bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antarctic glossopterid diversity on a local scale: The presence of multiple megasporophyll genera, Upper Permian, Mt. Achernar, Transantarctic Mountains, Antarctica
Authors: Ryberg Patricia E. , Taylor Edith L. , Taylor Thomas N. 
Published: August 2012

• Premise of the study: The glossopterids are a group of plants that thrived during a time of global warming similar to what is happening on the Earth today as well as the transition from archaic plant groups to the ancestors of modern groups. The diversity of the glossopterid clade is based on the megasporangiate structures assigned to the group, because the vegetative and pollen‐bearing structures vary little. The presence of numerous reproductive genera from a single Upper Permian locality in the central Transantarctic Mountains provides important data on local glossopterid diversity in Antarctica.• Methods: Impression/compression fossils were imaged with a Leica 5000C digital camera on a dissecting microscope or a Fujifilm FinePix S1pro digital camera.• Key results: Two megasporangiate taxa are described: Scutum leiophyllum, which represents the first confirmed record of the genus in Antarctica, and Lidgettoniopsis ramulus, a new morphology consisting of a pinnate structure with oppositely attached megasporophylls. Plumsteadia ovata specimens indicate that this genus can be larger than previously recorded and illustrate the vegetative surface with a distinct midrib.• Conclusions: The presence of a laminar, multiovulate structure and a pinnate structure at the same site indicates that local‐level glossopterid diversity in Antarctica is greater than previously hypothesized. The discovery of a new megasporophyll morphology in Antarctica (confirming the presence of three distinctive morphologies on the continent) shows that Antarctic glossopterid heterogeneity is on a par with other Gondwanan continents. The diversity of the Antarctic landscape reveals that high polar latitudes can sustain a diverse ecosystem during times of global warming.
Overall Neutralization of Complement Factor H by Autoantibodies in the Acute Phase of the Autoimmune Form of Atypical Hemolytic Uremic Syndrome
Authors: Blanc Caroline , Roumenina Lubka T. , Ashraf Yahya , Hyvärinen Satu , Sethi Sidharth Kumar , Ranchin Bruno , Niaudet Patrick , Loirat Chantal , Gulati Ashima , Bagga Arvind , Fridman Wolf Herman , Sautès-Fridman Catherine , Jokiranta T. Sakari , Frémeaux-Bacchi Véronique , Dragon-Durey Marie-Agnès 
Published: August 2012

Abstract
Complement is a major innate immune surveillance system. One of its most important regulators is the plasma protein factor H (FH). FH inactivation by mutations or by autoantibodies is associated with a thrombotic microangiopathy disease, atypical hemolytic uremic syndrome. In this study, we report the characterization of blood samples from 19 anti-FH Ab-positive atypical hemolytic uremic syndrome patients collected at the acute phase of the disease. Analyses of the functional consequences and epitope mapping, using both fluid phase and solid phase approaches, were performed. The anti-FH Abs perturbed FH-mediated cell protection (100%), inhibited FH interaction with C3 (46%), and caused C3 consumption (47%). The Abs were directed against multiple FH epitopes located at the N and C termini. In all tested patients, high titers of FH-containing circulating immune complexes were detected. The circulating immune complex titers correlated with the disease stage better than did the Ab titers. Our results show that anti-FH autoantibodies induce neutralization of FH at acute phase of the disease, leading to an overall impairment of several functions of FH, extending the role of autoantibodies beyond the impairment of the direct cell surface protection.
Molecular and Cellular Mechanisms of Mycobacterium avium-Induced Thymic Atrophy
Authors: Borges Margarida , Barreira-Silva Palmira , Flórido Manuela , Jordan Michael B. , Correia-Neves Margarida , Appelberg Rui 
Published: August 2012

