bluuebunny/crossref_metadata_2025 huggingface dataset:
Ligand Based Pharmacophore Modeling and Virtual Screening Studies to Design Novel HDAC2 Inhibitors
Authors: Kandakatla Naresh , Ramakrishnan Geetha
Published: November 2014

Histone deacetylases 2 (HDAC2), Class I histone deacetylase (HDAC) family, emerged as an important therapeutic target for the treatment of various cancers. A total of 48 inhibitors of two different chemotypes were used to generate pharmacophore model using 3D QSAR pharmacophore generation (HypoGen algorithm) module in Discovery Studio. The best HypoGen model consists of four pharmacophore features namely, one hydrogen bond acceptor (HBA), and one hydrogen donor (HBD), one hydrophobic (HYP) and one aromatic centres, (RA). This model was validated against 20 test set compounds and this model was utilized as a 3D query for virtual screening to validate against NCI and Maybridge database and the hits further screened by Lipinski’s rule of 5, and a total of 382 hit compounds from NCI and 243 hit compounds from Maybridge were found and were subjected to molecular docking in the active site of HDAC2 (PDB: 3MAX). Finally eight hit compounds, NSC108392, NSC127064, NSC110782, and NSC748337 from NCI database and MFCD01935795, MFCD00830779, MFCD00661790, and MFCD00124221 from Maybridge database, were considered as novel potential HDAC2 inhibitors.
Extension of Khan’s Homotopy Transformation Method via Optimal Parameter for Differential Difference Equations
Authors: Mohamed Mohamed S. , Gepreel Khaled A. , Al-Malki Faisal A. , Altalhi Nouf
Published: November 2014

A new scheme, deduced from Khan’s homotopy perturbation transform method (HPTM) (Khan, 2014; Khan and Wu, 2011) via optimal parameter, is presented for solving nonlinear differential difference equations. Simple but typical examples are given to illustrate the validity and great potential of Khan’s homotopy perturbation transform method (HPTM) via optimal parameter in solving nonlinear differential difference equation. The numerical solutions show that the proposed method is very efficient and computationally attractive. It provides more realistic series solutions that converge very rapidly for nonlinear real physical problems. The results reveal that the method is very effective and simple. This method gives more reliable results as compared to other existing methods available in the literature. The numerical results demonstrate the validity and applicability of the method.
The Lived Experience of Lupus Flares: Features, Triggers, and Management in an Australian Female Cohort
Authors: Squance Marline L. , Reeves Glenn E. M. , Bridgman Howard
Published: November 2014

Individuals living with lupus commonly experience daily backgrounds of symptoms managed to acceptable tolerance levels to prevent organ damage. Despite management, exacerbation periods (flares) still occur. Varied clinical presentations and unpredictable symptom exacerbation patterns provide management and assessment challenges. Patient perceptions of symptoms vary with perceived impact, lifestyles, available support, and self-management capacity. Therefore, to increase our understanding of lupus’ health impacts and management, it was important to explore lupus flare characteristics from the patient viewpoint. Lupus flares in 101 Australian female patients were retrospectively explored with the use of a novel flare definition. Qualitative methods were used to explore patient-perceived flare symptoms, triggers, and management strategies adopted to alleviate symptom exacerbations. A mean of 29.9 flare days, with 6.8 discrete flares, was experienced. The study confirmed that patients perceive stress, infection, and UV light as flare triggers and identified new potential triggers of temperature and weather changes, work, and chemical exposure from home cleaning. The majority of flares were self-managed with patients making considered management choices without medical input. Barriers to seeking medical support included appointment timings and past negative experiences reflecting incongruence between clinician and patient views of symptom impact, assessment, and ultimately flare occurrence.
Invasive Mold Infections in Solid Organ Transplant Recipients
Authors: Crabol Yoann , Lortholary Olivier
Published: November 2014

Invasive mold infections represent an increasing source of morbidity and mortality in solid organ transplant recipients. Whereas there is a large literature regarding invasive molds infections in hematopoietic stem cell transplants, data in solid organ transplants are scarcer. In this comprehensive review, we focused on invasive mold infection in the specific population of solid organ transplant. We highlighted epidemiology and specific risk factors for these infections and we assessed the main clinical and imaging findings by fungi and by type of solid organ transplant. Finally, we attempted to summarize the diagnostic strategy for detection of these fungi and tried to give an overview of the current prophylaxis treatments and outcomes of these infections in solid organ transplant recipients.
Analysis of the Evolution of Tannic Acid Stabilized Gold Nanoparticles Using Mie Theory
Authors: Senoudi Assia Rachida , Chabane Sari Sidi Mohammed , Hakem Ilhem Faiza
Published: November 2014

Spherical gold nanoparticles (GNPs) have been synthesized in aqueous solutions using sodium citrate (SC) and tannic acid (TA) as reducing and stabilizing agents. Upon addition of TA and compared to the GNP TA-free aqueous solutions, a reduction of the GNPs size and consequently a dramatic change of their optical properties have been observed and quantitatively analyzed using Mie theory. An increase in the concentration of TA reveals a modification of the colloidal solution refractive index that is evidenced by the shift in the peak position of the localized surface plasmon resonance (LSPR) band. The variations of the peak absorbance with the TA concentration are examined in the low and high concentration regimes.
Anatomo‐Functional Correlation between Head Zones and Acupuncture Channels and Points: A Comparative Analysis from the Perspective of Neural Therapy
Authors: Beltrán Molano Martha Liliana , Pinilla Bonilla Laura Bibiana , Beltrán Dussan Eduardo Humberto , Vásquez Londoño Carlos Alberto
Published: November 2014

