bluuebunny/crossref_metadata_2025 huggingface dataset:
STAT3-Mediated Autophagy Dependence Identifies Subtypes of Breast Cancer Where Autophagy Inhibition Can Be Efficacious
Authors: Maycotte Paola , Gearheart Christy M. , Barnard Rebecca , Aryal Suraj , Mulcahy Levy Jean M. , Fosmire Susan P. , Hansen Ryan J. , Morgan Michael J. , Porter Christopher C. , Gustafson Daniel L. , Thorburn Andrew
Published: March 2014

Autophagy is a protein and organelle degradation pathway that is involved in diverse diseases, including cancer. Recent evidence suggests that autophagy is a cell survival mechanism in tumor cells and that its inhibition, especially in combination with other therapy, could be beneficial but it remains unclear if all cancer cells behave the same way when autophagy is inhibited. We inhibited autophagy in a panel of breast cancer cell lines and found that some of them are dependent on autophagy for survival even in nutrient rich conditions without any additional stress, whereas others need autophagy only when stressed. Survival under unstressed conditions is due to cell type–specific autophagy regulation of STAT3 activity and this phenotype is enriched in triple-negative cell lines. This autophagy-dependency affects response to therapy because autophagy inhibition reduced tumor growth in vivo in autophagy-dependent but not in autophagy-independent breast tumors, whereas combination treatment with autophagy inhibitors and other agent was preferentially synergistic in autophagy-dependent cells. These results imply that autophagy-dependence represents a tumor cell–specific characteristic where autophagy inhibition will be more effective. Moreover, our results suggest that autophagy inhibition might be a potential therapeutic strategy for triple-negative breast cancers, which currently lack an effective targeted treatment. Cancer Res; 74(9); 2579–90. ©2014 AACR.
HLA-Binding Properties of Tumor Neoepitopes in Humans
Authors: Fritsch Edward F. , Rajasagi Mohini , Ott Patrick A. , Brusic Vladimir , Hacohen Nir , Wu Catherine J.
Published: March 2014

Cancer genome sequencing has enabled the rapid identification of the complete repertoire of coding sequence mutations within a patient's tumor and facilitated their use as personalized immunogens. Although a variety of techniques are available to assist in the selection of mutation-defined epitopes to be included within the tumor vaccine, the ability of the peptide to bind to patient MHC is a key gateway to peptide presentation. With advances in the accuracy of predictive algorithms for MHC class I binding, choosing epitopes on the basis of predicted affinity provides a rapid and unbiased approach to epitope prioritization. We show herein the retrospective application of a prediction algorithm to a large set of bona fide T cell–defined mutated human tumor antigens that induced immune responses, most of which were associated with tumor regression or long-term disease stability. The results support the application of this approach for epitope selection and reveal informative features of these naturally occurring epitopes to aid in epitope prioritization for use in tumor vaccines. Cancer Immunol Res; 2(6); 522–9. ©2014 AACR.
Endothelial Dysfunction and Enhanced Contractility in Microvessels From Ovariectomized Rats
Authors: Wang Dan , Wang Cheng , Wu Xie , Zheng Wei , Sandberg Kathryn , Ji Hong , Welch William J. , Wilcox Christopher S.
Published: March 2014

Ovarian hormone loss increases reactive oxidative species, endothelial dysfunction, and cardiovascular disease. Because perivascular adipose tissue (PVAT) regulates endothelial function, we hypothesized that reactive oxidative species in PVAT mediate adverse microvascular effects of ovarian hormone deficiency. Rats were ovariectomized or sham operated and given vehicle or tempol for 6 weeks. Mesenteric resistance arterioles from ovariectomized compared with sham-operated rats had dysfunctional responses to acetylcholine (ACh) including decreased ACh-induced endothelium-dependent relaxation (50±6% versus 72±2%) and endothelium-dependent relaxation factor (17±4% versus 37±2%) and increased endothelium-dependent contracting factor (27±5% versus 9±3%). OVX rat mesenteric arterioles had increased contractions to the thromboxane/prostanoid receptor agonist U-46 619 (58±3% versus 40±5%) and increased reactive oxidative species (tempo-9-AC fluorescence) with U-46 619 (0.65±0.17 versus 0.14±0.06 Δ unit) or ACh (0.49±0.09 versus 0.09±0.05 Δ unit) and increased p22
phox
protein expression (0.89±0.05 versus 0.18±0.04 Δ unit), whereas nitric oxide activity (DAF-FM [4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate] fluorescence) with ACh was reduced (0.39±0.1 versus 0.70±0.10 Δ unit). No differences were found in endothelium-dependent hyperpolarizing factor or contractile responses to phenylephrine. PVAT enhanced ACh-induced relaxation, endothelium-dependent relaxation factor, and nitric oxide only in sham-operated rats. Tempol prevented ovariectomy-induced endothelial dysfunction and restored the enhancing effects of PVAT on ACh-induced relaxation, endothelium-dependent relaxation factor, and nitric oxide in ovariectomized rat vessels, but both tempol and PVAT were required to normalize the enhanced U-46 619 contractions after ovariectomy. In conclusion, ovariectomy redirects endothelial responses from relaxation to contraction by reducing vascular nitric oxide, augmenting thromboxane/prostanoid receptor signaling, and attenuating the vasodilatory effects of PVAT, all of which were dependent on reactive oxidative species.
Diastrophic Dysplasia Sulfate Transporter (SLC26A2) Is Expressed in the Adrenal Cortex and Regulates Aldosterone Secretion
Authors: Spyroglou Ariadni , Bozoglu Tarik , Rawal Rajesh , De Leonardis Fabio , Sterner Christina , Boulkroun Sheerazed , Benecke Arndt G. , Monti Luca , Zennaro Maria-Christina , Petersen Ann-Kristin , Döring Angela , Rossi Antonio , Bidlingmaier Martin , Warth Richard , Gieger Christian , Reincke Martin , Beuschlein Felix
Published: March 2014

