Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesenchymal stem cell therapy for laryngotracheal stenosis: A systematic review of preclinical studies

Background Laryngotracheal stenosis (LTS) can be either congenital or acquired. Laryngeal stenosis is most often encountered after prolonged intubation. The mechanism for stenosis following intubation is believed to be hypertrophic scarring. Mesenchymal stem cells (MSCs) therapy has shown promising results in regenerative medicine. We aimed to systematically review the literature on MSC therapy for stenosis of the conductive airways. Methods PubMed, EMBASE, Google Scholar and the Cochrane Library were systematically searched from January 1980–January 2017 with the purpose of identifying all studies addressing the effect of MSC therapy on the airway. We assessed effect on inflammation, fibrosis, and MSC as a component in tissue engineering for treating defects in the airway. Results We identified eleven studies (n = 256 animals) from eight countries evaluating the effect of MSCs as a regenerative therapy in the upper airways. The studies indicate that MSC therapy may lead to a more constructive inflammatory response as well as support tissue regeneration. Conclusion There may be a favorable effect of MSCs in inhibiting inflammation and as a component in tissue engineering. Given the heterogeneous nature of the included animal studies, any clear conclusion regarding the effect of tracheal stenosis in human subjects cannot be drawn. The included preclinical studies are however encouraging for further research.
Capecitabine and oxaliplatin for advanced esophagogastric cancer.

BACKGROUND We evaluated capecitabine (an oral fluoropyrimidine) and oxaliplatin (a platinum compound) as alternatives to infused fluorouracil and cisplatin, respectively, for untreated advanced esophagogastric cancer. METHODS In a two-by-two design, we randomly assigned 1002 patients to receive triplet therapy with epirubicin and cisplatin plus either fluorouracil (ECF) or capecitabine (ECX) or triplet therapy with epirubicin and oxaliplatin plus either fluorouracil (EOF) or capecitabine (EOX). The primary end point was noninferiority in overall survival for the triplet therapies containing capecitabine as compared with fluorouracil and for those containing oxaliplatin as compared with cisplatin. RESULTS For the capecitabine-fluorouracil comparison, the hazard ratio for death in the capecitabine group was 0.86 (95% confidence interval [CI], 0.80 to 0.99); for the oxaliplatin-cisplatin comparison, the hazard ratio for the oxaliplatin group was 0.92 (95% CI, 0.80 to 1.10). The upper limit of the confidence intervals for both hazard ratios excluded the predefined noninferiority margin of 1.23. Median survival times in the ECF, ECX, EOF, and EOX groups were 9.9 months, 9.9 months, 9.3 months, and 11.2 months, respectively; survival rates at 1 year were 37.7%, 40.8%, 40.4%, and 46.8%, respectively. In the secondary analysis, overall survival was longer with EOX than with ECF, with a hazard ratio for death of 0.80 in the EOX group (95% CI, 0.66 to 0.97; P=0.02). Progression-free survival and response rates did not differ significantly among the regimens. Toxic effects of capecitabine and fluorouracil were similar. As compared with cisplatin, oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia, alopecia, renal toxicity, and thromboembolism but with slightly higher incidences of grade 3 or 4 diarrhea and neuropathy. CONCLUSIONS Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer. (Current Controlled Trials number, ISRCTN51678883 [controlled-trials.com].).
Raf‐1 provides a dominant but not exclusive signal for the induction of CD69 expression on T cells

Stimulation of the T cell antigen receptor (TCR) induces a number of intracellular signaling pathways which lead to the transcription of a variety of new genes. Of the newly synthesized proteins, the earliest to be detected on the cell surface is the type II integral membrane protein CD69. Cross‐linking of this activation antigen induces signaling events related to T cell activation. The proto‐oncogene product Ras has been reported to up‐regulate CD69. However, which of the potential effectors of Ras induces the expression of CD69 has remained unclear. Using transient transfection, we have shown a constitutively active form of the serine/threonine kinase Raf‐1 to be sufficient to induce CD69 expression in human Jurkat T cells. Raf‐1 was further shown to be necessary for PMA‐induced CD69 expression, since transfection of a dominant inhibitory form of Raf‐1 blocked the up‐regulation of CD69 by PMA. In addition, studies with the calcium ionophore ionomycin identified a previously uncharacterized pathway regulating the expression of CD69 in T cells. Elevation of intracellular calcium induced the expression of CD69 in both Jurkat cells and peripheral blood T cells. This effect was sensitive to the immunosuppressive drug cyclosporin A, indicating that calcium‐induced CD69 expression is mediated by the protein phosphatase calcineurin. Taken together, these results define Raf‐1 as the major signaling mediator of CD69 expression in T cells and suggest that multiple mechanisms exist to regulate the level of CD69 expression following TCR stimulation.
An integrated microfluidic device for C. elegans early embryogenesis studies and drug assays

