bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal expressions of follicle-stimulating hormone receptor and luteinizing hormone receptor in the scented gland of the male muskrat (Ondatra zibethicus)
Authors: Zhang Haolin , Zhang Fengwei , Zhu Manyu , Wang Junjie , Sheng Xia , Yuan Zhengrong , Han Yingying , Watanabe Gen , Taya Kazuyoshi , Weng Qiang
Published: February 2017

Accumulating evidence has shown that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) may influence the functions of nongonadal tissues in addition to their classic target gonads. Our previous studies revealed that the scented glands of male muskrats expressed prolactin receptor, steroidogenic enzymes, and inhibin/activin subunits. To further seek the evidence of the activities of pituitary gonadotropins in scented glands, we investigated the seasonal expression patterns of FSH receptor (FSHR) and LH/choriogonadotropin receptor (LHCGR). The weight and size of scented glands during the breeding season were significantly higher than those during the nonbreeding season. Immunohistochemical studies showed that FSHR was present in the serous cells of scented glands, whereas LHCGR was present in the interstitial cells. The protein and mRNA expression levels of FSHR and LHCGR were significantly higher in the scented glands during the breeding season than those during the nonbreeding season. Importantly, the levels of circulating FSH and LH were remarkably higher during the breeding season. Taken together, these results suggested that gonadotropins may affect the function of muskrat scented gland via the locally expressed receptors in a season-dependent manner.
Childhood Nephrotic Syndrome Management and Outcome: A Single Center Retrospective Analysis
Authors: Wang Chia-shi , Yan Jia , Palmer Robert , Bost James , Wolf Mattie Feasel , Greenbaum Larry A.
Published: February 2017

There is a paucity of information on outpatient management and risk factors for hospitalization and complications in childhood nephrotic syndrome (NS). We described the management, patient adherence, and inpatient and outpatient usage of 87 pediatric NS patients diagnosed between 2006 and 2012 in the Atlanta Metropolitan Statistical Area. Multivariable analyses were performed to examine the associations between patient characteristics and disease outcome. We found that 51% of the patients were treated with two or more immunosuppressants. Approximately half of the patients were noted to be nonadherent to medications and urine protein monitoring. The majority (71%) of patients were hospitalized at least once, with a median rate of 0.5 hospitalizations per patient year. Mean hospital length of stay was 4.0 (3.8) days. Fourteen percent of patients experienced at least one serious disease complication. Black race, frequently relapsing/steroid-dependent and steroid-resistant disease, and the first year following diagnosis were associated with higher hospitalization rates. The presence of comorbidities was associated with longer hospital length of stay and increased risk of serious disease complications. Our results highlight the high morbidity and burden of NS and point to particular patient subgroups that may be at increased risk for poor outcome.
YCl3 Promotes Neuronal Cell Death by Inducing Apoptotic Pathways in Rats
Authors: Ding Yechun , Tian Yuantong , Zeng Zhaoyi , Shuai Ping , Lan Haiying , Zhu Xianshen , Zhong Yi , Wu Longhuo , Fan Xiaona
Published: February 2017

The pollutants rare earth elements (REEs) have posed great threats to human health. To investigate the cytotoxicity of yttrium (Y), a model that rats have free access to water containing YCl3 for 6 months is utilized. The results showed that YCl3 treatment promoted neuronal cell apoptosis by upregulating the proapoptotic factors Bax, caspase-3, Cyto c, and DAPK and by downregulating the antiapoptotic factors Bcl-2 and XIAP at both mRNA and protein levels. Conclusively, YCl3 exhibited cytotoxicity and promoted neuronal cell death by the induction of apoptotic pathways.
Extensive Renal Arteriovenous Malformations Treated by Transcatheter Arterial Embolization
Authors: Tabei Tadashi , Tajirika Hironao , Yoshigi Jun , Kobayashi Kazuki
Published: February 2017

An 84-year-old woman was referred to our department due to gross hematuria. Enhanced computed tomography revealed early enhancement of the right renal vein and multiple tortuous vessels around the right renal hilus, part of which had invaded into the renal parenchyma and renal calix. We diagnosed her with arteriovenous malformations (AVMs) and performed transcatheter arterial embolization (TAE). Angiography showed extensive and complex AVMs located in the central and peripheral areas of her kidney. After TAE, the hematuria resolved and she became hemodynamically stable.
Performance Evaluation of MDO Architectures within a Variable Complexity Problem
Authors: Zhang Daiyu , Song Baowei , Wang Peng , He Yanru
Published: February 2017

Though quite a number of multidisciplinary design optimization (MDO) architectures have been proposed for the optimal design of large‐scale multidisciplinary systems, how their performance changes with the complexity of MDO problem varied is not well studied. In order to solve this problem, this paper presents a variable complexity problem which allows people to obtain a MDO problem with arbitrary complexity by specifying its changeable parameters, such as the number of disciplines and the numbers of design variables. Then four investigations are performed to evaluate how the performance of different MDO architectures changes with the number of disciplines, global variables, local variables, and coupling variables varied, respectively. Finally, the results supply guidance for the selection of MDO architectures in solving practical engineering problems with different complexity.
Could Perinatal Asphyxia Induce a Synaptopathy? New Highlights from an Experimental Model
Authors: Herrera María Inés , Otero-Losada Matilde , Udovin Lucas Daniel , Kusnier Carlos , Kölliker-Frers Rodolfo , de Souza Wanderley , Capani Francisco
Published: February 2017

