bluuebunny/crossref_metadata_2025 huggingface dataset:
Snowball: resampling combined with distance-based regression to discover transcriptional consequences of a driver mutation
Authors: Xu Yaomin , Guo Xingyi , Sun Jiayang , Zhao Zhongming
Published: September 2014

Motivation: Large-scale cancer genomic studies, such as The Cancer Genome Atlas (TCGA), have profiled multidimensional genomic data, including mutation and expression profiles on a variety of cancer cell types, to uncover the molecular mechanism of cancerogenesis. More than a hundred driver mutations have been characterized that confer the advantage of cell growth. However, how driver mutations regulate the transcriptome to affect cellular functions remains largely unexplored. Differential analysis of gene expression relative to a driver mutation on patient samples could provide us with new insights in understanding driver mutation dysregulation in tumor genome and developing personalized treatment strategies.

Results: Here, we introduce the Snowball approach as a highly sensitive statistical analysis method to identify transcriptional signatures that are affected by a recurrent driver mutation. Snowball utilizes a resampling-based approach and combines a distance-based regression framework to assign a robust ranking index of genes based on their aggregated association with the presence of the mutation, and further selects the top significant genes for downstream data analyses or experiments. In our application of the Snowball approach to both synthesized and TCGA data, we demonstrated that it outperforms the standard methods and provides more accurate inferences to the functional effects and transcriptional dysregulation of driver mutations.

Availability and implementation: R package and source code are available from CRAN at http://cran.r-project.org/web/packages/DESnowball , and also available at http://bioinfo.mc.vanderbilt.edu/DESnowball/ .

Contact:  zhongming.zhao@vanderbilt.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Serum microRNAs in patients with genetic amyotrophic lateral sclerosis and pre-manifest mutation carriers
Authors: Freischmidt Axel , Müller Kathrin , Zondler Lisa , Weydt Patrick , Volk Alexander E. , Božič Anže Lošdorfer , Walter Michael , Bonin Michael , Mayer Benjamin , von Arnim Christine A. F. , Otto Markus , Dieterich Christoph , Holzmann Karlheinz , Andersen Peter M. , Ludolph Albert C. , Danzer Karin M. , Weishaupt Jochen H.
Published: September 2014

Knowledge about the nature of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis is largely lacking. It could not only pave the way for the discovery of valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained comprehensive expression profiles of microRNAs in the serum of patients with familial amyotrophic lateral sclerosis, asymptomatic mutation carriers and healthy control subjects. We observed a strikingly homogenous microRNA profile in patients with familial amyotrophic lateral sclerosis that was largely independent from the underlying disease gene. Moreover, we identified 24 significantly downregulated microRNAs in pre-manifest amyotrophic lateral sclerosis mutation carriers up to two decades or more before the estimated time window of disease onset; 91.7% of the downregulated microRNAs in mutation carriers overlapped with the patients with familial amyotrophic lateral sclerosis. Bioinformatic analysis revealed a consensus sequence motif present in the vast majority of downregulated microRNAs identified in this study. Our data thus suggest specific common denominators regarding molecular pathogenesis of different amyotrophic lateral sclerosis genes. We describe the earliest pathomolecular alterations in amyotrophic lateral sclerosis mutation carriers known to date, which provide a basis for the discovery of novel therapeutic targets and strongly argue for studies evaluating presymptomatic disease-modifying treatment in amyotrophic lateral sclerosis.
Vasoconstrictor Responses to Vasopressor Agents in Human Pulmonary and Radial Arteries
Authors: Currigan Dale A. , Hughes Richard J. A. , Wright Christine E. , Angus James A. , Soeding Paul F.
Published: September 2014

Background:

Vasopressor drugs, commonly used to treat systemic hypotension and maintain organ perfusion, may also induce regional vasoconstriction in specialized vascular beds such as the lung. An increase in pulmonary vascular tone may adversely affect patients with pulmonary hypertension or right heart failure. While sympathomimetics constrict pulmonary vessels, and vasopressin does not, a direct comparison between these drugs has not been made. This study investigated the effects of clinically used vasopressor agents on human isolated pulmonary and radial arteries.

Methods:

Isolated pulmonary and radial artery ring segments, mounted in organ baths, were used to study the contractile responses of each vasopressor agent. Concentration–response curves to norepinephrine, phenylephrine, metaraminol, and vasopressin were constructed.

Results:

The sympathomimetics norepinephrine, phenylephrine, and metaraminol caused concentration-dependent vasoconstriction in the radial (pEC50: 6.99 ± 0.06, 6.14 ± 0.09, and 5.56 ± 0.07, respectively, n = 4 to 5) and pulmonary arteries (pEC50: 6.86 ± 0.11, 5.94 ± 0.05 and 5.56 ± 0.09, respectively, n = 3 to 4). Vasopressin was a potent vasoconstrictor of the radial artery (pEC50 9.13 ± 0.20, n = 3), whereas in the pulmonary artery, it had no significant effect.

