bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treat-to-target strategies in pulmonary arterial hypertension: the importance of using multiple goals
Authors: Sitbon O. , Galiè N. 
Published: December 2010

Major advances have occurred in the treatment of pulmonary arterial hypertension (PAH) over the past decade. The advent of PAH-specific pharmacological treatments has offered hope to patients with a debilitating, progressive disease and a poor prognosis. Combined drug treatment offers improved benefits over monotherapy, and current treatment guidelines for PAH recommend a sequential add-on approach to combination therapy for patients in New York Heart Association (NYHA)/World Health Organization functional class (WHO FC) II–IV.Goal-oriented therapy determines the timing of treatment escalation by inadequate response to known prognostic indicators. Close monitoring of patients aids the early identification of inadequate response, so that treatment can be escalated promptly and before the patient's condition deteriorates further. Existing treatment goals are based on baseline values of prognostic indicators, but it is vital to identify risk factors that are both relevant during treatment and that can be assessed during follow-up appointments. Data from different PAH aetiologies indicate that NYHA/WHO FC is the most appropriate prognostic marker, with 6-min walk distance and several haemodynamic parameters representing alternatives.Future refinement of goal-oriented therapy could include the use of multiple prognostic markers, while additional, large clinical trials will answer questions concerning choice and combination of treatment goals.
High resolution mapping and positional cloning of ENU-induced mutations in the Rw region of mouse chromosome 5
Authors: Ching Yung-Hao , Munroe Robert J , Moran Jennifer L , Barker Anna K , Mauceli Evan , Fennell Tim , diPalma Frederica , Lindblad-Toh Kerstin , Abcunas Lindsay M , Gilmour Joyanna F , Harris Tanya P , Kloet Susan L , Luo Yunhai , McElwee John L , Mu Weipeng , Park Hyo K , Rogal David L , Schimenti Kerry J , Shen Lishuang , Shindo Mami , Shou James Y , Stenson Erin K , Stover Patrick J , Schimenti John C 
Published: December 2010

Abstract

Background
Forward genetic screens in mice provide an unbiased means to identify genes and other functional genetic elements in the genome. Previously, a large scale ENU mutagenesis screen was conducted to query the functional content of a ~50 Mb region of the mouse genome on proximal Chr 5. The majority of phenotypic mutants recovered were embryonic lethals.

Results
We report the high resolution genetic mapping, complementation analyses, and positional cloning of mutations in the target region. The collection of identified alleles include several with known or presumed functions for which no mutant models have been reported (Tbc1d14, Nol14, Tyms, Cad, Fbxl5, Haus3), and mutations in genes we or others previously reported (Tapt1, Rest, Ugdh, Paxip1, Hmx1, Otoe, Nsun7). We also confirmed the causative nature of a homeotic mutation with a targeted allele, mapped a lethal mutation to a large gene desert, and localized a spermiogenesis mutation to a region in which no annotated genes have coding mutations. The mutation in Tbc1d14 provides the first implication of a critical developmental role for RAB-GAP-mediated protein transport in early embryogenesis.

Conclusion
This collection of alleles contributes to the goal of assigning biological functions to all known genes, as well as identifying novel functional elements that would be missed by reverse genetic approaches.
A genomic perspective on the potential of Actinobacillus succinogenes for industrial succinate production
Authors: McKinlay James B , Laivenieks Maris , Schindler Bryan D , McKinlay Anastasia A , Siddaramappa Shivakumara , Challacombe Jean F , Lowry Stephen R , Clum Alicia , Lapidus Alla L , Burkhart Kirk B , Harkins Victoria , Vieille Claire 
Published: December 2010