Abstract
Thymic atrophy has been described as a consequence of infection by several pathogens and shown to be induced through diverse mechanisms. Using the mouse model of Mycobacterium avium infection, we show in this study that the production of NO from IFN-γ–activated macrophages plays a major role in mycobacterial infection-induced thymic atrophy. Our results show that disseminated infection with a highly virulent strain of M. avium, but not with a low-virulence strain, led to a progressive thymic atrophy. Thymic involution was prevented in genetically manipulated mice unable to produce IFN-γ or the inducible NO synthase. In addition, mice with a selective impairment of IFN-γ signaling in macrophages were similarly protected from infection-induced thymic atrophy. A slight increase in the concentration of corticosterone was found in mice infected with the highly virulent strain, and thymocytes presented an increased susceptibility to dexamethasone-induced death during disseminated infection. The administration of an antagonist of glucocorticoid receptors partially reverted the infection-induced thymic atrophy. We observed a reduction in all thymocyte populations analyzed, including the earliest thymic precursors, suggesting a defect during thymic colonization by T cell precursors and/or during the differentiation of these cells in the bone marrow in addition to local demise of thymic cells. Our data suggest a complex picture underlying thymic atrophy during infection by M. avium with the participation of locally produced NO, endogenous corticosteroid activity, and reduced bone marrow seeding.
Prevalence of human papilloma virus in cytological abnormalities: Association of risk factors and cytomorphological findings
Authors: Izaaks Christo D. , Truter Ernest J. , Khan Sehaam 
Published: August 2012

Background:
Previous studies demonstrated the etiological role of human papilloma virus (HPV) in cervical carcinogenesis. Assessing the distribution of HPV may elucidate these observations.

Materials and Methods:
In total, we examined 3839 specimens, of which 187 abnormally classified cervical smears were immunostained using the p16INK4A assay. DNA was extracted from 182 specimens, and polymerase chain reaction (PCR) was performed. Participants’ socio-demographics, sexual and reproductive history, HIV status, contraceptive use, and Pap smear history were recorded.

Results:
Subject ages, number of sexual partners, and age at first sexual encounter ranged from 15 to 49 years, from 1 to 37 partners, and from 13 to 34 years, respectively. P16 immunoreactivity was detected in 60.4% of cases. The distribution of epithelial lesions and P16 overexpression (bracketed) was: 28 (5) atypical squamous cells of undetermined significance (ASC-US), 96 (50) lower grade squamous intraepithelial lesion (LSIL), 9 (7) atypical squamous cells-cannot exclude HSIL (ASC-H), and 54 (51) higher grade squamous intraepithelial lesion (HSIL). Ninety-four percent of HSIL expressed P16. Fifty-two percent of LSIL expressed P16. P16 expression declined from 61% (25–34 year age group) to 5% (45–49 year age group) for different age groups. HPV-DNA by PCR was detected in 94.5% of P16-positive samples. Type-specific PCR (HPV 16 and 18) was found in 12.2% and 14.5% of abnormal lesions, respectively. Younger age at first sexual encounter and HIV infection predominated in HPV type(s) 16 and/or 18 positive subjects.

Conclusion:
This study reinforced the value of the p16INK4A surrogate marker in identifying women with progressive cervical disease.
Low Leukocyte MGMT Accompanies Temozolomide-Induced Myelotoxicity in Brain Tumor Patients
Authors: Julia E. Stokes  , Michael S. Bobola  , Marc C. Chamberlain  , John R. Silber  
Published: August 2012

