bluuebunny/crossref_metadata_2025 huggingface dataset:
Frankia Diversity in Host Plant Root Nodules Is Independent of Abundance or Relative Diversity of Frankia Populations in Corresponding Rhizosphere Soils
Authors: Ben Tekaya Seifeddine , Guerra Trina , Rodriguez David , Dawson Jeffrey O. , Hahn Dittmar
Published: December 2017

Actinorhizal plants form nitrogen-fixing root nodules in symbiosis with soil-dwelling actinobacteria within the genus
Frankia
, and specific
Frankia
taxonomic clusters nodulate plants in corresponding host infection groups. In same-soil microcosms, we observed that some host species were nodulated (
Alnus glutinosa
,
Alnus cordata
,
Shepherdia argentea
,
Casuarina equisetifolia
) while others were not (
Alnus viridis
,
Hippophaë rhamnoides
). Nodule populations were represented by eight different sequences of
nifH
gene fragments. Two of these sequences characterized frankiae in
S. argentea
nodules, and three others characterized frankiae in
A. glutinosa
nodules. Frankiae in
A. cordata
nodules were represented by five sequences, one of which was also found in nodules from
A. glutinosa
and
C. equisetifolia
, while another was detected in nodules from
A. glutinosa
. Quantitative PCR assays showed that vegetation generally increased the abundance of frankiae in soil, independently of the target gene (i.e.,
nifH
or the 23S rRNA gene). Targeted Illumina sequencing of
Frankia
-specific
nifH
gene fragments detected 24 unique sequences from rhizosphere soils, 4 of which were also found in nodules, while the remaining 4 sequences in nodules were not found in soils. Seven of the 24 sequences from soils represented >90% of the reads obtained in most samples; the 2 most abundant sequences from soils were not found in root nodules, and only 2 of the sequences from soils were detected in nodules. These results demonstrate large differences between detectable
Frankia
populations in soil and those in root nodules, suggesting that root nodule formation is not a function of the abundance or relative diversity of specific
Frankia
populations in soils.

IMPORTANCE
The nitrogen-fixing actinobacterium
Frankia
forms root nodules on actinorhizal plants, with members of specific
Frankia
taxonomic clusters nodulating plants in corresponding host infection groups. We assessed
Frankia
diversity in root nodules of different host plant species, and we related specific populations to the abundance and relative distribution of indigenous frankiae in rhizosphere soils. Large differences were observed between detectable
Frankia
populations in soil and those in root nodules, suggesting that root nodule formation is not a function of the abundance or relative diversity of specific
Frankia
populations in soils but rather results from plants potentially selecting frankiae from the soil for root nodule formation. These data also highlight the necessity of using a combination of different assessment tools so as to adequately address methodological constraints that could produce contradictory data sets.
Families First Home Visiting programme reduces population-level child health and social inequities
Authors: Chartier Mariette , Nickel Nathan C , Chateau Dan , Enns Jennifer E , Isaac Michael R , Katz Alan , Sarkar Joykrishna , Burland Elaine , Taylor Carole , Brownell Marni
Published: December 2017

Background

Home visiting has been shown to reduce child maltreatment and improve child health outcomes. In this observational study, we explored whether Families First, a home visiting programme in Manitoba, Canada, decreased population-level inequities in children being taken into care of child welfare and receiving complete childhood immunisations.

Methods

De-identified administrative health and social services data for children born 2003–2009 in Manitoba were linked to home visiting programme data. Programme eligibility was determined by screening for family risk factors. We compared probabilities of being taken into care and receiving immunisations among programme children (n=4575), eligible children who did not receive the programme (n=5186) and the general child population (n=87 897) and tested inequities using differences of risk differences (DRDs) and ratios of risk ratios (RRRs).

Results

Programme children were less likely to be taken into care (probability (95% CI) at age 1, programme 7.5 (7.0 to 8.0) vs non-programme 10.0 (10.0 to 10.1)) and more likely to receive complete immunisations (probability at age 1, programme 77.3 (76.5 to 78.0) vs non-programme 73.2 (72.1 to 74.3)). Inequities between programme children and the general population were reduced for both outcomes (being taken into care at age 1, DRD −2.5 (−3.7 to 1.2) and RRR 0.8 (0.7 to 0.9); complete immunisation at age 1, DRD 4.1 (2.2 to 6.0) and RRR 1.1 (1.0 to 1.1)); these inequities were also significantly reduced at age 2.

Conclusion

Home visiting programmes should be recognised as effective strategies for improving child outcomes and reducing population-level health and social inequities.
Older women exhibit greater airway 8-isoprostane responses to strenuous exercise compared with older men and younger controls
Authors: Kurti Stephanie P. , Emerson Sam R. , Smith Joshua R. , Rosenkranz Sara K. , Alexander Samantha A. , Lovoy Garrett M. , Harms Craig A.
Published: December 2017

