bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging
Authors: Eckerbom Per , Hansell Peter , Cox Eleanor , Buchanan Charlotte , Weis Jan , Palm Fredrik , Francis Susan , Liss Per
Published: January 2019

Noninvasive methods of magnetic resonance imaging (MRI) can quantify parameters of kidney function. The main purpose of this study was to determine baseline values of such parameters in healthy volunteers. In 28 healthy volunteers (15 women and 13 men), arterial spin labeling to estimate regional renal perfusion, blood oxygen level-dependent transverse relaxation rate (R2*) to estimate oxygenation, and apparent diffusion coefficient (ADC), true diffusion (D), and longitudinal relaxation time (T1) to estimate tissue properties were determined bilaterally in the cortex and outer and inner medulla. Additionally, phase-contrast MRI was applied in the renal arteries to quantify total renal blood flow. The results demonstrated profound gradients of perfusion, ADC, and D with highest values in the kidney cortex and a decrease towards the inner medulla. R2* and T1 were lowest in kidney cortex and increased towards the inner medulla. Total renal blood flow correlated with body surface area, body mass index, and renal volume. Similar patterns in all investigated parameters were observed in women and men. In conclusion, noninvasive MRI provides useful tools to evaluate intrarenal differences in blood flow, perfusion, diffusion, oxygenation, and structural properties of the kidney tissue. As such, this experimental approach has the potential to advance our present understanding regarding normal physiology and the pathological processes associated with acute and chronic kidney disease.
Role of regulatory T cells in experimental autoimmune glomerulonephritis
Authors: Klinge Stefanie , Yan Karsten , Reimers Daniel , Brede Karen-Maria , Schmid Joanna , Paust Hans-Joachim , Krebs Christian F. , Panzer Ulf , Hopfer Helmut , Mittrücker Hans-Willi
Published: January 2019

Anti-glomerular basement membrane (anti-GBM) disease is characterized by antibodies and T cells directed against the Goodpasture antigen, the noncollagenous domain of the α3-chain of type IV collagen [α3(IV)NC1] of the GBM. Consequences are the deposition of autoantibodies along the GBM and the development of crescentic glomerulonephritis (GN) with rapid loss of renal function. Forkhead box protein P3 (Foxp3)+regulatory T (Treg) cells are crucial for the maintenance of peripheral tolerance to self-antigens and the prevention of immunopathology. Here, we use the mouse model of experimental autoimmune GN to characterize the role of Treg cells in anti-GBM disease. Immunization of DBA/1 mice with α3(IV)NC1 induced the formation of α3(IV)NC1-specific T cells and antibodies and, after 8–10 wk, the development of crescentic GN. Immunization resulted in increased frequencies of peripheral Treg cells and renal accumulation of these cells in the stage of acute GN. Depletion of Treg cells during immunization led to enhanced generation of α3(IV)NC1-specific antibodies and T cells and to aggravated GN. In contrast, depletion or expansion of the Treg cell population in mice with established autoimmunity had only minor consequences for renal inflammation and did not alter the severity of GN. In conclusion, our results indicate that in anti-GBM disease, Treg cells restrict the induction of autoimmunity against α3(IV)NC1. However, Treg cells are inefficient in preventing crescentic GN after autoimmunity has been established.
Similarities and differences in circuit responses to applied Gly1-SIFamide and peptidergic (Gly1-SIFamide) neuron stimulation
Authors: Blitz Dawn M. , Christie Andrew E. , Cook Aaron P. , Dickinson Patsy S. , Nusbaum Michael P.
Published: January 2019

Microcircuit modulation by peptides is well established, but the cellular/synaptic mechanisms whereby identified neurons with identified peptide transmitters modulate microcircuits remain unknown for most systems. Here, we describe the distribution of GYRKPPFNGSIFamide (Gly1-SIFamide) immunoreactivity (Gly1-SIFamide-IR) in the stomatogastric nervous system (STNS) of the crab Cancer borealis and the Gly1-SIFamide actions on the two feeding-related circuits in the stomatogastric ganglion (STG). Gly1-SIFamide-IR localized to somata in the paired commissural ganglia (CoGs), two axons in the nerves connecting each CoG with the STG, and the CoG and STG neuropil. We identified one Gly1-SIFamide-IR projection neuron innervating the STG as the previously identified modulatory commissural neuron 5 (MCN5). Brief (~10 s) MCN5 stimulation excites some pyloric circuit neurons. We now find that bath applying Gly1-SIFamide to the isolated STG also enhanced pyloric rhythm activity and activated an imperfectly coordinated gastric mill rhythm that included unusually prolonged bursts in two circuit neurons [inferior cardiac (IC), lateral posterior gastric (LPG)]. Furthermore, longer duration (>30 s) MCN5 stimulation activated a Gly1-SIFamide-like gastric mill rhythm, including prolonged IC and LPG bursting. The prolonged LPG bursting decreased the coincidence of its activity with neurons to which it is electrically coupled. We also identified local circuit feedback onto the MCN5 axon terminals, which may contribute to some distinctions between the responses to MCN5 stimulation and Gly1-SIFamide application. Thus, MCN5 adds to the few identified projection neurons that modulate a well-defined circuit at least partly via an identified neuropeptide transmitter and provides an opportunity to study peptide regulation of electrical coupled neurons in a functional context.

