bluuebunny/crossref_metadata_2025 huggingface dataset:
Complexity of shadows and traversing flows in terms of the simplicial volume
Authors: Katz Gabriel
Published: November 2015

We combine Gromov’s amenable localization technique with the Poincaré duality to study the traversally generic vector flows on smooth compact manifolds [Formula: see text] with boundary. Such flows generate well-understood stratifications of [Formula: see text] by the trajectories that are tangent to the boundary in a particular canonical fashion. Specifically, we get lower estimates of the numbers of connected components of these flow-generated strata of any given codimension. These universal bounds are basically expressed in terms of the normed homology of the fundamental groups [Formula: see text] and [Formula: see text], where [Formula: see text] denotes the double of [Formula: see text]. The norm here is the Gromov simplicial semi-norm in homology. It turns out that some close relatives of the normed homology spaces [Formula: see text], [Formula: see text] form obstructions to the existence of [Formula: see text]-convex traversally generic vector flows on [Formula: see text].
Dielectric properties of BaMg1∕3Nb2∕3O3 doped Ba0.45Sr0.55Tio3 thin films for tunable microwave applications
Authors: Alema Fikadu , Pokhodnya Konstantin
Published: November 2015

Ba(Mg[Formula: see text]Nb[Formula: see text]O3 (BMN) doped and undoped Ba[Formula: see text]Sr[Formula: see text]TiO3 (BST) thin films were deposited via radio frequency magnetron sputtering on Pt/TiO2/SiO2/Al2O3 substrates. The surface morphology and chemical state analyses of the films have shown that the BMN doped BST film has a smoother surface with reduced oxygen vacancy, resulting in an improved insulating properties of the BST film. Dielectric tunability, loss, and leakage current (LC) of the undoped and BMN doped BST thin films were studied. The BMN dopant has remarkably reduced the dielectric loss ([Formula: see text]38%) with no significant effect on the tunability of the BST film, leading to an increase in figure of merit (FOM). This is attributed to the opposing behavior of large Mg[Formula: see text] whose detrimental effect on tunability is partially compensated by small Nb[Formula: see text] as the two substitute Ti[Formula: see text] in the BST. The coupling between [Formula: see text] and V[Formula: see text] charged defects suppresses the dielectric loss in the film by cutting electrons from hopping between Ti ions. The LC of the films was investigated in the temperature range of 300–450[Formula: see text]K. A reduced LC measured for the BMN doped BST film was correlated to the formation of defect dipoles from [Formula: see text], V[Formula: see text] and Nb[Formula: see text] charged defects. The carrier transport properties of the films were analyzed in light of Schottky thermionic emission (SE) and Poole–Frenkel (PF) emission mechanisms. The result indicated that while the carrier transport mechanism in the undoped film is interface limited (SE), the conduction in the BMN doped film was dominated by bulk processes (PF). The change of the conduction mechanism from SE to PF as a result of BMN doping is attributed to the presence of uncoupled Nb[Formula: see text] sitting as a positive trap center at the shallow donor level of the BST.
Nucleon and Δ electromagnetic form factors
Authors: Bartoš Erik , Dubnička Stanislav , Dubničková Anna-Zuzana
Published: November 2015

The unitary and analytic model for nucleons works very well. The model for spin [Formula: see text] baryons can predict static parameters for [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]. We prepared the scheme how to construct the model also for [Formula: see text] nucleon resonance. It was used to describe transition form factor [Formula: see text] and the experimentally measured ratio [Formula: see text] with the help of relations for magnetic dipole transition and charge quadrupole form factors.
Self-similarity of negative particle production from the Beam Energy Scan Program at STAR
Authors: Tokarev Mikhail
Published: November 2015

We present the spectra of negative charged particle production in Au [Formula: see text] Au collisions from STAR for the first phase of the RHIC Beam Energy Scan Program measured over a wide range of collision energy [Formula: see text], and transverse momentum of produced particle in different centralities at [Formula: see text]. The spectra demonstrate strong dependence on collision energy which enhances with [Formula: see text]. An indication of self-similarity of negative charged particle production in Au [Formula: see text] Au collisions is found. The constituent energy loss as a function of energy and centrality of collisions and transverse momentum of inclusive particle was estimated in the [Formula: see text]-scaling approach. The energy dependence of the model parameters - the fractal and fragmentation dimensions and “specific heat”, was studied.
Physical observables in the decay Λb → Λc(→ Λ + π) + τ− + ν̄τ
Authors: Habyl N. , Gutsche Thomas , Ivanov Mikhail A. , Körner Jürgen G. , Lyubovitskij Valery E. , Santorelli Pietro
Published: November 2015

We analyze the tauonic semileptonic baryon decays [Formula: see text] with particular emphasis on the lepton helicity flip contributions which vanish for zero lepton masses. We calculate the total rate, differential decay distributions, the longitudinal and transverse polarization components of the [Formula: see text] and the [Formula: see text], and the lepton-side forward-backward asymmetries. We use the covariant confined quark model to provide numerical results on these observables.
The plasma membrane as a capacitor for energy and metabolism
Authors: Ray Supriyo , Kassan Adam , Busija Anna R. , Rangamani Padmini , Patel Hemal H.
Published: November 2015