Development of late-onset respiratory diseases is associated with elevated 8-isoprostane, a marker of oxidative stress, in the airways. However, sex differences exist in development of these diseases. Using an exhaustive exercise bout as a physiological stressor may elucidate whether there is a sex difference with aging in pre- to postexercise airway 8-isoprostane generation. The purpose of this study was to determine whether older women exhibit a greater airway 8-isoprostane response to exhaustive exercise compared with older men and younger controls. Thirty-six individuals completed the study (12 postmenopausal older women (OW) and 12 age-matched older men (OM), 65 ± 4 years of age; and 12 younger controls (YC), 21 ± 2 years of age). Baseline measurements included exhaled breath condensate (EBC) for assessment of airway 8-isoprostane and standard pulmonary function tests (PFTs) to assess forced expiratory volume in 1-s (FEV1), forced vital capacity (FVC), FEV1/FVC, and forced expiratory flow at 25%–75% of FVC. Subjects then performed a peak oxygen uptake test to exhaustion on a cycle ergometer. Immediately postexercise, PFTs and EBC were performed. The generation of airway 8-isoprostane from pre- to postexercise was greater in OW compared with OM and YC (p < 0.01), increasing ∼74% ± 77% in OW, while decreasing in OM (∼12% ± 50%) and YC (∼20.9% ± 30%). The OW exhibited a greater airway 8-isoprostane response to exhaustive exercise compared with OM and YC, which may suggest that sex differences in oxidative stress generation following exhaustive exercise may provide a mechanistic rationale for sex differences in late-onset respiratory diseases.
Modelling deformation and strains induced by waste settlement in a centrifuge test
Authors: Yu Yan , Rowe R. Kerry
Published: December 2017

A numerical model to estimate the tensile strains (loads) of the geomembrane liner in the waste containment facility due to waste settlement is presented. A centrifuge test of the geomembrane-lined landfill is used to validate the numerical model. The calculated surface settlement at the centre of the landfill and the geomembrane tensile strains on intermediate benches are generally in good agreement with the measured data. Parametric analyses associated with foundation shear strength as well as interface shear strength and stiffness are performed. The influence of geometric nonlinearity on the geomembrane tensile strains is also examined. The numerical analyses indicate that the maximum geomembrane tensile strain occurs at the crest of the side slope near the intermediate bench for the cases and conditions examined. The lessons learned are likely to be useful to landfill design engineers using numerical models to aid in the design of the geosynthetic liner system for the waste containment facilities.
Synthesis of carotol using a formal (4+1)-cycloaddition of chiral dialkoxycarbenes
Authors: Gund Machhindra , Déry Martin , Spino Claude
Published: December 2017

We report formal intramolecular (4+1)-cycloadditions of dialkoxycarbenes used in the synthesis of the daucane-type sesquiterpene carotol. We found a chiral dialkoxycarbene capable of diastereoselective formation of a key oxabicyclo[3.3.0]octene adduct. Carotol was synthesized in 14 linear steps from simple starting materials.
Geotechnical characterization of the Miocene formations at the location of Ivens shaft, Lisbon
Authors: Pedro António , Zdravković Lidija , Potts David , Almeida e Sousa Jorge
Published: December 2017

The design of complex underground structures in an urban environment requires in the first instance an appropriate characterization and interpretation of the ground conditions and of the mechanical behaviour of soil formations in the ground profile. With such information it is then possible to select and calibrate appropriate soil constitutive models for application in advanced numerical analysis, with the objective of predicting the induced ground movements and the potential damage to existing structures and services. This paper provides an interpretation of the site investigation data collected for the numerical analysis and design of the Ivens shaft excavation in Lisbon, Portugal. For the first time a comprehensive set of interpreted data is obtained for two of the main formations in the Lisbon area, Argilas e Calcários dos Prazeres (AP) and Areolas da Estefânia (AE), improving the understanding of their mechanical behaviour and making the data available for application in most soil constitutive frameworks. It is evident from the results that even with careful testing procedures the data may appear to be inconsistent, requiring further assumptions when deriving soil parameters. Such assumptions are discussed and emphasis is placed on the need to combine data from laboratory and field investigations.
SWI/SNF (BAF) Complexes: Guardians of the Epigenome
Authors: Mathur Radhika , Roberts Charles W.M.
Published: December 2017

The genomics-era search for cancer-causing mutations has identified subunits of SWI/SNF (BAF) chromatin remodeling complexes as major targets of mutation. The mechanism by which mutations in SWI/SNF complexes might drive cancer has become the subject of debate, as these complexes have roles in both transcriptional regulation and maintenance of genomic integrity. Recent discoveries now reveal that SWI/SNF complexes broadly control the activity of transcriptional enhancers to regulate lineage-specific differentiation. Here, we synthesize an integrative model of SWI/SNF complex function, identifying perturbed control of enhancer activity as the central mechanism underlying tumor suppression and highlighting how this yields new opportunities for therapeutic intervention.
Cure Models in Survival Analysis
Authors: Amico Maïlis , Van Keilegom Ingrid
Published: December 2017

When analyzing time-to-event data, it often happens that a certain fraction of the data corresponds to subjects who will never experience the event of interest. These event times are considered as infinite and the subjects are said to be cured. Survival models that take this feature into account are commonly referred to as cure models. This article reviews the literature on cure regression models in which the event time (response) is subject to random right censoring and has a positive probability to be equal to infinity.
Co(II) Coordination in Prokaryotic Zinc Finger Domains as Revealed by UV-Vis Spectroscopy
Authors: Sivo Valeria , D’Abrosca Gianluca , Russo Luigi , Iacovino Rosa , Pedone Paolo Vincenzo , Fattorusso Roberto , Isernia Carla , Malgieri Gaetano
Published: December 2017

Co(II) electronic configuration allows its use as a spectroscopic probe in UV-Vis experiments to characterize the metal coordination sphere that is an essential component of the functional structure of zinc-binding proteins and to evaluate the metal ion affinities of these proteins. Here, exploiting the capability of the prokaryotic zinc finger to use different combinations of residues to properly coordinate the structural metal ion, we provide the UV-Vis characterization of Co(II) addition to Ros87 and its mutant Ros87_C27D which bears an unusual CysAspHis2 coordination sphere. Zinc finger sites containing only one cysteine have been infrequently characterized. We show for the CysAspHis2 coordination an intense d-d transition band, blue-shifted with respect to the Cys2His2 sphere. These data complemented by NMR and CD data demonstrate that the tetrahedral geometry of the metal site is retained also in the case of a single-cysteine coordination sphere.
A New Murine Model of Chronic Kidney Disease-Mineral and Bone Disorder
Authors: Frauscher Bianca , Artinger Katharina , Kirsch Alexander H. , Aringer Ida , Moschovaki-Filippidou Foteini , Kétszeri Máté , Schabhüttl Corinna , Rainer Peter P. , Schmidt Albrecht , Stojakovic Tatjana , Fahrleitner-Pammer Astrid , Rosenkranz Alexander R. , Eller Philipp , Eller Kathrin
Published: December 2017