Conclusions:

Sympathomimetic-based vasopressor agents constrict both human radial and pulmonary arteries with similar potency in each. In contrast, vasopressin, although a potent vasoconstrictor of radial vessels, had no effect on pulmonary vascular tone. These findings provide some support for the use of vasopressin in patients with pulmonary hypertension.
Cancer Rates in Adults After Cardiac Interventions
Authors: Alameddine Abdallah K. , Visintainer Paul , Normand Sharon-Lise T. , Wolf Robert E. , Alameddine Yvonne A.
Published: September 2014

Background:

The postprocedural state after cardiac revascularization interventions is characterized by intense inflammation and activation of inflammatory cytokines due to myonecrosis and ischemia/reperfusion injury. Involvement of similar processes also participates in cellular malignant transformation. In this study, the association between cardiac interventions and subsequent cancer risk development was therefore evaluated.

Methods:

The 5-year cumulative incidence of cancer was examined in 2 cardiac care cohorts: all patients undergoing either open heart surgery or percutaneous coronary interventions (PCI) at hospitals in the commonwealth of Massachusetts. The observed cases of cancer were compared with the number of expected cases based on the state cancer rates, adjusting for sex and 5-year age groups. The standardized morbidity ratio (SMR) was used for this comparison.

Results:

Of 10,301 patients in the surgical cohort, 804 (7.8%) incident cancers developed over 5 years of follow-up, whereas 245.7 incident cancers were expected. This yielded an SMR of 3.27 (95% CI, 3.05-3.51; P<0.0001). In the PCI cohort comprising 13,001 patients, 1029 (7.9%) incident cancers developed over 5 years, resulting in an SMR of 3.53 (95% CI, 3.32-3.75; P<0.0001). Excluding respiratory cancers from the analysis (to limit smoking-related cancers) reduced risk estimates only slightly. For the surgical cohort: SMR=2.80; 95% CI, 2.59-3.01; P<0.0001. For the PCI cohort: SMR=2.97; 95% CI, 2.78-3.18; P<0.0001.

Conclusions:

Undergoing heart revascularization procedures was associated with increased rate of cancer development as compared with the state general population. This cohort may warrant increased monitoring.
MYB118 Represses Endosperm Maturation in Seeds of Arabidopsis
Authors: Barthole Guillaume , To Alexandra , Marchive Chloé , Brunaud Véronique , Soubigou-Taconnat Ludivine , Berger Nathalie , Dubreucq Bertrand , Lepiniec Loïc , Baud Sébastien
Published: September 2014

In the exalbuminous species Arabidopsis thaliana, seed maturation is accompanied by the deposition of oil and storage proteins and the reduction of the endosperm to one cell layer. Here, we consider reserve partitioning between embryo and endosperm compartments. The pattern of deposition, final amount, and composition of these reserves differ between the two compartments, with the embryo representing the principal storage tissue in mature seeds. Complex regulatory mechanisms are known to prevent activation of maturation-related programs during embryo morphogenesis and, later, during vegetative growth. Here, we describe a regulator that represses the expression of maturation-related genes during maturation within the endosperm. MYB118 is transcriptionally induced in the maturing endosperm, and seeds of myb118 mutants exhibit an endosperm-specific derepression of maturation-related genes associated with a partial relocation of storage compounds from the embryo to the endosperm. Moreover, MYB118 activates endosperm-induced genes through the recognition of TAACGG elements. These results demonstrate that the differential partitioning of reserves between the embryo and endosperm in exalbuminous Arabidopsis seeds does not only result from developmental programs that establish the embryo as the preponderant tissue within seeds. This differential partitioning is also regulated by MYB118, which regulates the biosynthesis of reserves at the spatial level during maturation.
Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis
Authors: van der Velden Walter J. F. M. , Herbers Alexandra H. E. , Netea Mihai G. , Blijlevens Nicole M. A.
Published: September 2014

Infection remains one of the most prominent complications after cytotoxic treatment for cancer. The connection between neutropenia and both infections and fever has long been designated as ‘febrile neutropenia’, but treatment with antimicrobial agents and haematopoietic growth factors has failed to significantly reduce its incidence. Moreover, emerging antimicrobial resistance is becoming a concern that necessitates the judicious use of available antimicrobial agents. In addition to neutropenia, patients who receive cytotoxic therapy experience mucosal barrier injury (MBI) or ‘mucositis’. MBI creates a port‐de‐entrée for resident micro‐organisms to cause blood stream infections and contributes directly to the occurrence of fever by disrupting the highly regulated host‐microbe interactions, which, even in the absence of an infection, can result in strong inflammatory reactions. Indeed, MBI has been shown to be a pivotal factor in the occurrence of inflammatory complications after cytotoxic therapy. Hence, the concept ‘febrile neutropenia’ alone may no longer suffice and a new concept ‘febrile mucositis’ should be recognized as the two are at least complementary. This review we summarizes the existing evidence for both paradigms and proposes new therapeutic approaches to tackle the perturbed host‐microbe interactions arising from cytotoxic therapy‐induced tissue damage in order to reduce fever in neutropenic patients with cancer.
Reference values for serum dehydroepiandrosterone‐sulphate in healthy children and adolescents with emphasis on the age of adrenarche and pubarche
Authors: Guran Tulay , Firat Irfan , Yildiz Feyza , Kaplan Bulut Ipek , Dogru Mahmut , Bereket Abdullah
Published: September 2014

Objective

Adrenarche is a component of normal pubertal development. Recent decades have witnessed changes in the timing and tempo of puberty in different populations. We aimed to obtain normative data on dehydroepiandrosterone‐sulphate (DHEA‐S) secretion in healthy children and to evaluate the age of adrenarche, pubarche and the DHEA‐S levels at which pubarche starts in both sexes.