When considering which components of the cell are the most critical to function and physiology, we naturally focus on the nucleus, the mitochondria that regulate energy and apoptotic signaling, or other organelles such as the endoplasmic reticulum, Golgi, ribosomes, etc. Few people will suggest that the membrane is the most critical element of a cell in terms of function and physiology. Those that consider the membrane critical will point to its obvious barrier function regulated by the lipid bilayer and numerous ion channels that regulate homeostatic gradients. What becomes evident upon closer inspection is that not all membranes are created equal and that there are lipid-rich microdomains that serve as platforms of signaling and a means of communication with the intracellular environment. In this review, we explore the evolution of membranes, focus on lipid-rich microdomains, and advance the novel concept that membranes serve as “capacitors for energy and metabolism.” Within this framework, the membrane then is the primary and critical regulator of stress and disease adaptation of the cell.
Phenotypic plasticity in the common snapping turtle (Chelydra serpentina): long-term physiological effects of chronic hypoxia during embryonic development
Authors: Wearing Oliver H. , Eme John , Rhen Turk , Crossley Dane A.
Published: November 2015

Studies of embryonic and hatchling reptiles have revealed marked plasticity in morphology, metabolism, and cardiovascular function following chronic hypoxic incubation. However, the long-term effects of chronic hypoxia have not yet been investigated in these animals. The aim of this study was to determine growth and postprandial O2consumption (V̇o2), heart rate ( fH), and mean arterial pressure ( Pm, in kPa) of common snapping turtles ( Chelydra serpentina) that were incubated as embryos in chronic hypoxia (10% O2, H10) or normoxia (21% O2, N21). We hypothesized that hypoxic development would modify posthatching body mass, metabolic rate, and cardiovascular physiology in juvenile snapping turtles. Yearling H10 turtles were significantly smaller than yearling N21 turtles, both of which were raised posthatching in normoxic, common garden conditions. Measurement of postprandial cardiovascular parameters and O2consumption were conducted in size-matched three-year-old H10 and N21 turtles. Both before and 12 h after feeding, H10 turtles had a significantly lower fHcompared with N21 turtles. In addition, V̇o2was significantly elevated in H10 animals compared with N21 animals 12 h after feeding, and peak postprandial V̇o2occurred earlier in H10 animals. Pmof three-year-old turtles was not affected by feeding or hypoxic embryonic incubation. Our findings demonstrate that physiological impacts of developmental hypoxia on embryonic reptiles continue into juvenile life.
Prostaglandin E2/cyclooxygenase pathway in human skeletal muscle: influence of muscle fiber type and age
Authors: Liu Sophia Z. , Jemiolo Bozena , Lavin Kaleen M. , Lester Bridget E. , Trappe Scott W. , Trappe Todd A.
Published: November 2015

Prostaglandin E2(PGE2) produced by the cyclooxygenase (COX) pathway regulates skeletal muscle protein turnover and exercise training adaptations. The purpose of this study was twofold: 1) define the PGE2/COX pathway enzymes and receptors in human skeletal muscle, with a focus on type I and II muscle fibers; and 2) examine the influence of aging on this pathway. Muscle biopsies were obtained from the soleus (primarily type I fibers) and vastus lateralis (proportionally more type II fibers than soleus) of young men and women ( n = 8; 26 ± 2 yr), and from the vastus lateralis of young ( n = 8; 25 ± 1 yr) and old ( n = 12; 79 ± 2 yr) men and women. PGE2/COX pathway proteins [COX enzymes (COX-1 and COX-2), PGE2synthases (cPGES, mPGES-1, and mPGES-2), and PGE2receptors (EP1, EP2, EP3, and EP4)] were quantified via Western blot. COX-1, cPGES, mPGES-2, and all four PGE2receptors were detected in all skeletal muscle samples examined. COX-1 ( P < 0.1) and mPGES-2 were ∼20% higher, while EP3 was 99% higher and EP4 57% lower in soleus compared with vastus lateralis ( P < 0.05). Aging did not change the level of skeletal muscle COX-1, while cPGES increased 45% and EP1 ( P < 0.1), EP3, and EP4 decreased ∼33% ( P < 0.05). In summary, PGE2production capacity and receptor levels are different in human skeletal muscles with markedly different type I and II muscle fiber composition. In aging skeletal muscle, PGE2production capacity is elevated and receptor levels are downregulated. These findings have implications for understanding the regulation of skeletal muscle adaptations to exercise and aging by the PGE2/COX pathway and related inhibitors.
Evidence against perfect integration of sensory information during perceptual decision making
Authors: Carland Matthew A. , Marcos Encarni , Thura David , Cisek Paul
Published: November 2015

Perceptual decision making is often modeled as perfect integration of sequential sensory samples until the accumulated total reaches a fixed decision bound. In that view, the buildup of neural activity during perceptual decision making is attributed to temporal integration. However, an alternative explanation is that sensory estimates are computed quickly with a low-pass filter and combined with a growing signal reflecting the urgency to respond and it is the latter that is primarily responsible for neural activity buildup. These models are difficult to distinguish empirically because they make similar predictions for tasks in which sensory information is constant within a trial, as in most previous studies. Here we presented subjects with a variant of the classic constant-coherence motion discrimination (CMD) task in which we inserted brief motion pulses. We examined the effect of these pulses on reaction times (RTs) in two conditions: 1) when the CMD trials were blocked and subjects responded quickly and 2) when the same CMD trials were interleaved among trials of a variable-motion coherence task that motivated slower decisions. In the blocked condition, early pulses had a strong effect on RTs but late pulses did not, consistent with both models. However, when subjects slowed their decision policy in the interleaved condition, later pulses now became effective while early pulses lost their efficacy. This last result contradicts models based on perfect integration of sensory evidence and implies that motion signals are processed with a strong leak, equivalent to a low-pass filter with a short time constant.
Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer’s Disease
Authors: Verdile Giuseppe , Keane Kevin N. , Cruzat Vinicius F. , Medic Sandra , Sabale Miheer , Rowles Joanne , Wijesekara Nadeeja , Martins Ralph N. , Fraser Paul E. , Newsholme Philip
Published: November 2015