Birth asphyxia also termed perinatal asphyxia is an obstetric complication that strongly affects brain structure and function. Central nervous system is highly susceptible to oxidative damage caused by perinatal asphyxia while activation and maturity of the proper pathways are relevant to avoiding abnormal neural development. Perinatal asphyxia is associated with high morbimortality in term and preterm neonates. Although several studies have demonstrated a variety of biochemical and molecular pathways involved in perinatal asphyxia physiopathology, little is known about the synaptic alterations induced by perinatal asphyxia. Nearly 25% of the newborns who survive perinatal asphyxia develop neurological disorders such as cerebral palsy and certain neurodevelopmental and learning disabilities where synaptic connectivity disturbances may be involved. Accordingly, here we review and discuss the association of possible synaptic dysfunction with perinatal asphyxia on the basis of updated evidence from an experimental model.
Dasatinib and Prednisolone Induction Therapy for a Case of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia with Dilated Cardiomyopathy Accompanied by Life-Threatening Ventricular Tachycardia
Authors: Nishimoto Mitsutaka , Nakamae Hirohisa , Matsumoto Kana , Morita Kunihiko , Koga Yuki , Momose Dai , Hino Masayuki
Published: February 2017

A 56-year-old man being treated for dilated cardiomyopathy presented with epigastralgia. He was diagnosed with ventricular tachycardia and Philadelphia chromosome-positive acute lymphoblastic leukemia. After treating incessant ventricular tachycardia, we commenced induction therapy for leukemia with dasatinib and prednisolone to minimize toxicity towards cardiomyocytes and the cardiac conduction system. Although dasatinib was temporarily withheld because of a recurrence of ventricular tachycardia, we rechallenged dasatinib while using bisoprolol and amiodarone and achieved a complete hematological response three weeks later. Although drug interactions between dasatinib and amiodarone were of concern, the blood concentration of each drug remained within the safe range after concomitant use, and there were no adverse cardiac effects such as QT prolongation after rechallenging dasatinib. Induction therapy with dasatinib and prednisolone may be an acceptable therapeutic option for Philadelphia chromosome-positive acute lymphoblastic leukemia with severe cardiac complications.
A Rare Adrenal Mass in a 3-Month-Old: A Case Report and Literature Review
Authors: Garg Ashish , Pollak-Christian Elza , Unnikrishnan Navneetha
Published: February 2017

A three-month-old female infant presented with abdominal distention for 2 months. A large palpable mass in right upper quadrant was noted on physical exam. Abdominal ultrasound revealed a large heterogeneous mass with multiple cystic components. Mass was surgically excised and pathology was consistent with mature adrenal teratoma. Teratoma is a germ cell tumor mainly found in gonadal tissues. Occurrence of adrenal gland teratoma in children is very rare with less than 10 pediatric case reports in English literature. We present a rare case of primary adrenal tumor in an infant and a review of the literature.
Duodenal Atresia: Open versus MIS Repair—Analysis of Our Experience over the Last 12 Years
Authors: Chiarenza Salvatore Fabio , Bucci Valeria , Conighi Maria Luisa , Zolpi Elisa , Costa Lorenzo , Fasoli Lorella , Bleve Cosimo
Published: February 2017

Objective. Duodenal atresia (DA) routinely has been corrected by laparotomy and duodenoduodenostomy with excellent long-term results. We revisited the patients with DA treated in the last 12 years (2004–2016) comparing the open and the minimally invasive surgical (MIS) approach.Methods. We divided our cohort of patients into two groups. Group 1 included 10 patients with CDO (2004–09) treated with open procedure: 5, DA; 3, duodenal web; 2, extrinsic obstruction. Three presented with Down’s syndrome while 3 presented with concomitant malformations. Group 2 included 8 patients (2009–16): 1, web; 5, DA; 2, extrinsic obstruction. Seven were treated by MIS; 1 was treated by Endoscopy. Three presented with Down’s syndrome; 3 presented with concomitant malformations.Results. Average operating time was 120 minutes in Group 1 and 190 minutes in Group 2. In MIS Group the visualization was excellent. We recorded no intraoperative complications, conversions, or anastomotic leakage. Feedings started on 3–7 postoperative days. Follow-up showed no evidence of stricture or obstruction. In Group 1 feedings started within 10–22 days and we have 1 postoperative obstruction.Conclusions. Laparoscopic repair of DA is one of the most challenging procedures among pediatric laparoscopic procedures. These patients had a shorter length of hospitalization and more rapid advancement to full feeding compared to patients undergoing the open approach. Laparoscopic repair of DA could be the preferred technique, safe, and efficacious, in the hands of experienced surgeons.
An Approach to Macroscopic Central Lymph Nodes Detected during Surgery in Patients with Thyroid Micropapillary Carcinoma: Should We Resort to Dissection?
Authors: Kurukahvecioglu Osman , Dikmen Kursat , Bostanci Hasan , Akin Murat , Taneri Ferit
Published: February 2017

Background. High-resolution ultrasonography and the ability to perform fine-needle aspiration biopsy even for nodules smaller than three millimeters have considerably increased the detection rate of thyroid micropapillary carcinoma (TMPC). Despite favorable prognosis, the prevalence of cervical lymph node metastases in patients with TMPC is approximately 30%. Aim. In this study, we aimed to determine the central lymph node metastasis rate and its relation to the characteristics of the tumor. Methods. One hundred nine patients who underwent surgery due to TMPC between December 2009 and January 2014 were analyzed retrospectively. Patients were divided into two groups according to whether they underwent lymph node dissection and the two groups were then compared with respect to tumor size and multicentricity, age, and presence of lymphocytic thyroiditis. Results. There were no statistically significant differences between the two groups of patients in terms of tumor size, tumor multicentricity, age, and presence of lymphocytic thyroiditis. When the patient group that received lymph node dissection was further analyzed, it was found that patients with lymphocytic thyroiditis had a significantly lower number of metastatic lymph nodes. Conclusion. Central lymph node dissection in TMPC patients with macroscopic lymph node detected intraoperatively would ensure accurate staging without an increase in morbidity.
Ameliorating Effect of Gemigliptin on Renal Injury in Murine Adriamycin-Induced Nephropathy
Authors: Kim Da Rae , Lee Shin Yeong , Kim Jin Sug , Kim Yang Gyun , Moon Ju-Young , Lee Sang Ho , Lee Tae Won , Ihm Chun Gyoo , Jeong Kyung Hwan
Published: February 2017