Methods

Serum DHEA‐S concentrations were measured in 531 healthy (291 female) Turkish children aged 1 month–18 years by an automated chemiluminescence method. Pubic hair development was evaluated. DHEA‐S concentrations >108·4 nmol/l (40 μg/dl) were regarded as adrenarche. Age‐related normative data were constructed. Age at adrenarche and pubarche and the DHEA‐S levels at pubarche were estimated using ROC analyses.

Results

Serum DHEA‐S levels were high in the first 6 months of life then declined below 108·4 nmol/l (40 μg/dl) with a cut‐off age of 0·46 years for girls and 0·61 years for boys with 98% and 96% statistical sensitivity. Stable minimum levels were observed for the following 5 years. The cut‐off age for DHEA‐S levels rising above 108·4 nmol/l (40 μg/dl) was 8·0 and 7·0 years for girls for boys, respectively. DHEA‐S levels at transition from Tanner stage P1 to P2 was 90·5 nmol/l (33·4 μg/dl) in girls and 118 nmol/l (43·6 μg/dl) in boys. Median (CI) DHEA‐S levels were 170·7(94·8–336) and 244(119·2–357·7) nmo/l [63(35–124) and 90(44–132) μg/dl] in girls and boys, respectively, with Tanner stage P2 pubic hair.

Conclusions

We established reference data of serum DHEA‐S levels in a large group of children. Currently, adrenarche (DHEA‐S>108·4 nmol/l) starts 1 year earlier in boys but higher DHEA‐S levels are needed for transition from P1 to P2 in boys.
Inhibin B plus LH vs GnRH agonist test for distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism in boys
Authors: Binder Gerhard , Schweizer Roland , Blumenstock Gunnar , Braun Regina
Published: September 2014

Objective

The distinction between constitutional delay of growth and puberty (CDGP) and isolated hypogonadotropic hypogonadism (IHH) in males with delayed puberty is difficult but important for timely treatment. We assessed the accuracy of the GnRH agonist test (triptorelin 0·1 mg) in comparison with inhibin B alone or in combination with basal LH for the diagnosis of IHH.

Patients and measurements

Ninety‐seven prepubertal males aged 13·7–17·5 year, with testicular volumes ≤4 ml, were examined every 6 months. CDGP was defined by a testicular volume ≥8 ml after 18 months, and IHH was defined by a testicular volume <5 ml after 24 months follow‐up. Inhibin B concentrations were measured by ELISA, and LH concentrations were measured by CLIA.

Results

At follow‐up, the cohort comprised 52 boys with CDGP and nine with IHH. The other patients were lost for follow‐up (n = 10), had not reached follow‐up yet (n = 20) or did not reach a definite testicular volume (n = 6). Basal LH <0·3 IU/l, stimulated LH (4 h) <5·3 IU/l or inhibin B <111 pg/ml had 100% sensitivity for IHH. Only LH (4 h) <5·3 IU/l had a specificity of 100%, and the specificities of basal LH <0·3 IU/l (88%) or inhibin B <110 pg/ml (92%) were lower. The combination of LH <0·3 IU/l with inhibin B <111 pg/ml increased the specificity to 98·1%.

Conclusions

The LH response 4 h after GnRH agonist stimulation has an excellent accuracy for the diagnosis of IHH in prepubertal boys with delayed puberty. However, the measurement of inhibin B and basal LH in combination is a valid, reliable and less‐invasive alternative test.
Using Web searches to track interest in synthetic cannabinoids (aka ‘herbal incense’)
Authors: Curtis Brenda , Alanis‐Hirsch Kelly , Kaynak Övgü , Cacciola John , Meyers Kathy , McLellan Anthony Thomas
Published: September 2014

Introduction and Aims

This article reports a content analysis of Internet websites related to an emerging designer drug, synthetic cannabinoids. The number of synthetic cannabinoids searchers in the USA has steadily increased from November 2008 to November 2011.

Design and Methods

To determine the information available on the Internet in relation to synthetic cannabinoids, sites were identified using the Google search engine and the search term ‘herbal incense’. The first 100 consecutive sites were visited and classified by two coders. The websites were evaluated for type of content (retail, information, news, other). US unique monthly visitor data were examined for the top 10 retail sites, and these sites were coded for the quality of information available regarding the legality of synthetic cannabinoids sale and use.

Results

The Google search yielded 2 730 000 sites for ‘herbal incense’ (for comparison of search terms: ‘synthetic marijuana’, 1 170 000; ‘K2 Spice’, 247 000; and ‘synthetic weed’, 122 000). Moreover, in the Google search, 87% of the sites were retail sites, 5% news, 4% informational and 4% non‐synthetic cannabinoid sites.