Type 2 diabetes (T2DM), Alzheimer’s disease (AD), and insulin resistance are age‐related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer’s disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid‐β (Aβ) protein accumulation, and mitochondrial dysfunction link T2DM and AD.
Synergistic Apoptotic Effect of Crocin and Paclitaxel or Crocin and Radiation on MCF-7 Cells, a Type of Breast Cancer Cell Line
Authors: Vali Faeze , Changizi Vahid , Safa Majid
Published: November 2015

Background.Chemotherapy, radiotherapy, and surgery are routine treatments of breast cancer. However, these methods could only improve the living survival. Nowadays the combined therapy including herbals such as crocin is to study for improving breast cancer treatment. The purpose of this study was to evaluate the effects of crocin, paclitaxel, and radiation on MCF-7 cell.Methods.To evaluate the effect of crocin, paclitaxel, and radiation on survival rate of MCF-7 cells MTT assay was done. To investigate the apoptotic effect of experimental groups PI-flow cytometry was used and expression of apoptotic proteins (caspase-7, caspase-9, PARP, and p53) was studied by western blot.Results.This study revealed that the combined therapy of 0.01µmol/mL paclitaxel and 2.5 mg/mL crocin after 48 h could cause IC50 for MCF-7 cell line. This study showed that the combined therapy of 2 Gy gamma radiation with crocin could rise apoptosis in MCF-7 cell line from 21% (related to using 2 Gy gamma radiation alone) to 46.6%.Conclusion.Crocin and paclitaxel and crocin and gamma radiation had synergistic effect on MCF-7 cell line to get more significant apoptosis.
C-Reactive Protein and Breast Cancer: New Insights from Old Molecule
Authors: Asegaonkar Shilpa Balaji , Asegaonkar Balaji Narayanrao , Takalkar Unmesh Vidyadhar , Advani Suresh , Thorat Anand Pandurang
Published: November 2015

Recently an association between breast cancer and inflammation has emerged as the seventh hallmark of cancer. Chronic inflammation is a key contributor in the development and progression of carcinogenesis. Inflammatory pathways play an important role in the causation of breast cancer. C-reactive protein (CRP) an acute-phase reactant inflammatory protein is synthesized in hepatocytes in response to cytokines that are released from leucocytes within the tumor microenvironment. Several epidemiological studies appraised an association of CRP with breast cancer risk with inconsistent findings. Elevated levels at the time of diagnosis of breast cancer indicate aggressiveness of the tumor. CRP is also a well-established independent prognostic marker. Breast cancer survivors with the state of chronic inflammation are at risk of recurrence and metabolic disturbances. CRP lowering agents along with chemotherapeutic drugs will improve the survival of breast cancer patients. Also, it is a risk predictor for subsequent cardiotoxicity in patients receiving chemotherapy. The present review is aimed at elucidating the role of C-reactive protein, as an inflammatory risk marker and prognostic predictor of breast cancer. It also focuses on conflicting views on the role of CRP in breast cancer and its impact on therapeutic interventions.
Caregiver Preferences regarding Technology’s Role in Supporting Adolescent Weight Management
Authors: Bianchi-Hayes Josette M. , Schoenfeld Elinor R. , Cataldo Rosa , Huang Jiayu , Pati Susmita
Published: November 2015

Background. Health technology provides a wealth of strategies to address chronic health issues, such as childhood obesity. Few studies have assessed parental preferences regarding use of health technology to support weight management for adolescents. Objective. This study determined caregiver beliefs, attitudes, and practices towards using traditional methods and technology-based health applications to address weight management among overweight adolescents. Methods. Self-administered surveys were distributed to caregivers of children ages 11–18 years in Stony Brook Children’s Hospital outpatient offices with a BMI ≥ 85th percentile for age, gender. The data were entered into StudyTrax research platform and analyzed using SAS. Results.  N=114. Mean BMI z-score = 1.95 ± 0.50. Two-thirds (65.8%) of caregivers preferred a weight management program that includes both traditional and technology components. Most parents rated involvement in program development (68.1%), access to content (72.4%) as very important. Those who believed their child’s weight was a problem (p=0.01) were more likely than other parents to prefer a program that combined both traditional and technology components. Conclusions. Parents’ perceptions of their child’s weight drove preferences about incorporating technology elements into a weight management program. Future weight management programs should incorporate parental content preferences and be tailored to different age groups.
Histomorphometric Evaluation of Superovulation Effect on Follicular Development after Autologous Ovarian Transplantation in Mice
Authors: Tamadon Amin , Raayat Jahromi Alireza , Rahmanifar Farhad , Ayaseh Mohammad , Koohi-Hosseinabadi Omid , Moghiminasr Reza
Published: November 2015

