bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoid Exposure and Fracture Risk in a Cohort of US Patients With Selected Conditions
Authors: Balasubramanian Akhila , Wade Sally W , Adler Robert A , Saag Kenneth , Pannacciulli Nicola , Curtis Jeffrey R 
Published: June 2018

ABSTRACT

The purpose of this work was to evaluate systemic glucocorticoid exposure and fracture among patients with newly-diagnosed inflammatory and immune-modulated conditions. Using administrative data, inception cohorts of rheumatoid arthritis (RA), asthma/chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), multiple sclerosis (MS), lupus, and sarcoidosis patients age 18 to 64 years with benefits coverage ≥12 months before diagnosis (January 1, 2005 to December 31, 2012) were followed to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IRs) per 1000 person-years were stratified by prednisone equivalent doses. Cox's proportional hazards models assessed risk by daily and cumulative dose, and by time since discontinuation, adjusted for baseline characteristics. Most patients (72% of 403,337) had glucocorticoid exposure; 52% were under age 50. IR (95% confidence interval [CI]) of any osteoporotic fracture was elevated at doses &lt;5 mg/day (IR 9.33; 95% CI, 7.29 to 11.77) versus 0 mg/day (IR 4.87 (95% CI, 4.72 to 5.02). Fracture rates were elevated at doses &lt;5 mg/day in patients &lt;50 years and those ≥50 years. In both age groups, fracture risk increased with increasing cumulative exposure, being approximately 2.5-fold higher at cumulative dose ≥5400 mg compared to &lt;675 mg. At ≥5400 mg, IR values were 5.69 (95% CI, 4.32 to 7.35) in patients &lt;50 years and 17.10 (95% CI, 14.97 to 19.46) in older patients. Fracture risk decreased significantly within months following glucocorticoid discontinuation. In patients with a variety of inflammatory conditions, fracture risk increased at doses as low as &lt;5 mg/day. Risk increased with increasing cumulative exposure and decreased soon following glucocorticoid discontinuation. Trends were similar between patients older and younger than 50 years. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
Number, Location, and Time Since Prior Fracture as Predictors of Future Fracture in the Elderly From the General Population
Authors: Beaudoin Claudia , Jean Sonia , Moore Lynne , Gamache Philippe , Bessette Louis , Ste-Marie Louis-Georges , Brown Jacques P 
Published: June 2018

ABSTRACT

Prognostic tools are available to identify individuals at high risk of osteoporotic fracture and to assist physicians in management decisions. Some authors have suggested improving the predictive ability of these tools by integrating characteristics of prior fractures (number, location, and time since prior fracture). The objectives of this study were: (1) to evaluate the sex- and age-specific associations between characteristics of prior fractures and the occurrence of a future osteoporotic fracture; and (2) to assess whether the characteristics of prior fractures could increase the discriminative ability of fracture risk prediction tools. A retrospective cohort study was conducted using administrative data. Men and women aged ≥66 years were selected and grouped into two cohorts. In cohort #1 (N = 759,500), history of fractures was measured between fiscal years 1997–1998 and 2003–2004, and future fractures were identified between 2004–2005 and 2013–2014. In cohort #2 (N = 807,245), history of fractures was measured between 1997–1998 and 2008–2009, and future fractures were identified between 2009–2010 and 2013–2014. Time until a first hip/femur and major osteoporotic fracture were the outcomes of interest. Adjusted HRs and c-indices were calculated. The association between history of prior fractures and future fracture was stronger in men and younger individuals. The locations of prior fractures associated with the lowest and highest risks were foot/ankle/tibia/fibula (maximal HR = 1.64) and hip/femur (maximal HR = 9.02), respectively. The association was stronger for recent fractures (maximal HR = 4.93), but was still significant for fractures occurring 10 to 12 years prior to the beginning of follow-up (maximal HR = 1.99). Characteristics of prior fractures did not increase model discrimination. Our study confirms that the risk of future fracture increases with the number of prior fractures, varies according to prior fracture location, and decreases with time since prior fracture. However, the integration of these characteristics in current fracture risk prediction tools is not required because it does not improve predictive ability. © 2018 American Society for Bone and Mineral Research.
Identification of an Epigenetic Signature of Osteoporosis in Blood DNA of Postmenopausal Women
Authors: Cheishvili David , Parashar Surabhi , Mahmood Niaz , Arakelian Ani , Kremer Richard , Goltzman David , Szyf Moshe , Rabbani Shafaat A 
Published: June 2018

