bluuebunny/crossref_metadata_2025_split huggingface dataset:
The C-terminus of CBFβ-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis
Authors: Kamikubo Yasuhiko , Hyde R. Katherine , Zhao Ling , Alemu Lemlem , Rivas Cecilia , Garrett Lisa J. , Liu P. Paul 
Published: November 2012

Abstract
The C-terminus of CBFβ-SMMHC, the fusion protein produced by a chromosome 16 inversion in acute myeloid leukemia subtype M4Eo, contains domains for self-multimerization and transcriptional repression, both of which have been proposed to be important for leukemogenesis by CBFβ-SMMHC. To test the role of the fusion protein's C-terminus in vivo, we generated knock-in mice expressing a C-terminally truncated CBFβ-SMMHC (CBFβ-SMMHCΔC95). Embryos with a single copy of CBFβ-SMMHCΔC95 were viable and showed no defects in hematopoiesis, whereas embryos homozygous for the CBFβ-SMMHCΔC95 allele had hematopoietic defects and died in mid-gestation, similar to embryos with a single-copy of the full-length CBFβ-SMMHC. Importantly, unlike mice expressing full-length CBFβ-SMMHC, none of the mice expressing CBFβ-SMMHCΔC95 developed leukemia, even after treatment with a mutagen, although some of the older mice developed a nontransplantable myeloproliferative disease. Our data indicate that the CBFβ-SMMHC's C-terminus is essential to induce embryonic hematopoietic defects and leukemogenesis.
P2TF: a comprehensive resource for analysis of prokaryotic transcription factors
Authors: Ortet Philippe , De Luca Gilles , Whitworth David E , Barakat Mohamed 
Published: November 2012

Abstract

Background
Transcription factors (TFs) are DNA-binding proteins that regulate gene expression by activating or repressing transcription. Some have housekeeping roles, while others regulate the expression of specific genes in response to environmental change. The majority of TFs are multi-domain proteins, and they can be divided into families according to their domain organisation. There is a need for user-friendly, rigorous and consistent databases to allow researchers to overcome the inherent variability in annotation between genome sequences.

Description
P2TF (Predicted Prokaryotic Transcription Factors) is an integrated and comprehensive database relating to transcription factor proteins. The current version of the database contains 372,877 TFs from 1,987 completely sequenced prokaryotic genomes and 43 metagenomes. The database provides annotation, classification and visualisation of TF genes and their genetic context, providing researchers with a one-stop shop in which to investigate TFs. The P2TF database analyses TFs in both predicted proteomes and reconstituted ORFeomes, recovering approximately 3% more TF proteins than just screening predicted proteomes. Users are able to search the database with sequence or domain architecture queries, and resulting hits can be aligned to investigate evolutionary relationships and conservation of residues. To increase utility, all searches can be filtered by taxonomy, TF genes can be added to the P2TF cart, and gene lists can be exported for external analysis in a variety of formats.

Conclusions
P2TF is an open resource for biologists, allowing exploration of all TFs within prokaryotic genomes and metagenomes. The database enables a variety of analyses, and results are presented for user exploration as an interactive web interface, which provides different ways to access and download the data. The database is freely available athttp://www.p2tf.org/.
Isolation of Pediococcus acidilacticiKp10 with ability to secrete bacteriocin-like inhibitory substance from milk products for applications in food industry
Authors: Abbasiliasi Sahar , Tan Joo Shun , Ibrahim Tengku Azmi Tengku , Ramanan Ramakrishnan Nagasundara , Vakhshiteh Faezeh , Mustafa Shuhaimi , Ling Tau Chuan , Rahim Raha Abdul , Ariff Arbakariya B 
Published: November 2012

Abstract

Background
Lactic acid bacteria (LAB) can be isolated from traditional milk products. LAB that secrete substances that inhibit pathogenic bacteria and are resistant to acid, bile, and pepsin but not vancomycin may have potential in food applications.

