bluuebunny/crossref_metadata_2025 huggingface dataset:
Reassessment of tigecycline bone concentrations in volunteers undergoing elective orthopedic procedures
Authors: Bhattacharya Indranil , Gotfried Mark H. , Ji Allena J. , Saunders James P. , Gourley Ian , Diehl Annette , Korth‐Bradley Joan M.
Published: October 2013

The goal of the this study was to re‐evaluate tigecycline bone concentrations in subjects undergoing elective orthopedic surgery, using multiple doses and a more robust bone assay than was used in a previous study. Each subject received three intravenous doses of tigecycline (one 100‐mg infusion followed by two 50‐mg infusions, each administered over 30 minutes). A single bone sample was collected from each subject at one of the following times: 1, 2, 4, 6, 8, or 12 hours after the third dose. Four blood samples were collected from each subject: before the first dose, before and after the third dose, and within 15 minutes of the collection time of the bone sample. Noncompartmental pharmacokinetic analysis serum and bone area under the curve for the given dose interval (AUCτ) values were 2,402 ng h/mL and 11,465 ng h/g, and maximum concentration (Cmax) values were 974 ng/mL and 2,262 ng/g, respectively. The bone to serum ratio calculated using the AUCτ values was 4.77, confirming tigecycline penetration into bone.
Short‐ and long‐term results of lateral pancreaticojejunostomy for chronic pancreatitis: a retrospective Japanese single‐center study
Authors: Sudo Takeshi , Murakami Yoshiaki , Uemura Kenichiro , Hashimoto Yasushi , Kondo Naru , Nakagawa Naoya , Sueda Taijiro
Published: October 2013

Background

The study aim was to determine the short‐ and long‐term results of lateral pancreaticojejunostomy for chronic pancreatitis at a single center in Japan.

Methods

The records of 64 consecutive patients were retrospectively reviewed. All patients underwent surgery at Hiroshima University Hospital between December 1996 and April 2013. Long‐term follow‐up was performed in 58 patients (91%) for a median period of 34 months.

Results

The 53 men (83%) and 11 women (17%) had a mean age of 55 years. The etiology of pancreatitis was chronic alcohol abuse in 44 patients (69%). The major indication for surgery was acute pancreatitis exacerbation (80%). There was no postoperative mortality. Postoperative morbidity occurred in 21 patients (33%), with severe complications requiring non‐surgical intervention in four (6%). The percentage of pain‐free patients after surgery was 91%, and further acute exacerbation was prevented in 95%. Four patients (7%) required subsequent surgery for pancreatitis‐related complications. Of the patients that completed follow‐up, 33 (57%) had diabetes mellitus, including 11 patients (19%) with new‐onset diabetes; 30 patients (56%) developed pancreatic exocrine insufficiency.

Conclusions

Full‐length lateral pancreaticojejunostomy is safe, feasible, and effective for managing chronic pancreatitis. The technique prevents further exacerbations and maintains appropriate pancreatic endocrine and exocrine function.
Diversity of HPV types in cancerous and pre‐cancerous penile lesions of South African men: Implications for future HPV vaccination strategies
Authors: Lebelo Ramokone L. , Boulet Gaëlle , Nkosi Cornelius M. , Bida Mechack N. , Bogers John‐Paul , Mphahlele M. Jeffrey
Published: October 2013

This study reports the detection of HPV types from cancerous and pre‐cancerous penile lesions that were diagnosed histologically. Sixty‐six (22 pre‐cancerous and 44 cancerous lesions) tissue biopsies, received between 2004 and 2011 by the Anatomical Pathology Department at Dr. George Mukhari Hospital were selected for this study. Total DNA was extracted and genotyped using type specific real‐time quantitative polymerase chain reaction (qPCR) for 18 HPV types. Of 66 samples, only 51 were included in the analysis. Overall, HPV 11 (50.9%) and HPV 16 (49.1%) showed almost similar incidence in the study patients. In pre‐cancerous lesions, HPV 11 was more frequent (80.0%), followed by HPV 31 and HPV 16 at 25.0% each and other HPV types included 35 (15.0%), 59 (15.0%), 53 (10.0%), 33 (10.0%), 18 (5.0%), 51 (5.0%), 52 (5.0%), 56 (5.0%), and 67 (5.0%). For cancerous lesions, HPV 16 was the most detected (62.9%), followed by HPV 11 (34.3%), and other HPV types included 18 (11.4%), 33 (5.7%), 39 (5.7%), 45 (5.7%), 66 (5.7%), 52 (2.9%), 58 (2.9%), 6 (2.9%), and 67 (2.9%). Several lesions demonstrated multiple HPV infections, ranging from two to six different types in one lesion. The study showed high diversity of HPV types in cancerous and pre‐cancerous lesions of South African males with the most frequent being HPV types 11 and 16. The data suggest that boys could directly benefit from vaccination as they are exposed to variety of HPV types as early as 10 years of age in Africa. J. Med. Virol. 86:257–265, 2014. © 2013 Wiley Periodicals, Inc.
Evolutionary dynamics of HBV‐D1 genotype epidemic in Turkey
Authors: Ciccozzi Massimo , Ciccaglione Anna Rita , Lo Presti Alessandra , Equestre Michele , Cella Eleonora , Ebranati Erika , Gabanelli Elena , Villano Umbertina , Bruni Roberto , Yalcinkaya Tulay , Tanzi Elisabetta , Zehender Gianguglielmo
Published: October 2013