The Caenorhabditis elegans embryo is a widely used model for the functional analysis of dynamic cellular processes, such as chromosome segregation, cytokinesis or lineage analysis. However, the conventional embryo preparation method that relies on manually dissecting gravid worms to extract embryos is somewhat time consuming and does not lend itself to high throughput assays. Here, we report a fully integrated microfluidic approach for C. elegans early embryogenesis assays with unprecedented accuracy and throughput. The device consists of a compressible microfluidic pillar-array chamber for robust and fast on-chip extraction of embryos from the uterus of gravid nematodes. Subsequently, embryos are immobilized by automated fluidic transfer in a microtrap array for individual tracking of a large number of embryos, including fragile mutants with drug-permeable eggshells. Our device allows high-resolution live imaging of very early events in embryogenesis, starting from the one-cell stage. We also demonstrate the feasibility of well-controlled compound application in versatile microfluidic pharmacological assays performed on early embryos.
Microdosimetry of low-energy electrons

Abstract Purpose: To investigate differences in energy depositions and microdosimetric parameters of low-energy electrons in liquid and gaseous water using Monte Carlo track structure simulations. Materials and methods: KURBUC-liq (Kyushu University and Radiobiology Unit Code for liquid water) was used for simulating electron tracks in liquid water. The inelastic scattering cross sections of liquid water were obtained from the dielectric response model of Emfietzoglou et al. (Radiation Research 2005;164:202–211). Frequencies of energy deposited in nanometre-size cylindrical targets per unit absorbed dose and associated lineal energies were calculated for 100–5000 eV monoenergetic electrons and the electron spectrum of carbon K edge X-rays. The results for liquid water were compared with those for water vapour. Results: Regardless of electron energy, there is a limit how much energy electron tracks can deposit in a target. Phase effects on the frequencies of energy depositions are largely visible for the targets with diameters and heights smaller than 30 nm. For the target of 2.3 nm by 2.3 nm (similar to dimension of DNA segments), the calculated frequency- and dose-mean lineal energies for liquid water are up to 40% smaller than those for water vapour. The corresponding difference is less than 12% for the targets with diameters ≥ 30 nm. Conclusions: Condensed-phase effects are non-negligible for microdosimetry of low-energy electrons for targets with sizes smaller than a few tens of nanometres, similar to dimensions of DNA molecular structures and nucleosomes.
The hazards of scoring the quality of clinical trials for meta-analysis.

CONTEXT Although it is widely recommended that clinical trials undergo some type of quality review, the number and variety of quality assessment scales that exist make it unclear how to achieve the best assessment. OBJECTIVE To determine whether the type of quality assessment scale used affects the conclusions of meta-analytic studies. DESIGN AND SETTING Meta-analysis of 17 trials comparing low-molecular-weight heparin (LMWH) with standard heparin for prevention of postoperative thrombosis using 25 different scales to identify high-quality trials. The association between treatment effect and summary scores and the association with 3 key domains (concealment of treatment allocation, blinding of outcome assessment, and handling of withdrawals) were examined in regression models. MAIN OUTCOME MEASURE Pooled relative risks of deep vein thrombosis with LMWH vs standard heparin in high-quality vs low-quality trials as determined by 25 quality scales. RESULTS Pooled relative risks from high-quality trials ranged from 0.63 (95% confidence interval [CI], 0.44-0.90) to 0.90 (95% CI, 0.67-1.21) vs 0.52 (95% CI, 0.24-1.09) to 1.13 (95% CI, 0.70-1.82) for low-quality trials. For 6 scales, relative risks of high-quality trials were close to unity, indicating that LMWH was not significantly superior to standard heparin, whereas low-quality trials showed better protection with LMWH (P<.05). Seven scales showed the opposite: high quality trials showed an effect whereas low quality trials did not. For the remaining 12 scales, effect estimates were similar in the 2 quality strata. In regression analysis, summary quality scores were not significantly associated with treatment effects. There was no significant association of treatment effects with allocation concealment and handling of withdrawals. Open outcome assessment, however, influenced effect size with the effect of LMWH, on average, being exaggerated by 35% (95% CI, 1%-57%; P= .046). CONCLUSIONS Our data indicate that the use of summary scores to identify trials of high quality is problematic. Relevant methodological aspects should be assessed individually and their influence on effect sizes explored.
CRISPR/Cas9-mediated ApoE-/- and LDLR-/- double gene knockout in pigs elevates serum LDL-C and TC levels