Objective: The methylating agent temozolomide (TMZ) has markedly improved clinical outcome for patients with glioblastoma and other gliomas. While TMZ has comparatively low systemic toxicity, a minority of patients experience severe myelotoxicity that compromises TMZ treatment, necessitating dose reductions and treatment delays. These limitations emphasize the need to develop markers to identify individuals susceptible to TMZ-induced myelosuppression. The purpose of this small pilot study is to examine the association between treatment-limiting myelosuppression in primary brain tumor patients receiving TMZ and expression of O6-methylguanine-DNA methyltransferase (MGMT) in peripheral blood leukocytes (PBL). MGMT is the sole human activity that removes TMZ-induced, cytotoxic O6-methylguanine adducts from DNA.
Methods: MGMT biochemical activity and MGMT promoter methylation status, a surrogate measure of MGMT expression, were assayed in PBL from 10 patients who experienced treatment-limiting myelotoxicity during TMZ therapy, 8 patients who experienced no myelotoxicity during TMZ treatment, and 10 disease-free, untreated controls.
Results: MGMT activity was detectable in all 28 PBL samples, and all displayed an unmethylated promoter indicative of MGMT expression. Mean PBL MGMT activity was 2-fold lower in patients who experienced myelotoxicity compared to patients without myelotoxicity (8.9 ± 3.9 vs. 18 ± 8.1 fmol/106 cells; P 0.015) and to untreated controls (8.9 ± 3.9 vs. 16 ± 6.8 fmol/106 cells; P 0.015).
Conclusions: These preliminary data indicate that low MGMT activity in PBL is associated with myelotoxicity in primary brain tumor patients receiving TMZ, and may have value if confirmed in a larger study as a marker to identify patients at greater risk of treatment-limiting myelosuppression.
EGFR Tyrosine Kinase Inhibitors Prolong Overall Survival in EGFR Mutated Non-Small-Cell Lung Cancer Patients with Postsurgical Recurrence
Authors: Kenichi Suda  , Simon Ito  , Hiroshi Mizuuchi  , Yoshihiko Maehara  , Yasushi Yatabe  , Tetsuya Mitsudomi  
Published: August 2012

It is indisputable that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) prolong progression-free survival in non-small-cell lung cancer (NSCLC) patients with EGFR mutations better than cytotoxic chemotherapy. However, it is unclear whether EGFR-TKIs prolong the overall survival of NSCLC patients, especially in those with postsurgical recurrence.We retrospectively examined 304 NSCLC patients with known EGFR mutational status (excluding those with squamous cell carcinoma), who had undergone pulmonary resection and experienced postsurgical recurrence. Of these patients, 137 carried EGFR mutations and 167 did not. Of the 137 patients with EGFR mutations, 83 were treated with EGFR-TKIs for their recurrent disease, and 32 of the 167 patients without EGFR mutations were treated with EGFR-TKIs. Postsurgical survival was divided into two parts: recurrence-free survival (RFS) and postrecurrence survival (PRS), and these were compared between the subgroups with a multivariate analysis, adjusted for baseline clinical characteristics.There was no significant difference in RFS between patients with EGFR mutations and those without (P = 0.88). PRS was also similar in these two subgroups when we excluded patients who had been treated with EGFR-TKIs (P = 0.64). In patients with EGFR mutations, PRS was significantly longer in those who were treated with EGFR-TKIs than in those who were not given EGFR-TKIs (P = 0.04). However, among patients without EGFR mutations, PRS was similar in patients who had and had not been treated with EGFR-TKIs (P = 0.87). In conclusion, among NSCLC patients with postsurgical recurrence, EGFR-TKIs prolonged PRS in those with EGFR mutations.
Treatment of Chemotherapy - Induced Peripheral Neuropathy: The Physicians Need Guidelines, the Patients Need Help
Authors: Brzezinsk Krzysztof 
Published: August 2012

