varied using tilted blocks. Three sets of tests were carried out. 1. Intra-instrument variability: seven monitors were tested three times in each of the four quadrants. 2. All 23 monitors were used for inter-instrument tests. 3. The effects of tilt at 15 degrees, 30 degrees, and 45 degrees were carried out on six monitors. RESULTS Intra-instrument coefficients of variation (CV) never exceeded 2% for fast or medium speed and achieved "between run" intra-class correlation coefficients (ICC) of 0.92 and 0.84 respectively. There were no significant differences between the monitors in terms of repeatability (fast: = 0.97, medium: = 0.77). Although there were significant differences between monitors in terms of mean score, inter-instrument variability did not exceed 5% at either speed. Inter-batch ICCs ranged from 0.87 to 0.98 for fast and from 0.71 to 0.99 for medium. The angle test results corresponded closely to those predicted theoretically, with a loss in mean score of only 6% when the monitor was tilted from 0 degrees to 15 degrees. CONCLUSION The CSA monitor provides a precise tool for measuring changes in acceleration in laboratory settings. Technically, the device performs well, and is likely to prove a useful tool in the assessment of physical activity in children and adults.
Influence of Neck Proprioception on Vibration-induced Postural Sway

Objective --Several reports have shown that the direction of the postural responses induced by vestibular stimulation is affected by the positions of the neck and torso. The aim of this study was to investigate whether the postural responses to vibratory proprioceptive stimulation of the calf muscles are affected by the position of the head and thus by proprioceptive and vestibular information from the neck and head. Material and Methods --Ten normal subjects were exposed to vibratory proprioceptive stimulation of the calf muscles when the head was maintained in five different positions: in a neutral position facing forwards, with the head turned to the right or left sides or with the head tilted backwards or forwards. Body movements were evaluated by analyzing the anteroposterior and lateral torques induced towards the supporting surface. Results --The analysis showed that only the anteroposterior body sway was significantly affected by the position of the head. The anteroposterior postural responses were primarily increased during the tests with the head tilted backwards or forwards, whereas the postural responses were unaffected by head torsion towards the sides. The lateral responses were primarily affected by vision and not by the position of the head. Conclusion --The findings suggest that the responses evoked by vibratory proprioceptive stimulation of the calf muscles may be affected by different mechanisms, either by purely proprioceptive information or by an interaction between proprioceptive and vestibular information. Moreover, the increasing difference between the test conditions over time suggests that fatigue of the neck muscles may be one of the factors affecting the responses induced by the perturbations.
Comparison of outcome after patent foramen ovale closure in older versus younger patients.

AIMS Percutaneous patent foramen ovale (PFO) closure seems to be effective for secondary prevention of cryptogenic stroke in patients younger than 55 years of age. The efficacy in older patients remains uncertain. We compared the efficacy of PFO closure between patients younger and older than 55 years. METHODS AND RESULTS All 335 patients (mean age 50.2 ± 12.6 years; 205 men) with cryptogenic thromboembolism who underwent PFO closure in our centres between 1998 and 2008 were included. Mean follow-up period was 4.2 ± 1.9 years in the elderly (n=120) and 3.8 ± 2.4 years in the younger patients (n=215) (p=0.15). Prevalence of hypertension, diabetes, hyperlipidaemia and coronary and peripheral artery disease was higher in the elderly (p<0.05 for all). Re-occurrence of stroke or TIA was higher in the elderly compared to the younger (annual event rate 2.4% versus 0.6%; log rank, p=0.005). Re-occurrence of stroke alone was higher in the elderly (annual event rate 1.2% versus 0.1%; log rank, p=0.01). Multivariate analysis showed that an age of >55 years was an independent predictor of recurrent stroke or TIA (HR 3.2, p=0.03). CONCLUSIONS Percutaneous PFO closure appears to be effective for secondary prevention of cryptogenic stroke in younger patients but seems to be related with less beneficial outcome in elderly. Randomised controlled trials are needed to confirm our findings.
Electrocochleography in Meniere's disease: recovery from adaptation of the auditory action potential