The effect of superovulation by pregnant mare serum gonadotropin (PMSG) on autologous transplanted ovaries in the lumbar muscles of mice was histomorphometrically evaluated using the indices of number and volume of different kind of follicles and volume of corpora lutea, ovary, and stroma. Angiogenesis was observed after mouse ovarian transplantation on days 14 and 21 after ovarian grafting. After transplantation, the total number and volume of primary and secondary follicles reduced, while PMSG superovulation increased the total number and total volume of tertiary follicles and also the ovarian volume after transplantation. Transplantation increased the average size of primary, secondary, and tertiary follicles. Therefore, primary and secondary follicles can survive after autologous transplantation but their reservations diminished by increasing the time of transplantation. However, number of tertiary follicles and their response to superovulation increased over time after transplantation.
Frequency Distribution of Mannose Binding Lectin-2 and Vitamin D Receptor Gene Variants: Putative Markers for Tuberculosis
Authors: Gupta Anuroopa , Padh Harish
Published: November 2015

Genetic polymorphism in Mannose Binding Lectin-2 (MBL-2) and Vitamin D Receptor (VDR) is known to influence the susceptibility to tuberculosis. The objective of the present study was to evaluate the frequency distribution of theMBL-2promoter and structural polymorphism (−550 H/L, −221 Y/X, and +4 P/Q; R52C, G54D, and G57F) andVDRpolymorphism (FokI,BsmI,TaqI, andApaI) in healthy individuals of Indian population and comparative analysis with the global population. In Indian population, the frequency ofVDRmutant alleles “f” forFokI, “b” forBsmI, “t” forTaqI, and “a” forApaIwas 25%, 54%, 30%, and 61%, respectively. The allelic frequency ofMBL-2promoter polymorphism −550 H/L was H versus L: 32% versus 68%, −221 Y/X was Y versus X: 68% versus 32%, and +4 P/Q was P versus Q: 78% versus 22%. Mutant allelic frequencies of theMBL-2exon 1 D, B, and C allele were 6%, 11%, and 3%, respectively. Comparative analysis with global populations showed a noteworthy difference forMBL-2andVDRpolymorphism frequency distribution, indicating the ethnic variability of Indians. The study signifies the differential distribution of susceptibility genes in Indian population, which can influence the understanding of the pathophysiology of tuberculosis in Indian population.
DOA Estimation Based on Sparse Signal Recovery Utilizing Double-Threshold Sigmoid Penalty
Authors: Wang Hanbing , Li Hui , Li Bin
Published: November 2015

This paper proposes a new algorithm based on sparse signal recovery for estimating the direction of arrival (DOA) of multiple sources. The problem model we build is about the sample covariance matrix fitting by unknown source powers. We enhance the sparsity by the double-threshold sigmoid penalty function which can approximate thel0norm accurately. Our method can distinguish closely spaced sources and does not need the knowledge of the number of the sources. In addition, our method can also perform well in low SNR. Besides, our method can handle more sources accurately than other methods. Simulations are done to certify the great performance of the proposed method.
Fingolimod Real World Experience: Efficacy and Safety in Clinical Practice
Authors: Fonseca Joaquim
Published: November 2015

Fingolimod is a multiple sclerosis treatment licensed in Europe since 2011. Its efficacy has been demonstrated in three large phase III trials, used in the regulatory submissions throughout the world. As usual, in these trials the inclusion and exclusion criteria were designed to obtain a homogeneous population, with interchangeable characteristics in the different treatment arms. Although this is the best strategy to achieve a robust answer to the investigation question, it does not guaranty the treatment efficacy in the clinical practice, since in the real world there are concomitant treatments, comorbidities, adherence, and persistence challenges. But, to make informed treatment decision for a real life patient, we need to have evidence of the treatment efficacy, what has been called treatment effectiveness. This work aims to review fingolimod effectiveness, using, as source of information, abstracts, posters, and manuscripts. This unorthodox strategy was developed because more than half of the published experience with fingolimod is still on abstracts and posters. Only a small part of the studies reviewed are already published in peer reviewed journals. Fingolimod seems to be, at least, as effective and safe as it was on clinical trials, and with its long-term experience no new safety signals were observed.
Quantitative Evaluation of Growth Plates around the Knees of Adolescent Soccer Players by Diffusion-Weighted Magnetic Resonance Imaging
Authors: Krajnc Zmago , Rupreht Mitja , Drobnič Matej
Published: November 2015

Purpose. To quantitatively evaluate growth plates around the knees in adolescent soccer players utilizing the diffusion-weighted MR imaging (DWI).Methods. The knees and adjacent growth plates of eleven 14-year-old male soccer players were evaluated by MRI before (end of season’s summer break) and after two months of intense soccer training. MRI evaluation was conducted in coronal plane by PD-FSE and DWI. All images were screened for any major pathological changes. Later, central growth plate surface area (CGPSA) was measured and the apparent diffusion coefficient (ADC) values were calculated in two most central coronal slices divided into four regions: distal femur medial (DFM), distal femur lateral (DFL), proximal tibia medial (PTM), and proximal tibia lateral (PTL).Results. No gross pathology was diagnosed on MRI. CGPSA was not significantly reduced: DFM 278 versus 272, DFL 265 versus 261, PTM 193 versus 192, and PTL 214 versus 210. ADC decrease was statistically significant only for PTM: DFM 1.27 versus 1.22, DFL 1.37 versus 1.34, PTM 1.13 versus 1.03 (p=0.003), and PTL 1.28 versus 1.22.Conclusions. DWI measurements indicate increased cellularity in growth plates around knees in footballers most prominent in PTM after intense training. No detectable differences on a standard PD-FSE sequence were observed.
Durability Study on High Calcium Fly Ash Based Geopolymer Concrete
Authors: Lavanya Ganesan , Jegan Josephraj
Published: November 2015