Discussion and Conclusions

Many tools found within Google free services hold promise in providing a technique to identify emerging drug markets. We recommend continued surveillance of the Internet using the online tools presented in this brief report by both drug researchers and policy‐makers to identify the emerging trends in synthetic drugs' availability and interest.[Curtis C, Alanis‐Hirsch K, Kaynak Ö, Cacciola J, Meyers K, McLellan AT. Using Web searches to track interest in synthetic cannabinoids (aka ‘herbal incense’) Drug Alcohol Rev 2015;34:108–108]
A typology of prescription drug misuse: A latent class approach to differences and harms
Authors: Kelly Brian C. , Rendina H. Jonathon , Vuolo Mike , Wells Brooke E. , Parsons Jeffrey T.
Published: September 2014

Introduction and Aims

Prescription drug misuse is a considerable problem among young adults, and the identification of types of misuse among this population remains important for prevention and intervention efforts. We use latent class analysis to identify possible distinct latent groups of prescription drug misusers across multiple prescription drug types (pain killers, sedatives and stimulants).

Design and Methods

Our data are comprised of a sample of 404 young adults recruited from nightlife scenes via time–space sampling. Through the specification of a zero‐inflated Poisson latent class analysis, we evaluate differences in class membership by various demographic factors as well as assess the relationship between class membership and health outcomes, including indications of dependence, problems associated with substance use and mental health.

Results

Our assessment of fit indices led to a four‐class solution (dabblers, primary stimulant users, primary downers users and extensive regulars). No demographic differences existed between latent classes. The extensive regular class report the greatest number of symptoms related to dependence, greatest number of problems related to misuse and the greatest mental health problems. The dabblers report the fewest problems and symptoms, while the other two classes experiences problems and symptoms in between the classes on the extremes.

Discussion and Conclusions

Prevention efforts should take into account that young adults who misuse prescription drug have different profiles of misuse, and there may be a need for varied interventions to target these different types of misuse. [Kelly BC, Rendina HJ, Vuolo M, Wells BE, Parsons JT. A typology of prescription drug misuse: A latent class approach to differences and harms. Drug Alcohol Rev 2015;34:211–20]
Primary Intimal (Spindle Cell) Sarcoma of the Left Atrium
Authors: Fu Bo , Yu Hui , Yang Jian
Published: September 2014

Mini‐Abstract

A previously healthy 50‐year‐old man presented to our hospital with a history of progressive shortness of breath and diminished exercise tolerance for 3 months. A transthoracic echocardiogram was interpreted as showing a left atrial mass that was mobile and protruding into the left ventricle and noted that it was “like a myxoma, though its attachment was not visualized.” He was taken to the operating room with the initial diagnosis of left atrial myxoma, but upon surgical inspection of the left atrium, it was noted that the appearance of the tumor was more suggestive of malignancy. Pathologic examination revealed sheets of high‐grade densely packed spindle cells replacing and infiltrating into the atrial wall.
Disruption of actin‐binding domain‐containing Dystonin protein causes dystonia musculorum in mice
Authors: Horie Masao , Watanabe Keisuke , Bepari Asim K. , Nashimoto Jun‐ichiro , Araki Kimi , Sano Hiromi , Chiken Satomi , Nambu Atsushi , Ono Katsuhiko , Ikenaka Kazuhiro , Kakita Akiyoshi , Yamamura Ken‐ichi , Takebayashi Hirohide
Published: September 2014

The Dystonin gene (Dst) is responsible for dystonia musculorum (dt), an inherited mouse model of hereditary neuropathy accompanied by progressive motor symptoms such as dystonia and cerebellar ataxia. Dst‐a isoforms, which contain actin‐binding domains, are predominantly expressed in the nervous system. Although sensory neuron degeneration in the peripheral nervous system during the early postnatal stage is a well‐recognised phenotype in dt, the histological characteristics and neuronal circuits in the central nervous system responsible for motor symptoms remain unclear. To analyse the causative neuronal networks and roles of Dst isoforms, we generated novel multipurpose Dst gene trap mice, in which actin‐binding domain‐containing isoforms are disrupted. Homozygous mice showed typical dt phenotypes with sensory degeneration and progressive motor symptoms. The gene trap allele (DstGt) encodes a mutant Dystonin‐LacZ fusion protein, which is detectable by X‐gal (5‐bromo‐4‐chloro‐3‐indolyl‐β‐D‐galactoside) staining. We observed wide expression of the actin‐binding domain‐containing Dystonin isoforms in the central nervous system (CNS) and peripheral nervous system. This raised the possibility that not only secondary neuronal defects in the CNS subsequent to peripheral sensory degeneration but also cell‐autonomous defects in the CNS contribute to the motor symptoms. Expression analysis of immediate early genes revealed decreased neuronal activity in the cerebellar‐thalamo‐striatal pathway in the homozygous brain, implying the involvement of this pathway in the dt phenotype. These novel DstGt mice showed that a loss‐of‐function mutation in the actin‐binding domain‐containing Dystonin isoforms led to typical dt phenotypes. Furthermore, this novel multipurpose DstGt allele offers a unique tool for analysing the causative neuronal networks involved in the dt phenotype.
Transition in lesional focal epilepsy, and following epilepsy surgery
Authors: Cross J. Helen , Duchowny Michael
Published: September 2014