Background. Neural therapy and traditional Chinese medicine (TCM) are part of complementary and alternative medicine in western world. Both of them share characteristics in diagnosis and therapeutics in search of changes in tenderness, pain, and skin stiffness related to visceral disease, as well as therapeutic procedures with specific stimuli on the skin that generate local, segmental, or remote reactions. Head zones explain segmental viscerocutaneous relations in neural therapy; however, interference fields and remote reactions after infiltration of local anesthetic go beyond this segmental distribution. Methods. This descriptive research required review and analysis of texts of Henry Head and traditional Chinese medicine. Results. Anatomical and functional relationships were found between Head zones in body, and head and neck with 14 acupuncture channels and their points. Anatomical areas of strong correlations were found: Head zones of heart and lung with heart and pericardium channels; Head zones of genitals with bladder and kidney channels. Strong functional relations between all Head zones, channels, and acupoints were found when following the pattern of segmental dermatomes; 235 acupuncture points were found in concordance.
An Unusual Metallic Foreign Body inside the Knee Medial Femoral Condyle
Authors: Helito Camilo Partezani , Faria Carlos Eduardo Nunes , Bonadio Marcelo Batista , Pecora Jose Ricardo , Camanho Gilberto Luis , Demange Marco Kawamura
Published: November 2014

Foreign bodies in the knee joint are uncommon, particularly those not related to surgical procedures. In this paper, we present a case of an intraosseous metallic foreign body situated in the medial femoral condyle for one year, causing pain, which was removed with complete resolution of the symptoms.
A Novel Adjustment Method for Shearer Traction Speed through Integration of T-S Cloud Inference Network and Improved PSO
Authors: Si Lei , Wang Zhongbin , Liu Xinhua , Yang Yinwei , Zhang Lin
Published: November 2014

In order to efficiently and accurately adjust the shearer traction speed, a novel approach based on Takagi-Sugeno (T-S) cloud inference network (CIN) and improved particle swarm optimization (IPSO) is proposed. The T-S CIN is built through the combination of cloud model and T-S fuzzy neural network. Moreover, the IPSO algorithm employs parameter automation adjustment strategy and velocity resetting to significantly improve the performance of basic PSO algorithm in global search and fine-tuning of the solutions, and the flowchart of proposed approach is designed. Furthermore, some simulation examples are carried out and comparison results indicate that the proposed method is feasible, efficient, and is outperforming others. Finally, an industrial application example of coal mining face is demonstrated to specify the effect of proposed system.
Evaluation of Selected Honey and One of Its Phenolic Constituent Eugenol against L1210 Lymphoid Leukemia
Authors: Jaganathan Saravana Kumar , Mondhe Dilip , Wani Z. A. , Supriyanto Eko
Published: November 2014

People affected with leukemia are on the rise and several strategies were employed to thwart this deadly disease. Recent decade of research focuses on phenolic constituents as a tool for combating various inflammatory, cancer, and cardiac diseases. Our research showed honey and its phenolic constituents as crusaders against cancer. In this work, we explored the antileukemic activity of selected honey and one of its phenolic constituent eugenol against L1210 leukemia animal model. Results of this experiment showed that the selected honey samples as well as eugenol after intraperitoneal injection could not increase the median survival time (MST) of animals. Further, there was only slight marginal increase in the %T/Cvalues of honey and eugenol treated groups. The number of phenolics present in the honey may not be a prime factor to promote antileukemic effect since there was no difference in the MST of two different honeys tested. This study limits the use of selected honey and eugenol against leukemia animal model.
Glucagon-Like Peptide-1 as Predictor of Body Mass Index and Dentate Gyrus Neurogenesis: Neuroplasticity and the Metabolic Milieu
Authors: Coplan Jeremy D. , Syed Shariful , Perera Tarique D. , Fulton Sasha L. , Banerji Mary Ann , Dwork Andrew J. , Kral John G.
Published: November 2014

Glucagon-like peptide-1 (GLP-1) regulates carbohydrate metabolism and promotes neurogenesis. We reported an inverse correlation between adult body mass and neurogenesis in nonhuman primates. Here we examine relationships between physiological levels of the neurotrophic incretin, plasma GLP-1 (pGLP-1), and body mass index (BMI) in adolescence to adult neurogenesis and associations with a diabesity diathesis and infant stress. Morphometry, fasting pGLP-1, insulin resistance, and lipid profiles were measured in early adolescence in 10 stressed and 4 unstressed male bonnet macaques. As adults, dentate gyrus neurogenesis was assessed by doublecortin staining. High pGLP-1, low body weight, and low central adiposity, yet peripheral insulin resistance and high plasma lipids, during adolescence were associated with relatively high adult neurogenesis rates. High pGLP-1 also predicted low body weight with, paradoxically, insulin resistance and high plasma lipids. No rearing effects for neurogenesis rates were observed. We replicated an inverse relationship between BMI and neurogenesis. Adolescent pGLP-1 directly predicted adult neurogenesis. Two divergent processes relevant to human diabesity emerge—high BMI, low pGLP-1, and low neurogenesis and low BMI, high pGLP-1, high neurogenesis, insulin resistance, and lipid elevations. Diabesity markers putatively reflect high nutrient levels necessary for neurogenesis at the expense of peripheral tissues.
Retrospective Analysis of Cushing’s Disease with or without Hyperprolactinemia
Authors: Huan Cheng , Lu Chao , Xu Guang-ming , Qu Xin , Qu Yuan-ming
Published: November 2014

