Miracle-dz/UniFAR-FTUs huggingface dataset:
A laboratory study of the effects of processing blood through a cell salvage device and leucocyte depletion filter on levels of pro‐inflammatory cytokines and bradykinin

We investigated changes in concentrations of interleukin‐1β, interleukin‐6, tumour necrosis factor‐α and bradykinin in blood during passage through a cell salvage device and a leucocyte depletion filter, with or without application of subatmospheric pressure across the filter. Blood samples from 19 healthy women undergoing scheduled caesarean section showed concentrations of cytokines and bradykinin in blood filtered under gravity flow that were equal to or significantly lower than those of pre‐operative venous blood samples. They were also significantly lower than that in postoperative orthopaedic shed blood, which is commonly reinfused after orthopaedic surgery. A minority of samples taken from blood that had been filtered using subatmospheric pressure showed raised interleukin‐6 concentrations. We suggest that use of a leucocyte depletion filter for cell‐salvaged blood with gravity flow is likely to be safe with regard to concentrations of cytokines and bradykinin. However, this may not hold true for the filter used with subatmospheric pressure. If transfusion of salvaged blood using a leucocyte depletion filter seems to induce hypotension, elevation of interleukin‐6 should be suspected.
Treatment of dentinal hypersensitivity using low-level laser therapy and 5% potassium nitrate: A randomized, controlled, three arm parallel clinical study

Aim: The present randomized study was aimed to compare the efficacy 5% potassium nitrate (KNO 3 ) toothpaste, low-level laser therapy (LLLT), and LLLT with 5% KNO 3 toothpaste in the treatment of dentinal hypersensitivity (DH). Materials and Methods: Total of 45 patients complaining of DH with visual analog scale (VAS) score being ≥2 were recruited and were divided into three groups. Group A was treated with 5% KNO 3 toothpaste, Group B using LLLT along with the application of 5% KNO 3 toothpaste, and Group C using LLLT alone. VAS scores were recorded at the baseline, 1 st , 2 nd , and 3 rd weeks by the examiner who is blinded toward the treatment. The sensitivity response was evaluated using air spray and tactile sensation (explorer). Results: A greater reduction of DH was recorded at the end of 3 weeks in Group C and Group B when compared to Group A. Better results were noted in Group C at the end of the 1 st week when compared to Group B. According to this study, there was no additional benefit of using toothpaste along with LLLT. Conclusion: A greater reduction of DH was recorded at the end of 3 weeks in Group C and Group B when compared to Group A. Better results were noted in Group C at the end of the 1 st week when compared to Group B. According to this study, there was no additional benefit of using toothpaste along with LLLT.
SPIO‐enhanced magnetic resonance imaging study of placental perfusion in a rat model of intrauterine growth restriction

Please cite this paper as: Deloison B, Siauve N, Aimot S, Balvay D, Thiam R, Cuenod C, Ville Y, Clement O, Salomon L. SPIO‐enhanced magnetic resonance imaging study of placental perfusion in a rat model of intrauterine growth restriction. BJOG 2012;119:626–633.
Identification of Heterotrophic Nitrification in a Sierran Forest Soil

A potential for heterotrophic nitrification was identified in soil from a mature conifer forest and from a clear-cut site. Potential rates of NO2− production were determined separately from those of NO3− by using acetylene to block autotrophic NH4+ oxidation and chlorate to block NO2− oxidation to NO3− in soil slurries. Rates of NO2− production were similar in soil from the forest and the clear-cut site and were strongly inhibited by acetylene. The rate of NO3− production was much greater than that of NO2− production, and NO3− production was not significantly affected by acetylene or chlorate. Nitrate production was partially inhibited by cycloheximide, but was not significantly reduced by streptomycin. Neither the addition of ammonium nor the addition of peptone stimulated NO3− production. 15N labeling of the NH4+ pool demonstrated that NO3− was not coming from NH4+. The potential for heterotrophic nitrification in these forest soils was greater than that for autotrophic nitrification.
Occupational endotoxin exposure in association with atopic sensitization and respiratory health in adults: Results of a 5-year follow-up

