bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of matrix metalloproteinase‐9 in breast cancer cell lines remarkably increases the cell malignancy largely via activation of transforming growth factor beta/SMAD signalling
Authors: Dong Haodi , Diao Hongxiu , Zhao Ying , Xu Huihao , Pei Shimin , Gao Jiafeng , Wang Jie , Hussain Tariq , Zhao Deming , Zhou Xiangmei , Lin Degui 
Published: July 2019

AbstractObjectivesMatrix metalloproteinase 9 (MMP‐9) has been frequently noticed in the breast cancers. In this study, we aim to investigate the associations of MMP‐9 with the activation of transforming growth factor beta (TGF‐β)/SMAD signalling and the malignancy of breast malignant tumour cells.Materials and methodsThe distributions of MMP‐9 and TGF‐β in the tissues of canine breast cancers were screened by immunohistochemical assays. A recombinant plasmid expressing mouse MMP‐9 was generated and transiently transfected into three different breast cancer cell lines. Cell Counting Kit‐8 and colony formation assay were used to study cell viability. Migration and invasion ability were analysed by wound assay and transwell filters. Western blot and quantitative real‐time PCR were used to determine the protein and mRNA expression.ResultRemarkable strong MMP‐9 and TGF‐β signals were observed in the malignant tissues of canine breast cancers. In the cultured three cell lines receiving recombinant plasmid expressing mouse MMP‐9, the cell malignancy was markedly increased, including the cell colony formation, migration and epithelial‐mesenchymal transition. The levels of activated TGF‐β, as well as SMAD4, SMAD2/3 and phosphorylation of SMAD2, were increased, reflecting an activation of TGF‐β/SMAD signalling. We also demonstrated that the inhibitors specific for MMP‐9 and TGF‐β sufficiently blocked the overexpressing MMP‐9 induced the activation of SMAD signalling and enhancement on invasion in the tested breast cancer cell lines.ConclusionOverexpression of MMP‐9 increases the malignancy of breast cancer cell lines, largely via activation of the TGF‐β/SMAD signalling.
Aurora B prevents aneuploidy via MAD2 during the first mitotic cleavage in oxidatively damaged embryos
Authors: Li Jiena , Ha Siyao , Li Zhiling , Huang Yue , Lin En , Xiao Wanfen 
Published: July 2019

AbstractObjectivesA high rate of chromosome aneuploidy is exhibited in in vitro fertilization (IVF)‐derived embryos. Our previous experiments suggested that reactive oxygen species (ROS) can activate Mad2, a key protein in the spindle assembly checkpoint (SAC), and delay the first mitotic, providing time to prevent the formation of embryonic aneuploidy. We aimed to determine whether mitotic kinase Aurora B was involved in the SAC function to prevent aneuploidy in IVF‐derived embryos.Materials and MethodsWe analysed aneuploidy formation and repair during embryo pre‐implantation via 4ʹ,6‐diamidino‐2‐phenylindole (DAPI) staining and karyotype analysis. We assessed Aurora B activation by immunofluorescence and investigated the effect of Aurora B inhibition on embryo injury‐related variables, such as embryonic development, ROS levels, mitochondrial membrane potential and γH2AX‐positive expression.ResultsWe observed the expression and phosphorylation of Thr232 in Aurora B in oxidative stress‐induced zygotes. Moreover, inhibition of Aurora B caused chromosome mis‐segregation, abnormal spindle structures, abnormal chromosome number and reduced expression of Mad2 in IVF embryos. Our results suggest that Aurora B causes mitotic arrest and participates in SAC via Mad2 and H3S10P, which is required for self‐correction of aneuploidies.ConclusionsWe demonstrate here that oxidative stress–induced DNA damage triggers Aurora B‐mediated activation of SAC, which prevents aneuploidy at the first mitotic cleavage in early mouse IVF embryos.
Long‐term effects of energy development on winter distribution and residency of pronghorn in the Greater Yellowstone Ecosystem
Authors: Sawyer Hall , Beckmann Jon P. , Seidler Renee G. , Berger Joel 
Published: July 2019

