bluuebunny/crossref_metadata_2025 huggingface dataset:
A new insight into the molecular hydrogen effect on coenzyme Q and mitochondrial function of rats
Authors: Gvozdjáková Anna , Kucharská Jarmila , Kura Branislav , Vančová Ol’ga , Rausová Zuzana , Sumbalová Zuzana , Uličná Ol’ga , Slezák Ján
Published: September 2019

Mitochondria are the major source of cellular energy metabolism. In the cardiac cells, mitochondria produce by way of the oxidative phosphorylation more than 90% of the energy supply in the form of ATP, which is utilized in many ATP-dependent processes, like cycling of the contractile proteins or maintaining ion gradients. Reactive oxygen species (ROS) are by-products of cellular metabolism and their levels are controlled by intracellular antioxidant systems. Imbalance between ROS and the antioxidant defense leads to oxidative stress and oxidative changes to cellular biomolecules. Molecular hydrogen (H2) has been proved as beneficial in the prevention and therapy of various diseases including cardiovascular disorders. It selectively scavenges hydroxyl radical and peroxynitrite, reduces oxidative stress, and has anti-inflammatory and anti-apoptotic effects. The effect of H2on the myocardial mitochondrial function and coenzyme Q levels is not well known. In this paper, we demonstrated that consumption of H2-rich water (HRW) resulted in stimulated rat cardiac mitochondrial electron respiratory chain function and increased levels of ATP production by Complex I and Complex II substrates. Similarly, coenzyme Q9levels in the rat plasma, myocardial tissue, and mitochondria were increased and malondialdehyde level in plasma was reduced after HRW administration. Based on obtained data, we hypothesize a new metabolic pathway of the H2effect in mitochondria on the Q-cycle and in mitochondrial respiratory chain function. The Q-cycle contains three coenzyme Q forms: coenzyme Q in oxidized form (ubiquinone), radical form (semiquinone), or reduced form (ubiquinol). H2may be a donor of both electron and proton in the Q-cycle and thus we can suppose stimulation of coenzyme Q production. When ubiquinone is reduced to ubiquinol, lipid peroxidation is reduced. Increased CoQ9concentration can stimulate electron transport from Complex I and Complex II to Complex III and increase ATP production via mitochondrial oxidative phosphorylation. Our results indicate that H2may function to prevent/treat disease states with disrupted myocardial mitochondrial function.
Dynamical and thermal stabilities of nonlinearly charged AdS black holes
Authors: Sajadi S. N. , Riazi N. , Hendi S. H.
Published: September 2019

In this paper, we study an extended phase space thermodynamics of a nonlinearly charged AdS black hole. We examine both the local and global stabilities, and possible phase transition of the black hole solutions. Finally, we compute quasi-normal modes via scalar perturbations and compare the obtained results with those of Reissner-Nordström black hole.
Operational Accepting State Complexity: The Unary and Finite Case
Authors: Dassow Jürgen
Published: September 2019

Let [Formula: see text] be the minimal number of accepting states which is sufficient for deterministic finite automata to accept [Formula: see text]. For a number [Formula: see text] and an [Formula: see text]-ary regularity preserving operation ∘, we define [Formula: see text] as the set of all integers [Formula: see text] such that there are [Formula: see text] languages [Formula: see text], [Formula: see text], with [Formula: see text] In this paper, we study these sets for the operations union, catenation, star, complement, set-subtraction, and intersection where we restrict to unary or finite or unary and finite languages [Formula: see text].
Variants of Networks of Evolutionary Processors with Polarizations and a Small Number of Processors
Authors: Freund Rudolf , Rogojin Vladimir , Verlan Sergey
Published: September 2019

We improve previous results obtained for networks of evolutionary processors — using the operations insertion, deletion, and substitution on strings — with elementary polarizations [Formula: see text] by showing that only seven processors are needed to obtain computational completeness. In the case of not requiring a special output node, only five processors are shown to be sufficient. We also prove that if the communication structure is allowed to be a directed graph without self-loops, then two polarizations are sufficient (with 12 or 17 nodes, depending on the definition). Moreover, we consider the case of not restricting the number of polarizations, thus obtaining the minimal number of three nodes for hybrid systems and even only one node where all three operations can be carried out.
Recognizing Union-Find Trees is NP-Complete, Even Without Rank Info
Authors: Gelle Kitti , Iván Szabolcs
Published: September 2019

Disjoint-Set forests, consisting of Union-Find trees, are data structures having a widespread practical application due to their efficiency. Despite them being well-known, no exact structural characterization of these trees is known (such a characterization exists for Union trees which are constructed without using path compression) for the case assuming union-by-rank strategy for merging. In this paper we provide such a characterization by means of a simple PUSH operation and show that the decision problems whether a (ranked or unranked) tree is a Union-Find tree are NP-complete, complementing our earlier similar result for the union-by-size strategy.
A new hyperchaotic particle motion system and its control
Authors: Cui Ning , Li Junhong
Published: September 2019

