bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fear of the Brown Envelope: Exploring Welfare Reform with Long‐Term Sickness Benefits Recipients
Authors: Garthwaite Kayleigh 
Published: October 2013

AbstractThis article presents qualitative data taken from in‐depth interviews with 25 long‐term sickness benefits recipients in the north east of England, UK. A key theme emerging from the research is the importance of listening to the narratives of long‐term sick and disabled benefits recipients, particularly in relation to the formation of policy responses and in terms of practice. The findings also illustrate how stigma associated with claiming benefits can deter people from accessing the support they need, leading to under‐claiming and the risk of amplified financial strain and hardship. Further, the importance of evidence that emerges from research which focuses upon the lived experiences of sickness benefits recipients to provide evidence in the framing of disability and welfare policy is crucial. Lastly, the article discusses how the narratives presented have implications for social policy and practice, alongside the potential implications for sick and disabled people themselves.
Treatment Failure and Miltefosine Susceptibility in Dermal Leishmaniasis Caused by Leishmania Subgenus Viannia Species
Authors: Obonaga Ricardo , Fernández Olga Lucía , Valderrama Liliana , Rubiano Luisa Consuelo , Castro Maria del Mar , Barrera Maria Claudia , Gomez Maria Adelaida , Gore Saravia Nancy 
Published: October 2013

ABSTRACT

Treatment failure and parasite drug susceptibility in dermal leishmaniasis caused by
Leishmania
(
Viannia
) species are poorly understood. Prospective evaluation of drug susceptibility of strains isolated from individual patients before drug exposure and at clinical failure allows intrinsic and acquired differences in susceptibility to be discerned and analyzed. To determine whether intrinsic susceptibility or loss of susceptibility to miltefosine contributed to treatment failure, we evaluated the miltefosine susceptibility of intracellular amastigotes and promastigotes of six
Leishmania
(
Viannia
)
braziliensis
and six
Leishmania
(
Viannia
)
panamensis
strains isolated sequentially, at diagnosis and treatment failure, from two children and four adults ≥55 years old with concurrent conditions. Four patients presented only cutaneous lesions, one had mucosal disease, and one had disseminated mucocutaneous disease. Expression of the
Leishmania
drug transporter genes
abca2
,
abca3
,
abcc2
,
abcc3
,
abcg4
,
abcg6
, and
LbMT
was evaluated by quantitative reverse transcription-PCR (qRT-PCR). Intracellular amastigotes (median 50% effective concentration [EC
50
], 10.7 μmol/liter) were more susceptible to miltefosine than promastigotes (median EC
50
, 55.3 μmol/liter) (
P
< 0.0001). Loss of susceptibility at failure, demonstrated by a miltefosine EC
50
of >32 μmol/liter (the upper limit of intracellular amastigote assay), occurred in
L. panamensis
infection in a child and in
L. braziliensis
infection in an adult and was accompanied by decreased expression of the miltefosine transporter LbMT (LbMT/β-tubulin, 0.42- to 0.26-fold [
P
= 0.039] and 0.70- to 0.57-fold [
P
= 0.009], respectively). LbMT gene polymorphisms were not associated with susceptibility phenotype.
Leishmania
ABCA3 transporter expression was inversely correlated with miltefosine susceptibility (
r
= −0.605;
P
= 0.037). Loss of susceptibility is one of multiple factors involved in failure of miltefosine treatment in dermal leishmaniasis.
Dormant Intracellular Salmonella enterica Serovar Typhimurium Discriminates among Salmonella Pathogenicity Island 2 Effectors To Persist inside Fibroblasts
Authors: Núñez-Hernández Cristina , Alonso Ana , Pucciarelli M. Graciela , Casadesús Josep , García-del Portillo Francisco 
Published: October 2013

