bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Conserved Tandem Cyclophilin-Binding Site in Hepatitis C Virus Nonstructural Protein 5A Regulates Alisporivir Susceptibility
Authors: Grisé Henry , Frausto Stephen , Logan Timothy , Tang Hengli 
Published: February 2012

ABSTRACT
Cyclophilin A (CyPA) and its peptidyl-prolyl isomerase (PPIase) activity play an essential role in hepatitis C virus (HCV) replication, and mounting evidence indicates that nonstructural protein 5A (NS5A) is the major target of CyPA. However, neither a consensus CyPA-binding motif nor specific proline substrates that regulate CyPA dependence and sensitivity to cyclophilin inhibitors (CPIs) have been defined to date. We systematically characterized all proline residues in NS5A domain II, low-complexity sequence II (LCS-II), and domain III with both biochemical binding and functional replication assays. A tandem cyclophilin-binding site spanning domain II and LCS-II was identified. The first site contains a consensus sequence motif of AØPXW (where Ø is a hydrophobic residue) that is highly conserved in the majority of the genotypes of HCV (six of seven; the remaining genotype has VØPXW). The second tandem site contains a similar motif, and the ØP sequence is again conserved in six of the seven genotypes. Consistent with the similarity of their sequences, peptides representing the two binding motifs competed for CyPA binding in a spot-binding assay and induced similar chemical shifts when bound to the active site of CyPA. The two prolines (P310 and P341 of Japanese fulminant hepatitis 1 [JFH-1]) contained in these motifs, as well as a conserved tryptophan in the spacer region, were required for CyPA binding, HCV replication, and CPI resistance. Together, these data provide a high-resolution mapping of proline residues important for CyPA binding and identify critical amino acids modulating HCV susceptibility to the clinical CPI Alisporivir.
Metagenomic Analysis of Viruses from Bat Fecal Samples Reveals Many Novel Viruses in Insectivorous Bats in China
Authors: Ge Xingyi , Li Yan , Yang Xinglou , Zhang Huajun , Zhou Peng , Zhang Yunzhi , Shi Zhengli 
Published: February 2012

ABSTRACT
Increasing data indicate that bats harbor diverse viruses, some of which cause severe human diseases. In this study, sequence-independent amplification and high-throughput sequencing (Solexa) were applied to the metagenomic analysis of viruses in bat fecal samples collected from 6 locations in China. A total of 8,746,417 reads with a length of 306,124,595 bp were obtained. Among these reads, 13,541 (0.15%) had similarity to phage sequences and 9,170 (0.1%) had similarity to eukaryotic virus sequences. A total of 129 assembled contigs (>100 nucleotides) were constructed and compared with GenBank: 32 contigs were related to phages, and 97 were related to eukaryotic viruses. The most frequent reads and contigs related to eukaryotic viruses were homologous to densoviruses, dicistroviruses, coronaviruses, parvoviruses, and tobamoviruses, a range that includes viruses from invertebrates, vertebrates, and plants. Most of the contigs had low identities to known viral genomic or protein sequences, suggesting that a large number of novel and genetically diverse insect viruses as well as putative mammalian viruses are transmitted by bats in China. This study provides the first preliminary understanding of the virome of some bat populations in China, which may guide the discovery and isolation of novel viruses in the future.
Sensing Adenovirus Infection: Activation of Interferon Regulatory Factor 3 in RAW 264.7 Cells
Authors: Stein Saskia C. , Falck-Pedersen Erik 
Published: February 2012

