bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of the Hermansky–Pudlak syndrome type 4 (HPS4) gene variants with cognitive function in patients with schizophrenia and healthy subjects
Authors: Kuratomi Go , Saito Atsushi , Ozeki Yuji , Watanabe Takashi , Fujii Kumiko , Shimoda Kazutaka , Inukai Toshihiko , Mori Harunobu , Ohmori Kenichi , Akiyama Kazufumi 
Published: October 2013

Abstract

Background
The Hermansky–Pudlak Syndrome Type 4 (HPS4) gene, which encodes a subunit protein of the biogenesis of lysosome-related organelles complex (BLOC)-3, which is involved in late endosomal trafficking, is associated with schizophrenia; however, its clinical relevance in schizophrenia remains unknown. The purpose of the present study was to investigate whether HPS4 is associated with cognitive functions in patients with schizophrenia and healthy controls and with the clinical profiles of patients with schizophrenia.

Methods
We investigated the association of variants of HPS4 with clinical symptoms and cognitive function in Japanese patients with schizophrenia (n = 240) and age-matched healthy control subjects (n = 240) with single nucleotide polymorphisms (SNP)- or haplotype-based linear regression. We analyzed five tagging SNPs (rs4822724, rs61276843, rs9608491, rs713998, and rs2014410) of HPS4 and 2–5 locus haplotypes of these five SNPs. The cognitive functions of patients and healthy subjects were evaluated with the Brief Assessment of Cognition in Schizophrenia, Japanese-language version, and the patients were assessed for their symptomatology with the Positive and Negative Symptom Scale (PANSS).

Results
In patients with schizophrenia, rs713998 was significantly associated with executive function under the dominant genetic model (P = 0.0073). In healthy subjects, there was a significant association between working memory and two individual SNPs under the recessive model (rs9608491: P = 0.001; rs713998: P = 0.0065) and two haplotypes (rs9608491-713998: P = 0.0025; rs61276843-9608491-713998: P = 0.0064). No significant association was found between HPS4 SNPs and PANSS scores or premorbid IQ, as measured by the Japanese version of the National Adult Reading Test.

Conclusions
These findings suggested the involvement of HPS4 in the working memory of healthy subjects and in the executive function deficits in schizophrenia.
Effect of oral administration of ethanolic extract of Vitex negundo on thioacetamide-induced nephrotoxicity in rats
Authors: Kadir Farkaad A , Kassim Normadiah M , Abdulla Mahmood A , Yehye Wageeh A 
Published: October 2013

Abstract

Background
Oxidative stress due to abnormal induction of reactive oxygen species (ROS) molecules is believed to be involved in the etiology of many diseases. Evidences suggest that ROS is involved in nephrotoxicity through frequent exposure to industrial toxic agents such as thioacetamide (TAA). The current investigation was designed to explore the possible protective effects of the leaves of Vitex negundo(VN) extract against TAA-induced nephrotoxicity in rats.

Methods
Twenty four Sprague Dawley rats were divided into four groups: (A) Normal control, (B) TAA (0.03% w/v in drinking water), (C) VN100 (VN 100 mg/kg + TAA) and (D) VN300 (VN 300 mg/kg + TAA). Blood urea and serum creatinine levels were measured,supraoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels of renal tissue were assayed. Histopathological analysis together with the oxidative stress nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox in kidney sections were examined in all experimental groups.

Results
Blood urea and serum creatinine levels were increased in TAA group as a result of the nephrotoxicity compared to the VN100 and VN300 groups where, the levels were significantly decreased (p < 0.05). Renal MDA level was significantly decreased (p < 0.05) in the VN-treated groups with increased CAT and SOD activities compared to the TAA group. Light microscopic examination of renal tissues stained by H&E stain and Masson’s Trichrome for TAA-treated groups revealed severe histopathological changes, whereas specimens obtained from VN-treated groups showed only mild changes. These findings were supported by immunohistochemical results.