Chronic kidney disease (CKD) is associated with mineral and bone disorder (MBD), which is the main cause of the extensively increased cardiovascular mortality in the CKD population. We now aimed to establish a new murine experimental CKD-MBD model. Dilute brown non-Agouti (DBA/2) mice were fed with high-phosphate diet for 4 (HPD4) or 7 (HPD7) days, then with standard chow diet (SCD) and subsequently followed until day 84. They were compared to DBA/2 mice maintained on SCD during the whole study period. Both 4 and 7 days HPD-fed mice developed phosphate nephropathy with tubular atrophy, interstitial fibrosis, decreased glomerular filtration rate, and increased serum urea levels. The abdominal aorta of HPD-treated mice showed signs of media calcification. Histomorphometric analysis of HPD-treated mice showed decreased bone volume/tissue volume, low mineral apposition rate, and low bone formation rate as compared to SCD-fed mice, despite increased parathyroid hormone levels. Overall, the observed phenotype was more pronounced in the HPD7 group. In summary, we established a new, noninvasive, and therefore easy to perform reproducible CKD-MBD model, which showed media calcification, secondary hyperparathyroidism, and low-turnover bone disease.
Time‐Varying Noise Statistic Estimator Based Adaptive Simplex Cubature Kalman Filter
Authors: Li Zhaoming , Yang Wenge , Ding Dan
Published: December 2017

To address the problem that filtering accuracy is reduced with the inaccurate time‐varying noise statistic in conventional cubature Kalman filter, a noise statistic estimator based adaptive simplex cubature Kalman filter is put forward in this paper. First, the simplex cubature rule is adopted to approximate the intractable nonlinear Gaussian weighted integral in the filter. Secondly, a suboptimal unbiased constant noise statistic estimator is derived based on the maximum a posteriori estimation criterion. For the time‐varying noise, the above estimator is modified using an exponential weighted attenuation method to realize the oblivion of stale data which results in a fading memory estimator, which has the ability to estimate the time‐varying noise statistic to revise the filter online. The simulation results indicate that the proposed filter can achieve higher accuracy than conventional filters with inaccurate noise statistic.
Robust Speed Tracking Control for a Micro Turbine as a Distributed Energy Resource via Feedback Domination and Disturbance Observer
Authors: Xu Ancheng , Chen Hui
Published: December 2017

Micro turbine (MT) is characterized with complex dynamics, parameter uncertainties, and variable working conditions. In this paper, a novel robust controller is investigated for a single‐shaft micro turbine as a distributed energy resource by integrating a feedback domination control technique and a feedforward disturbance compensation. An active estimation process of the mismatched disturbances is firstly enabled by constructing a disturbance observer. Secondly, we adopt a feedback domination technique, rather than popularly used feedback linearization methods, to handle the system nonlinearities. In an explicit way, the composite controllers are then derived by recursive design based on Lyapunov theory while a global input‐to‐state stability can be guaranteed. Abundant comparison simulation results are provided to demonstrate the effectiveness of the proposed scheme, which not only perform an improved closed‐loop control performance comparing to all existing results, but also render a simple control law which will ease its practical implementation.
Different Effects of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2 on Myogenic Differentiation of Human Mesenchymal Stem Cells
Authors: Aboalola Doaa , Han Victor K. M.
Published: December 2017

Insulin-like growth factors (IGFs) are critical components of the stem cell niche, as they regulate proliferation and differentiation of stem cells into different lineages, including skeletal muscle. We have previously reported that insulin-like growth factor binding protein-6 (IGFBP-6), which has high affinity for IGF-2, alters the differentiation process of placental mesenchymal stem cells (PMSCs) into skeletal muscle. In this study, we determined the roles of IGF-1 and IGF-2 and their interactions with IGFBP-6. We showed that IGF-1 increased IGFBP-6 levels within 24 hours but decreased after 3 days, while IGF-2 maintained higher levels of IGFBP-6 throughout myogenesis. IGF-1 increased IGFBP-6 in the early phase as a requirement for muscle commitment. In contrast, IGF-2 enhanced muscle differentiation as shown by the expression of muscle differentiation markers MyoD, MyoG, and MHC. IGF-1 and IGF-2 had different effects on muscle differentiation with IGF-1 promoting early commitment to muscle and IGF-2 promoting complete muscle differentiation. We also showed that PMSCs acquired increasing capacity to synthesize IGF-2 during muscle differentiation, and the capacity increased as the differentiation progressed suggesting an autocrine and/or paracrine effect. Additionally, we demonstrated that IGFBP-6 could enhance the muscle differentiation process in the absence of IGF-2.
Mesenchymal Stem Cells Protect Nucleus Pulposus Cells from Compression-Induced Apoptosis by Inhibiting the Mitochondrial Pathway
Authors: Chen Sheng , Zhao Lei , Deng Xiangyu , Shi Deyao , Wu Fashuai , Liang Hang , Huang Donghua , Shao Zengwu
Published: December 2017