Children with intractable epilepsy benefit from early surgical treatment when possible to reduce long‐term morbidity. Issues for transition are variable according to type and timing of surgery, and the outcome. When surgery is successful, cognitive and behavioral improvements may not be apparent for several years. The value of continuing antiepileptic drug (AED) treatment after successful surgery remains unclear, and the adjustment to a life without seizures may be challenging.
Characterisation of immune responses in healthy foals when a multivalent vaccine protocol was initiated at age 90 or 180 days
Authors: Davis E. G. , Bello N. M. , Bryan A. J. , Hankins K. , Wilkerson M.
Published: September 2014

Reasons for performing study

Protection from infectious disease requires antigen‐specific immunity. In foals, most vaccine protocols are delayed until 6 months to avoid maternal antibody interference. Susceptibility to disease may exist prior to administration of vaccination at age 4–6 months.

Objectives

The aim of this investigation was to characterise immune activation among healthy foals in response to a multivalent vaccine protocol and compare immune responses when foals were vaccinated at age either 90 or 180 days.

Study design

Randomised block design.

Methods

Twelve healthy foals with colostral transfer were blocked for age and randomly assigned to vaccination at age 90 days (treatment) or at age 180 days (control). Vaccination protocols included a 3‐dose series and booster vaccine administered at age 11 months.

Results

Immune response following vaccination at age 90 or 180 days was comparable for several measures of cellular immunity. Antigen specificCD4+ andCD8+ expression of interleukin‐4, interferon‐γ and granzymeBto eastern equine encephalomyelitis, western equine encephalomyelitis, West Nile virus, tetanus toxoid, equine influenza and equine herpesvirus‐1/4 antigens were evident for both groups 30 days after initial vaccine and at age 344 days. Both groups showed a significant increase in antigen‐specific immunoglobulinGexpression following booster vaccine at age 11 months, thereby indicating memory immune responses.

Conclusions

The data presented in this report demonstrate that young foals are capable of immune activation following a 3‐dose series with a multivalent vaccine, despite presence of maternal antibodies. Although immune activation does not automatically confer protection, several of the immune indicators measured showed comparable expression in foals vaccinated at 3 months relative to control foals vaccinated at age 6 months. In high‐risk situations where immunity may be required earlier than following a conventional vaccine series, our data provide evidence that foals respond to immunisation initiated at 3 months in a comparable manner to foals initiated at an older age.
Normal range of bleeding scores for the ISTH‐BAT: adult and pediatric data from the merging project
Authors: Elbatarny M. , Mollah S. , Grabell J. , Bae S. , Deforest M. , Tuttle A. , Hopman W. , Clark D. S. , Mauer A. C. , Bowman M. , Riddel J. , Christopherson P. A. , Montgomery R. R. ,   Zimmerman Program Investigators, Rand M. L. , Coller B. , James P. D.
Published: September 2014

Bleeding Assessment Tools (BATs) have been developed to aid in the standardized evaluation of bleeding symptoms. The Vicenza Bleeding Questionnaire (BQ), published in 2005, established a common framework and scoring key that has undergone subsequent modification over the years, culminating in the publication of the ISTH‐BAT in 2010. Understanding the normal range of bleeding scores is critical when assessing the utility of a BAT. Within the context of The Merging Project, a bioinformatics system was created to facilitate the merging of legacy data derived from four different (but all Vicenza‐based) BATs; the MCMDM1‐VWD BQ, the Condensed MCMDM‐1VWD BQ, the Pediatric Bleeding Questionnaire and the ISTH‐BAT. Data from 1040 normal adults and 328 children were included in the final analysis, which showed that the normal range is 0–3 for adult males, 0–5 for adult females and 0–2 in children for both males and females. Therefore, the cut‐off for a positive or abnormal BS is ≥4 in adult males, ≥6 in adult females and ≥3 in children. This information can now be used to objectively assess bleeding symptoms as normal or abnormal in future studies.
Five‐year cumulative incidence of invasive anal cancer among HIV‐infected patients according to baseline anal cytology results: an inception cohort analysis
Authors: Cachay E , Agmas W , Mathews C
Published: September 2014

Objectives

The aim of the study was to estimate the cumulative incidence of, and rates of progression to, invasive anal cancer (IAC) according to baseline anal cytology screening category in an unselected HIV clinical care cohort in the antiretroviral era.

Methods

A retrospective cohort analysis of HIV‐infected patients under care at the University of California at San Diego Owen Clinic was carried out. Patients were eligible for this analysis if they had at least two anal cytohistological results available for longitudinal analysis. Kaplan−Meier analysis was used to estimate the cumulative incidence of IAC over time according to baseline cytology category [less than high‐grade intraepithelial lesion (HSIL) versus HSIL]. Cox regression analysis was used to adjust for the following covariates: antiretroviral use, level of HIV viraemia, smoking status and infrared photocoagulation (IRC) ablation therapy.