The traditional method to establish a cardiovascular disease model induced by high fat and high cholesterol diets is time consuming and laborious and may not be appropriate in all circumstances. A suitable pig model to study metabolic disorders and subsequent atherosclerosis is not currently available. For this purpose, we applied the CRISPR/Cas9 system to Bama minipigs, targeting apolipoprotein E (ApoE) and low density lipoprotein receptor (LDLR) gene simultaneously. Six biallelic knockout pigs of these two genes were obtained successfully in a single step. No off-target incidents or mosaic mutations were detected by an unbiased analysis. Serum biochemical analyses of gene-modified piglets showed that the levels of low density lipoprotein choleserol (LDL-C), total cholesterol (TC) and apolipoprotein B (APOB) were elevated significantly. This model should prove valuable for the study of human cardiovascular disease and related translational research.
Hemispheric Synchronized Sounds and Perioperative Analgesic Requirements

BACKGROUND: Data on the effect of Hemisync® sounds on perioperative analgesic requirements are scant. METHODS: We randomized surgical outpatients into a treatment group that received Hemisync sounds (n = 20), a music group that received music (n = 20), and a control group that had a blank cassette tape (n = 20). All subjects underwent a controlled standardized propofol-nitrous-vecuronium and fentanyl general anesthesia. RESULTS: The treatment group had significantly reduced intraoperative fentanyl consumption (P < 0.05). Postoperatively, pain visual analog scale scores were significantly lower in the Hemisync group at 1 h (P = 0.02) and 24 h (P = 0.005). Subjects in the Hemisync group were also discharged earlier (P = 0.048). CONCLUSION: The use of Hemisync sounds before and during general anesthesia reduces intraoperative analgesic requirements, postoperative pain scores, and discharge time.
Relationships: Do Parents' Advance Directives Help or Hurt? The Impact of Late-Life Parental Death on Adult Sibling

The authors examined whether the effect of parental death on adults siblings’ relationship quality varies on the basis of the presence and perceived effectiveness of a deceased parent’s formal preparations for end-of-life care. The authors used data from the Wisconsin Longitudinal Study and focused on the relationship quality of a bereaved adult child and his or her randomly selected sibling. Parental death was associated with a decrease in sibling closeness. The parent’s use of advance directives (living will and durable power of attorney for health care) did not have uniformly positive effects on adult siblings’ relationship quality. Sibling relationships suffered when the living will was believed to “cause problems,” but relationships improved when the deceased parent named someone other than his or her spouse or a child as durable power of attorney for health care. The authors discuss the implications for developing effective end-of-life preparations that benefit both the decedent and surviving kin.
Motion-based moving object detection and tracking using automatic K-means

Multiple objects detection and tracking are amongst the most important tasks in computer vision-based surveillance and activity recognition. This paper proposes a real-time multiple objects detection method and compares its performance with three existing methods. ‘Good Features to Track’ algorithm is used to extract feature points from each frame. Based on the motion-based information, feature points corresponding to moving objects are extracted from next frame. Then, the number of moving objects in each frame is determined according to their motion-based information and position, and are later clustered using the k-means algorithm. Clustering of moving objects in this paper is performed using feature vectors made of pixels' intensities, motion magnitudes, motion directions and feature point positions. In terms of accuracy and efficiency, the proposed method is shown to be highly accurate in determining the number of moving objects and also fast in tracking them in the scene.
Sliding mode observer of submodular capacitor voltages in Modular Multilevel Converter