Elucidation of the molecular mechanisms leading to autonomous aldosterone secretion is a prerequisite to define potential targets and biomarkers in the context of primary aldosteronism. After a genome-wide association study with subjects from the population-based Cooperative Health Research in the Region of Augsburg F4 survey, we observed a highly significant association (
P
=6.78×10
–11
) between the aldosterone to renin ratio and a locus at 5q32. Hypothesizing that this locus may contain genes of relevance for the pathogenesis of primary aldosteronism, we investigated solute carrier family 26 member 2 (SLC26A2), a protein with known transport activity for sulfate and other cations. Within murine tissues, adrenal glands showed the highest expression levels for SLC26A2, which was significantly downregulated on in vivo stimulation with angiotensin II and potassium. SLC26A2 expression was found to be significantly lower in aldosterone-producing adenomas in comparison with normal adrenal glands. In adrenocortical NCI-H295R cells, specific knockdown of SLC26A2 resulted in a highly significant increase in aldosterone secretion. Concomitantly, expression of steroidogenic enzymes, as well as upstream effectors including transcription factors such as NR4A1, CAMK1, and intracellular Ca
2+
content, was upregulated in knockdown cells. To substantiate further these findings in an SLC26A2 mutant mouse model, aldosterone output proved to be increased in a sex-specific manner. In summary, these findings point toward a possible effect of SLC26A2 in the regulation of aldosterone secretion potentially involved in the pathogenesis of primary aldosteronism.
Clinical Effect of Naturally Random Allocation to Lower Systolic Blood Pressure Beginning Before the Development of Hypertension
Authors: Ference Brian A. , Julius Stevo , Mahajan Nitin , Levy Phillip D. , Williams Kim Allan , Flack John M.
Published: March 2014

Systolic blood pressure (SBP) rises approximately linearly with age in most societies. The cause of this rise is unclear. We tested the hypothesis that SBP is causally associated with the rate of rise in SBP with age by evaluating the effect of 12 polymorphisms associated with lower SBP on the age-related rate of rise in SBP in a series of meta-regression analyses involving ≤199 477 participants in 63 studies. We then evaluated the effect of these polymorphisms on the odds of coronary heart disease in 22 223 case and 64 762 control subjects and compared it with the effect of lower SBP observed in both prospective cohort studies and blood pressure–lowering randomized trials. All 12 polymorphisms were associated with both lower SBP and a slower age-related rise in SBP. The weighted mean effect of these 12 polymorphisms was associated with a 0.32-mm Hg lower SBP (
P
=1.79×10
−7
) and a 0.093-mm Hg/decade slower age-related rise in SBP (
P
=3.05×10
−5
). The effect of long-term exposure to lower SBP on coronary heart disease mediated by these polymorphisms was 2-fold greater than that observed in prospective cohort studies (
P
=0.006) and 3-fold greater than that observed in short-term blood pressure treatment trials (
P
=0.001). We conclude therefore that SBP seems to be causally associated with the rate of rise in SBP with age and has a cumulative effect on the risk of coronary heart disease.
Adjusted Drug Treatment Is Superior to Renal Sympathetic Denervation in Patients With True Treatment-Resistant Hypertension
Authors: Fadl Elmula Fadl Elmula M. , Hoffmann Pavel , Larstorp Anne C. , Fossum Eigil , Brekke Magne , Kjeldsen Sverre E. , Gjønnæss Eyvind , Hjørnholm Ulla , Kjær Vibeke N. , Rostrup Morten , Os Ingrid , Stenehjem Aud , Høieggen Aud
Published: March 2014

We aimed to investigate for the first time the blood pressure (BP)–lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (
P
<0.0005 and
P
=0.02, SBP and diastolic BP, respectively) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg (
P
=0.42 and
P
=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months (
P
=0.002 and
P
=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (
P
=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01673516
The Emergence of Islamic Liberation Theology in South Africa
Authors: Palombo Matthew
Published: March 2014

Abstract

There is a growing interest in Islamic liberation theology today, and seminal authors such as Ali Shariati, Alighar Ali Engineer (1984, 1990), Farid Esack (1984, 1997), and Hamid Dabashi (2008) have developed its central commitments. In South Africa the earliest representative text was the ‘Review of Faith’ (1984) by Farid Esack, used by the Call of Islam (est. 1984) for cultivating personal piety and conscientization (critical consciousness) against apartheid. Based on recent interviews, unpublished manuscripts, and published works, this article demonstrates how Islamic liberation theology emerged in the political praxis of Muslims against settler colonialism and apartheid. In this subaltern history, political Islam as political praxis and not state building generated a unique discursive space for an Islamic liberation theology to emerge within the confluence of two ideological paths: those of humanism and Islamism.
The Era of Overseas Scholarships: Islam, Modernization, and Decolonization in Northern Nigeria, c. 1954-1966
Authors: Thurston Alexander
Published: March 2014