NEW & NOTEWORTHY Limited insight exists regarding how identified peptidergic neurons modulate microcircuits. We show that the modulatory projection neuron modulatory commissural neuron 5 (MCN5) is peptidergic, containing Gly1-SIFamide. MCN5 and Gly1-SIFamide elicit similar output from two well-defined motor circuits. Their distinct actions may result partly from circuit feedback onto the MCN5 axon terminals. Their similar actions include eliciting divergent activity patterns in normally coactive, electrically coupled neurons, providing an opportunity to examine peptide modulation of electrically coupled neurons in a functional context.
Evaluation of Polyphenolics Content and Antioxidant Activity in Edible Wild Fruits
Authors: Shan Sharui , Huang Xuming , Shah Munir H. , Abbasi Arshad Mehmood
Published: January 2019

Plant diversity is a basic source of food and medicines for the local communities of the Himalayas. Current study was intended to assess polyphenolics content and antioxidant potential in edible wild fruits used as food and to treat various diseases by the inhabitants of Himalayan region of Pakistan. The fruits of 20 plant species were evaluated using standard protocols, whereas information on medicinal uses was gathered through semistructured interviews. Comparatively,Prunus domesticaandRubus ellipticusfruits exhibited highest levels of phenolics and flavonols contents (113.55 ± 0.61 mg GAE/100 g and 200.06 ± 1.57 mg RtE/100 g FW, respectively) in acetone extract. Nevertheless, flavonoids were maximum in the water extract ofRosa moschata(194.82 ± 3.46 mg RtE/100 g FW). Contrary,Duchesnea indicafruit depicted significant potential to scavenge DPPH and H2O2radicals at 94.66 ± 8.89% in acetone extract and 83.54± 9.37% in water extract, while acetone extract ofRubus ellipticushad maximum potential to reduce ferric ions (133.66 ± 15.00µM GAE/100 g FW). Additionally, total antioxidant capacity was highest in the acetone extract ofBerberis lyciumfruit (332.08 ± 21.90µM AAE/100 g FW). The relationships between polyphenolics and antioxidant activity revealed synergistic role of secondary metabolites in the prevention of diseases. Our study revealed that wild fruits consumed by the local communities of Himalayas are rich in health beneficial phytochemicals and hold significant potential to treat chronic diseases, particularly associated with free radicals.
Guaranteeing Prescribed Performance Control for Gyrostabilized Platform with Unknown Control Direction Preceded by Hysteresis
Authors: Wang Yexing , Lei Humin , Ye Jikun , Bu Xiangwei , Xue Yali
Published: January 2019

This paper investigates the problem of precise and quick tracking for gyrostabilized platform (GSP) with unknown hysteresis, unknown control directions, and unknown compound disturbance. Firstly, the dynamic model of GSP is transformed into a strict feedback formulation by designed FD to facilitate the backstepping control system. Secondly, performance functions are constructed at each step of backstepping design to force tracking errors to fall within the prescribed boundaries. Besides, through ingenious transformation, radial basis function neural network (RBFNN) is applied to estimate the unknown control gains preceded by hysteresis. Hence, the problem of prescribed performance control with unknown compound disturbances, unknown hysteresis, and unknown control directions is creatively solved. Furthermore, the exploited controllers are accurate model independent, which guarantees satisfactory robustness of control laws against unknown uncertainties. Finally, the stability of the closed-loop control system is confirmed via Lyapunov stability theory, and numerical simulations are given for a GSP to validate the effectiveness of the proposed controller.
Some Notes on Concordance between Optimization and Statistics
Authors: Mu Weiyan , Wei Qiuyue , Xiong Shifeng
Published: January 2019

Many engineering problems require solutions to statistical optimization problems. When the global solution is hard to attain, engineers or statisticians always use the better solution because we intuitively believe a principle, called better solution principle (BSP) in this paper, that a better solution to a statistical optimization problem also has better statistical properties of interest. This principle displays some concordance between optimization and statistics and is expected to widely hold. Since theoretical study on BSP seems to be neglected by statisticians, this paper presents a primary discussion on BSP within a relatively general framework. We demonstrate two comparison theorems as the key results of this paper. Their applications to maximum likelihood estimation are presented. It can be seen that BSP for this problem holds under reasonable conditions; i.e., an estimator with greater likelihood is better in some statistical sense.
CD5-Positive Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type
Authors: Papoudou-Bai Alexandra , Marinos Leonidas , Vassou Amalia , Kapsali Eleni , Kanavaros Panagiotis
Published: January 2019

Most primary cutaneous B-cell lymphomas (PCBCL) are CD5 negative, and only a few cases were found to express CD5. We report the first well-documented CD5+ primary cutaneous diffuse large B-cell lymphoma-leg type (PCDLBCL-LT). A 71-year-old woman with a history of Multiple Sclerosis was admitted because of a nodule at the left thigh. Histological examination of the skin biopsy disclosed a diffuse dermal infiltration by large lymphoid cells. Immunohistochemistry revealed that these large cells were positive for CD5, CD20, CD79a, MUM1/IRF4, Bcl6, Bcl2, and cytoplasmic IgM/λ, whereas CD3, CD56, CD23, CD21, CD10, CD30, cyclin D1, CD68, lysozyme, myeloperoxidase, and CD34 were not detected. Thus, the diagnosis of a CD5+ PCDLBCL-LT was made. Despite treatment, the patient died 11 months after initial diagnosis.
Separating Acute Rheumatic Fever from Nonrheumatic Streptococcal Myocarditis
Authors: Derbas Laith A. , Samanta Anweshan , Potla Srinivasa , Younis Moustafa , Schmidt Laura M. , Saeed Ibrahim M.
Published: January 2019