ABSTRACT

We have used the RAW 264.7 murine macrophage-like cell line as a platform to characterize the recognition and early signaling response to recombinant adenoviral vectors (rAdV). Infection of RAW 264.7 cells triggers an early response (2 to 6 h postinfection) that includes phosphorylation of the interferon (IFN) response factor 3 (IRF3) transcription factor, upregulation of IRF3 primary response genes (interferon-stimulated gene 56 [ISG56], beta IFN [IFN-β]), and subsequent type I IFN secondary signaling (STAT1/2 phosphorylation). Using short hairpin RNA (shRNA) lentiviral vectors, we show an essential role for Tank binding kinase 1 (TBK1) in this pathway. Data also support a role for STING (MITA) as an adaptor functioning in response to rAdV infection. Using UV/psoralen (Ps)-inactivated virus to block viral transcription, Ps-inactivated virus stimulated primary (IRF3) and secondary (STAT1/2) activation events to the same degree as untreated virus. IRF3 phosphorylation was not blocked in RAW 264.7 cells pretreated with the RNA polymerase III inhibitor ML60218. However, they were compromised in the type I IFN-dependent secondary response (phosphorylation of STAT1/STAT2). At 24 h postinfection, ML60218-treated cells were compromised in the overall antiviral response. Therefore, initial sensing of rAdV or viral DNA (vDNA) does not depend on viral template transcription, but ML60218 treatment influences cellular cascades required for an antiviral response to rAdV. Using overexpression or knockdown assays, we examined how four DNA sensors influence the antiviral response. Knockdown of DNA Activator of Interferon (DAI) and p204, the murine ortholog to IFI16, had minimal influence on IRF3 phosphorylation. However, knockdown of absent in melanoma 2 (AIM2) and the helicase DDX41 resulted in diminished levels of
pser388
IRF3 following rAdV infection. Based on these data, multiple DNA sensors contribute to an antiviral DNA recognition response, leading to TBK1-dependent IRF3 phosphorylation in RAW 264.7 cells.
Qualitative cross-sectional study of the perceived causes of depression in South Asian origin women in Toronto: Table 1
Authors: Ekanayake Samanthika , Ahmad Farah , McKenzie Kwame 
Published: February 2012

ObjectiveTo explore how South Asian origin women in Toronto, Canada, understand and explain the causes of their depression.DesignCross-sectional in-depth qualitative interviews.SettingOutpatient service in Toronto, Ontario.ParticipantsTen women with symptoms of depression aged between 22 and 65 years of age. Seven were from India, two from Sri Lanka and one from Pakistan. Four were Muslim, three Hindu and three Catholic. Two participants had university degrees, one a high school diploma and seven had completed less than a high school education. Eight were married, one was unmarried and one a widow.ResultsThree main factors emerged from the participant narratives as the causes of depression: family and relationships, culture and migration and socioeconomic. The majority of the participants identified domestic abuse, marital problems and interpersonal problems in the family as the cause of their depression. Culture and migration and socioeconomic factors were considered contributory. None of our study participants reported spiritual, supernatural or religious factors as causes of depression.ConclusionA personal–social–cultural model emerged as the aetiological paradigm for depression. Given the perceived causation, psycho-social treatment methods may be more acceptable for South Asian origin women.
The role of the general practitioner in the Australian approach to HIV care: interviews with ‘key informants’ from government, non-government and professional organisations
Authors: Newman Christy E , de Wit John B F , Kippax Susan C , Reynolds Robert H , Canavan Peter G , Kidd Michael R 
Published: February 2012

ObjectivesHIV care is provided in a range of settings in Australia, but advances in HIV treatment and demographic and geographic changes in the affected population and general practitioner (GP) workforce are testing the sustainability of the special role for GPs. This paper explores how a group of ‘key informants’ described the role of the GP in the Australian approach to HIV care, and conceptualised the challenges currently inspiring debate around future models of care.MethodsA thematic analysis was conducted of semistructured interviews carried out in 2010 with 24 professionals holding senior roles in government, non-government and professional organisations that influence Australian HIV care policy.ResultsThe strengths of the role of the GP were described as their community setting, collaborative partnership with other medical and health professions, and focus on patient needs. A number of associated challenges were also identified including the different needs of GPs with high and low HIV caseloads, the changing expectations of professional roles in general practice, and barriers to service accessibility for people living with HIV.ConclusionsWhile there are many advantages to delivering HIV services in primary care, GPs need flexible models of training and accreditation, support in strengthening relationships with other health and medical professionals, and assistance in achieving service accessibility. Consideration of how to support the GP workforce so that care can be made available in the broadest range of geographical and service settings is also critical if systems of HIV care delivery are to be realistic and cost-effective and meet consumer needs.
Hopes interrupted: accessing and experiences of antiretroviral therapy in South Africa
Authors: Fried Jana , Harris Bronwyn , Eyles John 
Published: February 2012