Objective. We compared the characteristics of patients with Cushing’s disease alone with those of patients with Cushing’s disease and hyperprolactinemia.Methods. Eighty-four patients were enrolled between 2002 and 2011, in a hospital in China. Clinical, endocrinological, and histopathological data, MRI scans, and surgical outcomes were reviewed throughout the follow-up period.Results. Patients with Cushing’s disease and hyperprolactinemia had a younger age at diagnosis (30.28 ± 14.23 versus 36.08 ± 10.91 years;P=0.037) and a larger adenoma maximal diameter (2.44 ± 1.32 versus 1.44 ± 1.05 cm;P<0.001) than patients with Cushing’s disease alone. Menstrual disorders (P=0.027) and visual field defects (P=0.021) were more common and progressive obesity (P=0.009) and hypertension (P<0.001) were less common in patients with Cushing’s disease and hyperprolactinemia. The rate of normalization of hormonal levels was lower (41.7% versus 91.7%;P<0.001) and the recurrence rate was higher (36.1% versus 8.3%;P<0.001) in patients with Cushing’s disease and hyperprolactinemia.Conclusions. Careful long-term follow-up is needed of patients with Cushing’s disease and hyperprolactinemia.
Bilateral Simultaneous Femoral Neck Fracture Mimicking Abdominal Pain in a Cerebral Palsy Patient
Authors: Mariani P. , Buttaro M. , Comba F. , Zanotti E. , Ali P. , Piccaluga F.
Published: November 2014

Simultaneous bilateral femoral neck fractures are unusual lesions, generally associated with an underlying condition which causes impaired bone mineralization, triggered by an increased bone stress. We present a 24-year-old cerebral palsy patient, who was previously evaluated in another institution due to inability to walk, interpreted as abdominal pain. No alteration in blood analysis or abdominal X-rays was found. As no response to treatment was observed, a new abdominal X-ray was taken, which incidentally depicted bilateral medial femoral neck fracture. He was referred to our practice after a resection arthroplasty was offered in another institution. After admission, bilateral one-stage THA was performed. Several reports emphasize bone disease as a major precipitating factor, and there is an increased incidence of hip fractures in chronic epilepsy, renal osteodystrophy, and chronic steroid use. Femoral head resection has been proven to be effective in immobilized patients, whereas this was not a reasonable option in this patient who presented walking ability. Despite the treatment election, primary care physicians should be aware of and alert to the possibility of fractures in patients with neurological disorders and calcium metabolism alterations. Late diagnosis of orthopedic injuries in this type of patients may lead to permanent disability.
A Class of Approximate Damped Oscillatory Solutions to Compound KdV-Burgers-Type Equation with Nonlinear Terms of Any Order: Preliminary Results
Authors: Zhao Yan , Zhang Weiguo
Published: November 2014

This paper is focused on studying approximate damped oscillatory solutions of the compound KdV-Burgers-type equation with nonlinear terms of any order. By the theory and method of planar dynamical systems, existence conditions and number of bounded traveling wave solutions including damped oscillatory solutions are obtained. Utilizing the undetermined coefficients method, the approximate solutions of damped oscillatory solutions traveling to the left are presented. Error estimates of these approximate solutions are given by the thought of homogeneous principle. The results indicate that errors between implicit exact damped oscillatory solutions and approximate damped oscillatory solutions are infinitesimal decreasing in the exponential form.
Cone-Like Rectification Properties of cGMP-Gated Channels in Transmutated Retinal Photoreceptors of Nocturnal Geckoes
Authors: Vellani Vittorio , Giacomoni Chiara
Published: November 2014

Photoreceptors of nocturnal geckoes are scotopic, with rod-shaped outer segments, and sensitivities to light similar to the one of retinal rods from other species of lower vertebrates. However, these cells are not rods, but they originated from cones of ancestral diurnal geckoes with pure-cone retinas, after being forced to adapt to a nocturnal behavior. Several interesting adaptations of these rod-like cones have been studied to date; molecular biology and functional studies confirmed that several proteins of the phototransductive cascade display structural and functional properties that indicate their origin from cones rather than from rods. In this paper, we investigate, with whole cell voltage clamp in the photoreceptor detached outer segment preparation, the voltage rectification properties of cGMP-gated channels in three species,Gekko gecko,Tarentola mauritanica, andHemidactylus frenatus. We show that the current-voltage properties in the physiological voltage range are reminiscent of the ones of cGMP-gated channels from cones rather than from rods of other cold-blooded vertebrates. The origin and the relevance of the mechanisms investigated are discussed.
The Use of Humoral Responses as a Marker of CMV Burden in HIV Patients on ART Requires Consideration of T-Cell Recovery and Persistent B-Cell Activation
Authors: Brunt Samantha J. , Lee Silvia , D’Orsogna Lloyd , Bundell Christine , Burrows Sally , Price Patricia
Published: November 2014