Introduction. Streptococcal pharyngitis has been historically complicated with systemic involvement manifesting as acute rheumatic fever, which is a serious condition that can lead to permanent damage to heart valves. A recent association between streptococcal pharyngitis and nonrheumatic heart disease is emerging in literature. We present a case of nonrheumatic streptococcal myocarditis diagnosed using cardiac MRI. Case Presentation. A 25-year-old male, presented with complaints of sore throat, nonproductive cough, fever, pleuritic chest pain, and progressive dyspnea for four days. The patient had elevated troponins at presentation of 0.47 (ng/L) that peaked at 4.0 (ng/L). ECG showed sinus rhythm and ST elevations in leads V2, V3, V4, and V5. NT-Pro-BNP was 1740. Transthoracic echocardiogram (TTE) showed reduced ejection fraction (EF) of 37% and global hypokinesis. The rapid strep test was positive for group A streptococcus and C-reactive protein was elevated at 161. Cardiac MRI demonstrated an EF of 53% and edema in the anterior wall without delayed gadolinium enhancement. Cardiac catheterization showed normal coronaries. Discussion. According to modified Jones criteria, the patient did not meet the full major or minor criteria to be diagnosed with acute rheumatic fever. The course of the nonrheumatic myocarditis is favorable and includes a full recovery of cardiac function, no involvement of cardiac valves, or long-term use of antibiotics. Conclusion. It is crucial to make a separate distinction between acute rheumatic fever and nonrheumatic myocarditis because this will have huge implications on management and long-term use of antibiotics. Cardiac imaging modalities can aid in distinction between the two disease entities.
Squamous Carcinoma of the Neovagina after Male-to-Female Reconstruction Surgery: A Case Report and Review of the Literature
Authors: Fierz Ronja , Ghisu Gian-Piero , Fink Daniel
Published: January 2019

Squamous cell carcinoma (SCC) of the neovagina after genital reconstruction surgery is a rare occurrence with only very few cases published up to the present. We report a case of a 43-year-old transgender woman who developed neovaginal SCC 23 years after vaginoplasty. The patient tested positive for high-risk human papillomavirus (HPV). At the time of diagnosis, radiological investigations revealed already existing lymph node and osseous metastases. The treatment consisted of various cycles of chemotherapy and radiation therapy. Unfortunately, the formation of additional metastases, including cerebral, pulmonary, and hepatic metastases, could not be prevented. After comparing the literature on the topic, we conclude that neovaginal carcinoma often appears years and decades after genital reconstruction surgery. We therefore recommend the continuation of regular clinical follow-up for transgender women after postoperative follow-up is completed. With this approach, potential lesions may be detected at an earlier stage and a better outcome may be achieved. Follow-up should include neovaginal examination and cytological smear testing. At a later age, we recommend additional regular prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Moreover, transgender women are advised to take part in mammography screening starting at the age of 50, especially when additional risk factors are present.
Application of Wasted Oolong Tea as a Biosorbent for the Adsorption of Methylene Blue
Authors: Hu Yunfei , Zhang Yue , Hu Yuqun , Chu Chen-Yao , Lin Jinke , Gao Shuilian , Lin Dongyi , Lu Jing , Xiang Ping , Ko Tzu-Hsing
Published: January 2019

Tea powder, a biosorbent prepared from wasted oolong tea, was collected as a prospective adsorbent for the adsorption of methylene blue (MB) from aqueous solution. The effect of factors on adsorption efficiency, isotherms, kinetics, and potential mechanism was carried out. Adsorption capacity of MB onto wasted tea powder increased with the MB concentration and contact time, whereas the increase in pH value and ion strength appeared to have a negative effect for the adsorption process. The adsorption efficiency increased rapidly and reached a stable state within 120 min. The optimal tea powder loading weight is suggested to be at 0.1 to 0.2 g, and the highest efficiency of 94.8% is achieved at 333 K. There were no significant changes in adsorption efficiency when the effect of temperature is considered. The Langmuir isotherm model was found to be the best isotherm models to elucidate the adsorption mechanism in this study. The maximum adsorption capacities calculated at different temperatures by the Langmuir model ranging from 312.5 to 333.3 mg·g−1 were much close to the experimental results. From the kinetic analysis, the pseudo--second-order model was found to be the best model to describe the adsorption behavior. The calculated adsorption capacities at different initial MB concentrations by the pseudo-second-order model ranging from 92.34 to 400 mg·g−1 were well close to the experimental data. The fitting results obtained from the intraparticle diffusion model suggested that the intraparticle diffusion was not the only rate-controlling step and some other mechanisms along with the intraparticle diffusion were probably involved. The intraparticle diffusion of MB molecules into pore structures of wasted tea powder is the rate-limiting step for the adsorption process in this study. The repetitive cycle experiments indicated that the wasted oolong tea powder was efficiently regenerated using NaOH and thus be used for many times.
Utility of the Serum Cystatin C Level for Diagnosis of Osteoporosis among Middle-Aged and Elderly People
Authors: Tanaka Satoshi , Ando Kei , Kobayashi Kazuyoshi , Hida Tetsuro , Ito Kenyu , Tsushima Mikito , Morozumi Masayoshi , Machino Masaaki , Ota Kyotaro , Suzuki Koji , Seki Taisuke , Ishiguro Naoki , Hasegawa Yukiharu , Imagama Shiro
Published: January 2019