AbstractAn increasing global demand for energy assures continued disturbance to previously undeveloped landscapes, but understanding broader impacts to wildlife remains elusive. Among groups of species most vulnerable to habitat disruption are those requiring large tracts of land. Pronghorn (Antilocapra americana) are an obligate to the open plains and basins that, similar to other transcontinental large herbivores, rely primarily on habitats where development of energy resources such as oil, natural gas, coal, wind, and solar are intensifying. To understand behavioral response to a burgeoning energy development project, we evaluated avoidance, displacement, and winter residency patterns of pronghorn in the southern Greater Yellowstone Ecosystem across a 15‐year period using 171 collared individuals. Distance from natural gas well pads increased through time and was concurrent with declines in winter residency. Between 2005 and 2017, we found that (a) pronghorn avoidance of well pads likely increased by 408 m, (b) the overall displacement of pronghorn relative to well pads in the final year of study increased by 800 m, (c) the time pronghorn spent in the study area was reduced by 22% (nearly 1 month), and (d) the percentage of pronghorn leaving the study area increased by 57%. Such directional changes signal a strong behavioral response of an open‐plain obligate to energy infrastructure, and together, these metrics indicate that pronghorn response to energy development involves both avoidance of infrastructure and partial abandonment of their traditional winter ranges. While comparable long‐term data sets are generally unavailable for other functionally equivalent ungulate groups in similar ecological topographies of Asia, Africa, and South America, our study may serve as a reasonable surrogate and highlights that behavioral changes elicited from energy development which at first appear subtle can proliferate and may portend demographic consequences.
Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma
Authors: Pisano Sorana G. , Hoffman Sarah E. , Legasto Carlo S. , McLaughlin Eric M. , Porter Kyle , Chen James L. 
Published: July 2019

Pazopanib (PAZ), a tyrosine kinase inhibitor used in the treatment of soft tissue sarcoma (STS), should not be administered with acid‐suppressive medications (ASMs) due to decreased drug solubility. Common practice for patients requiring ASM with PAZ is to separate administration by 12 hours; however, there is little real‐world evidence describing clinical outcomes using this strategy. The aim of this study was to determine whether concomitant ASM impacted efficacy and adverse event rates in patients with STS receiving PAZ. Medical records were retrospectively reviewed for patients with STS who received PAZ from June 2011 to July 2017. Patients were stratified into two groups, PAZ with or without ASM (PAZ + ASM or PAZ only). The primary objective was to determine whether progression‐free survival (PFS) differed between groups. Secondary objectives were to determine overall survival (OS) and occurrence of grade 3/4 toxicities. Ninety‐one patients were included in the study, 42 patients in the PAZ + ASM group and 49 in the PAZ only group. Median PFS was significantly shorter in the PAZ + ASM group than the PAZ only group (5.3 vs. 6.7 months). The PAZ + ASM group also had a 74% higher relative risk of progression or death than the PAZ only group, but there was no difference in OS. Regarding adverse events, the PAZ + ASM group trended toward lower levels of grade 3/4 hypertension (19% vs. 37%). These results suggest that ASM should be avoided in patients with STS receiving PAZ. Larger studies are needed to further elucidate the impact of ASM use with PAZ in clinical practice.
Switching to insulin glargine 300 units/mL in real‐world older patients with type 2 diabetes (DELIVER 3)
Authors: Bailey Timothy S. , Wu Jasmanda , Zhou Fang L. , Gupta Rishab A. , Menon Arjun A. , Berhanu Paulos , Westerbacka Jukka , Van Vleet John , Blonde Lawrence 
Published: July 2019

