Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Deletion or Pharmacological Inhibition of Dipeptidyl Peptidase-4 Improves Cardiovascular Outcomes After Myocardial Infarction in Mice

OBJECTIVE Glucagon-like peptide-1 (7-36)amide (GLP-1) is cleaved by dipeptidyl peptidase-4 (DPP-4) to GLP-1 (9-36)amide. We examined whether chemical inhibition or genetic elimination of DPP-4 activity affects cardiovascular function in normoglycemic and diabetic mice after experimental myocardial infarction. RESEARCH DESIGN AND METHODS Cardiac structure and function was assessed by hemodynamic monitoring and echocardiography in DPP-4 knockout (Dpp4−/−) mice versus wild-type (Dpp4+/+) littermate controls and after left anterior descending (LAD) coronary artery ligation–induced myocardial infarction (MI). Effects of sustained DPP-4 inhibition with sitagliptin versus treatment with metformin were ascertained after experimental MI in a high-fat diet–streptozotocin model of murine diabetes. Functional recovery from ischemia-reperfusion (I/R) injury was measured in isolated hearts from Dpp4−/− versus Dpp4+/+ littermates and from normoglycemic wild-type (WT) mice treated with sitagliptin or metformin. Cardioprotective signaling in the murine heart was examined by RT-PCR and Western blot analyses. RESULTS Dpp4−/− mice exhibited normal indexes of cardiac structure and function. Survival post-MI was modestly improved in normoglycemic Dpp4−/− mice. Increased cardiac expression of phosphorylated AKT (pAKT), pGSK3β, and atrial natriuretic peptide (ANP) was detected in the nonischemic Dpp4−/− heart, and HO-1, ANP, and pGSK3β proteins were induced in nonischemic hearts from diabetic mice treated with sitagliptin or metformin. Sitagliptin and metformin treatment of wild-type diabetic mice reduced mortality after myocardial infarction. Sitagliptin improved functional recovery after I/R injury ex vivo in WT mice with similar protection from I/R injury also manifest in hearts from Dpp4−/− versus Dpp4+/+ mice. CONCLUSIONS Genetic disruption or chemical inhibition of DPP-4 does not impair cardiovascular function in the normoglycemic or diabetic mouse heart.
Properties of poly(3-hydroxybutyrate) depolymerase from a marine bacterium, Alcaligenes faecalis AE122

Alcaligenes faecalis AE122 that used poly(3-hydroxybutyrate) (PHB) as a sole source of carbon was newly isolated from a coastal seawater sample. The strain required seawater for growth on PHB as well as in a nutrient broth, in which seawater could be replaced by an appropriate concentration of NaCl. PHB depolymerase was purified to homogeneity from the culture supernatant of A. faecalis AE122 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme consisted of a monomer subunit with a molecular mass of 95.5 kDa. The N-terminal amino acid sequence was GAWQNNLAGGFNKV. The dimeric and trimeric esters of 3-hydroxybutyrate were the main hydrolysis products of the purified enzyme. The enzyme was most active at pH 9.0 and 55 degrees C and was inhibited by phenylmethylsulfonyl fluoride. Several cations in seawater greatly enhanced the enzyme activity.
Ran Binding Protein 9 (RanBP9) is a novel mediator of cellular DNA damage response in lung cancer cells

Ran Binding Protein 9 (RanBP9, also known as RanBPM) is an evolutionary conserved scaffold protein present both in the nucleus and the cytoplasm of cells whose biological functions remain elusive. We show that active ATM phosphorylates RanBP9 on at least two different residues (S181 and S603). In response to IR, RanBP9 rapidly accumulates into the nucleus of lung cancer cells, but this nuclear accumulation is prevented by ATM inhibition. RanBP9 stable silencing in three different lung cancer cell lines significantly affects the DNA Damage Response (DDR), resulting in delayed activation of key components of the cellular response to IR such as ATM itself, Chk2, γH2AX, and p53. Accordingly, abrogation of RanBP9 expression reduces homologous recombination-dependent DNA repair efficiency, causing an abnormal activation of IR-induced senescence and apoptosis. In summary, here we report that RanBP9 is a novel mediator of the cellular DDR, whose accumulation into the nucleus upon IR is dependent on ATM kinase activity. RanBP9 absence hampers the molecular mechanisms leading to efficient repair of damaged DNA, resulting in enhanced sensitivity to genotoxic stress. These findings suggest that targeting RanBP9 might enhance lung cancer cell sensitivity to genotoxic anti-neoplastic treatment.
Concise Review: Stem Cell Interventions for People With Cerebral Palsy: Systematic Review With Meta‐Analysis

