bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of Metformin on LPS-Induced Bacterial Myocarditis
Authors: Li Minghua , Gou Yawei , Yu Hongmei , Ji Tiefeng , Li Yi , Qin Ling , Sun Wei 
Published: May 2019

Aims: Metformin is commonly used to treat type 2 diabetes mellitus; however, in recent years, it was found to play a potential role in the protection of myocardial injury. In this study, we intended to investigate whether metformin had protective effects on bacterial myocarditis. Methods and Results: We stimulated rat cardiac myoblast H9c2 cells with lipopolysaccharide (LPS) and administrated with metformin. The results showed that cell viability after LPS stimulation was greatly reduced. The expression levels of phosphorylated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinases (JNK), nuclear factor (NF)-κB (NF-κB), BAX, and cleaved Caspase3 were significantly increased, while the expression of antiapoptotic protein Bcl-2 showed a prominent decrease compared to control. Nevertheless, the cells activity increased remarkably after metformin administration, and the expression levels of intracellular related proteins showed the opposite trend to that of the LPS group. Conclusion: We demonstrate that LPS stimulation may activate intracellular MAPK/JNK and NF-κB signaling pathways and thus induce cell apoptosis. In contrast, metformin reduced apoptosis by inhibiting this signaling pathway and increasing the expression level of Bcl-2. Moreover, it was found that metformin could enhance the ability of cells to antagonize redox damage by regulating the activities of superoxide dismutase and lactate dehydrogenase and subsequently promote the recovery of cardiomyocyte function.
Dystrophic mineralisation in chronic exogenous lipid pneumonia in cats
Authors: Mallol Claudia , Espada Yvonne , Lloret Albert , Altuzarra Raúl , Anselmi Carlo , Novellas Rosa 
Published: May 2019

Case series summary Exogenous lipid pneumonia with mineralisation of the lung parenchyma was diagnosed in three cats with radiographs, CT and/or bronchoalveolar lavage cytological findings. All three cats had a common clinical history of chronic constipation and long-term forced oral administration of mineral oil. All three cases showed radiographic findings compatible with aspiration pneumonia, with an alveolar pattern in the ventral part of the middle and/or cranial lung lobes. Minor improvement of the radiographic lung pattern in the follow-up studies was seen in two cats, and a miliary ‘sponge-like’ mineralised pattern appeared in the previously affected lung lobes months to years after the diagnosis. In one cat, patchy fat-attenuating areas in the consolidated lung lobes were present on thoracic CT. Cases 1 and 2 showed respiratory signs at the initial presentation, while in case 3 the radiographic findings were incidental and the cat had never exhibited respiratory signs. Relevance and novel information This is the first report to describe dystrophic mineralisation of the lung in exogenous lipid pneumonia and also the first to describe the CT features in cats. Exogenous lipid pneumonia should be included in the differential diagnosis in cases of miliary ‘sponge-like’ mineral opacities in the dependent part of the lung lobes on thoracic radiographs or CT in cats, especially in cases of chronic constipation, previously exposed to mineral oil.
The simpler, the better: oral arsenic for acute promyelocytic leukemia
Authors: Zhu Hong-Hu , Hu Jiong , Lo-Coco Francesco , Jin Jie 
Published: May 2019

Abstract
Arsenic trioxide and all-trans retinoic acid have become the frontline treatments for patients with acute promyelocytic leukemia (APL). Despite the long wait for an oral arsenic drug, a commercially available agent, realgar–indigo naturalis formula (RIF), was not launched in China until 2009. Since then, over 5000 APL patients have been treated with oral RIF in China. Oral arsenic not only shows a clinical efficacy comparable to that of IV formulations but also displays a better safety profile, improved quality of life, and lower medical costs for patients. The promising results promote incorporating an outpatient postremission therapy model into clinical practice for both low-risk and high-risk APL patients in China. In this review, we discuss the evolution of oral arsenic RIF in the treatment of APL, with a special focus on how to address the related complications during induction therapy.
The effect of social connectedness on consumer adoption of social commerce in apparel shopping
Authors: Cho Eunjoo , Son Jihyeong 
Published: May 2019