Background. Previous studies have shown the antiapoptotic and anti-inflammatory potential of DPP-IV inhibitor in experimental models of renal injury. We tested whether DPP-IV inhibitor (gemigliptin) ameliorates renal injury by suppressing apoptosis, inflammation, and oxidative stress in mice with adriamycin nephropathy.Methods. Mice were treated with normal saline (control), gemigliptin (GM), adriamycin (ADR), or adriamycin combined with gemigliptin (ADR+GM). Apoptosis, inflammation, and oxidative stress were analyzed via western blotting, real-time PCR, light microscopy, and immunofluorescence.Results. In the ADR+GM group, urine albumin creatinine ratio decreased significantly compared with that in the ADR group on day 15. Glomerulosclerosis index and tubulointerstitial injury index in mice with adriamycin-induced nephropathy decreased after gemigliptin treatment. ADR group showed higher levels of apoptosis, inflammation, and oxidative stress-related molecules compared with the control group. The upregulation of these molecules was significantly reduced by gemigliptin. In the ADR group, the staining intensities of WT-1 and nephrin reduced, but these changes were ameliorated in the ADR+GM group.Conclusion. We demonstrated that gemigliptin ameliorates nephropathy by suppressing apoptosis, inflammation, and oxidative stress in mice administered adriamycin. Our data demonstrate that gemigliptin has renoprotective effects on adriamycin-induced nephropathy.
Shigella sonneiBacteremia Presenting with Profound Hepatic Dysfunction
Authors: Shogbesan Oluwaseun , Rettew Andrew , Shaikh Bilal , Abdulkareem Abdullateef , Donato Anthony
Published: February 2017

Worldwide, Shigellosis is a significant public health issue, associated with nearly one million deaths annually. About half a million cases ofShigellainfection are reported annually in the United States.Shigellabacteremia is uncommon and generally seen in children and immunocompromised adults. We present a case of aShigella sonneibacteremia with marked hepatic derangement in a 27-year-old previously healthy homosexual male with history of Roux-en-Y gastric bypass, who presented to the emergency room with a 4-day history of loose watery stool, abdominal cramps, nausea and vomiting, and yellow skin of 2-day duration. He reports similar diarrhea illness in two close contacts in preceding days. On examination, he was fully oriented but dehydrated, icteric, and febrile. Laboratory data revealed WBC of 2200/μL, elevated AST and ALT (201 IU/L, 73 IU/L resp.), normal alkaline phosphatase, elevated total and direct bilirubin of 8.2 mg/dL and 4.4 mg/dL, albumin of 3.2 g/dL, INR of 2.9, prothrombin time of 31.7, and platelet of 96,000/μL. Workup for infectious, autoimmune and medication-induced hepatitis, Wilson’s disease, and hemochromatosis was negative. Abdominal ultrasound and computed tomography of the abdomen showed hepatic steatosis and right-sided colitis. Stool and blood cultures were positive forShigella sonnei. He was treated with ciprofloxacin with improvement in liver function. Follow-up blood test 4 months later was within normal limits.
Impacted Maxillary Canine Prevalence and Its Association with Other Dental Anomalies in a Mexican Population
Authors: Herrera-Atoche José Rubén , Agüayo-de-Pau María del Rosario , Escoffié-Ramírez Mauricio , Aguilar-Ayala Fernando Javier , Carrillo-Ávila Bertha Arelly , Rejón-Peraza Marina Eduviges
Published: February 2017

Objective. We quantified the prevalence of impacted maxillary canines (IMC) and their association with other dental anomalies (DAs).Materials and Methods. A retrospective study was done with 860 patients 12 to 39 years of age. The prevalence of IMC was calculated and compared by sex. The sample was divided into a control group and an impaction group, and the prevalence was calculated in both for a series of anomalies: agenesis, supernumerary teeth, shape anomalies of the upper laterals (microdontia, peg and barrel shape, and talon cusp), fusion, gemination, other impacted teeth, transposition, and amelogenesis imperfecta. The prevalence values for both groups were compared (Pearson’sχ2test,p≤0.05).Results. IMC were present in 6.04% of the sample with no difference by sex (p=0.540). Other DAs occurred in 51.92% of the IMC group and in 20.17% of the controls (p<0.05). Significant associations (p<0.05) were identified between IMC and four other DAs: microdontia, barrel shape, other impacted teeth, and transposition. The prevalence of all anomalies was lower in the control group.Conclusion. IMC were seen in 6.04% of patients. Patients with this condition also had a higher prevalence of other DAs. These other anomalies should be used as risk indicators for early diagnosis.
Time Reversal Aided Bidirectional OFDM Underwater Cooperative Communication Algorithm with the Same Frequency Transmission
Authors: Zhang Lingling , Huang Jianguo , Tang Chengkai , Song Houbing
Published: February 2017