Results

Between 2000 and 2012, we followed 2804 HIV‐infected patients for a median of 4 years under a clinic protocol requiring baseline anal cytology screening. Incident IAC was diagnosed in 23 patients. Patients with a baseline HSIL anal cytology had an estimated 5‐year probability of progression to IAC of 1.7% and an estimated annual progression risk of 1 in 263. None of the examined covariates was significantly associated with IAC incidence when examined in separate unadjusted Cox models.

Conclusions

HIV‐infected patients with a baseline HSIL anal cytology had a 5‐year cumulative incidence of IAC of 1.65%, with an upper 95% confidence bound of 4.5%. This population‐based study provides quantitative risk estimates that may be used for counselling patients regarding management options for abnormal cytology results.
Antigen/IgG immune complex‐primed mucosal mast cells mediate antigen‐specific activation of co‐cultured T cells
Authors: Ding Jie , Fang Yu , Xiang Zou
Published: September 2014

Mast cells are proposed to be one of the targets for mucosal vaccine adjuvants. We previously demonstrated that mucosal adjuvants containing IgG immune complexes could activate connective tissue mast cells enhancing immune responses. Here we suggest that mucosal mast cells (MMC) may also contribute to augmentation of antigen‐specific immune responses following treatment with antigens complexed with IgG. We demonstrated that both bone marrow‐derived cultured MMC and tissue resident MMC incorporated ovalbumin (OVA) at a greater level in the presence of anti‐OVA IgG. Co‐culture of OVA/IgG‐pulsed bone marrow‐derived MMC with splenocytes from OT‐II mice promoted OVA‐specific activation and proliferation of T cells, a process known as cross‐presentation. Furthermore, bone marrow‐derived cultured MMC underwent apoptosis following treatment with IgG immune complexes, a feature that has been described as favouring phagocytosis of mast cells by professional antigen‐presenting cells.
Hypoxia‐inducible factors in regulation of immune responses in tumour microenvironment
Authors: Kumar Vinit , Gabrilovich Dmitry I.
Published: September 2014

Hypoxia is one of the hallmarks of the tumour microenvironment. It is the result of insufficient blood supply to support proliferating tumour cells. In response to hypoxia, the cellular machinery uses mechanisms whereby the low level of oxygen is sensed and counterbalanced by changing the transcription of numerous genes. Hypoxia‐inducible factors (HIF) play a critical role in the regulation of cellular responses to hypoxia. In recent years ample evidence has indicated that HIF play a prominent role in tumour immune responses. Up‐regulation of HIF1α promotes immune suppressive activity of myeloid‐derived suppressive cells (MDSC) and tumour‐associated macrophages (TAM) and rapid differentiation of MDSC to TAM. HIF1α does not affect MDSC differentiation to dendritic cells (DC) but instead causes DC activation. HIF inhibit effector functions of tumour‐infiltrating lymphocytes. HIF1α inhibits regulatory T (Treg) cell development by switching the balance towards T helper type 17 cells. However, as a major part of Treg cell differentiation does not take place in the tumour site, a functionally more important role of HIF1α is in the promotion of Treg cell recruitment to the tumour site in response to chemokines. As a result, the presence of Treg cells inside tumours is increased. Hence, HIF play a largely negative role in the regulation of immune responses inside tumours. It appears that therapeutic strategies targeting HIF in the immune system could be beneficial for anti‐tumour immune responses.
2ZrO2·Y2O3 Thermal Barrier Coatings Resistant to Degradation by Molten CMAS: Part II, Interactions with Sand and Fly Ash
Authors: Krause Amanda R. , Garces Hector F. , Senturk Bilge S. , Padture Nitin P.
Published: September 2014

Based on the application of OB considerations (Part I) to various major thermal barrier coating (TBC) compositions and two types of important calcium–magnesium–alumino–silicates (CMAS)—desert sand and fly ash—the 2ZrO2·Y2O3 solid solution (ss) TBC composition, with high CMAS‐resistance potential, is chosen for studying molten‐CMAS/TBC interactions. It is demonstrated that 2ZrO2·Y2O3(ss) air plasma sprayed (APS) TBCs are highly resistant to high‐temperature attack by both sand‐CMAS and fly‐ash‐CMAS. Despite the differences in the compositions of the two CMASs, the overall CMAS‐attack mitigation mechanisms in both cases appear to be similar, viz reaction between 2ZrO2·Y2O3(ss) APS TBC and the CMAS, and the formation of main reaction products of Y‐depleted c‐ZrO2 and nonstoichiometric Ca–Y apatite. Large differences in the OBs (ΔΛ) between the 2ZrO2·Y2O3(ss) and the CMASs are good predictors of ready reaction between this TBC and these CMASs. While the details of the CMAS‐mitigation mechanisms can depend critically on various other aspects, the OB difference (ΔΛ) calculations could be used for the initial screening of CMAS‐resistant TBC compositions.
Characterization of CVD Bonded Tyranno® Fibers Oxidized at High Temperatures
Authors: Remirez de Esparza Natalia , Cocera Nerea , Vazquez Lexuri , Alkorta Jon , Ocaña Ibon , Sanchez Jose M.
Published: September 2014