Abstract Conclusions: High prevalence rate of an enhanced summating potential (SP)/action potential (AP) ratio (≥0.35) is considered to result largely from the imbalances of Ca2+ homeostasis in the endolymphatic space. An increase in Ca2+ is thought to augment the SP. Furthermore, a greater inflow of Ca2+ into inner hair cells is supposed to influence the disturbed release of neurotransmitter, which may induce pathological functioning of inner hair cell synapses. We speculate that such abnormal synaptic functioning is responsible for the development of abnormally increased AP recovery from adaptation (iR). Objectives: This study aimed to record the AP recovery from adaptation (AP recovery) and to investigate its clinical significance in association with other electrocochleography (ECochG) findings in Meniere's disease. Methods: ECochG was performed transtympanically in 27 patients with Meniere's disease. AP recovery was measured by a paired-click stimulation paradigm as a function of interclick intervals from 5 to 100 ms. Results: High prevalence of SP/AP ratio was observed in 27 patients. iR, suggesting abnormal functioning of inner hair cell synapse, was in many cases combined with an enhanced SP/AP ratio.
STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: A critical role of STAT3 in innate immunity

Signal transducer and activator of transcription 3 (STAT3) is a key transcriptional mediator for many cytokines and is essential for normal embryonic development. We have generated a unique strain of mice with tissue-specific disruption of STAT3 in bone marrow cells during hematopoiesis. This specific STAT3 deletion causes death of these mice within 4–6 weeks after birth with Crohn's disease-like pathogenesis in both the small and large intestine, including segmental inflammatory cell infiltration, ulceration, bowel wall thickening, and granuloma formation. Deletion of STAT3 causes significantly increased cell autonomous proliferation of cells of the myeloid lineage, both in vivo and in vitro. Most importantly, Stat3 deletion during hematopoiesis causes overly pseudoactivated innate immune responses. Although inflammatory cytokines, including tumor necrosis factor α and IFN-γ, are overly produced in these mice, the NAPDH oxidase activity, which is involved in antimicrobial and innate immune responses, is inhibited. The signaling responses to lipopolysaccharide are changed in the absence of STAT3, leading to enhanced NF-κB activation. Our results suggest a model in which STAT3 has critical roles in the development and regulation of innate immunity, and deletion of STAT3 during hematopoiesis results in abnormalities in myeloid cells and causes Crohn's disease-like pathogenesis.
Infusion of long-chain fatty acids varying in saturation and chain length into the abomasum of lactating dairy cows.

Free long-chain fatty acids were infused into the abomasum of lactating dairy cows to determine postruminal effects on feed intake, production and composition of milk, nutrient digestibilities, and metabolites in blood. Four Holstein cows averaging 120 DIM and fitted with ruminal cannulas were used in a 4 x 4 Latin square design with 14-d periods. Treatments were abomasal infusions of 1) control, 168 g/d of meat solubles (carrier for fatty acids), 2) control plus 450 g/d of mostly saturated fatty acids (C16:C18 = .75), 3) control plus 450 g/d of a mixture of saturated and unsaturated fatty acids (C16:C18 = .40), and 4) control plus 450 g/d of mostly unsaturated fatty acids (C16:C18 = .11). Production of milk and milk components, DMI, and intake of digestible energy decreased linearly as unsaturation and chain length of infused fatty acids increased. Percentages of fat, CP, and SNF in milk and total tract apparent digestibilities of DM, OM, ADF, NDF, energy, and fatty acids were not affected significantly by treatments. Infusing fatty acids decreased proportions and yields of short- and medium-chain fatty acids and increased proportions and yields of unsaturated C18 fatty acids in milk fat. Increasing unsaturation and chain length of infused fatty acids linearly decreased proportion and yield of palmitic acid but increased proportions and yields of polyunsaturated C18 fatty acids in milk fat. Infusing fatty acids increased concentrations of NEFA and cholesterol in blood plasma. The profile of fatty acids reaching the intestine may be an important determinant of responses to supplemental fats fed to lactating dairy cows.
Support vector method for minutiae detection in fingerprint images

Fingerprint minutiae (i.e. ridge endings and ridge bifurcations) form a pattern that is unique to each fingerprint. Almost all automatic fingerprint comparison systems rely on minutiae matching, and hence the minutiae extraction from fingerprint images highly influences the performance of every such system. A minutiae extraction method based on support vector machines is proposed here. The method does not require a ridge thinning processing step in contrast with most of the previously proposed methods of minutiae detection and classification. Because of this, the number of spurious minutiae detected is maintained low, such that a subsequent processing step of spurious minutiae elimination becomes unnecessary.
Clinical outcomes and toxicities of proton radiotherapy for gastrointestinal neoplasms: a systematic review.