This paper formulates a new hyperchaotic system for particle motion. The continuous dependence on initial conditions of the system’s solution and the equilibrium stability, bifurcation, energy function of the system are analyzed. The hyperchaotic behaviors in the motion of the particle on a horizontal smooth plane are also investigated. It shows that the rich dynamic behaviors of the system, including the degenerate Hopf bifurcations and nondegenerate Hopf bifurcations at multiple equilibrium points, the irregular variation of Hamiltonian energy, and the hyperchaotic attractors. These results generalize and improve some known results about the particle motion system. Furthermore, the constraint of hyperchaos control is obtained by applying Lagrange’s method and the constraint change the system from a hyperchaotic state to asymptotically state. The numerical simulations are carried out to verify theoretical analyses and to exhibit the rich hyperchaotic behaviors.
Information propagation based on historical memory
Authors: Nian Fuzhong , Cong Anhui , Liu Rendong
Published: September 2019

This paper aims at the phenomenon of information selective propagation based on historical memory. A network model with memory strength and edge strength is established. The information propagation model with memory-clustering ability is designed with SIR model. And unsupervised learning is introduced to modify the performance. Based on the new network model, the core network and critical path that play a key role in the information propagation are found through the K-shell decomposition method. The research shows that the memory network contains an inertial channel for information propagation, it makes information propagation smooth. And information is selectively propagated in the new network, information is more inclined to propagate between nodes with powerful memory strength and close connections, in other words, people are more willing to propagate information to old friends who have been in contact for a long time instead of new friends.
Rolling tuning microstructure and tensile properties of nano/microcrystalline 304 stainless steel
Authors: Shi Yu , La Peiqing , Han Yijun , Wei Fuan , Sheng Jie , Li Zhengning
Published: September 2019

The effect of rolling parameters on microstructure and tensile properties of nanocrystalline/microcrystalline 304 stainless steel (SS) casted by the aluminothermic reaction was investigated in this work. It was found that majority of the nanocrystalline austenite of the 304 SS rolled at 700[Formula: see text]C and 900[Formula: see text]C grew up and transformed to sub-microcrystalline. While the nanocrystalline/microcrystalline structure still retained rolled at 900[Formula: see text]C with 40% deformation followed 600[Formula: see text]C with 70% thickness reduction, and microcrystalline austenite grains distributed evenly. The strength and ductility of the various rolled 304 SS were improved compared with the as-casted 304 SS steel. The steel rolled at 900[Formula: see text]C with 80% deformation exhibited a uniform elongation as large as 31.3%, which is almost the same ductility level of counterpart coarse-grained steel. The rolled steel at 700[Formula: see text]C with 80% deformation achieved the maximum tensile strength but the smallest elongation. The sample, two-step rolled at 900[Formula: see text]C with 40% thickness reduction and then 600[Formula: see text]C with 70% thickness reduction, yielded the satisfactory combination of strength and ductility. The yield strength and elongation were appropriate 767 MPa and 22.8%, respectively, which resulted from the optimized nanocrystalline/microcrystalline structure and distribution.
Intrinsic linking and knotting in tournaments
Authors: Fleming Thomas , Foisy Joel
Published: September 2019

A directed graph [Formula: see text] is intrinsically linked if every embedding of that graph contains a nonsplit link [Formula: see text], where each component of [Formula: see text] is a consistently oriented cycle in [Formula: see text]. A tournament is a directed graph where each pair of vertices is connected by exactly one directed edge.

We consider intrinsic linking and knotting in tournaments, and study the minimum number of vertices required for a tournament to have various intrinsic linking or knotting properties. We produce the following bounds: intrinsically linked ([Formula: see text]), intrinsically knotted ([Formula: see text]), intrinsically 3-linked ([Formula: see text]), intrinsically 4-linked ([Formula: see text]), intrinsically 5-linked ([Formula: see text]), intrinsically [Formula: see text]-linked ([Formula: see text]), intrinsically linked with knotted components ([Formula: see text]), and the disjoint linking property ([Formula: see text]).

We also introduce the consistency gap, which measures the difference in the order of a graph required for intrinsic [Formula: see text]-linking in tournaments versus undirected graphs. We conjecture the consistency gap to be nondecreasing in [Formula: see text], and provide an upper bound at each [Formula: see text].
Null helices and Cartan slant helices in Lorentz–Minkowski 3-space
Authors: Liu Tongchang , Pei Donghe
Published: September 2019

In this paper, we study null helices, Cartan slant helices and two special developable surfaces associated to them in Lorentz–Minkowski 3-space. We give a method using a special plane curve to construct a null helix. We also define the null tangential Darboux developable of a null Cartan curve, and we give a classification of singularities of it. Moreover, we study the relationship between null helices (or Cartan slant helices) with the developable surfaces of them.
Are We in the Right Path in Using Early Warning Systems?
Authors: Thandlam Venugopal , Rutgersson Anna , Rahaman Hasibur
Published: September 2019

This paper focusses on the recent tsunami in Indonesia and the factors led to the mass killing. We also discussed the failure of early warning systems, steps, methods, and technologies, in general, to improve the early warning systems in the future to mitigate the loss of lives and property during these impending disasters. We believe that this paper is timely as Indonesia has seen one of the worst tsunamis in recent years and the threat is still on. Hence, we stress the importance of improving and strengthening the existing early warning systems.
Predicting Women's Persistence in Computer Science- and Technology-Related Majors from High School to College
Authors: Weston Timothy J. , Dubow Wendy M. , Kaminsky Alexis
Published: September 2019