Objective. Excessive apoptosis of nucleus pulposus cells (NPCs) induced by various stresses, including compression, contributes to the development of intervertebral disc degeneration (IVDD). Mesenchymal stem cells (MSCs) can benefit the regeneration of NPCs and delay IVDD, but the underlying molecular mechanism is poorly understood. This study aimed to evaluate the antiapoptosis effects of bone marrow-derived MSC (BMSC) on rat NPCs exposed to compression and investigate whether the mitochondrial pathway was involved. Methods. BMSCs and NPCs were cocultured in the compression apparatus at 1.0 MPa for 36 h. Cell viability, apoptosis, mitochondrial function, and the expression of apoptosis-related proteins were evaluated. Results. The results showed that coculturing with BMSCs increased the cell viability and reduced apoptosis of NPCs exposed to compression. Meanwhile, BMSCs could relieve the compression-induced mitochondrial damage of NPCs by decreasing reactive oxygen species level and maintaining mitochondrial membrane potential as well as mitochondrial integrity. Furthermore, coculturing with BMSCs suppressed the activated caspase-3 and activated caspase-9, decreased the expressions of cytosolic cytochrome c and Bax, and increased the expression of Bcl-2. Conclusions. Our results suggest that BMSCs can protect against compression-induced apoptosis of NPCs by inhibiting the mitochondrial pathway and thus enhance our understanding on the MSC-based therapy for IVDD.
Preclinical Evaluation of SCC244 (Glumetinib), a Novel, Potent, and Highly Selective Inhibitor of c-Met in MET-dependent Cancer Models
Authors: Ai Jing , Chen Yi , Peng Xia , Ji Yinchun , Xi Yong , Shen Yanyan , Yang Xinying , Su Yi , Sun Yiming , Gao Yinglei , Ma Yuchi , Xiong Bing , Shen Jingkang , Ding Jian , Geng Meiyu
Published: December 2017

Because the receptor tyrosine kinase c-Met plays a critical role in tumor growth, metastasis, tumor angiogenesis, and drug resistance, the c-Met axis represents an attractive therapeutic target. Herein, we report the first preclinical characterization of SCC244, a novel, potent, and highly selective inhibitor of c-Met kinase. SCC244 showed subnanomolar potency against c-Met kinase activity and high selectivity versus 312 other tested protein kinases, making it one of the most selective c-Met inhibitors described to date. Moreover, this inhibitor profoundly and specifically inhibits c-Met signal transduction and thereby suppresses the c-Met–dependent neoplastic phenotype of tumor and endothelial cells. In xenografts of human tumor cell lines or non–small cell lung cancer and hepatocellular carcinoma patient-derived tumor tissue driven by MET aberration, SCC244 administration exhibits robust antitumor activity at the well-tolerated doses. In addition, the in vivo antitumor activity of SCC244 involves the inhibition of c-Met downstream signaling via a mechanism of combined antiproliferation and antiangiogenic effects. The results of the current study provide a strong foundation for the clinical investigation of SCC244 in patients with tumors harboring c-Met pathway alterations. Mol Cancer Ther; 17(4); 751–62. ©2017 AACR.
Genome-Wide Transcriptome Analysis of Estrogen Receptor-Positive and Human Epithelial Growth Factor Receptor 2-Positive Breast Cancers by Ribonucleic Acid Sequencing
Authors: Chen Pengtao  , Song Wei  , Liu Liangli 
Published: December 2017

Aim: The aim is to identify complex pathogenesis of breast cancer subtypes and disclose the whole landscape of altered transcriptional activities in these cancers. Methods: We downloaded raw expression data from public database, and performed transcriptome analysis of 8 estrogen receptor-positive (ER+) breast cancer tissue samples, 8 human epithelial growth factor receptor 2-positive (HER2+) breast cancer tissue samples, and 3 normal breast tissues by identification, functional annotation, and prediction of upstream regulators and cell-surface biomarkers of differentially expressed genes (DEGs). Results: We identified over 5,000 DEGs in each of ER+ and HER2+ breast cancers compared to normal tissues. Functional enrichment analysis of shared DEGs indicated significant changes in the regulation of immune ­systems in the 2 subtypes. We further identified 1,871 DEGs between the 2 subtypes and disclosed great tumor heterogeneity. We identified 533 shared upregulated genes and predicted 17 upstream transcription factors, as well as identified differentially expressed cell-surface biomarkers for distinguishing our ER+ and HER2+ breast cancers. Further analysis also highlighted the limitation of the usage of HER2 alone in breast cancer classification. Conclusion: Our findings in ER+ and HER2+ breast cancers provided novel insights into heterogeneous transcriptional activities underlying complex mechanisms of oncogenesis in breast cancers.
Chronic Central Serous Chorioretinopathy-Like Maculopathy as Atypical Presentation of Chorioretinal Folds
Authors: Xirou Tina , Kabanarou Stamatina A. , Gkizis Ilias , Garnavou-Xirou Christina , Velissaris Stavros , Theodossiadis Panagiotis , Chatziralli Irini
Published: December 2017