Results
LAB isolated from a range of traditional fermented products were screened for the production of bacteriocin-like inhibitory substances. A total of 222 LAB strains were isolated from fermented milk products in the form of fresh curds, dried curds, and ghara (a traditional flavor enhancer prepared from whey), and fermented cocoa bean. Eleven LAB isolates that produced antimicrobial substances were identified as Lactococcus lactis, Lactobacillus plantarum, and Pediococcus acidilactici strains by biochemical methods and 16S rDNA gene sequencing. Of these, the cell-free supernatant of Kp10 (P. acidilactici) most strongly inhibited Listeria monocytogenes. Further analysis identified the antimicrobial substance produced by Kp10 as proteinaceous in nature and active over a wide pH range. Kp10 (P. acidilactici) was found to be catalase-negative, able to produce β-galactosidase, resistant to bile salts (0.3%) and acidic conditions (pH 3), and susceptible to most antibiotics.

Conclusion
Traditionally prepared fermented milk products are good sources of LAB with characteristics suitable for industrial applications. The isolate Kp10 (P. acidilactici) shows potential for the production of probiotic and functional foods.
Prognostic value of admission heart rate in patients with ST-segment elevation myocardial infarction: Role of Type 2 diabetes mellitus
Authors: Han Zhang , Yan-min Yang , Jun Zhu , Li-sheng Liu , Hui-qiong Tan , Yao Liu 
Published: November 2012

Abstract

Background
It’s unknown whether the prognostic value of admission heart rate (HR) was different in patients with ST-segment elevation myocardial infarction (STEMI) with or without concomitant type 2 diabetes mellitus (T2DM).

Methods
Consecutive STEMI patients who presented within 12 hours of symptom onset were recruited from 274 hospitals in China. Participants were stratified into quartiles by admission HR. Baseline characteristics, current therapeutic recommenda- tions, laboratory biochemical tests, 30-day all-cause mortality and Cardiovascular Events (CVE, including all-cause death, reinfarction and stroke) were compared across admission HR quartiles.

Results
We evaluated 7294 STEMI patients, of these 820 (11.2%) had known T2DM. The admission HR quartile stratification was significantly associated with all-cause mortality and CVE regardless of T2DM status (P < 0.001 both for survival and CVE). After adjusted other risk factors, in patients without T2DM, comparing with HR <66 b.p.m., the increase of HR level was associated with worse prognosis (P < 0.05). In patients with T2DM, the hazard ratios for 30-day CVE were 1.75 (95%CI), 1.92 (95%CI), 3.00 (95%CI) in the HR of 66–76 b.p.m., 77–88 b.p.m., and >88 b.p.m., respectively. Results were similar for 30-day all-cause mortality, but the hazard ratios in Q2 (P = 0.139 and P =0.086 for survival and CVE, respectively) and Q3 groups were non-significant (P = 0.072 and P =0.033 for survival and CVE, respectively). There was a significant interaction effect of HR and T2DM on 30-day CVE mortality (P = 0.035), which was not found on all-cause mortality (P = 0.126).

Conclusion
Admission heart rate was an important risk factor of 30-day all-cause mortality and CVE in patients with STEMI with or without T2DM. However, the predictive effect was modified by T2DM.
Spatial morphological and molecular differences within solid tumors may contribute to the failure of vascular disruptive agent treatments
Authors: Nguyen Linh , Fifis Theodora , Malcontenti-Wilson Caterina , Chan Lie Sam , Costa Patricia Nunes Luiza , Nikfarjam Mehrdad , Muralidharan Vijayaragavan , Christophi Christopher 
Published: November 2012

Abstract

Background
Treatment of solid tumors with vascular disrupting agent OXi4503 results in over 90% tumor destruction. However, a thin rim of viable cells persists in the tumor periphery following treatment, contributing to subsequent recurrence. This study investigates inherent differences in the microenvironment of the tumor periphery that contribute to treatment resistance.

Methods
Using a murine colorectal liver metastases model, spatial morphological and molecular differences within the periphery and the center of the tumor that may account for differences in resistance to OXi4503 treatment were investigated. H&E staining and immunostaining were used to examine vessel maturity and stability, hypoxia and HIF1α levels, accumulation of immune cells, expression of proangiogenic factors/receptors (VEGF, TGF-β, b-FGF, and AT1R) and expression of EMT markers (ZEB1, vimentin, E-cadherin and β-catenin) in the periphery and center of established tumors. The effects of OXi4503 on tumor vessels and cell kinetics were also investigated.