Objectives.Elevated humoral responses to cytomegalovirus (CMV) associate with increased risk of cardiovascular disease (CVD) in HIV patients on antiretroviral therapy (ART). To better understand the persistence of CMV humoral responses in relation to CVD, we determined trends in CMV antibody levels over the first 10 years on ART.Design.We describe longitudinal analyses of plasma from 13 HIV patients commencing ART with <210 CD4 T-cells/µL and 27 controls. Antibodies reactive with CMV (fibroblast lysate, gB and IE-1 antigens), EBV-VCA, and HIVgp41 were quantitated. B-cell activation was assessed via total IgG and sBAFF. Inflammation was assessed via sTNF-RI and sCD14.Results.Amongst CMV seropositive HIV patients, levels of antibody reactive with CMV(P=0.03)and EBV-VCA(P=0.02)peaked after 1 year on ART. Levels of total IgG, sCD14, and sTNF-RI declined to approximate those in controls after 10 years, but sBAFF(P=0.0002), EBV-VCA(P=0.001), and CMV(P=0.0004)antibodies remained elevated. A strong correlation between sBAFF and CMVgB antibody was seen at 10 years(R=0.93,  P=0.0009)and verified in a second cohort.Conclusions.CMV antibody titres peak on ART and remain high. A correlation between CMV antibody and sBAFF suggests a role for HIV-induced B-cell pathology that may affect its use as a marker of CMV burden.
Guaranteed Cost Nonfragile Robust Controller for Walking Simulation of Quadruped Search Robot on a Slope of VRML Model
Authors: Wang Peng , Li Jixiang , Zhang Yuan
Published: November 2014

The problem of walking simulation for the quadruped search robot on a slope is described as an uncertainty system. In order to create the virtual ramp road environment, VRML modeling language is used to build a real environment, which is a 3D terrain scene in Matlab platform. According to the VRML model structure of the quadruped search robot, a guaranteed cost nonfragile robust controller is designed for ramp road walking simulation. The constraint inequation is transformed into a strict linear inequality by using two equalities; the controller and the guaranteed cost upper bound are given based on the solutions of the linear matrix inequality. And the approaches of designing the controller are given in terms of linear matrix inequalities. The walking stability of quadruped search robot is observed using the VRML model established with the change of gravity curve. Simulation results show that the gravity displacement curve of the robot is smooth. The results given by linear matrix inequalities indicate that the proposed guaranteed cost controller is correct and effective.
The Perception of Family Function by Adolescents with Epilepsy in a Rural Nigerian Community
Authors: Eseigbe Edwin E. , Nuhu Folorunsho T. , Sheikh Taiwo L. , Adama Sam J. , Eseigbe Patricia , Oguizu Okechukwu J.
Published: November 2014

The family plays a significant role in epilepsy management in sub-Saharan Africa and how this role is perceived by persons with epilepsy could influence epilepsy outcomes. The objective of the study was to assess perception of family function by adolescents with epilepsy (AWE). The sociodemographic and epilepsy characteristics of AWE in a rural Nigerian community were assessed and the Family APGAR tool was used in assessing their perception of satisfaction with family functioning. Adolescents (n=1708) constituted 26% of the community’s population and 18 (10.5/1000) had epilepsy. The AWE age range was 11–19 years (mean 16.7±2.6 years) with a male preponderance (15, 83.3%). The family was the only source of care. Family dysfunction (Family APGAR Score <7) was indicated by 15 (83.3%) of the AWE. The strongest perception of family function was in adaptability while the weakest was with growth. The indication of family dysfunction was significant (P<0.05) in the older (age 14–19 years) AWE when compared with the younger AWE (11–13 years) in the study. Most of the AWE indicated living in a dysfunctional family setting. The study highlights the need to address the role of the family in the provision of comprehensive epilepsy care.
Spermatogenic Waves and Expression of AR and ERs in Germ Cells ofPodarcis sicula
Authors: Verderame Mariailaria , Angelini Francesco , Limatola Ermelinda
Published: November 2014

Androgens are considered the main hormones that regulate spermatogenesis, but a lot of evidence confers to estrogen a key role in this process. In the testis of the seasonal breeder lizardPodarcis siculawe analyzed by means ofin situhybridization the expression of the androgen receptor (AR) and of the two types,αandβ, of the estrogen receptors (ERs) throughout the three periods of the annual cycle: mating (spring-early summer), postmating-refractory (late summer), and autumnal recrudescence. The results show that during the mating period AR and ERs are expressed in all germ cells present in the tubules from spermatogonia to spermatozoa. During the postmating-refractory period, when only spermatogonia are present in the tubules, almost all express ERs and very few AR mRNA. During the autumnal recrudescence the localization of AR and ERs is the same of the mating period except for the population of the primary spermatocytes. The expression of the investigated receptors is peculiar in these cells that are positive in the middle-late pachytene stage of the meiotic prophase and negative in preleptotene. A possible functional role of the observed differences during spermatogenesis and in the spermatozoa is also discussed.
Diagnostic Difficulties in Woman with Crohn’s Disease, Ascites, and Elevated Value of Serum CA125 Antigen
Authors: Kłopocka Maria , Liebert Ariel , Bielińska Joanna , Manerowski Marcin
Published: November 2014