Purpose. Osteoporosis is a common age-related disorder leading to increased bone fragility and risk of fracture. Early diagnosis of osteoporosis is a vital step in providing early therapeutic intervention. Serum cystatin C is a marker of early renal dysfunction, a predictor of cardiovascular and inflammatory diseases, and an inhibitor of the differentiation of osteoclast precursor cells. The purpose of this study was to evaluate the relationship between serum cystatin C and osteoporosis. Methods. We enrolled 46 subjects who attended a health checkup and underwent measurement of bone status by quantitative ultrasound and determination of the level of serum cystatin C. A comparative study was conducted between those with and without osteoporosis for all subjects collectively and in two subgroups aged <65 and ≥65 years. Results. Serum cystatin C levels were strongly correlated with age, creatinine, and bone status data, with significant negative correlations with stiffness, T-score, and percentage of young adult mean. Among patients with osteoporosis, serum cystatin C was significantly higher even after adjustment for age and sex, whereas no significant difference was noted in creatinine. For patients aged ≥ 65 years, serum cystatin C was significantly higher in subjects with osteoporosis, although there was no significant difference in age between normal subjects and those with osteoporosis. Conclusions. To the best of our knowledge, this is the first study to demonstrate an association between serum cystatin C and osteoporosis. Serum cystatin C is significantly higher in osteoporosis and in particular may be a useful marker for osteoporosis among middle and elderly people aged ≥ 65 years. Measurement of serum cystatin C can be carried out easily and may contribute to early diagnosis and treatment of osteoporosis.
Evaluation of Pathological Association between Stroke-Related QTL and Salt-Induced Renal Injury in Stroke-Prone Spontaneously Hypertensive Rat
Authors: Reza Mohammad Farhadur , Ngarashi Davis , Koike Masamichi , Misumi Masaki , Ohara Hiroki , Nabika Toru
Published: January 2019

The stroke-prone spontaneously hypertensive rat (SHRSP) suffers from severe hypertension and hypertensive organ damage such as cerebral stroke and kidney injury under salt-loading. By a quantitative trait locus (QTL) analysis between SHRSP and SHR (the stroke-resistant parental strain of SHRSP), two major QTLs for stroke susceptibility were identified on chromosomes 1 and 18 of SHRSP, which were confirmed in congenic strains constructed between SHRSP and SHR. As the progression of renal dysfunction was suggested to be one of the key factors inducing stroke in SHRSP, we examined effects of the stroke-related QTLs on kidney injury using two congenic strains harboring either of SHRSP-derived fragments of chromosomes 1 and 18 in the SHR genome. The congenic strains were challenged with 1% NaCl solution for 4 weeks; measurement of systolic blood pressure and urinary isoprostane level (a marker for oxidative stress) and evaluation of renal injury by quantification of genetic marker expression and histological examination were performed. We found that the congenic rats with SHRSP-derived fragment of chromosome 18 showed more severe renal damage with higher expression of Col1α-1 (a genetic marker for renal fibrosis) and higher urinary isoprostane level. In contrast, the fragment of chromosome 1 from SHRSP did not give such effects on SHR. Blood pressure was not greater in either of the congenic strains when compared with SHR. We concluded that the QTL region on chromosome 18 might deteriorate salt-induced renal injury in SHR through a blood pressure-independent mechanism.
Rapid Separation of All Four Tocopherol Homologues in Selected Fruit Seeds via Supercritical Fluid Chromatography Using a Solid-Core C18 Column
Authors: Urvaka Elise , Mišina Inga , Soliven Arianne , Górnaś Paweł
Published: January 2019

Tocopherol separations employing the same Kinetex™ C18 column via supercritical fluid chromatography (SFC) and reversed-phase liquid chromatography (RP-LC) were compared. The application of the SFC system with UV diode array detection (DAD) resulted in rapid separation of all four tocopherol homologues with a total analysis time below 2 min. The RP-LC approach could not separate the isomers β and γ. The developed SFC-DAD method was precise, accurate, and most importantly more environmentally friendlier compared to the RP-LC method due to the 125-fold decrease in methanol consumption. The present study illustrated the selectivity differences between LC and SFC and how the C18 column can be used for tocopherol characterization. The optimized SFC method was successfully applied for the tocopherol determination in the seeds of nine different fruit species.
Morphological Seed Characterization of Common (Phaseolus vulgarisL.) and Runner (Phaseolus coccineusL.) Bean Germplasm: A Slovenian Gene Bank Example
Authors: Sinkovič Lovro , Pipan Barbara , Sinkovič Eva , Meglič Vladimir
Published: January 2019

Genetic resources comprised of 953 accessions of common (Phaseolus vulgarisL.) and 47 accessions of runner (Phaseolus coccineusL.) bean from the national Slovene gene bank were characterized using fourteen morphological seed descriptors. Seeds of each accession were evaluated for six quantitative characteristics: seed length, seed thickness, seed width, seed length/width ratio, seed width/thickness ratio, and 100 or 10 seed weight. Furthermore, seeds were evaluated using eight qualitative characteristics: seed colour; number of seed colours; primary/main seed colour; predominant secondary seed colour; distribution of secondary seed colour; seed veining; seed shape; and seed colour (primary and secondary) and coat pattern. For each, common, and runner bean collection, first four components within principal component analysis explained 75.03% and 80.16% of morphological variability, respectively. Regarding Ward’s method and squared Euclidian distance, three clusters with the most distinct characteristics were established for each species. The results of morphological seed characterization indicate the origin (Andean, Mesoamerican, putative hybrids between gene pools) and domestication pathways of common and runner bean. This is the first study describing morphological seed characteristics of the entire common and runner bean germplasm conserved in one of the Central European bean collections. The results obtained in this study are serving as the useful information on genetic diversity of common and runner bean accessions at the Slovene gene bank, which could be used for development of new bean varieties for studied seed characteristics.
A New Generalized Inequality for Covariance in N Dimensions
Authors: Liu Mei , Šindelka Milan , Lin Shi-you
Published: January 2019