In underwater acoustic channel, signal transmission may experience significant latency and attenuation that would degrade the performance of underwater communication. The cooperative communication technique can solve it but the spectrum efficiency is lower than traditional underwater communication. So we proposed a time reversal aided bidirectional OFDM underwater cooperative communication algorithm. The algorithm allows all underwater sensor nodes to share the same uplink and downlink frequency simultaneously to improve the spectrum efficiency. Since the same frequency transmission would produce larger intersymbol interference, we adopted the time reversal method to degrade the multipath interference at first; then we utilized the self-information cancelation module to remove the self-signal of OFDM block because it is known for sensor nodes. In the simulation part, we compare our proposed algorithm with the existing underwater cooperative transmission algorithms in respect of bit error ratio, transmission rate, and computation. The results show that our proposed algorithm has double spectrum efficiency under the same bit error ratio and has the higher transmission rate than the other underwater communication methods.
A Child as a Donor for Hematopoietic Stem Cell Transplantation: Bioethical Justification—A Case Study on Sickle Cell Disease
Authors: Pereira Andrea Z. , Hellman Ricardo , Hamerschlak Nelson , Kondo Andrea , Souza Polianna Mara Rodrigues de , Pedreira Wilson Leite , Mantovani Luiz Fernando Alves Lima , Troster Eduardo Juan , Grunspun Henrique , Bueno Marco Aurélio Scarpinella
Published: February 2017

Hematopoietic stem cell transplantation (HSCT) is an important treatment option for children with severe and refractory sickle cell disease (SCD) with debilitating clinical complications. HSCT with cells from the bone marrow of a HLA-identical sibling used in SCD has a low mortality risk, high cure rate, and high event-free survival rate after a median follow-up of 5-6 years. However, matched donors are found in only about 20% of the patients. A boy aged 8 years with SCD had a sister, <2 years old, a fully compatible donor. The boy met all eligibility criteria to undergo HSCT, and he was suffering from cognitive and neurologic impairment due to ischemic events. A Bioethical Committee jointly discussed the ethical issues on this case after a pediatric evaluation released the very young sister for donation. The justification was that the sister would benefit from the donation too because of the greater likelihood of survival and cure and less suffering of her brother. The parents were informed about the risks and benefits for both children, and the family was psychologically evaluated. After their consent, HSCT was performed and the patient is cured from SCD. The complication for the donor was the need for blood transfusion.
Study of the Dynamic Uptake of Free Drug and Nanostructures for Drug Delivery Based on Bioluminescence Measurements
Authors: Fang Zhongjian , Xu Houchao , Ji Xiangjun , Liu Congbiao , Wang Kai , Qian Xiaoqing , Zhou Wencong
Published: February 2017

The past two decades have witnessed the great growth of the development of novel drug carriers. However, the releasing dynamics of drug from drug carriers in vivo and the interactions between cells and drug carriers remain unclear. In this paper, liposomes were prepared to encapsulate D-luciferin, which was the substrate of luciferase and served as a model drug. Based on the theoretical calculation of active loading, methods of preparation for liposomes were optimized. Only when D-luciferin was released from liposomes or taken in by the cells could bioluminescence be produced under the catalysis of luciferase. Models of multicellular tumor spheroid (MCTS) were built with 4T1-luc cells that expressed luciferase stably. The kinetic processes of uptake and distribution of free drugs and liposomal drugs were determined with models of cell suspension, monolayer cells, MCTS, and tumor-bearing nude mice. The technology platform has been demonstrated to be effective for the study of the distribution and kinetic profiles of various liposomes as drug delivery systems.
Implementation of an Agent-Based Parallel Tissue Modelling Framework for the Intel MIC Architecture
Authors: Cytowski Maciej , Szymańska Zuzanna , Umiński Piotr , Andrejczuk Grzegorz , Raszkowski Krzysztof
Published: February 2017

Timothy is a novel large scale modelling framework that allows simulating of biological processes involving different cellular colonies growing and interacting with variable environment. Timothy was designed for execution on massively parallel High Performance Computing (HPC) systems. The high parallel scalability of the implementation allows for simulations of up to 109 individual cells (i.e., simulations at tissue spatial scales of up to 1 cm3 in size). With the recent advancements of the Timothy model, it has become critical to ensure appropriate performance level on emerging HPC architectures. For instance, the introduction of blood vessels supplying nutrients to the tissue is a very important step towards realistic simulations of complex biological processes, but it greatly increased the computational complexity of the model. In this paper, we describe the process of modernization of the application in order to achieve high computational performance on HPC hybrid systems based on modern Intel® MIC architecture. Experimental results on the Intel Xeon Phi™ coprocessor x100 and the Intel Xeon Phi processor x200 are presented.
The Dynamics of Type 2 Diabetes Mellitus Prevalence and Management Rates among Rural Population in Henan Province, China
Authors: Liu Xiaotian , Wang Ling , Wang Panpan , Liu Ruihua , Yang Kaili , Qian Xinling , Fan Jingjing , Yu Songcheng , Li Yuqian , Wang Chongjian
Published: February 2017