This study presents an investigation into the durability of geopolymer concrete prepared using high calcium fly ash along with alkaline activators when exposed to 2% solution of sulfuric acid and 5% magnesium sulphate for up to 45 days. The durability was also assessed by measuring water absorption and sorptivity. Ordinary Portland cement concrete was also prepared as control concrete. The grades chosen for the investigation were M20, M40, and M60. The alkaline solution used for present study is the combination of sodium silicate and sodium hydroxide solution with the ratio of 2.50. The molarity of sodium hydroxide was fixed as 12. The test specimens were150×150×150 mm cubes,100×200 mm cylinders, and100×50 mm discs cured at ambient temperature. Surface deterioration, density, and strength over a period of 14, 28, and 45 days were observed. The results of geopolymer and ordinary Portland cement concrete were compared and discussed. After 45 days of exposure to the magnesium sulfate solution, the reduction in strength was up to 12% for geopolymer concrete and up to 25% for ordinary Portland cement concrete. After the same period of exposure to the sulphuric acid solution, the compressive strength decrease was up to 20% for geopolymer concrete and up to 28% for ordinary Portland cement concrete.
Bianchi Type-I Universe with Cosmological Constant and Quadratic Equation of State inf(R,T)Modified Gravity
Authors: Singh G. P. , Bishi Binaya K.
Published: November 2015

This paper deals with the study of Bianchi type-I universe in the context off(R,T)gravity. Einstein’s field equations inf(R,T)gravity have been solved in the presence of cosmological constantΛand quadratic equation of state (EoS)p=αρ2-ρ, whereα≠0is a constant. Here, we have discussed two classes off(R,T)gravity; that is,f(R,T)=R+2f(T)andf(R,T)=f1(R)+f2(T). A set of models has been taken into consideration based on the plausible relation. Also, we have studied some physical and kinematical properties of the models.
Bessel Beam Diffraction by an Aperture in an Opaque Screen
Authors: Basdemir Husnu Deniz
Published: November 2015

The scattering of the Bessel beam by a circular aperture in an opaque screen is investigated by the geometrical theory of diffraction approach. The geometrical optics and diffracted and scattered fields are obtained. The effect of the aperture to the scattering process is analyzed. The uniform versions of field expressions are derived. The geometrical optics and diffracted and scattered fields are examined numerically.
PPAR-αAgonist Fenofibrate Decreased Serum Irisin Levels in Type 2 Diabetes Patients with Hypertriglyceridemia
Authors: Feng Xiaomeng , Gao Xia , Jia Yumei , Zhang Heng , Pan Qingrong , Yao Zhi , Yang Ning , Liu Jia , Xu Yuan , Wang Guang , Yang Xinchun
Published: November 2015

Irisin is related to insulin resistance and metabolic disorders. The physiologic effects of irisin are partially mediated through peroxisome proliferator-activated receptor-α(PPAR-α). We investigated the effect of fenofibrate, a PPAR-αagonist, on serum irisin in type 2 diabetes patients with hypertriglyceridemia. This study evaluated cross-sectional and interventional studies of 25 type 2 diabetes patients with hypertriglyceridemia (group A) and 40 controls (group B). Group A was treated with fenofibrate (200 mg/day) for 8 weeks. Serum irisin and clinical characteristics were examined. Serum irisin was significantly higher in group A compared with group B (45.15±10.48versus35.38±9.97 ng/ml,P<0.001) and correlated with body mass index (r=0.314,P=0.011), fasting blood glucose (r=0.399,P=0.001), total cholesterol (r=0.256,P=0.040), and high-density lipoprotein cholesterol (r=0.247,P=0.047). In multiple regression analysis after controlling for confounders, only fasting blood glucose (β=5.615,P<0.001) and high-density lipoprotein cholesterol (β=19.483,P<0.001) were independently related to serum irisin. After 8 weeks of fenofibrate treatment, serum irisin significantly decreased in group A compared with baseline (45.15±10.48versus38.74±12.54 ng/ml,P=0.011). Conclusively, fenofibrate decreased serum irisin in type 2 diabetes patients with hypertriglyceridemia, indicating that PPAR-αagonists may protect against metabolic disorders by improving irisin resistance.
Opportunistic Infections in Patients with HTLV-1 Infection
Authors: Tanaka Toshiki , Sekioka Toshio , Usui Masakatsu , Imashuku Shinsaku
Published: November 2015

As an acquired immunodeficiency, human immunodeficiency virus (HIV) infection is primarily responsible for opportunistic infections in infected patients. However, opportunistic infections also occur in individuals with human T cell lymphotrophic virus type 1 (HTLV-1) infection. Here, we report opportunistic infections in two Japanese HTLV-1-seropositive patients. The first patient was a 67-year-old male, who had cytomegalovirus infection associated with esophagogastritis and terminal ileitis. The patient was HTLV-1-positive and was diagnosed with smoldering adult T cell leukemia (ATL). High levels of serum soluble IL-2 receptor (sIL-2R; 4,304 U/mL) and an increased percentage of CD4+CD25+ T cells (75.5%) in peripheral blood were also detected. The second patient was a 78-year-old female, a known asymptomatic HTLV-1 carrier, who presented with persistent herpes zoster, followed byPneumocystis jiroveciipneumonia. Disease progression of smoldering ATL along opportunistic infections was observed with very high levels of serum sIL-2R (14,058 U/mL) and an increased percentage of CD4+CD25+ T cells (87.2%) in peripheral blood. In patients with suspected opportunistic infections, both HTLV-1 and HIV should be considered. In HTLV-1-positive patients, an increase in the CD4+CD25+ T cell subset may have its value as a prognostic marker.
Transvaginal Resection of a Bladder Leiomyoma Misdiagnosed with a Vaginal Mass: A Case Report and Literature Review
Authors: Yin Fu-Fen , Wang Ning , Wang You-Lin , Bi Xiao-Ning , Xu Xiao-Hui , Wang Yan-Kui
Published: November 2015