The aim of the study was to verify the effectiveness of two methods of introducing standard CIPN-treatment drugs into the therapy. Materials and Methods: Group A included patients attending weekly appointments, while group B monthly. Standard treatment with amitriptyline, gabapentin (GAB), and oxycodone (OXY) was administered. In group A, the drugs were gradually introduced, while in group B - within one week. After a month and six months of treatment, the therapy effectiveness was assessed by examination of pain intensity (VAS), symptoms of peripheral neuropathy (sNCI-CTC), occurrence of tactile and brush allodynia, and the daily dose of GAB andOXY. Results: Pain intensity during the study decreased from 5.59 to 2.9 and 2.76 in group A, and from 5.07 to 2.52 and 2.81 in group B. The sNCI-CTC values declined too and were, respectively. 1.9; 1.48; 1.34 in group A and 1.93; 1.52; 1.44 in group B. Tactile allodynia occurred in 15; 5; 5 group A patients and 18; 6; 5 group B patients. Brush allodynia decreased in group A (9; 5; 5) and B (11; 6; 5). The daily GAB dose was 0; 951.72; 927.41 in group A and 900.0; 900.0; 1000.0 in group B. The daily OXY dose was 0; 21.72; 22.07 in group A and 20.0; 20.0; 27.04 in group B; a statistically significant difference was found in the final stage. The results do not allow recommendation of non-schematic treatment and they should be regarded as a preliminary study. Randomized trials are indispensable for assessment of advantages and drawbacks such treatment.
High-Expression of PTEN and an Absence of PCNA in Osteoclast-Like Multinucleated Giant Cells of Giant Cell Tumors in Bone
Authors: Chao Lou  , Rong Qiang  , Hongmin Yan  , Jie Li  
Published: August 2012

Giant cell tumors (GCTs) found in bone are so named for the conspicuous presence of numerous osteoclast-like multinucleated giant cells (OLMGCs). Although GCT studies have revealed that the OLMGCs are the cells responsible for tumor formation, these cells continue to receive a good deal of research attention. The tumor -suppressor gene, PTEN, is known to be involved in various malignancies. Recently, however, PTEN has been reported to be important for neuron enlargement and cardiomyocyte hypertrophy. Given the role of PTEN in both carcinomas as well as cell hypertrophy, we sought to elucidate the relationship between PTEN and OLMGCs. In this study, we confirmed the existence of PTEN in GCTs in bone using PCR. In particular, exons-3,4 and 5 of the PTEN gene was detected. Exons-3,4,5 of PTEN gene were found by PCR in all of 8 cases. Single cells microdissection was used to isolate OLMGCs from GCTs and verify the existence of the PTEN gene in the osteoclast-like multinucleated giant cells through PCR amplication of PTEN exon-3. Exon-3 of PTEN were detected by PCR in 5 of the 10 microdissected samples. PTEN mRNA expression was detected by in situ hybridization and the expressions of PTEN protein and proliferating cell nuclear antigen (PCNA) in GCTs were detected by immunohistochemistry. High expression levels of PTEN mRNA was detected only in OLMGCs in 23 of 27 GCT cases. Likewise,high expression of PTEN protein was also found only in OLMGCs in 21 of the 27 GCT cases and the giant cells did not express PCNA. In contrast, the neoplastic stromal cells with high PCNA labeling were almost always PTEN-negative by immunohistochemical staining. These results suggested that high-expression of PTEN in OLMGCs may involve in the formation size of GCTs.
Blind deconvolution by a Newton method on the non‐unitary hypersphere
Authors: Fiori S. 
Published: August 2012

SUMMARYBlind deconvolution is an inverse filtering technique that has received increasing attention from academia as well as industry because of its theoretical implications and practical applications, such as in speech dereverberation, nondestructive testing and seismic exploration. An effective blind deconvolution technique is known as ‘Bussgang’, which relies on the iterative Bayesian estimation of the source sequence. Automatic gain control in blind deconvolution keeps constant the energy of the inverse filter impulse response and controls the magnitude of the estimated source sequence. The aim of the present paper is to introduce a class of Newton‐type algorithms to optimize the Bussgang cost function on the inverse‐filter parameter space whose geometrical structure is induced by the automatic‐gain‐control constraint. As the parameter space is a differentiable manifold, the Newton‐like optimization method is formulated in terms of differential geometrical concepts. The present paper also discusses convergence issues related to the introduced Newton‐type optimization algorithms and illustrates their performance on a comparative basis.Copyright © 2012 John Wiley & Sons, Ltd.
Total Synthesis of Marinoquinoline A Using a Palladium(0)‐Catalyzed Ullmann Cross‐Coupling Reaction
Authors: Ma Xinghua , Vo Yen , Banwell Martin G. , Willis Anthony C. 
Published: August 2012