Purpose: The purpose of this case report was to present the clinical data and management of a 69-year-old female patient with chorioretinal folds who developed chronic central serous chorioretinopathy-like maculopathy. Case Presentation: A 69-year-old female patient presented with a recent-onset slight decrease in visual acuity in her left eye. Her past ocular history was clear. Regarding her medical history, she had only hypertension, treated with per os medications. The patient underwent a complete ophthalmological examination. At presentation, the visual acuity was 6/6 in the right eye and 6/7.5 in the left eye. Intraocular pressure was 16 mm Ηg in both eyes. On fundoscopy, chorioretinal folds were noticed in the left eye. Spectral-domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography confirmed the diagnosis of chronic central serous chorioretinopathy-like maculopathy in the left eye, since other causes of chorioretinal folding were excluded. The right eye was normal. No treatment was given to the patient, and at the 6-month follow-up there was improvement in visual acuity, which was 6/6, and decreased subretinal fluid. Conclusions: Central serous chorioretinopathy-like maculopathy should be taken into account for the differential diagnosis of patients with chorioretinal folds.
Using Controlled Substance Receipt Patterns to Predict Prescription Overdose Death
Authors: Holt Christina T. , McCall Kenneth L. , Cattabriga Gary , Tu Chunhao , Smalley Elenna K. , Nichols Stephanie D.
Published: December 2017

Background: This study evaluates complete state data from controlled substance prescribing trends in the prescription monitoring program (PMP) database and their association with the risk of prescription drug overdose death. Summary: Maine PMP records of individuals who died of prescription overdose deaths between 2006 and 2010 were selected (n = 690). For each subject, an age, gender, and residence matched cohort of PMP users in a 50: 1 ratio was identified (n = 34,500). Key Messages: Prescription opioids contributed to 480 of 690 prescription deaths, many co-ingestions were noted, and OR for overdose death increased with milligram of morphine equivalent (MME)/day >100. The majority who were prescribed MME >100 per day received a prescription within 90 days of overdose matching the toxicology cause of death. Conclusions: Medication profiles available through state PMP can identify dosing of prescriptions associated with drug overdose death.
Ghrelin is Negatively Correlated with Iron in the Serum in Human and Mice
Authors: Luo Qian-Qian , Zhou Gan , Huang Su-Na , Mu Ming-Dao , Chen Yun-Jin , Qian Zhong-Ming
Published: December 2017

Background/Aims: The studies in the patients with iron deficiency anemia (IDA) implied the existence of the association of ghrelin with iron or hepcidin levels in the plasma under the pathophysiological conditions. We hypothesized that fasting may be able to affect iron metabolism via ghrelin under the physiological conditions. Methods: We investigated the effects of fasting on serum ghrelin and iron contents in healthy volunteers (23–31 years) and C57BL/6 male mice (8-week-olds) under the physiological conditions. Results: Fasting induced a significant elevation in both total ghrelin and acylated ghrelin and a reduction in iron levels in the serum of both human and mice. Correlation analysis demonstrated that total ghrelin or acylated ghrelin is negatively correlated with iron in the serum in human and mice. Conclusion: Ghrelin has a role to reduce serum iron under the conditions of fasting.
Combination Cyclophosphamide/Glucocorticoids Provide Better Tolerability and Outcomes versus Glucocorticoids Alone in Patients with Sjogren’s Associated Chronic Interstitial Nephritis
Authors: Shen Yuqi , Xie Jingyuan , Lin Li , Li Xiao , Shen Pingyan , Pan Xiaoxia , Ren Hong , Chen Nan
Published: December 2017

Background: Steroid therapy has become an effective option for patients with primary Sjogren’s syndrome with tubulointerstitial nephritis (TIN), while the use of cytotoxic agents is still debated. Our study aimed to compare the clinical outcomes of patients treated with cyclophosphamide (CTX) combined with glucocorticoids with those of patients treated with glucocorticoids alone. Methods: All patients with primary Sjogren’s syndrome with chronic TIN admitted to the Division of Nephrology, Ruijin Hospital, from January 1, 2002, to April 30, 2016, and treated with steroids alone or combined with CTX were included. The immunological prognosis, improvements of renal function, and acquired tubular defects of the patients were retrospectively compared between the 2 therapeutic groups. Results: A total of 70 cases were included. Of these, 36 were diagnosed by renal biopsy. A total of 56 patients were treated with glucocorticoids alone, while 14 patients received glucocorticoids combined with CTX. There were no significant differences in clinical characteristics and laboratory parameters between the 2 therapeutic groups at baseline. Compared with patients in the steroid group, patients in the CTX group showed better estimated glomerular filtration rate (eGFR) improvement (21.35 ± 19.63 vs. 2.72 ± 19.11 mL/min/1.73 m2, p = 0.006) but a similar decline in immunoglobulin G (IgG; 450 [interquartile range, IQR 910] vs.176 [IQR 1,910] mg/dL, p = 0.93) at 12 months of follow-up. CTX therapy was associated with better eGFR improvement (β = 12.96 [2.95–22.97]) even after adjusting for dry mouth, anti-Sjögren’s-syndrome-related antigen A and anti-Sjögren’s-syndrome-related antigen B positivity, hemoglobin, initial steroid dose, and baseline eGFR by linear regression analyses. Subgroup analyses revealed that the beneficial effects of CTX therapy on renal function were only observed in patients with baseline IgG ≥1,560 mg/dL or eGFR <90 mL/min/1.73 m2. The urine α1-microglobulin improvement was better in the CTX group than in the steroid group at 12 months of follow-up (β = 1.29, 95% CI 0.56–2.02, p = 0.001). Conclusions: CTX therapy is suggested for primary Sjogren’s syndrome patients with chronic TIN, especially those with higher IgG levels and abnormal renal function at baseline.
The Clinical Efficacy of Radium-223 for Bone Metastasis in Patients with Castration-Resistant Prostate Cancer: An Italian Clinical Experience
Authors: De Luca Rossella , Costa Renato Patrizio , Tripoli Vincenzo , Murabito Alessandra , Cicero Giuseppe
Published: December 2017

