Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigation of procoagulant activity in extracellular vesicles isolated by differential ultracentrifugation

ABSTRACT Tissue factor (TF) is the main initiator of coagulation and procoagulant phospholipids (PPL) are key components in promoting coagulation activity in blood. Both TF and PPL may be presented on the surface of extracellular vesicles (EVs), thus contributing to their procoagulant activity. These EVs may constitute a substantial part of pathological hypercoagulability that is responsible for triggering a higher risk of thrombosis in certain patients. The aim of this study was to describe a model system for the isolation of EVs required for investigating their effect on coagulation. Differential ultracentrifugation (DUC) with and without a single washing step was used to isolate and evaluate the procoagulant capacity of EVs from healthy volunteers through analysis of thrombin generation and PPL activity. Ultracentrifugation at 20,000 × g and 100,000 × g resulted in pellets containing larger vesicles and smaller vesicles, respectively. Isolation yield of particle concentration was assessed by nanoparticle tracking analysis. Immunoelectron microscopy and western blotting revealed vesicles positive for the commonly used EV-marker CD9. Plasma proteins and lipoproteins were co-isolated with the EVs; however, application of a washing step clearly diminished the amount of contaminants. The isolated EVs were capable of enhancing thrombin generation, mainly due to PPL predominantly present in pellets from 20,000 × g centrifugation, and correlated with the activity measured by a PPL activity assay. Thus, DUC was proficient for the isolation of EVs with minimal contamination from plasma proteins and lipoproteins, and the setup can be used to study EV-associated procoagulant activity. This may be useful in determining the procoagulant activity of EVs in patients at potentially increased risk of developing thrombosis, e.g. cancer patients. Abbreviations: TF: Tissue factor; PL: Phospholipids; EVs: Extracellular vesicles; FXa: Activated coagulation factor X; TGA: Thrombin generation assay; PPL: Procoagulant phospholipids; DUC: Differential ultracentrifugation; NTA: Nanoparticle tracking analysis; TEM: Transmission electron microscopy; SPP: Standard pool plasma; CTI: Corn trypsin inhibitor; 20K: 20,000 × g; 100K: 100,000 × g; FVIII: Coagulation factor VIII
In Vitro Wound Healing Model: Effects of Chitosan Films Loaded with Gentamicin and Silver Sulfadiazine on the Wound Filling Rate

Currently, animals use in research experiments has been widely questioned by Animal Protect Institutions and Organizations. Moreover, preliminary tests and scientific validation of research hypothesis are required before in vivo tests approval. Thus, animal testing could take a long time. For all these reasons, the development of an in vitro test that could simulate and/or replace animal research would be very interesting. The aim of this work was the development of an in vitro wound healing model for evaluation of the healing potential of drug-loaded cross-linked chitosan films. MG-63, a cell line derived from human osteosarcoma, was used as cell line model. The monolayer was cultured and when 100% confluence was reached, a wound was created using a scraper. The healing process was evaluated for 21 days and cells were stained after 0, 7, 14 and 21 days of incubation. Wounds were treated with chitosan film (CH), chitosanbisulfite blocked diisocyanate cross-linked film (CH-X), chitosan cross-linked film loaded with gentamicin (CH-X-GE) and chitosan cross-linked film loaded with silver sulfadiazine (CH-X-SS). The effects of chitosan (CH), bisulfite blocked diisocyanate (BBDI), gentamincin (GE) and silver sulfadiazine (SS) on the wound healing response were microscopically analyzed by the wound filling rate. CH and CH-X films did not show deleterious effects on cell growth compared to the positive control (no film) during the studied period. CH-X-GE demonstrated a reduced wound filling rate at the first week due to the burst release of gentamicin at this period. CH-X-SS showed reduced wound filling rates during all period studied probably due to silver cytotoxicity and its accumulation by the cells. Finally, in vitro wound healing rates were compared to in vivo results reported in the Literature. Similar behavior was observed, suggesting that the proposed in vitro wound healing model could potentially replace preliminary in vivo studies.
A centennial record of fluvial organic matter input from the discontinuous permafrost catchment of Lake Torneträsk