Conclusions
VN extract acts as a natural potent antioxidant to prevent ongoing TAA-induced nephrotoxicity in rats, both biochemically and morphologically.
Myc is required for β-catenin-mediated mammary stem cell amplification and tumorigenesis
Authors: Moumen Mejdi , Chiche Aurélie , Decraene Charles , Petit Valérie , Gandarillas Alberto , Deugnier Marie-Ange , Glukhova Marina A , Faraldo Marisa M 
Published: October 2013

Abstract

Background
Basal-like breast cancer is a heterogeneous disease characterized by the expression of basal cell markers, no estrogen or progesterone receptor expression and a lack of HER2 ov erexpression. Recent studies have linked activation of the Wnt/β-catenin pathway, and its downstream target, Myc, to basal-like breast cancer. Transgenic mice K5ΔNβcat previously generated by our team present a constitutive activation of Wnt/β-catenin signaling in the basal myoepithelial cell layer, resulting in focal mammary hyperplasias that progress to invasive carcinomas. Mammary lesions developed by K5ΔNβcat mice consist essentially of basal epithelial cells that, in contrast to mammary myoepithelium, do not express smooth muscle markers.

Methods
Microarray analysis was used to compare K5ΔNβcat mouse tumors to human breast tumors, mammary cancer cell lines and the tumors developed in other mouse models. Cre-Lox approach was employed to delete Myc from the mammary basal cell layer of K5ΔNβcat mice. Stem cell amplification in K5ΔNβcat mouse mammary epithelium was assessed with 3D-culture and transplantation assays.

Results
Histological and microarray analyses of the mammary lesions of K5ΔNβcat females revealed their high similarity to a subset of basal-like human breast tumors with squamous differentiation. As in human basal-like carcinomas, the Myc pathway appeared to be activated in the mammary lesions of K5ΔNβcat mice. We found that a basal cell population with stem/progenitor characteristics was amplified in K5ΔNβcat mouse preneoplastic glands. Finally, the deletion of Myc from the mammary basal layer of K5ΔNβcat mice not only abolished the regenerative capacity of basal epithelial cells, but, in addition, completely prevented the tumorigenesis.

Conclusions
These results strongly indicate that β-catenin-induced stem cell amplification and tumorigenesis rely ultimately on the Myc pathway activation and reinforce the hypothesis that basal stem/progenitor cells may be at the origin of a subset of basal-like breast tumors.
TLR2 stimulation induces cardiac inflammation but not cardiac depression in vivo
Authors: Boehm Olaf , Knuefermann Pascal , Plueck Johannes , Schwederski Markus , Ehrentraut Heidi , Kebir Sied , Lohner Ralph , Velten Markus , Morath Siegfried , Koch Alexander , Zacharowski Kai , Grohé Christian , Hoeft Andreas , Baumgarten Georg , Meyer Rainer 
Published: October 2013

Abstract

Background
Bacteria such as Staphylococcus aureus induce myocardial dysfunction in vivo. To rectify conflicting evidence about the role of TLR2 signaling and cardiac dysfunction, we hypothesized that the specific TLR2 agonist purified lipoteichoic acid (LTA) from S. aureus contributes to cardiac dysfunction in vitro and in vivo.

Methods
Wildtype (WT-) and TLR2-deficient (TLR2-D) mice were challenged with LTA and in comparison with equivalent doses of lipopolysaccharide (LPS) and CpG-oligodeoxynucleotide (CpG-ODN). TLR2-expression, NFκB as well as cytokine response were determined. Sarcomere shortening of isolated cardiomyocytes was analyzed in vitro and cardiac function in vivo after stimulation with LTA.

Results
LTA induced up-regulation of TLR2 mRNA, activation of NFκB and cytokine expression within 2–6 h in WT-, but not in TLR2-D hearts. Cytokines were also elevated in the serum. LPS and CpG-ODN induced a more severe cardiac inflammation. In vitro incubation of cardiomyocytes with LTA reduced sarcomere shortening via NO at stimulation frequencies ≤ 8 Hz only in WT cells. However, hemodynamic parameters in vivo were not affected by LTA challenge.

Conclusions
LTA induced cardiac inflammation was relatively weak and sarcomere shortening was reduced only below physiological heart rates. This may explain the apparent contradiction between the in vivo and in vitro LTA effects.
Breast adenomyoepithelioma: a case report with malignant proliferation of epithelial and myoepithelial elements
Authors: Petrozza Vincenzo , Pasciuti Giulia , Pacchiarotti Alberto , Tomao Federica , Zoratto Federica , Rossi Luigi , Fontana Antonella , Censi Fabiana , Sardella Barbara , Di Cristofano Claudio , Porta Natale , Della Rocca Carlo 
Published: October 2013

Abstract

Background
Breast adenomyoepithelioma is an unusual tumor characterized by a biphasic proliferation of epithelial and myoepithelial cells. Most breast adenomyoepitheliomas are considered to be benign or to have a low-grade malignant potential, characterized by propensity for local recurrence. Malignant changes arising in this lesion are extremely rare and may involve one or both cellular components.