The objective of the present longitudinal study was to investigate the effects of occupational endotoxin exposure on respiratory health and atopic sensitization in adults. Health outcomes and personal endotoxin exposure estimates were determined for 234 farmers and agricultural workers both at baseline and 5 years later. A questionnaire was used to assess respiratory symptoms, spirometry tests were performed and total and specific IgE levels were measured in serum. A twofold increase in personal endotoxin exposure was associated with less hay fever (OR 0.68, 95%CI 0.54-0.87) and grass IgE positivity (OR 0.81, 95%CI 0.68-0.97) at both time points (“persistent” versus “never”). Although not statistically significant, a consistent protective pattern was observed for an increased loss of hay fever symptoms (OR 2.19, 95%CI 0.96-4.99) and grass IgE positivity (OR 1.24, 95%CI 0.76-2.02), and for less new-onset of hay fever (OR 0.87, 95%CI 0.65-1.17), grass IgE positivity (OR 0.83, 95%CI 0.61-1.12) and atopic sensitization (OR 0.75, 95%CI 0.55-1.02). Endotoxin exposure was not associated with changes in lung function. We showed that occupational endotoxin exposure is associated with a long-term protective effect on hay fever and grass IgE positivity. Results on longitudinal changes in hay fever, atopy and grass IgE positivity in adulthood were consistent with a protective effect of endotoxin exposure, but results need to be confirmed in larger cohorts. An effect of endotoxin exposure on lung function decline was not found.
Galectin‐4 interacts with the drug transporter human concentrative nucleoside transporter 3 to regulate its function

The intracellular N‐terminal domain of the nucleoside and drug transporter human concentrative nucleoside transporter (hCNT)3 was used as bait in a glutathione S‐transferase pull‐down approach, to identify hCNT3 protein partners, using human colon homogenates as a prey source. Galectin (Gal)‐4 was identified as a potential hCNT3 partner in the colon. The biochemical validation of the Gal‐4‐hCNT3 interaction was verified by targeted pull‐down assays and coimmunoprecipitation experiments in HT‐29 cells, which endogenously express hCNT3 and Gal‐4. Furthermore, Gal‐4 was shown to colocalize with hCNT3 in HT‐29 cells. The biologic significance of this interaction was obtained from experiments in which Gal‐4 was knocked down, showing that this protein is a regulator of hCNT3 trafficking and retention at the cell membrane, reducing its plasma membrane location by 70%. Conversely, the addition of Gal‐4 increased hCNT3 location at the plasma membrane by 77%, thereby demonstrating that this lectin modulates hCNT3 function in colonic cells. The integrity of this partnership may be clinically relevant, because hCNT3 may be responsible for the translocation of thiopurines, such as 6‐mercaptopurine, a front‐line treatment in inflammatory bowel disease. The expression of Gal‐4 and hCNT3 proteins is not impaired in inflamed colon from patients with Crohn's disease, thereby anticipating the integrity of this system for drug targeting. —Fernández‐Calotti, P., Casulleras, O. , Antolin, M. , Guarner, F. , Pastor‐Anglada, M. Galectin‐4 interacts with the drug transporter human concentrative nucleoside transporter 3 to regulate its function. FASEB J. 30, 544‐554 (2016). www.fasebj. org
Ponatinib

Objective: To review the pharmacology, pharmacokinetics, clinical trials, adverse effects, and formulary considerations of ponatinib, a pan-tyrosine kinase inhibitor (TKI). Data Sources: A literature search of articles published between January 1966 and June 2013 was performed using PubMed with the following search terms: ponatinib, AP24534, and Iclusig. ARIAD Pharmaceuticals, Inc, was contacted for unpublished information. Other sources included American Society of Hematology abstracts, the Food and Drug Administration Center for Drug Evaluation and Research Web site, and clinicaltrials.gov. Study Selection/Data Extraction: Included articles and abstracts were published in English and contain information about ponatinib, particularly in the treatment of chronic myeloid leukemia (CML) or Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL). Data Synthesis: Following the phase II PACE trial, ponatinib was approved for the treatment of patients with chronic-phase (CP), accelerated-phase (AP), or blast-phase (BP) CML or Ph+ ALL who have become intolerant or resistant to previous therapy. Unlike other BCR-ABL TKIs, ponatinib was designed to overcome the T315I mutation. At 15.3 months, 46% of patients with CP-CML achieved a complete cytogenetic response, and 34% achieved a major molecular response. Complete hematologic responses occurred in 47% of patients with AP-CML, 21% with BP-CML, and 34% with Ph+ ALL after 1 year. Severe toxicities included myelosuppression, hepatotoxicity, pancreatitis, and arterial thrombosis. Conclusions: Ponatinib is a potent TKI that can overcome several resistance mechanisms in previously treated patients with CML and Ph+ ALL. Ponatinib should be reserved for patients who have failed first-line therapy, have the T315I mutation, or have progressed.
UK Renal Registry 15th Annual Report: Chapter 5 Survival and Causes of Death of UK Adult Patients on Renal Replacement Therapy in 2011: National and Centre-Specific Analyses