Hepatitis B virus (HBV), is the leading cause of liver diseases infecting an estimated 240 million persons worldwide. The HBV prevalence rates are variables between different countries, with an high level of endemicity in the south‐eastern part of Europe. Seven main HBV‐D subgenotypes have been described until now (D1–D7). Turkey, seems to have played an important role in the penetration of HBV‐D1 in the Mediterranean area. The importance of Turkey in the European epidemiology of HBV is also suggested by the observation that the highest spread of HBV infection in the Continent are reported in Turkey with Romania, Bulgaria, Greece, Albania and some southern regions of Italy. In this paper the molecular epidemiology and the epidemiological history of HBV‐D in Turkey was studied, by characterizing 34 new Turkish isolates and performing a phylogeographic reconstruction. By using a phylodynamic and phylogeographic Bayesian approach, the analysis suggested that HBV‐D1 originated in Turkey about in the early 1940s. The large prevalence of D1 in comparison to the other subgenotypes in Turkey confirms the importance of this Country as epidemiological reservoir of HBV‐D1 dispersion. The phylogeny suggests that after each initial introduction of the virus in a specific population, separate transmission clusters have been evolving along independent phylogenetic lineages. Better characterization and continuous monitoring of such groups are going to be crucial to understand in detail the epidemiology of HBV‐D1 subgenotype in Turkey and to assess the efficacy of prevention, vaccination and therapy in controlling the epidemic. J. Med. Virol. 86:109–116, 2014. © 2013 Wiley Periodicals, Inc.
Distribution of human papillomavirus genotypes, assessment of HPV 16 and 18 viral load and anal related lesions in HIV positive patients: A cross‐sectional analysis
Authors: Tamalet Catherine , Obry‐Roguet Veronique , Ressiot Emmanuelle , Bregigeon Sylvie , Del Grande Jean , Poizot‐Martin Isabelle
Published: October 2013

Natural history of anal intraepithelial neoplasia and anal cancer is not fully understood. Factors associated with cytological abnormalities and predictors of progression to high‐grade anal intraepithelial neoplasia still deserve investigation. The aim of this cross‐sectional study was to assess the prevalence of HPV types, the relationship between HPV genotypes, HPV 16/18 viral load and cytological abnormalities in male and female HIV‐infected patients. One hundred and twenty‐two (72.6%) patients were infected with HPV, 75 (61%) had multiple HPV infection, and 94 (77%) had high‐risk HPV infection. The most frequently identified HPV types were HPV 16 (64%), HPV 6 (39%), HPV 18 (31%), HPV 53 (14.7%), HPV 33 (10.6%), HPV 11 (8.2%), HPV 70 (5.7%), and HPV 61 (4.9%). The HPV types which were most frequently found in combination were HPV 6 + 16 (9.8%), 6 + 16 + 18 (8.2%), 16 + 18 (6.6%), 6 + 18 (4.9%), 16 + 33 (3.3%), 16 + 53 (3.3%). Median HPV16 and 18 viral loads were 6.1 log10 copies/106 cells [IQR 5.0–7.3] and 6.1 log10 copies/106 cells [IQR 5.7–6.0], respectively. Male gender (P = 0.03, OR: 1.2 [1.0–1.4]) and homo/bisexual transmission routes (P = 0.044, OR: 1.4 [1.0–1.9]) were associated with HPV 16 infection. An HPV 16 viral load cut‐off ≥5.3 log10 copies/106 cells and a CD4+ cell count ≤200/µl were independent factors associated with abnormal cytology. In the absence of national consensus guidelines, a strict regular follow‐up at shorter intervals is recommended for HIV‐infected patients with abnormal cytology, especially low grade squamous intraepithelial lesions, an HPV 16 viral load ≥5.3 log/106 cells and a CD4+ cell count ≤200/µl. J. Med. Virol. 86:419–425, 2014. © 2013 Wiley Periodicals, Inc.
A non‐conforming multi‐element DGTD method for the simulation of human exposure to electromagnetic waves
Authors: Durochat Clément , Lanteri Stéphane , Léger Raphaël
Published: October 2013

The great majority of numerical calculations of electric energy deposition in human tissues exposed to microwaves are performed using the finite‐difference time‐domain (FDTD) method and voxel‐based geometrical models of the tissues. The straightforward implementation of the method and its computational efficiency are among the main reasons for FDTD being currently the leading method for numerical assessment of human exposure to electromagnetic waves. However, the rather difficult departure from the commonly used Cartesian grid and cell size limitations regarding the discretization of very detailed structures of human tissues are often recognized as the main weaknesses of the FDTD method in this application context. In particular, interfaces between tissues where sharp gradients of the electromagnetic field may occur are hardly modeled rigorously in these studies (this is generally referred as the staircasing effect). We present here an alternative numerical dosimetry methodology that is based on a DGTD method designed to work with non‐conforming cubic‐tetrahedral meshes for more flexibility in the discretization process of complex propagation scenes. For example, in the context of head tissues exposure to mobile phone radiation, the computation domain is divided in two regions: an unstructured tetrahedral mesh‐based heterogeneous model of head tissues and an orthogonal cartesian mesh of the vacuum part of the propagation domain. We present numerical results comparing this approach with strategies based on fully Cartesian and fully tetrahedral meshes of the whole computational domain. Copyright © 2013 John Wiley & Sons, Ltd.
Governing plant development in barley (Hordeum vulgare L.): relation to protein composition and breakdown rates of protein polymers during malting
Authors: Malik Ali H , Holm Lena , Johansson Eva
Published: October 2013

BACKGROUND

This study aimed at investigating opportunities to manipulate development rhythms of barley (Hordeum vulgare L.) and to relate such rhythms to protein concentration, composition and breakdown during malting. The spring malting barley cultivar Tipple was grown in daylight chambers at various sowing dates, nitrogen application timings and temperature levels to govern the development rhythms.