While demand for computer science and information technology skills grows, the proportion of women entering computer science (CS) fields has declined. One critical juncture is the transition from high school to college. In our study, we examined factors predicting college persistence in computer science- and technology-related majors from data collected from female high school students. We fielded a survey that asked about students’ interest and confidence in computing as well as their intentions to learn programming, game design, or invent new technology. The survey also asked about perceived social support from friends and family for pursuing computing as well as experiences with computing, including the CS Advanced Placement (AP) exam, out-of-school time activities such as clubs, and internships. Multinomial regression was used to predict persistence in computing and tech majors in college. Programming during high school, taking the CS Advanced Placement exam, and participation in the Aspirations awards program were the best predictors of persistence three years after the high school survey in both CS and other technology-related majors. Participation in tech-related work, internships, or after-school programs was negatively associated with persistence, and involvement with computing sub-domains of game design and inventing new applications were not associated with persistence. Our results suggest that efforts to broaden participation in computing should emphasize education in computer programming.
Invasion Biology, Ecology, and Management of Western Flower Thrips
Authors: Reitz Stuart R. , Gao Yulin , Kirk William D.J. , Hoddle Mark S. , Leiss Kirsten A. , Funderburk Joe E.
Published: September 2019

Western flower thrips, Frankliniella occidentalis, first arose as an important invasive pest of many crops during the 1970s–1980s. The tremendous growth in international agricultural trade that developed then fostered the invasiveness of western flower thrips. We examine current knowledge regarding the biology of western flower thrips, with an emphasis on characteristics that contribute to its invasiveness and pest status. Efforts to control this pest and the tospoviruses that it vectors with intensive insecticide applications have been unsuccessful and have created significant problems because of the development of resistance to numerous insecticides and associated outbreaks of secondary pests. We synthesize information on effective integrated management approaches for western flower thrips that have developed through research on its biology, behavior, and ecology. We further highlight emerging topics regarding the species status of western flower thrips, as well as its genetics, biology, and ecology that facilitate its use as a model study organism and will guide development of appropriate management practices.
Polycystin-1 Inhibits Cell Proliferation through Phosphatase PP2A/B56α
Authors: Tang Yan , Yang JungWoo , Zheng Wang , Tang Jingfeng , Chen Xing-Zhen , Yang Jianzheng , Wang Zuocheng
Published: September 2019

Autosomal dominant polycystic kidney disease (ADPKD) is associated with a number of cellular defects such as hyperproliferation, apoptosis, and dedifferentiation. Mutations in polycystin-1 (PC1) account for ∼85% of ADPKD. Here, we showed that wild-type (WT) or mutant PC1 composed of the last five transmembrane (TM) domains and the C-terminus (termed PC1-5TMC) inhibits cell proliferation and protein translation, as well as the downstream effectors of mTOR, consistent with previous reports. Knockdown of B56α, a subunit of the protein phosphatase 2A (PP2A) complex, or application of PP2A inhibitor okadaic acid or calyculin A, abolished the inhibitory effect of PC1 and PC1-5TMC on proliferation, indicating that PP2A/B56α mediates the regulation of cell proliferation by PC1. In addition to the phosphorylated S6 and 4EBP1, B56α was also downregulated by PC1 and PC1-5TMC. Furthermore, the downregulation of B56α, which may be mediated by mTOR but not AKT, can account for the dependence of PC1-inhibited proliferation on PP2A.
Grouting Mechanism of Cement‐Based Slurry in a Concentric Annulus under High Groundwater Pressure
Authors: Zhang Weijie , Han Chenghao , Zhang Lianzhen , Wei Jiuchuan , Yin Huiyong , Han Weiwei , Xie Chao , Zhou Wenwu
Published: September 2019

The flow of cement‐based slurry within concentric annular geometry is a major problem of study in the field of engineering, especially regarding the prevention of water ingress in an annulus formed during shaft construction utilizing the artificial freezing technique in China. In this study, an analytical governing equation of motion for the axial flow of an incompressible Newtonian fluid in a long concentric annulus is derived under the condition of high groundwater pressure. A stepwise calculation method is proposed to describe the grouting process based on two injection modes, namely, flow rate control and pressure control. The injection time is divided into a series of time segments; correspondingly, the grouted zone is subdivided into infinitesimal elements. Some key parameters, such as the location, dimension, slurry viscosity, and pressure gradient of each element, can be obtained using the developed MATLAB program. On this basis, the distribution of pressure and slurry viscosity in the grouted zone and the variations in injection pressure at the grouting point and grouting flow rate are determined. Two injection mode cases are investigated to reveal the grout propagation in the concentric annulus. Finally, numerical simulations are conducted and employed to validate and calibrate the calculated results. The results obtained by the present stepwise calculation method show good agreement with the numerical results.
Hypoglycemic and Toxic Effect ofMorus mesozygiaLeaf Extract on the Liver and Kidneys of Alloxan-Induced Hyperglycemic Wistar Rats
Authors: Tirwomwe Michael , Echoru Isaac , Maseruka Richard , Kimanje Kyobe Ronald , Byarugaba Wilson
Published: September 2019