Introduction: These analyses examine a) survival from the start of renal replacement therapy (RRT) based on the total incident UK RRT population reported to the UK Renal Registry, b) survival of prevalent patients. Changes in survival between 1997 and 2011 are also reported. Methods: Survival was calculated for both incident and prevalent patients on RRT and compared between the UK countries after adjustment for age. Survival of incident patients (starting RRT during 2010) was calculated both from the start of RRT and from 90 days after starting RRT, both with and without censoring at transplantation. Prevalent dialysis patients were censored at transplantation; this means that the patient is considered alive up to the point of transplantation, but the patient's status post-transplant is not considered. Both Kaplan-Meier and Cox adjusted models were used to calculate survival. Causes of death were analysed for both groups. The relative risk of death was calculated compared with the general UK population. Results: The unadjusted 1 year after 90 day survival for patients starting RRT in 2010 was 87.3%, representing an increase from the previous year (86.6%). In incident patients aged 18-64 years, the unadjusted 1 year survival had risen from 86.0% in patients starting RRT in 1997 to 92.6% in patients starting RRT in 2010 and for those aged ≥65 it had increased from 63.9% to 77.0% over the same period. The age-adjusted one year survival (adjusted to age 60) of prevalent dialysis patients increased from 88.1% in the 2001 cohort to 89.8% in the 2010 cohort. Prevalent diabetic patient one year survival rose from 82.1% in the 2002 cohort to 84.7% in the 2010 cohort. The age-standardised mortality ratio for prevalent RRT patients compared with the general population was 18 for age group 30-34 and 2.5 at age 85+ years. In the prevalent RRT dialysis population, cardiovascular disease accounted for 22% of deaths, infection and treatment withdrawal 18% each and 25% were recorded as other causes of death. Treatment withdrawal was a more frequent cause of death in those incident patients aged ≥65 than in younger patients. The median life years remaining for a 25-29 year old on RRT was 18 years and approximately three years for a 75+ year old. Conclusions: Survival of patients starting RRT has improved in the 2010 incident cohort. The relative risk of death on RRT compared with the general population has fallen since 2001.
In Situ Determination of Macroparticle Velocities in a Copper Vacuum Arc

The velocity components of individual macroparticles (molten droplets) moving through the interelectrode plasma of copper vacuum arc were measured by applying the forward-scattering laser Doppler anemometry method (LDA). The arc was sustained between two cylindrical copper electrodes, 14 mm in diameter and spaced 4 mm apart. Two current waveforms, with rise times to peak currents of 1 and 6 ms and duration of about 5 and 30 ms, respectively, were used in the experiment, while in both cases peak currents were either 1 or 2 kA. Macroparticles traversing through the ellipsoid shaped "probe-volume," which was produced by the intersection of the two He-Ne laser beams, scattered the laser light, through a monochromator, used as a 1.7-A bandpass filter, onto a photomultiplier. The Doppler-frequency component of the photomultiplier was recorded after appropriate filtering and amplification. The macroparticle velocity component obtained from the Doppler frequency was in the plane defined by the illuminating laser beams and directed perpendicularly to the optical axis. Macroparticles were detected during the whole period of the discharge, and their velocity was determined either at the instant of peak current or when the current decreased to 10 percent of its peak value, at several spatial locations inside the discharge volume. The measured macroparticle velocity components ranged from about 10-20 m/s up to about 700 m/s, showing a systematic dependence on the instantaneous value of the arc-current and on the spatial position of the "probe-volume," e. g.
Fine Particulate Matter Air Pollution, Proximity to Traffic, and Aortic Atherosclerosis

