bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Serum hs‐CRP Levels With the Presence of Obesity, Diabetes Mellitus, and Other Cardiovascular Risk Factors
Authors: Ebrahimi Mahmoud , Heidari‐Bakavoli Ali Reza , Shoeibi Sara , Mirhafez Seyed Reza , Moohebati Mohsen , Esmaily Habibollah , Ghazavi Hamed , Saberi Karimian Maryam , Parizadeh Seyed Mohammad Reza , Mohammadi Maryam , Mohaddes Ardabili Hossein , Ferns Gordon A. , Ghayour‐Mobarhan Majid 
Published: February 2016

BackgroundDiabetes mellitus remains one of the major health problems of the 21st century and is associated with comorbidities including obesity and metabolic abnormalities. The study was conducted to evaluate serum high‐sensitivity C‐reactive protein (hs‐CRP) levels, as a marker of inflammation, in a large sample of Iranian population without a history of cardiovascular or inflammatory disease and cancer, and to relate this to fasting blood glucose (FBG) and the presence of diabetes mellitus.MethodsThe study consisted of 7,762 subjects divided into four groups—nonobese/nondiabetic, obese/nondiabetic, nonobese/diabetic and obese/diabetic—based on the BMI classification and their FBG. Anthropometric characteristics were measured and blood was collected for the evaluation of fasted lipid profile, FBG and serum hs‐CRP levels.ResultsSeveral clinical and biochemical characteristics were significantly different among the four groups: FBG, P < 0.001; total cholesterol (TC), P < 0.001; and triglyceride (TG), P < 0.001. The subjects with a serum hs‐CRP >3 mg/dl had higher TC (P < 0.001), low‐density lipoprotein cholesterol (LDL‐C, P < 0.001), TG (P < 0.001), fat percentage (P < 0.001), and systolic and diastolic blood pressure (P < 0.001) compared with subjects with a serum hs‐CRP <3 mg/dl. Multivariate analysis showed FBG, LDL‐C, and waist circumference (WC) associated with increased serum hs‐CRP levels (P < 0.001).ConclusionsFBG, LDL‐C, WC and gender are independently associated with serum hs‐CRP concentrations.
Dysfunction of subtelomeric methylation and telomere length in gallstone disease and gallbladder cancer patients of North Central India
Authors: Poojary Satish S , Mishra Gunja , Gupta Sanjiv , Shrivastav Braj Raj , Tiwari Pramod Kumar 
Published: February 2016

AbstractBackgroundTelomeres play an important role in cancer progression. Recently it has been shown that subtelomeric methylation negatively regulates telomere length in various diseases, including cancers. Here, we evaluated the influence of subtelomeric methylation in telomere dysfunction in gallbladder cancer (GBC), and whether this dysfunction is affected by the presence of gallstones.MethodsRelative telomere length and subtelomeric methylation levels were assessed using monochrome multiplex quantitative polymerase chain reaction and bisulfite sequencing, respectively, in different gallbladder tissue types including different grades of GBC, gallstones and adjacent non‐tumor.ResultsWe found telomere length to shorten significantly in overall GBC, but specifically in early grade cancer. We also found D4Z4 and DNF92 subtelomeric sequences to be hypermethylated and hypomethylated, respectively, in GBC; however, their methylation levels differed significantly, only in early grade cancer. We could not find any specific correlation between subtelomeric methylation and telomere length in GBC. Interestingly, telomere length and subtelomeric methylation differed significantly in GBC without gallstones but not in GBC with gallstones.ConclusionsThis study, thus, suggests that telomere dysfunction and changes in methylation levels may occur earlier in the progression of GBC, while the presence of gallstones may have no influence on telomere length as well as on methylation levels.
GCV for Tikhonov regularization via global Golub–Kahan decomposition
Authors: Fenu Caterina , Reichel Lothar , Rodriguez Giuseppe 
Published: February 2016

SummaryGeneralized cross validation is a popular approach to determining the regularization parameter in Tikhonov regularization. The regularization parameter is chosen by minimizing an expression, which is easy to evaluate for small‐scale problems, but prohibitively expensive to compute for large‐scale ones. This paper describes a novel method, based on Gauss‐type quadrature, for determining upper and lower bounds for the desired expression. These bounds are used to determine the regularization parameter for large‐scale problems. Computed examples illustrate the performance of the proposed method and demonstrate its competitiveness. Copyright © 2016 John Wiley & Sons, Ltd.
The clinical characteristics and hospital and post‐hospital survival of patients with the obesity hypoventilation syndrome: analysis of a large cohort
Authors: Marik P. E. , Chen C. 
Published: February 2016