The aim of this study was to estimate the dynamics of type 2 diabetes mellitus (T2DM) prevalence and management rates based on a rural cohort study in Henan Province of China. The rural prospective study was conducted for 20194 Chinese population ≥18 years in 2007-2008 and followed during 2013-2014. A total of 14009 individuals were recruited for the prospective analysis ultimately. Over 5.74 years of follow-up, the age-standardized prevalence, awareness, treatment, and control of T2DM increased from 6.18%, 44.41%, 34.39%, and 19.08% at baseline to 7.87%, 59.64%, 52.17%, and 26.52% at follow-up in total population, respectively. Similar changes were found in men and women except the age-standardized control in men. The four parameters of T2DM were higher among various factors at follow-up than those at baseline. There was no statistical difference in awareness (P=0.089) and treatment (P=0.257) in the newly diagnosed T2DM compared with the rates at baseline. The current study indicated that the prevalence, awareness, treatment, and control of T2DM displayed chronological increasing trends while the awareness, treatment, and control of T2DM were still disproportionally low in central China. More works are needed urgently to popularize public health education and improve the quality of medical care in T2DM.
Evaluation of Prepubertal Patients with Suspected Neurosecretory Dysfunction of Growth Hormone Secretion: Diagnostic Steps and Treatment Response
Authors: Sydlik Carmen , Weißenbacher Claudia , Roeb Julia , Bechtold-Dalla Pozza Susanne , Schmidt Heinrich
Published: February 2017

Background and Aims.Existence and diagnostic procedures of neurosecretory dysfunction of growth hormone (NSD) are still a matter of debate. The aim of our study was (a) to find out if prediagnostic auxological and laboratory data could serve as an indicator for pathologic and normal spontaneous GH-secretion and (b) to evaluate the response to GH-therapy in NSD-patients.Methods.Of 90 children (unicentric study) with normal response to GH-stimulation tests, in whom 12-hour night profiles for GH-secretion were performed, 49 were diagnosed with NSD (NSD group). Their auxologic data, IGF-I/IGFBP3-levels as well as the night profiles, were analysed and compared to those of the non-NSD group. Additionally, follow-up auxological data of the GH-treated NSD-patients were collected.Results.Prediagnostic auxologic and laboratory data did not differ between the two groups. Instead, for all analysed criteria of spontaneous GH-secretion (number of peaks, maximal and mean secretion) a significant difference was found. Children with NSD showed a good response to GH-treatment after 1 (ΔH-SDS +0,77 ± 0,48) as well as 4 years (+1,51 ± 0,75).Conclusion.According to our results, analysing spontaneous GH-secretion remains the only method to identify NSD. Yet, as response to GH-treatment is comparable to results in idiopathic GHD, it is worth to consider this diagnosis.
Predictors of Recovery from Traumatic Brain Injury-Induced Prolonged Consciousness Disorder
Authors: Abe Hiroaki , Shimoji Keigo , Nagamine Yoshihide , Fujiwara Satoru , Izumi Shin-Ichi
Published: February 2017

We investigated the clinical predictors of the degree of recovery in patients with prolonged disorders of consciousness (PDC) caused by traumatic brain injury. Fourteen patients with PDC underwent two diffusion tensor imaging (DTI) studies; the first and second scans were performed at 345.6±192.6 and 689.1±272.2 days after the injury, respectively. In addition to the temporal changes in each of these diffusion parameters, fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), and radial diffusivity were assessed over a 1-year period. Relationship of clinical and DTI parameters with recovery from PDC (RPDC) was evaluated using Spearman’s rank-correlation and stepwise multiple linear regression analysis. The mean FA and number of voxels with FA values > 0.4 (VsFA0.4) were significantly decreased at the second scan. A significant positive correlation was observed between the degree of RPDC and mean FA (r=0.60) and VsFA0.4 (r=0.68) as well as between the difference in VsFA0.4 (r=0.63) and AD (r=0.54) between the first and second scans. On multiple linear regression analysis, initial severity of PDC and the difference in AD remained significantly associated with the degree of RPDC. The microstructural white matter changes observed in this study indicate their potential relation with the degree of RPDC over the longer term.
Algebraic Cryptanalysis Scheme of AES-256 Using Gröbner Basis
Authors: Zhao Kaixin , Cui Jie , Xie Zhiqiang
Published: February 2017

The zero-dimensional Gröbner basis construction is a crucial step in Gröbner basis cryptanalysis on AES-256. In this paper, after performing an in-depth study on the linear transformation and the system of multivariate polynomial equations of AES-256, the zero-dimensional Gröbner basis construction method is proposed by choosing suitable term order and variable order. After giving a detailed construction process of the zero-dimensional Gröbner basis, the necessary theoretical proof is presented. Based on this, an algebraic cryptanalysis scheme of AES-256 using Gröbner basis is proposed. Analysis shows that the complexity of our scheme is lower than that of the exhaustive attack.
Impact of Disseminated Neuroblastoma Cells on the Identification of the Relapse-Seeding Clone
Authors: Abbasi M. Reza , Rifatbegovic Fikret , Brunner Clemens , Mann Georg , Ziegler Andrea , Pötschger Ulrike , Crazzolara Roman , Ussowicz Marek , Benesch Martin , Ebetsberger-Dachs Georg , Chan Godfrey C.F. , Jones Neil , Ladenstein Ruth , Ambros Inge M. , Ambros Peter F.
Published: February 2017

Purpose: Tumor relapse is the most frequent cause of death in stage 4 neuroblastomas. Since genomic information on the relapse precursor cells could guide targeted therapy, our aim was to find the most appropriate tissue for identifying relapse-seeding clones.

Experimental design: We analyzed 10 geographically and temporally separated samples of a single patient by SNP array and validated the data in 154 stage 4 patients.

Results: In the case study, aberrations unique to certain tissues and time points were evident besides concordant aberrations shared by all samples. Diagnostic bone marrow–derived disseminated tumor cells (DTCs) as well as the metastatic tumor and DTCs at relapse displayed a 1q deletion, not detected in any of the seven primary tumor samples. In the validation cohort, the frequency of 1q deletion was 17.8%, 10%, and 27.5% in the diagnostic DTCs, diagnostic tumors, and DTCs at relapse, respectively. This aberration was significantly associated with 19q and ATRX deletions. We observed a significant increased likelihood of an adverse event in the presence of 19q deletion in the diagnostic DTCs.