Inspired by the work of Zhefei He and Mingjin Wang which was published in the Journal of Inequalities and Applications in 2015, this paper further generalizes some related results to the case of multidimensional random variables. The resulting inequality for covariance is then applied to different multidimensional statistical distributions (multiuniform, multinomial, and multinormal). Coordinate dependence of the inequality is also examined. The obtained formulas could be useful for making estimates in multivariate statistics.
Echocardiogram: The GPS to GPA’s Heart (Granulomatosis with Polyangiitis)
Authors: Parmar Manpreet K. , Alikhan Mariam , Hsu Vivien M. , Borham Amanda
Published: January 2019

Granulomatosis with polyangiitis (GPA) is a rare ANCA-associated necrotizing granulomatous vasculitis affecting small- to medium-sized vessels. Common manifestations of this disease process affect the ear, nose, throat, upper and lower airways, and kidneys. Cardiac involvement has been reported in 6–44% of patients, primarily as coronary arteritis and pericarditis. A majority of case reports of pericardial effusions in patients with GPA identify patients having constrictive pericarditis secondary to uremia. We are presenting a case of hemorrhagic pericarditis in a patient with GPA in which the underlying inflammatory vasculitis likely played the primary role in the patient’s presentation. Echocardiographic abnormalities have been found in 80% of patients with GPA. Given the high mortality from cardiac involvement in patients with GPA, screening echocardiograms for this patient population may serve as a helpful tool in gauging disease severity, thereby guiding therapy to prevent serious cardiac complications, such as cardiac tamponade as presented in this case report.
Curcumin Suppresses Hepatic Stellate Cell-Induced Hepatocarcinoma Angiogenesis and Invasion through Downregulating CTGF
Authors: Shao Shan , Duan Wanxing , Xu Qinhong , Li Xuqi , Han Liang , Li Wei , Zhang Dong , Wang Zheng , Lei Jianjun
Published: January 2019

Microenvironment plays a vital role in tumor progression; we focused on elucidating the role of hepatic stellate cells (HSCs) in hepatocarcinoma (HCC) aggressiveness and investigated the potential protective effect of curcumin on HSC-driven hepatocarcinoma angiogenesis and invasion. Our data suggest that HSCs increase HCC reactive oxygen species (ROS) production to upregulate hypoxia-inducible factor-1α(HIF-1α) expression to promote angiogenesis, epithelial to mesenchymal transition (EMT) process and invasion. And HSCs could secrete soluble factors, such as interleukin-6 (IL-6), vascular endothelial cell growth factor (VEGF), and stromal-derived factor-1 (SDF-1) to facilitate HCC progression. Curcumin could significantly suppress the above HSC-induced effects in HCC and could abrogate ROS and HIF-1αexpression in HCC. HIF-1αor connective tissue growth factor (CTGF) knockdown could abolish the aforementioned curcumin affection. Moreover, CTGF is a downstream gene of HIF-1α. In addition, nuclear factor E2-related factor 2 (Nrf2) and glutathione (GSH) are involved in curcumin protection of HCC. These data indicate that curcumin may induce ROS scavenging by upregulating Nrf2 and GSH, thus inhibiting HIF-1αstabilization to suppress CTGF expression to exhibit its protection on HCC. Curcumin has a promising therapeutic effect on HCC. CTGF is responsible for curcumin-induced protection in HCC.
The Modified Bushen Antai Recipe Upregulates Estrogen and Progesterone Receptors at the Maternal-Fetal Interface in Pregnant Rats with Mifepristone-Induced Pregnancy Loss
Authors: Sun Li , Yuan Zhengwei , Jian Lingyan , Jiang Qinghua , Zhang Siwen , Tan Jichun
Published: January 2019

Background. The modified Bushen Antai recipe (BSAT) is a centuries-old traditional Chinese medicine that we use in our center as a therapy against pregnancy loss. Our study aimed to explore the potential benefit and mechanism of BSAT in pregnant rats with mifepristone-induced pregnancy loss.Materials and Methods. The signature compounds of the eight BSAT ingredients were analyzed by high-performance liquid chromatography (HPLC). The BSAT group (n = 8) was treated daily with 6.3 ml/kg BSAT from gestation day (D) 0.5 to 10.5 and once with 1.25 mg/kg mifepristone on D 10.5. Normal saline replaced BSAT in the model group (n = 8), and both BSAT and mifepristone in the control group (n = 8). Morphological and histological analyses were performed on D 13.5.Results. BSAT contains eight medicinal ingredients includingCuscuta chinensisandDipsacus asperoides. The HPLC analysis detected the signature compounds of seven medicinal ingredients in the extract. Embryo resorption rate in the BSAT group was significantly lower than that in the model group, although the number of surviving embryos was similar between the two groups. Hematoxylin and eosin (HE) staining suggested that the maximum cross-sectional area of the placenta and the area ratio of the placental labyrinth in the BSAT group were higher than those in the model group. Immunohistochemical (IHC) staining indicated that the expression of ki67, estrogen receptor alpha (ERα), and progesterone receptor (PR) in the placental labyrinth of the BSAT group was higher than that of the model group. Furthermore, the protein levels of ERα, PR, phospho-Akt/Akt, and phospho-Erk1/2/Erk1/2 in the BSAT group were higher than those in the control group. The mRNA levels of ERαand PR in the BSAT group were higher than those in the control group.Conclusions. BSAT may induce estrogen and progesterone receptors by phosphorylation via the classic Akt and Erk1/2 signaling pathways in the maternal-fetal interface of pregnant rats, thereby reducing the pregnancy loss rate and improving the live birth rate.
Endpoint Estimates for Oscillatory Singular Integrals with Hölder Class Kernels
Authors: Al-Qassem Hussain , Cheng Leslie , Pan Yibiao
Published: January 2019