Abstract

In independence-era Northern Nigeria, different segments of the modernizing elite contended over defining the place of Islam in society. This article argues that the case of Northern Nigeria disrupts scholarly periodizations of twentieth-century Islamic thought and activism that depict the 1950s and 1960s as a time of secularist dominance. The specificity of Muslim communities’ experiences of colonialism and decolonization helped shape the role Islam played in different societies during this period. This article develops this thesis by examining the semiautonomous Northern Nigerian regional government’s program of sending young, Arabophone Muslim scholars to Arab and British universities between 1954 and 1966. The overseas scholarships system was to be the culmination of British colonial efforts to produce ‘modern’ Muslim judges and teachers. However, Arabophones’ experiences overseas, and their ambivalent relationship with the Northern government after their return highlight the unintended consequences of colonial policies and of scholarship winners’ encounters with the broader Muslim world.
Transforming Cattle into Blessings: The Moral Economy of Mbororo Pilgrimage
Authors: Virtanen Tea
Published: March 2014

Abstract

In this essay I explore the meaning of cattle for the Mbororo pastoralists of the Adamaoua Region, Cameroon, in realising and conceptualising the pilgrimage to Mecca. As an analytic frame I employ the concept of moral economy and the related discussion of cycles of exchange by Jonathan Parry and Maurice Bloch (1989), which, I argue, open up new ways of understanding and theorising the pilgrimage process. For the Mbororo cattle form the material base for the pilgrimage, as it is only through cattle sales that they are able to carry out the journey. Furthermore, the possibility of going on a public pilgrimage through selling cattle has significance for local intraethnic relations because it has blurred the traditional power hierarchy by providing the relatively marginalised Mbororo a more visible Muslim status in the region. The cattle also shape the way in which the Mbororo conceptualise the pilgrimage experience by forming an elemental part of a set of symbolic transformations through which the blessing (barka) of Mecca reaches the Mbororo camps of Adamaoua, and the pilgrimage is absorbed into the sociocosmic order of the pastoral community. Finally, in the Mbororo moral discourse these ‘pastoral’ transformations, guided by sociospiritual reasons, are contrasted with other Adamaouan pilgrims’ purely economically motivated transactions during the journey.
Biblical Languages and National-Religious Boundaries in Muscovy
Authors: Gruber Isaiah
Published: March 2014

Inspired in part by conversations with David Goldfrank, this essay considers aspects of how attitudes toward biblical language contributed to representations of national and religious identity in late medieval and early modern Muscovite Russia. At roughly the same time in history that revived Hebrew and Greek study in Western Europe helped to stimulate the Renaissance and Reformation, bookmen in East Slavia also reconsidered the original languages of sacred writings. Contrary to what is sometimes assumed, such interest was neither unknown nor marginal within Muscovite religious culture. Hebrew-Russian glossaries circulated in leading monasteries from at least the thirteenth century; major infusions of Greek (and other) words and definitions in the sixteenth century transformed these texts into multilingual dictionaries. This mainstream tradition in Russian Orthodoxy can be linked to such important religious figures as Nil Sorskii and Maksim Grek. I argue that by “appropriating” biblical languages and terminology, often via inaccurate translations, Muscovite Russian literati created and defended their distinctive identity vis-à-vis Jews and Greeks, who were considered God’s former chosen peoples. These findings suggest reconsideration of the nature and boundaries of faith in Muscovy in the “age of confessionalism.”
Clerical Mutual Aid and Famine Relief during Russia’s Crop Failure of 1905
Authors: Scarborough Daniel
Published: March 2014

The clerical estate (soslovie) of late Imperial Russia was legally segregated from the rest of the population, subject to separate systems of education, justice, taxation, and access to employment. The state permitted participation in free associations within the clerical soslovie in order to encourage the practice of mutual aid among clergymen and their families. By the late nineteenth century, the parish clergy had begun to use these mutual-aid associations to provide education, charity, and disaster relief to the non-clerical communities on which they and their families depended for tithes. By using their own mutual-aid networks as tools of pastoral work, the parish clergy expanded those networks, in terms of both beneficiaries and participants, beyond the limits of the clerical soslovie. Key reforms of the diocesan structure in 1905 both loosened central control over the clerical networks and authorized the direct participation of non-clergy in their work. The associations of the parish clergy thus obtained unprecedented independence and social integration at the moment when they were confronted with the humanitarian disaster of 1905. Focusing on the dioceses of Moscow and Tver, this article examines the parish clergy’s use of their own soslovie networks to provide famine relief to fellow clerics and the general population between 1905 and 1909. This famine relief campaign demonstrated the independence and initiative of voluntary associations in late Imperial Russia. It also revealed the potential for cooperation and social integration among seemingly disparate communities, even within the divisive framework of the soslovie system.
The identity of the Sarawak freshwater crab Parathelphusa oxygona Nobili, 1901, with description of a new species, Parathelphusa nobilii, from Western
Kalimantan, Indonesia, Borneo (Crustacea: Brachyura: Gecarcinucidae)
Authors: NG PETER K. L.
Published: March 2014