Variety of symptoms and atypical clinical course of Crohn’s disease (CD) often create the need for additional diagnostic procedures. In the described case of woman with CD, there was a suspicion of coexistence of ovarian cancer. This issue is particularly important in patients treated with immunosuppressants and biological agents. The discussion focused on the usefulness of CA125 (cancer antigen 125, mucin 16) serum level estimation in clinical practice and draws attention to the possible reasons for the increase of its value which is not associated to ovarian cancer.
Imaging Intratumor Heterogeneity: Role in Therapy Response, Resistance, and Clinical Outcome
Authors: O'Connor James P.B. , Rose Chris J. , Waterton John C. , Carano Richard A.D. , Parker Geoff J.M. , Jackson Alan
Published: November 2014

Tumors exhibit genomic and phenotypic heterogeneity, which has prognostic significance and may influence response to therapy. Imaging can quantify the spatial variation in architecture and function of individual tumors through quantifying basic biophysical parameters such as CT density or MRI signal relaxation rate; through measurements of blood flow, hypoxia, metabolism, cell death, and other phenotypic features; and through mapping the spatial distribution of biochemical pathways and cell signaling networks using PET, MRI, and other emerging molecular imaging techniques. These methods can establish whether one tumor is more or less heterogeneous than another and can identify subregions with differing biology. In this article, we review the image analysis methods currently used to quantify spatial heterogeneity within tumors. We discuss how analysis of intratumor heterogeneity can provide benefit over more simple biomarkers such as tumor size and average function. We consider how imaging methods can be integrated with genomic and pathology data, instead of being developed in isolation. Finally, we identify the challenges that must be overcome before measurements of intratumoral heterogeneity can be used routinely to guide patient care. Clin Cancer Res; 21(2); 249–57. ©2014 AACR.
First-in-Human Dose Study of the Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Patients with Advanced Cancer and Glioma
Authors: Rodon Jordi , Carducci Michael A. , Sepulveda-Sánchez Juan M , Azaro Analia , Calvo Emiliano , Seoane Joan , Braña Irene , Sicart Elisabet , Gueorguieva Ivelina , Cleverly Ann L. , Pillay N. Sokalingum , Desaiah Durisala , Estrem Shawn T. , Paz-Ares Luis , Holdhoff Matthias , Blakeley Jaishri , Lahn Michael M. , Baselga Jose
Published: November 2014

Purpose: TGFβ signaling plays a key role in tumor progression, including malignant glioma. Small-molecule inhibitors such as LY2157299 monohydrate (LY2157299) block TGFβ signaling and reduce tumor progression in preclinical models. To use LY2157299 in the treatment of malignancies, we investigated its properties in a first-in-human dose (FHD) study in patients with cancer.

Experimental Design: Sixty-five patients (58 with glioma) with measurable and progressive malignancies were enrolled. Oral LY2157299 was given as a split dose morning and evening on an intermittent schedule of 14 days on and 14 days off (28-day cycle). LY2157299 monotherapy was studied in dose escalation (part A) first and then evaluated in combination with standard doses of lomustine (part B). Safety was assessed using Common Terminology Criteria for Adverse Events version 3.0, echocardiography/Doppler imaging, serum troponin I, and brain natriuretic peptide (BNP) levels. Antitumor activity was assessed by RECIST and Macdonald criteria.

Results: In part A, 16.6% (5/30) and in part B, 7.7% (2/26) of evaluable patients with glioma had either a complete (CR) or a partial response (PR). In both parts, 15 patients with glioma had stable disease (SD), 5 of whom had SD ≥6 cycles of treatment. Therefore, clinical benefit (CR+PR+SD ≥6 cycles) was observed in 12 of 56 patients with glioma (21.4%). LY2157299 was safe, with no cardiac adverse events.

Conclusions: On the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation. Clin Cancer Res; 21(3); 553–60. ©2014 AACR.
Sequential Intravesical Mitomycin plus Bacillus Calmette–Guérin for Non–Muscle-Invasive Urothelial Bladder Carcinoma: Translational and Phase I Clinical Trial
Authors: Svatek Robert S. , Zhao Xiang Ru. , Morales Edwin E. , Jha Mithilesh K. , Tseng Timothy Y. , Hugen Cory M. , Hurez Vincent , Hernandez Javier , Curiel Tyler J.
Published: November 2014

Purpose: To determine the safety and toxicities of sequential MMC (mitomycin C) + BCG (bacillus Calmette–Guérin) in patients with non–muscle-invasive bladder cancer (NMIBC) and explore evidence for potentiation of BCG activity by MMC.

Experimental Design: A 3 + 3 phase I dose-escalation trial of six weekly treatments was conducted in patients with NMIBC. MMC (10, 20, or 40 mg) was instilled intravesically for 30 minutes, followed by a 10-minute washout with gentle saline irrigation and then instillation of BCG (half or full strength) for 2 hours. Urine cytokines were monitored and compared with levels in a control cohort receiving BCG only. Murine experiments were carried out as described previously.

Results: Twelve patients completed therapy, including 3 patients receiving full doses. The regimen was well tolerated with no treatment-related dose-limiting toxicities. Urinary frequency and urgency, and fatigue were common. Eleven (91.7%) patients were free of disease at a mean (range) follow-up of 21.4 (8.4–27.0) months. Median posttreatment urine concentrations of IL2, IL8, IL10, and TNFα increased over the 6-week treatment period. A greater increase in posttreatment urinary IL8 during the 6-week period was observed in patients receiving MMC + BCG compared with patients receiving BCG monotherapy. In mice, intravesical MMC + BCG skewed tumor-associated macrophages (TAM) toward a beneficial M1 phenotype.