We prove the uniformL1→L1,∞andHE1→L1boundedness of oscillatory singular integral operators whose kernels are the products of an oscillatory factor with bilinear phase and a Calderón-Zygmund kernelK(x,y)satisfying a Hölder condition. This Hölder condition appreciably weakens theC1condition imposed in existing literature.
Radiation-Induced Malignant Transformation of Preneoplastic and Normal Breast Primary Epithelial Cells
Authors: Repullés Joan , Anglada Teresa , Soler David , Ramírez Juan Carlos , Genescà Anna , Terradas Mariona
Published: January 2019

Radiation is used in multiple procedures as a therapeutic and diagnostic tool. However, ionizing radiation can induce mutations in the DNA of irradiated cells, which can promote tumorigenesis. As malignant transformation is a process that takes many years, there are intermediate stages of cells that have initiated the process but have not yet evolved into cancer. The study here aimed to investigate the effect of ionizing radiation on normal and partially transformed human mammary epithelial cells. Breast primary epithelial cells were derived from normal breast tissue from two different donors and modified by transduction with the SV40 small and large T antigen and hTERT genes to obtain partially transformed cells and also with HRAS to completely and experimentally transform them. After exposure to different doses of ionizing radiation, oncogenic features were analyzed by means of an anchorage-independent growth assay and 3D cell culture. The addition of radiation exposure resulted in an increase in the number and size of colonies formed in each of the conditions analyzed and in the reduction of the capacity of partially transformed cells to form properly polarized 3D structures. Moreover, partially transformed cells require lower doses of radiation than healthy cells to enhance anchorage-independent growth capacity. Although cells from different donors have a different degree of sensitivity in the response to radiation, a higher sensitivity to the radiation-induced cell transformation process was observed in those cells that had already initiated the oncogenic process, which require higher doses of radiation to complete the transformation process.

Implications:

Individuals carrying accumulation of genetic alterations may have an increased susceptibility to radiation-induced neoplastic transformation.
The Germline Variants rs61757955 and rs34988193 Are Predictive of Survival in Lower Grade Glioma Patients
Authors: Chatrath Ajay , Kiran Manjari , Kumar Pankaj , Ratan Aakrosh , Dutta Anindya
Published: January 2019

Lower grade gliomas are invasive brain tumors that are difficult to completely resect neurosurgically. They often recur following resection and progress, resulting in death. Although previous studies have shown that specific germline variants increase the risk of tumor formation, no previous study has screened many germline variants to identify variants predictive of survival in patients with glioma. In this study, we present an approach to identify the small fraction of prognostic germline variants from the pool of over four million variants that we variant called in The Cancer Genome Atlas whole-exome sequencing and RNA sequencing datasets. We identified two germline variants that are predictive of poor patient outcomes by Cox regression, controlling for eleven covariates. rs61757955 is a germline variant found in the 3′ UTR of GRB2 associated with increased KRAS signaling, CIC mutations, and 1p/19q codeletion. rs34988193 is a germline variant found in the tumor suppressor gene ANKDD1a that causes an amino acid change from lysine to glutamate. This variant was found to be predictive of poor prognosis in two independent lower grade glioma datasets and is predicted to be within the top 0.06% of deleterious mutations across the human genome. The wild-type residue is conserved in all 22 other species with a homologous protein.

Implications:

This is the first study presenting an approach to screening many germline variants to identify variants predictive of survival and our application of this methodology revealed the germline variants rs61757955 and rs34988193 as being predictive of survival in patients with lower grade glioma.
LIN28/let-7/PD-L1 Pathway as a Target for Cancer Immunotherapy
Authors: Chen Yanlian , Xie Chen , Zheng Xiaohui , Nie Xin , Wang Zining , Liu Haiying , Zhao Yong
Published: January 2019

The immunocheckpoint protein PD-1/PD-L1 is considered a promising target for cancer immunotherapeutics. However, the objective response rate using antibodies that block the interaction between PD-1 and PD-L1 was less than 40%, and the mechanism underlying regulation of PD-1/PD-L1 expression is poorly understood. In this study, we identified the miRNA let-7 that posttranscriptionally suppresses PD-L1 expression. LIN28, an RNA binding protein upregulated in most cancer cells, inhibits the biogenesis of let-7, thus promoting PD-L1 expression. Therefore, inhibition of LIN28 may be a strategy to prevent immune evasion of cancer cells. We found that treatment with a LIN28 inhibitor, the small compound C1632, increases let-7 and suppresses PD-L1 expression, leading to reactivation of antitumor immunity in vitro and in vivo. In addition, C1632 also displayed the capacity to inhibit cancer cell proliferation and tumor growth in mice. Altogether, these findings identified LIN28/let-7 as a target for PD-L1–mediated immunotherapeutics and reveal the potential of C1632 and its derivatives as promising oncotherapeutic agents.
Antagonism of IAPs Enhances CAR T-cell Efficacy
Authors: Michie Jessica , Beavis Paul A. , Freeman Andrew J. , Vervoort Stephin J. , Ramsbottom Kelly M. , Narasimhan Vignesh , Lelliott Emily J. , Lalaoui Najoua , Ramsay Robert G. , Johnstone Ricky W. , Silke John , Darcy Phillip K. , Voskoboinik Ilia , Kearney Conor J. , Oliaro Jane
Published: January 2019