Background: The initiation and acceleration of atherosclerosis is hypothesized as a physiologic mechanism underlying associations between air pollution and cardiovascular effects. Despite toxicologic evidence, epidemiologic data are limited. Methods: In this cross-sectional analysis we investigated exposure to fine particulate matter (PM2.5) and residential proximity to major roads in relation to abdominal aortic calcification, a sensitive indicator of systemic atherosclerosis. Aortic calcification was measured by computed tomography among 1147 persons, in 5 US metropolitan areas, enrolled in the Multi-Ethnic Study of Atherosclerosis. The presence and quantity of aortic calcification were modeled using relative risk regression and linear regression, respectively, with adjustment for potential confounders. Results: We observed a slightly elevated risk of aortic calcification (RR = 1.06; 95% confidence interval = 0.96–1.16) with a 10 &mgr;g/m3 contrast in PM2.5. The PM2.5-associated risk of aortic calcification was stronger among participants with long-term residence near a PM2.5 monitor (RR = 1.11; 1.00–1.24) and among participants not recently employed outside the home (RR = 1.10; 1.00–1.22). PM2.5 was not associated with an increase in the quantity of aortic calcification (Agatston score) and no roadway proximity effects were noted. There was indication of PM2.5 effect modification by lipid-lowering medication use, with greater effects among users, and PM2.5 associations were observed most consistently among Hispanics. Conclusions: Although we did not find persuasive associations across our full study population, associations were stronger among participants with less exposure misclassification. These findings support the hypothesis of a relationship between particulate air pollution and systemic atherosclerosis.
Climate Change: A Wicked Problem: Complexity and Uncertainty at the Intersection of Science, Economics, Politics, and Human Behavior

Under one cover, Frank Incropera provides a comprehensive, objective, and critical assessment of all issues germane to the climate change debate: science, technology options, economic ramifications, cultural and behavioral issues, the influence of special interests and public policy, geopolitics, and ethical dimensions. The underlying science is treated in depth, but in an approachable and accessible manner. A strong case is made for the reality of anthropogenic climate change, while confronting the range of issues that remain uncertain and deconstructing opposing views. Incropera assesses the strengths and weaknesses of technology options for mitigating the effects of climate change, analyzes nontechnical factors – economic, cultural, and political – and provides an in-depth treatment of ethical implications. This book is intended for those wishing to become fully informed about climate change and is designed to provide the reader with a firm foundation for drawing his or her own conclusions.
Mitochondrial Transcription Factor A and Its Downstream Targets Are Up-regulated in a Rat Hepatoma*

Mitochondrial transcription factor A is a key regulator involved in mitochondrial DNA transcription and replication. In a poorly differentiated rat hepatoma, Morris hepatoma 3924A, the mRNA and protein levels of this factor were elevated about 10- and 11-fold, respectively, relative to the host liver. The mRNA levels for the hepatoma cytochrome c oxidase I, II, and NADH dehydrogenase 5, 6, the downstream targets of Tfam, were augmented 10-, 8-, 5-, and 3-fold, respectively. Interestingly, Tfam was also found in the hepatoma nucleus. The mRNA levels for nuclear respiratory factor 1 and 2 (NRF-1 and -2), the proteins that are known to interact with specific regulatory elements on human TFAMpromoter, were 5- and 3-fold higher, respectively, in the hepatoma relative to the host liver. Unlike the human promoter, the ratTfam promoter did not form a specific complex with the NRF-1 in the liver or hepatoma nuclear extracts, which is consistent with the absence of an NRF-1 consensus sequence in the proximal rat promoter. A single specific complex formed between the rat promoter and the NRF-2 protein was comparable in the two extracts. The DNA binding activity of Sp1 in the hepatoma nuclear extract was 4-fold greater than that in the liver extract. In vivo genomic footprinting showed occupancy of NRF-2 and Sp1 consensus sites on the promoter of rat Tfam gene. Tfam was also up-regulated in other hepatoma cells. Together, these results show up-regulation of Tfam in some tumors, particularly the liver tumors. Further, the relatively high level of Sp1 binding to the promoter in the hepatoma could play a major role in the up-regulation ofTfam in these tumor cells.
Preoperative Variables Predicting Massive Blood Loss During Surgical Management of Adolescent Idiopathic Scoliosis