Conclusions: Different frequencies of 1q and 19q deletions in the primary tumors as compared with DTCs, their relatively high frequency at relapse, and their effect on event-free survival (19q deletion) indicate the relevance of analyzing diagnostic DTCs. Our data support the hypothesis of a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. Therefore, searching for biomarkers to identify the relapse-seeding clone should involve diagnostic DTCs alongside the tumor tissue. Clin Cancer Res; 23(15); 4224–32. ©2017 AACR.
Prognostic Markers and Histologic Subtypes in Patients with Meningeal Carcinomatosis in Breast Cancer
Authors: Alnajar Hussein , Rosen Lauren , Javidiparsijani Sara , Al-Ghamdi Yahya , Gattuso Paolo
Published: February 2017

Objective: Meningeal carcinomatosis (MC) is a rare complication in breast cancer patients. It is defined as a diffuse or multifocal leptomeningeal metastasis. Study Design: From our institution database, we retrospectively studied 19 patients diagnosed with MC in the cerebrospinal fluid (CSF) in 1997-2015, in order to evaluate tumor prognostic markers, histologic subtypes, and clinical outcome. Results: All patients were female, with a mean age of 53 years (range 36-75 years). The mean interval between diagnosis of breast carcinoma and MC was 28 months (range 6-62 months). The median survival from the time of diagnosis was 2 months (1-51 months). Sixteen cases (84%) were the ductal phenotype, 62% of which were of a high grade (grade 3), and 3 cases (16%) were lobular. Estrogen and progesterone receptors were positive on immunohistochemistry (IHC) in 53 and 33% of patients, respectively. HER2 IHC was positive (3+) in 20% of the cases; all were amplified by fluorescence in situ hybridization. The incidence of MC in triple-negative tumors was 40%. Twelve patients (63%) already had known metastasis at the time of diagnosis. Conclusions: Most cases of MC are high-grade ductal. MC is more common in triple-negative breast cancers. The outcome of these breast cancer patients with MC was poor. There was no survival difference according to age, histologic subtype, grade, or hormonal or HER2 status.
Mating of 2 Laboratory Saccharomyces cerevisiae Strains Resulted in Enhanced Production of 2-Phenylethanol by Biotransformation of L-Phenylalanine
Authors: Mierzejewska Jolanta , Tymoszewska Aleksandra , Chreptowicz Karolina , Krol Kamil
Published: February 2017

2-Phenylethanol (2-PE) is an aromatic alcohol with a rosy scent which is widely used in the food, fragrance, and cosmetic industries. Promising sources of natural 2-PE are microorganisms, especially yeasts, which can produce 2-PE by biosynthesis and biotransformation. Thus, the first challenging goal in the development of biotechnological production of 2-PE is searching for highly productive yeast strains. In the present work, 5 laboratory Saccharomyces cerevisiae strains were tested for the production of 2-PE. Thereafter, 2 of them were hybridized by a mating procedure and, as a result, a new diploid, S. cerevisiae AM1-d, was selected. Within the 72-h batch culture in a medium containing 5 g/L of L-phenylalanine, AM1-d produced 3.83 g/L of 2-PE in a shaking flask. In this way, we managed to select the diploid S. cerevisiae AM1-d strain, showing a 3- and 5-fold increase in 2-PE production in comparison to parental strains. Remarkably, the enhanced production of 2-PE by the hybrid of 2 yeast laboratory strains is demonstrated here for the first time.
Drug Interactions in the Treatment of Malignancy in HIV-Infected Patients
Authors: Welz Tanya , Wyen Christoph , Hensel Manfred
Published: February 2017

The number of patients with HIV (human immunodeficiency virus) requiring treatment for malignancy is increasing worldwide. Concurrent treatment of HIV and malignancy is complicated by unpredictable drug-drug interactions, which can cause potentially life-threatening toxicities and ineffective treatment of either disease. This article aims to provide a practical approach to drug interactions and their management in this context to help deliver effective and safe treatment of both the malignancy and HIV.
Pharmacokinetics of recombinant human soluble thrombomodulin in disseminated intravascular coagulation patients with acute renal dysfunction
Authors: Kushimoto Shigeki , Watanabe Eizo , Goto Koji , Suzuki Yasushi , Kotani Toru , Kiguchi Takeyuki , Yatabe Tomoaki , Tagawa Jun , Komatsu Fumiyo , Gando Satoshi , Hayakawa Mineji
Published: February 2017

Recombinant human soluble thrombomodulin (ART-123) is a novel anticoagulant for patients with disseminated intravascular coagulation (DIC). It is widely used in clinical settings throughout Japan. Furthermore, a global Phase 3 study is currently being conducted. In healthy subjects, ART-123 is excreted mainly via the kidneys. Therefore, ART-123 dose decrease was recommended in DIC patients with severe renal dysfunction. However, the pharmacokinetics of ART-123 in DIC patients with severe acute renal dysfunction has not been elucidated. In an open-label, multicentre, prospective, clinical pharmacological study, we investigated the pharmacokinetics and safety of ART-123 upon repeated administration to DIC patients. ART-123 was administered to patients at a dose of 130 or 380 U/kg/day for six consecutive days. Plasma concentrations of ART-123 were measured at 21 time points until eight days after the final administration. Urinary excretion rates during the first 24 hours (h) were calculated. Patient renal functions were evaluated by measuring 24-h creatinine clearance (Ccr). Forty-three patients were enrolled in the present study. The urinary excretion rates of ART-123 correlated closely with 24-h Ccr. Total body clearance of ART-123 was also weakly related with 24-h Ccr. However, the plasma concentrations of ART-123 were not considerably different among patients with different renal function. Two patients had subcutaneous haemorrhage as an adverse event related to ART-123. In conclusion, plasma concentrations of ART-123 may not be different among patients with different renal functions. ART-123 was well tolerated in these patients.
Mutation in a highly conserved glycine residue in strand 5B of plasminogen activator inhibitor 1 causes polymerisation
Authors: Nagahashi Kotomi , Takano Katsuhiro , Suzuki-Inoue Katsue , Kanayama Naohiro , Umemura Kazuo , Urano Tetsumei , Iwaki Takayuki
Published: February 2017