AbstractThe title natural product, 1, has been synthesized. The pivotal steps are a Pd0‐catalyzed Ullmann cross‐coupling of the 3‐iodopyrrole‐2‐carboxaldehyde 13 with o‐bromonitrobenzene (14), conversion of the resulting 3‐arylpyrrole 15 into methylketone 17, and reductive cyclization of 17 by using magnesium in methanol to give target 1 in 85 % yield.
Soprano singing in gibbons
Authors: Koda Hiroki , Nishimura Takeshi , Tokuda Isao T. , Oyakawa Chisako , Nihonmatsu Toshikuni , Masataka Nobuo 
Published: August 2012

AbstractDiversifications in primate vocalization, including human speech, are believed to reflect evolutionary modifications in vocal anatomy and physiology. Gibbon song is acoustically unique, comprising loud, melodious, penetrating pure tone‐like calls. In a white‐handed gibbon, Hylobates lar, the fundamental frequency (f0) of song sounds is amplified distinctively from the higher harmonics in normal air. In a helium‐enriched atmosphere, f0 does not shift, but it is significantly suppressed and 2f0 is emphasized. This implies that the source is independent of the resonance filter of the supralaryngeal vocal tract (SVT) in gibbons, in contrast to musical wind instruments, in which the filter primarily determines f0. Acoustic simulation further supported that gibbons' singing is produced analogously to professional human soprano singing, in which a precise tuning of the first formant (F1) of the SVT to f0 amplifies exclusively the f0 component of the source. Thus, in gibbons, as in humans, dynamic control over the vocal tract configuration, rather than anatomical modifications, has been a dominant factor in determining call structure. The varied dynamic movements were adopted in response to unique social and ecological pressures in gibbons, allowing monogamous gibbons to produce pure‐tonal melodious songs in the dense tropical forests with poor visibility. Am J Phys Anthropol, 2012. © 2012 Wiley Periodicals, Inc.
Role of reduced ADAMTS13 in arterial ischemic stroke: A Pediatric Cohort Study
Authors: Lambers Moritz , Goldenberg Neil A. , Kenet Gili , Kirkham Fenella J. , Manner Daniela , Bernard Timothy , Mesters Rolf M. , Junker Ralf , Stoll Monika , Nowak‐Göttl Ulrike 
Published: August 2012