ObjectivesUsing the example of South Africa, this study aimed to examine and obtain a better understanding of the experiences and challenges of urban and rural patients on antiretroviral therapy (ART) in accessing this complex treatment in a resource-limited setting.MethodsFollowing a narrative approach, in-depth interviews were conducted with 20 patients successfully and unsuccessfully (ie, with interruptions) receiving ART in urban Johannesburg and rural Bushbuckridge, using a detailed interview guide structured to illuminate interviewees' life circumstances and contextualise illness and treatment trajectories. Participants were interviewed by trained fieldworkers in their local languages. The translated and transcribed interviews were coded by several team members. Codes were cross-examined and showed good congruence.ResultsAll interviewees emphasised the positive aspects of receiving ART, the lifeline and hope it provided by improving health, increasing their ability to live actively and reducing visible signs of (stigmatised) illness. Important factors supporting continuing adherence included social and economic support by individuals, role models and networks as well as positive experiences within the healthcare system and of the treatment itself. The main challenges were linked to patients' difficult life circumstances, especially those related to poverty (eg, transport and food costs) and health system constraints, including perceived lack of compassion and flexibility by healthcare workers.ConclusionsWhile there are many challenges for the sustainability of ART on an individual and health system level, this study emphasised the need for a patient-centric focus to continue to provide and increase the number of HIV-positive people receiving this lifeline, receiving hope.
Is there a role for primary care clinicians in providing shared care in HIV treatment? A systematic literature review
Authors: Wong W C W , Luk C W , Kidd M R 
Published: February 2012

BackgroundDespite HIV being increasingly considered as a chronic illness, there is as yet no consensus about how primary care should be integrated with specialty care to provide optimal clinical management for people living with HIV.ObjectiveTo examine the effectiveness of shared care models of HIV between primary care and specialty care and how primary care providers can assist in improving the care of people with HIV.MethodsThree databases, PubMed, Medline and EMBase, were searched for relevant terms from studies published in the period from 1996 to 2011. Studies that integrated primary care in HIV management and included highly active antiretroviral therapy (HAART) as part of the treatment modality were included.ResultsEleven studies that met the inclusion criteria were included in this review. Primary care was found to be at least as effective in HIV counselling, testing and treatment and, to a lesser degree, prevention, when compared with specialty care alone. Screening for HIV at a primary care level was cost-effective, especially in a high HIV prevalence and high-risk community. There were no significant adverse clinical outcomes reported in a primary care approach. Effectiveness of various interventions using a primary care approach was demonstrated in the review, including HAART adherence programmes, home care, the involvement of peer health workers and perinatal use of HAART.ConclusionsPrimary care has an important role in the shared care of the diagnosis and management of people with HIV. Some improvements with current guidelines on the management in primary care of people with HIV in developing countries should be considered.
Indicators of political commitment to respond to HIV
Authors: Goldberg Allison B , Fox Ashley M , Gore Radhika J , Bärnighausen Till 
Published: February 2012