The identity of the common lowland freshwater crab in western Sarawak, Borneo, East Malaysia, Parathelphusa oxygona Nobili, 1901 (family Gecarcinucidae), is clarified. The species is redescribed and figured, and its taxonomy discussed. Specimens from western Kalimantan, Borneo, Indonesia, which have been referred to P. oxygona are here referred to a new species, Parathelphusa nobilii. The new species can be differentiated from congeners by its relatively more swollen branchial regions of the carapace, wider and lower external orbital tooth, relatively more slender male abdomen and a straight male first gonopod.
A new species of troglobitic crab of the genus Stygothelphusa Ng, 1989, from Sarawak, Malaysia (Crustacea: Decapoda: Brachyura: Gecarcinucidae)
Authors: NG Peter K. L. , GRINANG JONGKAR
Published: March 2014

A new species of cave crab, Stygothelphusa antu new species, is described from limestone formations in Temurang, Sarawak, Malaysia. The new species is the most highly adapted to a cavericolous lifestyle among the four known species of Stygothelphusa, having a pale body pigmentation, reduced eyes and elongated pereopods. In contrast, the other three species have normal eyes that almost completely fill the orbits. The new species also differs from its congeners by a number of carapace, pereopod and gonopod characters.
What Do Healthcare Providers Know About Nutrition Support? A Survey of the Knowledge, Attitudes, and Practice of Pharmacists and Doctors Toward Nutrition Support in Malaysia
Authors: Karim Sarah A. , Ibrahim Baharudin , Tangiisuran Balamurugan , Davies J. Graham
Published: March 2014

Background and Aims: Malnutrition is one of the health problems that can be prevented by appropriate nutrition care provided by healthcare providers. However, this practice is still lacking possibly because of the providers' inadequate knowledge. The aim of this study was to evaluate the self‐reported knowledge, attitudes, and practices of pharmacists and doctors toward nutrition support in a tertiary care hospital setting. Methods: A validated questionnaire was distributed to all the doctors and pharmacists working in a tertiary hospital in Penang, Malaysia. Seven individuals including academics, general surgeons, and pharmacists performed the face and content validity. The questionnaire was piloted using 24 healthcare providers at a different hospital. Result: Of 400 surveyed, 158 doctors and 72 pharmacists from various grades completed the questionnaire. More doctors (31.6%) than pharmacists (15.3%) reported adequate knowledge to perform patients' nutrition screening. However, in the knowledge assessment, pharmacists had a higher mean score (6.07 ± 1.77) than the doctors did (4.59 ± 1.87; P < .001), and most (70.4%) of them were grouped in the “average” score range. In addition, both pharmacists and doctors have ambivalent attitudes toward nutrition support. Only 31.3% stated that they perform nutrition screening on admission, and half of them performed nutrition assessment during hospitalization. Conclusion: Inappropriate nutrition care might be due to the lack of guidelines and insufficient knowledge among doctors and pharmacists. Special nutrition training and education for both pharmacists and doctors should be established.
Functions of flt3 in zebrafish hematopoiesis and its relevance to human acute myeloid leukemia
Authors: He Bai-Liang , Shi Xiangguo , Man Cheuk Him , Ma Alvin C. H. , Ekker Stephen C. , Chow Howard C. H. , So Chi Wai Eric , Choi William W. L. , Zhang Wenqing , Zhang Yiyue , Leung Anskar Y. H.
Published: March 2014

Key Points

Zebrafish flt3 plays an important role in the initiation of definitive hematopoietic stem cells. Expression of human FLT3-ITD activates endogenous flt3 signaling and induces myeloid expansion.
High-resolution mapping of epitopes on the C2 domain of factor VIII by analysis of point mutants using surface plasmon resonance
Authors: Nguyen Phuong-Cac T. , Lewis Kenneth B. , Ettinger Ruth A. , Schuman Jason T. , Lin Jasper C. , Healey John F. , Meeks Shannon L. , Lollar Pete , Pratt Kathleen P.
Published: March 2014

Key Points

Amino acid residues comprising B-cell epitopes recognized by neutralizing anti-factor VIII antibodies (inhibitors) have been identified. Amino acids contributing significant antigen–antibody binding avidity are candidates for mutagenesis in the design of less antigenic proteins.
On a half-discrete reverse Mulholland-type inequality and an extension
Authors: Liu Tuo , Yang Bicheng , He Leping
Published: March 2014

By using the way of weight functions and the Hermite-Hadamard inequality, a half-discrete reverse Mulholland-type inequality with a best constant factor is given. The extension with multi-parameters, the equivalent forms as well as the relating homogeneous inequalities are also considered.

MSC:26D15.
Aetiology, antimicrobial therapy and outcome of patients with community acquired severe sepsis: a prospective study in a Norwegian university hospital
Authors: Nygård Siri Tandberg , Langeland Nina , Flaatten Hans K , Fanebust Rune , Haugen Oddbjørn , Skrede Steinar
Published: March 2014

Background

Severe sepsis is recognized as an inflammatory response causing organ dysfunction in patients with infection. Antimicrobial therapy is the mainstay of treatment. There is an ongoing demand for local surveillance of sepsis aetiology and monitoring of empirical treatment recommendations. The present study was established to describe the characteristics, quality of handling and outcome of patients with severe sepsis admitted to a Norwegian university hospital.

Methods

A one year prospective, observational study of adult community acquired case-defined severe sepsis was undertaken. Demographics, focus of infection, microbiological findings, timing and adequacy of empirical antimicrobial agents were recorded. Clinical diagnostic practice was evaluated. Differences between categorical groups were analysed with Pearson’s chi-squared test. Predictors of in-hospital mortality were identified in a multivariate stepwise backward logistic regression model.