RESULTS

Extensive options were shown to be available for manipulating the plant development rhythm of spring malting barley. Individually, sowing times, N application timings and temperature levels were negatively correlated with the development time. The combination of early sowing and 100% N application at sowing/low temperature during the grain maturation period (GMP) resulted in a long development time before and after anthesis. The combination of late sowing and 50% N at sowing/high temperature during GMP led to short development time before and after anthesis. The highest protein concentration and lowest percentage of sodium dodecyl sulfate‐unextractable polymeric proteins in total polymeric proteins were found to be associated with short development time. Extensive degradation of proteins during malting was the result of short development time as compared to long development time.

CONCLUSION

The development rhythm of barley affects protein concentration, composition and breakdown and might thus not only influence the end‐use quality of barley but also the next generation of plants. © 2013 Society of Chemical Industry
A systematic review of Gymnema sylvestre in obesity and diabetes management
Authors: Pothuraju Ramesh , Sharma Raj Kumar , Chagalamarri Jayasimha , Jangra Surender , Kumar Kavadi Praveen
Published: October 2013

The prevalence of obesity is associated with many health‐related problems. Currently, more than 300 million people are considered to be obese. According to the World Health Organization (WHO), by 2030, 87 and 439 million people will be affected in India and the world, respectively. Today, herbal medicines are gaining interest in the treatment of obesity and diabetes, because of their minimal side effects. Gymnemic acid – an active component isolated from Gymnema sylvestre – has anti‐obesity and antidiabetic properties, decreases body weight and also inhibits glucose absorption. Several components extracted from Gymnema prevent the accumulation of triglycerides in muscle and liver, and also decrease fatty acid accumulation in the circulation. In this paper, an attempt has been made to review the effects of various extracts from Gymnema sylvestre in the regulation of carbohydrate and lipid metabolism in both animal and clinical studies. © 2013 Society of Chemical Industry
Prognostic role of internal jugular vein preservation in neck dissection for head and neck cancer
Authors: Gallo O. , Santoro R. , Fiorini F.R. , MecCariello G. , Laganà R.M. , Paiar F. , Maio V.
Published: October 2013

Background and Objectives

Sparing internal jugular vein (IJV) in neck dissection for head and neck cancer is controversial. We aimed at evaluating the prognostic impact of IJV preservation.

Methods

We examined 206 files of head and neck cancer patients who underwent radical or modified radical neck dissection at the Otolaryngology University of Florence. The site of primary tumor was larynx and hypopharynx in 44.66%, oropharynx in 25.24%, oral cavity in 23.3%, unknown in 4.85%, salivary glands and rhinopharynx in 0.97%. In 60.19% the IJV was resected, in 39.81% preserved. Prognostic impact of IJV preservation was assessed by Kaplan–Meier and multivariate analysis.

Results

Neck recurrence occurred in 25.2%: the IJV was resected in 42.31%, in 57.69% preserved (P = 0.02). At multivariate analysis, neck recurrence resulted significantly associated to extracapsular spread (ECS) (P = 0.009), IJV preservation (P = 0.01), positive margins (P = 0.02). In ECS positive patients, a higher risk of neck recurrence was documented for IJV preservation (P = 0.012). A worse prognosis was observed for patients with IJV spared (P = 0.06).

Conclusions

IJV preservation is associated with an increased risk of neck failure and a worse outcome, mainly in patients with ECS of nodes. J. Surg. Oncol. 2013; 108:579–583. © 2013 Wiley Periodicals, Inc.
Peritoneal debulking/intraperitoneal chemotherapy—non‐sarcoma
Authors: Kelly Kaitlyn J. , Nash Garrett M.
Published: October 2013

The combination of cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) is widely practiced for appendiceal, colorectal, gastric, and ovarian cancers with isolated peritoneal metastasis as well as for primary peritoneal cancer. The aim of this report is to explain the rationale and available techniques for CRS and IPC, and to highlight disease‐specific considerations that should be taken into account when evaluating potential candidates for CRS and IPC. J. Surg. Oncol. 2014 109:14–22. © 2013 Wiley Periodicals, Inc.
Risk of biochemical recurrence and positive surgical margins in patients with pT2 prostate cancer undergoing radical prostatectomy
Authors: Røder Martin Andreas , Thomsen Frederik Birkebæk , Berg Kasper Drimer , Christensen Ib Jarle , Brasso Klaus , Vainer Ben , Iversen Peter
Published: October 2013

Background and Objective

To investigate risk factors associated with positive surgical margins (PSM) and biochemical recurrence (BR) in organ confined tumors (pT2) after radical prostatectomy (RP) for localized prostate cancer (PCa).

Methods

Between 1995 and 2011, 1,649 patients underwent RP at our institution. The study includes the 1,133 consecutive patients with pT2 tumors at final histopathology. Logistic regression analysis was used for risk of PSM. Risk of BR, defined as the first PSA ≥ 0.2 ng/ml, was analyzed with Kaplan–Meier and Cox regression analysis.

Results

Median follow‐up was 3.6 years (range: 0.5–15.5 years). In logistic regression, NS surgery was independently associated with an increased risk of pT2 PSM (OR = 1.68, 95% CI: 1.3–2.0, P = 0.01) relative to non‐NS surgery. NS surgery was not independently associated with BR but the interaction of PSM and NS surgery trended (P = 0.08) to increase the risk of BR compared to PSM and non‐NS surgery.