Bladder leiomyoma is a rare benign tumor and it could be easily misdiagnosed with many other pelvic diseases, especially obstetrical and gynecological diseases; abdominal, laparoscopic, and transurethral resection of bladder leiomyoma have been reported. Herein, we present a case of bladder leiomyoma misdiagnosed with a vaginal mass preoperatively; the mass was isolated, enucleated from the bladder neck, and removed transvaginally; to the best of our knowledge, this is the first case of intramural leiomyoma of bladder neck that has been enucleated transvaginally only without cystotomy.
The Predictive and Prognostic Value of Early Metabolic Response Assessed by Positron Emission Tomography in Advanced Gastric Cancer Treated with Chemotherapy
Authors: Wang Chenchen , Guo Weijian , Zhou Min , Zhu Xiaodong , Ji Dongmei , Li Wenhua , Liu Xin , Tao Zhonghua , Zhang Xiaowei , Zhang Yingjian , Li Jin
Published: November 2015

Purpose: To evaluate the feasibility of early metabolic change assessed by PET in predicting clinical response to chemotherapy and investigate its prognostic value in patients with advanced gastric cancer.

Experimental Design: A total of 64 patients with advanced gastric cancer were prospectively enrolled and examined by PET with 18F-fluorodeoxyglucose (FDG) and 18F-fluoro-3′-deoxy-3′-L-fluorothymidine (FLT) at baseline and 14 days after treatment initiation. PET findings were analyzed for the correlation with best clinical response of patients, disease control status, and survival after identifying the threshold of metabolic change percentage by ROC analysis.

Results: For FDG-PET, the total uptake value reduction percentage (δ-SUV) of 40% was the cut-off point with the maximum of sensitivity (70%) and specificity (83%) to predict clinical responding and that of prediction for disease control status was 30%, with the highest sensitivity (58%) and specificity (100%). The δ-SUV of FLT-PET played no predictive role for clinical response (AUC = 0.62; P = 0.134) and disease control (AUC = 0.66; P = 0.157). The univariate Cox regression analysis revealed no significant prognostic impact. FDG uptake reduction in liver metastases could predict both clinical response (P = 0.010) and disease control status (P = 0.002) at thresholds of 35% and 15%, respectively. Those with greater FDG uptake reduction in liver lesions had a longer overall survival (P = 0.004).

Conclusions: Early metabolic change in FDG-PET might be a predictive marker for response and disease control in advanced gastric cancer. Early FDG uptake change in liver metastases might be a useful prognostic factor and needs further exploration. Clin Cancer Res; 22(7); 1603–10. ©2015 AACR.
Molecular Pathways: Increased Susceptibility to Infection Is a Complication of mTOR Inhibitor Use in Cancer Therapy
Authors: Eiden Adrian M. , Zhang Shuling , Gary Joy M. , Simmons John K. , Mock Beverly A.
Published: November 2015

As one of the earliest examples of “chemical biology,” the Mechanistic Target of Rapamycin (mTOR) protein and its chemical inhibitors have been extensively studied across a spectrum of physiologic and pathologic processes at the molecular, organismal, and patient population levels. There are several FDA-approved mTOR inhibitors (sirolimus, everolimus, and temsirolimus) with indications for cancer treatment and for prevention of solid organ rejection. Dozens of mTOR inhibitors are currently being evaluated in hundreds of ongoing clinical trials across a spectrum of diseases, including numerous cancer indications, autoimmune diseases, and a number of congenital disorders. As many of the approved and investigational indications for mTOR inhibitors require long-term treatment, the magnitude and incidence of particular side effects differ from those observed in shorter-term treatments. Here, we focus on the increased risk of infections in patients being treated with mTOR inhibitors. While increased infection rates might be expected from a class of drugs approved as posttransplant immunosuppressants, we review reports from clinical, mechanistic, and genetically engineered mouse model studies detailing a much more nuanced view of mTOR inhibitor drug action and target biology. Clin Cancer Res; 22(2); 277–83. ©2015 AACR.
Differential Regulation of ZEB1 and EMT by MAPK-Interacting Protein Kinases (MNK) and eIF4E in Pancreatic Cancer
Authors: Kumar Krishan , Chow Christina R. , Ebine Kazumi , Arslan Ahmet D. , Kwok Benjamin , Bentrem David J. , Eckerdt Frank D. , Platanias Leonidas C. , Munshi Hidayatullah G.
Published: November 2015

Human pancreatic ductal adenocarcinoma (PDAC) tumors are associated with dysregulation of mRNA translation. In this report, it is demonstrated that PDAC cells grown in collagen exhibit increased activation of the MAPK-interacting protein kinases (MNK) that mediate eIF4E phosphorylation. Pharmacologic and genetic targeting of MNKs reverse epithelial–mesenchymal transition (EMT), decrease cell migration, and reduce protein expression of the EMT-regulator ZEB1 without affecting ZEB1 mRNA levels. Paradoxically, targeting eIF4E, the best-characterized effector of MNKs, increases ZEB1 mRNA expression through repression of ZEB1-targeting miRNAs, miR-200c and miR-141. In contrast, targeting the MNK effector hnRNPA1, which can function as a translational repressor, increases ZEB1 protein without increasing ZEB1 mRNA levels. Importantly, treatment with MNK inhibitors blocks growth of chemoresistant PDAC cells in collagen and decreases the number of aldehyde dehydrogenase activity–positive (Aldefluor+) cells. Significantly, MNK inhibitors increase E-cadherin mRNA levels and decrease vimentin mRNA levels in human PDAC organoids without affecting ZEB1 mRNA levels. Importantly, MNK inhibitors also decrease growth of human PDAC organoids.