[1] High-latitude regions are underlain by the most organic carbon (OC)-rich soils on earth and currently subject to intense climate warming, potentially increasing remobilization and mineralization of soil OC. Sub-Arctic Scandinavia is located on the 0°C mean annual isotherm and is therefore particularly vulnerable to climate change. This study aimed to establish a baseline for soil OC release over the past century into Lake Tornetrask, the largest lake in sub-Arctic Scandinavia, through bulk geochemical and molecular radiocarbon analyses in chronologically constrained sediment cores. Our results suggest a dominance of peat-derived terrestrial OC inflow. We show that the annual terrestrial OC inflow to the lake is ∼12 times higher than the in-lake produced particulate OC, and consists for a large part (ca. 60%) of old OC from deep reservoirs in the catchment. The sedimentary record shows signs of increasing inflow of more degraded terrestrial matter since ∼1975, as indicated by increasing %TOC concentrations, a lowerδ13C value and lower TOC:TN ratios. Based on simultaneous changes in local climate and reported signs of permafrost degradation (e.g., active layer deepening, mire/peat erosion), the observed changes in the sedimentary record of Scandinavia's largest mountain lake likely reflect a climate warming-induced change in terrestrial OC inflow.
Comparison of Arterial Oxygenation Following Head-Down and Head-Up Laparoscopic Surgery

Background Regarding the role of gas entry in abdomen and cardiorespiratory effects, the ability of anesthesiologists would be challenged in laparoscopic surgeries. Considering few studies in this area and the relevance of the subject, this study was performed to compare the arterial oxygen alterations before operation in comparison with after surgery between laparoscopic cholecystectomy and ovarian cystectomy. Methods In this prospective cohort, 70 consecutive women aged from 20 to 60 years who were candidate for laparoscopic cholecystectomy (n = 35) and ovarian cystectomy (n = 35) with reverse (20 degrees) and direct (30 degrees) Trendelenburg positions, respectively, with ASA class I or II were enrolled. After intubation and before operation, for the first time, the arterial blood gas from radial artery in supine position was obtained for laboratory assessment. Then, the second blood sample was collected from radial artery in supine position and sent to the lab to be assessed with the same device after 30 minutes from surgery termination. The measured variables from arterial blood gas were arterial partial pressure of oxygen (PaO2) and Oxygen saturation (SpO2) alterations. Results Total PaO2 was higher in the first measurement. The higher values of PaO2 in cholecystectomy (upward) than in ovarian cystectomy (downward) were not significant in univariate (P = 0.060) and multivariate analysis (P = 0.654). Furthermore, higher values of SpO2 in cholecystectomy (upward) than in ovarian cystectomy (downward) were not significant in univariate (P = 0.412) and multivariate analysis (P = 0.984). Conclusions In general, based on the results of this study, the values of PaO2 in cholecystectomy (upward) were not significantly higher than the values in cystectomy (downward) in laparoscopic surgeries when measured 30 minutes after surgery.
BEHAVIORAL REPERTORY OF THE NEOTROPICAL HARVESTMAN ILHAIA CUSPIDATA (OPILIONES, GONYLEPTIDAE)

Abstract In this study, we provide an ethogram for the harvestman Ilhaia cuspidata and describe the daily activity pattern of captive individuals. We also provide a comparison between the behavioral repertory of this species with that of the syntopic Discocyrtus oliverioi. Five females and four males of I. cuspidata were maintained in the same terrarium from November 1999–November 2000 for qualitative and quantitative observations. Twenty behavioral acts were recorded, classified in seven categories and the relative frequency of each was determined: exploration (69.8%), resting (16.7%), feeding (6.3%), grooming (4.4%), social interactions (2.6%), reproduction (0.1%) and others (0.3%). There was a marked difference in the frequency of the behavioral categories between sexes: females fed more frequently than males and males were involved in social interactions more frequently than females. During most of the daylight hours, individuals remained inside shelters and became active from 19:00–09:00 h. Although I. cuspidata and D. oliverioi showed almost the same behavioral acts, there were quantitative differences in their repertories: the relative frequency of behavioral categories “resting” and “social interactions” were higher for I. cuspidata whereas “reproduction” and “grooming” were higher for D. oliverioi. The main qualitative difference between these two species was related to the forms of parental care: females of D. oliverioi guard their eggs and first instar juveniles, whereas females of I. cuspidata scatter their eggs in time and space and do not actively protect their offspring. Since both species share the same habitats (sometimes in multi-species aggregations), the behavioral differences between them may be explained by particular morphological and physiological characteristics of the species, as well as by phylogenetic constraints.
Statistical Discrimination or Prejudice? A Large Sample Field Experiment

Abstract A model of racial discrimination provides testable implications for two features of statistical discriminators: differential treatment of signals by race and heterogeneous experience that shapes perception. We construct an experiment in the U.S. rental apartment market that distinguishes statistical discrimination from taste-based discrimination. Responses from over 14,000 rental inquiries with varying applicant quality show that landlords treat identical information from applicants with African American– and white-sounding names differently. This differential treatment varies by neighborhood racial composition and signal type in a manner consistent with statistical discrimination and in contrast to patterns predicted by a model of taste-based discrimination.
High-Pressure Acceleration of Nanoliter Droplets in the Gas Phase in a Microchannel