Conclusion

Several factors influence the risk of pT2 PSMs in radical prostatectomy. In our cohort pT2 PSM is associated with NS surgery and trend to increase risk of BR compared to non‐NS surgery. The optimal selection of candidates for NS surgery is still not clear. J. Surg. Oncol. 2014 109:132–138. © 2013 Wiley Periodicals, Inc.
Subgroups of patients with very large gastrointestinal stromal tumors with distinct prognoses: A multicenter study
Authors: Wada Noriko , Kurokawa Yukinori , Nishida Toshirou , Takahashi Tsuyoshi , Toyokawa Takahiro , Kusanagi Hiroshi , Hirota Seiichi , Tsujinaka Toshimasa , Mori Masaki , Doki Yuichiro
Published: October 2013

Background and Objectives

Any gastrointestinal stromal tumors (GISTs) larger than 10 cm are classified as “high risk” according to the modified National Institutes of Health consensus criteria. We conducted a multicenter study to identify a subgroup with moderate prognosis even within the “high‐risk” group.

Methods

We retrospectively collected data on 107 patients with tumors ≥10 cm from a multicenter database of GIST patients. Patients with macroscopic residual lesions or tumor rupture were excluded. The relationship between recurrence‐free survival (RFS) and clinicopathological factors was analyzed.

Results

The median tumor size and mitotic count were 12.5 cm and 8/50 HPF. The RFS rate was 58.5% at 3 years, 52.1% at 5 years. Only mitotic count was an independent prognostic factor of RFS in the multivariate analysis (P = 0.001). The hazard ratio for recurrence in the subgroup with mitotic count >5/50 HPF was 2.91 (95% confidence interval, 1.53 to 5.56). The subgroup with mitotic count ≤5/50 HPF showed significantly better RFS than the mitotic count >5/50 HPF subgroup (P < 0.001).

Conclusions

Mitotic count is closely associated with outcome in patients with large GISTs. This suggests that the subset of large GISTs with low mitotic counts may be considered as “intermediate‐risk” lesions. J. Surg. Oncol. 2014 109:67–70. © 2013 Wiley Periodicals, Inc.
Round window membrane vibration may increase the effect of intratympanic dexamethasone injection
Authors: Park Soon Hyung , Moon In Seok
Published: October 2013

Objectives/Hypothesis

We investigated whether the round window membrane (RWM) vibration can facilitate dexamethasone perfusion via the RWM in patients with sudden hearing loss.

Study Design

Prospective study.

Methods

We first performed an in vitro study using a semipermeable membrane. In the subsequent in vivo study, 20 mice were randomized into two groups: an intratympanic dexamethasone injection (ITDI)‐only group, and an ITDI with RWM vibration group. Concentration of dexamethasone was investigated using high performance liquid chromatography. Third, we performed a prospective clinical study. Fifty‐five refractory sudden hearing loss patients were divided into two groups: those who received ITDI only (n = 36) and those who received ITDI with RWM vibration (n = 19). Final hearing assessments were conducted 2 months after salvage treatment.

Results

In the in vitro study, the concentration of dexamethasone increased with vibration time with the peak concentration observed at 3 minutes of vibration. In the in vivo study, ITDI with RWM vibration resulted in a significantly higher perilymph concentration of dexamethasone (7.68 ± 3.13 µg/ml) than that in the ITDI‐only group (2.66 ± 1.73 µg/ml). In a clinical setting, the overall improvement in hearing was similar between the two groups. However, when we compared the speech discrimination score between the two groups, we found that the relative discrimination gain in the ITDI with RWM vibration group (18.11 ± 23.54%) was higher than that in the ITDI‐only group (7.00 ± 15.54%) (P = 0.042).

Conclusion

RWM vibration can enhance the effect of intratympanic dexamethasone injection and is a viable treatment option for sudden hearing loss.

Levels of Evidence

N/A. Laryngoscope, 124:1444–1451, 2014
trans‐10, cis‐12 conjugated linoleic acid enhances in vitro maturation of porcine oocytes
Authors: Jia Baoyu , Wu Guoquan , Fu Xiangwei , Mo Xianhong , Du Ming , Hou Yunpeng , Zhu Shien
Published: October 2013

The aim of this study was to determine the effects of trans‐10, cis‐12 conjugated linoleic acid (t10c12 CLA) supplementation on oocyte maturation and embryo development in pigs. Compared with the control, supplementation of 50 µM t10c12 CLA to in vitro maturation (IVM) medium significantly increased the proportion of oocytes at the metaphase‐II (MII) stage and subsequent parthenogenetic embryo development in terms of cleavage rate, blastocyst formation rate, and cell numbers in blastocysts. The t10c12 CLA‐treated oocytes resumed meiotic maturation and progressed to the MII stage significantly faster than those of control. The expression of phosphorylated mitogen‐activated protein kinase 3/1 (p‐MAPK3/1) and cyclooxygenase‐2 (COX2) in cumulus oocyte complexes (COCs) at 5, 10, and 22 hr of IVM were significantly increased in the t10c12 CLA‐treatment group. The level of p‐MAPK3/1 in t10c12 CLA‐treated MII oocytes was also higher (P < 0.05) than that of control. Moreover, t10c12 CLA supplementation partially overcame the negative effects of U0126 on cumulus expansion and nuclear maturation, and completely recovered COX2 protein levels in the presence of U0126. Treatment of COCs with NS398 also significantly suppressed cumulus expansion and nuclear maturation, which was overcome by t10c12 CLA. Yet, this simulatory effect of t10c12 CLA was blocked in the presence of both U0126 and NS398. The t10c12 CLA treatment significantly reduced reactive oxygen species level and increased glutathione concentrations in MII oocyte. In conclusion, supplementation of t10c12 CLA during porcine oocyte maturation exerts its beneficial effects on nuclear and cytoplasmic maturation, which contributes to enhancing subsequent embryo development. Mol. Reprod. Dev. 81: 20–30, 2014. © 2013 Wiley Periodicals, Inc.
Synthesis, characterization, AC conductivity, and diode properties of polyaniline–CaTiO3 composites
Authors: Roy Aashis S. , Hegde Shruti Gopalkrishna , Parveen Ameena
Published: October 2013