The oxidation of highly porous ceramic matrix composites (PCMCs) based on different Tyranno® fibers has been analyzed by means of thermogravimetry and electron microscopy. Both uncoated fibers and PCMC materials exhibit parabolic kinetics between 900°C and 1250°C, these being faster for Ti‐doped than for Zr‐doped Tyranno fibers. Oxide layers in Ti‐doped fibers are porous and partially crystalline, whereas in Zr‐doped materials a significant fraction of relatively coarse β‐SiC grains is still found embedded in the amorphous silica matrix. On the other hand, the CVD‐SiC coatings exhibit higher oxidation rates from the outer surface than from the inner one, a phenomenon that has been associated not only with the more difficult access of oxygen to the inner face but also with the highly <111>  textured structure of these coatings, for which very different oxidation rates have been published for the inward and outward directions. Cracking phenomena observed above 1100°C for long dwelling times do not lead to an acceleration of the oxidation process, which could be due to the simultaneous crystallization of the amorphous silica layers.
Visualizing surface area and volume of lumens in three dimensions using images from histological sections
Authors: LIVINGSTON DAVID P. , TUONG TAN D. , KISSLING GRACE E. , CULLEN JOHN M.
Published: September 2014

Visualizing the interior (lumen) of a tubular structure within tissue can provide a unique perspective on anatomical organization of the tissue. Portal tracts of the liver contain several vessels and ducts in various patterns of intertwining branches and are an example of such spaces. An inexpensive method, using light microscopy and a sample of conventionally stained canine livers, was used to colorize and allow visualization of the lumens of vessels within the portal tract in three dimensions. When the colour of the background was digitally cleared and the lumen filled with a solid colour, it was possible to measure areas and volumes of the portal vein, arteries, bile ducts and lymphatics. Significant differences between vessels and ducts across lobes and gender in control samples are discussed. Differences were also found between control and mixed breed dogs and between controls and a dog that died of accidental traumatic haemorrhage. These differences are discussed in relation to visualizing lumens using images generated from a light microscope. Vessels in plants such as xylem and continuously formed spaces resulting from ice formation are other examples where this technique could be applied.
Phenylephrine enhances glutamate release in the medial prefrontal cortex through interaction with N‐type Ca2+ channels and release machinery
Authors: Luo Fei , Li Si‐hai , Tang Hua , Deng Wei‐ke , Zhang Yu , Liu Ying
Published: September 2014

α1‐adrenoceptors (α1‐ARs) stimulation has been found to enhance excitatory processes in many brain regions. A recent study in our laboratory showed that α1‐ARs stimulation enhances glutamatergic transmission via both pre‐ and post‐synaptic mechanisms in layer V/VI pyramidal cells of the rat medial prefrontal cortex (mPFC). However, a number of pre‐synaptic mechanisms may contribute to α1‐ARs‐induced enhancement of glutamate release. In this study, we blocked the possible post‐synaptic action mediated by α1‐ARs to investigate how α1‐ARs activation regulates pre‐synaptic glutamate release in layer V/VI pyramidal neurons of mPFC. We found that the α1‐ARs agonist phenylephrine (Phe) induced a significant enhancement of glutamatergic transmission. The Phe‐induced potentiation was mediated by enhancing pre‐synaptic glutamate release probability and increasing the number of release vesicles via a protein kinase C‐dependent pathway. The mechanisms of Phe‐induced potentiation included interaction with both glutamate release machinery and N‐type Ca2+ channels, probably via a pre‐synaptic Gq/phospholipase C/protein kinase C pathway. Our results may provide a cellular and molecular mechanism that helps explain α1‐ARs‐mediated influence on PFC cognitive functions.

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Alpha1‐adrenoceptor (α1‐ARs) stimulation has been reported to enhance glutamatergic transmission in layer V/VI pyramidal neurons of the rat medial prefrontal cortex (mPFC). We found that α1‐ARs agonist phenylephrine (Phe) increases pre‐synaptic glutamate release probability and the number of released vesicles via interaction with both glutamate release machinery and N‐type Ca2+ channels. Our results may provide a cellular and molecular mechanism that helps explain α1‐ARs‐mediated influence on PFC cognitive functions. Gq, Gq protein; PLC, phospholipase C; PKC, protein kinase C; AMPA, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid; NMDA, N‐methyl‐d‐aspartate; Glu, glutamate; Phe, phenylephrine.
Evaluation of the effect of fractional CO2 laser on histopathological picture and TGF‐β1 expression in hypertrophic scar
Authors: Makboul Mohamed , Makboul Rania , Abdelhafez Assem HK , Hassan Safaa Said , Youssif Sherif M
Published: September 2014

Background and Aims

Hypertrophic scar is a form of abnormal wound healing process in which tissue repair regulating mechanism is disrupted. Transforming growth factor β1 has a particular importance in the fibrotic scarring response. Treatment of hypertrophic scar included many chemical, physical, and surgical options. Fractional CO2 laser devices have gained acceptance as a way for managing hypertrophic scar. Aims of this study are: (a) to determine the clinical and histopathological effects of fractional CO2 laser on hypertrophic scar, (b) to evaluate the expression pattern of transforming growth factor‐β1 (TGF‐β1) as an important fibrogenic factor before and 6 months after fractional CO2 laser treatment.