Purpose. We investigated the hypoglycemic and toxic effect ofMorus mesozygialeaf extract on the liver and kidneys of alloxan-induced hyperglycemic wistar rats.Method. Phytochemical analysis was done. Diabetes was induced by the use of alloxan monohydrate in six groups of rats, i.e., 200 mg/kg, 400 mg/kg, 800 mg/kg, glibenclamide, normal saline, and normal control group. Blood glucose was measured at the time of inoculation, then at 1, 2, 3, and 4 hours after. After 14 days, rats were killed under anesthesia; blood collected for measurement of total protein, albumin, TAGs, cholesterol, AST, ALT, urea, and creatinine; and whole tissue of liver and kidneys used for histological studies.Results. The extract possessed antidiabetic effects between 400 mg/kg and 800 mg/kg doses, which we attributed to the presence of flavonoids, tannins, terpenoids, and amino acids. There was a drop in total protein and albumin with no statistical significance (P≥0.05). The changes in levels of ALT, TAGs, cholesterol, AST, creatinine, and urea were not statistically different from the standard diabetic drug. The extract was protective against histological damage as there were no significant lesions suggestive of toxicities in the liver and kidneys at doses below 800 mg/kg.Conclusion. We established credible evidence thatMorus mesozygialeaf extract has hypoglycemic effects between 400 mg/kg and 800 mg/kg and that it is safe on the liver and kidneys of wistar rats at doses less than 800 mg/kg.
Fusion of Vibration and Current Signatures for the Fault Diagnosis of Induction Machines
Authors: Liu Meng-Kun , Tran Minh-Quang , Weng Peng-Yi
Published: September 2019

Induction machines are widely used in the industry as one of the major actuators, such as water pumps, air compressors, and fans. It is necessary to monitor and diagnose these induction motors to prevent any sudden shut downs caused by premature failures. Numerous fault detection and isolation techniques for the diagnosis of induction machines have been proposed over the past few decades. Among these techniques, motor current signature analysis (MCSA) and vibration analysis are two of the most common signal‐based condition monitoring methods. They are often adopted independently, but each method has its strengths and weaknesses. This research proposed a systemic method to integrate the information received from the vibration and current measurements. We applied the wavelet packet decomposition to extract the time‐frequency features of the vibration and current measurements and used the support vector machines as classifiers for the initial decision‐making. The significant features were identified, and the performances of several classifiers were compared. As a result, the decision‐level sensor fusion based on the Sugeno fuzzy integral was proposed to integrate the vibration and current information to improve the accuracy of the diagnosis.
Macrophage Exclusion after Radiation Therapy (MERT): A First in Human Phase I/II Trial using a CXCR4 Inhibitor in Glioblastoma
Authors: Thomas Reena P. , Nagpal Seema , Iv Michael , Soltys Scott G. , Bertrand Sophie , Pelpola Judith S. , Ball Robyn , Yang Jaden , Sundaram Vandana , Chernikova Sophia B. , Lavezo Jonathan , Born Donald , Vogel Hannes , Brown J. Martin , Recht Lawrence D.
Published: September 2019

Purpose:

Preclinical studies have demonstrated that postirradiation tumor revascularization is dependent on a stromal cell–derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4)-driven process in which myeloid cells are recruited from bone marrow. Blocking this axis results in survival improvement in preclinical models of solid tumors, including glioblastoma (GBM). We conducted a phase I/II study to determine the safety and efficacy of Macrophage Exclusion after Radiation Therapy (MERT) using the reversible CXCR4 inhibitor plerixafor in patients with newly diagnosed glioblastoma.

Patients and Methods:

We enrolled nine patients in the phase I study and an additional 20 patients in phase II using a modified toxicity probability interval (mTPI) design. Plerixafor was continuously infused intravenously via a peripherally inserted central catheter (PICC) line for 4 consecutive weeks beginning at day 35 of conventional treatment with concurrent chemoradiation. Blood serum samples were obtained for pharmacokinetic analysis. Additional studies included relative cerebral blood volume (rCBV) analysis using MRI and histopathology analysis of recurrent tumors.

Results:

Plerixafor was well tolerated with no drug-attributable grade 3 toxicities observed. At the maximum dose of 400 μg/kg/day, biomarker analysis found suprathreshold plerixafor serum levels and an increase in plasma SDF-1 levels. Median overall survival was 21.3 months [95% confidence interval (CI), 15.9–NA] with a progression-free survival of 14.5 months (95% CI, 11.9–NA). MRI and histopathology support the mechanism of action to inhibit postirradiation tumor revascularization.

Conclusions:

Infusion of the CXCR4 inhibitor plerixafor was well tolerated as an adjunct to standard chemoirradiation in patients with newly diagnosed GBM and improves local control of tumor recurrences.
Pioglitazone, Nuclear Receptors, and Aerodigestive Prevention
Authors: Ondrey Frank G.
Published: September 2019

There has been intense interest in nuclear receptor targeting for cancer prevention. With the exception of estrogen antagonism in breast carcinoma there has not been widespread adoption or success of this strategy in clinical cancer prevention. Keith and colleagues have performed a careful study, which utilized the PPARγ nuclear receptor agonist, pioglitazone, a common type II diabetes agent, in subjects at risk for lung carcinoma. Although the results are not promising with this strategy, the study provides evidence for feasibility accrual and biomarker strategies that could be utilized to gain additional insight in future trials.
Transventricular Migration of Choroid Plexus Carcinoma Causing an Intraoperative Conundrum: A Case Report with a Review of the Literature
Authors: Ratha Vishwaraj , Kumar V.R. Roopesh
Published: September 2019