AbstractAimTo compare the second‐generation basal insulin glargine 300 units/mL (Gla‐300) and first‐generation basal insulins on glycaemic control and hypoglycaemia risk in older adults with type 2 diabetes (T2D).Materials and methodsDELIVER 3 was a retrospective observational cohort study of electronic medical records. A total of 1176 older adults (aged ≥ 65 years) with T2D and ≥1 HbA1c value during 6 month baseline and 3 to 6 month follow‐up who switched from basal insulin to Gla‐300 were propensity score‐matched to 1176 older adults who switched to a first‐generation basal insulin [insulin detemir (IDet) or insulin glargine 100 units/mL (Gla‐100)]. Outcomes were follow‐up HbA1c, achievement of HbA1c <7% and <8%, hypoglycaemia incidence and event rates, and healthcare resource utilization.ResultsFollowing basal insulin switching, HbA1c reductions were greater/similar with Gla‐300 versus IDet/Gla‐100 (variable follow‐up: −0.45% ± 1.40% vs. −0.29% ± 1.57%; P = .021; fixed follow‐up: −0.48% ± 1.49% vs. −0.38% ± 1.59%; P = .114), while HbA1c goal attainment was similar in both cohorts. Gla‐300 was associated with less hypoglycaemia [event rate: adjusted rate ratio (aRR): 0.63, 95% CI: 0.53‐0.75; P < .001] and inpatient/emergency department‐associated hypoglycaemia (adjusted hazard ratio: 0.58, 95% CI: 0.37‐0.90; P = .016; aRR: 0.43, 95% CI: 0.31‐0.60; P < .001) by variable follow‐up. By fixed follow‐up, hypoglycaemia results significantly or numerically favoured Gla‐300.ConclusionAmong older adults with T2D, switching to Gla‐300 versus Gla‐100/IDet was associated with greater/similar improvements in glycaemic control, and generally less hypoglycaemia.
Sodium glucose cotransporter 2 inhibitors and risk of genital mycotic and urinary tract infection: A population‐based study of older women and men with diabetes
Authors: Lega Iliana C. , Bronskill Susan E. , Campitelli Michael A. , Guan Jun , Stall Nathan M. , Lam Kenneth , McCarthy Lisa M. , Gruneir Andrea , Rochon Paula A. 
Published: July 2019

AbstractAimsThe objective of the study was to quantify the association between SGLT2 inhibitors and genital mycotic infection and between SGLT2 inhibitors and urinary tract infection (UTI) within 30 days of drug initiation among older women and men.Materials and methodsThis was a retrospective cohort study using linked administrative databases of women and men with diabetes, aged 66 years or older, in Ontario, Canada. We compared the incidence of genital mycotic infection or UTI within 30 days between new users of an SGLT2 inhibitor and of a dipeptidyl‐peptidase‐4 (DPP4) inhibitor.ResultsWe identified 21 444 incident users of SGLT2 inhibitor and 22 463 incident users of DPP4 inhibitor. Among SGLT2 inhibitor users, there were 8848 (41%) women and the mean age at index was 71.8 ± 5 (SD) years. After adjusting for propensity score, age, sex and recent UTI, there was a 2.47‐fold increased risk of genital mycotic infection with incident use of SGLT2 inhibitors (adjusted hazard ratio (HR), 2.47; 95% confidence interval (CI), 2.08‐2.92; P < 0.001) within 30 days compared to incident use of DPP4 inhibitors. For UTI, the adjusted HR was 0.89 (95% CI, 0.78‐1.00; P = 0.05).ConclusionsIncident use of SGLT2 inhibitors among older women and men is associated with increased risk of genital mycotic infections within 30 days; there is no associated increased risk of UTI. These findings from a real‐world setting provide evidence of the potential harms of SGLT2 inhibitors.
A two‐step ovariohysterectomy with unilateral left flank laparoscopic assistance in a Quarter Horse mare
Authors: Kadic D. T. N. , Bonilla A. G. 
Published: July 2019

SummaryThis case report describes the technique and outcome of a two‐step laparoscopic‐assisted ovariohysterectomy in a Quarter Horse mare performed through the left paralumbar fossa for the treatment of chronic pyometra. Ovariohysterectomy is a procedure uncommonly performed in the horse. It is surgically demanding, invasive and can be associated with significant complications when a ventral midline approach is performed. Laparoscopic‐assisted techniques reduce the invasiveness and some of the complications associated with ovariohysterectomy through ventral midline alone. The described modification further reduces the invasiveness of laparoscopic‐assisted ovariohysterectomy and has the potential to reduce the overall surgical time of the procedure. Further work is needed to determine if the technique could be extrapolated to large‐sized mares.
Sarcocystis myositis and vitamin E deficiency in a Gypsy Vanner stallion suspected of having equine motor neuron disease
Authors: Trimble A. C. , Delph K. M. , Perry E. R. , Valberg S. J. 
Published: July 2019