ObjectivesNational political commitment is likely to become particularly crucial to sustaining antiretroviral treatment programmes in the coming decade, as donor contributions to HIV funding decreases. The objective of this study is to synthesise information on existing indicators of political commitment to respond to national HIV epidemics.MethodsThe authors describe and critically evaluate the existing indicators and propose studies to validate them.ResultsSeveral indicators have been developed to measure governments' political commitment to respond to national HIV epidemics—theAIDS Program Effort Index, theUnited Nations General Assembly Special Session on HIV/AIDS Declaration of Commitment Indicatorsand theAIDS Policy Aggressiveness Indicators—but the validity of these measures has not been systematically assessed. The indicators differ in their intended use, collection methods, content categories, data coverage, and strengths and limitations. Several types of studies could be used to test indicator validity (based on indicator content, comparisons of the same indicator using different elicitation methods, relationship patterns between indicators, relations between indicators and other variables and the consequences of using the indicators).ConclusionsThe existing indicators of political commitment to respond to national HIV epidemics are useful for many purposes, including research, policymaking and advocacy. A range of studies could improve the understanding of indicator validity. New data collection and measurement approaches offer opportunities to improve how actors in the HIV community capture the complicated, multidimensional concept of political commitment.
The Mixed Lineage Leukemia (MLL) Fusion–Associated Gene AF4 Promotes CD133 Transcription
Authors: Mak Anthony B. , Nixon Allison M.L. , Moffat Jason 
Published: February 2012

Abstract
The AC133 epitope has been used as a marker for both normal and cancer stem cells from multiple tissue lineages. To identify transcription factors that regulate CD133 expression, we conducted parallel large-scale RNA interference screens in Caco-2 cancer cells that endogenously express CD133 and in engineered HEK293 cells that express CD133 from a heterologous promoter. The transcription factor AF4 was identified following a comparative analysis between the two screens. We then showed that AF4 is a promoter of CD133 transcription in multiple cancer cell lines. Knockdown of AF4 resulted in a dramatic reduction in CD133 transcript levels. Importantly, a subset of pediatric acute lymphoblastic leukemias (ALL) harbor a fusion oncogene results from a chromosomal translocation that juxtaposes the mixed-lineage leukemia (MLL) gene and the AF4 gene. An investigation of the functional role of CD133 in the MLL-AF4–dependent ALL cells revealed that CD133 was required for leukemia cell survival. Together, our findings show AF4-dependent regulation of CD133 expression, which is required for the growth of ALL cells. CD133 may therefore represent a therapeutic target in a subset of cancers. Cancer Res; 72(8); 1929–34. ©2012 AACR.
The Antitumor Immunity of Ipilimumab: (T-cell) Memories to Last a Lifetime?
Authors: Postow Michael A. , Callahan Margaret K. , Wolchok Jedd D. 
Published: February 2012

Abstract
Ipilimumab has shown an overall survival benefit in 2 randomized phase III studies. A minority of patients achieve long-term disease control, highlighting the potential of this immunotherapeutic approach. In ongoing efforts, investigators are continuing to characterize these patients' unique clinical courses and correlate their responses with underlying mechanisms of antitumor immunity. Clin Cancer Res; 18(7); 1821–3. ©2012 AACR.
Cloud Coverage in the Joint OSSE Nature Run
Authors: McCarty Will , Errico Ronald M. , Gelaro Ronald 
Published: February 2012

Abstract
A successful observing system simulation experiment (OSSE) is fundamentally dependent on the simulation of the global observing system used in the experiment. In many applications, a free-running numerical model simulation, called a nature run, is used as the meteorological truth from which the observations are simulated. To accurately and realistically simulate observations from any nature run, the simulated observations must contain realistic cloud effects representative of the meteorological regimes being sampled. This study provides a validation of the clouds in the Joint OSSE nature run generated at ECMWF. Presented is the methodology used to validate the nature run cloud fraction fields with seasonally aggregated combined CloudSat/Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) cloud geometric profile retrievals and the Wisconsin High Resolution Infrared Radiation Sounder (HIRS) cloud climatology. The results show that the Joint OSSE nature run has a correct vertical distribution of clouds but lacks globally in cloud amount compared to the validation data. The differences between the nature run and validation datasets shown in this study should be considered and accounted for in the generation of the global observing system for use in full OSSE studies.
The premonitory phase of migraine and migraine management
Authors: Becker Werner J 
Published: February 2012