Migrating intracranial tumors are extremely rare occurrences in the neurosurgery literature. Introduction of any factor causing disequilibrium in cerebrospinal fluid circulation and pressure can potentially precipitate transventricular migration of pedunculated intraventricular lesions. The identification of such factors, prior to excision of intraventricular pedunculated tumors, is imperative to avoid intraoperative mismanagement. We report an extremely rare case of transventricular migration of a choroid plexus carcinoma in an infant, possibly precipitated by a ventriculoperitoneal (VP) shunt on the opposite side. This resulted in intraoperative confusion and a subsequent re-exploration of the opposite side for excision of the tumor. The literature provided only two similar occurrences in the past; however, in both cases, the migration was within the same ventricle and was documented prior to definitive resection. We report the first instance of transventricular migration of a tumor to the opposite ventricle following VP shunt which resulted in a negative intraoperative finding requiring a subsequent re-intervention on the opposite side. We believe that for any pedunculated intraventricular lesion, where an emergency management of hydrocephalus takes priority, a repeat neuroimaging is a must prior to definitive resection.
Evaluating Ketosis in Primate Field Studies: Validation of Urine Test Strips in Wild Bornean Orangutans (Pongo pygmaeus wurmbii)
Authors: Naumenko Daniel J. , Watford Malcolm , Atmoko Sri Suci Utami , Erb Wendy M. , Vogel Erin R.
Published: September 2019

The use of urine test strips (e.g., Roche Chemstrip®) has become the standard for quickly assessing the physiological condition and/or health of wild primates. These strips have been used to detect ketosis as a marker of fat catabolism in several primate taxa in their natural environments in response to changing food availability. However, the use of urine strips to determine ketosis has only been validated in human studies, and thus it remains unclear whether these strips accurately detect and quantify ketone bodies in nonhuman primates. We examined variations in ketone body concentrations in urine samples collected from wild Bornean orangutans at the Tuanan Orangutan Research Station. We assessed the accuracy of qualitative results from Chemstrip test strips in the field (i.e., negative, small, moderate, and large) using an enzyme-linked assay in the laboratory to determine the concentrations of acetoacetate of the same urine samples. Urine samples that tested positive for ketones in the field had significantly higher levels of ketones in the enzymatic assay compared to those that tested negative. There was significant variation in acetoacetate concentrations among the 4 Chemstrip values; however, post hoc tests revealed no significant differences between negative and small samples. We conclude that urinary test strips provide a useful tool for determining ketotic state in wild orangutans, but caution should be taken when interpreting results from samples showing only small levels of ketones on these strips.
Distinct Association of Serum Vitamin D Concentration with Disease Activity and Trough Levels of Infliximab and Adalimumab during Inflammatory Bowel Disease Treatment
Authors: Mechie Nicolae-Catalin , Mavropoulou Eirini , Ellenrieder Volker , Kunsch Steffen , Cameron Silke , Amanzada Ahmad
Published: September 2019

Background: Studies of serum vitamin D (Vit-D) levels in patients with inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor-alpha (anti-TNF-α) agents are scarce. The conjunction of Vit-D as well as zinc levels and anti-TNF-α-trough concentrations (TC) has not yet been explored. Objectives: To determine the association of serum Vit-D, zinc and C-reactive protein (CRP) levels with clinical and biochemical remission and a possible correlation with serum TC and antibody levels of anti-TNF-α. Methods: Serum Vit-D and zinc levels as well as Infliximab (IFX) and Adalimumab (ADA) TC during the maintenance phase of treatment were measured in 112 IBD patients. Statistical analysis were performed for clinical and biochemical remission. Results: Vit-D and zinc deficiency were detected in 58 and 4.5% of the patients respectively. In IFX-treated patients, IFX-TC, Vit-D and CRP levels were associated independently with clinical remission with an OR of 20 (95% CI 1.3–333, p = 0.03), 1.3 (95% CI 1.1–1.7, p = 0.02) and 0.4 (95% CI 0.2–0.8, p = 0.01) respectively. Serum IFX-TC and Vit-D levels correlated positively (r = 0.39, p = 0.001), while serum IFX-TC and CRP levels showed an inverse correlation (r = –0.43, p < 0.001). Only ­IFX-TC associated independently with biochemical remission with a threshold of 3.1 µg/mL. In ADA-treated patients, ADA-TC associated independently with clinical and biochemical remission with an OR of 2.5 (95% CI 1.1–5.0, p = 0.04) and 1.3 (95% CI 1.1–1.4, p = 0.03) respectively. The serum zinc level was associated neither with clinical nor with biochemical remission in either cohort. Conclusions: Our results indicate that serum Vit-D level may be a predictive marker in addition to drug trough levels in IBD patients treated with IFX. Furthermore, due to the correlation between serum IFX and Vit-D levels, Vit-D substitution should be conducted in patients with low Vit-D levels.
CRM197-Coupled Der p 2 Peptides Suppress Allergic Airway Inflammation in a Der p 2-Induced Asthma Mouse Model
Authors: Wang Cong , Wang Luo , Chen Ban-Cheng , Yu Hao , Li Lu , Zhang Kao-Yuan  , Yu Bo , Wei Zhun , Chen Xiao-Fan
Published: September 2019