Polyaniline–CaTiO3 composites of different weight percentages were prepared by in situ polymerization. The prepared composites were characterized by Fourier transform infrared spectroscopy for structural studies, and a morphology analysis was carried out by scanning electron microscopy studies. Real and imaginary parts of the complex impedance were determined for given samples as a function of frequency. Current–voltage and capacitance–voltage measurements were also carried out. The carrier mobility μ values of neat polyaniline and polyaniline–CaTiO3 composites were found to be 5.37 × 10−3 and 2.73 × 10−2, respectively, and a significant enhancement, as compared with the reported data, was observed. Therefore, this study may provide a better route for technological applications in all fields in the near future and can also be represented by a pure electronic model. Copyright © 2013 John Wiley & Sons, Ltd.
Development of composites based on recycled polyethylene/sugarcane bagasse fibers
Authors: de Carvalho Neto Alberto Gomes Vieira , Ganzerli Thiago Amaral , Cardozo Adriano Luciano , Fávaro Silvia Luciana , Pereira Antonio Guilherme Basso , Girotto Emerson Marcelo , Radovanovic Eduardo
Published: October 2013

In this work, sugarcane bagasse fibers were used as filler in composites having recycled high‐density polyethylene (PEr) as matrix. Because of the poor interaction between fibers surface and the PEr, the surface of bagasse was chemically modified. This modification consists of washing with water at 80°C, a mercerization process using sodium hydroxide and acetylation reaction with acetic anhydride. The chemical modification was characterized by Fourier transform infrared–horizontal attenuated total reflectance (FTIR‐HATR) and 13C nuclear magnetic resonance spectroscopies (NMR), thermogravimetric analysis (TGA), and scanning electronic microscopy (SEM). The composites were prepared from modified and unmodified fibers into PEr matrix, containing 5, 10, and 20% (w/w) of fiber. The samples were processed by extrusion and molds were prepared by injection process in order to perform mechanical tests. These materials were analyzed by SEM, TGA, and the water uptake was evaluated. Also, their mechanical properties were analyzed. Morphological analysis indicated that the chemical modification of sugarcane bagasse increased the compatibility between matrix and reinforcement. Tensile, flexural, and impact tests showed that the mechanical properties of the composite were improved compared to PEr due to the presence of the fibers. POLYM. COMPOS., 35:768–774, 2014. © 2013 Society of Plastics Engineers
Assessment of reproducibility in depletion and enrichment workflows for plasma proteomics using label‐free quantitative data‐independent LC‐MS
Authors: Hakimi Amirmansoor , Auluck Janica , Jones George D. D. , Ng Leong L. , Jones Donald J. L.
Published: October 2013

Quantitation in plasma‐based proteomics necessitates the reproducible removal of highly abundant proteins to enable the less abundant proteins to be visible to the mass spectrometer. We have evaluated immunodepletion (proteoprep20) and enrichment (Bio‐Rad beads), as the current predominant approaches. Label‐free analysis offers an opportunity to estimate the effectiveness of this approach without incorporating chemical labels. Human plasma samples were used to quantitatively assess the reproducibility of these two methods using nano‐LC‐data‐independent acquisition MS. We have selected 18 candidate proteins and a comparison of both methodologies showed that both of the methods were reproducible and fell below 20% residual SD. With the same candidate proteins, individual inter‐day variability for the samples was also processed, allowing us to monitor instrument reproducibility. Overall, a total of 131 proteins were identified by both methods with 272 proteins identified by enrichment and 200 identified by immunodepletion. Reproducibility of measurements of the amount of protein in the processed sample for individual proteins is within analytically acceptable standards for both methodologies. This enables both methods to be used for biomarker studies. However, when sample is limited, enrichment is not suitable as larger volumes (>1.0 mL) are required. In experiments where sample is not limited then a greater number of proteins can be reliably identified using enrichment.
Molecular interaction networks for the analysis of human disease: Utility, limitations, and considerations
Authors: Schramm Sarah‐Jane , Jayaswal Vivek , Goel Apurv , Li Simone S. , Yang Yee Hwa , Mann Graham J. , Wilkins Marc R.
Published: October 2013

High‐throughput ‘‐omics’ data can be combined with large‐scale molecular interaction networks, for example, protein–protein interaction networks, to provide a unique framework for the investigation of human molecular biology. Interest in these integrative ‘‐omics’ methods is growing rapidly because of their potential to understand complexity and association with disease; such approaches have a focus on associations between phenotype and “network‐type.” The potential of this research is enticing, yet there remain a series of important considerations. Here, we discuss interaction data selection, data quality, the relative merits of using data from large high‐throughput studies versus a meta‐database of smaller literature‐curated studies, and possible issues of sociological or inspection bias in interaction data. Other work underway, especially international consortia to establish data formats, quality standards and address data redundancy, and the improvements these efforts are making to the field, is also evaluated. We present options for researchers intending to use large‐scale molecular interaction networks as a functional context for protein or gene expression data, including microRNAs, especially in the context of human disease.
The human oligodendrocyte proteome
Authors: Iwata Keiko , Café‐Mendes Cecilia C. , Schmitt Andrea , Steiner Johann , Manabe Takayuki , Matsuzaki Hideo , Falkai Peter , Turck Christoph W. , Martins‐de‐Souza Daniel
Published: October 2013