AbstractBackgroundSuccinate is produced petrochemically from maleic anhydride to satisfy a small specialty chemical market. If succinate could be produced fermentatively at a price competitive with that of maleic anhydride, though, it could replace maleic anhydride as the precursor of many bulk chemicals, transforming a multi-billion dollar petrochemical market into one based on renewable resources.Actinobacillus succinogenesnaturally converts sugars and CO2into high concentrations of succinic acid as part of a mixed-acid fermentation. Efforts are ongoing to maximize carbon flux to succinate to achieve an industrial process.ResultsDescribed here is the 2.3 MbA. succinogenesgenome sequence with emphasis onA. succinogenes's potential for genetic engineering, its metabolic attributes and capabilities, and its lack of pathogenicity. The genome sequence contains 1,690 DNA uptake signal sequence repeats and a nearly complete set of natural competence proteins, suggesting thatA. succinogenesis capable of natural transformation.A. succinogeneslacks a complete tricarboxylic acid cycle as well as a glyoxylate pathway, and it appears to be able to transport and degrade about twenty different carbohydrates. The genomes ofA. succinogenesand its closest known relative,Mannheimia succiniciproducens, were compared for the presence of known Pasteurellaceae virulence factors. Both species appear to lack the virulence traits of toxin production, sialic acid and choline incorporation into lipopolysaccharide, and utilization of hemoglobin and transferrin as iron sources. Perspectives are also given on the conservation ofA. succinogenesgenomic features in other sequenced Pasteurellaceae.ConclusionsBothA. succinogenesandM. succiniciproducensgenome sequences lack many of the virulence genes used by their pathogenic Pasteurellaceae relatives. The lack of pathogenicity of these two succinogens is an exciting prospect, because comparisons with pathogenic Pasteurellaceae could lead to a better understanding of Pasteurellaceae virulence. The fact that theA. succinogenesgenome encodes uptake and degradation pathways for a variety of carbohydrates reflects the variety of carbohydrate substrates available in the rumen,A. succinogenes's natural habitat. It also suggests that many different carbon sources can be used as feedstock for succinate production byA. succinogenes.
"Pee-in-a-Pot": acceptability and uptake of on-site chlamydia screening in a student population in the Republic of Ireland
Authors: Vaughan Deirdre , O'Connell Emer , Cormican Martin , Brugha Ruairi , Faherty Colette , Balfe Myles , O'Donovan Diarmuid 
Published: December 2010

Abstract

Background
The aim of the study was to explore the acceptability and uptake of on-campus screening using a youth friendly approach in two Third Level higher education institutions (HEIs). This study is part of wider research exploring the optimal setting for chlamydia screening in Ireland.

Methods
Male and female students were given the opportunity to take a free anonymous test for chlamydia during a one week programme of "pee-in-a-pot" days at two HEI campuses in the West of Ireland. The study was set up after extensive consultation with the two HEIs and advertised on the two campuses using a variety of media in the two weeks preceding the screening days. Screening involved the provision and distribution of testing packs at communal areas and in toilet facilities. In Ireland, chlamydia notifications are highest amongst 20-29 year olds and hence the screening criterion was aimed at 18-29 year olds. Urine samples were tested using a nucleic acid amplification test (NAAT). Following the screening days, qualitative in-depth interviews were conducted with participants about their experiences of the event.

Results
Out of 1,249 test kits distributed in two HEIs, 592 specimens were collected giving a return rate of 47.5%. Tests excluded (54) were due to labelling errors or ineligibility of participants' age. Two thirds of those tested were females and the mean age was 21 years. Overall,3.9% (21/538) of participants tested positive, 5% (17/336) among females and 2% (4/191) among males. Participant interviews identified factors which enhanced student participation such as anonymity, convenience, accessibility of testing, and the informal and non-medical approach to testing.

Conclusions
Screening for chlamydia using on-campus "pee-in-a-pot" days is an acceptable strategy in this population. This model can detect and treat asymptomatic cases of chlamydia and avoid many of the barriers associated with testing for sexually transmitted infections (STIs) in clinical settings.
KRAS analysis in colorectal carcinoma: Analytical aspects of Pyrosequencing and allele-specific PCR in clinical practice
Authors: Sundström Magnus , Edlund Karolina , Lindell Monica , Glimelius Bengt , Birgisson Helgi , Micke Patrick , Botling Johan 
Published: December 2010

Abstract

Background
Epidermal growth factor receptor inhibitor therapy is now approved for treatment of metastatic colorectal carcinomas (CRC) in patients with tumors lacking KRAS mutations. Several procedures to detect KRAS mutations have been developed. However, the analytical sensitivity and specificity of these assays on routine clinical samples are not yet fully characterised.

Methods
The practical aspects and clinical applicability of a KRAS-assay based on Pyrosequencing were evaluated in a series of 314 consecutive CRC cases submitted for diagnostic KRAS analysis. The performance of Pyrosequencing compared to allele-specific, real-time PCR was then explored by a direct comparison of CE-IVD-marked versions of Pyrosequencing and TheraScreen (DxS) KRAS assays for a consecutive subset (n = 100) of the 314 clinical CRC samples.