Microfluidics has been used to perform various chemical operations for pL–nL volumes of samples, such as mixing, reaction and separation, by exploiting diffusion, viscous forces, and surface tension, which are dominant in spaces with dimensions on the micrometer scale. To further develop this field, we previously developed a novel microfluidic device, termed a microdroplet collider, which exploits spatially and temporally localized kinetic energy. This device accelerates a microdroplet in the gas phase along a microchannel until it collides with a target. We demonstrated 6000-fold faster mixing compared to mixing by diffusion; however, the droplet acceleration was not optimized, because the experiments were conducted for only one droplet size and at pressures in the 10–100 kPa range. In this study, we investigated the acceleration of a microdroplet using a high-pressure (MPa) control system, in order to achieve higher acceleration and kinetic energy. The motion of the nL droplet was observed using a high-speed complementary metal oxide semiconductor (CMOS) camera. A maximum droplet velocity of ~5 m/s was achieved at a pressure of 1–2 MPa. Despite the higher fluid resistance, longer droplets yielded higher acceleration and kinetic energy, because droplet splitting was a determining factor in the acceleration and using a longer droplet helped prevent it. The results provide design guidelines for achieving higher kinetic energies in the microdroplet collider for various microfluidic applications.
In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes

In vitro folate deficiency is associated with S phase accumulation and apoptosis in various cell types. To investigate the role of p53 and two apoptosis-related molecules, bcl-2 and Fas antigen (Apo-1, CD95), in the mechanism whereby folate-deficient lymphocytes accumulate and undergo apoptosis in the S phase, normal human peripheral blood lymphocytes were cultured for 3–9 d in control medium or in specially ordered and formulated HAM’ F-10 medium lacking folic acid, thymidine and hypoxanthine. Cells were stimulated with phytohaemagglutinin for the final 72 h prior to harvesting. The results indicate that p53 expression was downregulated in folate-deficient lymphocytes when compared with the control lymphocytes during the relevant period of S phase accumulation and apoptosis. In addition, folate deficiency was also found to downregulate IL-2, Fas antigen and bcl-2 expression, in terms of either mRNA or protein levels. The downregulation of Fas antigen suggests that folate deficiency-induced apoptosis probably does not occur via the Fas pathway. As IL-2 is a known inducer of bcl-2, and the downregulation of bcl-2 induces apoptosis, the downregulation of IL-2 and bcl-2 is suggested to play an important role in apoptosis. The complete rescue of folate-deficient lymphocytes from apoptosis was achieved by folic acid, thymidine or hypoxanthine alone or thymidine and hypoxanthine in combination. These results suggest that IL-2 depletion by folate deficiency in lymphocytes reduces the bcl-2 level, thereby triggering deoxynucleoside triphosphate pool imbalance and p53-independent apoptosis.
Case-finding instruments for depression. Two questions are as good as many.

OBJECTIVE To determine the validity of a two-question case-finding instrument for depression as compared with six previously validated instruments. DESIGN The test characteristics of a two-question case-finding instrument that asks about depressed mood and anhedonia were compared with six common case-finding instruments, using the Quick Diagnostic Interview Schedule as a criterion standard for the diagnosis of major depression. SETTING Urgent care clinic at the San Francisco Department of Veterans Affairs Medical Center. PARTICIPANTS Five hundred thirty-six consecutive adult patients without mania or schizophrenia. MEASUREMENTS AND MAIN RESULTS Measurements were two questions from the Primary Care Evaluation of Mental Disorders patient questionnaire, both the long and short forms of the Center for Epidemiologic Studies Depression Scale, both the long and short forms of the Book Depression Inventory, the Symptom-Driven Diagnostic System for Primary Care, the Medical Outcomes Study depression measure, and the Quick Diagnostic Interview Schedule. The prevalence of depression, as determined by the standardized interview, was 18% (97 of 536). Overall, the case-finding instruments had sensitivities of 89% to 96% and specificities of 51% to 72% for diagnosing major depression. A positive response to the two-item instrument had a sensitivity of 96% (95% confidence interval [CI], 90-99%) and a specificity of 57% (95% CI 53-62%). Areas under the receiver operating characteristic curves were similar for all of the instruments, with a range of 0.82 to 0.89. CONCLUSIONS The two-question case-finding instrument is a useful measure for detecting depression in primary care. It has similar test characteristics to other case-finding instruments and is less time-consuming.
Identification of Novel Metabolic Pathways of Sitagliptin (STG) by LC/MS and LC/MS2 after Incubations with Rat Hepatocytes