Results
Significant differences were found between tumor periphery and central regions, including association of the periphery with mature vessels, higher accumulation of immune cells, increased growth factor expression, minimal levels of hypoxia and increased evidence of EMT. OXi4503 treatment resulted in collapse of vessels in the tumor center; however vasculature in the periphery remained patent. Similarly, tumor apoptosis and proliferation were differentially modulated between centre and periphery after treatment.

Conclusions
The molecular and morphological differences between tumor periphery and center may account for the observed differential resistance to OXi4503 treatment and could provide targets for drug development to totally eliminate metastases.
Electrochemotherapy of cutaneous metastasis from breast cancer in elderly patients: a preliminary report
Authors: Benevento Raffaella , Santoriello Antonio , Perna Giuseppe , Canonico Silvestro 
Published: November 2012

Abstract

Background
The management of cutaneous metastases often represents a challenge because they may be widespread and may recur after radiotherapy or chemotherapy; breast cancer accounts for 51% of the total cases of cutaneous metastases. When surgical excision of chest wall recurrences is not possible and other local treatments such as radiotherapy or radiotherapy with hyperthermia fail, topical chemotherapy and electrochemotherapy (ECT) might be taken into account.
ECT is a new local treatment of solid tumors which can be defined as the local potentiation, by means of permeabilizing electric pulses, of the antitumor activity of a non permeating anticancer drug with high intrinsic cytotoxicity.

Methods
This prospective observational study took place throughout March 2010 to October 2011. Twelve consecutive elderly patients (1 man and 11 women, median age of 76 years) with regional or distant skin or subcutaneous metastases from breast cancer, with or without visceral disease, were included in the study. Patient enrollment was carried out according to the ESOPE criteria. Bleomycin administration was followed by the application of brief electric pulses to each tumor nodule within 8 min after intravenous infusion of the drug. Electric currents were delivered by means of a 2–3 cm long needle electrode according to lesion size. All treatments were performed using the CliniporatorTM device.

Results
We observed Complete Response(CR) in 75.3% (107 metastases), Partial Response(PR) in 17% (24 metastases), no change in 7.7% (11 metastases) . No serious ECT-related adverse events were reported; adverse events consisted of pain in the treated area one to two days after treatment (1 patient, 8.3%) and ulceration of treated area (1 patient, 8.3%).

Conclusion
ECT could be suggested as a primary local therapy in patients not suitable for surgical removal of the primary tumor, and clinicians should not hesitate to use it even in the elderly.
Temporal aggregation impacts on epidemiological simulations employing microcontact data
Authors: Hashemian Mohammad , Qian Weicheng , Stanley Kevin G , Osgood Nathaniel D 
Published: November 2012

Abstract

Background
Microcontact datasets gathered automatically by electronic devices have the potential augment the study of the spread of contagious disease by providing detailed representations of the study population’s contact dynamics. However, the impact of data collection experimental design on the subsequent simulation studies has not been adequately addressed. In particular, the impact of study duration and contact dynamics data aggregation on the ultimate outcome of epidemiological models has not been studied in detail, leaving the potential for erroneous conclusions to be made based on simulation outcomes.

Methods
We employ a previously published data set covering 36 participants for 92 days and a previously published agent-based H1N1 infection model to analyze the impact of contact dynamics representation on the simulated outcome of H1N1 transmission. We compared simulated attack rates resulting from the empirically recorded contact dynamics (ground truth), aggregated, typical day, and artificially generated synthetic networks.

Results
No aggregation or sampling policy tested was able to reliably reproduce results from the ground-truth full dynamic network. For the population under study, typical day experimental designs – which extrapolate from data collected over a brief period – exhibited too high a variance to produce consistent results. Aggregated data representations systematically overestimated disease burden, and synthetic networks only reproduced the ground truth case when fitting errors systemically underestimated the total contact, compensating for the systemic overestimation from aggregation.