ABSTRACT

Salmonella enterica
uses effector proteins delivered by type III secretion systems (TTSS) to colonize eukaryotic cells. Recent
in vivo
studies have shown that intracellular bacteria activate the TTSS encoded by
Salmonella
pathogenicity island-2 (SPI-2) to restrain growth inside phagocytes. Growth attenuation is also observed
in vivo
in bacteria colonizing nonphagocytic stromal cells of the intestinal lamina propria and in cultured fibroblasts. SPI-2 is required for survival of nongrowing bacteria persisting inside fibroblasts, but its induction mode and the effectors involved remain unknown. Here, we show that nongrowing dormant intracellular bacteria use the two-component system OmpR-EnvZ to induce SPI-2 expression and the PhoP-PhoQ system to regulate the time at which induction takes place, 2 h postentry. Dormant bacteria were shown to discriminate the usage of SPI-2 effectors. Among the effectors tested, SseF, SseG, and SseJ were required for survival, while others, such as SifA and SifB, were not. SifA and SifB dispensability correlated with the inability of intracellular bacteria to secrete these effectors even when overexpressed. Conversely, SseJ overproduction resulted in augmented secretion and exacerbated bacterial growth. Dormant bacteria produced other effectors, such as PipB and PipB2, that, unlike what was reported for epithelial cells, did not to traffic outside the phagosomal compartment. Therefore, permissiveness for secreting only a subset of SPI-2 effectors may be instrumental for dormancy. We propose that the
S. enterica
serovar Typhimurium nonproliferative intracellular lifestyle is sustained by selection of SPI-2 effectors that are produced in tightly defined amounts and delivered to phagosome-confined locations.
TECHNOLOGIES FOR LARGE DATA MANAGEMENT IN SCIENTIFIC COMPUTING
Authors: PACE ALBERTO 
Published: October 2013

In recent years, intense usage of computing has been the main strategy of investigations in several scientific research projects. The progress in computing technology has opened unprecedented opportunities for systematic collection of experimental data and the associated analysis that were considered impossible only few years ago. This paper focuses on the strategies in use: it reviews the various components that are necessary for an effective solution that ensures the storage, the long term preservation, and the worldwide distribution of large quantities of data that are necessary in a large scientific research project. The paper also mentions several examples of data management solutions used in High Energy Physics for the CERN Large Hadron Collider (LHC) experiments in Geneva, Switzerland which generate more than 30,000 terabytes of data every year that need to be preserved, analyzed, and made available to a community of several tenth of thousands scientists worldwide.
miRNA-95 Mediates Radioresistance in Tumors by Targeting the Sphingolipid Phosphatase SGPP1
Authors: Huang Xiaoyong , Taeb Samira , Jahangiri Sahar , Emmenegger Urban , Tran Elisa , Bruce Jeff , Mesci Aruz , Korpela Elina , Vesprini Danny , Wong C. Shun , Bristow Robert G. , Liu Fei-Fei , Liu Stanley K. 
Published: October 2013

Abstract
Radiation resistance poses a major clinical challenge in cancer treatment, but little is known about how microRNA (miR) may regulate this phenomenon. In this study, we used next-generation sequencing to perform an unbiased comparison of miR expression in PC3 prostate cancer cells rendered resistant to fractionated radiation treatment. One miR candidate found to be upregulated by ionizing radiation was miR-95, the enforced expression of which promoted radiation resistance in a variety of cancer cells. miR-95 overexpression recapitulated an aggressive phenotype including increased cellular proliferation, deregulated G2–M checkpoint following ionizing radiation, and increased invasive potential. Using combined in silico prediction and microarray expression analyses, we identified and validated the sphingolipid phosphatase SGPP1, an antagonist of sphingosine-1-phosphate signaling, as a target of miR-95 that promotes radiation resistance. Consistent with this finding, cell treatment with FTY720, a clinically approved small molecule inhibitor of S1P signaling, sensitized miR-95 overexpressing cells to radiation treatment. In vivo assays extended the significance of these results, showing that miR-95 overexpression increased tumor growth and resistance to radiation treatment in tumor xenografts. Furthermore, reduced tumor necrosis and increased cellular proliferation were seen after radiation treatment of miR-95 overexpressing tumors compared with control tumors. Finally, miR-95 expression was increased in human prostate and breast cancer specimens compared with normal tissue. Together, our work reveals miR-95 expression as a critical determinant of radiation resistance in cancer cells. Cancer Res; 73(23); 6972–86. ©2013 AACR.
Decoding the Histone Code: Role of H3K36me3 in Mismatch Repair and Implications for Cancer Susceptibility and Therapy
Authors: Li Guo-Min 
Published: October 2013