Sitagliptin (STG), a drug for treating Type Ii Diabetes Mellitus (T2DM), has been associated with severe joint pain in some patients. In this paper the metabolic profile of the drug has been investigated in order to determine metabolism and formation of reactive compounds which may contribute to this adverse effect. Metabolism of STG was investigated in vitro by incubation with freshly isolated Sprague-Dawley rat hepatocytes, to characterize Phase I and II metabolites, and the reaction mixture analysed on a zwitter ionic hydrophilic interaction (ZIC®-HILIC) column using LC-MS and LC-MS2 utilising electrospray ionization (ESI) in the positive ion mode. STG was metabolised to yield eleven metabolites, but in total only 3.1% of the parent drug was metabolised over 2 hrs incubation. These metabolites were structurally characterized on the basis of accurate mass analyses and the major metabolic routes for STG determined to be via aromatic oxidation (0.86%) and desaturation of N-C and C-C of the piperazine (0.44%). Novel metabolites of STG detected using these methods included STG N-glucuronide (M6) and a di-ketone metabolite (M4), hydroxylation of both the amine group and aromatic ring followed by formation of glucuronide metabolites (M5, M5’), oxidative desaturation of NH2 and di-hydroxylation of metabolites followed by loss of HF. Also, observed was an N-sulfate metabolite (0.07%) and acetylation followed by glucuronide conjugation was also found in trace amounts (<0.01%). MS2 fragment ions provide additional structural confirmation providing a possible structure for most metabolites such as by fragment ion loss of the glucuronide group (176 Da) from metabolite M5 and loss of the phenolic sulfate (80 Da) of N-Sulfate metabolite (M7). Reduction reaction of piperazine ring probably generates highly electrophilic metabolite of STG, which may be susceptible to produce adverse effects. Furthermore, N-oxidation reaction forming reactive intermediates metabolic to give a hydroxylamine metabolite that may undergo further reactions to yield electrophilic intermediate metabolites.
A NeuRetrieval Model for Human-Computer Conversations

To establish an automatic conversation system between human and computer is regarded as one of the most hardcore problems in computer science. It requires interdisciplinary techniques of information retrieval, natural language processing, data management as well as artificial intelligence. The arrival of big data era reveals the feasibility to create a conversation system empowered by data-driven approaches. Now we are able to collect extremely large conversational data on Web, and organize them to launch a human-computer conversation system. Owing to the diversity of Web resources available, a retrieval-based conversation system will be able to find at least some responses from the massive data repository for any user inputs. Given a human issued utterance, i.e., a query, a retrieval-based conversation system will search for appropriate replies, conduct a relevance ranking, and then output the highly relevant one as the response. In this paper, we propose a novel retrieval model named NeuRetrieval for short text understanding, representation and semantic matching. The proposed model is general and unified for both single-turn and multi-turn conversation scenarios in open domain. In the experiments, we investigate the effectiveness of the proposed deep neural network model for human-computer conversations. We demonstrate performance improvement against a series of baseline methods in several evaluation metrics. In contrast with previously proposed methods, NeuRetrieval is tailored for conversation scenarios and demonstrated to be more effective.
Gastric Adenocarcinomas in Central Tunisia: Evolution Specificities through Two Decades and Relation with Helicobacter pylori

Introduction: In developed countries, authors have reported variations over time in the seat and histological type of gastric adenocarcinomas, which were explained by Helicobacter pylori infection (HPI) incidence changes. In North-African countries and the Arabic world, epidemiological changes in gastric adenocarcinomas are still unknown. Our study aims to explore and to describe those changes in central Tunisia. Materials and Methods: This is a retrospective observational and descriptive study including 876 cases based on the National Central Tunisian Register of Cancers over a period of 21 years. Two groups were formed and compared (group A: 337 patients from 1995 to 2005; group B: 539 patients from 2006 to 2015). Results: HPI decreased from 32.6% in group A to 11.2% in group B (p < 0.05). Signet ring cell carcinomas increased in 2 decades from 14% in group A to 36% in group B (p < 0.05). Proximal cancers were 16.61% in group A and increased to 19.66% in group B (p = 0.3). Total gastrectomy rate was 10.4% in group A versus 23.2% in group B (p < 0.05). Conclusion: This study has shown a significant increase of signet ring cell carcinomas with a simultaneous decrease in HPI in the last decade in central Tunisia.
Emerging equity markets and economic development q

We provide an analysis of real economic growth prospects in emerging markets after financial liberalizations. We identify the financial liberalization dates and examine the influence of liberalizations while controlling for a number of other macroeconomic and financial variables. Our work also introduces an econometric methodology that allows us to use extensive time-series as well as cross-sectional information for our tests. We find across a number of different specifications that financial liberalizations are associated with significant increases in real economic growth. The effect is larger for countries with high education levels. q 2001 Elsevier Science B.V. All rights reserved. JEL classification: F3; G0; O1
Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

Abstract. The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%/100%, for SCC and BCC versus AK (57 versus 14 lesions) was 95%/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.