bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning methods can replace 3D profile method in classification of amyloidogenic hexapeptides
Authors: Stanislawski Jerzy , Kotulska Malgorzata , Unold Olgierd 
Published: January 2013

Abstract

Background
Amyloids are proteins capable of forming fibrils. Many of them underlie serious diseases, like Alzheimer disease. The number of amyloid-associated diseases is constantly increasing. Recent studies indicate that amyloidogenic properties can be associated with short segments of aminoacids, which transform the structure when exposed. A few hundreds of such peptides have been experimentally found. Experimental testing of all possible aminoacid combinations is currently not feasible. Instead, they can be predicted by computational methods. 3D profile is a physicochemical-based method that has generated the most numerous dataset - ZipperDB. However, it is computationally very demanding. Here, we show that dataset generation can be accelerated. Two methods to increase the classification efficiency of amyloidogenic candidates are presented and tested: simplified 3D profile generation and machine learning methods.

Results
We generated a new dataset of hexapeptides, using more economical 3D profile algorithm, which showed very good classification overlap with ZipperDB (93.5%). The new part of our dataset contains 1779 segments, with 204 classified as amyloidogenic. The dataset of 6-residue sequences with their binary classification, based on the energy of the segment, was applied for training machine learning methods. A separate set of sequences from ZipperDB was used as a test set. The most effective methods were Alternating Decision Tree and Multilayer Perceptron. Both methods obtained area under ROC curve of 0.96, accuracy 91%, true positive rate ca. 78%, and true negative rate 95%. A few other machine learning methods also achieved a good performance. The computational time was reduced from 18-20 CPU-hours (full 3D profile) to 0.5 CPU-hours (simplified 3D profile) to seconds (machine learning).

Conclusions
We showed that the simplified profile generation method does not introduce an error with regard to the original method, while increasing the computational efficiency. Our new dataset proved representative enough to use simple statistical methods for testing the amylogenicity based only on six letter sequences. Statistical machine learning methods such as Alternating Decision Tree and Multilayer Perceptron can replace the energy based classifier, with advantage of very significantly reduced computational time and simplicity to perform the analysis. Additionally, a decision tree provides a set of very easily interpretable rules.
Novel aspects of grapevine response to phytoplasma infection investigated by a proteomic and phospho-proteomic approach with data integration into functional networks
Authors: Margaria Paolo , Abbà Simona , Palmano Sabrina 
Published: January 2013

Abstract

Background
Translational and post-translational protein modifications play a key role in the response of plants to pathogen infection. Among the latter, phosphorylation is critical in modulating protein structure, localization and interaction with other partners. In this work, we used a multiplex staining approach with 2D gels to study quantitative changes in the proteome and phosphoproteome of Flavescence dorée-affected and recovered ‘Barbera’ grapevines, compared to healthy plants.

Results
We identified 48 proteins that differentially changed in abundance, phosphorylation, or both in response to Flavescence dorée phytoplasma infection. Most of them did not show any significant difference in recovered plants, which, by contrast, were characterized by changes in abundance, phosphorylation, or both for 17 proteins not detected in infected plants. Some enzymes involved in the antioxidant response that were up-regulated in infected plants, such as isocitrate dehydrogenase and glutathione S-transferase, returned to healthy-state levels in recovered plants. Others belonging to the same functional category were even down-regulated in recovered plants (oxidoreductase GLYR1 and ascorbate peroxidase). Our proteomic approach thus agreed with previously published biochemical and RT-qPCR data which reported down-regulation of scavenging enzymes and accumulation of H2O2 in recovered plants, possibly suggesting a role for this molecule in remission from infection. Fifteen differentially phosphorylated proteins (| ratio | > 2, p < 0.05) were identified in infected compared to healthy plants, including proteins involved in photosynthesis, response to stress and the antioxidant system. Many were not differentially phosphorylated in recovered compared to healthy plants, pointing to their specific role in responding to infection, followed by a return to a steady-state phosphorylation level after remission of symptoms. Gene ontology (GO) enrichment and statistical analysis showed that the general main category “response to stimulus” was over-represented in both infected and recovered plants but, in the latter, the specific child category “response to biotic stimulus” was no longer found, suggesting a return to steady-state levels for those proteins specifically required for defence against pathogens.