ABSTRACT

Osteoporosis is one of the most common age-related progressive bone diseases in elderly people. Approximately one in three women and one in five men are predisposed to developing osteoporosis. In postmenopausal women, a reduction in BMD leads to an increased risk of fractures. In the current study, we delineated the DNA methylation signatures in whole blood samples of postmenopausal osteoporotic women. We obtained whole blood DNA from 22 normal women and 22 postmenopausal osteoporotic women (51 to 89 years old) from the Canadian Multicenter Osteoporosis Study (CaMos) cohort. These DNA samples were subjected to Illumina Infinium human methylation 450 K analysis. Illumina 450K raw data were analyzed by Genome Studio software. Analysis of the female participants with early and advanced osteoporosis resulted in the generation of a list of 1233 differentially methylated CpG sites when compared with age-matched normal women. T test, ANOVA, and post hoc statistical analyses were performed, and 77 significantly differentially methylated CpG sites were identified. From the 13 most significant genes, ZNF267, ABLIM2, RHOJ, CDKL5, and PDCD1 were selected for their potential role in bone biology. A weighted polygenic DNA methylation score of these genes predicted osteoporosis at an early stage with high sensitivity and specificity and correlated with measures of bone density. Pyrosequencing analysis of these genes was performed to validate the results obtained from Illumina 450 K methylation analysis. The current study provides proof of principal for the role of DNA methylation in osteoporosis. Using whole blood DNA methylation analysis, women at risk of developing osteoporosis can be identified before a diagnosis of osteoporosis is made using BMD as a screening method. Early diagnosis will help to select patients who might benefit from early therapeutic intervention. © 2018 American Society for Bone and Mineral Research.
A New Fracture Risk Assessment Tool (FREM) Based on Public Health Registries
Authors: Rubin Katrine Hass , Möller Sören , Holmberg Teresa , Bliddal Mette , Søndergaard Jens , Abrahamsen Bo 
Published: June 2018

ABSTRACT

Some conditions are already known to be associated with an increased risk of osteoporotic fractures. Other conditions may also be significant indicators of increased risk. The aim of the current study was to identify conditions for inclusion in a fracture prediction model (fracture risk evaluation model [FREM]) for automated case finding of high-risk individuals of hip or major osteoporotic fractures (MOFs). We included the total population of Denmark aged 45+ years (N = 2,495,339). All hospital diagnoses from 1998 to 2012 were used as possible conditions; the primary outcome was MOFs during 2013. Our cohort was split randomly 50/50 into a development and a validation dataset for deriving and validating the predictive model. We applied backward selection on ICD-10 codes (International Classification of Diseases and Related Health Problems, 10th Revision) by logistic regression to develop an age-adjusted and sex-stratified model. The FREM for MOFs included 38 and 43 risk factors for women and men, respectively. Testing FREM for MOFs in the validation cohort showed good accuracy; it produced receiver-operating characteristic (ROC) curves with an area under the ROC curve (AUC) of 0.750 (95% CI, 0.741 to 0.795) and 0.752 (95% CI, 0.743 to 0.761) for women and men, respectively. The FREM for hip fractures included 32 risk factors for both genders and showed an even higher accuracy in the validation cohort as AUCs of 0.874 (95% CI, 0.869 to 0.879) and 0.851 (95% CI, 0.841 to 0.861) for women and men were found, respectively. We have developed and tested a prediction model (FREM) for identifying men and women at high risk of MOFs or hip fractures by using solely existing administrative data. The FREM could be employed either at the point of care integrated into electronic patient record systems to alert physicians or deployed centrally in a national case-finding strategy where patients at high fracture risk could be invited to a focused DXA program. © 2018 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
Chiari I Malformation and Basilar Invagination in Fibrous Dysplasia: Prevalence, Mechanisms, and Clinical Implications
Authors: Pan Kristen S , Heiss John D , Brown Sydney M , Collins Michael T , Boyce Alison M 
Published: June 2018