Results
Using Pyrosequencing, 39% of the 314 CRC samples were found KRAS-mutated and several of the mutations (8%) were located in codon 61. To explore the analytical sensitivity of the Pyrosequencing assay, mutated patient DNA was serially diluted with wild-type patient DNA. Dilutions corresponding to 1.25-2.5% tumor cells still revealed detectable mutation signals. In clinical practice, our algorithm for KRAS analysis includes a reanalysis of samples with low tumor cell content (< 10%, n = 56) using an independent assay (allele-specific PCR, DxS). All mutations identified by Pyrosequencing were then confirmed and, in addition, one more mutated sample was identified in this subset of 56 samples. Finally, a direct comparison of the two technologies was done by re-analysis of a subset (n = 100) of the clinical samples using CE-IVD-marked versions of Pyrosequencing and TheraScreen KRAS assays in a single blinded fashion. The number of samples for which the KRAS codon 12/13 mutation status could be defined using the Pyrosequencing or the TheraScreen assay was 94 and 91, respectively, and both assays detected the same number of codon 12 and 13 mutations.

Conclusions

KRAS mutation detection using Pyrosequencing was evaluated on a consecutive set of clinical CRC samples. Pyrosequencing provided sufficient analytical sensitivity and specificity to assess the mutation status in routine formalin-fixed CRC samples, even in tissues with a low tumor cell content.
An assessment of early diagnosis and treatment of malaria by village health volunteers in the Lao PDR
Authors: Phommanivong Viengvaly , Thongkham Khanti , Deyer Gopinath , Rene Jean P , Barennes Hubert 
Published: December 2010

Abstract

Background
Early diagnosis and treatment (EDAT) is crucial to reducing the burden of malaria in low-income countries. In the Lao PDR, this strategy was introduced in 2004-2005 and an assessment was performed at the community level in January 2007.

Methods
EDAT with malaria rapid diagnostic test (MRDT) and artemisinin combination therapy (ACT) was prospectively assessed among 36 randomized village health volunteers (VHVs) and 720 patients in six malaria-endemic provinces of Laos (three pilot provinces (PP), and three non-pilots provinces (NPP)). ACT was also retrospectively assessed among 2188 patients within the same areas from June to November 2006. Two checklists were used and scores were calculated.

Results
EDAT performance of the VHVs was rated better in PP than in NPP (16.67% versus 38.89%, respectively, p = 0.004). Nearly all VHVs could diagnose malaria but only 16 (44%) could describe the symptoms of severe malaria. In January 2007, 31/720 (4%) patients tested positive using the Paracheck® test, 35 (5%) with microscopy (sensibility: 74.3%, specificity 99.3%, positive and negative predictive values: 83.9% and 98.7%, respectively). Patients from June to November were at higher risk of malaria: 35.19% of 2,188 febrile patients were positive (OR: 10.6, 95%CI: 7.4-15.5, p < 0.000). VHVs reported the MRDT easy to use, and yielded a satisfactory performance score. EDAT performance was rated as poor despite satisfactory results regarding ACT treatment, duration and dosages. Pre-referral treatment of severe malaria was infrequent and often inadequate, with 20% of these patients dying. Results suggest a higher mortality from severe malaria than officially reported. Shortage of ACT was frequent.

Discussion and conclusion
MRDT and ACT are useful and efficient and can be used by VHVs. VHVs' global EDAT performance is enhanced through training and monitoring. Persistent gaps in knowledge, care of patients and wrong treatment have to be addressed.
Dendritic cell subsets dynamics and cytokine production in SIVmac239-infected Chinese rhesus macaques
Authors: Xia Hou-Jun , Zhang Gao-Hong , Ma Jian-Ping , Dai Zheng-Xi , Li Shao-You , Han Jian-Bao , Zheng Yong-Tang 
Published: December 2010

Abstract

Background
Several studies have demonstrated that SIV infection progresses more slowly to experimental AIDS in Chinese rhesus macaques (Ch Rhs) than in Indian rhesus macaques (Ind Rhs). Here we investigated the dynamic and functional changes in dendritic cell (DC) subsets in SIVmac239-infected Ch Rhs.