SummaryObjectiveThe worldwide prevalence of obesity has reached epidemic proportions. Obesity hypoventilation syndrome (OHS) is a common yet largely undiagnosed and mistreated condition that likely carries a high mortality. The aim of this study was to determine the clinical characteristics, hospital outcome, outcome following hospital discharge and predictors of death in a large cohort of patients hospitalized with OHS. OHS is an important condition as many patients with this syndrome are misdiagnosed and receive inappropriate treatment.MethodsWe reviewed the electronic medical records of patients with unequivocal OHS admitted to a 525‐bed tertiary‐care teaching hospital over a 5‐year period. Demographic and clinical data as well as hospital disposition were recorded. In order to determine the patients' post‐discharge status, we linked our database to the database of death certificates of the State Registrar of Vital Records.ResultsWe identified 600 patients who met the inclusion criteria for this study. The patients' mean age was 58 ± 15 years with a mean body mass index of 48.2 ± 8.3 kg m−2; 64% were women. Thirty‐seven percent had a history of diabetes and 43% had been misdiagnosed as having chronic obstructive pulmonary disease, while none had been previously diagnosed with OHS. The most common admission diagnoses were respiratory failure, heart failure and sepsis. Ninety (15%) patients died during the index hospitalization. The patients' age, S‐creatinine, respiratory failure, sepsis and admission to the ICU were independent predictors of hospital mortality. The hospital survivors were followed for a mean of 1,174 ± 501 d (3.2 ± 1.3 years) from the index hospitalization. On follow‐up, 98 of the 510 (19%) hospital survivors died, with an overall cumulative mortality of 31.3%. The patients' age, S‐creatinine and admission to the ICU were independent predictors of post‐hospital mortality.ConclusionObesity hypoventilation syndrome is a common disease that is frequently misdiagnosed and mistreated and carries a 3‐year morality, which is significantly worse than that for most cancers combined. Considering the high mortality of this disease, all patients with a body mass index > 35 kg m−2 should be screened for OHS; those patients with both early and established OHS should be referred to a pulmonary and/or sleep specialist for evaluation for non‐invasive positive pressure ventilation, to a dietician for dietary counseling and lifestyle modification and to a bariatric surgeon for evaluation for bariatric surgery.
Morphometric human embryonic brain features according to developmental stage
Authors: Kobayashi Ami , Ishizu Koichi , Yamada Shigehito , Uwabe Chigako , Kose Katsumi , Takakuwa Tetsuya 
Published: February 2016

AbstractObjectivesThe present study investigated linear, area, and volume measurements of human brain samples according to Carnegie stages (CS) in an attempt to select suitable morphometric features that reflect embryonic development.MethodsUsing magnetic resonance imaging, we measured seven linear segments, three separate areas, and three regional volumes in 101 samples between CS13 and 23. Brain volume was determined via manual segmentation of the magnetic resonance image, whereby a formula was generated to estimate the volume of each linear measurement.ResultsAll parameters correlated with crown‐rump length. Bitemporal length and mesencephalic height increased linearly according to the CS, and a high correlation between bitemporal length and both whole‐brain (r = 0.98) and prosencephalon (r = 0.99) volumes was found when brain cavity volume was excluded.ConclusionMorphometric data related to human embryonic stages are valuable for correcting and comparing sonographic data. The present approach may contribute to improvements in prenatal diagnostics by enabling the selection of more suitable measurements during early embryonic stages. © 2016 John Wiley & Sons, Ltd.
Myocardial effects of fetal endoscopic tracheal occlusion in lambs with CDH
Authors: Zambaiti Elisa , Bussani Rossana , Calcaterra Valeria , Zandonà Lorenzo , Silvestri Furio , Peiró José Luis , Marotta Mario , Andreatta Erika , Pelizzo Gloria 
Published: February 2016