AbstractThe purpose of this study is to examine the effect of social connectedness on social media users’ attitudes and intentions towards adopting social commerce in the technology acceptance model (TAM). Data collected from young adult social media users (n = 446) in the US support the proposed model. A structural equation model shows that social connectedness positively influences social media users’ perceptions of ease of use, usefulness, and enjoyment, which in turn, influence their attitudes and intentions towards adopting social commerce in apparel shopping. The impact of social connectedness is stronger on perceived ease of use than other TAM variables. Perceived enjoyment has the strongest impact on attitudes, and attitudes strongly influence consumer intentions for adopting social commerce for apparel purchases. Results of this study reveal that social connectedness enhances social media users’ perceptions of social commerce and positively leads to the adoption of social commerce in apparel shopping. Findings indicate that social connectedness has an indirect effect on attitudes towards social commerce through utilitarian (i.e., ease of use and usefulness) and hedonic (i.e., enjoyment) perceptions of social commerce. These findings highlight the importance of social connectedness through utilitarian and hedonic perceptions in enhancing consumers’ adoption of social commerce for purchasing apparel products.
Determining the Cancer Diagnostic Interval Using Administrative Health Care Data in a Breast Cancer Cohort
Authors: Groome Patti A. , Webber Colleen , Whitehead Marlo , Moineddin Rahim , Grunfeld Eva , Eisen Andrea , Gilbert Julie , Holloway Claire , Irish Jonathan C. , Langley Hugh 
Published: May 2019

PURPOSE Population-based administrative health care data could be a valuable resource with which to study the cancer diagnostic interval. The objective of the current study was to determine the first encounter in the diagnostic interval and compute that interval in a cohort of patients with breast cancer using an empirical approach. METHODS This is a retrospective cohort study of patients with breast cancer diagnosed in Ontario, Canada, between 2007 and 2015. We used cancer registry, physician claims, hospital discharge, and emergency department visit data to identify and categorize cancer-related encounters that were more common in the three months before diagnosis. We used statistical control charts to define lookback periods for each encounter category. We identified the earliest cancer-related encounter that marked the start of the diagnostic interval. The end of the interval was the cancer diagnosis date. RESULTS The final cohort included 69,717 patients with breast cancer. We identified an initial encounter in 97.8% of patients. Median diagnostic interval was 36 days (interquartile range [IQR], 19 to 71 days). Median interval decreased with increasing stage at diagnosis and varied across initial encounter categories, from 9 days (IQR, 1 to 35 days) for encounters with other cancer as the diagnosis to 231 days (IQR 77 to 311 days) for encounters with cyst aspiration or drainage as the procedure. CONCLUSION Diagnostic interval research can inform early detection guidelines and assess the success of diagnostic assessment programs. Use of administrative data for this purpose is a powerful tool for improving diagnostic processes at the population level.
Improved Interpretability of Machine Learning Model Using Unsupervised Clustering: Predicting Time to First Treatment in Chronic Lymphocytic Leukemia
Authors: Chen David , Goyal Gaurav , Go Ronald S. , Parikh Sameer A. , Ngufor Che G. 
Published: May 2019

PURPOSE Time to event is an important aspect of clinical decision making. This is particularly true when diseases have highly heterogeneous presentations and prognoses, as in chronic lymphocytic lymphoma (CLL). Although machine learning methods can readily learn complex nonlinear relationships, many methods are criticized as inadequate because of limited interpretability. We propose using unsupervised clustering of the continuous output of machine learning models to provide discrete risk stratification for predicting time to first treatment in a cohort of patients with CLL. PATIENTS AND METHODS A total of 737 treatment-naïve patients with CLL diagnosed at Mayo Clinic were included in this study. We compared predictive abilities for two survival models (Cox proportional hazards and random survival forest) and four classification methods (logistic regression, support vector machines, random forest, and gradient boosting machine). Probability of treatment was then stratified. RESULTS Machine learning methods did not yield significantly more accurate predictions of time to first treatment. However, automated risk stratification provided by clustering was able to better differentiate patients who were at risk for treatment within 1 year than models developed using standard survival analysis techniques. CONCLUSION Clustering the posterior probabilities of machine learning models provides a way to better interpret machine learning models.
Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study
Authors: Barrington Sally F. , Phillips Elizabeth H. , Counsell Nicholas , Hancock Barry , Pettengell Ruth , Johnson Peter , Townsend William , Culligan Dominic , Popova Bilyana , Clifton-Hadley Laura , McMillan Andrew , Hoskin Peter , O’Doherty Michael J. , Illidge Tim , Radford John 
Published: May 2019