Myelination of the CNS is performed by oligodendrocytes (OLs), which have been implicated in brain disorders, such as multiple sclerosis and schizophrenia. We have used the human oligodendroglial cell line MO3.13 to establish an OL reference proteome database. Proteins were prefractionationated by SDS‐PAGE and after in‐gel digestion subjected to nanoflow LC‐MS analysis. Approximately 11 600 unique peptides were identified and, after stringent filtering, resulted in 2290 proteins representing nine distinct biological processes and various molecular classes and functions. OL‐specific proteins, such as myelin basic protein (MBP) and 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNP), as well as other proteins involved in multiple sclerosis and schizophrenia were also identified and are discussed. Proteins of this dataset have also been classified according to their chromosomal origin for providing useful data to the Chromosome‐centric Human Proteome Project (C‐HPP). Given the importance of OLs in the etiology of demyelinating and oligodendrogial disorders, the MO3.13 proteome database is a valuable data resource. The MS proteomics data have been deposited to the ProteomeXchange with identifier PXD000263 (http://proteomecentral.proteomexchange.org/dataset/PXD000263).
Proteomic strategy for probing complementary lethality of kinase inhibitors against pancreatic cancer
Authors: Lee Jin‐Gyun , McKinney Kimberly Q. , Mougeot Jean‐Luc , Bonkovsky Herbert L. , Hwang Sun‐Il
Published: October 2013

In the present study, proteomic analysis was performed to discover combinational molecular targets for therapy and chemoresistance by comparing differential protein expression from Panc‐1 cells treated with FDA‐approved drugs such as sunitinib, imatinib mesylate, dasatinib, and PD184352. A total of 4041 proteins were identified in the combined data from all of the treatment groups by nano‐electrospray ultra‐performance LC and MS/MS analysis. Most of the proteins with significant changes are involved in apoptosis, cytoskeletal remodeling, and epithelial‐to‐mesenchymal transition. These processes are associated with increased chemoresistance and progression of pancreatic cancer. Among the differentially expressed proteins, heme oxygenase‐1 (HO‐1) was found in the sunitinib and imatinib mesylate treatment groups, which possibly acts as a specific target for synthetic lethality in combinational treatment. HO‐1 was found to play a key role in sensitizing the chemoresistant Panc‐1 cell line to drug therapy. Viability was significantly decreased in Panc‐1 cells cotreated with sunitinib and imatinib mesylate at low doses, compared to those treated with sunitinib or imatinib mesylate alone. The results suggest that induction of chemosensitization by manipulating specific molecular targets can potentiate synergistic chemotherapeutic effects at lower, better tolerated doses, and in turn reduce the toxicity of multidrug treatment of pancreatic cancer.
Quantum chemical calculation of amino‐substituted but‐2‐yne dications: Distonic and gitonic character?
Authors: Kottmann Jakob , Wassiljew Olga , Drandarov Konstantin , Kantlehner Willi , Siehl Hans‐Ullrich
Published: October 2013

The tetrakis‐dimethylamino substituted but‐2‐yne dication 1 and related model cations are investigated by DFT, MP2, CCSD and CCSD(T)) quantum chemical calculations to elucidate structural and electronic details, energy barriers and conformational preferences in order to rationalize experimental NMR‐spectra and crystallographic structural data of tetrafluoroborate and tetraphenylborate salts of 1. Very small energy differences (<2 kJ mol−1) between different conformations are caused by electronic and steric effects in the cation. In addition, solid‐state effects such as anion cation interactions may lead to conformational differences in the salts. In dication 1 and analogous model cations, the distonic arrangement of the charges is preferred over a gitonic configuration. Copyright © 2013 John Wiley & Sons, Ltd.
Understanding the catalytic activity of single‐chain polymeric nanoparticles in water
Authors: Artar Müge , Terashima Takaya , Sawamoto Mitsuo , Meijer E. W. , Palmans Anja R. A.
Published: October 2013

The structuring role of benzene‐1,3,5‐tricarboxamide (BTA) groups for the catalytic activity of single chain polymeric nanoparticles in water was investigated in the transfer hydrogenation of ketones. To this end, a set of segmented, amphiphilic copolymers was prepared, which comprised oligo(ethylene glycol) side chains to impart water solubility, BTA and/or lauryl side chains to induce hydrophobicity and diphenylphosphinostyrene (SDP) units in the middle part as a ligand to bind a ruthenium catalyst. All copolymers were obtained by reversible addition‐fragmentation chain transfer (RAFT) polymerization and showed low dispersities (Mw/Mn = 1.23–1.38) and controlled molecular weights (Mn = 44–28 kDa). A combination of circular dichroism (CD) spectroscopy and dynamic light scattering (DLS) showed that all copolymers fold into a single chain polymeric nanoparticles (SCPNs) as a result of the helical self‐assembly of the pendant BTA units and/or hydrophilic–hydrophobic phase separation. To create catalytic sites, RuCl2(PPh3)3 was incorporated into the copolymers. The Cotton effects of the copolymers before and after Ru(II) loading were identical, indicating that the helical self‐assembly of the BTA units and the complexation of SDP ligands and Ru(II) occurs in an orthogonal manner. DLS revealed that after Ru(II) loading, SDP‐bearing copolymers retained their single chain character in water, while copolymers lacking SDP units clustered into larger aggregates. The Ru(II) loaded SCPNs were tested in the transfer hydrogenation of cyclohexanone. This study reveals that BTA induced stack formation is not crucial for SCPN formation and catalytic activity; SDP‐bearing copolymers folded by Ru(II) complexation and hydrophobic pendants suffice to provide hydrophobic, isolated reaction pockets around Ru(II) complexes. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 12–20
The prevalence of asthma in Canadian children of South Asian descent
Authors: Moerman Joost Nico , Ratjen Felix , Subbarao Padmaja , Sears Malcolm R. , Anand Sonia S. , Stanojevic Sanja
Published: October 2013

Background

Asthma is the most common disease in childhood. The prevalence of asthma is known to vary greatly between and within countries and among different ethnic groups. In this study, we aimed to determine the prevalence of asthma and wheezing symptoms in South Asian children living in Canada.