Abstract
DNA mismatch repair (MMR) maintains genome stability primarily by correcting replication-associated mismatches. Defects in MMR lead to several human cancers characterized by frequent alterations in simple repetitive DNA sequences, a phenomenon called microsatellite instability (MSI). In most MSI-positive cancers, genetic or epigenetic changes that alter the function or expression of an essential MMR protein have been identified. However, in a subset of MSI-positive cancers, epigenetic or genetic changes have not been found in known MMR genes, such that the molecular basis of the MMR defect in these cells remains unknown. A possible answer to this puzzle emerged recently when it was discovered that H3K36me3, a well-studied posttranslational histone modification or histone mark, plays a role in regulating human MMR in vivo. In this review, potential roles for this histone mark to modulate genome stability and cancer susceptibility in human cells are discussed. Cancer Res; 73(21); 6379–83. ©2013 AACR.
Long-term Outcomes After First-Generation Autologous Chondrocyte Implantation for Cartilage Defects of the Knee
Authors: Niemeyer Philipp , Porichis Stella , Steinwachs Matthias , Erggelet Christoph , Kreuz Peter C. , Schmal Hagen , Uhl Markus , Ghanem Nadir , Südkamp Norbert P. , Salzmann Gian 
Published: October 2013

Background: Autologous chondrocyte implantation (ACI) represents an established surgical therapy for large cartilage defects of the knee joint. Although various studies report satisfying midterm results, little is known about long-term outcomes. Purpose: To evaluate long-term clinical and magnetic resonance imaging (MRI) outcomes after ACI. Study Design: Case series; Level of evidence, 4. Methods: Between January 1997 and June 2001, a total of 86 patients were treated with ACI for isolated cartilage defects of the knee. The mean patient age at the time of surgery was 33.3 ± 10.2 years, and the mean defect size was 6.5 ± 4.0 cm2. Thirty-four defects were located on the medial femoral condyle and 13 on the lateral femoral condyle, while 6 patients were treated for cartilage defects of the trochlear groove and 17 for patellar lesions. At a mean follow-up of 10.9 ± 1.1 years, 70 patients (follow-up rate, 82%) treated for 82 full-thickness cartilage defects of the knee were available for an evaluation of knee function using standard instruments, while 59 of these patients were additionally evaluated by 1.5-T MRI to quantify the magnetic resonance observation of cartilage repair tissue (MOCART) score. Clinical function at follow-up was assessed by means of the Lysholm score, the International Knee Documentation Committee (IKDC) score, and the Knee injury and Osteoarthritis Outcome Score (KOOS). Patient activity was assessed by the Tegner score. In addition, pain on a visual analog scale (VAS) and patient satisfaction were evaluated separately. Results: At follow-up, 77% reported being “satisfied” or “very satisfied.” The mean IKDC score at follow-up was 74.0 ± 17.3. The mean Lysholm score improved from 42.0 ± 22.5 before surgery to 71.0 ± 17.4 at follow-up ( P < .01). The mean pain score on the VAS decreased from 7.2 ± 1.9 preoperatively to 2.1 ± 2.1 postoperatively. The mean MOCART score was 44.9 ± 23.6. Defect-associated bone marrow edema was found in 78% of the cases. Nevertheless, no correlation between the MOCART score and clinical outcome (IKDC score) could be found (Pearson coefficient, r = 0.173). Conclusion: First-generation ACI leads to satisfying clinical results in terms of patient satisfaction, reduction of pain, and improvement in knee function. Nevertheless, full restoration of knee function cannot be achieved. Although MRI reveals lesions in the majority of the cases and the overall MOCART score seems moderate, this could not be correlated with long-term clinical outcomes.
Universal newborn screening for haemoglobinopathies in Guadeloupe (French West Indies): A 27-year experience
Authors: Saint-Martin Christian , Romana Marc , Bibrac Alix , Brudey Karine , Tarer Vanessa , Divialle-Doumdo Lydia , Petras Marie , Keclard-Christophe Lisiane , Lamothe Sandrine , Broquere Cédric , Etienne-Julan Maryse 
Published: October 2013