ABSTRACT

Fibrous dysplasia (FD) is a mosaic disorder of benign fibro-osseous lesions, which may be associated with extraskeletal features as part of McCune-Albright syndrome (MAS). Cranial base abnormalities, including Chiari I malformation (CM1), in which the cerebellum extends below the foramen magnum, and secondary basilar invagination (BI), in which the odontoid prolapses into the posterior cranial fossa, are potentially serious complications of metabolic bone disorders. The purpose of this study was to determine the prevalence, natural history, and risk factors for CM1 and BI in patients with FD/MAS, and to determine mechanisms of cranial base deformities. Clinical and radiographic data from subjects in an FD/MAS natural history study were evaluated and compared to normal controls. In 158 patients with craniofacial FD, 10 (6.3%) cases of CM1 and 12 (7.6%) cases of BI were diagnosed. No cranial base abnormalities were identified in 10 control subjects. Craniomorphometric and volumetric analyses identified cranial constriction and cranial settling as the primary mechanisms of cranial base abnormalities, whereas intracranial hypertension was a contributing factor in a minority of subjects. Longitudinal analyses found progression of odontoid position with age, but no progression of tonsillar position. No endocrinopathies were associated with CM1. MAS endocrinopathies associated with BI included hyperthyroidism (odds ratio [OR] 12.0; 95% confidence interval [CI], 2.9 to 55.6; p &lt; 0.01), precocious puberty (OR 5.6; 95% CI, 1.2 to 26.0; p &lt; 0.05), and hypophosphatemia (OR 7.7; 95% CI, 1.9 to 27.0; p &lt; 0.01). Scoliosis was associated with both CM1 (OR 4.8; 95% CI, 1.1 to 22.8; p &lt; 0.05) and BI (OR = infinity; 95% CI, 4.7 to infinity; p &lt; 0.01). This study successfully characterized cranial base abnormalities in FD/MAS and the pathophysiological connection between them. These findings support routine screening for cranial base abnormalities in patients with craniofacial FD, as well as aggressive management of contributory risk factors. © 2018 American Society for Bone and Mineral Research.
Betulinic acid induces apoptosis and inhibits metastasis of human renal carcinoma cells in vitro and in vivo
Authors: Yang Chunming , Li Yan , Fu Liye , Jiang Tao , Meng Fandong 
Published: June 2018

AbstractBetulinic acid (BA), a natural product with a broad range of biological properties, is a lupane‐type pentacyclic triterpene isolated from various plants. Evidence is accumulating that BA is cytotoxic against multiple types of human cancer cells; however, its effects on renal carcinoma cells remain obscure. This study aimed to evaluate the anticancer activity of BA in human renal cancer cells in vitro and in vivo. In the current study, we found that BA inhibited renal cancer cell proliferation in a time‐dependent and dose‐dependent manner in vitro. Moreover, flow cytometry analysis revealed that BA affected the survival of renal cancer cells via the induction of apoptosis. Western blot analysis showed that the occurrence of apoptosis was associated with upregulation of Bcl2‐associated X protein and cleaved caspase‐3 and downregulation of B‐cell lymphoma 2 in renal cancer cells. Additionally, BA treatment augmented the production of reactive oxygen species and induced a significant loss of mitochondrial membrane potential in renal cancer cells, suggesting that BA may trigger apoptosis via the mitochondria‐mediated apoptotic pathway. Furthermore, the migrative and invasive capabilities of renal cancer cells were markedly repressed by BA treatment, which was related to upregulation of matrix metalloproteinase (MMP)2, MMP9, and vimentin, and downregulation of tissue inhibitor of metalloproteinase 2 and E‐cadherin. Notably, administration of BA retarded tumor growth in 786‐O–bearing mice in vivo. Taken together, our results demonstrated the anticancer potential of BA in human renal cancer cells by triggering apoptosis and suppressing migration and invasion.
Inhibition of maternally expressed gene 3 attenuated lipopolysaccharide‐induced apoptosis through sponging miR‐21 in renal tubular epithelial cells
Authors: Yang Ru , Liu Suxuan , Wen Jian , Xue Leixi , Zhang Yi , Yan Dong , Wang Guokun , Liu Zhichun 
Published: June 2018