Methods

In a cross sectional study, data from the Phase III International Study on Asthma and Allergies in Childhood (ISAAC) were analyzed. A surname algorithm to determine South Asian ethnic descent was used. Prevalence was calculated and compared to non‐South Asian children from the same survey and to the reported prevalence from the Indian subcontinent ISAAC III survey for children ages 6–9 and 13–16.

Results

The prevalence of asthma and wheezing did not differ between children of South Asian descent and non‐South Asians living Canada. When compared to the children living in India, the prevalence of asthma, wheeze, and exercise induced wheeze was significantly higher in the South Asian children living in Canada. Higher body mass index of the child, parental smoking, and pet ownership were strongly associated with asthma and wheeze.

Conclusions

In contrast to other studies these data suggest that South Asian children living in Canada have a similar asthma prevalence to non‐South Asian children; both of whom had higher asthma prevalence compared with children residing in South Asia. This suggests that environmental and social factors play a role in asthma prevalence. Risk factors for asthma in children of South Asian descent living in Canada are similar to those of the overall population. Pediatr Pulmonol. 2014; 49:43–48. © 2013 Wiley Periodicals, Inc.
Low level of tracheal cellular fibronectin in extremely premature infants with funisitis: Relationship with respiratory distress 1 month after birth
Authors: Arai Hirokazu , Ito Tomoo , Adachi Hiroyuki , Goto Ryoji , Takahashi Tsutomu
Published: October 2013

Background

Funisitis reflects the fetal systemic inflammatory response in premature infants. Macrophages and neutrophils have been identified as key elements in the inflammatory process of the lungs, and secrete proteases that cause the destruction of the extracellular matrix (ECM). Fibronectin (FN) is the major constituent of the pulmonary ECM and exists in multiple isoforms arising from alternative RNA splicing. Extra domain A (EDA) is the major alternatively spliced segment, and the expression of EDA containing FN (EDA + FN) in the lungs is associated with distal pulmonary cell proliferation during alveolar formation.

Objective

To study the relationship between the presence of funisitis and EDA + FN levels in the tracheal aspirate fluid (TAF) of infants of less than 28 weeks' gestation.

Methods

The subjects included in this study were 26 extremely premature infants of <28 weeks' gestation at <24 hr of age, from whom the TAF was collected. These preterm infants were divided into two groups according to placental histology. The funisitis (+) group (n = 9) was compared with the funisitis (−) group (n = 17). The TAF supernatants were analyzed for IL‐1β, IL‐6, IL‐8, neutrophil elastase, and EDA + FN using enzyme‐linked immunosorbent assay (ELISA).

Results

There were no significant differences in gestational age or birthweight between these groups. The funisitis (+) group had a significantly higher ventilator setting (inspired O2 × mean airway pressure) at Day 28 than the funisitis (−) group. In the TAF, the concentrations of IL‐1β were significantly higher in the funisitis (+) group than in the funisitis (−) group, as were the concentrations of neutrophil elastase. The concentrations of EDA + FN were significantly lower in the funisitis (+) group than in the funisitis (−) group.

Conclusions

Decreased EDA + FN in TAF might be one of the risk factors leading to respiratory distress in extremely premature infants with funisitis. Pediatr Pulmonol. 2014; 49:905–910. © 2013 Wiley Periodicals, Inc.
Comparison of two aspiration techniques of bronchoalveolar lavage in children
Authors: Rosas‐Salazar Christian , Walczak Stephen A. , Winger Daniel G. , Kurland Geoffrey , Spahr Jonathan E.
Published: October 2013

Background

Although bronchoalveolar lavage (BAL) via flexible bronchoscopy is an essential diagnostic tool, its technique is not standardized in children. Our objective was to compare two different aspiration techniques of BAL in children (continuous wall suction vs. handheld syringe suction) in regards to the percentage of fluid recovered and the odds of performing a technically acceptable procedure (i.e., >40% of volume return).

Methods

We conducted a review of all pediatric flexible bronchoscopies with BAL conducted at our institution over a 2‐year period. To minimize the differences between groups at baseline and reduce the possibility of bias, we used one‐to‐one propensity score (PS) caliper matching with no replacement for statistical analyses.

Results

We identified 539 procedures that met pre‐specified criteria. There were considerable covariate imbalances between procedures in the handheld syringe group (n = 147) and those in the continuous wall group (n = 392); however, these imbalances were substantially reduced after the PS matching. In the matched sample (n = 236), children in the handheld syringe group had ∼7% higher volume return (95% CI = 3.4–11.0, P < 0.001) from BAL and threefold higher odds (95% CI = 1.5–8.6, P = 0.002) of performing a technically acceptable procedure.