Background: Massive blood loss is one of the most important concerns in scoliosis surgery. There are some factors suggested to predict the massive blood loss in patients with adolescent idiopathic scoliosis (AIS), however, their predictive value remained unclear. Objectives: The current study aimed to investigate whether preoperative variables can predict perioperative massive blood loss in patients with AIS. Patients and Methods: There were 60 patients with AIS who underwent surgical treatment in the current retrospective study. Posterior spinal fusion (PSF) was performed on 36 patients and PSF and anterior spinal fusion (ASF) for the other 24. Estimated blood loss (EBL) was calculated intraoperative. The correlation between preoperative radiographic and demographic variables with EBL was investigated. Results: Among the variables, only AVB-R ratio positively correlated with the amount of intraoperative blood transfusion (r = 0.28; P = 0.03). Also, preoperative lateral rib hump positively correlated with blood loss in the PSF group (r = 0.39; P < 0.05). Also, the classification of the scoliosis did not affect the amount of blood loss and the number of transfused units. Conclusions: The preoperative lateral rib hump is an important factor positively correlated with the EBL.
Mechanism of Action of Camptothecin

Camptothecin (CPT) class of compounds has been demonstrated to be effective against a broad spectrum of tumors. Their molecular target has been firmly established to be human DNA topoisomerase I (topo I). CPT inhibits topo I by blocking the rejoining step of the cleavage/religation reaction of topo-I, resulting in accumulation of a covalent reaction intermediate, the cleavable complex. The primary mechanism of cell killing by CPT is S-phase-specific killing through potentially lethal collisions between advancing replication forks and topo-I cleavable complexes. Collisions with the transcription machinery have also been shown to trigger the formation of long-lived covalent topo-I DNA complexes, which contribute to CPT cytotoxicity. Two novel repair responses to topo-I-mediated DNA damage involving covalent modifications of topo-I have been discovered. The first involves activation of the ubiquitin/26S proteasome pathway, leading to degradation of topo-I (CPT-induced topo-I downregulation). The second involves SUMO conjugation to topo-I. The potentials roles of these new mechanisms for repair of topo-I-mediated DNA damage in determining CPT sensitivity/resistance in tumor cells are discussed.
Epstein-Barr Virus Infection of Langerhans Cell Precursors as a Mechanism of Oral Epithelial Entry, Persistence, and Reactivation

ABSTRACT Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with many malignant and nonmalignant human diseases. Life-long latent EBV persistence occurs in blood-borne B lymphocytes, while EBV intermittently productively replicates in mucosal epithelia. Although several models have previously been proposed, the mechanism of EBV transition between these two reservoirs of infection has not been determined. In this study, we present the first evidence demonstrating that EBV latently infects a unique subset of blood-borne mononuclear cells that are direct precursors to Langerhans cells and that EBV both latently and productively infects oral epithelium-resident cells that are likely Langerhans cells. These data form the basis of a proposed new model of EBV transition from blood to oral epithelium in which EBV-infected Langerhans cell precursors serve to transport EBV to the oral epithelium as they migrate and differentiate into oral Langerhans cells. This new model contributes fresh insight into the natural history of EBV infection and the pathogenesis of EBV-associated epithelial disease.
The Capable ABL: What Is Its Biological Function?

ABSTRACT The mammalian ABL1 gene encodes the ubiquitously expressed nonreceptor tyrosine kinase ABL. In response to growth factors, cytokines, cell adhesion, DNA damage, oxidative stress, and other signals, ABL is activated to stimulate cell proliferation or differentiation, survival or death, retraction, or migration. ABL also regulates specialized functions such as antigen receptor signaling in lymphocytes, synapse formation in neurons, and bacterial adhesion to intestinal epithelial cells. Although discovered as the proto-oncogene from which the Abelson leukemia virus derived its Gag–v-Abl oncogene, recent results have linked ABL kinase activation to neuronal degeneration. This body of knowledge on ABL seems confusing because it does not fit the one-gene-one-function paradigm. Without question, ABL capabilities are encoded by its gene sequence and that molecular blueprint designs this kinase to be regulated by subcellular location-dependent interactions with inhibitors and substrate activators. Furthermore, ABL shuttles between the nucleus and the cytoplasm where it binds DNA and actin—two biopolymers with fundamental roles in almost all biological processes. Taken together, the cumulated results from analyses of ABL structure-function, ABL mutant mouse phenotypes, and ABL substrates suggest that this tyrosine kinase does not have its own agenda but that, instead, it has evolved to serve a variety of tissue-specific and context-dependent biological functions.