Chimeric antigen receptor (CAR) T-cell therapy has proven successful in the treatment of hematological malignancies, notably acute lymphoblastic leukemia and B-cell lymphoma. However, the efficacy of CAR T cells against solid tumors is poor, likely due to tumor-associated immunosuppression. Here, we demonstrated that antagonizing the “inhibitor of apoptosis proteins” with the clinical smac-mimetic, birinapant, significantly enhanced the antitumor activity of CAR T cells in a tumor necrosis factor (TNF)-dependent manner. Enhanced tumor cell death occurred independently of the perforin-mediated granule exocytosis pathway, underscoring the cytotoxic potential of CAR T-cell–derived TNF. Combining CAR T-cell therapy with birinapant significantly reduced established tumor growth in vivo, where either therapy alone was relatively ineffective. Using patient biopsy-derived tumoroids, we demonstrated the synergistic potential of combining CAR T-cell therapy with smac-mimetics. Taken together, we identified CAR T-cell–derived TNF as a potent antitumor effector, which can be further harnessed by smac-mimetics.
Anterior Corpus Callosotomy Using Laser Interstitial Thermal Therapy for Refractory Epilepsy
Authors: Ball Tyler , Sharma Mayur , White Andrew C. , Neimat Joseph S.
Published: January 2019

Corpus callosotomy is a viable treatment for patients with refractory generalized or multifocal epilepsy, particularly those who have drop attacks. Laser interstitial thermal therapy (LITT) is a minimally invasive surgical option for various intracranial lesions. In this report, we present a 2-trajectory thermal ablation using the NeuroBlate® system (Monteris Medical, MN, USA) for an anterior two-thirds callosotomy in a patient with refractory epilepsy and frequent drop attacks. Adequate ablation of the corpus callosum was confirmed by MRI during the procedure. At the 1-month follow-up, the frequency had decreased from multiple seizures per day to only 3 over the course of 1 month. In addition, he had not suffered any drop attacks or tonic-clonic movements since the procedure. Five months after surgery, seizures had decreased to 1 per month with no drop attacks or loss of consciousness, consistent with an Engel class II outcome. In conclusion, LITT ablation of the corpus callosum is a safe, feasible, and minimally invasive treatment option for patients with refractory epilepsy, and it may be an attractive alternative for patients unwilling or unable to undergo open surgery.
Recent Advances in the Diagnosis, Risk Stratification, and Management of Systemic Light-Chain Amyloidosis
Authors: Vaxman Iuliana , Gertz Morie
Published: January 2019

The term amyloidosis refers to a group of disorders in which protein fibrils accumulate in certain organs, disrupt their tissue architecture, and impair the function of the effected organ. The clinical manifestations and prognosis vary widely depending on the specific type of the affected protein. Immunoglobulin light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, characterized by deposition of a misfolded monoclonal light-chain that is secreted from a plasma cell clone. Demonstrating amyloid deposits in a tissue biopsy stained with Congo red is mandatory for the diagnosis. Novel agents (proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, venetoclax) and autologous stem cell transplantation, used for eliminating the underlying plasma cell clone, have improved the outcome for low- and intermediate-risk patients, but the prognosis for high-risk patients is still grave. Randomized studies evaluating antibodies that target the amyloid deposits (PRONTO, VITAL) were recently stopped due to futility and currently there is an intensive search for novel treatment approaches to AL amyloidosis. Early diagnosis is of paramount importance for effective treatment and prognosis, due to the progressive nature of this disease.
Acute Respiratory Distress Syndrome following Cardiac Surgery: Comparison of the American-European Consensus Conference Definition versus the Berlin Definition
Authors: Kogan Alexander , Segel Michael J. , Ram Eilon , Raanani Ehud , Peled-Potashnik Yael , Levin Shany , Sternik Leonid
Published: January 2019

Background: Lung injury with development of the acute respiratory distress syndrome (ARDS) is a serious complication which can occur after major surgery, including cardiac surgery. Objective: The aim of our study was to compare the prevalence, risk factors, and mortality of ARDS following cardiac surgery according to the American-European Consensus Conference (AECC) definition and the new Berlin definition of ARDS. Methods: We performed a retrospective, observational study that included prospectively collected data from consecutive adult patients, aged from 18 to 92 years, who had undergone cardiac surgery (both on and off pump) at a large tertiary university hospital over 5 years (from September 2012 to September 2017). Results: During the study period, 3,972 patients underwent cardiac surgery, and 3,946 patients were included in the study. Fifty-five patients developed ARDS (1.14%) according to the AECC definition and 59 patients (1.15%) according to the Berlin definition, with a mortality of 32.7 and 30.5%, respectively (18 patients). Multivariate regression analysis identified prior cardiac surgery, complex cardiac surgery, emergency procedures, and transfusion of > 3 packed red blood cell units as predictors for ARDS. Conclusion: The development of ARDS in patients after cardiac surgery is a rare but serious complication associated with significant mortality. Moreover, our findings showed that prevalence, mortality, and risk factors for developing ARDS were similar according to both the AECC and the new Berlin definition.
Amblyceps cerinum, a new catfish (Teleostei: Amblycipitidae) from northeastern India
Authors: NG HEOK HEE , WRIGHT JEREMY J.
Published: January 2019

Amblyceps cerinum, a new South Asian amblycipitid catfish species, is described from the Brahmaputra River drainage in northern West Bengal, India. The new species can be distinguished from congeners in having a combination of upper jaw longer than lower, incomplete lateral line terminating beneath posterior insertion of dorsal fin, length of adipose-fin base 32.4–38.3% SL, caudal peduncle length 21.9–24.5% SL, caudal peduncle depth 9.2–11.2% SL, 41–44 postWeberian vertebrae, posterior end of adipose fin separated from dorsal procurrent caudal-fin rays by distinct notch, and truncate caudal fin. The taxonomic status of A. tenuispinis is also discussed and a neotype designated for this species.
Fourteen new species of the genus Stenoloba Staudinger, 1892 from South East Asia (Lepidoptera: Noctuidae, Bryophilinae)
Authors: BEHOUNEK G. , KONONENKO V. S.
Published: January 2019