Results
The numbers of both mDC and pDC strongly fluctuated but were not significantly changed during the acute and chronic phases of infection. However, the concentration of both poly (I:C)-induced IL-12 and HSV-1-induced IFN-α significantly increased in the acute phase of infection but returned to normal levels at the chronic phase of infection. The peak of IFN-α emerged earlier than that of IL-12, and it had a significantly positive correlation with IL-12, which indicated that IFN-α may initiate the immune activation. We also found that only the concentration of IFN-α was positively correlated with CD4+ T-cell counts, but it was negatively correlated with viral load.

Conclusion
High levels of IFN-α in the early stage of infection may contribute to effective control of virus replication, and normal levels of IFN-α during chronic infection may help Ch Rhs resist the disease progression. The change in DC subsets dynamics and cytokine production may help further our understanding of why Ch Rhs are able to live longer without progressing to an AIDS-like illness.
Involvement of Lysophosphatidic Acid in Bone Cancer Pain by Potentiation of TRPV1 via PKCe Pathway in Dorsal Root Ganglion Neurons
Authors: Pan Hai-Li , Zhang Yu-Qiu , Zhao Zhi-Qi 
Published: December 2010

Background: It has been demonstrated that lysophosphatidic acid (LPA) released from injury tissue and transient receptor potential vanilloid 1 (TRPV1) receptor are implicated in the induction of chronic pain. In the present study we examined whether an interaction between LPA receptor LPA1 and TRPV1 in dorsal root ganglion (DRG) neurons contributes to the development of bone cancer pain. Results: Bone cancer was established by injection of mammary gland carcinoma cells into the rat tibia. Following the development of bone cancer pain, the TRPV1 expression and capsaicin-evoked currents were up-regulated in rat DRG neurons at L4–6 segments. Immunohistochemistry staining revealed a high co-localization of LPA1 with TRPV1 in DRG neurons. In isolated DRG neurons, whole-cell patch recording showed that capsaicin-induced currents were potentiated by LPA in a dose-dependent manner. The potentiation was blocked by either LPA1 antagonist, protein kinase C (PKC) inhibitor or PKCε inhibitor, but not by protein kinase A (PKA) inhibitor or Rho inhibitor. In the behavioral tests, both mechanical allodynia and thermal hyperalgesia in bone cancer rats were attenuated by LPA1 antagonist. Conclusion: LPA potentiates TRPV1 current via a PKCe-dependent pathway in DRG neurons of rats with bone cancer, which may be a novel peripheral mechanism underlying the induction of bone cancer pain.
Thymic large cell neuroendocrine carcinoma: report of a resected case - a case report
Authors: Ogawa Fumihiro , Iyoda Akira , Amano Hideki , Nezu Kenji , Jiang Shi-Xu , Okayasu Isao , Satoh Yukitoshi 
Published: December 2010

Abstract
Thymic large cell neuroendocrine carcinomas (LCNECs) are very rare. We here describe a case in which the tumor could be completely resected. A 55-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor found at a regular health check-up. The patient underwent an extended thymectomy of an invasive thymoma of Masaoka's stage II that had been suspected preoperatively. The tumor was located in the right lobe of the thymus and was completely resected. Final pathological diagnosis of the surgical specimen was thymic LCNEC. The patient underwent adjuvant chemotherapy with irinotecan and cisplatin in accordance with the diagnosis of a lung LCNEC, and is alive without recurrence or metastasis 16 months after surgery.
Presentation and management of keloid scarring following median sternotomy: a case study
Authors: Patel Rikesh , Papaspyros Sotiris C , Javangula Kalyana C , Nair Unnikrishnan 
Published: December 2010

Abstract

Introduction
Keloid scars following median sternotomy are rare and occur more frequently in pigmented skin. Different management strategies have been described with variable success. We present a case of keloid scar formation following cardiac surgery including our management and the final aesthetic result.

Case description
A 64 year old female of fair complexion underwent mitral valve replacement. The procedure and postoperative recovery were uncomplicated, however, during the following year, thick keloid scars formed over the incision sites. Initial non surgical measures failed to relieve pain and did not offer any tangible aesthetic benefit. Eventually surgical excision was attempted. She presented to our clinic for nine months follow up with significant improvement in pain and aesthetic result.