Implications: These results demonstrate differential regulation of ZEB1 and EMT by MNKs and eIF4E, and identify MNKs as potential targets in pancreatic cancer. Mol Cancer Res; 14(2); 216–27. ©2015 AACR.
Frequency of Perceived Poststress Symptoms in Inpatients, Outpatients and Healthy Controls: The Role of Perceived Exhaustion and Stress
Authors: Waeldin Sandra , Vogt Dominic , Linden Michael , Hellhammer Dirk H.
Published: November 2015

Background: Poststress symptoms occur as a consequence of stress, most commonly during leisure periods such as weekends and vacations. However, the prevalence and the pathological mechanisms of poststress symptoms are poorly understood. Methods: Here, we compared the frequency of poststress symptoms in healthy controls (n = 984), outpatients (n = 420), and inpatients (n = 101). In outpatients, demographic factors, psychosocial stress, and perceived exhaustion were tested as predictors of poststress symptoms with multivariate regression analysis. Poststress symptoms and perceived exhaustion were assessed using 2 Neuropattern Questionnaires (the NPQ - Patient Questionnaire and the NPQ - Symptom List), and psychosocial stress was evaluated using the Patient Health Questionnaire (PHQ). Results: Poststress symptoms appeared in 2.9% of healthy controls, 20.0% of outpatients, and 34.7% of inpatients. Predictors were educational level, psychosocial stress, and perceived exhaustion. Poststress symptoms differed primarily between exhausted (75.0%) and nonexhausted patients (25.0%). Conclusion: Poststress symptoms are rather common in clinical populations, and they are primarily associated with the degree of perceived exhaustion. Preliminary evidence suggests that poststress symptoms are possibly related to depletion of norepinephrine stores, which may facilitate a stratified preventive and therapeutic treatment of these subjects.
A Randomized Controlled Clinical Trial of Dialogical Exposure Therapy versus Cognitive Processing Therapy for Adult Outpatients Suffering from PTSD after Type I Trauma in Adulthood
Authors: Butollo Willi , Karl Regina , König Julia , Rosner Rita
Published: November 2015

Background: Although there are effective treatments for posttraumatic stress disorder (PTSD), there is little research on treatments with non-cognitive-behavioural backgrounds, such as gestalt therapy. We tested an integrative gestalt-derived intervention, dialogical exposure therapy (DET), against an established cognitive-behavioural treatment (cognitive processing therapy, CPT) for possible differential effects in terms of symptomatic outcome and drop-out rates. Methods: We randomized 141 treatment-seeking individuals with a diagnosis of PTSD to receive either DET or CPT. Therapy length in both treatments was flexible with a maximum duration of 24 sessions. Results: Dropout rates were 12.2% in DET and 14.9% in CPT. Patients in both conditions achieved significant and large reductions in PTSD symptoms (Impact of Event Scale - Revised; Hedges' g = 1.14 for DET and d = 1.57 for CPT) which were largely stable at the 6-month follow-up. At the posttreatment assessment, CPT performed statistically better than DET on symptom and cognition measures. For several outcome measures, younger patients profited better from CPT than older ones, while there was no age effect for DET. Conclusions: Our results indicate that DET merits further research and may be an alternative to established treatments for PTSD. It remains to be seen whether DET confers advantages in areas of functioning beyond PTSD symptoms.
DYT6 Dystonia: A Neuropathological Study
Authors: Paudel Reema , Li Abi , Hardy John , Bhatia Kailash P. , Houlden Henry , Holton Janice
Published: November 2015

Background: Mutations in the thanatos-associated protein domain containing apoptosis-associated protein 1 gene (THAP1) are responsible for adult-onset isolated dystonia (DYT6). However, no neuropathological studies of genetically proven DYT6 cases have been previously reported. Objective: We report the first detailed neuropathological investigation carried out on two DYT6 brains. Methods: Genetic screening for THAP1 gene mutations using standard Sanger polymerase chain reaction sequencing identified 2 cases, 1 with a known pathogenic mutation and the other with a novel mutation. A detailed neuropathological assessment of the cases was performed. Results: Both DYT6 cases showed no significant neurodegeneration and no specific disease-related pathology. Conclusions: No neuropathological features that could be defined as hallmark features of DYT6 dystonia were identified. Our study supports the notion that in isolated dystonia, there is no significant neurodegeneration or morphological lesions that can be identified using routine methods.
The New Conceptualization of Alzheimer's Disease under the Microscope of Influential Definitions of Disease
Authors: Alexopoulos Panagiotis , Kurz Alexander
Published: November 2015