Serpinopathy is characterised as abnormal accumulation of serine protease inhibitors (SERPINs) in cells and results in clinical symptoms owing to lack of SERPIN function or excessive accumulation of abnormal SERPIN. We recently identified a patient with functional deficiency of plasminogen activator inhibitor-1 (PAI-1), a member of the SERPIN superfamily. The patient exhibited life-threatening bleeding tendencies, which have also been observed in patients with a complete deficiency in PAI-1. Sequence analysis revealed a homozygous singlenucleotide substitution from guanine to cytosine at exon 9, which changed amino acid residue 397 from glycine to arginine (c.1189G>C; p.Gly397Arg). This glycine was located in strand 5B and was well conserved in other serpins. The mutant PAI-1 was polymerised in the cells, interfering with PAI-1 secretion. The corresponding mutations in SERPINC1 (anti-thrombin III) at position 456 (Gly456Arg) and SERPINI1 (neuroserpin) at position 392 (Gly392Glu) caused an anti-thrombin deficiency and severe dementia due to intracellular retention of the polymers. Glycine is the smallest amino acid, and these mutated amino acids were larger and charged. To determine which factors were important, further mutagenesis of PAI-1 was performed. Although the G397A, C, I, L, S, T, and V were secreted, the G397D, E, F, H, K, M, N, P, Q, W, and Y were not secreted. The results revealed that the size was likely triggered by the polymerisation of SEPRINs at this position. Structural analyses of this mutated PAI-1 would be useful to develop a novel PAI-1 inhibitor, which may be applicable in the context of several pathological states.
Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation
Authors: Parkash Ratika , Wells George A. , Sapp John L. , Healey Jeffrey S. , Tardif Jean-Claude , Greiss Isabelle , Rivard Lena , Roux Jean-Francois , Gula Lorne , Nault Isabelle , Novak Paul , Birnie David , Ha Andrew , Wilton Stephen B. , Mangat Iqwal , Gray Christopher , Gardner Martin , Tang Anthony S.L.
Published: February 2017

Background:

Radiofrequency catheter ablation for atrial fibrillation has become an important therapy for AF; however, recurrence rates remain high. We proposed to determine whether aggressive blood pressure (BP) lowering prevents recurrent atrial fibrillation (AF) after catheter ablation in patients with AF and a high symptom burden.

Methods:

We randomly assigned 184 patients with AF and a BP >130/80 mm Hg to aggressive BP (target <120/80 mm Hg) or standard BP (target <140/90 mm Hg) treatment before their scheduled AF catheter ablation. The primary outcome was symptomatic recurrence of AF/atrial tachycardia/atrial flutter lasting >30 seconds, determined 3 months beyond catheter ablation by a blinded end-point evaluation.

Results:

The median follow-up was 14 months. At 6 months, the mean systolic BP was 123.2±13.2 mm Hg in the aggressive BP treatment group versus 135.4±15.7 mm Hg (
P
<0.001) in the standard treatment group. The primary outcome occurred in 106 patients, 54 (61.4%) in the aggressive BP treatment group compared with 52 (61.2%) in the standard treatment group (hazard ratio=0.94; 95% confidence interval, 0.65–1.38;
P
=0.763). In the prespecified subgroup analysis of the influence of age, patients ≥61 years of age had a lower primary outcome event rate with aggressive BP (hazard ratio=0.58; 95% confidence interval, 0.34–0.97;
P
=0.013). There was a higher rate of hypotension requiring medication adjustment in the aggressive BP group (26% versus 0%).

Conclusions:

In this study, this duration of aggressive BP treatment did not reduce atrial arrhythmia recurrence after catheter ablation for AF but resulted in more hypotension.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00438113.
Proof-of-Concept Randomized Trial of the Monoclonal Antibody GSK249320 Versus Placebo in Stroke Patients
Authors: Cramer Steven C. , Enney Lori A. , Russell Colleen K. , Simeoni Monica , Thompson Thomas R.
Published: February 2017

Background and Purpose—

One class of poststroke restorative therapy focuses on promoting axon outgrowth by blocking myelin-based inhibitory proteins such as myelin-associated glycoprotein. The purpose of the current study was to extend preclinical and clinical findings of GSK249320, a humanized monoclonal antibody to myelin-associated glycoprotein with disabled Fc region, to explore effects on motor outcomes poststroke.

Methods—

In this phase IIb double-blind, randomized, placebo-controlled study, patients at 30 centers with ischemic stroke 24 to 72 hours prior and gait deficits were randomized to 2 IV infusions of GSK249320 or placebo. Primary outcome measure was change in gait velocity from baseline to day 90.

Results—

A total of 134 subjects were randomized between May 2013 and July 2014. The 2 groups were overall well matched at baseline. The study was stopped at the prespecified interim analysis because the treatment difference met the predefined futility criteria cutoff; change in gait velocity to day 90 was 0.55±0.46 (mean±SD) in the GSK249320 group and 0.56±0.50 for placebo. Secondary end points including upper extremity function were concordant. The 2 IV infusions of GSK249320 were well tolerated. No neutralizing antibodies to GSK249320 were detected.