Background/Aim: Prostate cancer frequently causes bone metastases and skeletal events that impair quality of life (QoL) and survival. The alpha emitter radium-223 is a new drug that improves treatment in men with castration-resistant prostate cancer (CRPC) and bone metastases. Our aim was to evaluate the effectiveness of radium-223. Subjects and Methods: In this retrospective study we enrolled 48 subjects. Pain reduction, alkaline phosphatase (ALP), time to first symptomatic skeletal event, and QoL were the variables we evaluated. Results: Radium-223 was well tolerated, with a manageable toxicity profile and a modest objective response rate. A considerable difference in serum ALP levels before and after treatment was observed, with a significant correlation between pain relief and QoL, which showed a value of R2 to 0.44 with a slope of 1.50 (p = 0.0021). Conclusions: Radium-223 showed a clinical benefit, with a reduction in pain symptoms in 58% of patients. Radium-223 was shown to be an effective and well-tolerated therapeutic option in patients with metastatic CRPC progressing after docetaxel plus prednisone treatment.
Successful Subcutaneous Allergen-Specific Immunotherapy in Refractory Atopic Keratoconjunctivitis: A Case Report
Authors: Jongkhajornpong Passara , Laisuan Wannada
Published: December 2017

Purpose: We report a case of refractory atopic keratoconjunctivitis (AKC) which was successfully treated with subcutaneous immunotherapy (SCIT). Case Report: A 22-year-old woman presented with severe allergic conjunctivitis for one and a half year. She failed to respond to conventional topical anti-allergic medications, topical corticosteroid, as well as topical cyclosporine A. Therefore, oral corticosteroids had to be prescribed to control the exacerbation for 1 year. Due to refractory AKC and to avoid long-term corticosteroid use, we referred her to an allergy clinic for considering the role of SCIT. Allergology investigations showed positive skin prick test and strongly elevated serum-specific IgE to Dermatophagoides farinae (Der f) and Dermatophagoides pteronyssinus (Der p). She received a conventional protocol of SCIT using Der f and Der p allergen extracts. Results: The patient’s ocular signs and symptoms were dramatically improved 2 months after the initiation of SCIT, and oral corticosteroids could be discontinued within 3 months of the treatment. She was maintained with mast cell stabilizers and preservative-free tears without any episodes of exacerbation. Conclusions: SCIT may contribute to successful outcomes in controlling symptoms and preventing exacerbation in AKC patient. It should be considered as an alternative or even a primary treatment for patients with refractory AKC. However, the optimal SCIT protocol must be discussed with an allergist on an individual basis for the best outcome.
Serum Magnesium Abnormality and Influencing Factors of Serum Magnesium Level in Peritoneal Dialysis Patients: A Single-Center Study in Northern China
Authors: Tsai Shihming , Zhao Huiping , Wu Bei , Zuo Li , Wang Mei
Published: December 2017

Background/Aims: Both hypomagnesemia and hypermagnesemia have been associated with cardiovascular diseases, bone diseases, and mortality in dialysis patients. We aimed to investigate the prevalence of and influencing factors for abnormal serum Mg levels in patients on peritoneal dialysis (PD). Methods: A cross-sectional study in Peking University People’s Hospital recorded the demographic information, clinical characteristics, and laboratory data. Data were assessed and compared with the results from 2 other studies in China. Results: Of 180 enrolled PD patients, the primary diseases were glomerulonephritis (38.3%) and diabetic nephropathy (38.3%). Mean serum Mg concentration was 1.02 ± 0.16 mmol/L; 67% had normal serum Mg concentrations, and 33% had hypermagnesemia. Conclusions: Hypermagnesemia is likely to occur in patients with higher serum phosphate, lower intact parathyroid hormone, and lower high-sensitivity C-reactive protein levels. Serum Mg level distributions in PD patients vary throughout China, may have different potential causes (such as geographical location and dietary habits) and should be further studied.
Evaluation of Behavioral and Susceptibility Patterns in Premenopausal Women with Recurrent Urinary Tract Infections: A Case Control Study
Authors: Al Demour Saddam , Ababneh Mera A.
Published: December 2017

Recurrent urinary tract infections (UTI) are a major source of morbidity and healthcare costs. Risk factors associated with recurrence rates in premenopausal women can be attributed to patient lifestyle behavior. The aim of this study was to assess hygienic risk factors, determine pathogen distribution, and susceptibility patterns in premenopausal women with recurrent UTI. This was case-control study in which a face-to-face interview was conducted to obtain information from premenopausal women with recurrent UTI. Microbiology cultures and susceptibility results were obtained to analyze pathogen distribution and resistance. In this study, 214 cases and 230 controls were compared and the following practices were associated with increased risk of recurrent UTI in multivariable analysis: washing genitals from back to front (OR 1.64 [95% CI 1.05–2.56]), not voiding within 15 min after intercourse (OR 2.81 [95% CI 1.72–4.66]), not drinking water after intercourse (OR 1.69 [95% CI 1.12–2.58]), using any soap to clean after urination (OR 2.11 [95% CI 1.42–3.17]). Escherichia coli were the most prevalent pathogens isolated (66.4%), followed by Klebsiella spp. (12.6%), Pseudomonas aeruginosa (12.1%), and Proteus spp., (6.6%). This study identified several modifiable sexual and hygienic practices associated with recurrent UTI in premenopausal women. Continuous surveillance of antimicrobial susceptibility patterns is important to overcome resistance.
Calycosin Inhibits the Migration and Invasion of Human Breast Cancer Cells by Down-Regulation of Foxp3 Expression
Authors: Li Shuangxi , Wang Yafei , Feng Chan , Wu Guoli , Ye Yu , Tian Jing 
Published: December 2017