Fourteen new species of the East Asian genus Stenoloba Staudinger, 1892 (Noctuidae, Bryophilinae) (S. ansari sp. n.; S. wolfgangi sp. n.; S. albibasis sp. n.; S. futioides sp. n.; S. javensis sp. n.; S. viridibrunnea sp. n.; S. benjamini sp. n.; S. dentilinea sp. n.; S. siamensis sp. n.; S. mossy sp. n.; S. ronkayi sp. n.; S. sacculata sp. n.; S. pinratanai sp. n. and S. matovi sp. n.) are described from Indonesia, Thailand and Vietnam. Nine species of Stenoloba are recorded from Indonesia and Malaysia, and the total number of species in the genus increases from 61 to 75. Adults and male and female genitalia are illustrated for the new species, and an updated checklist of the genus presented.
Two new flea beetle genera: Alasia alpina gen. et sp. nov. from a Costa Rican cloud forest and Pseudostenophyma gen. nov. from Brazil (Coleoptera: Chrysomelidae: Alticinae)
Authors: FURTH DAVID G. , ZHAUROVA KIRA M.
Published: January 2019

Alasia alpina is described as a new genus and species from high altitude cloud forests in Heredia, Costa Rica. Morphologically it is distinctive by its overall smooth shiny surface, dark-brown to black coloration, elongate body form; very long antennae, long, slender femora, broadly triangular, subconcave frons with shagreened surface, elytra weakly striate, and structure of the genitalia and metafemoral spring. It apparently prefers Melastomataceae host plants in the forest understory. It is most similar to Pseudostenophyma modesta com. nov. from which it differs in morphology, color, size, altitude of occurrence, and habitat. Stenophyma elegans Baly (type species) was discovered not to be congeneric with the other species in that genus S. modesta Weise, resulting in Pseudostenophyma being established as a new generic name for this taxon (P. modesta).
A review of the Eastern Palaearctic genera Paragona Staudinger, 1892 and Paragabara Hampson, 1926 with description of two new species and a new genus (Lepidoptera, Noctuidae: Aventiinae, Hypeninae)
Authors: KONONENKO VLADIMIR S. , HAN HUI-LIN , МАТОV ALEXEJ YU.
Published: January 2019

Two Palaearctic genera, Paragona Staudinger, 1892 and Paragabara Hampson, 1926, in the subfamilies Aventiinae and Hypeninae respectively are revised. The genus Paragona is recognized as a member of the subfamily Aventiinae. Paragona nemorata sp. n. is described as new and Paragona inchoata (Wileman, 1911) is reported for China for the first time. The genus Paragabara is recognized as a member of the subfamily Hypeninae. A lectotype is designated for P. flavomacula (Oberthür, 1880) and a new species Paragabara curvicornuta sp. n. described. Paragabara ochreipennis Sugi, 1962 and Remmigabara secunda, comb. n. are reported for the first time from China; Paragabara secunda Remm, 1973 is removed from the genus Paragabara. In addition, a new genus Remmigabara gen. n., with type species Paragabara secunda, is described in the subfamily Aventiinae. Adults and genitalia of the new taxa are illustrated and compared to related taxa.
A new species of Leptolalax (Anura: Megophryidae) from Laos
Authors: ROWLEY JODI J. L. , STUART BRYAN L. , RICHARDS STEPHEN J. , PHIMMACHAK SOMPOUTHONE , SIVONGXAY NIANE
Published: January 2019

We describe a new species of megophryid frog in the genus Leptolalax from southern Laos. Leptolalax aereus sp. nov. is distinguished from its congeners by a combination of size (25.1–28.9 mm in 28 adult males, 27.1–38.6 mm in 12 adult females), absence of distinct black or dark brown dorsolateral markings on head, near immaculate white chest and belly, head length greater than head width, no webbing or lateral fringing on fingers, rudimentary webbing between toes I–IV and no webbing between toes IV–V, toes with weak lateral fringing, and a call consisting of an average of 3–4 notes containing 1–2 pulses, and with a dominant frequency of 6187.5–7875 Hz. The new species is associated with rocky streams in semi-evergreen and evergreen forest between 284–511 m elevation.
A new species of Homidia from China, and description of the dorsal chaetotaxy of all Chinese Homidia species (Collembola: Entomobryidae)
Authors: JIA SHAO-BO , ZHANG YU-PING , ZHAO YAN , JORDANA RAFAEL
Published: January 2019

In the present paper a new species, Homidia sichuanensis Jia, Zhang & Jordana sp. nov. from West China, is described and figured. The new species is separated from the other Homidia by the presence of macrochaeta p4 on Th. III and the distribution of macrochaetae on A6–A10 areas of Abd. IV. Using the description of this new species, the generalized chaetotaxy for Homidia is described and figured, following Szeptycki (1979) and Jordana and Baquero (2005). Dorsal macrochaetotaxy of all known Homidia species from China are provided. For first time we give the chaetotaxy for H. phjongiangica Szeptycki, 1973 from types, H. sauteri (Börner, 1909) from Japanese material, H. sinensis Denis, 1929 from types, H. socia Denis, 1929 from Japanese material and H. transitoria Denis, 1929 from types. A key to the Chinese species of Homidia with known chaetotaxy are also given.