Conclusions: Instillation of sequential MMC + BCG is safe tolerable up to 40-mg MMC plus full-strength BCG. This approach could provide improved antitumor activity over BCG monotherapy by augmenting beneficial M1 TAMs. Clin Cancer Res; 21(2); 303–11. ©2014 AACR.
Ex vivo Approach to Treat Failing Organs: Expanding the Limits
Authors: Ciubotaru Anatol , Haverich Axel
Published: November 2014

Background: Advanced organ failure is often classified as an end-stage disease where the treatment options are limited only to transplantation. As an alternative, different attempts have been undertaken to improve the outcome of the treatment of failing organs by using targeted ex vivo approaches. This may solve the issue of organ shortage by treating the donor organs before transplantation and the number of patients requiring transplantation may also be reduced by applying extensive ex vivo treatment followed by autotransplantation. Methods: We performed a literature review of PubMed and included articles published between 1962 and 2013. The following keywords were used (and; or): ex vivo, therapy, surgery, organ perfusion and autotransplantation. This review includes specific methods and attempts related to ex vivo organ perfusion and preservation, temporary life support systems, surgical and other therapeutic approaches, and diagnostic methods applied ex vivo to an isolated organ. Results: For the practical clinical use of ex vivo therapies, we could identify three major directions: (1) ex vivo pretransplant organ reconditioning, (2) ex vivo surgery and (3) ex vivo medical treatment. Different attempts have been made worldwide in the above-mentioned areas focusing on ex vivo organ preservation and treatment. We summarize in the present review the developments in the field of ex vivo organ recovery and evaluate the possibilities of combining and applying different technologies such as organ perfusion and storage, ex vivo exact topographical diagnosis, ex vivo locoregional medical treatment and ex vivo surgical correction. Conclusion: Ex vivo therapies open new horizons in the treatment of end-stage organ pathologies.
Screening for Diabetic Retinopathy in the Central Region of Portugal. Added Value of Automated ‘Disease/No Disease' Grading
Authors: Ribeiro Luisa , Oliveira Carlos Manta , Neves Catarina , Ramos João Diogo , Ferreira Hélder , Cunha-Vaz José
Published: November 2014

Purpose: To describe the procedures of a nonmydriatic diabetic retinopathy (DR) screening program in the Central Region of Portugal and the added value of the introduction of an automated disease/no disease analysis. Methods: The images from the DR screening program are analyzed in a central reading center using first an automated disease/no disease analysis followed by human grading of the disease cases. The grading scale used is as follows: R0 - no retinopathy, RL - nonproliferative DR, M - maculopathy, RP - proliferative DR and NC - not classifiable. Results: Since the introduction of automated analysis in July 2011, a total of 89,626 eyes (45,148 patients) were screened with the following distribution: R0 - 71.5%, RL - 22.7%, M - 2.2%, RP - 0.1% and NC - 3.5%. The implemented automated system showed the potential for human grading burden reduction of 48.42%. Conclusions: Screening for DR using automated analysis allied to a simplified grading scale identifies DR vision-threatening complications well while decreasing human burden.
Expression Analysis of sox3 during Testicular Development, Recrudescence, and after hCG Induction in Catfish, Clarias batrachus
Authors: Rajakumar Anbazhagan , Senthilkumaran Balasubramanian
Published: November 2014

In teleosts, the expression of steroidogenic enzymes and related transcription factor genes occurs in a stage- and tissue-specific manner causing sexual development. The role of sox3, an evolutionary ancestor of SRY, has not been studied in detail. Therefore, the full-length cDNA of sox3 (1,197 kb) was cloned from catfish testis, and mRNA expression was analyzed during gonadal development, during the seasonal reproductive cycle, and after human chorionic gonadotropin (hCG) induction. Tissue distribution analysis showed that sox3 expression was higher in testis, ovary, and brain compared to other tissues analyzed. Developing and mature testis showed higher sox3 expression than ovary of corresponding stages, and more sox3 transcripts were found during the spawning phase of the seasonal reproductive cycle. Expression of sox3 was upregulated by hCG after in vivo and in vitro induction, suggesting that gonadotropins might stimulate it. In situ hybridization and immunohistochemistry showed the presence of sox3 mRNA and protein in somatic and interstitial cell layers of the testis. Sox3 could also be found in the zona radiata of developing and mature oocytes. Exposure of methyltestosterone (1 µg/l) and ethinylestradiol (1 µg/l) for 21 days during testicular development showed lower sox3 expression levels in the testis and brain, indicating a certain feedback intervention. These results suggest a possible role for Sox3 in the regulation of testicular development and function.
Ventriculoperitoneal Shunt Infection with Non-Typhoidal Salmonella Species in an Infant
Authors: Bodman Alexa , Hall Walter
Published: November 2014

Shunt infections are common in pediatric neurosurgery. We present a case of a 3-month-old male with a history of a ventriculoperitoneal shunt for posthemorrhagic hydrocephalus after premature birth who presented to the emergency department with irritability and decreased oral intake. His presentation was concerning for shunt infection and evaluation for this was undertaken. He was found to have a shunt infection due to non-Salmonellatyphi species, a rare cause of meningitis in children in the United States and rarer cause of shunt infection. With effective treatment for this organism, the patient did well and was discharged home in good condition.
A Web-Based Weight Loss Programme Including Breakfast Cereals Results in Greater Loss of Body Mass than a Standardised Web-Based Programme in a Randomised Controlled Trial
Authors: Margaret Ashwell Margaret , Howarth Elaine , Chesters David , Allan Peter , Hoyland Alexa , Walton Jenny
Published: November 2014