Evidence for stem cells as a potential intervention for cerebral palsy is emerging. Our objective was to determine the efficacy and safety of stem cells for improving motor and cognitive function of people with cerebral palsy. Searches were conducted in October 2015 in CENTRAL, EMBASE, MEDLINE, and Cochrane Libraries. Randomized controlled trials and controlled clinical trials of stem cells for cerebral palsy were included. Two authors independently decided upon included trials, extracted data, quality, and risk of bias. The primary outcome was gross motor function. Secondary outcomes were cognitive function and adverse events (AEs). Effects were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI), using a random‐effects model. Five trials comprising 328 participants met inclusion criteria. Four cell types were studied: olfactory ensheathing, neural, neural progenitors, and allogeneic umbilical cord blood (UCBs). Transplantation procedures differed from central nervous system neurosurgical transplantation to intravenous/arterial infusion. Participants were followed short‐term for only 6 months. Evidence of variable quality indicated a small statistically significant intervention effect from stem cells on gross motor skills (SMD 1.27; 95% CI 0.22, 2.33), with UCBs most effective. There were insufficient and heterogeneous data to compare cognitive effects. Serious AEs were rare (n = 4/135 [3%] stem cells; n = 3/139 [2%] controls). Stem cells appeared to induce short‐term improvements in motor skills. Different types of stem cell interventions were compared, meaning the data were heterogeneous and are a study limitation. Further randomized controlled trials are warranted, using rigorous methodologies.
Rheological response and dynamics of the amphiphilic diamond phase from kinetic lattice–Boltzmann simulations

The purpose of the present paper is to report on the first computational study of the dynamical and rheological response of a self-assembled diamond mesophase under Couette flow in a ternary mixture composed of oil, water and an amphiphilic species. The amphiphilic diamond mesophase arises in a wide range of chemical and biological systems, and a knowledge of its rheological response has important implications in materials science and biotechnological applications. The simulations reported here are performed using a kinetic lattice–Boltzmann method. Lyotropic liquid crystals exhibit characteristic rheological responses in experiments that include shear-banding and a non-Newtonian flow curve as well as viscoelasticity under oscillatory shear. Their behaviour under steady and oscillatory shear is correctly reproduced in our simulations. On cessation of shear, as the morphology returns to the diamond phase, the relaxation of the stress response follows a stretched-exponential form for low initial strain rates.
Protective Role of False Tendon in Subjects with Left Bundle Branch Block: A Virtual Population Study

False tendons (FTs) are fibrous or fibromuscular bands that can be found in both the normal and abnormal human heart in various anatomical forms depending on their attachment points, tissue types, and geometrical properties. While FTs are widely considered to affect the function of the heart, their specific roles remain largely unclear and unexplored. In this paper, we present an in silico study of the ventricular activation time of the human heart in the presence of FTs. This study presents the first computational model of the human heart that includes a FT, Purkinje network, and papillary muscles. Based on this model, we perform simulations to investigate the effect of different types of FTs on hearts with the electrical conduction abnormality of a left bundle branch block (LBBB). We employ a virtual population of 70 human hearts derived from a statistical atlas, and run a total of 560 simulations to assess ventricular activation time with different FT configurations. The obtained results indicate that, in the presence of a LBBB, the FT reduces the total activation time that is abnormally augmented due to a branch block, to such an extent that surgical implant of cardiac resynchronisation devices might not be recommended by international guidelines. Specifically, the simulation results show that FTs reduce the QRS duration at least 10 ms in 80% of hearts, and up to 45 ms for FTs connecting to the ventricular free wall, suggesting a significant reduction of cardiovascular mortality risk. In further simulation studies we show the reduction in the QRS duration is more sensitive to the shape of the heart then the size of the heart or the exact location of the FT. Finally, the model suggests that FTs may contribute to reducing the activation time difference between the left and right ventricles from 12 ms to 4 ms. We conclude that FTs may provide an alternative conduction pathway that compensates for the propagation delay caused by the LBBB. Further investigation is needed to quantify the clinical impact of FTs on cardiovascular mortality risk.
Efficacy and Safety of Omalizumab in Patients with Chronic Idiopathic / Spontaneous Urticaria Who Remain Symptomatic on H 1 Antihistamines : A Randomized , Placebo-Controlled Study