Conclusions
Proteomic data were integrated into biological networks and their interactions were represented through a hypothetical model, showing the effects of protein modulation on primary metabolic ways and related secondary pathways. By following a multiplex-staining approach, we obtained new data on grapevine proteome pathways that specifically change at the phosphorylation level during phytoplasma infection and following recovery, focusing for the first time on phosphoproteome changes during pathogen infection in this host.
Male circumcision and prevalence of genital human papillomavirus infection in men: a multinational study
Authors: Albero Ginesa , Villa Luisa L , Lazcano-Ponce Eduardo , Fulp William , Papenfuss Mary R , Nyitray Alan G , Lu Beibei , Castellsagué Xavier , Abrahamsen Martha , Smith Danélle , Bosch F Xavier , Salmerón Jorge , Quiterio Manuel , Giuliano Anna R 
Published: January 2013

Abstract

Background
Accumulated evidence from epidemiological studies and more recently from randomized controlled trials suggests that male circumcision (MC) may substantially protect against genital HPV infection in men. The purpose of this study was to assess the association between MC and genital HPV infection in men in a large multinational study.

Methods
A total of 4072 healthy men ages 18–70 years were enrolled in a study conducted in Brazil, Mexico, and the United States. Enrollment samples combining exfoliated cells from the coronal sulcus, glans penis, shaft, and scrotum were analyzed for the presence and genotyping of HPV DNA by PCR and linear array methods. Prevalence ratios (PR) were used to estimate associations between MC and HPV detection adjusting for potential confounders.

Results
MC was not associated with overall prevalence of any HPV, oncogenic HPV types or unclassified HPV types. However, MC was negatively associated with non-oncogenic HPV infections (PR 0.85, 95% confident interval: 0.76-0.95), in particular for HPV types 11, 40, 61, 71, and 81. HPV 16, 51, 62, and 84 were the most frequently identified genotypes regardless of MC status.

Conclusions
This study shows no overall association between MC and genital HPV infections in men, except for certain non-oncogenic HPV types for which a weak association was found. However, the lack of association with MC might be due to the lack of anatomic site specific HPV data, for example the glans penis, the area expected to be most likely protected by MC.
Plasmodium vivax malaria in Mali: a study from three different regions
Authors: Bernabeu Maria , Gomez-Perez Gloria P , Sissoko Sibiri , Niambélé Mohamed B , Haibala Allassane Ag , Sanz Ariadna , Théra Mahamadou A , Fernandez-Becerra Carmen , Traoré Klénon , Alonso Pedro L , Bassat Quique , del Portillo Hernando A , Doumbo Ogobara 
Published: January 2013

Abstract

Background

Plasmodium vivax has traditionally been considered virtually absent from Western and Central Africa, due to the absence of the Duffy blood group in most of the population living in these areas. Recent reports, however, suggest the circulation of P. vivax in sub-Saharan Africa.

Methods
Giemsa/Field-stained smears from febrile patients recruited in five different cities (Goundam, Tombouctou, Gao, Bourem and Kidal) pertaining to three regions from Northern Mali were examined. Nested-PCR and DNA sequence analyses of selected samples were performed to fully confirm the presence of P. vivax infections.

Results
Results demonstrated the presence of P. vivax infections in close to 30% of the cases as detected by Giemsa/Field-stained smears and nested-PCR and DNA-sequence analyses of selected samples unequivocally confirmed the presence of P. vivax.

Conclusions
The diagnostics of this human malaria parasite should be taken into account in the context of malaria control and elimination efforts, not only in Mali, but also in sub-Saharan Africa.
Trends in multiplicity of Plasmodium falciparum infections among asymptomatic residents in the middle belt of Ghana
Authors: Agyeman-Budu Akua , Brown Charles , Adjei George , Adams Mohammed , Dosoo David , Dery Dominic , Wilson Michael , Asante Kwaku P , Greenwood Brian , Owusu-Agyei Seth 
Published: January 2013

Abstract

Background
Malaria is the most important cause of mortality and morbidity in children living in the Kintampo districts in the middle part of Ghana. This study has investigated the multiplicity of infection (MOI) within asymptomatic residents of the Kintampo districts, and the influence of age and seasonality on MOI, by studying the distribution of the polymorphic Plasmodium falciparum antigen merozoite surface protein 2 (MSP2).