Results

In total 220 patients were identified, yielding an estimated annual incidence of 0.5/1000 inhabitants. The focus of infection was established at admission in 69%. Respiratory tract infection was present in 52%, while genitourinary, soft tissue and abdominal infections each were found in 12-14%. Microbiological aetiology was identified in 61%; most prevalent were Streptococcus pneumoniae, Escherichia coli and Staphylococcus aureus. Independent predictors of in-hospital mortality were malignancy, cardiovascular disease, endocarditis, abdominal infections, undefined microbiological aetiology, delay in administration of empirical antimicrobial agents ≥ 6 hours and use of inadequate antimicrobial agents. In patients ≥ 75 years, antimicrobial therapy was less in compliance with current recommendations and more delayed.

Conclusions

Community acquired severe sepsis is common. Initial clinical aetiology is often revised. Compliance with recommendations for empirical antimicrobial treatment is lowest in elderly patients. Our results emphasizes that quick identification of correct source of infection, proper sampling for microbiological analyses, and fast administration of adequate antimicrobial agents are crucial points in the management of severe sepsis.
Incidence, pathogens and resistance patterns of nosocomial infections at a rural hospital in Gabon
Authors: Scherbaum Micha , Kösters Katrin , Mürbeth Raymund Egid , Ngoa Ulysse Ateba , Kremsner Peter Gottfried , Lell Bertrand , Alabi Abraham
Published: March 2014

Background

Nosocomial infections pose substantial risk to patients receiving care in hospitals. In Africa, this problem is aggravated by inadequate infection control due to poor hygiene, resource and structural constraints, deficient surveillance data and lack of awareness regarding nosocomial infections. We carried out this study to determine the incidence and spectrum of nosocomial infections, pathogens and antibiotic resistance patterns in a tertiary regional hospital in Lambaréné, Gabon.

Methods

This prospective case study was carried out over a period of six months at the Albert Schweitzer Hospital, Lambaréné, Gabon. All patients admitted to the departments of surgery, gynecology/obstetrics and internal medicine were screened daily for signs and symptoms of hospital-acquired infections.

Results

A total of 2925 patients were screened out of which 46 nosocomial infections (1.6%) were diagnosed. These comprised 20 (44%) surgical-site infections, 12 (26%) urinary-tract infections, 9 (20%) bacteraemias and 5 (11%) other infections. High rates of nosocomial infections were found after hysterectomies (12%) and Caesarean sections (6%). Most frequent pathogens were Staphylococcus aureus and Escherichia coli. Eight (40%) of 20 identified E. coli and Klebsiella spp. strains were ESBL-producing organisms.

Conclusion

The cumulative incidence of nosocomial infections in this study was low; however, the high rates of surgical site infections and multi-resistant pathogens necessitate urgent comprehensive interventions of infection control.
Invasive neuroendocrine carcinoma of the breast: a population-based study from the surveillance, epidemiology and end results (SEER) database
Authors: Wang Jun , Wei Bing , Albarracin Constance T , Hu Jianhua , Abraham Susan C , Wu Yun
Published: March 2014

Background

Neuroendocrine carcinoma (NEC) of the breast is a rare type of carcinoma that has not been well studied or characterized. Of the limited number of studies reported in the literature, most are case reports. A few small retrospective series studies have been reported.

Methods

We reviewed data on 142 cases of mammary NEC recorded in the surveillance, epidemiology, and end results (SEER) database during 2003–2009 and evaluated disease incidence and patient age, sex, and race/ethnicity; clinicopathologic characteristics; and survival in comparison to invasive mammary carcinoma, not otherwise specified. We also performed univariate and multivariate analyses to identify prognostic factors in this disease.

Results

Review of the 142 SEER cases revealed that NEC is an aggressive variant of invasive mammary carcinoma. It generally occurred in older women (>60 years); present with larger tumor size (>20 mm), higher histologic grade, and higher clinical stage; and result in shorter overall survival and disease-specific survival than invasive mammary carcinoma, not otherwise specified (IMC-NOS). Overall survival and disease-specific survival were shorter in NEC at each stage than in IMC-NOS of the same stage. Furthermore, when all NEC and IMC-NOS cases were pooled together, neuroendocrine differentiation itself was an adverse prognostic factor independent of other known prognostic factors, including age, tumor size, nodal status, histologic grade, estrogen/progesterone receptor status, and therapy.

Conclusions

NEC is a rare but aggressive type of mammary carcinoma. Novel therapeutic approaches should be explored for this uniquely clinical entity.
The role of CXC-chemokine receptor CXCR2 and suppressor of cytokine signaling-3 (SOCS-3) in renal cell carcinoma
Authors: Stofas Anastasios , Levidou Georgia , Piperi Christina , Adamopoulos Christos , Dalagiorgou Georgia , Bamias Aristotelis , Karadimou Alexandra , Lainakis George A , Papadoukakis Stefanos , Stravodimos Konstantinos , Dimopoulos Meletios-Athanasios , Patsouris Efstratios , Gakiopoulou Hariklia , Korkolopoulou Penelope
Published: March 2014

Background

Chemokine receptor signaling pathways are implicated in the pathobiology of renal cell carcinoma (RCC). However, the clinical relevance of CXCR2 receptor, mediating the effects of all angiogenic chemokines, remains unclear. SOCS (suppressor of cytokine signaling)-3 is a negative regulator of cytokine-driven responses, contributing to interferon-α resistance commonly used to treat advanced RCC with limited information regarding its expression in RCC.