Background: According to its new conceptualization, Alzheimer's disease (AD) has preclinical and symptomatic phases, and biomarker abnormality justifies the diagnosis of the disease. Methods: The conceptual validity of AD is assessed on the basis of the disease definitions of T. Szasz, R.E. Kendell and J.G. Scadding, C. Boorse, K.W.M. Fulford and J.C. Wakefield, as well as of the DSM-5 classification system. Results: The new AD conceptualization could fit the Szaszian disease definition, provided that AD biomarkers reflected the pathological hallmarks of a singular disease, but it seems that they do not. Moreover, preclinical AD does not yield a biological disadvantage, being a central criterion for justifying the presence of a disease according to the disease definition of Scadding and Kendell. In addition, it remains unclear whether abnormality of biomarkers in elderly people embodies a statistical deviation from normal ageing and a pathological characteristic. Furthermore, not all stages of AD are related to experiences of failure of intentional doing, which is the criterion of the disease definition of Fulford, whilst the Wakefieldian harmful dysfunction and the DSM-5 mental disorder criteria are fulfilled only in the symptomatic phases of the disease course. Discussion: Our analytical endeavours unveiled weak sides and the fuzzy boundaries of the new conceptualization of AD. Future refinements of the criteria should address them so that the validity of the AD concept is increased.
Omega-3 Fatty Acids and Age-Related Macular Degeneration
Authors: Souied Eric H. , Aslam Tariq , Garcia-Layana Alfredo , Holz Frank G. , Leys Anita , Silva Rufino , Delcourt Cécile
Published: November 2015

Against a background of considerable epidemiological and other evidence implicating omega-3 fatty acids in the prevention of age-related macular degeneration (AMD), the negative results of the Age-Related Disease Study 2 (AREDS2) were unexpected. The possibility that the design, setting, intake or subjects of AREDS2 may not have permitted the prophylactic potential of omega-3 to be adequately demonstrated is considered. Epidemiological studies had indicated potential preventative effects of omega-3, and an earlier randomised prospective study (NAT2) showed that patients who achieved high red blood cell membrane EPA/DHA (eicosapentaenoic acid/docosahexaenoic acid) levels were significantly protected against AMD compared with those with permanently low EPA/DHA levels. Various methodological differences between these studies are considered. NAT2 included a true placebo group, whereas control subjects in AREDS2 received a nutritional formula already found to be effective in AREDS1, but no placebo for DHA/EPA supplementation. Differences in the handling of non-compliant subjects and the formulation of the test formulations are considered. Given these considerations, and other lines of evidence from laboratory and clinical studies, closing the chapter on omega-3 in AMD prevention may be premature.
Skewed X Inactivation in Women Carrying the FMR1 Premutation and Its Relation with Fragile-X-Associated Tremor/Ataxia Syndrome
Authors: Alvarez-Mora Maria Isabel , Rodriguez-Revenga Laia , Feliu Aina , Badenas Celia , Madrigal Irene , Milà Montserrat
Published: November 2015

Background: Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a late-onset multisystem neurological disorder characterized by intention tremor and cerebellar ataxia. Objective: We hypothesized that in FMR1 premutation females with FXTAS, a normal X chromosome might more frequently be inactivated; therefore, the aim of this study was to determine the relationship between skewed X chromosome inactivation (XCI) and FXTAS. Methods: We studied the XCI patterns of cases of FMR1 premutation in 10 women with FXTAS and 21 without FXTAS. Results: The distribution of XCI patterns in the FXTAS and no-FXTAS groups showed differences regarding the allele presenting severe skewed XCI. In the FXTAS group, all cases preferentially inactivated the non-expanded X chromosome, whereas in the no-FXTAS group, all inactivated the expanded X chromosome. Nevertheless, no significant differences were found on comparing XCI frequencies among FMR1 premutation carriers with and without FXTAS. As expected, we found statistically significant differences in the skewed XCI on comparing FMR1 premutation women and controls. Conclusion: Although the reduced sample size and blood XCI patterns are two limitations of this study, our results suggest that the skewed XCI of the normal FMR1 allele may be a risk factor for the development of FXTAS. Furthermore, our findings also support the protective effect of the expression of a normal FMR1 allele.
Choroidal Neovascularization Associated with Punctate Inner Choroidopathy: Combination of Intravitreal Anti-VEGF and Systemic Immunosuppressive Therapy
Authors: Hohberger Bettina , Rudolph Michael , Bergua Antonio
Published: November 2015

Purpose: Choroidal neovascularization (CNV) associated with punctate inner choroidopathy (PIC) is a rare clinical entity, yet still a challenge for medical treatment. A case of a young myopic woman developing CNV secondary to unilateral PIC is presented. Clinical morphology, diagnostic procedure and follow-up are reported. Case Report: A 29-year-old woman presented with multiple yellowish dots at the posterior pole. No other signs of inflammation could be seen. Angiography with fluorescein yielded hyperfluorescent signals in the affected areas with a diffuse leak, and SD-OCT showed a slightly elevated retinal pigment epithelial layer, consistent with the diagnosis of PIC. Additionally a classic CNV was observed. Results: Anti-inflammatory therapy with local prednisolone acetate eye drops in combination with intravitreal injection of anti-vascular endothelial growth factor (VEGF, bevacizumab) yielded an increased best-corrected visual acuity. As CNV reappeared, systemic medication with prednisone and azathioprine in combination with two further intravitreal injections of anti-VEGF stabilized CNV and increased visual acuity again. Conclusion: Combined therapy of immunosuppression with intravitreal anti-VEGF injections can be considered as therapeutic strategy in the management of recurrent CNV associated with PIC.