Methods
DNA was extracted from an asymptomatic cohort of children and adults infected with P. falciparum during the period November 2003 to October 2004. Polymerase chain reaction was carried out and multiplicity of infection (MOI) was determined.

Results
Children under 10 years of age had an average MOI of 2.3 while adults 18 years and above had an average MOI of 1.4. Children below five years had high and low average MOIs of 2.8 in the March/April survey and 0.9 in the May/June survey respectively. A similar trend in the monthly distribution of MOI was observed for the entire cohort. IC/3D7 strains outnumbered the FC27 strains throughout the year by a ratio of about 4:1 with the difference between the prevalence of the two strains being least marked in the March/April survey, at the beginning of the rainy season. MOI was not linked to the level of malaria transmission as measured by the entomological inoculation rate.

Discussion/conclusion
The impact of interventions, introduced since this baseline study was carried out on the parasite diversity of asymptomatic residents will be the subject of further investigations.
Extranodal Natural Killer/T-cell lymphoma, nasal type: ‘midline lethal granuloma.’ A case report
Authors: Tlholoe Martha M. , Kotu Monica , Khammissa Razia A. G. , Bida Meschack , Lemmer Johan , Feller Liviu 
Published: January 2013

Abstract
Extranodal natural killer/T cell lymphoma, nasal type, is a non-Hodgkin lymphoma, most commonly affecting the nasal cavity, paranasal sinuses and nasopharynx. Clinically it is characterised by destruction of facial tissues, commencing in the midline. In most cases it arises from malignant transformation of natural killer cells (NK); sometimes from malignant transformation of cytotoxic T cells.
Extranodal NK/T cell lymphoma, nasal type, is rare, but even more rare in black persons. The purpose of this article is to report a severe case of extranodal NK/T cell lymphoma, nasal type, in an elderly black male.
Impact of a board-game approach on current smokers: a randomized controlled trial
Authors: Khazaal Yasser , Chatton Anne , Prezzemolo Roberto , Zebouni Fadi , Edel Yves , Jacquet Johan , Ruggeri Ornella , Burnens Emilie , Monney Grégoire , Protti Anne-Sylvie , Etter Jean-François , Khan Riaz , Cornuz Jacques , Zullino Daniele 
Published: January 2013

Abstract

Background
The main objective of our study was to assess the impact of a board game on smoking status and smoking-related variables in current smokers. To accomplish this objective, we conducted a randomized controlled trial comparing the game group with a psychoeducation group and a waiting-list control group.

Methods
The following measures were performed at participant inclusion, as well as after a 2-week and a 3-month follow-up period: “Attitudes Towards Smoking Scale” (ATS-18), “Smoking Self-Efficacy Questionnaire” (SEQ-12), “Attitudes Towards Nicotine Replacement Therapy” scale (ANRT-12), number of cigarettes smoked per day, stages of change, quit attempts, and smoking status. Furthermore, participants were assessed for concurrent psychiatric disorders and for the severity of nicotine dependence with the Fagerström Test for Nicotine Dependence (FTND).

Results
A time × group effect was observed for subscales of the ANRT-12, ATS-18 and SEQ-12, as well as for the number of cigarettes smoked per day. At three months follow-up, compared to the participants allocated to the waiting list group, those on Pick-Klop group were less likely to remain smoker.
Outcomes at 3 months were not predicted by gender, age, FTND, stage of change, or psychiatric disorders at inclusion.

Conclusions
The board game seems to be a good option for smokers. The game led to improvements in variables known to predict quitting in smokers. Furthermore, it increased smoking-cessation rates at 3-months follow-up. The game is also an interesting alternative for smokers in the precontemplation stage.
Selenium and sulindac are synergistic to inhibit intestinal tumorigenesis in Apc/p21 mice
Authors: Bi Xiuli , Pohl Nicole , Dong Huali , Yang Wancai 
Published: January 2013

Abstract

Background
Both selenium and non-steroidal anti-inflammatory drug (NSAID) sulindac are effective in cancer prevention, but their effects are affected by several factors including epigenetic alterations and gene expression. The current study was designed to determine the effects of the combination of selenium and sulindac on tumor inhibition and the underlying mechanisms.