Methods

In this study, CXCR2 and SOCS-3 were immunohistochemically investigated in 118 RCC cases in relation to interleukin (IL)-6 and (IL)-8, their downstream transducer phosphorylated (p-)STAT-3, and VEGF expression, being further correlated with microvascular characteristics, clinicopathological features and survival. In 30 cases relationships with hypoxia-inducible factors, i.e. HIF-1a, p53 and NF-κΒ (p65/RelA) were also examined. Validation of immunohistochemistry and further investigation of downstream transducers, p-JAK2 and p-c-Jun were evaluated by Western immunoblotting in 5 cases.

Results

Both CXCR2 and IL-8 were expressed by the neoplastic cells their levels being interrelated. CXCR2 strongly correlated with the levels of HIF-1a, p53 and p65/RelA in the neoplastic cells. Although SOCS-3 was simultaneously expressed with p-STAT-3, its levels tended to show an inverse relationship with p-JAK-2 and p-c-Jun in Western blots and were positively correlated with HIF-1a, p53 and p65/p65/RelA expression. Neither CXCR2 nor SOCS-3 correlated with the extent of microvascular network. IL-8 and CXCR2 expression was associated with high grade, advanced stage and the presence/number of metastases but only CXCR2 adversely affected survival in univariate analysis. Elevated SOCS-3 expression was associated with progression, the presence/number of metastasis and shortened survival in both univariate and multivariate analysis.

Conclusions

Our findings implicate SOCS-3 overexpression in RCC metastasis and biologic aggressiveness advocating its therapeutic targeting. IL-8/CXCR2 signaling also contributes to the metastatic phenotype of RCC cells but appears of lesser prognostic utility. Both CXCR2 and SOCS-3 appear to be related to transcription factors induced under hypoxia.
Baccalaureate nursing Students’ perspectives on learning about caring in China: a qualitative descriptive study
Authors: Ma Fang , Li Jiping , Liang Hongmin , Bai Yangjuan , Song Jianhua
Published: March 2014

Background

The need to provide humanistic care in the contemporary healthcare system is more imperative now and the importance of cultivating caring in nursing education is urgent. Caring as the primary work of nursing has been discussed extensively, such as the meaning of caring, and teaching and learning strategies to improve nursing students’ caring ability. Yet attempts to understand students’ perspectives on learning about caring and to know their learning needs are seldom presented. The aim of this qualitative descriptive study was to explore the baccalaureate nursing students’ perspectives on learning about caring in China.

Methods

A qualitative descriptive study using focus group interviews were undertaken in two colleges in Yunnan Province, China from February 2010 to April 2010. Purposeful sampling of 20 baccalaureate nursing students were recruited. Content analysis of the transcribed data was adopted to identify the themes.

Results

Four categories with some sub-categories related to students’ perspectives on learning about caring were identified from the data: 1) Learning caring by role model; 2) conducive learning environment as the incentive to the learning about caring; 3) lack of directive substantive way of learning as the hindrance to the learning about caring; 4) lack of cultural competency as the barrier to the learning about caring.

Conclusions

Both caring and uncaring experiences can promote the learning about caring in a way of reflective practice. The formal, informal and hidden curricula play an important role in the learning about caring. Cultural awareness, sensitivity and humility are important in the process of learning to care in a multicultural area.
ICAM-2 regulates vascular permeability and N-cadherin localization through ezrin-radixin-moesin (ERM) proteins and Rac-1 signalling
Authors: Amsellem Valerie , Dryden Nicola H , Martinelli Roberta , Gavins Felicity , Almagro Lourdes Osuna , Birdsey Graeme M , Haskard Dorian O , Mason Justin C , Turowski Patric , Randi Anna M
Published: March 2014

Background

Endothelial junctions control functions such as permeability, angiogenesis and contact inhibition. VE-Cadherin (VECad) is essential for the maintenance of intercellular contacts. In confluent endothelial monolayers, N-Cadherin (NCad) is mostly expressed on the apical and basal membrane, but in the absence of VECad it localizes at junctions. Both cadherins are required for vascular development. The intercellular adhesion molecule (ICAM)-2, also localized at endothelial junctions, is involved in leukocyte recruitment and angiogenesis.

Results

In human umbilical vein endothelial cells (HUVEC), both VECad and NCad were found at nascent cell contacts of sub-confluent monolayers, but only VECad localized at the mature junctions of confluent monolayers. Inhibition of ICAM-2 expression by siRNA caused the appearance of small gaps at the junctions and a decrease in NCad junctional staining in sub-confluent monolayers. Endothelioma lines derived from WT or ICAM-2-deficient mice (IC2neg) lacked VECad and failed to form junctions, with loss of contact inhibition. Re-expression of full-length ICAM-2 (IC2 FL) in IC2neg cells restored contact inhibition through recruitment of NCad at the junctions. Mutant ICAM-2 lacking the binding site for ERM proteins (IC2 ΔERM) or the cytoplasmic tail (IC2 ΔTAIL) failed to restore junctions. ICAM-2-dependent Rac-1 activation was also decreased in these mutant cell lines. Barrier function, measured in vitrovia transendothelial electrical resistance, was decreased in IC2neg cells, both in resting conditions and after thrombin stimulation. This was dependent on ICAM-2 signalling to the small GTPase Rac-1, since transendothelial electrical resistance of IC2neg cells was restored by constitutively active Rac-1. In vivo, thrombin-induced extravasation of FITC-labeled albumin measured by intravital fluorescence microscopy in the mouse cremaster muscle showed that permeability was increased in ICAM-2-deficient mice compared to controls.