AbstractIntroductionFetal endoscopic tracheal occlusion in congenital diaphragmatic hernia (CDH) may reduce pulmonary hypertension and ameliorate postnatal cardiac output. The effects of sustained early (ETO) and late (LTO) tracheal occlusion on left ventricular (LV) cells in the lamb model have not been described.Materials and methodsCDH was created in lambs at 70 days' gestation (term = 145 days). ETO (85 days) or LTO (105 days) was sustained till term. After cesarean section (140 days) fetuses were euthanized and hearts harvested. LV myocardial cells were studied by histological and immunofluorescence (TGF‐beta 1, endothelin‐1) assays in CDH, ETO, LTO, and the control group (two subjects per group). Small intramyocardial arteries were evaluated by traditional histology.ResultsLV myocardial histology in CDH and LTO was similar. ETO‐induced LV myocardial cell enlargement and increased endothelin‐1 and TGF‐beta 1 staining; a weaker immunofluorescence signal was observed in LTO compared with ETO. Myocardial vascular wall thickness was greater in CDH than in controls. ETO was associated with a vascular wall thickness within the range of controls.ConclusionWith only two fetuses in each group, only an explorative evaluation was possible. The time point at which TO is performed seems to have an effect on cardiac morphology. Functional studies as well as confirmation in clinical samples are mandatory. © 2016 John Wiley & Sons, Ltd.
Structure of iron saturated C‐lobe of bovine lactoferrin at pH 6.8 indicates a weakening of iron coordination
Authors: Rastogi Nilisha , Singh Avinash , Singh Prashant K. , Tyagi Tapesh K. , Pandey Sada , Shin Kouichirou , Kaur Punit , Sharma Sujata , Singh Tej P. 
Published: February 2016

ABSTRACTThe bilobal lactoferrin is an approximately 76 kDa glycoprotein. It sequesters two Fe3+ ions together with two
ions. The C‐terminal half (residues, Tyr342–Arg689, C‐lobe) of bovine lactoferrin (BLF) (residues Ala1–Arg689) was prepared by limited proteolysis using trypsin. Both C‐lobe and intact BLF were saturated to 100%. Both of them retained up to nearly 85% of iron at pH 6.5. At pH 5.0, C‐lobe retained 75% of iron whereas intact protein could retain only slightly more than 60%. At pH 4.0 both contained 25% iron and at pH 2.0 they were left with iron concentration of only 10%. The structure of iron saturated C‐lobe was determined at 2.79 Å resolution and refined to Rcryst and Rfree factors of 0.205 and 0.273, respectively. The structure contains two crystallographically independent molecules, A and B. They were found to have identical structures with an r.m.s. shift of 0.5 Å for their Cα atoms. A high solvent content of 66% was observed in the crystals. The average value of an overall B‐factor was 68.0 Å2. The distance of 2.9 Å observed for the coordination bond between Fe3+ ion and Ne2 of His595 appeared to be considerably longer than the normally observed values of 1.9–2.2 Å. This indicated that the coordination bond involving His595 may be absent. Other coordination distances were observed in the range of 2.1–2.3 Å. Based on the present structure of iron saturated C‐lobe, it may be stated that His595 is the first residue to dissociate from ferric ion when the pH is lowered. Proteins 2016; 84:591–599. © 2016 Wiley Periodicals, Inc.
Structure prediction using sparse simulated NOE restraints with Rosetta in CASP11
Authors: Ovchinnikov Sergey , Park Hahnbeom , Kim David E. , Liu Yuan , Wang Ray Yu‐Ruei , Baker David 
Published: February 2016

ABSTRACTIn CASP11 we generated protein structure models using simulated ambiguous and unambiguous nuclear Overhauser effect (NOE) restraints with a two stage protocol. Low resolution models were generated guided by the unambiguous restraints using continuous chain folding for alpha and alpha‐beta proteins, and iterative annealing for all beta proteins to take advantage of the strand pairing information implicit in the restraints. The Rosetta fragment/model hybridization protocol was then used to recombine and regularize these models, and refine them in the Rosetta full atom energy function guided by both the unambiguous and the ambiguous restraints. Fifteen out of 19 targets were modeled with GDT‐TS quality scores greater than 60 for Model 1, significantly improving upon the non‐assisted predictions. Our results suggest that atomic level accuracy is achievable using sparse NOE data when there is at least one correctly assigned NOE for every residue. Proteins 2016; 84(Suppl 1):181–188. © 2016 Wiley Periodicals, Inc.
Molecular modeling of antibodies for the treatment of TNFα‐related immunological diseases
Authors: Pierri Ciro Leonardo , Bossis Fabrizio , Punzi Giuseppe , De Grassi Anna , Cetrone Michela , Parisi Giovanni , Tricarico Domenico 
Published: February 2016