Objective: To test the hypothesis that promoting breakfast cereal consumption, as part of a web-based programme, results in loss of body mass. Methods: Single centre, single blind, randomised parallel study. Test group followed a fully interactive website (B) with ‘prescribed' breakfast cereals. Control group followed website (A) giving standard advice on weight loss. Study site visits at 0, 4, 12 and 24 weeks for measurements of height, weight, skinfolds, body fat, waist and hip circumference. 180 subjects were randomly allocated to two equal groups. Subjects were in good health and aged 19-50 years, with a BMI ranging from 25-40 kg/m2. At baseline there was no difference in mean age or BMI between the two groups. Results: The percentage change in body mass loss was greater when following website B than website A (n = 90; ITT repeated measures p = 0.013). For completers (website A: n = 62, website B: n = 64), the percentage change in body mass loss was also greater for website B than website A (repeated measures p = 0.023). Conclusion: The advice and motivation offered by an interactive website, including provision and consumption of breakfast cereals, results in significantly greater loss of body mass compared to the use of a standard website. It is not possible to discern which of the three factors is responsible.
Akinetic Crisis in Parkinson's Disease Is Associated with a Severe Loss of Striatal Dopamine Transporter Function: A Report of Two Cases
Authors: Kaasinen Valtteri , Joutsa Juho , Noponen Tommi , Päivärinta Markku
Published: November 2014

Akinetic crisis or acute akinesia is a life-threatening complication of Parkinson's disease (PD) with unknown pathophysiological mechanisms. Clinically, it resembles the neuroleptic malignant syndrome, and dopaminergic drugs are transiently ineffective in the acute phase of the condition. There are no published dopaminergic functional imaging studies on PD patients with akinetic crisis. Here we report 2 advanced PD patients with akinetic crisis who were scanned with SPECT using brain dopamine transporter ligand [123I]FP-CIT. The first patient was additionally scanned before the condition developed, and the second patient was scanned after recovery. Striatal dopamine transporter binding was lower during than before the crisis, and both patients showed a nearly complete loss of dopamine transporter binding during the crisis. Serial imaging showed that the uptake remained negligible despite an improvement in motor function after recovery. Akinetic crisis in PD appears to be associated with a particularly severe loss of presynaptic striatal dopamine function that does not improve after recovery. Apart from presynaptic dopaminergic function, other dopaminergic or nondopaminergic mechanisms are involved in the clinical improvement of motor functions after akinetic crisis in PD.
Bioinformatics Approach Reveals Evidence for Impaired Endometrial Maturation Before and During Early Pregnancy in Women Who Developed Preeclampsia
Authors: Rabaglino Maria B. , Post Uiterweer Emiel D. , Jeyabalan Arun , Hogge William A. , Conrad Kirk P.
Published: November 2014

Impaired uterine invasion by extravillous trophoblast in early gestation is implicated in the genesis of preeclampsia, a potentially lethal malady of human pregnancy. However, reasons for extravillous trophoblast dysfunction remain unclear because of virtual inaccessibility of early placental and uterine tissues from women who develop preeclampsia, and the absence of animal models in which the disease spontaneously occurs. Consequently, the possibility that deficient or defective maturation of the endometrium (decidualization) may compromise extravillous trophoblast invasion in preeclampsia remains unexplored. Using a bioinformatics approach, we tested this hypothesis identifying 396 differentially expressed genes (DEG) in chorionic villous samples from women at ≈11.5 gestational weeks who developed severe preeclampsia symptoms 6 months later compared with chorionic villous samples from normal pregnancies. A large number, 154 or 40%, overlapped with DEG associated with various stages of normal endometrial maturation before and after implantation as identified by other microarray data sets (
P
=4.7×10
−14
). One-hundred and sixteen of the 154 DEG or 75% overlapped with DEG associated with normal decidualization in the absence of extravillous trophoblast, ie, late-secretory endometrium (LSE) and endometrium from tubal ectopic pregnancy (EP;
P
=4.2×10
−9
). Finally, 112 of these 154 DEG or 73% changed in the opposite direction in microarray data sets related to normal endometrial maturation (
P
=0.01), including 16 DEG upregulated in decidual (relative to peripheral blood) natural killer cells that were downregulated in chorionic villous samples from women who developed preeclampsia (
P
<0.0001). Taken together, these results suggest that insufficient or defective maturation of endometrium and decidual natural killer cells during the secretory phase and early pregnancy preceded the development of preeclampsia.
Initial Body Temperature in Ischemic Stroke
Authors: Kim Seo Hyun , Saver Jeffrey L.
Published: November 2014

Background and Purpose—

Body temperature (BT) is an important physiological factor in acute ischemic stroke. However, the relationship of initial BT to stroke severity and degree of benefit from thrombolytic therapy has been delineated incompletely.

Methods—

We analyzed the public data set of the 2 National Institute of Neurological Disorders and Stroke Tissue-Type Plasminogen Activator (tPA) stroke trials, comparing patients with lower (<37.0°C) and higher (≥37.0°C) presenting BT.