Conclusions

These results indicate that ICAM-2 regulates endothelial barrier function and permeability through a pathway involving N-Cadherin, ERMs and Rac-1.
Tibialis Anterior muscle coherence during controlled voluntary activation in patients with spinal cord injury: diagnostic potential for muscle strength, gait and spasticity
Authors: Bravo-Esteban Elisabeth , Taylor Julian , Aleixandre Manuel , Simon-Martínez Cristina , Torricelli Diego , Pons José L , Gómez-Soriano Julio
Published: March 2014

Background

Coherence estimation has been used as an indirect measure of voluntary neurocontrol of residual motor activity following spinal cord injury (SCI). Here intramuscular Tibialis Anterior (TA) coherence estimation was performed within specific frequency bands for the 10-60 Hz bandwidth during controlled ankle dorsiflexion in subjects with incomplete SCI with and without spasticity.

Methods

In the first cohort study 15 non-injured and 14 motor incomplete SCI subjects were recruited to evaluate TA coherence during controlled movement. Specifically 15-30 Hz EMG was recorded during dorsiflexion with: i) isometric activation at 50, 75 and 100% of maximal voluntary torque (MVT), ii) isokinetic activation at 60 and 120°/s and iii) isotonic dorsiflexion at 50% MVT. Following identification of the motor tasks necessary for measurement of optimal TA coherence a second cohort was analyzed within the 10-16 Hz, 15-30 Hz, 24-40 Hz and 40-60 Hz bandwidths from 22 incomplete SCI subjects, with and without spasticity.

Results

Intramuscular 40-60 Hz, but not 15-30 Hz TA, coherence calculated in SCI subjects during isometric activation at 100% of MVT was lower than the control group. In contrast only isometric activation at 100% of MVT 15-30 Hz TA coherence was higher in subjects with less severe SCI (AIS D vs. AIS C), and correlated functionally with dorsiflexion MVT. Higher TA coherence was observed for the SCI group during 120°/s isokinetic movement. In addition 15-30 Hz TA coherence calculated during isometric activation at 100% MVT or 120°/s isokinetic movement correlated moderately with walking function and time from SCI, respectively. Spasticity symptoms correlated negatively with coherence during isometric activation at 100% of MVT in all tested frequency bands, except for 15-30 Hz. Specifically, 10-16 Hz coherence correlated inversely with passive resistive torque to ankle dorsiflexion, while clinical measures of muscle hypertonia and spasm severity correlated inversely with 40-60 Hz.

Conclusion

Analysis of intramuscular 15-30 Hz TA coherence during isometric activation at 100% of MVT is related to muscle strength and gait function following incomplete SCI. In contrast several spasticity symptoms correlated negatively with 10-16 Hz and 40-60 Hz TA coherence during isometric activation at 100% MVT. Validation of the diagnostic potential of TA coherence estimation as a reliable and comprehensive measure of muscle strength, gait and spasticity should facilitate SCI neurorehabilation.
Unplanned medication discontinuation as a potential pharmacovigilance signal: a nested young person cohort study
Authors: Sun Angela Peichen , Kirby Bradley , Black Corri , Helms Peter John , Bennie Marion , McLay James Stuart
Published: March 2014

Background

Because of relatively small treatment numbers together with low adverse drug reaction (ADR) reporting rates the timely identification of ADRs affecting children and young people is problematic. The primary objective of this study was to assess the utility of unplanned medication discontinuation as a signal for possible ADRs in children and young people.

Methods

Using orlistat as an exemplar, all orlistat prescriptions issued to patients up to 18 years of age together with patient characteristics, prescription duration, co-prescribed medicines and recorded clinical (Read) codes were identified from the Primary Care Informatics Unit database between 1st Jan 2006-30th Nov 2009. Binary logistic regression was used to assess association between characteristics and discontinuation.

Results

During the study period, 79 patients were prescribed orlistat (81% female, median age 17 years). Unplanned medication discontinuation rates for orlistat were 52% and 77% at 1 and 3-months. Almost 20% of patients were co-prescribed an anti-depressant. One month unplanned medication discontinuation was significantly lower in the least deprived group (SIMD 1–2 compared to SIMD 9–10 OR 0.09 (95% CI0.01 – 0.83)) and those co-prescribed at least one other medication. At 3 months, discontinuation was higher in young people (≥17 yr versus, OR 3.07 (95% CI1.03 – 9.14)). Read codes were recorded for digestive, respiratory and urinary symptoms around the time of discontinuation for 24% of patients. Urinary retention was reported for 7.6% of patients.