Results
We fed the intestinal tumor model Apc/p21 mice with selenium- and sulindac-supplemented diet for 24 weeks, and found that the combination of selenium and sulindac significantly inhibited intestinal tumorigenesis, in terms of reducing tumor incidence by 52% and tumor multiplicities by 80% (p<0.01). Mechanistic studies revealed that the combination of selenium and sulindac led to the significant induction of the expression of p27 and p53 and JNK1 phosphorylation, and led to the suppression of β-catenin and its downstream targets. Impressively, the data also showed that demythelation on p21 promoter was associated with tumor inhibition by the combination of selenium and sulindac.

Conclusions
The selenium is synergistic with sulindac to exert maximal effects on tumor inhibition. This finding provides an important chemopreventive strategy using combination of anti-cancer agents, which has a great impact on cancer prevention and has a promising translational potential.
Mechanisms of chemoresistance in cancer stem cells
Authors: Abdullah Lissa Nurrul , Chow Edward Kai‐Hua 
Published: January 2013

AbstractChemotherapy is one of the standard methods of treatment in many cancers. While chemotherapy is often capable of inducing cell death in tumors and reducing the tumor bulk, many cancer patients experience recurrence and ultimately death because of treatment failure. In recent years, cancer stem cells (CSCs) have gained intense interest as key tumor‐initiating cells that may also play an integral role in recurrence following chemotherapy. As such, a number of mechanisms of chemoresistance have been identified in CSCs. In this review, we describe a number of these mechanisms of chemoresistance including ABC transporter expression, aldehyde dehydrogenase (ALDH) activity, B‐cell lymphoma‐2 (BCL2) related chemoresistance, enhanced DNA damage response and activation of key signaling pathways. Furthermore, we evaluate studies that demonstrate potential methods for overcoming chemoresistance and treating chemoresistant cancers that are driven by CSCs. By understanding how tumor‐initiating cells such as CSCs escape chemotherapy, more informed approaches to treating cancer will develop and may improve clinical outcomes for cancer patients.
Imaging heterogeneity in the mitochondrial redox state of premalignant pancreas in the pancreas-specific PTEN-null transgenic mouse model
Authors: Xu He N , Nioka Shoko , Li Lin Z 
Published: January 2013

Abstract

Background
Metabolic alteration is one of the hallmarks of carcinogenesis. We aimed to identify certain metabolic biomarkers for the early detection of pancreatic cancer (PC) using the transgenic PTEN-null mouse model. Pancreas-specific deletion of PTEN in mouse caused progressive premalignant lesions such as highly proliferative ductal metaplasia. We imaged the mitochondrial redox state of the pancreases of the transgenic mice approximately eight months old using the redox scanner, i.e., the nicotinamide adenine dinucleotide/oxidized flavoproteins (NADH/Fp) fluorescence imager at low temperature. Two different approaches, the global averaging of the redox indices without considering tissue heterogeneity along tissue depth and the univariate analysis of multi-section data using tissue depth as a covariate were adopted for the statistical analysis of the multi-section imaging data. The standard deviations of the redox indices and the histogram analysis with Gaussian fit were used to determine the tissue heterogeneity.

Results
All methods show consistently that the PTEN deficient pancreases (Pdx1-Cre;PTENlox/lox) were significantly more heterogeneous in their mitochondrial redox state compared to the controls (PTENlox/lox). Statistical analysis taking into account the variations of the redox state with tissue depth further shows that PTEN deletion significantly shifted the pancreatic tissue to an overall more oxidized state. Oxidization of the PTEN-null group was not seen when the imaging data were analyzed by global averaging without considering the variation of the redox indices along tissue depth, indicating the importance of taking tissue heterogeneity into account for the statistical analysis of the multi-section imaging data.