Case report
We discuss a case of a 60 year-old woman who began to experience pain in her right breast in January 2009. Breast ultrasound and mammography were performed showing a rounded, hypoechoic solid lesion with ill-defined margins in the right inner-inferior quadrant, suspicious of malignancy. Quadrantectomy of the inner-inferior quadrant of the right breast with sampling of ipsilateral axillary lymph nodes was performed. The histological analysis confirmed the diagnosis of adenomyoepithelioma with focal malignant change of the epithelial component, associated with high-grade malignant myoepithelial change. The patient was treated with adjuvant radiotherapy and her right breast received a dose of Gy 50 with a boost of Gy 10 to the tumor bed. At present, the patient shows no sign of tumor recurrence.

Conclusion
Breast malignant adenomyoepithelioma is a rare tumor which should be considered in the differential diagnosis of other solid breast lesions. Only few cases have been reported in the literature. Diagnosis, optimal therapy and predicting the outcome are problematic issues due to the rarity of this disease which appears to have hematogenous rather than lymphatic spread and usually occurs in primary tumors ≥ 1.6 cm in size.
Mo doping-enhanced dye absorption of Bi2Se3 nanoflowers
Authors: Zhong Mianzeng , Meng Xiuqing , Wu Fengmin , Li Jingbo , Fang Yunzhang 
Published: October 2013

Abstract
A simple solvothermal approach is explored to prepare Bi2−x
Mo
x
Se3 nanostructures by employing N,N-dimethylformamide (DMF) as the solvent. Mo plays an important role in the assembly of the Bi2−x
Mo
x
Se3 nanostructures from nanoplates to nanoflowers. Structural and morphological studies indicate that the resulting products are large specific surface area single-crystalline Bi2−x
Mo
x
Se3 nanoflowers self-assembled from thin nanoplates during the reaction process. The absorption properties of the as-prepared samples are investigated with Rhodamine B (RhB) as dye, and it is found that the Bi1.85Mo0.15Se3 nanoflowers show an optimal adsorption capacity, implying that Mo doping not only changes the morphologies of the nanostructures but also enhances their absorption behaviors.
Identification of a new genotype of Torque Teno Mini virus
Authors: Farsani Seyed Mohammad Jazaeri , Jebbink Maarten F , Deijs Martin , Canuti Marta , van Dort Karel A , Bakker Margreet , Grady Bart PX , Prins Maria , van Hemert Formijn J , Kootstra Neeltje A , van der Hoek Lia 
Published: October 2013

Abstract

Background
Although human torque teno viruses (TTVs) were first discovered in 1997, still many associated aspects are not clarified yet. The viruses reveal a remarkable heterogeneity and it is possible that some genotypes are more pathogenic than others. The identification of all genotypes is essential to confirm previous pathogenicity data, and an unbiased search for novel viruses is needed to identify TTVs that might be related to disease.

Method
The virus discovery technique VIDISCA-454 was used to screen serum of 55 HIV-1 positive injecting drug users, from the Amsterdam Cohort Studies, in search for novel blood-blood transmittable viruses which are undetectable via normal diagnostics or panvirus-primer PCRs.

Results
A novel torque teno mini virus (TTMV) was identified in two patients and the sequence of the full genomes were determined. The virus is significantly different from the known TTMVs (< 40% amino acid identity in ORF1), yet it contains conserved characteristics that are also present in other TTMVs. The virus is chronically present in both patients, and these patients both suffered from a pneumococcal pneumonia during follow up and had extremely low B-cells counts.