Allergic diseases affect more than 25% of the global population. Der p 2 is the major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus. Allergen-specific immunotherapy is the only treatment to change the course of allergic diseases. In this study, two synthesized Der p 2 peptides coupled to cross-reacting material 197 (CRM197) showed reduced IgE reactivity and allergenic activity. CRM197-coupled Der p 2 peptides induced rDer p 2-specific IgG1 antibodies in mice, which could inhibit HDM-allergic patients’ IgE binding to rDer p 2. The immunity effects of CRM197-coupled Der p 2 peptides were studied in an rDer p 2-induced asthma mouse model. CRM197-coupled Der p 2 peptides can suppress asthmatic airway inflammation in this model. Analysis of IL-4, IL-5, and IFN-γ levels in bronchoalveolar lavage fluid revealed that the suppression was associated with a shift from a Th2 to a Th1 response. Thus, CRM197-bound Der p 2 peptides exhibited less allergenic activity than the rDer p 2 allergen, which preserved immunogenicity and may be candidates for mite allergy vaccines.
Extremely Low Birth Weight Predisposes to Impaired Renal Health: A Pooled Analysis
Authors: Gilarska Maja , Raaijmakers Anke , Zhang Zhen-Yu , Staessen Jan A. , Levtchenko Elena , Klimek Małgorzata , Grudzień Andrzej , Starzec Katarzyna , Allegaert Karel , Kwinta Przemko
Published: September 2019

Background: A number of studies examined the association between preterm delivery and kidney size and function later in life. However, the number of cases in published cohort studies is low. This study was aimed at performing a multicenter collaboration to pool data to obtain more accurate results to quantify the extent of renal impairment in former extremely low birth weight (ELBW; <1,000 g) children. Methodology: We performed a subject-level meta-analysis to pool data from Cracow (64 cases/34 controls) and Leuven (93 cases/87 controls). We assessed and analyzed cystatin C, estimated glomerular filtration rate (eGFR), ultrasound kidney length, and blood pressure (BP) in 11-year-old ELBW children compared with controls born at term. The prevalence of hypertension (HT) and prehypertension (preHT) in both groups was also analyzed. Results: The study group comprised 157 former ELBW children (gestational age 23–33 weeks and birth weight 430–1,000 g) and 123 children born at term. Former ELBW children had lower mean eGFR (100.62 ± 16.53 vs. 111.89 ± 15.26 mL/min/1.73 m2; p < 0.001), smaller absolute kidney length (8.56 ± 0.78 vs. 9.008 ± 0.73 cm; <0.001), and higher systolic (111.8 ± 9.8 vs. 107.2 ± 9.07 mm Hg; p = 0.01) and diastolic (68.6 ± 6.8 vs. 66.3 ± 7.7 mm Hg; p = 0.03) BP. Smaller renal size in former ELBW children was positively associated with lower birth weight, shorter gestational age, and severity of perinatal complications (intraventricular hemorrhage, length of stay, mechanical ventilation, and oxygen therapy). Conclusion: ELBW is associated with lower eGFR and a high frequency of preHT and HT.
Oncologic Outcome of Patients with (Low-Risk) Endometrial Carcinoma Undergoing Laparotomy versus Minimally Invasive Hysterectomy: A Retrospective Analysis
Authors: Dieterich Max , Schröter Victoria , Stubert Johannes , Reimer Toralf , Gerber Bernd , Stachs Angrit
Published: September 2019

Background: Patients with endometrial carcinoma (EC) frequently are obese and have various secondary diseases. We investigated the oncologic safety and complication rates of early-stage EC treated with laparotomy (LAP) versus minimally invasive hysterectomy (MIH). A secondary study aim was the evaluation of risk factors for relapse and complications. Methods: Data from the Cancer Registry Rostock, Germany, and the medical records of women diagnosed with type 1 EC between January 2005 and December 2014 were retrospectively evaluated. The baseline characteristics were analyzed with the χ2 test and Fisher’s exact test. Multivariate analysis with the Cox proportional-hazards model and logistic regression were performed to identify prognostic factors for time to event and risk factors for complications. Kaplan-Meier analysis was performed for disease-free and overall survival. Results: Of 350 evaluated patients, 242 underwent traditional LAP; on 108 patients, MIH was performed. The median follow-up period in the LAP group and the MIH group was 82 ± 31.1 and 71.1 ± 33.6 months, respectively (p = 0.10). The median time to event was 40.3 ± 28.1 months in the LAP group and 38.0 ± 27.5 months in the MIH group (p = 0.476). Significantly longer surgery times (p < 0.001) and more complications (p < 0.001) were observed in the LAP group. Disease-free survival after MIH was not significantly different from that after LAP (log-rank p = 0.052). Multimorbidity remained as the single risk factor for event/recurrence (p = 0.019) in multivariate analysis. Conclusions: MIH for early-stage EC may be an oncologically safe approach when compared to LAP, and its complication rates are lower; therefore, MIH represents the preferred approach for this patient cohort.
Prolonged Remission of Prostate Cancer Presenting as Endobronchial Metastases Following Total Androgen Blockade: A Case Report and Literature Review
Authors: Freund Robert S. , Pickens Peter V. , McDonald John Z. , Mino Robert D.
Published: September 2019