Citation for pulished version (APA): Saini, S. S. , Bindslev-Jensen, C. , Maurer, M. , Grob, J-J., Bülbül Baskan, E. , Bradley, M. S. , . Rosén, K. (2015). Efficacy and safety of omalizumab in patients with chronic idiopathic/spontaneous urticaria who remain symptomatic on H1 antihistamines: a randomized, placebo-controlled study. Journal of Investigative Dermatology, 135(1), 67-75. https://doi.org/10.1038/jid.2014. 306
Electrogram Analysis and Pacing Are Complimentary for Recognition of Abnormal Conduction and Far-Field Potentials During Substrate Mapping of Infarct-Related Ventricular Tachycardia

Background—Mapping to identify scar-related ventricular tachycardia re-entry circuits during sinus rhythm focuses on sites with abnormal electrograms or pace-mapping findings of QRS morphology and long stimulus to QRS intervals. We hypothesized that (1) these methods do not necessarily identify the same sites and (2) some electrograms are far-field potentials that can be recognized by pacing. Methods and Results—From 12 patients with coronary disease and recurrent ventricular tachycardia undergoing catheter ablation, we retrospectively analyzed electrograms and pacing at 546 separate low bipolar voltage (<1.5 mV) sites. Electrograms were characterized as showing evidence of slow conduction if late potentials (56%) or fractionated potentials (76%) were present. Neither was present at (13%) sites. Pacing from the ablation catheter captured 70% of all electrograms. Higher bipolar voltage and fractionation were independent predictors for pace capture. There was a linear correlation between the stimulus to QRS duration during pacing and the lateness of a capturing electrogram (P<0.001), but electrogram and pacing markers of slow conduction were discordant at 40% of sites. Sites with far-field potentials, defined as those that remained visible and not captured by pacing stimuli, were identified at 48% of all pacing sites, especially in areas of low bipolar voltage and late potentials. Initial radiofrequency energy application rendered 74% of targeted sites electrically unexcitable. Conclusions—Far-field potentials are common in scar areas. Combining analysis of electrogram characteristics and assessment of pace capture may refine identification of substrate targets for radiofrequency ablation.
Effects of Serum Leptin and Resistin Levels on Cancer Cachexia in Patients With Advanced-Stage Non–Small Cell Lung Cancer

Introduction: Cancer cachexia is one of the most frequent effects of malignancy, is often associated with poor prognosis, and may account for up to 20% of cancer deaths. The aim of our study was to evaluate the relationship of cancer cachexia and serum levels of resistin and leptin in patients with advanced non–small cell lung cancer. Methods: A total of 67 chemotherapy-naïve patients with advanced-stage non–small cell cancer and a control group containing 20 healthy individuals without a known chronic disease were enrolled in this study. All individuals in the control group were age and sex matched. Demographic, anthropometric, laboratory data and serum levels of adipokines were measured for 2 groups. Progression-free survival and overall survival were estimated using the Kaplan-Meier method. Survival among various factors was calculated using the log-rank test. Results: Patients presented significantly higher serum resistin (P = .0001) and lower serum leptin levels (P = .025) than the control group. Lower serum levels of leptin were correlated with overall survival (P = .011). Conclusions: Serum leptin and resistin levels play key role as proinflammatory cytokines in lung cancer and cancer cachexia; however, their use as diagnostic or prognostic markers is not possible yet, and further large-scale studies are required to confirm our findings.
Classifying networked entities with modularity kernels

Statistical machine learning techniques for data classification usually assume that all entities are i.i. d. (independent and identically distributed). However, real-world entities often interconnect with each other through explicit or implicit relationships to form a complex network. Although some graph-based classification methods have emerged in recent years, they are not really suitable for complex networks as they do not take the degree distribution of network into consideration. In this paper, we propose a new technique, Modularity Kernel, that can effectively exploit the latent community structure of networked entities for their classification. A number of experiments on hypertext datasets show that our proposed approach leads to excellent classification performance in comparison with the state-of-the-art methods.
Translating PrEP effectiveness into public health impact: key considerations for decision-makers on cost-effectiveness, price, regulatory issues, distributive justice and advocacy for access