Background/Aims: Calycosin, a phytoestrogenic compound, has recently emerged as a promising antitumor drug. It has been shown that calycosin suppresses growth and induces apoptosis of breast cancer cells. However, the effect of calycosin on migration and invasion of breast cancer cells and the underlying molecular mechanisms have not been elucidated. Methods: Human breast cancer cells MCF-7 and T47D were treated with, or without, different doses (0, 6.25, 12.5, 25, 50, 100 or 150 μM) of calycosin, and the viability of different groups was determined by MTT assay. Next, the inhibitory effect of higher doses (50, 100 or 150 μM) of calycosin on migration and invasion of the two cell lines was determined by wound healing and transwell assay. The relative expression levels of forkhead box P3 (Foxp3), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in MCF-7 and T47D cells were determined by quantitative RT-PCR and Western blot. Results: Treatment with lower doses (6.25 or 12.5 μM) promoted proliferation of breast cancer cells, but with higher doses significantly reduced the viability of MCF-7 and T47D cells. Furthermore, higher doses of calycosin were found to inhibit migration and invasion of the two cell lines in a dose-dependent manner. Additionally, treatment with a higher dose of calycosin significantly reduced the expression levels of Foxp3, followed by down-regulation of VEGF and MMP-9 in both MCF-7 and T47D breast cancer cells. Conclusion: Treatment with a higher dose of calycosin tends to reduce migration and invasion capacity of human breast cancer cells, by targeting Foxp3-mediated VEGF and MMP-9 expression.
YAP Inhibits the Apoptosis and Migration of Human Rectal Cancer Cells via Suppression of JNK-Drp1-Mitochondrial Fission-HtrA2/Omi Pathways
Authors: Li Haijun , He Fucheng , Zhao Xin , Zhang Yuan , Chu Xi , Hua Chunlan , Qu Yunhui , Duan Yu , Ming Liang
Published: December 2017

Background/Aims: The Hippo-Yap pathway is associated with tumor development and progression. However, little evidence is available concerning its role in cancer cell apoptosis and migration via mitochondrial homeostasis. Here, we identify mitochondrial fission as a regulator of the Hippo–Yap pathway in human rectal cancer tumorigenesis and metastasis. Methods: In this study, we performed loss-of function assays concerning Yap in RCC via shRNA. Cellular viability and apoptosis were measured via MTT, the TUNEL assay and trypan blue staining. Mitochondrial function was assessed via JC1 staining, the mPTP opening assay, mitochondrial respiratory function analysis, electron microscopy and immunofluorescence analysis of HtrA2/Omi. Mitophagy and mitochondrial fission were assessed via western blots and immunofluorescence. Cell migration was evaluated via the Transwell assay, wound-healing assay and immunofluorescence analysis of F-actin. The interaction between JNK and Yap was detected via co-immunoprecipitation and Yap recombinant mutagenic plasmid transfection. Western blots were used to analyze signaling pathways in conjunction with JNK inhibitors or HtrA2/Omi siRNA. Results: Yap is upregulated in human rectal cancer cells, where its expression correlates positively with cell survival and migration. Functional studies established that silencing of Yap drove JNK phosphorylation, which induced Drp1 activation and translocation to the surface of mitochondria, initiating mitochondrial fission. Excessive mitochondrial fission mediated HtrA2/Omi leakage from the mitochondria into the cytoplasm, where HtrA2/Omi triggered cellular apoptosis via the mitochondrial apoptosis pathway. Moreover, released HtrA2/Omi also phosphorylated cofilin and inhibited cofilin-mediated F-actin polymerization. F-actin collapse perturbed lamellipodia formation and therefore impaired cellular migration and invasion. Conclusion: Collectively, our results demonstrate that Hippo-Yap can serve as a tumor promoter in human rectal cancer and acts by restricting JNK/Drp1/mitochondrial fission/ HtrA2/Omi, with potential implications for new approaches to human rectal cancer therapy.
Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury
Authors: Luo Qiancheng , Guo Dongfeng , Liu Guorong , Chen Guo , Hang Min , Jin Mingming
Published: December 2017

Background/Aims: Recent studies have indicated that exosomes play an important role in adipose-derived stem cell (ADSC) transplant-mediated ischaemic heart disease therapy. However, the treatment effect is not obvious. The aim of this study is to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-126 have a more protective effect on acute myocardial infarction (AMI). Methods: Exosomes were characterized by transmission electron microscopy, and the exosome particles were further examined using nanoparticle tracking analyses. A rat model of myocardial infarction and in vitro model of hypoxia-induced H9c2 myocardial cell injury were established to study the protective mechanism of exosomes from miR-126-overexpressing ADSCs. Results: The in vitro results showed that exosomes derived from miR-126-overexpressing ADSCs decreased H9c2 myocardial cell injury by reducing inflammation factor expression during hypoxia induction. The miR-126-enriched exosomes also decreased the expression of fibrosis-related proteins of H9c2 cells under hypoxic conditions. Matrigel® and Transwell® assays showed that miR-126-enriched exosomes significantly promoted microvascular generation and migration, respectively. In vivo studies confirmed that exosomes derived from ADSCs significantly decreased the myocardial injury area of infarction, especially after miR-126-enriched exosome treatment. Cardiac fibrosis and inflammatory cytokine expression were also decreased after treatment with miR-126-enriched exosomes. However, blood vessel formation was promoted in the infarction region of AMI rats. Conclusions: The results suggested that the expression of miR-126-enhanced ADSC-derived exosomes prevented myocardial damage by protecting myocardial cells from apoptosis, inflammation, fibrosis, and increased angiogenesis.
Familial Aggregation of Aortic Valvular Stenosis
Authors: Martinsson Andreas , Li Xinjun , Zöller Bengt , Andell Pontus , Andersson Charlotte , Sundquist Kristina , Smith J. Gustav
Published: December 2017

Background—

Aortic valvular stenosis (AS) is the most common cause of cardiac valvular replacement surgery. During the last century, the pathogenesis of AS has undergone transitions in developed countries, from rheumatic heart disease to a degenerative calcific pathogenesis. Although a familial component has been described for a subset of cases with a bicuspid valve, data are limited on the overall familial aggregation of this disease.