Conclusions

Our results suggest that handheld syringe suction offers a higher percentage of volume return from BAL and increases the odds of performing a technically acceptable procedure in children when compared to continuous wall suction. Pediatr Pulmonol. 2014; 49:978–984. © 2013 Wiley Periodicals, Inc.
Cholesterol as a co‐solvent and a ligand for membrane proteins
Authors: Song Yuanli , Kenworthy Anne K. , Sanders Charles R.
Published: October 2013

As of mid 2013 a Medline search on “cholesterol” yielded over 200,000 hits, reflecting the prominence of this lipid in numerous aspects of animal cell biology and physiology under conditions of health and disease. Aberrations in cholesterol homeostasis underlie both a number of rare genetic disorders and contribute to common sporadic and complex disorders including heart disease, stroke, type II diabetes, and Alzheimer's disease. The corresponding author of this review and his lab stumbled only recently into the sprawling area of cholesterol research when they discovered that the amyloid precursor protein (APP) binds cholesterol, a topic covered by the Hans Neurath Award lecture at the 2013 Protein Society Meeting. Here, we first provide a brief overview of cholesterol‐protein interactions and then offer our perspective on how and why binding of cholesterol to APP and its C99 domain (β‐CTF) promotes the amyloidogenic pathway, which is closely related to the etiology of Alzheimer's disease.
Refined structures of mouse P‐glycoprotein
Authors: Li Jingzhi , Jaimes Kimberly F. , Aller Stephen G.
Published: October 2013

The recently determined C. elegans P‐glycoprotein (Pgp) structure revealed significant deviations compared to the original mouse Pgp structure, which suggested possible misinterpretations in the latter model. To address this concern, we generated an experimental electron density map from single‐wavelength anomalous dispersion phasing of an original mouse Pgp dataset to 3.8 Å resolution. The map exhibited significantly more detail compared to the original MAD map and revealed several regions of the structure that required de novo model building. The improved drug‐free structure was refined to 3.8 Å resolution with a 9.4 and 8.1% decrease in Rwork and Rfree, respectively, (Rwork = 21.2%, Rfree = 26.6%) and a significant improvement in protein geometry. The improved mouse Pgp model contains ∼95% of residues in the favorable Ramachandran region compared to only 57% for the original model. The registry of six transmembrane helices was corrected, revealing amino acid residues involved in drug binding that were previously unrecognized. Registry shifts (rotations and translations) for three transmembrane (TM)4 and TM5 and the addition of three N‐terminal residues were necessary, and were validated with new mercury labeling and anomalous Fourier density. The corrected position of TM4, which forms the frame of a portal for drug entry, had backbone atoms shifted >6 Å from their original positions. The drug translocation pathway of mouse Pgp is 96% identical to human Pgp and is enriched in aromatic residues that likely play a collective role in allowing a high degree of polyspecific substrate recognition.
Blind prediction of interfacial water positions in CAPRI
Authors: Lensink Marc F. , Moal Iain H. , Bates Paul A. , Kastritis Panagiotis L. , Melquiond Adrien S. J. , Karaca Ezgi , Schmitz Christophe , van Dijk Marc , Bonvin Alexandre M. J. J. , Eisenstein Miriam , Jiménez‐García Brian , Grosdidier Solène , Solernou Albert , Pérez‐Cano Laura , Pallara Chiara , Fernández‐Recio Juan , Xu Jianqing , Muthu Pravin , Praneeth Kilambi Krishna , Gray Jeffrey J. , Grudinin Sergei , Derevyanko Georgy , Mitchell Julie C. , Wieting John , Kanamori Eiji , Tsuchiya Yuko , Murakami Yoichi , Sarmiento Joy , Standley Daron M. , Shirota Matsuyuki , Kinoshita Kengo , Nakamura Haruki , Chavent Matthieu , Ritchie David W. , Park Hahnbeom , Ko Junsu , Lee Hasup , Seok Chaok , Shen Yang , Kozakov Dima , Vajda Sandor , Kundrotas Petras J. , Vakser Ilya A. , Pierce Brian G. , Hwang Howook , Vreven Thom , Weng Zhiping , Buch Idit , Farkash Efrat , Wolfson Haim J. , Zacharias Martin , Qin Sanbo , Zhou Huan‐Xiang , Huang Shen‐You , Zou Xiaoqin , Wojdyla Justyna A. , Kleanthous Colin , Wodak Shoshana J.
Published: October 2013

We report the first assessment of blind predictions of water positions at protein–protein interfaces, performed as part of the critical assessment of predicted interactions (CAPRI) community‐wide experiment. Groups submitting docking predictions for the complex of the DNase domain of colicin E2 and Im2 immunity protein (CAPRI Target 47), were invited to predict the positions of interfacial water molecules using the method of their choice. The predictions—20 groups submitted a total of 195 models—were assessed by measuring the recall fraction of water‐mediated protein contacts. Of the 176 high‐ or medium‐quality docking models—a very good docking performance per se—only 44% had a recall fraction above 0.3, and a mere 6% above 0.5. The actual water positions were in general predicted to an accuracy level no better than 1.5 Å, and even in good models about half of the contacts represented false positives. This notwithstanding, three hotspot interface water positions were quite well predicted, and so was one of the water positions that is believed to stabilize the loop that confers specificity in these complexes. Overall the best interface water predictions was achieved by groups that also produced high‐quality docking models, indicating that accurate modelling of the protein portion is a determinant factor. The use of established molecular mechanics force fields, coupled to sampling and optimization procedures also seemed to confer an advantage. Insights gained from this analysis should help improve the prediction of protein–water interactions and their role in stabilizing protein complexes. Proteins 2014; 82:620–632. © 2013 Wiley Periodicals, Inc.