AbstractTherapeutic monoclonal antibodies (mAbs) have high efficacy in treating TNFα‐related immunological diseases. Other than neutralizing TNFα, these IgG1 antibodies exert Fc receptor‐mediated effector functions such as the complement‐dependent cytotoxicity (CDC) and antibody‐dependent cell cytotoxicity (ADCC). The crystallizable fragment (Fc) of these IgG1 contains a single glycosylation site at Asn 297/300 that is essential for the CDC and ADCC. Glycosylated antibodies lacking core fucosylation showed an improved ADCC. However, no structural data are available concerning the ligand‐binding interaction of these mAbs used in TNFα‐related diseases and the role of the fucosylation. We therefore used comparative modeling for generating complete 3D mAb models that include the antigen‐binding fragment (Fab) portions of infliximab, complexed with TNFα (4G3Y.pdb), the Fc region of the human IGHG1 fucosylated (3SGJ) and afucosylated (3SGK) complexed with the Fc receptor subtype FcγRIIIA, and the Fc region of a murine immunoglobulin (1IGT). After few thousand steps of energy minimization on the resulting 3D mAb models, minimized final models were used to quantify interactions occurring between FcγRIIIA and the fucosylated/afucosylated Fc fragments. While fucosylation does not affect Fab‐TNFα interactions, we found that in the absence of fucosylation the Fc–mAb domain and FcγRIIIA are closer and new strong interactions are established between G129 of the receptor and S301 of the Chimera 2 Fc mAb; new polar interactions are also established between the Chimera 2 Fc residues Y299, N300, and S301 and the FcγRIIIA residues K128, G129, R130, and R155. These data help to explain the reduced ADCC observed in the fucosylated mAbs suggesting the specific AA residues involved in binding interactions.
Taurolidine and congeners activate hTRPA1 but not hTRPV1 channels and stimulate CGRP release from mouse tracheal sensory nerves
Authors: Kichko Tatjana I. , Pfirrmann Rolf W. , Reeh Peter W. 
Published: February 2016

AbstractTaurolidine has long been in clinical use as an antimicrobial irrigation that does not impede wound healing. It can even be administered intravenously (30 g/day) to treat sepsis or to exert newly recognized antineoplastic actions. Only one irritant effect is reported, that is, to temporarily induce burning pain of unknown origin when applied to body cavities or peripheral veins. The structure of the molecule suggested the chemoreceptor channel TRPA1 as a potential target, which was verified measuring stimulated CGRP release from sensory nerves of the isolated mouse trachea and calcium influx in hTRPA1‐transfected HEK293 cells. With both methods, the concentration–response relationship of taurolidine exceeded the threshold value below 500 μmol/L and 100 μmol/L, respectively, and reached saturation at 1 mmol/L. The clinical 2% taurolidine solution did not evoke greater or longer lasting responses. The reversible tracheal response was abolished in TRPA1−/− but retained in TRPV1−/− mice. Consistently, hTRPV1‐HEK showed no calcium influx as a response, likewise native HEK293 cells and hTRPA1‐HEK deprived of extracellular calcium did not respond to taurolidine 1 mmol/L. The metabolite taurultam and its oxathiazine derivative, expected to cause less burning pain, showed weak tracheal irritancy only at 10 mmol/L, acting also through hTRPA1 but not hTRPV1. In conclusion, taurolidine, its metabolite, and a novel derivative showed no unspecific cellular effects but selectively, concentration‐dependently and reversibly activated the irritant receptor TRPA1 in CGRP‐expressing, thus nociceptive, neurons. The clinical solution of 2% taurolidine (~70 mmol/L) can, thus, rightly be expected to cause transient burning pain and neurogenic inflammation.
Preclinical and translational evaluation of coagulation factor IXa as a novel therapeutic target
Authors: Ankrom Wendy , Wood Harold B. , Xu Jiayi , Geissler Wayne , Bateman Tom , Chatterjee Manash S. , Feng Kung‐I , Metzger Joseph M. , Strapps Walter R. , Tadin‐Strapps Marija , Seiffert Dietmar , Andre Patrick 
Published: February 2016