PURPOSE Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) –adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes. PATIENTS AND METHODS Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS). RESULTS High PET score was associated with inferior EFS, before ( P < .001) and after adjustment ( P = .01) for baseline risk stratification. Only patients with a postchemotherapy PET score of 5 (uptake ≥ three times maximum liver uptake) had an increased risk of progression or HL-related death (hazard ratio, 9.4 v score of 3; 95% CI, 2.8 to 31.3 and hazard ratio, 6.7 v score of 4; 95% CI, 1.4 to 31.7). Patients with a PET score of 5 also had inferior progression-free and overall survival. There was no association between European Organisation for Research and Treatment of Cancer or German Hodgkin Study Group risk group and EFS, before or after adjusting for PET score (all P > .4). CONCLUSION In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL.
WITHDRAWN: GLP-1 Has an Anti-Inflammatory Effect on Adipose Tissue Expression of Cytokines, Chemokines, and Receptors in Obese Women
Authors: Manning P J , Dixit P , Satthenapalli V R , Katare R , Sutherland W H F 
Published: May 2019

Abstract
The above-named article by Manning PJ, Dixit P, Satthenapalli VR, Katare R, and Sutherland WHF (J Clin Endocrinol Metab. [published online ahead of print 21 May 2019]; doi: 10.1210/jc.2018-00197) has been withdrawn by the authors.
The authors report, “The reason for this decision is that the statistical methodology we used did not adequately limit the impact of outlier data points on our findings. This was evident after reanalysis of the data using a different method.”
doi: 10.1210/jc.2019-01393
Comprehensive Analysis of Circulating miRNAs in the Plasma of Patients With Pituitary Adenomas
Authors: Németh Kinga , Darvasi Ottó , Likó István , Szücs Nikolette , Czirják Sándor , Reiniger Lilla , Szabó Borbála , Krokker Lilla , Pállinger Éva , Igaz Péter , Patócs Attila , Butz Henriett 
Published: May 2019

Abstract

Background
Circulating miRNAs in pituitary adenomas would improve patient care, especially as minimally invasive biomarkers of tumor recurrence and progression in nonfunctioning adenoma cases.

Aim
Our aim was to investigate plasma miRNA profiles in patients with pituitary adenomas.

Materials and Methods
A total of 149 plasma and extracellular vesicle (preoperative, early postoperative, and late postoperative) samples were collected from 45 patients with pituitary adenomas. Adenomas were characterized on the basis of anterior pituitary hormones and transcription factors by immunostaining. miRNA next-generation sequencing was performed on 36 samples (discovery set). Individual TaqMan assays were used for validation on an extended sample set. Pituitary adenoma tissue miRNAs were evaluated by TaqMan array and data in the literature.

Results
Global downregulation of miRNA expression was observed in plasma samples of pituitary adenomas compared with normal samples. Expression of 29 miRNAs and isomiR variants were able to distinguish preoperative plasma samples from normal controls. miRNAs with altered expression in both plasma and different adenoma tissues were identified. Three, seven, and 66 miRNAs expressed differentially between preoperative and postoperative plasma samples in GH-secreting, FSH/LH+, and hormone-immunonegative groups, respectively. miR‒143-3p was downregulated in late postoperative but not in early postoperative plasma samples compared with preoperative ones exclusively in FSH/LH+ adenomas. The plasma level of miR‒143-3p discriminated these samples with 81.8% sensitivity and 72.3% specificity (area under the curve = 0.79; P = 0.02).

Conclusions
Differentially expressed miRNAs in pituitary adenoma tissues have low abundance in plasma, minimizing their role as biomarkers. Plasma miR‒143-3p level decreased in patients with FSH/LH+ adenomas, indicating successful surgery, but its application for evaluating tumor recurrence needs further investigation.
Unique Inflammatory Changes in Exocrine and Endocrine Pancreas in Enterovirus-Induced Fulminant Type 1 Diabetes
Authors: Takita Mikako , Jimbo Erika , Fukui Tomoyasu , Aida Kaoru , Shimada Akira , Oikawa Yoichi , Yagihashi Soroku , Miura Junnosuke , Babazono Tetsuya , Kobayashi Tetsuro 
Published: May 2019

Abstract

Context
There are scant reports on the pathological changes of the exocrine and endocrine pancreas in fulminant type 1 diabetes mellitus (FT1DM).