Methods and Results—

Contemporary information on 6 117 263 Swedish siblings, of which 13 442 had a clinical diagnosis of AS, was collected from the nationwide Swedish Multi-Generation Register and the National Patient Register. A total of 4.8% of AS cases had a sibling history of AS. Having at least 1 sibling with AS was associated with a hazard ratio of 3.41 (95% confidence interval, 2.23–5.21) to be diagnosed with AS in an adjusted model. Individuals with >1 sibling with AS had an exceptionally high risk (hazard ratio, 32.84) but were uncommon (34 siblings from 11 sibships). In contrast, spouses of subjects with AS were only slightly more likely to be diagnosed with AS compared with subjects without spousal AS (hazard ratio 1.16 for husbands and 1.18 for wives).

Conclusions—

A sibling history of clinically diagnosed AS was associated with increased risk of AS. Spouses of patients with AS only had a modest risk increase, suggesting that shared adult environmental factors contribute less to the development of AS than genetic factors.
Diagnosis and Prognosis in Sudden Cardiac Arrest Survivors Without Coronary Artery Disease
Authors: Rodrigues Patricia , Joshi Abhishek , Williams Howell , Westwood Mark , Petersen Steffen E. , Zemrak Filip , Schilling Richard J. , Kirkby Claire , Wragg Andrew , Manisty Charlotte , Mohiddin Saidi
Published: December 2017

Background—

Determining the pathogenesis of sudden cardiac arrest or periarrest without significant coronary artery disease is crucial for management and prognosis. Cardiovascular magnetic resonance (CMR) can detect morphological, functional, or tissue abnormalities, and we sought to evaluate the role of CMR in determining sudden cardiac arrest pathogenesis and prognosis in survivors.

Methods and Results—

We retrospectively reviewed cardiac investigations and clinical outcomes in consecutive survivors of potentially fatal arrhythmias without coronary artery disease admitted to our institutions from 2008 to 2014. After coronary angiography and echocardiography, all underwent CMR and, when indicated, electrophysiology studies. Major adverse cardiac events (MACE), comprising significant nonfatal ventricular arrhythmia or death, was the primary outcome. Of 164 included subjects (65% men; mean age 48 [18–80] years), CMR contributed to the diagnosis in 80 (49%) and was decisive in 50 cases (30%). Dilated cardiomyopathy (n=27), myocarditis or sarcoidosis (n=22), occult myocardial infarction (n=13), and hypertrophic cardiomyopathy (n=9) were most frequent. Arrhythmic causes were found in 14% while no cause was identified in 36%. MACE occurred in 31% of subjects during a median follow-up of 32 months. MACE associated with presence of a CMR diagnosis, extent of late gadolinium enhancement, and left and right ventricular ejection fractions. Right ventricular ejection fraction was an independent predictor of MACE.

Conclusions—

CMR identified a likely pathogenesis for sudden cardiac arrest in nearly half of survivors in whom coronary artery disease had been excluded. One in 3 subjects had MACE; risk doubled in those with a CMR diagnosis and some CMR parameters—late gadolinium enhancement, left ventricular ejection fraction, and especially right ventricular ejection fraction—associated with prognosis.
Dyspnea Among Patients With Chronic Total Occlusions Undergoing Percutaneous Coronary Intervention
Authors: Qintar Mohammed , Grantham J. Aaron , Sapontis James , Gosch Kensey L. , Lombardi William , Karmpaliotis Dimitri , Moses Jeffery , Salisbury Adam C. , Cohen David J. , Spertus John A. , Arnold Suzanne V.
Published: December 2017

Background—

Dyspnea is a common angina equivalent that adversely affects quality of life, but its prevalence in patients with chronic total occlusions (CTOs) and predictors of its improvement after CTO percutaneous coronary intervention (PCI) are unknown. We examined the prevalence of dyspnea and predictors of its improvement among patients selected for CTO PCI.

Methods and Results—

In the OPEN CTO registry (Outcomes, Patient health status, and Efficiency iN Chronic Total Occlusion) of 12 US experienced centers, 987 patients undergoing CTO PCI (procedure success 82%) were assessed for dyspnea with the Rose Dyspnea Scale at baseline and 1 month after CTO PCI. Rose Dyspnea Scale scores range from 0 to 4 with higher scores indicating more dyspnea with common activities. A total of 800 (81%) reported some dyspnea at baseline with a mean (±SD) Rose Dyspnea Scale of 2.8±1.2. Dyspnea improvement was defined as a ≥1 point decrease in Rose Dyspnea Scale from baseline to 1 month. Predictors of dyspnea improvement were examined with a modified Poisson regression model. Patients with dyspnea were more likely to be female, obese, smokers, and to have more comorbidities and angina. Among patients with baseline dyspnea, 70% reported less dyspnea at 1 month after CTO PCI. Successful CTO PCI was associated with more frequent dyspnea improvement than failure, even after adjustment for other clinical variables. Anemia, depression, and lung disease were associated with less dyspnea improvement after PCI.

Conclusions—

Dyspnea is a common symptom among patients undergoing CTO PCI and improves significantly with successful PCI. Patients with other potentially noncardiac causes of dyspnea reported less dyspnea improvement after CTO PCI.