Modular Multilevel Converter (MMC) has attracted the attention of researchers particularly those working in the area of transformer-less medium to high power conversion. This topology has adopted several interesting operational characteristics such as modularity, voltage scalability, multilevel waveform capability, safe failure management, redundancy and high reliability. MMC consists of cascaded connection of multiple, identical and individually controlled bidirectional half-bridge sub modules with floating DC capacitors. A significant aspect of MMC operation is maintaining the total sum of capacitor voltages of the sub modules per arm equal to the input DC bus voltage and ensuring equal voltage sharing among the submodules. In this paper, sliding mode observer is introduced to complement a Phase shifted Pulse Width Modulation based capacitor voltage balancing controller for a three-level MMC. Also, the mathematical model of MMC, voltage balancing control algorithm, and sliding mode submodular capacitor voltage observer are included in this paper. Finally, the proposed observer design is verified through computer simulation.
Taste and smell complaints in HIV‐infected patients

Objectives:To define the scope of taste and smell (chemosensory) complaints amongst HIV-infected persons in the study population; to evaluate the clinical factors associated with chemosensory complaints; and to determine the impact of chemosensory complaints on quality of life. Design:Cross-sectional survey. Setting:Tertiary care university medical center clinic. Participants:A total of 207 HIV-infected patients. Main outcome measures:Chemosensory complaint score from taste and smell questionnaire and quality of life scores from the Medical Outcomes Study HIV Health Survey (MOS-HIV). Results:A total of 144 patients (70%) reported chemosensory complaints, 91 (44%) reported both taste and smell complaints, 47 (23%) reported only taste complaints, and six (3%) reported only smell complaints. Many patients complained that drugs interfered with their sense of taste, or that medications tasted bad. Higher chemosensory complaint scores were associated with a greater number of medications taken, tobacco use, and hay fever. Patients with chemosensory complaints had significantly lower scores in all domains of the MOS-HIV than those without complaints. Quality of life as measured by the MOS-HIV was lower in patients with chemosensory complaints even after controlling for number of AIDS diagnoses, number of medications, CD4 cell count, and HIV-1 viral load. Conclusions:Chemosensory complaints were common in the patient population and were associated with a poor quality of life. Medications played an important role in chemosensory complaints. Measures to optimize taste and smell function may improve quality of life and medication adherence, and prevent complications such as inadequate oral intake, malnutrition, weight loss, and ultimately wasting.
A Balun-BPF Using a Dual Mode Ring Resonator

In this letter, a Balun-bandpass filter (BPF) is proposed by using a dual-mode ring resonator. The Balun-BPF is not a simply combined or integrated component of a BPF and a Balun but a single BPF with the balun function. We obtained the proper balanced outputs and two-pole BPF characteristic by symmetrically placing the output ports at lambda/2 distance from each other on the dual-mode ring resonator. The fabricated Balun-BPF has a bandwidth of 40 MHz and an insertion loss of 2.4 dB at a center frequency of 2.45 GHz. The differences between the two outputs are 180-184deg in phase and within 1dB in magnitude. The measured frequency responses agree well with simulated ones.
Removal of gating in voltage‐dependent ClC‐2 chloride channel by point mutations affecting the pore and C‐terminus CBS‐2 domain

Functional and structural studies demonstrate that Cl− channels of the ClC family have a dimeric double‐barrelled structure, with each monomer contributing an identical pore. Studies with ClC‐0, the prototype ClC channel, show the presence of independent mechanisms gating the individual pores or both pores simultaneously. A single‐point mutation in the CBS‐2 domain of ClC‐0 has been shown to abolish slow gating. We have taken advantage of the high conservation of CBS domains in ClC channels to test for the presence of a slow gate in ClC‐2 by reproducing this mutation (H811A). ClC‐2‐H811A showed faster opening kinetics and opened at more positive potentials than ClC‐2. There was no difference in [Cl−]i dependence. Additional neutralization of a putative pore gate glutamate side chain (E207V) abolished all gating. Resolving slow and fast gating relaxations, however, revealed that the H811A mutation affected both fast and slow gating processes in ClC‐2. This suggests that slow and fast gating in ClC‐2 are coupled, perhaps with slow gating contributing to the operation of the pore E207 as a protopore gate.
No direct influence of EU on domestic consolidation and reform: two fiscal ‘hardliners’, Netherlands and Estonia