Objective
To clarify the distinct pathological changes in the exocrine as well as the endocrine pancreas shortly after onset of diabetes in FT1DM.

Design
The exocrine and endocrine pancreases of 3 patients with FT1DM and 17 nondiabetic controls were immunohistochemically examined for islet and exocrine tissue inflammation, infiltrating mononuclear cell (MNC) CD subtype, enterovirus capsid protein 1 (VP1) localization, and CXC chemokine ligand 10 (CXCL10) and CXC chemokine receptor 3 (CXCR3) expressions.

Results
The median frequency of insulitis in the 3 FT1DM pancreases was 60%. In the nondiabetic control pancreases, no insulitis was observed. In the islets of FT1DM, the numbers of CD45+, CD3+, CD8+, CD68+, and CD11c+ MNCs were significantly higher than those of the control group. In the exocrine pancreas of FT1DM, the numbers of CD3+ T cells, CD8+ T cells, CD68+ macrophages, and CD11c+ dendritic cells were significantly higher than those of the control group. Infiltrating CD8+ T cells, CD68+ macrophages, and CD11c+ dendritic cells were observed around exocrine acinar cells in FT1DM. There was a close association between VP1 and CXCL10 expression in pancreatic exocrine ductal cells and acinar cells as well as islet cells in FT1DM. CXCL10+ exocrine cells were surrounded by CXCR3+ T cells.

Conclusion
The pathological findings suggested that suppression of the activated CXCL10–CXCR3 axis in the exocrine as well as the endocrine pancreas is a novel therapeutic target in FT1DM and possibly in enterovirus-associated acute-onset type 1 diabetes.
Insulin Stimulates GLUT4 Trafficking to the Syncytiotrophoblast Basal Plasma Membrane in the Human Placenta
Authors: James-Allan Laura B , Arbet Jaron , Teal Stephanie B , Powell Theresa L , Jansson Thomas 
Published: May 2019

AbstractContextPlacental transport capacity influences fetal glucose supply. The syncytiotrophoblast is the transporting epithelium in the human placenta, expressing glucose transporters (GLUTs) and insulin receptors (IRs) in its maternal-facing microvillous plasma membrane (MVM) and fetal-facing basal plasma membrane (BM).ObjectiveThe objectives of this study were to (i) determine the expression of the insulin-sensitive GLUT4 glucose transporter and IR in the syncytiotrophoblast plasma membranes across gestation in normal pregnancy and in pregnancies complicated by maternal obesity, and (ii) assess the effect of insulin on GLUT4 plasma membrane trafficking in human placental explants.Design, Setting, and ParticipantsPlacental tissue was collected across gestation from women with normal body mass index (BMI) and mothers with obesity with appropriate for gestational age and macrosomic infants. MVM and BM were isolated.Main Outcome MeasuresProtein expression of GLUT4, GLUT1, and IR were determined by western blot.ResultsGLUT4 was exclusively expressed in the BM, and IR was predominantly expressed in the MVM, with increasing expression across gestation. BM GLUT1 expression was increased and BM GLUT4 expression was decreased in women with obesity delivering macrosomic babies. In placental villous explants, incubation with insulin stimulated Akt (S473) phosphorylation (+76%, P = 0.0003, n = 13) independent of maternal BMI and increased BM GLUT4 protein expression (+77%, P = 0.0013, n = 7) in placentas from lean women but not women with obesity.ConclusionWe propose that maternal insulin stimulates placental glucose transport by promoting GLUT4 trafficking to the BM, which may enhance glucose transfer to the fetus in response to postprandial hyperinsulinemia in women with normal BMI.
Cortisol Secretion, Sensitivity, and Activity Are Associated With Hypertension in Postmenopausal Eucortisolemic Women
Authors: Chiodini Iacopo , Gaudio Agostino , Eller-Vainicher Cristina , Morelli Valentina , Aresta Carmen , Zhukouskaya Volha V , Merlotti Daniela , Orsi Emanuela , Barbieri Anna Maria , Fustinoni Silvia , Polledri Elisa , Gennari Luigi , Falchetti Alberto , Carnevale Vincenzo , Persani Luca , Scillitani Alfredo 
Published: May 2019