Objective: The objective was to determine, through a literature review, whether treatment during the premonitory phase of migraine is a potentially useful migraine management strategy. Methods: A general literature review was done with regard to the nature of migraine premonitory symptoms, their frequency, their reliability in predicting migraine attacks, and the effectiveness of medication treatment when given during the premonitory phase. Results: Many different symptoms have been reported as premonitory symptoms that occur before migraine attacks. Up to 87% of patients with migraine may experience premonitory symptoms, although some studies have provided estimates as low as 33%. In selected patients, premonitory symptoms may be relatively reliable predictors of a migraine attack to follow. Both naratriptan (open-label study) and domperidone (double-blind, randomized, placebo-controlled study) have been reported to be effective when given during the premonitory phase. Conclusions: More research is needed, but there is some evidence that medication treatment during the premonitory phase has the potential to be helpful in selected patients with migraine.
Doll therapy: A therapeutic means to meet past attachment needs and diminish behaviours of concern in a person living with dementia – a case study approach
Authors: Bisiani Leah , Angus Jocelyn 
Published: February 2012

The aim of this research study was to examine the impact of the provision of a lifelike baby doll as a therapeutic tool on the behaviour of a person living with dementia. Specifically, this single case study assessed the potential benefits, if any, of the use of doll therapy in reducing behaviours of concern such as anxiety and agitation that may be associated with observed attachment needs of a person living with dementia. Method: A single case study of a female participant, with moderately advanced Alzheimer’s disease, was the subject of this research. The case study used both qualitative and quantitative research design and methodology in data collection and analysis. Results: Demonstrated that doll therapy was a positive intervention for the person living with dementia who was the participant in this research. The findings indicate a reduction in behaviours of concern related to the need for attachment and a considerable decline in levels of anxiety and agitation. There was extensive ongoing improvement in social interaction and communication. Conclusion: This research supports doll therapy as a therapeutic intervention that may be utilized within the ongoing care of some persons with dementia to meet needs for attachment and to reduce behaviours of concern. Despite some controversy on this topic, doll therapy should be considered as a therapeutic approach to further dementia care in light of this positive outcome.
Is Four Twice as Nice as Two? A Natural Experiment on Electoral Effects of Term Length
Authors: Gaines Brian J. , Nokken Timothy P. , Groebe Collin 
Published: February 2012

AbstractIn Illinois and Texas, senate elections return members to serve terms of different length. Because term length schedules are randomized, these states provide a natural experiment. Cross-sectional comparison of chambers requires statistical controls for myriad factors that distinguish cases (chambers or periods). These two chambers, by contrast, produce direct evidence of term length's impact on electoral behavior. We test hypotheses about term length's impact on candidacies, campaign expenditures, and voter participation with data from 1968 to 2010. Surprisingly, there is little evidence of any significant differences between contests for two-year and four-year terms.
Periosteal Osteosarcoma of the Calcaneum
Authors: Singh Daljit , Sen Ramesh , Chaudhary Susheel , Tripathy Sujit Kumar 
Published: February 2012

A 30-year-old woman presented with a 6-month history of pain and swelling over the sole of her right foot. Plain radiograph showed a calcified mass in the heel pad, which appeared to be arising from the spur on inferior aspect of calcaneum. Magnetic resonance imaging showed a lesion, hypointense on T1-weighted and hyperintense on T2-weighted images over the plantar aspect of the foot. Open biopsy of the mass was indicative of periosteal osteosarcoma, the variety that has never been reported in calcaneum. Below-knee amputation was done with no recurrence or distance metastasis seen at 24 months of follow up. Level of Evidence: Therapeutic, Level IV