Conclusions
The interdepedendencies of contact dynamics and disease transmission require that detailed contact dynamics data be employed to secure high fidelity in simulation outcomes of disease burden in at least some populations. This finding serves as motivation for larger, longer and more socially diverse contact dynamics tracing experiments and as a caution to researchers employing calibrated aggregate synthetic representations of contact dynamics in simulation, as the calibration may underestimate disease parameters to compensate for the overestimation of disease burden imposed by the aggregate contact network representation.
Improving N-terminal protein annotation of Plasmodium species based on signal peptide prediction of orthologous proteins
Authors: Neto Armando de Menezes , Alvarenga Denise A , Rezende Antônio M , Resende Sarah S , Ribeiro Ricardo de Souza , Fontes Cor JF , Carvalho Luzia H , de Brito Cristiana F Alves 
Published: November 2012

Abstract

Background
Signal peptide is one of the most important motifs involved in protein trafficking and it ultimately influences protein function. Considering the expected functional conservation among orthologs it was hypothesized that divergence in signal peptides within orthologous groups is mainly due to N-terminal protein sequence misannotation. Thus, discrepancies in signal peptide prediction of orthologous proteins were used to identify misannotated proteins in five Plasmodium species.

Methods
Signal peptide (SignalP) and orthology (OrthoMCL) were combined in an innovative strategy to identify orthologous groups showing discrepancies in signal peptide prediction among their protein members (Mixed groups). In a comparative analysis, multiple alignments for each of these groups and gene models were visually inspected in search of misannotated proteins and, whenever possible, alternative gene models were proposed. Thresholds for signal peptide prediction parameters were also modified to reduce their impact as a possible source of discrepancy among orthologs. Validation of new gene models was based on RT-PCR (few examples) or on experimental evidence already published (ApiLoc).

Results
The rate of misannotated proteins was significantly higher in Mixed groups than in Positive or Negative groups, corroborating the proposed hypothesis. A total of 478 proteins were reannotated and change of signal peptide prediction from negative to positive was the most common. Reannotations triggered the conversion of almost 50% of all Mixed groups, which were further reduced by optimization of signal peptide prediction parameters.

Conclusions
The methodological novelty proposed here combining orthology and signal peptide prediction proved to be an effective strategy for the identification of proteins showing wrongly N-terminal annotated sequences, and it might have an important impact in the available data for genome-wide searching of potential vaccine and drug targets and proteins involved in host/parasite interactions, as demonstrated for five Plasmodium species.
Myxofibrosarcoma of the sinus piriformis: case report and literature review
Authors: Qiubei Zhu , Cheng Lin , Yaping Xu , Shunzhang Lin , Jingping Fan 
Published: November 2012

Abstract
Myxofibrosarcoma is a common sarcoma in the extremities of older people, but is rare in the head and neck region. Here, we report the case of a 42-year-old male patient in whom myxofibrosarcoma generated from the sinus piriformis. Histopathologically, the tumor was characterized by spindle cellular proliferation with moderate cellular density in fibromyxoid stroma. Immunohistochemically, the tumor cells showed positive reactivity for vimentin, Ki-67, smooth muscle actin, and CD34, but negative staining for S-100. Based on these results, the tumor was diagnosed as a low-grade myxofibrosarcoma. Resection of the tumor was performed via a transcervical approach. The patient’s postoperative clinical course was uneventful and no local recurrence or distant metastasis has been found so far. The pathology, clinical characteristics, and treatment of myxofibrosarcoma are also reviewed.
Clinical practice guidelines for patients with gastrointestinal stromal tumor in Taiwan
Authors: Yeh Chun-Nan , Hwang Tsann-Long , Huang Ching-Shui , Lee Po-Huang , Wu Chew-Wun , Chen-Guo Ker , Jan Yi-Yin , Chen Miin-Fu 
Published: November 2012