Conclusions

Identification of unplanned medication discontinuation using large primary care datasets may be a useful tool for pharmacovigilance signal generation and detection of potential ADRs in children and young people.
Cell cycle, oncogenic and tumor suppressor pathways regulate numerous long and macro non-protein-coding RNAs
Authors: Hackermüller Jörg , Reiche Kristin , Otto Christian , Hösler Nadine , Blumert Conny , Brocke-Heidrich Katja , Böhlig Levin , Nitsche Anne , Kasack Katharina , Ahnert Peter , Krupp Wolfgang , Engeland Kurt , Stadler Peter F , Horn Friedemann
Published: March 2014

Background

The genome is pervasively transcribed but most transcripts do not code for proteins, constituting non-protein-coding RNAs. Despite increasing numbers of functional reports of individual long non-coding RNAs (lncRNAs), assessing the extent of functionality among the non-coding transcriptional output of mammalian cells remains intricate. In the protein-coding world, transcripts differentially expressed in the context of processes essential for the survival of multicellular organisms have been instrumental in the discovery of functionally relevant proteins and their deregulation is frequently associated with diseases. We therefore systematically identified lncRNAs expressed differentially in response to oncologically relevant processes and cell-cycle, p53 and STAT3 pathways, using tiling arrays.

Results

We found that up to 80% of the pathway-triggered transcriptional responses are non-coding. Among these we identified very large macroRNAs with pathway-specific expression patterns and demonstrated that these are likely continuous transcripts. MacroRNAs contain elements conserved in mammals and sauropsids, which in part exhibit conserved RNA secondary structure. Comparing evolutionary rates of a macroRNA to adjacent protein-coding genes suggests a local action of the transcript. Finally, in different grades of astrocytoma, a tumor disease unrelated to the initially used cell lines, macroRNAs are differentially expressed.

Conclusions

It has been shown previously that the majority of expressed non-ribosomal transcripts are non-coding. We now conclude that differential expression triggered by signaling pathways gives rise to a similar abundance of non-coding content. It is thus unlikely that the prevalence of non-coding transcripts in the cell is a trivial consequence of leaky or random transcription events.
Introduction to this special section: Rock physics
Authors: Gonzalez Ezequiel , Torres-Verdín Carlos , Hofmann Ronny
Published: March 2014

The application of rock physics in exploration and development of hydrocarbon reservoirs has increased considerably over the last two decades. The number of technical sessions dedicated to a specific topic or theme in an SEG Annual Meeting directly reflects the activity and interest in the subject. Twenty years ago, there were only two sessions labeled rock physics. Ten years ago there were five, and last year's Annual Meeting in Houston featured an impressive 10 sessions in the technical program dealing specifically with rock physics. Some of the factors that have contributed to the ascendancy of rock physics include: advances in seismic processing generating amplitude data with enough fidelity to be quantitative in predicting rock properties, the need for derisking subsurface factors of prospects from an economical perspective, and the increase of knowledge on the topic in the industry.
On discriminating sand from shale using prestack inversion without wells: A proof of concept using well data as a surrogate for seismic amplitudes
Authors: Anderson M. , Gullco R.
Published: March 2014

A new method has been developed to discriminate sand from shale, from P-wave velocity, S-wave velocity, and density values obtained from elastic seismic inversion without well control. The method, based on empirical or semiempirical principles, has been tested with well data in thick Tertiary clastic columns in the Gulf of Mexico, where the input data (compressional and shear sonic logs and bulk density) are of good quality and where there is a lithology log to verify results. The method cannot be applied to gas-bearing sands. Gas sands should be separated prior to application of the method using, for instance, the VP/VSvalues as a criterion. A preliminary discrimination of sand from shale in areas without well control is indeed a useful exploration tool. It is also very useful in pore-pressure calculations in which, ideally, only shale points should be used to determine the normal compaction trend.
Relative rock physics
Authors: Ball Vaughn , Blangy J. P. , Schiott Christian , Chaveste Alvaro
Published: March 2014

A quantitative framework for relative rock physics includes a definition of relative elastic property that is rooted in inverse theory and that can be used practically to compute the properties. The framework also includes a set of rules that quantify how operations on absolute properties affect their relative counterparts. From these rules, a comprehensive table of relative elastic properties can be generated, all of which are expressed in terms of relative P-velocity, S-velocity, and density. Finally, the framework includes empirical and model-based rock-physics rules that can be applied directly to the relative properties without reverting to their absolute counterparts. That provides a practical route to such interpretation techniques as direct-to-seismic fluid substitution. The framework offers a quantitative alternative to workflows centered on absolute seismic inversion. In some cases, relative rock-physics workflows are preferable to absolute flows because they avoid statistical complications associated with the nonstationarity of the mean of absolute elastic properties.
RNA polymerase II pausing during development
Authors: Gaertner Bjoern , Zeitlinger Julia
Published: March 2014

The rapid expansion of genomics methods has enabled developmental biologists to address fundamental questions of developmental gene regulation on a genome-wide scale. These efforts have demonstrated that transcription of developmental control genes by RNA polymerase II (Pol II) is commonly regulated at the transition to productive elongation, resulting in the promoter-proximal accumulation of transcriptionally engaged but paused Pol II prior to gene induction. Here we review the mechanisms and possible functions of Pol II pausing and their implications for development.
Growing older gracefully - a review of the 10th edition of Developmental Biology
Authors: Weil Timothy T.
Published: March 2014

First published in 1985, Developmental Biology by Scott F. Gilbert has been an influential textbook for a generation of scientists. In this brief review I discuss the latest (10th) edition of the series, comment on updates to the text, highlight details of particular interest to lecturers and compare this book with other resources available in the internet era.