Discussion and Evaluation
Several theories have attempted to explore the pathophysiology of keloid scar formation. A number of predisposing factors have been documented however none existed in this case. A variety of invasive and non invasive approaches have been described but significant differences in success rates and methodology of investigations still precludes a standardized management protocol.

Conclusions
In this case study a rare presentation of keloid scar has been presented. The variety of methods used to improve pain and aesthetic result demonstrates the propensity of keloid scars to recur and the therapeutic challenges that surgeons have to face in their quest for a satisfactory patient outcome.
Developmental control of lateralized neuron size in the nematode Caenorhabditis elegans
Authors: Goldsmith Andrew D , Sarin Sumeet , Lockery Shawn , Hobert Oliver 
Published: December 2010

Abstract

Background
Nervous systems are generally bilaterally symmetric on a gross structural and organizational level but are strongly lateralized (left/right asymmetric) on a functional level. It has been previously noted that in vertebrate nervous systems, symmetrically positioned, bilateral groups of neurons in functionally lateralized brain regions differ in the size of their soma. The genetic mechanisms that control these left/right asymmetric soma size differences are unknown. The nematode Caenorhabditis elegans offers the opportunity to study this question with single neuron resolution. A pair of chemosensory neurons (ASEL and ASER), which are bilaterally symmetric on several levels (projections, synaptic connectivity, gene expression patterns), are functionally lateralized in that they express distinct chemoreceptors and sense distinct chemosensory cues.

Results
We describe here that ASEL and ASER also differ substantially in size (soma volume, axonal and dendritic diameter), a feature that is predicted to change the voltage conduction properties of the two sensory neurons. This difference in size is not dependent on sensory input or neuronal activity but developmentally programmed by a pathway of gene regulatory factors that also control left/right asymmetric chemoreceptor expression of the two ASE neurons. This regulatory pathway funnels via the DIE-1 Zn finger transcription factor into the left/right asymmetric distribution of nucleoli that contain the rRNA regulator Fibrillarin/FIB-1, a RNA methyltransferase implicated in the non-hereditary immune disease scleroderma, which we find to be essential to establish the size differences between ASEL and ASER.

Conclusions
Taken together, our findings reveal a remarkable conservation of the linkage of functional lateralization with size differences across phylogeny and provide the first insights into the developmentally programmed regulatory mechanisms that control neuron size lateralities.
Floral homeotic C function genes repress specific B function genes in the carpel whorl of the basal eudicot California poppy (Eschscholzia californica)
Authors: Yellina Aravinda L , Orashakova Svetlana , Lange Sabrina , Erdmann Robert , Leebens-Mack Jim , Becker Annette 
Published: December 2010

Abstract

Background
The floral homeotic C function gene AGAMOUS (AG) confers stamen and carpel identity and is involved in the regulation of floral meristem termination in Arabidopsis. Arabidopsis ag mutants show complete homeotic conversions of stamens into petals and carpels into sepals as well as indeterminacy of the floral meristem. Gene function analysis in model core eudicots and the monocots rice and maize suggest a conserved function for AG homologs in angiosperms. At the same time gene phylogenies reveal a complex history of gene duplications and repeated subfunctionalization of paralogs.

Results

EScaAG1 and EScaAG2, duplicate AG homologs in the basal eudicot Eschscholzia californica show a high degree of similarity in sequence and expression, although EScaAG2 expression is lower than EScaAG1 expression. Functional studies employing virus-induced gene silencing (VIGS) demonstrate that knock down of EScaAG1 and 2 function leads to homeotic conversion of stamens into petaloid structures and defects in floral meristem termination. However, carpels are transformed into petaloid organs rather than sepaloid structures. We also show that a reduction of EScaAG1 and EScaAG2 expression leads to significantly increased expression of a subset of floral homeotic B genes.

Conclusions
This work presents expression and functional analysis of the two basal eudicot AG homologs. The reduction of EScaAG1 and 2 functions results in the change of stamen to petal identity and a transformation of the central whorl organ identity from carpel into petal identity. Petal identity requires the presence of the floral homeotic B function and our results show that the expression of a subset of B function genes extends into the central whorl when the C function is reduced. We propose a model for the evolution of B function regulation by C function suggesting that the mode of B function gene regulation found in Eschscholzia is ancestral and the C-independent regulation as found in Arabidopsis is evolutionarily derived.