Conclusion
We describe a novel TTMV which we tentatively named TTMV-13. Further research is needed to address the epidemiology and pathogenicity of this novel virus.
Identification of B-cell epitopes in an antigen for inducing specific class of antibodies
Authors: Gupta Sudheer , Ansari Hifzur Rahman , Gautam Ankur ,   Open Source Drug Discovery Consortium, Raghava Gajendra PS 
Published: October 2013

AbstractBackgroundIn the past, numerous methods have been developed for predicting antigenic regions or B-cell epitopes that can induce B-cell response. To the best of authors’ knowledge, no method has been developed for predicting B-cell epitopes that can induce a specific class of antibody (e.g.,IgA, IgG) except allergenic epitopes (IgE). In this study, an attempt has been made to understand the relation between primary sequence of epitopes and the class of antibodies generated.ResultsThe dataset used in this study has been derived from Immune Epitope Database and consists of 14725 B-cell epitopes that include 11981 IgG, 2341 IgE, 403 IgA specific epitopes and 22835 non-B-cell epitopes. In order to understand the preference of residues or motifs in these epitopes, we computed and compared amino acid and dipeptide composition of IgG, IgE, IgA inducing epitopes and non-B-cell epitopes. Differences in composition profiles of different classes of epitopes were observed, and few residues were found to be preferred. Based on these observations, we developed models for predicting antibody class-specific B-cell epitopes using various features like amino acid composition, dipeptide composition, and binary profiles. Among these, dipeptide composition-based support vector machine model achieved maximum Matthews correlation coefficient of 0.44, 0.70 and 0.45 for IgG, IgE and IgA specific epitopes respectively. All models were developed on experimentally validated non-redundant dataset and evaluated using five-fold cross validation. In addition, the performance of dipeptide-based model was also evaluated on independent dataset.ConclusionPresent study utilizes the amino acid sequence information for predicting the tendencies of antigens to induce different classes of antibodies. For the first time,in silicomodels have been developed for predicting B-cell epitopes, which can induce specific class of antibodies. A web service called IgPred has been developed to serve the scientific community. This server will be useful for researchers working in the field of subunit/epitope/peptide-based vaccines and immunotherapy (http://crdd.osdd.net/raghava/igpred/).ReviewersThis article was reviewed by Dr. M Michael Gromiha, Dr Christopher Langmead (nominated by Dr Robert Murphy) and Dr Lina Ma (nominated by Dr Zhang Zhang).
Chemical and pharmacological investigation of micropropagated Hygrophila pogonocalyx produced from leaf explants
Authors: Ho Chin-Wen , Lin Rong-Dih , Lee Tzong-Huei , Lin Chien-Hung , Wen Chi-Luan , Tseng Yu-Ting , Lee Mei-Hsien 
Published: October 2013

Abstract

Background
An optimized method for indirect shoot organogenesis from the leaf explants of Hygrophila pogonocalyx, a rare and endemic species in Taiwan, was developed to supply enough quantity of plant materials for the first chemical and pharmacological investigation.

Results
Incubation of the young leaves on Murashige and Skoog (MS) medium supplemented with 6-benzylaminopurine (0.5 mg/l) and indole-3-acetic acid (0.1 mg/l) resulted in the best multiplication rate for organogenesis. The average number of adventitious buds per leaf was 22.8 ± 1.9 after 8-week culture. The adventitious buds rooted and developed into plantlets when cultured simply on MS medium. Using this protocol, up to 37,600 plants were produced from a single leaf explant in one year. From the ethanol extract of the leaves of this micropropagated plant, 13 compounds were isolated and identified, including two flavones (1, 11), four flavonols (9, 10, 12, and 13), three phenylethanoid glycosides (6–8), two alkylated glycosides (2–3), and two steroids (4–5). Of these, acteoside (7) exhibited anti-tyrosinase activity in human epidermal melanocytes and luteolin 7-O-β-d-glucopyranoside (11) exhibited the greatest neurocytoprotective activity.

Conclusions
The method, indirect shoot organogenesis from leaf explants of H. pogonocalyx, could be developed to supply enough quantity of plant materials for the chemical and pharmacological investigation. In the present study, the isolated active compounds may develop for whitening agents or treating neurodegenerative diseases in the future.
Efficacy and safety of rituximab treatment in early primary Sjögren's syndrome: a prospective, multi-center, follow-up study
Authors: Carubbi Francesco , Cipriani Paola , Marrelli Alessandra , Benedetto Paola Di , Ruscitti Piero , Berardicurti Onorina , Pantano Ilenia , Liakouli Vasiliki , Alvaro Saverio , Alunno Alessia , Manzo Antonio , Ciccia Francesco , Gerli Roberto , Triolo Giovanni , Giacomelli Roberto 
Published: October 2013