The extraordinary feat of proving the effectiveness of oral pre‐exposure prophylaxis (PrEP) in clinical trials in different populations in a variety of settings may prove to have been easier than ensuring it is used well. Decision‐makers must make difficult choices to realize the promise of antiretroviral prophylaxis for their countries. This paper outlines key economic, regulatory and distributive justice issues that must be addressed for effective and acceptable PrEP implementation.
Subtractive Hybridization Yields a Silver Resistance Determinant Unique to Nosocomial Pathogens in the Enterobacter cloacae Complex

ABSTRACT The heterogeneity and the increasing clinical importance of the Enterobacter cloacae complex have often been discussed. However, little is known about molecular factors causing pathogenicity within this nomenspecies. Here, we analyzed the genetic differences between an avirulent plant isolate and a pathogenic strain causing an outbreak with septicemia in three patients. We identified an IncHI-2 plasmid as a major difference between these two strains. Besides resistance to several antibiotics, this plasmid encoded a silver resistance determinant. We further showed that this sil determinant was present not only in the analyzed outbreak strain but also in the vast majority of clinical isolates of the E. cloacae complex, predominantly in (sub)species that frequently cause nosocomial infections. The identified sil determinant was highly conserved within the E. cloacae complex and mediated resistance to up to 600 μM silver nitrate. As silver is often used as a disinfectant and treatment for burn wounds, we present here an important fitness factor within the clinically most prevalent subspecies of the E. cloacae complex. This provides a possible explanation for their unequal involvement in nosocomial and especially burn wound infections.
A comparative study of pulsed dye laser versus long pulsed Nd:YAG laser treatment in recalcitrant viral warts

Abstract Background: Viral warts are common infectious skin disease induced by human papillomavirus (HPV). But the treatment of recalcitrant warts is still challenging. Objective: In this study, we compared the effectiveness of pulsed dye laser (PDL) and long pulsed Nd:YAG (LPNY) laser in the treatment of recalcitrant viral warts. Methods: We retrospectively analyzed the medical records of patients with recalcitrant warts treated with laser therapy between January 2013 and February 2016. Results: Seventy-two patients with recalcitrant warts were evaluated. Thirty-nine patients were treated with pulsed dye laser and thirty-three patients were treated with LPNY laser. The following parameters were used: PDL (spot size, 7 mm; pulse duration, 1.5 ms; and fluence, 10–14 J/cm2) and LPNY (spot size, 5 mm; pulse duration, 20 ms; and fluence, 240–300 J/cm2). Complete clearance of two patients (5.1%) in PDL group, and three patients (9.1%) in LPNY group were observed without significant side effects. The patients who achieved at least 50% improvement from baseline were 20 (51.3%) in PDL and 22 (66.7%) in LPNY, respectively. Conclusion: This research is meaningful because we compared the effectiveness of the PDL and LPNY in the recalcitrant warts. Both PDL and LPNY laser could be used as a safe and alternative treatment for recalcitrant warts.
Transcriptional Regulation of Oxytocin Receptor by Interleukin-1β and Interleukin-6.

The up-regulation of oxytocin (OT) receptors in late pregnancy results principally from increased synthesis of messenger RNA. The 5′-flanking region of the human OT receptor gene contains several putative binding sites for nuclear factor-interleukin-6 (NF-IL6), also known as CAAT/enhancer binding protein-β. This trans-acting factor modulates the expression of genes involved in acute inflammatory responses. Proinflammatory cytokines, such as IL-1β or IL-6, have been implicated as mediators in both preterm and term labor, particularly in association with intrauterine infection. We hypothesized that IL-1β and IL-6 induce OT receptor gene expression in human myometrial cells, and this is mediated by NF-IL6 and cognate response elements in the 5′-flanking region of the OT receptor gene. Contrary to the hypothesis, both IL-1β and IL-6 treatment resulted in a significant decrease in OT receptor messenger RNA measured by ribonuclease protection analysis. Using electrophoretic mobility shift assay, we have shown t.
Tuning Methods of PID Controller for DC Motor Speed Control