Conclusions
This study reveals a possible link between the mitochondrial redox state alteration of the pancreas and its malignant transformation and may be further developed for establishing potential metabolic biomarkers for the early diagnosis of pancreatic cancer.
Contracting with private providers for primary care services: evidence from urban China
Authors: Wang Yan , Eggleston Karen , Yu Zhenjie , Zhang Qiong 
Published: January 2013

AbstractControversy surrounds the role of the private sector in health service delivery, including primary care and population health services. China’s recent health reforms call for non-discrimination against private providers and emphasize strengthening primary care, but formal contracting-out initiatives remain few, and the associated empirical evidence is very limited. This paper presents a case study of contracting with private providers for urban primary and preventive health services in Shandong Province, China. The case study draws on three primary sources of data: administrative records; a household survey of over 1600 community residents in Weifang and City Y; and a provider survey of over 1000 staff at community health stations (CHS) in both Weifang and City Y. We supplement the quantitative data with one-on-one, in-depth interviews with key informants, including local officials in charge of public health and government finance.We find significant differences in patient mix: Residents in the communities served by private community health stations are of lower socioeconomic status (more likely to be uninsured and to report poor health), compared to residents in communities served by a government-owned CHS. Analysis of a household survey of 1013 residents shows that they are more willing to do a routine health exam at their neighborhood CHS if they are of low socioeconomic status (as measured either by education or income). Government and private community health stations in Weifang did not statistically differ in their performance on contracted dimensions, after controlling for size and other CHS characteristics. In contrast, the comparison City Y had lower performance and a large gap between public and private providers. We discuss why these patterns arose and what policymakers and residents considered to be the main issues and concerns regarding primary care services.
Implication of indolamine 2,3 dioxygenase in the tolerance toward fetuses, tumors, and allografts
Authors: Dürr Sophie , Kindler Vincent 
Published: January 2013

Abstract
Review on indolamine 2,3 dioxygenase as required to maintain peripheral tolerance, but if activated too vigorously, may impair pathogen tumor clearance or eradication.
Mammalian IDO is a heme-containing enzyme whose main activity in mammals is to degrade the essential amino acid tryp into l-kynurenine. Although the link between its enzymatic activity and the immune response is not straightforward, several lines of evidence suggest that this enzyme is involved in fighting infections and paradoxically, also in the establishment of the immune tolerance associated with fetus implantation and with the development of oncogenic processes. IDO is associated with the successful development of the fetus. It participates early in pregnancy to the efficient invasion of the uterine mucosa by the nascent trophoblast and remains active throughout the whole process, as illustrated by the decrease in systemic tryp from the second trimester of gestation and the return to normal values after delivery. The short-term activation of IDO in response to invading pathogens and emerging tumors participates in the elimination of these threats, whereas the sustained activation of IDO often results in a state of immune tolerance that may favor chronic infections and the uncontrolled proliferation of malignant cells. However, despite these potential deleterious effects of IDO, the enzyme is instrumental in maintaining the peripheral tolerance that is required to avoid autoimmune diseases. Below, we review the implication of IDO activation upon the physiological development of the fetus and the pathological development of tumors and discuss whether such an enzyme could be used as a therapeutic tool to decrease the rate of allograft rejections via its potent immunomodulatory properties.
Sirtuin deacylases: a molecular link between metabolism and immunity
Authors: Preyat Nicolas , Leo Oberdan 
Published: January 2013

Abstract
Review on the role of sirtuins in modulating an inflammatory response.
Lysine deacetylation by the NAD+-dependent family of sirtuins has been recognized as an important post-translational modification regulating a wide range of cellular processes. These lysine deacetylases have attracted much interest based on their ability to promote survival in response to stress. Sirtuins require NAD+ for their enzymatic activity, suggesting that these enzymes may represent molecular links between cell metabolism and several human disorders, including diabetes and cancer. Inflammation represents a pathological situation with clear connections to metabolism and aging in humans, raising the possibility that sirtuins may also play an important role during a normal and/or a pathological immune response. A growing body of data has confirmed the immunomodulatory properties of sirtuins, although often with contrasting and opposing conclusions. These observations will be summarized herein and the possible strategies that may lead to the development of novel therapeutic approaches to treat inflammation briefly discussed.