SummaryA 3‐year‐old Gypsy Vanner stallion was presented for evaluation of intermittent recumbency, muscle fasciculations, weakness, low head carriage, shifting of weight between the hindlimbs and an elevated tail head. History, physical examination and serum alpha tocopherol concentrations were suggestive of vitamin E deficiency and equine motor neuron disease (EMND). Sacrocaudalis dorsalis medialis muscle biopsy identified myositis secondary to sarcocystosis. Treatment with alpha tocopherol, ponazuril and sulfadiazine/pyrimethamine resulted in significant improvement in muscle weakness and body condition with resolution of sarcocystosis and inflammation on repeat muscle biopsy. This case illustrates the importance of muscle biopsy in horses with neuromuscular disease as concurrent diseases may be present that require specific treatment for a positive outcome.
A novel technique to diagnose non‐melanoma skin cancer by thermal conductivity measurements: Correlations with cancer stromal factors
Authors: Fujimura Taku , Okabe Takahiro , Tanita Kayo , Sato Yota , Lyu Chunbing , Kambayashi Yumi , Maruyama Shigenao , Aiba Setsuya 
Published: July 2019

AbstractThe skin surface temperature reflects the physiological state of the human body. Quantitative methods of identification of skin cancers based on accurate measurement of effective thermal conductivity (ETC) are among the promising diagnostic tools for differentiating non‐invasive and invasive melanomas before surgical treatment. To validate these findings, in this report, the diagnostic methods for invasive and non‐invasive extramammary Paget’s disease (EMPD) and squamous cell carcinoma (SCC) were further tested by measuring the absolute value of skin surface temperature and the ETC of the skin. In addition, to investigate the stromal factors that might affect ETC, immunohistochemical staining for LL37, periostin (POSTN), MMP12, and MMP28 was performed. The invasive SCC and EMPD group showed a relatively higher skin surface temperature compared to the in situ SCC group. The non‐invasive EMPD and SCC group showed significantly lower values of ETC at lesions, whereas the invasive EMPD group showed significantly higher ETC values at lesions compared to healthy skin. Immunohistochemical staining showed that the percentage of LL37‐producing cells was significantly increased in invasive EMPD and SCC compared to that in non‐invasive EMPD and SCC. Moreover, Spearman's rank correlation test showed a significant inverse correlation between the percentage of MMP12‐positive cells and increased levels of ETC‐expressing areas in EMPD and SCC (r = −.5997). The present study suggested that differences in ETC could be a novel high‐accuracy diagnostic technique for non‐melanoma skin cancer, especially for detecting dermal invasion of SCC and EMPD.
Exploration of a Marital Typology: Implications for Marital Functioning in a Multi‐Ethnic Sample
Authors: Lindahl Kristin M. , Malik Neena M. , Wigderson Sara 
Published: July 2019

Marital conflict is associated with multiple negative outcomes for couples, including marital dissatisfaction and divorce. Little research, however, has examined conflict in Hispanic/Latino couples or its association with marital satisfaction, which creates an unfortunate knowledge gap for clinicians working with diverse client groups. The present study sought to examine both marital conflict and satisfaction using a sample of 231 European American (EA; n = 108) and Hispanic/Latino (H/L; n = 123) couples. Through observational coding, couples were placed into four groups based on their type of conflict management strategies: Harmonious, Withdrawn, Conflictual‐Expressive, or Conflictual‐Hostile. For both ethnic groups, couples in the Harmonious group were nondistressed and couples in the Conflictual‐Hostile group were in the distressed range of marital satisfaction. Cross‐ethnic differences emerged. EA couples experienced distress when both hostile (Conflictual‐Hostile) and nonhostile conflict (Conflictual‐Expressive) communication types were observed, while only hostile conflict was associated with distress for the H/L group. H/L couples reported similar levels of satisfaction in both the Harmonious and Conflictual‐Expressive groups. H/L couples also fell within the distressed range when withdrawn communication patterns were observed; however, this was not the case for EA couples. These differences suggest that both types of conflict are associated with marital distress for EA couples, whereas hostile conflict and withdrawn behavior appear to be more negatively associated with marital satisfaction in H/L couples. Results provide support for the use of an observational coding system with H/L and EA couples and also suggest the importance of understanding how differences in expressions of conflict across ethnicities may relate to marital satisfaction.
Extrusion/intrusion structure as a fatigue indicator for uniaxial and multiaxial loading
Authors: Pejkowski Łukasz , Karuskevich Mikhail , Maslak Tetiana 
Published: July 2019

AbstractThe paper describes the experiments aimed at the extension of the method early proposed for the uniaxial fatigue monitoring to the multiaxial modes of loading. The common denominator for both methods approach is based on the possibility of computer‐aided optical analysis of extrusion/intrusion structure, called often surface deformation relief, to be used for quantitative assessment of accumulated fatigue damage and remaining life. Experimental data obtained under the different modes of loading are presented and described as well as some objectives for the future activities are outlined.
Did the German Minimum Wage Reform Influence (Un)employment Growth in 2015? Evidence from Regional Data
Authors: Garloff Alfred 
Published: July 2019