We present a rare case of prostatic endobronchial metastases that was successfully treated with total androgen blockade (TAB). This case demonstrates prolonged remission on continuous TAB and continued remission employing intermittent therapy.
A Prospective Study Evaluating the Clinical Utility of the Tag-Less Patency Capsule with Extended Time for Confirming Functional Patency
Authors: Watanabe Kenji , Ohmiya Naoki , Nakamura Masanao , Fujiwara Yasuhiro
Published: September 2019

Background: Patency confirmation is useful for avoiding the retention of capsule endoscopy (CE). We first evaluated the clinical utility of the tag-less PillCamTM Patency Capsule (PPC) for up to 72 h after ingestion prospectively. Methods: Excretion of an intact capsule or intact body within 72 h, or positive PPC image in the colon or negative PPC image by abdominal X-ray at 30 h was defined as confirmed functional patency. In patients with unconfirmed functional patency, balloon-assisted enteroscopy was performed to evaluate the reason. Results: Functional patency was confirmed in 44 of 57 patients. Patency was confirmed in 38 patients (66.7%) at 30 h. In 6 of 19 patients (31.6%) in whom patency was not confirmed at 30 h, patency was confirmed within 72 h and no capsule retention (CR) occurred. The rate of pan-enteroscopy did not differ between patients whose patency was confirmed at 30 h and those whose patency was confirmed within 72 h. Excretion time of the PPC significantly correlated with that of the capsule (r = 0.650). Severe adhesions (>5 cm) interfered with PPC passage in 2 patients, despite the absence of critical stricture. The rate of no CR in patients with functional patency confirmed by prior PPC was 97.7%. Misjudgment of the location of the PPC is a risk for CR. Conclusions: Extending the time to confirm functional patency to 72 h may be acceptable and increase the possibility to perform CE safely in whom CE can perform intrinsically. University Hospital Medical Information Network registration No: 000002564.
Lubiprostone Induces Claudin-1 and Protects Intestinal Barrier Function
Authors: Nishii Norio , Oshima Tadayuki , Li Min , Eda Hirotsugu , Nakamura Kumiko , Tamura Akio , Ogawa Tomohiro , Yamasaki Takahisa , Kondo Takashi , Kono Tomoaki , Tozawa Katsuyuki , Tomita Toshihiko , Fukui Hirokazu , Miwa Hiroto
Published: September 2019

Introduction: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro. Methods: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1β) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability. Results: IFNγ, IL-6, IL-1β, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1β, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone. Conclusion: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.
Comparison of a Modified Antegrade and Retrograde Ureteral Double-J Stenting Techniques during Laparoscopic and Robotic Pyeloplasty
Authors: Citgez Sinharib , Demirdag Cetin , Ozman Oktay , Ozden Sami Berk , Derekoylu Engin , Onal Bulent
Published: September 2019

Introduction: To compare the effect of a modified antegrade and retrograde double-J stenting techniques on stenting and operation time in patients who underwent laparoscopic or robotic pyeloplasty. Methods: A total of 74 patients undergoing transperitoneal laparoscopic or robotic pyeloplasty were enrolled into this study. The antegrade (Group 1) and retrograde (Group 2) techniques were compared for operation time, stenting time, complication, and reoperation rates. Results: There were 41 and 33 patients in Groups 1 and 2, respectively. Both groups were similar in terms of age, side, and gender distribution. The mean operation times were 122.4 and 139.7 min in Groups 1 and 2, respectively (p < 0.001). The stenting times were 2.39 and 14.15 min in Groups 1 and 2, respectively (p < 0.001). The reoperation and complication rates were 7.3 and 6%, respectively, and similar for both groups (p = 1). Conclusions: Our new technique significantly shortens the duration of laparoscopic and robotic pyeloplasty without compromising success and complication rates.
A Case Report of Locally Advanced Anal Cancer with Solitary Cutaneous Nodular Metastasis in the Ipsilateral Labia Majora Treated with Definitive Chemoradiotherapy
Authors: Sakanaka Katsuyuki , Ishida Yuichi , Mizowaki Takashi
Published: September 2019

Cutaneous metastasis from anal cancer is rare at the initial diagnosis. There is a dearth of information on definitive treatment for anal cancer with cutaneous metastasis. We report the case of a 63-year-old female with locally advanced anal cancer and solitary cutaneous nodular metastasis in the right labia majora identified at the initial diagnosis that was successfully treated with definitive chemoradiotherapy. She arrived at our hospital with complaints of an enlarging perineal itching nodule. Genital and rectal examination detected an anal tumor with perineal and rectal invasion. The biopsy specimen indicated it was a squamous cell carcinoma that was accompanied by right inguinal and external iliac lymph nodal metastases and solitary cutaneous nodular metastasis in the ipsilateral labia majora. She was diagnosed with anal cancer, clinical T3N1M1, stage IV (UICC-TNM 7th). She had good performance status and effective organ function. She received definitive chemoradiotherapy with irradiation fields that included the primary tumor, pelvic lymph nodal metastases, and solitary cutaneous genital metastasis. After completing the planned treatment, all tumors vanished without recurrences at 42 months after treatment. In conclusion, patients with locally advanced anal cancer may suffer genital cutaneous metastasis that develops with lymphatic drainage from the anus to the inguinal lymph nodes. Anal cancer with solitary genital cutaneous nodular metastasis can be considered as a local-regional disease and can be treated with chemoradiotherapy. Chemoradiotherapy achieved a cure in our case.
MCUB Regulates the Molecular Composition of the Mitochondrial Calcium Uniporter Channel to Limit Mitochondrial Calcium Overload During Stress
Authors: Lambert Jonathan P. , Luongo Timothy S. , Tomar Dhanendra , Jadiya Pooja , Gao Erhe , Zhang Xueqian , Lucchese Anna Maria , Kolmetzky Devin W. , Shah Neil S. , Elrod John W.
Published: September 2019