AbstractThe benefits of novel oral anticoagulants are hampered by bleeding. Since coagulation factor IX (fIX) lies upstream of fX in the coagulation cascade, and intermediate levels have been associated with reduced incidence of thrombotic events, we evaluated the viability of fIXa as an antithrombotic target. We applied translational pharmacokinetics/pharmacodynamics (PK/PD) principles to predict the therapeutic window (TW) associated with a selective small molecule inhibitor (SMi) of fIXa, compound 1 (CPD1, rat fIXa inhibition constant (Ki, 21 nmol/L) relative to clinically relevant exposures of apixaban (rat fXa Ki 4.3 nmol/L). Concentrations encompassing the minimal clinical plasma concentration (Cmin) of the 5 mg twice daily (BID) dose of apixaban were tested in rat arteriovenous shunt (AVS/thrombosis) and cuticle bleeding time (CBT) models. An Imax and a linear model were used to fit clot weight (CW) and CBT. The following differences in biology were observed: (1) antithrombotic activity and bleeding increased in parallel for apixaban, but to a lesser extent for CPD1 and (2) antithrombotic activity occurred at high (>99%) enzyme occupancy (EO) for fXa or moderate (>65% EO) for fIXa. translational PK/PD analysis indicated that noninferiority was observed for concentrations of CPD1 that provided between 86% and 96% EO and that superior TW existed between 86% and 90% EO. These findings were confirmed in a study comparing short interfering (si)RNA‐mediated knockdown (KD) modulation of fIX and fX mRNA. In summary, using principles of translational biology to relate preclinical markers of efficacy and safety to clinical doses of apixaban, we found that modulation of fIXa can be superior to apixaban.
ADME studies of [5‐3H]‐2′‐O‐methyluridine nucleoside in mice: a building block in siRNA therapeutics
Authors: Lozac'h Frederic , Christensen Jesper , Faller Thomas , van de Kerkhof Esther , Krauser Joel , Garnier Maxime , Litherland Karine , Catoire Alexandre , Natt Francois , Hunziker Jurg , Swart Piet 
Published: February 2016

AbstractThe chemical modification 2′‐O‐methyl of nucleosides is often used to increase siRNA stability towards nuclease activities. However, the metabolic fate of modified nucleosides remains unclear. Therefore, the aim of this study was to determine the mass balance, pharmacokinetic, and absorption, distribution, metabolism, and excretion (ADME)‐properties of tritium‐labeled 2′‐O‐methyluridine, following a single intravenous dose to male CD‐1 mice. The single intravenous administration of [5‐3H]‐2′‐O‐methyluridine was well tolerated in mice. Radioactivity was rapidly and widely distributed throughout the body and remained detectable in all tissues investigated throughout the observation period of 48 h. After an initial rapid decline, blood concentrations of total radiolabeled components declined at a much slower rate. [3H]‐2′‐O‐Methyluridine represented a minor component of the radioactivity in plasma (5.89% of [3H]‐AUC0‐48 h). Three [3H]‐2′‐O‐methyluridine metabolites namely uridine (M1), cytidine (M2), and uracil (M3) were the major circulating components representing 32.8%, 8.11%, and 23.6% of radioactivity area under the curve, respectively. The highest concentrations of total radiolabeled components and exposures were observed in kidney, spleen, pineal body, and lymph nodes. The mass balance, which is the sum of external recovery of radioactivity in excreta and remaining radioactivity in carcass and cage wash, was complete. Renal excretion accounted for about 52.7% of the dose with direct renal excretion of the parent in combination with metabolism to the endogenous compounds cytidine, uracil, cytosine, and cytidine.
Magnetic phase transitions in ZnO doped by transition metals
Authors: Yuldashev Shavkat , Yalishev Vadim , Yunusov Ziyodbek , Kwon Younghae , Kang Tae Won 
Published: February 2016

AbstractIn this work we present the results on experimental study of magnetic phase transitions in ZnO thin films doped by Mn and Co by using the thermal diffusivity and specific heat measurements. The inverted lambda‐shaped peaks observed in the temperature dependencies of the thermal diffusivity demonstrate the existence of the second order phase transitions in these samples. The magnetic entropy derived from the specific heat gives the number of magnetic ions involved in the magnetic ordering. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Evidence of exchange interaction of localized carriers and transition metals in diluted II‐VI nanostructures: ODMR study
Authors: Baranov P. G. , Romanov N. G. , Tolmachev D. O. , Gurin A. S. , Namozov B. R. , Kusrayev Yu. G. , Karczewski G. , Orlinskii S. , De Mello Donega C. , Schmidt J. 
Published: February 2016

AbstractOptically detected magnetic resonance study of (CdMn)Te/(CdMg)Te quantum wells allowed to reveal the formation of exchange‐coupled complexes consisting of Mn ions and localized holes in quantum wells with excess hole concentration and the directional electron tunneling towards wider wells in multiple quantum well structures. The existence of a distribution of Mn‐hole complexes that differ in a number of Mn ions interacting with a localized hole is justified.In colloidal cobalt doped ZnO nanocrystals, several nm in diameter, the interaction between the magnetic ions and the shallow donor electron in the confined system of ZnO quantum dots has been revealed. Direct evidence of interaction of Co ions with the interstitial Li shallow donor in the ZnO nanocrystal core and hyperfine coupling with 1H in the quantum dot shell have been demonstrated. (© 2016 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)