Abstract
Introduction
Primary Sjögren’s syndrome (pSS) is an autoimmune disorder affecting exocrine glands; however, a subgroup of pSS patients experience systemic extra-glandular involvement leading to a worsening of disease prognosis. Current therapeutic options are mainly empiric and often translated by other autoimmune diseases. In the last few years growing evidence suggests that B-cell depletion by rituximab (RTX) is effective also in pSS. Patients with early active disease appear to be those who could benefit the most from RTX. The aim of this study was to investigate the efficacy and safety of RTX in comparison to disease modifying anti-rheumatic drugs (DMARDs) in early active pSS patients.

Methods
Forty-one patients with early pSS and active disease (EULAR Sjogren’s syndrome disease activity index, ESSDAI ≥ 6) were enrolled in the study. Patients were treated with either RTX or DMARDs in two different Rheumatology centers and followed up for 120 weeks. Clinical assessment was performed by ESSDAI every 12 weeks up to week 120 and by self-reported global disease activity pain, sicca symptoms and fatigue on visual analogic scales, unstimulated saliva flow and Schirmer’s I test at week 12, 24, 48, 72, 96, and 120. Laboratory assessment was performed every 12 weeks to week 120. Two labial minor salivary gland (MSG) biopsies were obtained from all patients at the time of inclusion in the study and at week 120.

Results
Our study demonstrated that RTX treatment results in a faster and more pronounced decrease of ESSDAI and other clinical parameters compared to DMARDs treatment. No adverse events were reported in the two groups. We also observed that RTX is able to reduce glandular infiltrate, interfere with B/T compartmentalization and consequently with the formation of ectopic lymphoid structures and germinal center-like structures in pSS-MSGs.

Conclusions
To our knowledge, this is the first study performed in a large cohort of early active pSS patients for a period of 120 weeks. We showed that RTX is a safe and effective agent to be employed in pSS patients with systemic, extra-glandular involvement. Furthermore, our data on pSS-MSGs provide additional biological basis to employ RTX in this disease.
Hepatobiliary and Pancreatic Neoplasms in Patients With McCune-Albright Syndrome
Authors: Gaujoux Sébastien , Salenave Sylvie , Ronot Maxime , Rangheard Anne-Sophie , Cros Jérôme , Belghiti Jacques , Sauvanet Alain , Ruszniewski Philippe , Chanson Philippe 
Published: October 2013

Background:
McCune-Albright syndrome (MAS), which includes polycystic fibrous dysplasia, precocious puberty, and café au lait spots, is a rare disorder caused by somatic activating mutations of the GNAS gene. GNAS mutations have also been implicated in various sporadic tumors, including hepatobiliary and pancreatic neoplasms.

Aim:
The aim of this study was to assess the prevalence of hepatobiliary and pancreatic neoplasms in patients with McCune-Albright syndrome.

Patients and Methods:
Nineteen patients diagnosed between 1995 and 2012 with MAS in a tertiary referral center for rare growth disorders were screened with dedicated gadolinium-enhanced magnetic resonance imaging for hepatobiliary and pancreatic neoplasms between June 2011 and December 2012.

Results:
Six (32%) of the 19 screened patients were found to have hepatic, pancreatic, or biliary lesions, excluding liver hemangiomas, liver cysts, and focal nodular hyperplasia. This includes pancreatic ductal lesions observed in 4 patients, including numerous branch-duct intraductal papillary mucinous neoplasms in 3 patients. Biliary lesions were observed in 1 patient, with a large choledochal cyst also involving the left biliary branch. Finally, multiple inflammatory/telangiectatic hepatic adenomas were observed in 2 patients, including 1 with proven somatic GNAS mutation.

Conclusion:
We describe the first observation of syndromic intraductal papillary mucinous neoplasms and the new association between MAS and pancreatic neoplasms, namely intraductal papillary mucinous neoplasms of the pancreas but also rare hepatobiliary neoplasms including liver adenomas and choledochal cysts. These findings strongly suggest that somatic activating GNAS mutations, possibly through cAMP pathway disorders, are involved in the tumorigenesis of hepatobiliary and pancreatic tissues originating from the foregut endoderm and have led us to use a routine screening by dedicated magnetic resonance imaging including both pancreatobiliary and liver sequences in patients with MAS.