Background:

The mitochondrial calcium uniporter (mtCU) is an ≈700-kD multisubunit channel residing in the inner mitochondrial membrane required for mitochondrial Ca
2+
(
m
Ca
2+
) uptake. Here, we detail the contribution of MCUB, a paralog of the pore-forming subunit MCU, in mtCU regulation and function and for the first time investigate the relevance of MCUB to cardiac physiology.

Methods:

We created a stable
MCUB
knockout cell line (
MCUB
−/−
) using CRISPR-Cas9n technology and generated a cardiac-specific, tamoxifen-inducible MCUB mutant mouse (CAG-CAT-MCUB x MCM; MCUB-Tg) for in vivo assessment of cardiac physiology and response to ischemia/reperfusion injury. Live-cell imaging and high-resolution spectrofluorometery were used to determine intracellular Ca
2+
exchange and size-exclusion chromatography; blue native page and immunoprecipitation studies were used to determine the molecular function and impact of MCUB on the high-molecular-weight mtCU complex.

Results:

Using genetic gain- and loss-of-function approaches, we show that MCUB expression displaces MCU from the functional mtCU complex and thereby decreases the association of mitochondrial calcium uptake 1 and 2 (MICU1/2) to alter channel gating. These molecular changes decrease MICU1/2–dependent cooperative activation of the mtCU, thereby decreasing
m
Ca
2+
uptake. Furthermore, we show that MCUB incorporation into the mtCU is a stress-responsive mechanism to limit
m
Ca
2+
overload during cardiac injury. Indeed, overexpression of MCUB is sufficient to decrease infarct size after ischemia/reperfusion injury. However, MCUB incorporation into the mtCU does come at a cost; acute decreases in
m
Ca
2+
uptake impair mitochondrial energetics and contractile function.

Conclusions:

We detail a new regulatory mechanism to modulate mtCU function and
m
Ca
2+
uptake. Our results suggest that MCUB-dependent changes in mtCU stoichiometry are a prominent regulatory mechanism to modulate
m
Ca
2+
uptake and cellular physiology.
Use of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes in Preclinical Cancer Drug Cardiotoxicity Testing: A Scientific Statement From the American Heart Association
Authors: Gintant Gary , Burridge Paul , Gepstein Lior , Harding Sian , Herron Todd , Hong Charles , Jalife José , Wu Joseph C. ,   on behalf of the American Heart Association Council on Basic Cardiovascular Sciences
Published: September 2019

It is now well recognized that many lifesaving oncology drugs may adversely affect the heart and cardiovascular system, including causing irreversible cardiac injury that can result in reduced quality of life. These effects, which may manifest in the short term or long term, are mechanistically not well understood. Research is hampered by the reliance on whole-animal models of cardiotoxicity that may fail to reflect the fundamental biology or cardiotoxic responses of the human myocardium. The emergence of human induced pluripotent stem cell–derived cardiomyocytes as an in vitro research tool holds great promise for understanding drug-induced cardiotoxicity of oncological drugs that may manifest as contractile and electrophysiological dysfunction, as well as structural abnormalities, making it possible to deliver novel drugs free from cardiac liabilities and guide personalized therapy. This article briefly reviews the challenges of cardio-oncology, the strengths and limitations of using human induced pluripotent stem cell–derived cardiomyocytes to represent clinical findings in the nonclinical research space, and future directions for their further use.
Intra-genomic variability and pseudogenes in ribosomal ITS regions of Paraplagusia blochii (Pleuronectiformes: Cynoglossidae)
Authors: Gong Li , Kong Xiaoyu , Luo Hairong , Chen Shixi , Shi Wei , Yang Min
Published: September 2019

Eukaryotic nuclear ribosomal DNA (rDNA) typically evolves in a concerted manner, in which hundreds of rDNA sequences within species show little or no variations, whereas the sequences of different species diverge. There are few studies of the internal transcribed spacer regions (ITS1-5.8S-ITS2) in teleostean fishes and only one report on flatfishes. Here, we reported the discovery of two types of highly divergent ITS1-5.8S-ITS2 rDNA sequences (Type A and B) in the genome of the Bloch’s tonguesole, Paraplagusia blochii. These sequences mainly differ in sequence length, secondary structure, and minimum free energy. According to the potential features of pseudogenes, Type B sequences are speculated to be putative pseudogenic ITS regions. Cluster analyses also supported two major clades that corresponded to the sequence type. To the best of our knowledge, this is the first report of the ITS regions of tonguefish, and may therefore provide useful information for future studies of the rDNA of flatfishes as well as the patterns of rDNA evolution in teleostean fishes.