The traditional PID controllers are used for a long time to control the DC motor for many industrial processes, that because of the simplicity, flexibility, and satisfactory performance of this type of controller. This paper discusses the basic PID tuning method (Ziegler-Nichols) and its modification (Chien-Hrones-Reswick). Also, analysis the speed control DC motor response using the PID controller parameters that result from the tuning methods mentioned earlier. Moreover, explain the advantage and disadvantage of each formula of these methods. GUL/MATLAB windows used to implementing both methods to create more comfortable and friendly environment for better understanding of the PID controller tuning methods formula for engineering students and practicing engineers.
Antitumor Activity of Citrus maxima (Burm.) Merr. Leaves in Ehrlich's Ascites Carcinoma Cell-Treated Mice

Context. The plant Citrus maxima Merr. (Rutaceae), commonly known as shaddock or pomelo is indigenous to tropical parts of Asia. The objective of present study is to evaluate the methanol extract of Citrus maxima leaves for its antitumor activity against Ehrlich's Ascites Carcinoma cell in Swiss albino mice. Experimental design. The antitumor activity of methanol extract of Citrus maxima leaves (MECM) was evaluated against Ehrlich Ascites Carcinoma (EAC) cell line in Swiss albino mice. 2 × 106 cells were inoculated in different groups of animals. MECM (200 and 400 mg/kg BW i.p.) was administered for nine consecutive days. On day 10th half the animals of different groups were sacrificed for determination of tumor and haematological parameters and the rest half were kept with sufficient food and water ad libitum for determination of increase in life span. Result and Discussions. Oral administration of the extract at the doses of 200 and 400 mg/kg significantly decreased tumor parameters such as tumor volume, viable tumor cell count and increased body weight, hematological parameters and life span in respect of the EAC control mice. Conclusion. Experimental design exhibits significant antitumor activity of the extract (MECM) in a dose dependant manner.
Intrathalamic rhythmicity studied in vitro: nominal T-current modulation causes robust antioscillatory effects

Thalamocortical oscillations mediate both physiological and pathophysiological behaviors including sleep and generalized absence epilepsy (GA). Reciprocal intrathalamic circuitry and robust burst firing, dependent on underlying transient Ca current (IT) in thalamic neurons, support generation of such rhythms. In order to study the regulation of intrathalamic rhythm generation and the effects of GA anticonvulsants previously shown to reduce IT in acutely isolated thalamic neurons, we developed an in vitro rat thalamic slice preparation that retains sufficient intrathalamic circuitry to support evoked oscillations (range = 2.0–4.6 Hz, average = 2.7, n = 38), associated with burst firing in the thalamic reticular nucleus (nRt) and thalamic relay neurons. Extracellular stimulation of nRt evoked in relay neurons a biphasic inhibitory response with prominent GABAA and GABAB receptor-mediated components. The GABAA component was picrotoxin sensitive, outwardly rectifying and Cl- dependent, with a very negative reversal potential (-94 mV), indicating that an active extrusion mechanism exists in these cells to keep [Cl-]i < 5 mM. The GABAB component had a linear conductance, a reversal potential of -103 mV, and was quite long lasting (about 300 msec) so that rebound bursts often were generated on its decay phase, presumably leading to reexcitation of nRt through known excitatory connections. GABAB- mediated responses thus provide a timing mechanism for promoting slow intrathalamic oscillations. Reduction of IT (30–40%) by succinimides slightly increased the threshold for burst generation in relay and nRt cells, but there was little effect on either number of spikes/burst or intraburst frequency, and there were no other direct effects on other measures of cellular excitability. Intrathalamic oscillations were significantly reduced by these agents through a slight decrease in burst probability of thalamic neurons. We conclude that interactions between the intrinsic properties of thalamic neurons and intrathalamic circuitry lead to generation of slow oscillations. A similar mechanism may underlie the pathophysiological 3 Hz spike and wave EEG activity that characterizes GA. Furthermore, anti-GA drugs such as ethosuximide probably exert their action by reducing the burst-firing probability of neurons within populations of reciprocally interconnected relay and nRt neurons, thus producing a desynchronization of the thalamic circuit that prevents spike/wave generation.