Conclusions—

GSK249320, within 72 hours of stroke, demonstrated no improvement on gait velocity compared with placebo. Possible reasons include challenges translating findings into humans and no direct evidence that the therapy reached the biological target. The antibody was well tolerated and showed low immunogenicity, findings potentially useful to future studies aiming to use a monoclonal antibody to modify activity in specific biological pathways to improve recovery from stroke.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01808261.
Ten-Year Temporal Trends in Medical Complications After Acute Intracerebral Hemorrhage in the United States
Authors: Otite Fadar Oliver , Khandelwal Priyank , Malik Amer M. , Chaturvedi Seemant , Sacco Ralph L. , Romano Jose G.
Published: February 2017

Background and Purpose—

Data on medical complications after intracerebral hemorrhage (ICH) are sparse. We assessed trends in the prevalence of urinary tract infection, pneumonia, sepsis, deep venous thrombosis (DVT), pulmonary embolism, acute renal failure (ARF), and acute myocardial infarction after ICH in the United States.

Methods—

A total of 575 211 adult ICH cases were identified from the 2004 to 2013 Nationwide Inpatient Sample. Weighted complication risks were computed by sex and mechanical ventilation status. Multivariate models were used to evaluate trends in complications and assess their association with in-hospital mortality, cost, and length of stay.

Results—

Overall risks of urinary tract infection, pneumonia, sepsis, DVT, pulmonary embolism, ARF, and acute myocardial infarction after ICH were 14.8%, 7.8%, 4.1%, 2.7%, 0.7%, 8.2%, and 2.0%, respectively, but risk differed by sex and mechanical ventilation status. From 2004 to 2013, odds of DVT and ARF increased, whereas odds of pneumonia, sepsis, and mortality declined over time. All complications were associated with >2.5-day increase in length of stay and >$8000 increase in cost. ARF and acute myocardial infarction were associated with increased mortality in all patients; sepsis and pneumonia were associated with increased mortality only in nonmechanical ventilation patients, whereas urinary tract infection and DVT were associated with reduced mortality in all patients.

Conclusions—

Despite significant mortality reduction, ARF and DVT risk after ICH have increased, whereas odds of sepsis and pneumonia have declined over the last decade. All complications were associated with increased cost and length of stay, but their associations with mortality were variable, likely due in part to survival bias. Innovative strategies are needed to prevent ICH-associated medical complications.
Torture, Truth, and the Witnessing Body: Reading Christian Martyrdom with Page duBois
Authors: Burrus Virginia
Published: February 2017

Taking its departure from Page duBois’ monograph Torture and Truth, this essay points toward a gap in the history conveyed by duBois, yet hinted at by the painting reproduced on the book’s cover – Nicolas Poussin’s “Martyrdom of Saint Erasmus” (1629). DuBois relates classical Greek juridical practices, in which the tortured slave body is the site of the production of truth, to the subsequent history of Western philosophy, of which Heidegger is a privileged exemplum. This essay in turn inserts a history of Christian martyrdom (both early modern and ancient) into that narrative. The tight linking of truth with torture persists in martyrdom texts (including the Gospels), and the juridical context highlighted by duBois remains decisive for their interpretation. So too does the context of Roman imperial rule, together with the public spectacles of violence through which imperial power was performed. However, whereas classical Greek practice frames the slave as the passive container of a truth that another can claim, the ideology of Christian martyrdom assigns truth to the tortured subject herself. The legacy of martyrdom may explain the ease with which some today all too easily disavow complicity with torture to the point of denying that it continues, while also all too easily laying claim to the authority of suffering truth. It may illumine, as well, the limits of torture’s power and the potential sources of its subversion and critique.
Two new species of Pluteus (Agaricales, Pluteaceae) from China
Authors: XU JIANG , LI TAI HUI , JUSTO ALFREDO , GE ZAI WEI
Published: February 2017

Two new species of Pluteus section Pluteus, P. griseodiscus and P. purpureofuscus, are described from China. Pluteus griseodiscus is characterized by the pale basidiomata, non-pigmented lamellar edges, thick-walled cheilocystidia and the presence of caulocystidia. Pluteus purpureofuscus is characterized by a purple-brown pileus, presence of clamp-connections, and growth on coniferous wood. The phylogenetic position of both species is also discussed based on nrITS data.
Oreocharis synergia, a new species of Gesneriaceae from Northwestern Yunnan, China
Authors: Chen Wen-Hong , Möller Michael , Chen Run-Zheng , Rui Rong-Ju , Shui Yu-Min
Published: February 2017

A new species of Oreocharis (Gesneriaceae) from southwestern Yunnan, China, Oreocharis synergia is described and illustrated. The diagnostic characteristics are given with a comparison with its most similar species, Oreocharis bodinieri.
A revised typification of Jasione corymbosa and J. glabra (Campanulaceae) from the Western Mediterranean area
Authors: FERRER-GALLEGO PEDRO PABLO , Romo Ángel , Roselló Roberto , Laguna Emilio , Peris Juan Bautista
Published: February 2017

The genus Jasione Linnaeus (1753: 163) (Campanulaceae Juss.) is represented by ca. 16 species distributed throughout Europe and the Mediterranean Region, from coastal dunes to alpine zones, and growing on a wide variety of substrates as well (Sales & Hedge 2001b). The genus shows a high degree of polymorphism, which can be partially caused by its representation accross a wide range of ecological niches. This variability reaches its maximum expression within the Iberian Peninsula (Bokhari & Sales 2001).