Objectives In Guadeloupe, an island in the French West Indies, a universal newborn screening programme for sickle cell disease and other abnormal haemoglobins was initiated in 1984. In 1990, a comprehensive sickle cell centre was established to carry on the management programme. We here report the main results from the newborn screening programme from 1984 to 2010, and consider how the establishment of the sickle cell centre affected the programme. Methods All blood samples were screened for the haemoglobinopathies using two reference methods in a single reference diagnosis laboratory. DNA analyses were also performed for confirmatory tests and analysis of the globin gene status. Results Between 1 January 1984 and 31 December 2010, 178,428 newborns were screened at birth, and 585 children were diagnosed with major sickle cell syndromes (ie. an overall incidence of 1 in 304 births). Sickle cell anaemia (haemoglobin SS disease) was the most frequently observed (1 in 575 births), followed by haemoglobin SC disease (1 in 771 births) and haemoglobin Sβ-thalassemia disease (1 in 4,243 births). Some other rare haemoglobin variants were also detected, the most common being HbDPunjab. The establishment of a comprehensive sickle cell centre resulted in a significant improvement in the screening coverage ( p < 0.001) and a significant reduction of the delay between diagnosis and the first medical visit ( p < 0.001). Conclusion The universal screening programme has made it possible to establish the incidence of the major sickle cell syndromes in Guadeloupe, and the management centre has improved its efficiency.
Characteristics of Sexually Transmitted Infections among High-Risk HIV-Positive Patients Attending an Urban Clinic in Uganda
Authors: Katusiime Christine , Schlech Walter F. , Parkes-Ratanshi Rosalind , Sempa Joseph , Kambugu Andrew 
Published: October 2013

Background: Sexually transmitted infections (STIs) significantly increase HIV transmission. Sexually transmitted infections may be asymptomatic and therefore remain undiagnosed in HIV-positive persons. Routine screening and treatment of STIs in HIV-positive high-risk populations in sub-Saharan Africa have not been described previously. Methods: We reviewed data from an HIV-positive high-risk population at the Infectious Diseases Institute, Makerere University, a large urban HIV clinic, between July 2011 and April 2012. Our high-risk population cohort included female sex workers, long-distance drivers, barmaids, taxi drivers, commercial motorcycle “boda-boda” riders, soldiers, police officers, prison officers, security guards, prisoners, and fishermen. Results: Of 355 participants enrolled in the high-risk population’s program, 21.4% were diagnosed with an STI either clinically or microbiologically. The STIs diagnosed in this population were syphilis, hepatitis B, genital herpes, human papilloma virus infection (condylomata acuminata), nongonococcal urethritis (NGU), and gonorrhea. Rates of syphilis, hepatitis B, genital herpes, condylomata acuminata, NGU, and gonorrhea were 8.5%, 7.0%, 5.4%, 1.4%, 1.4%, and 0.3%, respectively. Conclusion: Clinical and microbiologically diagnosed STIs were diagnosed in nearly one-fourth of the HIV-positive high-risk population. HIV care programs should note our high rates of STIs among HIV-positive high-risk populations and consider routine screening and treatment algorithms for these populations in their own settings.
Genome-scale cold stress response regulatory networks in ten Arabidopsis thalianaecotypes
Authors: Barah Pankaj , Jayavelu Naresh Doni , Rasmussen Simon , Nielsen Henrik Bjørn , Mundy John , Bones Atle M 
Published: October 2013

Abstract

Background
Low temperature leads to major crop losses every year. Although several studies have been conducted focusing on diversity of cold tolerance level in multiple phenotypically divergent Arabidopsis thaliana (A. thaliana) ecotypes, genome-scale molecular understanding is still lacking.

Results
In this study, we report genome-scale transcript response diversity of 10 A. thaliana ecotypes originating from different geographical locations to non-freezing cold stress (10°C). To analyze the transcriptional response diversity, we initially compared transcriptome changes in all 10 ecotypes using Arabidopsis NimbleGen ATH6 microarrays. In total 6061 transcripts were significantly cold regulated (p < 0.01) in 10 ecotypes, including 498 transcription factors and 315 transposable elements. The majority of the transcripts (75%) showed ecotype specific expression pattern. By using sequence data available from Arabidopsis thaliana 1001 genome project, we further investigated sequence polymorphisms in the core cold stress regulon genes. Significant numbers of non-synonymous amino acid changes were observed in the coding region of the CBF regulon genes. Considering the limited knowledge about regulatory interactions between transcription factors and their target genes in the model plant A. thaliana, we have adopted a powerful systems genetics approach- Network Component Analysis (NCA) to construct an in-silico transcriptional regulatory network model during response to cold stress. The resulting regulatory network contained 1,275 nodes and 7,720 connections, with 178 transcription factors and 1,331 target genes.