ABSTRACT In the Netherlands and Estonia, the European Union (EU) did not exert direct influence on domestic fiscal consolidation. They managed to resolve their fiscal crises and balance their budgets without external financial assistance, thanks to strict fiscal discipline. Yet, domestic consolidations in both countries were to some extent influenced by the EU. The Netherlands was subject to excessive deficit procedure. Estonia was indirectly influenced because of its top priority to join the Eurozone. This paper begins with a conceptual look at EU influencing. Then, fiscal discipline and consolidation in the Netherlands and Estonia are explored, especially their similarities and differences.
Study of a low energy pulsed electron beam extraction system

A pulsed low energy (<100 keV) large cross-section ion induced secondary emission electron gun has been developed to decompose gaseous pollutants such as NOx. The emitted electron beam has been extracted through a thin foil supported by an aluminum honeycomb (depth 8 mm and area 64.5 cm/sup 2/) that serves as a partition between electron gun and atmospheric pressure processing chamber. In this paper, we report a design and construction of a robust electron window as well as performance of two commercial polymer foils (SiO/sub 2/ coated polyethylene and aluminum coated Mylar) as a window material. The performance of these polymer foils are compared with conventional aluminum foil in terms of various extraction mechanisms such as energy deposition, electron transmission, mechanical and thermal loadings etc. Both the polymer foils have been judged to be consistent with mechanical requirements but aluminum coated Mylar window showed high electron transmission (78%) comparing to SiO/sub 2/ coated polyethylene (64%) and aluminum (45%) window of same thickness (12 /spl mu/m) at 100 kV. The improved current transmission through the new window enhances the electrical efficiency of the electron gun up to 58.7% (from 33%).
ED(27) trophoblast-like cells isolated from first-trimester chorionic villi are genetically identical to HeLa cells yet exhibit a distinct phenotype.

ED(27) trophoblast-like cells were prepared from human chorionic villus samples obtained at 9 weeks gestation and have been grown continuously in vitro without phenotypic drift for nearly a decade. These cells express many trophoblast markers, including cytokeratin, placental alkaline phosphatase (PLAP), secretion of 17beta-estradiol, and a microvillous apical surface. The ED(27) cell line is a useful model system for studies of placental cell biology and has been distributed to laboratories world-wide. However, experiments to investigate their relationship to primary villous cytotrophoblast have shown that these cells do not secrete detectable amounts of human chorionic gonadotropin in culture and, when digested with trypsin, disperse into individual cells. Furthermore, immunocytochemical studies demonstrated that, unlike villous cytotrophoblasts, ED(27) cells were immunoreactive with monoclonal antibodies recognizing some HLA Class I antigens. This was not HLA-G, however, as would be expected if these cells originated from extravillous cytotrophoblasts, but rather classical HLA-A, B which is thought not to be expressed by any trophoblast subpopulations. These inconsistencies prompted us to question the authenticity of the continuous cell line as it now exists. Genetic haplotype analysis using the polymerase chain reaction (PCR) revealed that ED(27) was genetically identically to the HeLa cell line. Inasmuch as HeLa cells have never been grown in the laboratory (DAK), the only possible origin of HeLa cell contamination of ED(27) cells was the WISH cell line, and further PCR analysis revealed that this cell line was also genetically identical to HeLa. Like ED(27) cells, HeLa cells and WISH cells synthesized small amounts of estrogen and were found to express PLAP and antigens recognized by the monoclonal antibodies ED822, directed against the syncytiotrophoblast, and J1B5 directed against villous cytotrophoblast. These results point out the need for adherence to rigorous and consistent quality control measures to assure the authenticity of cell lines used as in vitro model systems.