AbstractObjective:Previous studies in adults and mice have implicated ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), also known as von Willebrand factor (VWF)‐cleaving protease, as a protective factor for stroke. Here we investigated ADAMTS13 in 208 pediatric patients with arterial ischemic stroke (AIS) and 125 population‐based control children in a frequency‐matched case–control study.Methods:The proportion of patients/controls with ADAMTS13 activity levels below and above the 10th percentile was compared. Additionally, in a quintile comparison, the proportion of patients versus controls in the lowest ADAMTS13 quintile was compared to those in the 2nd to 5th quintiles. Adjustment was performed for VWF antigen (VWF:Ag), factor VIII activity (FVIII:C), blood group, and age.Results:Forty‐six of 208 patients (22%) showed ADAMTS13 levels below the 10th percentile, compared with 5 of 125 controls (4%; p < 0.001). Odds ratios/95% confidence intervals were 7.30/2.73–19.50 for the lowest percentile and 2.44/1.15–5.16 in the quintile comparison after adjustment for VWF:Ag, FVIII:C, blood group, and age. Comparing the proportion of patients with ADAMTS13 activity below the 10th percentile within the different stroke subtypes (undetermined, cardioembolic, steno‐occlusive arteriopathies), no statistically significant differences were found (undetermined, 16 of 89; cardioembolic, 6 of 40; steno‐occlusive arteriopathies, 24 of 79; p = 0.08). ADAMTS13 levels did not significantly differ among stroke subtypes (p = 0.29).Interpretation:Our findings implicate reduced ADAMTS13 activity as a risk factor for pediatric AIS, and support the concept that ADAMTS13 has a role in the pathogenesis of pediatric AIS. ANN NEUROL 2013.
Phenotypic Spectrum of COL4A1 Mutations: Porencephaly to Schizencephaly
Authors: Yoneda Yuriko , Haginoya Kazuhiro , Kato Mitsuhiro , Osaka Hitoshi , Yokochi Kenji , Arai Hiroshi , Kakita Akiyoshi , Yamamoto Takamichi , Otsuki Yoshiro , Shimizu Shin‐ichi , Wada Takahito , Koyama Norihisa , Mino Yoichi , Kondo Noriko , Takahashi Satoru , Hirabayashi Shinichi , Takanashi Jun‐ichi , Okumura Akihisa , Kumagai Toshiyuki , Hirai Satori , Nabetani Makoto , Saitoh Shinji , Hattori Ayako , Yamasaki Mami , Kumakura Akira , Sugo Yoshinobu , Nishiyama Kiyomi , Miyatake Satoko , Tsurusaki Yoshinori , Doi Hiroshi , Miyake Noriko , Matsumoto Naomichi , Saitsu Hirotomo 
Published: August 2012

AbstractObjective:Recently, COL4A1 mutations have been reported in porencephaly and other cerebral vascular diseases, often associated with ocular, renal, and muscular features. In this study, we aimed to clarify the phenotypic spectrum and incidence of COL4A1 mutations.Methods:We screened for COL4A1 mutations in 61 patients with porencephaly and 10 patients with schizencephaly, which may be similarly caused by disturbed vascular supply leading to cerebral degeneration, but can be distinguished depending on time of insult.Results:COL4A1 mutations were identified in 15 patients (21%, 10 mutations in porencephaly and 5 mutations in schizencephaly), who showed a variety of associated findings, including intracranial calcification, focal cortical dysplasia, pontocerebellar atrophy, ocular abnormalities, myopathy, elevated serum creatine kinase levels, and hemolytic anemia. Mutations include 10 missense, a nonsense, a frameshift, and 3 splice site mutations. Five mutations were confirmed as de novo events. One mutation was cosegregated with familial porencephaly, and 2 mutations were inherited from asymptomatic parents. Aberrant splicing was demonstrated by reverse transcriptase polymerase chain reaction analyses in 2 patients with splice site mutations.Interpretation:Our study first confirmed that COL4A1 mutations are associated with schizencephaly and hemolytic anemia. Based on the finding that COL4A1 mutations were frequent in patients with porencephaly and schizencephaly, genetic testing for COL4A1 should be considered for children with these conditions. ANN NEUROL 2013.
Computational Modeling, Synthesis, and Antioxidant Potential of Novel Phenylcarbamoylbenzoic Acid Analogs in Combating Oxidative Stress
Authors: Bayoumi Waleed A. , Elsayed Magda A. , Baraka Hany N. , Abou‐zeid Laila 
Published: August 2012

AbstractA new series of phenylcarbamoylbenzoic acid analogs were designed, synthesized, and evaluated for their in vitro antioxidant activity, aiming to find a lead for the treatment of oxidative stress. The target compounds were prepared by substituting the core phenylcarbamoylbenzoic acid moiety with certain functionalities via simple and efficient synthetic strategies. A molecular modeling study was performed to evaluate the recognition of target compounds at the 3MNG binding pocket. The docking data revealed that compounds 8c and 9a selectively bind to the crucial amino acid residues in the active site of 3MNG. The in vitro antioxidant activity was determined by ABTS antioxidant assay. Compounds 8c, 9a, and 9b showed high antioxidant activity and are thus promising as potent antioxidant leads.