AbstractAcute kidney injury (AKI) results in retention of waste products and dysregulation of extracellular volume and electrolytes, thus leading to a variety of complications. Recent advances in long noncoding RNAs suggested their close relationship with disease progression. In the current study, we investigated the role and mechanism of maternally expressed gene 3 (MEG3) on AKI pathogenesis. Real‐time polymerase chain reaction found that the expression of MEG3 was significantly increased in both kidney tissues and TKPTS cells induced by lipopolysaccharide (LPS). Western blot assay showed that the expression of apoptosis regulator Bcl‐2 was increased in MEG3‐inhibited TKPTS cells. Flow cytometry assay confirmed that LPS‐induced apoptosis was significantly attenuated after transfection of si‐MEG3. The RNAhybrid informatics algorithm predicted that there was a strong binding capacity between miR‐21 and MEG3. Luciferase reporter assay confirmed that MEG3 could function as a competing endogenous RNA of miR‐21. The antiapoptotic effect of si‐MEG3 could be neutralized by a miR‐21 inhibitor, demonstrated by the decreased expression of Bcl‐2 and flow cytometry results. Further investigation showed that programmed cell death protein 4 (PDCD4), a validated target of miR‐21, was highly expressed in both injured kidney tissues and LPS‐stimulated TKPTS cells. Meanwhile, the protein expression of PDCD4 was significantly reduced by inhibition of MEG3, but retrieved by coinhibition of MEG3 and miR‐21. In conclusion, our results demonstrated that inhibition of MEG3 could attenuate LPS‐induced apoptosis in TKPTS cells by regulating the miR‐21/PDCD4 pathway, suggesting that the MEG3/miR‐21/PDCD4 axis could be developed as a potential therapeutic target of AKI.
Induction of endoplasmic reticulum stress under endotoxin tolerance increases inflammatory responses and decreases Pseudomonas aeruginosa pneumonia
Authors: Kim Sena , Joe Yeonsoo , Park Se-Ung , Jeong Sun Oh , Kim Jin-Kyung , Park Seong Hoon , Pae Hyun-Ock , Surh Young-Joon , Shin Jaekyoon , Chung Hun Taeg 
Published: June 2018

Abstract
Endotoxin tolerance develops in the late phase of sepsis to protect cells from an early hyperinflammatory response. Nonetheless, because it induces an immunosuppressive environment, patients with sepsis in its late phase are affected by secondary infections, particularly bacterial pneumonia. Here, we showed that induction of endoplasmic reticulum (ER) stress leads to activation of glycogen synthase kinase 3β (GSK-3β) and X-box–binding protein 1 (XBP-1) in an inositol-requiring enzyme 1α (IRE1α)-mediated manner, which in turn restores the inflammatory response in endotoxin-tolerant macrophages. Animal and in vitro models of endotoxin tolerance were studied along with a model of LPS-induced endotoxin tolerance and a model of cecal ligation and puncture (CLP)-induced endotoxin tolerance. To detect the suppressed inflammatory response during endotoxin tolerance, inflammatory-cytokine expression levels were measured by quantitative real-time PCR and an ELISA. Our research revealed that induction of ER stress alleviated lung injury in a septic host infected with Pseudomonas aeruginosa via the activation of GSK-3β and XBP-1 in an IRE1α-mediated manner. Consequently, in the lungs of the septic host infected with P. aeruginosa, symptoms of pneumonia improved and the infecting bacteria were cleared. Thus, for septic patients, determination of immune status may guide the selection of appropriate immunomodulation, and ER stress can be a novel therapeutic strategy restoring the immune response in patients with endotoxin tolerance.
Induction of ER stress alleviates the lung injury of septic host infected P. aeruginosa via the activation of GSK-3β and XBP-1 in an IRE1α-mediated manner.
177Lu‐DOTMP induces G2/M cell cycle arrest and apoptosis in MG63 cell line
Authors: Kumar Chandan , Sharma Rohit , Das Tapas , Korde Aruna , Sarma Haladhar , Banerjee Sharmila , Dash Ashutosh 
Published: June 2018

Bone pain is the major manifestation of skeletal metastases. Although various treatment modalities are available for bone pain palliation, use of radiolabeled phosphonates is documented to be more effective. Among radionuclides available for this purpose, lutetium‐177 is gaining popularity due to its moderate beta energy, theranostic capability, favorable half‐life and convenient production logistics. 177Lu‐DOTMP has shown considerable promise as a metastatic bone pain palliating agent in preliminary evaluations and recent clinical studies. Therefore, an attempt was made to elucidate the possible mechanism of in vitro cell death induced by 177Lu‐DOTMP in MG63 cells. 177Lu‐DOTMP binding studies were carried out in mineralized bone of MG63 cells and around 50% binding was observed. Skeletons of Wistar rats showed 1.78 ± 0.5% IA/g at a 3 h time period which was almost constant up to 7 days. MG63 cells were incubated with 3.7 and 37 MBq of 177Lu‐DOTMP for 48 h prior to perform assays. An increase in the magnitude of cell toxicity and apoptotic DNA fragmentation was observed. Enhancement of G2/M phase cell cycle arrest and apoptosis were documented which were dose‐dependent. Thus, 177Lu‐DOTMP induced apoptotic cell death in MG63 cells, which might be one of the primary causes of pain relief in osseous metastases.
What Happens to Nutrition Intake in the Post–Intensive Care Unit Hospitalization Period? An Observational Cohort Study in Critically Ill Adults
Authors: Ridley Emma J. , Parke Rachael L. , Davies Andrew R. , Bailey Michael , Hodgson Carol , Deane Adam M. , McGuinness Shay , Cooper D. James 
Published: June 2018