Results—

Among 595 patients (297 placebo and 298 tPA treated) with documented initial BT, 77.1% had initial BT <37.0°C and 22.9% ≥37.0°C. Patients with higher initial BT had lower baseline stroke severity in both tPA-treated patients (the National Institute of Health Stroke Scale median, 11 versus 15;
P
=0.05) and placebo-treated patients (median, 13 versus 16;
P
<0.01). Patients with higher initial BT also had lower infarction volume on computed tomography at 3 months in both tPA-treated patients (median, 9.6 versus 16.7 cm
3
;
P
=0.08) and placebo-treated patients (median, 13.1 versus 28.1 cm
3
;
P
=0.02), but no clinical outcome differences. Analysis of lytic treatment effect found no heterogeneity in the degree of tPA benefit in both higher and lower BT groups (≥37.0°C: odds ratio for the modified Rankin Scale 0–1 outcome, 2.55; 95% confidence interval, 1.05–6.21 and <37.0°C: odds ratio, 2.30; 95% confidence interval, 1.38–3.84; heterogeneity
P
=0.83).

Conclusions—

In patients with hyperacute stroke, higher presenting temperatures are associated with less severe neurological deficits and reduced final infarct volumes. Presenting temperature does not modify the benefit of tPA on 3-month favorable outcome.
Nostalgia, the Fleeting, and the Rare in Chilean Relationships to Nature and Nonhuman Species
Authors: Root-Bernstein Meredith
Published: November 2014

Semi-structured interviews and participant observation were used to understand how urban Chileans form relationships with nature and nonhuman species in central Chile. Most informants expressed dislike of the typical mediterranean-habitat landscape, characterizing it as dry, poor, and empty. Yet many people expressed nostalgic attachment to specific places, species, and activities that they had experienced, often as children. Most of the reminisced-about interactions were fleeting or had been lost over time. In the dominant discourse, nature in the mediterranean zone of Chile is closely associated with poverty, and it is considered to lack beauty, biodiversity, culture, and history. Appeals to personal nostalgia may break through this discourse to form private assemblages of value. Chileans also attributed social value to interactions with species who are rare or who are found “exclusively” in Chile. Appeals to nostalgia, rarity, and exclusivity help to draw these private discourses into the public realm.
Soft or Hard Law
Authors: Zhao Lijun
Published: November 2014

Historically, international regimes regulating maritime transport have aimed to develop uniform rules. However, these rules are relatively static and have been implemented differently based on different national understandings in a de-centralised, State-based manner. This article argues that greater global uniformity in maritime transport rules could be achieved through the framework of the World Trade Organization (‘wto’). The wto could update these rules dynamically, and could also enforce them. A wto-based negotiating forum could generate substantive, uniform seaborne cargo rules in two ways. Through a selective referral approach, it could incorporate the existing rules — including the un-administered rules — within the wto framework. It could also develop new uniform rules. The wto also provides international communities with a quasi-judicial procedure — the wto dispute settlement mechanism (‘dsm’) — which could also be used to protect and promote the global uniformity of seaborne cargo rules. Such an approach could further reduce divergent interpretations of uniform transport rules by providing a centralised system for the implementation of those rules.
Deconstructing the Religious Free Market
Authors: Chen Jianlin
Published: November 2014

Scholars have frequently alluded to the normative value of the religious free market fostered by the twin legal guarantees of the free exercise of religion and the absence of state establishment of religion. But given that the desirable normative interpretations of these two clauses differ widely, the nature of the resulting market is inevitably dependent on one’s choice of these contested interpretations. Similarly, the “entitlement to free competition” depends on the definition of “religion.” The present article deconstructs the religious free market into its legal components and discusses critically how the different interpretations and combinations of these legal components materially affect the resulting religious market.
To Hive or to Hold? Producing Professional Authority through Scut Work
Authors: Huising Ruthanne
Published: November 2014

This paper examines how professionals working in bureaucratic organizations, despite having formal authority, struggle to enact authority over the clients they advise, transforming their right to command into deference to commands. Drawing on a comparative ethnographic study of two professional groups overseeing compliance in university laboratories, I identify how choices about their task jurisdiction influence each profession’s ability to enact authority over and gain voluntary compliance from the same group of clients. One group constructs its work domain to include not only high-skilled tasks that emphasize members’ expertise but also scut work—menial work with contaminated materials—through which they gain regular entry into clients’ workspaces, developing knowledge about and relationships with clients. Using these resources to accommodate, discipline, and understand clients, they produce relational authority—the capacity to elicit voluntary compliance with commands. The other group outsources everyday scut work and interacts with lab researchers mostly during annual inspections and training, which leads to complaints by researchers to management and eventual loss of jurisdiction. The findings show the importance of producing relational authority in contemporary professional–client interactions in bureaucratic settings and challenge the relevance of expertise and professional identity in generating relational authority. I show how holding on to, not hiving off, scut work allows professionals to enact authority over clients.
Climate Change and Financial Market Efficiency
Authors: Liesen Andrea
Published: November 2014

This dissertation abstract and reflection commentary present the work of Dr. Andrea Liesen. The dissertation examines the informational efficiency of financial markets to price the systematic risk stemming from climate change for European companies. The abstract provides an overview of the underlying theory, introduces the development of hypotheses, the method applied, and data gathered, as well as selected implications of results. The reflection commentary discusses the author’s views of the research process as a junior scholar.