AbstractContextPrevious data suggest a possible association between type 2 diabetes (T2D) and fragility fractures (FX) with the degree of glucocorticoid suppressibility (GCS) and peripheral activation or sensitivity even in persons without hypercortisolemia.ObjectiveTo investigate whether the degree of GCS, GC sensitivity, and peripheral activation in persons without overt or mild hypercortisolism are associated with hypertension and with the number of the possible consequences of cortisol excess among patients with T2D, fragility FX, and hypertension.DesignCase-control study.SettingOutpatient clinic.PatientsA total of 216 postmenopausal women without hypercortisolemia (age, 50 to 80 years; 108 with hypertension); 68 and 99 patients had fragility FX and T2D, respectivelyMain outcome measuresWe assessed 24-hour urinary free cortisol (UFF), cortisone (UFE), their ratio (R-UFF/UFE), (F-1mgDST), and the GC receptor N363S single-nucleotide polymorphism (N363S-SNP).ResultsHypertension was associated with F-1 mgDST [odds ratio (OR), 3.3; 95% CI, 1.5 to 7.5; P = 0.004) and R-UFF/UFE (OR, 101.7; 95% CI, 2.6 to 4004.1; P = 0.014), regardless of age, body mass index, and presence of the N363S single nucleotide polymorphism and of T2D. The progressive increase in the number of possible consequences of cortisol excess was significantly associated with F-1mgDST levels (R2 = 0.125; P = 0.04), R-UFF/UFE (R2 = 0.46; P = 0.02), and the prevalence of N363S heterozygous variant (T = 0.46; P = 0.015), after adjustment for age.ConclusionsIn postmenopausal women without hypercortisolemia, hypertension is associated with GCS and GC peripheral activation. The number of possible consequences of cortisol excess (among patients with hypertension, T2D, and fragility FX) is associated with GCS, GC peripheral activation, and the prevalence of the N363S heterozygous variant.
Height Velocity Defined Metabolic Control in Children With Congenital Adrenal Hyperplasia Using Urinary Steroid GC-MS Analysis
Authors: Kamrath Clemens , Wettstaedt Lisa , Hartmann Michaela F , Wudy Stefan A 
Published: May 2019

Abstract

Background
Treatment of children with classic congenital adrenal hyperplasia (CAH) with glucocorticoids is a difficult balance between hypercortisolism and hyperandrogenism. Biochemical monitoring of treatment is not well defined. Achievement of a normal growth rate is the most important therapeutic goal.

Methods
We retrospectively evaluated 123 24-hour gas chromatography–mass spectrometry urinary steroid metabolome analyses together with their corresponding 1-year height velocity (HV) z scores in 63 prepubertal children aged 7.2 ± 1.6 years with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone.

Results
Multivariate linear mixed effects model analysis revealed a positive influence of CAH-specific z scores of summed urinary androgen metabolites (B = 0.97 ± 0.20, t = 4.87, P < 0.0001) and a negative influence of the cortisol metabolite tetrahydrocortisol (B = −1.75 ± 0.79, t = −2.20, P = 0.03) on HV z scores. Receiver operating characteristic analysis demonstrated that adrenal androgen excess, defined as HV >1.5 z, was best determined by a z score of all urinary androgen metabolites of >0.512 [accuracy, 66.2%; sensitivity, 57.1%; specificity, 74.4%; positive prediction value (PPV), 66.7%; negative prediction value (NPV), 65.9%]. Tetrahydrocortisol excretion >1480 µg/m2 BSA/d in conjunction with suppressed urinary androgen metabolites <0.163 z indicated overtreatment, defined as HV < −1.5 z (accuracy, 79.6%; sensitivity, 40.0%; specificity, 94.9%; PPV, 75.0%; NPV, 80.4%).

Conclusion
We established target values for urinary steroid metabolite excretions in children with CAH based on their growth rate. Urinary steroid metabolome analysis represents a highly suitable method for monitoring metabolic control in children with CAH.