AbstractBackgroundLittle is currently known about nutrition intake and energy requirements in the post–intensive care unit (ICU) hospitalization period in critically ill patients. We aimed to describe energy and protein intake, and determine the feasibility of measuring energy expenditure during the post‐ICU hospitalization period in critically ill adults.MethodsThis is a nested cohort study within a randomized controlled trial in critically ill patients. After discharge from ICU, energy and protein intake was quantified periodically and indirect calorimetry attempted. Data are presented as n (%), mean (SD), and median (interquartile range [IQR]).ResultsThirty‐two patients were studied in the post‐ICU hospitalization period, and 12 had indirect calorimetry. Mean age and BMI was 56 (18) years and 30 (8) kg/m2, respectively, 75% were male, and the median estimated energy and protein requirement were 2000 [1650–2550] kcal and 112 [84–129] g, respectively. Oral nutrition either alone (n = 124 days, 55%) or in combination with enteral nutrition (n = 96 days, 42%) was the predominant mode. Over 227 total days in the post‐ICU hospitalization period, a median [IQR] of 1238 [869–1813] kcal and 60 [35–89.5] g of protein was received from nutrition therapy. In the 12 patients who had indirect calorimetry, the median measured daily energy requirement was 1982 [1843–2345] kcal and daily energy deficit was −95 [−1050 to 347] kcal compared with the measured energy requirement.ConclusionsEnergy and protein intake in the post‐ICU hospitalization period was less than estimated and measured energy requirements. Oral nutrition provided alone was the most common mode of nutrition therapy.
Simultaneous screening and quantification of aminoglycoside antibiotics in honey using mixed‐mode liquid chromatography with quadrupole time‐of‐flight mass spectroscopy with heated electrospray ionization
Authors: Perkons Ingus , Pugajeva Iveta , Bartkevics Vadims 
Published: June 2018

AbstractAn analytical method based on liquid chromatography with quadrupole time‐of‐flight mass spectrometry has been developed for the simultaneous determination of six aminoglycoside antibiotics in honey. The sample pretreatment included extraction with aqueous trichloroacetic acid followed by solid‐phase extraction on Strata‐X polymeric reversed phase cartridges. Liquid chromatography separation was performed on an Obelisc R zwitterionic type mixed‐mode column. An ionBooster™ heated electrospray source was used and showed enhanced ionization efficiency in comparison to a conventional electrospray source. The observed signal enhancement ranged from 3‐ (neomycin) to 16‐fold (gentamicin C1). A data‐dependent mass spectrometry acquisition approach was employed, in which the full mass spectrometry dataset provided quantification and a scheduled precursor list was used to trigger an alternating data‐dependent acquisition of MS2 spectra for confirmation purposes. The described method was validated in accordance to CD 2002/657/EC. Decision limit values were in the range 11.2–33.6 ng/g, and satisfactory performance characteristics were obtained for recovery (65–76%), repeatability (3.8–7.3%), and linearity (≥0.995). The method was applied to the analysis of 49 real honey samples from the country of Georgia. Streptomycin was detected in two samples at 117 and 35 ng/g, and gentamicin C1 was detected in one sample at 32 ng/g.
Preparation, Post‐Modification, and Antibacterial Application of Gelatin Electrospun Membranes
Authors: Yu Xi , Wang Liang , Yang Pengfei , Xu Jinku , Moloney Mark G. , Liu Lian , Pan Yunlin , Wang Yongqing 
Published: June 2018

AbstractTwo bis(diaryldiazomethane)s substituted with amino groups are synthesized and used for the surface modification of membranes electrospun from gelatin. These membranes are then reacted with tolylene‐2,4‐diisocyanate to give urea‐functionalized materials, so that hydrogen peroxide can be reversibly bound onto their surface. These membranes are characterized by scanning electron microscopy, XPS, differential scanning calorimeter, and tensile test to show their surface properties and bulk properties. The surface modification with amino‐substituted diazomethanes and the subsequent cross‐linking reaction with diisocyanates contribute to high loadings of hydrogen peroxide, and greatly increase the antibacterial activity of gelatin‐derived membranes, which open a new horizon in the preparation of high loading antiseptic/antibacterial biomacromolecular surfaces and interfaces.