AbstractUsing the variation across space, age and sex and the variation across space and sectors, we analyse the relationship between the minimum wage and (un)employment growth in 2015. We use difference-in-differences specifications and instrument the bite of the minimum wage by the lagged bite. The results provide stable evidence that a higher minimum wage bite is related to a higher growth rate of regular employment. We also find stable evidence that a higher minimum wage bite is related to a lower growth rate of marginal employment. These results are consistent with a transformation of marginal to regular jobs. The relationship to total employment is slightly positive in our preferred specification but insignificant or negative in others. For unemployment, we find a positive relationship between the bite of the minimum wage and unemployment growth in our preferred specification but insignificant or negative results in others.
H2O Content Measurement in Phengite by Secondary Ion Mass Spectrometry: A New Set of Reference Materials
Authors: Luisier Cindy , Baumgartner Lukas , Siron Guillaume , Vennemann Torsten , Robyr Martin 
Published: July 2019

Five new natural white mica reference materials (RMs) were developed for in situ H2O content analyses by secondary ion mass spectrometry at the SwissSIMS laboratory of Lausanne University, Switzerland. The white mica reference materials cover a large part of the natural muscovite–phengite compositional range and are therefore suitable as reference materials for the analysis of natural rocks as well as individual minerals. The independent H2O content of the reference materials UNIL_WM1 to UNIL_WM5 was obtained by thermal conversion elemental analyser and corresponds to 4.35 ± 0.02, 4.33 ± 0.03, 4.30 ± 0.07, 4.50 ± 0.02 and 4.42 ± 0.11 (% m/m, ± 1s), respectively. SIMS determinations of H2O content revealed a matrix effect correlated to the FeO content of white mica. The compositional range in FeO of the reference materials that were calibrated for H2O determination is from 1.13% to 3.67% m/m. No crystallographic orientation dependency was observed at the level of homogeneity of these reference materials. An analytical precision of 0.02% to 0.08% m/m (1SE) is expected for the final uncertainty on measurements of unknown white micas in natural samples.
Impact of the Survey of Inhibitors in Plasma‐Product Exposed Toddlers (SIPPET) study and its post hoc analyses on clinical practice in the United States: A survey of Haemophilia and Thrombosis Research Society members
Authors: Sande Christopher M. , Al‐Huniti Ahmad , Ten Eyck Patrick , Sharathkumar Anjali A. 
Published: July 2019

AbstractIntroductionA recent randomized trial, the Survey of Inhibitors in Plasma‐Product Exposed Toddlers (SIPPET), confirmed that exposure to recombinant FVIII (rFVIII) products doubled the risk of inhibitor development compared to plasma‐derived FVIII (pdFVIII) in previously untreated (or minimally treated) patients (PUPs) with severe haemophilia A. SIPPET post hoc analyses showed that early exposure to rFVIII was more immunogenic and that rFVIII could harm low‐risk PUPs with non‐null mutations. Clinical implications of SIPPET findings for the haemophilia community were unclear.AimStudy the impact of the SIPPET study and its post hoc analyses on clinical practice for PUPs with severe haemophilia A in the United States.MethodsMembers of the North American Hemophilia and Thrombosis Research Society (HTRS) completed two online questionnaires related to SIPPET publications and PUP management (study period: 12/2016‐8/2018).ResultsOver 50% participated the study. Sixty per cent expressed methodological concerns about the SIPPET study, yet 55% shared the study with new families. During the study period, rFVIII selection fell from 43/61 (70%) to 15/54 (28%) while use of pdFVIII and shared decision‐making increased from 5/61 (8%) to 9/54 (17%) and from 4/61 (7%) to 10/54 (19%), respectively. Based on post hoc analyses, 44/54 (82%) would change their clinical practice with 31/44 (70%) using pdFVIII for PUPs. Barriers to translation of SIPPET analyses included study design concerns, non‐inclusion of novel therapies, inability to perform genetic testing at diagnosis and risk of plasma‐derived infections.ConclusionDespite the methodological concerns about the SIPPET study, this Grade I evidence appears to have influenced the clinical practice of haemophilia providers in the United States.