Conclusions

A. thaliana ecotypes exhibit considerable variation in transcriptome level responses to non-freezing cold stress treatment. Ecotype specific transcripts and related gene ontology (GO) categories were identified to delineate natural variation of cold stress regulated differential gene expression in the model plant A. thaliana. The predicted regulatory network model was able to identify new ecotype specific transcription factors and their regulatory interactions, which might be crucial for their local geographic adaptation to cold temperature. Additionally, since the approach presented here is general, it could be adapted to study networks regulating biological process in any biological systems.
Adult ciliary epithelial stem cells generate functional neurons and differentiate into both early and late born retinal neurons under non-cell autonomous influences
Authors: Del Debbio Carolina Beltrame , Peng Xu , Xiong Huangui , Ahmad Iqbal 
Published: October 2013

AbstractBackgroundThe neural stem cells discovered in the adult ciliary epithelium (CE) in higher vertebrates have emerged as an accessible source of retinal progenitors; these cells can self-renew and possess retinal potential. However, recent studies have cast doubt as to whether these cells could generate functional neurons and differentiate along the retinal lineage. Here, we have systematically examined the pan neural and retinal potential of CE stem cells.ResultsMolecular and cellular analysis was carried out to examine the plasticity of CE stem cells, obtained from mice expressing green fluorescent protein (GFP) under the influence of the promoter of the rod photoreceptor-specific gene,Nrl, using the neurospheres assay. Differentiation was induced by specific culture conditions and evaluated by both transcripts and protein levels of lineage-specific regulators and markers. Temporal pattern of their levels were examined to determine the expression of genes and proteins underlying the regulatory hierarchy of cells specific differentiationin vitro. Functional attributes of differentiation were examined by the presence of current profiles and pharmacological mobilization of intracellular calcium using whole cell recordings and Fura-based calcium imaging, respectively. We demonstrate that stem cells in adult CE not only have the capacity to generate functional neurons, acquiring the expression of sodium and potassium channels, but also respond to specific cues in culture and preferentially differentiate along the lineages of retinal ganglion cells (RGCs) and rod photoreceptors, the early and late born retinal neurons, respectively. The retinal differentiation of CE stem cells was characterized by the temporal acquisition of the expression of the regulators of RGCs and rod photoreceptors, followed by the display of cell type-specific mature markers and mobilization of intracellular calcium.ConclusionsOur study demonstrates the bonafide retinal potential of adult CE stem cells and suggests that their plasticity could be harnessed for clinical purposes once barriers associated with any lineage conversion, i.e., low efficiency and fidelity is overcome through the identification of conducive culture conditions.
Penicillin resistance and serotype distribution of Streptococcus pneumoniaein Ghanaian children less than six years of age
Authors: Dayie Nicholas TKD , Arhin Reuben E , Newman Mercy J , Dalsgaard Anders , Bisgaard Magne , Frimodt-Møller Niels , Slotved Hans-Christian 
Published: October 2013

Abstract

Background
The objective of this study was to determine the prevalence of nasopharyngeal carriage, serotype distribution, and penicillin resistance of Streptococcus pneumoniae in children ≤6 years of age in Ghana.

Methods
A cross-sectional study was carried out on a cluster-randomized sample of children ≤6 years of age attending nurseries and kindergartens in Accra and Tamale, Ghana. Basic data on age, sex and exposure to antimicrobials in the previous month were collected on all study subjects. Nasopharyngeal swabs were obtained from participants and all pneumococcal isolates were characterized by serotyping and their penicillin resistance determined.

Results
The overall prevalence of pneumococcal carriage among the children was 34% in Accra and 31% in Tamale. The predominant serotypes were 19F, 6B, 23F, and 6A with 23% of the isolates being non-typable in Accra and 12% in Tamale. Only two isolates (serotypes 19F and 6B) from Tamale had a MIC >2 μg/ml and were classified as fully penicillin resistant with 45% of the isolates having intermediate resistance.

Conclusions
These findings indicate that the 13-valent pneumococcal conjugate vaccine (PCV-13) recently introduced in Ghana will cover 48% and 51% of the serotypes identified in Accra and Tamale, respectively. The 23-valent pneumococcal polysaccharide vaccine (PPV-23) will cover 54% of all serotypes detected. The two penicillin resistant isolates (MIC 32 μg/ml) were serotypes included in both PCV-13 and PPV-23. A nationwide monitoring system of penicillin susceptibility patterns and pneumococcal serotypes is recommended.