Abstract
For many years, the understanding of gastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the gastrointestinal tract, has been very limited. However, it is now possible to provide a more precise definition through the use of pathology classification and molecular techniques. Coupled with the advancement of clinical practice, especially the development of targeted therapy, there is now a much better insight into its treatment. At present, organizations such as the National Comprehensive Cancer Network in the USA and the European Society for Medical Oncology in Europe have established a consensus and drawn up guidelines for the diagnosis, treatment, and follow-up of GISTs.
With experts coming from various districts in Taiwan and combining the most recent clinical data and experiences, the Taiwan Surgical Society of Gastroenterology drafted the first national GIST treatment guidelines after a consensus meeting in 2007. Following subsequent advances in GIST diagnosis and treatment, further revisions and modifications have been made to the original guidelines. We present here the updated consensus and recommendations of the Taiwan Surgical Society of Gastroenterology for the diagnosis and treatment of GIST. We hope these guidelines can help enhance the quality of diagnosis, treatment, and care of patients with GIST in Taiwan.
Compensatory substitutions in the HCV NS3/4A protease cleavage sites are not observed in patients treated unsuccessfully with telaprevir combination treatment
Authors: Sullivan James C , Zhang Eileen Z , Bartels Doug J , Tigges Ann , Dorrian Jennifer L , Kwong Ann D , Kieffer Tara L 
Published: November 2012

Abstract

Background
Development of compensatory mutations within the HIV p7/p1 and p1/p6 protease cleavage site region has been observed in HIV-infected patients treated with protease inhibitors. Mechanisms of fitness compensation may occur in HCV populations upon treatment of HCV protease inhibitors as well.

Findings
In this study, we investigated whether substitutions in protease cleavage site regions of HCV occur in response to a treatment regimen containing the NS3/4A protease inhibitor telaprevir (TVR). Evaluation of viral populations from 569 patients prior to treatment showed that the four NS3/4A cleavage sites were well conserved. Few changes in the cleavage site regions were observed in the 159 patients who failed TVR combination treatment, and no residues displayed evidence of directional selection after the acquisition of TVR-resistance.

Conclusions
Cleavage site mutations did not occur after treatment with the HCV protease inhibitor telaprevir.
Impact of sustained RNAi-mediated suppression of cellular cofactor Tat-SF1 on HIV-1 replication in CD4+ T cells
Authors: Green Victoria A , Arbuthnot Patrick , Weinberg Marc S 
Published: November 2012

Abstract

Background
Conventional anti-HIV drug regimens targeting viral enzymes are plagued by the emergence of drug resistance. There is interest in targeting HIV-dependency factors (HDFs), host proteins that the virus requires for replication, as drugs targeting their function may prove protective. Reporter cell lines provide a rapid and convenient method of identifying putative HDFs, but this approach may lead to misleading results and a failure to detect subtle detrimental effects on cells that result from HDF suppression. Thus, alternative methods for HDF validation are required. Cellular Tat-SF1 has long been ascribed a cofactor role in Tat-dependent transactivation of viral transcription elongation. Here we employ sustained RNAi-mediated suppression of Tat-SF1 to validate its requirement for HIV-1 replication in a CD4+ T cell-derived line and its potential as a therapeutic target.

Results
shRNA-mediated suppression of Tat-SF1 reduced HIV-1 replication and infectious particle production from TZM-bl reporter cells. This effect was not a result of increased apoptosis, loss of cell viability or an immune response. To validate its requirement for HIV-1 replication in a more relevant cell line, CD4+ SupT1 cell populations were generated that stably expressed shRNAs. HIV-1 replication was significantly reduced for two weeks (~65%) in cells with depleted Tat-SF1, although the inhibition of viral replication was moderate when compared to SupT1 cells expressing a shRNA targeting the integration cofactor LEDGF/p75. Tat-SF1 suppression was attenuated over time, resulting from decreased shRNA guide strand expression, suggesting that there is a selective pressure to restore Tat-SF1 levels.

Conclusions
This study validates Tat-SF1 as an HDF in CD4+ T cell-derived SupT1 cells. However, our findings also suggest that Tat-SF1 is not a critical cofactor required for virus replication and its suppression may affect cell growth. Therefore, this study demonstrates the importance of examining HIV-1 replication kinetics and cytotoxicity in cells with sustained HDF suppression to validate their therapeutic potential as targets.