BACKGROUND Proton beam radiotherapy (PBT) is frequently shown to be dosimetrically superior to photon radiotherapy (RT), though supporting data for clinical benefit are severely limited. Because of the potential for toxicity reduction in gastrointestinal (GI) malignancies, we systematically reviewed the literature on clinical outcomes (survival/toxicity) of PBT. METHODS A systematic search of PubMed, EMBASE, abstracts from meetings of the American Society for Radiation Oncology, Particle Therapy Co-Operative Group, and American Society of Clinical Oncology was conducted for publications from 2000-2015. Thirty-eight original investigations were analyzed. RESULTS Although results of PBT are not directly comparable to historical data, outcomes roughly mirror previous data, generally with reduced toxicities for PBT in some neoplasms. For esophageal cancer, PBT is associated with reduced toxicities, postoperative complications, and hospital stay as compared to photon radiation, while achieving comparable local control (LC) and overall survival (OS). In pancreatic cancer, numerical survival for resected/unresected cases is also similar to existing photon data, whereas grade ≥3 nausea/emesis and post-operative complications are numerically lower than those reported with photon RT. The strongest data in support of PBT for HCC comes from phase II trials demonstrating very low toxicities, and a phase III trial of PBT versus transarterial chemoembolization demonstrating trends towards improved LC and progression-free survival (PFS) with PBT, along with fewer post-treatment hospitalizations. Survival and toxicity data for cholangiocarcinoma, liver metastases, and retroperitoneal sarcoma are also roughly equivalent to historical photon controls. There are two small reports for gastric cancer and three for anorectal cancer; these are not addressed further. CONCLUSIONS Limited quality (and quantity) of data hamper direct comparisons and conclusions. However, the available data, despite the inherent caveats and limitations, suggest that PBT offers the potential to achieve significant reduction in treatment-related toxicities without compromising survival or LC for multiple GI malignancies. Several randomized comparative trials are underway that will provide more definitive answers.
Optimisation of client trust by evolutionary learning of financial planning strategies in an agent based model

In this paper we demonstrate how evolutionary learning can be employed to learn a fuzzy knowledge base (FKB) utilised in strategic decision making among financial planning advisors (FPAs). This is accomplished by building an agent based model (ABM) simulating the process of wealth management between clients and financial planning advisors. The agent based model is implemented in Java using RePast (RePast URL) as the agent based modelling toolkit. Due to the complex nature of the decision making process, fuzzy logic (FL) is used to represent behavioural rules of the agents in this multi-agent based simulation. We show how the proposed evolutionary learning process could be employed in maximising the clients' trust towards their FPA as well as their own financial wellbeing. Towards the end of the paper, the results obtained using the RePast based simulation are presented showing the advantages of the evolutionary learning process in the context of optimising FPA-client relationships and how it helps to adapt FPA strategies to reduce the number of clients, who leave their FPA and invest elsewhere
Land cover type and biomass classification using AirSAR data for evaluation of monitoring scenarios in the Colombian Amazon

The potential role of a spaceborne SAR component within a dedicated global monitoring system for tropical rain forest areas is investigated. Use is made of NASA's airborne radar system AirSAR, which acquired C-band, L-band, and P-band polarimetric data of a colonization area located at the edge of the Colombian Amazon. Classification accuracy for primary forest, secondary forest, recently deforested areas, and pastures are studied to determine optimal wave parameter combinations, using an extensive database of 778 plots. Kappa statistics are used to compare results for different combinations. The relevance of polarimetry and the effect of speckle level are studied by incorporating the multilook pdf's of polarimetric phase differences and the polarimetric correlations. Kolmogorov-Smirnov tests of fit well confirm the agreement of theoretical pdf's used and experimental observations. In addition, possibilities for biomass estimation are studied using detailed vegetation structure measurements of bush-invaded grasslands (5 plots), secondary forest (10 plots), and primary forest (13 plots). Accuracy for land cover-type classification over 90% can only be obtained when two frequency bands are combined. L-band with HV polarization and P-band show the best possibilities for biomass estimation. After land cover-type classification, eight biomass classes can be differentiated at a high level of confidence. The results clearly indicate how SAR systems may be designed to accurately monitor processes of deforestation, land and forest degradation, and secondary forest regrowth. The effect of Faraday rotation on P-band data collected from spaceborne SAR is also taken into consideration.