Patients and Methods

Forty patients of hypertrophic scar were selected, each patient was treated by four sessions with 1 month apart with fractional CO2 laser. Vancouver Scar Scale (VSS) was used to assess the patients before and after laser treatment. Skin biopsy was taken from eight cases before and 3 months after four fractional CO2 laser sessions and four normal skin control biopsies. All were assessed by hematoxylin‐eosin (H&E), Masson's trichrome, Van Gieson and immunohistochemical (IHC) staining with TGF‐β1. The epidermal thickness was assessed before and after treatment by image analyzing system software.

Results

There was statistically significant difference in VSS before and after fractional CO2 laser (P > 0.001). The epidermal thickness showed significant increase after laser treatment (P > 0.001), and there was also thinning in stratum corneum and replacement of the irregular collagen bands with organized new collagen fibrils as demonstrated by H&E and the other special stains. The study also showed significant decrease in TGF‐β1 expression after laser therapy (P = 0.008).

Conclusion

Fractional CO2 laser could be considered as a good way for hypertrophic scar management. It normalizes dermal collagen as imaged by histopathological picture and the change in TGF‐β1 expression.
Effect of low‐intensity, low‐frequency ultrasound treatment on anthropometry, subcutaneous adipose tissue, and body composition of young normal weight females
Authors: Milanese Chiara , Cavedon Valentina , Piscitelli Francesco , Zancanaro Carlo
Published: September 2014

Background

Low‐intensity, low‐frequency ultrasound is increasingly being used for noninvasive, external body contouring as an alternative to liposuction or laser treatments.

Objectives

To evaluate the effect of chronic localized treatment with a novel ultrasound device on subcutaneous adipose tissue thickness and fat mass in young, normal weight women.

Methods

Twenty‐eight females (mean age = 25.5 ± 0.66 [SE] year, mean BMI = 22.1 ± 0.37 kg/m2) underwent a 10‐week bilateral treatment with the device in the gluteus–buttock–thigh area (Lipolysis program: ultrasound frequency = 150 kHz; power = 1.65 W/cm2), 48 min per session, two sessions a week. Subcutaneous adipose tissue thickness and fat mass were evaluated before and after treatment with ultrasound and dual‐energy X‐ray absorptiometry, respectively.

Results

Treatment was well tolerated by all participants. At the end of treatment, statistically significant reduction of subcutaneous adipose tissue thickness was found bilaterally at the gluteus and thigh site (−2.03 ÷ −2.79%). Trunk and lower limb fat mass were reduced as well (−3.48 ÷ −3.97%).

Conclusions

A 10‐week, low‐intensity, low‐frequency localized external ultrasound treatment is effective in reducing adipose tissue in females.
Women's perceptions of the benefits and risks of skin‐lightening creams in two South African communities
Authors: Dlova Ncoza , Hamed Saja H , Tsoka‐Gwegweni Joyce , Grobler Anneke , Hift Richard
Published: September 2014

Background

Skin‐lightening products are commonly used by black communities in South Africa and worldwide. This practice has deep historical and cultural roots and is associated with adverse cutaneous effects.

Methods

A cross‐sectional survey of 579 African and Indian women aged 18–70 years was conducted in two large public hospitals in Durban, South Africa.

Results

There were 292 Africans and 287 Indians included in the survey sample. Of these 32.3% had used skin‐lightening products (60% of Africans and 40% of Indians). Most of those who had used skin lighteners (85 of Africans and 76% of Indians) claimed awareness of the adverse effects of the products, although this did not appear to inform knowledge of the product, how it was used, nor the decision to use the product. Most users (90%) expressed satisfaction with results achieved but 32% reported adverse events.

Conclusion

Skin‐lightening products are used by a third of African and Indian women in South Africa Cultural and historical perceptions equating a fairer skin with social advantage are pervasive and strongly reinforced by the media. There is a poor understanding of the risks associated with the use of these products. Public education campaigns are required to teach consumers about these risks and the importance of concomitant use of sunscreens with these products.
Effect of temperature and duration of ensiling on in vitro degradation of maize silages in rumen fluid
Authors: Ali M. , Cone J. W. , Khan N. A. , Hendriks W. H. , Struik P. C.
Published: September 2014

The effects of ensiling temperature and duration of ensiling on the feeding quality of whole‐crop maize (Zea mays L.) silages were investigated. Samples of one cultivar of maize plants were collected from two different fields, grown in different years on sandy soils. Samples were collected when the whole‐plant dry matter content was approximately 330 g/kg. Maize plants were chopped and ensiled in mini silos at three different ambient temperatures (5, 12 and 18 °C). The ensiling temperature affected the ensiling fermentation processes, causing different rates of pH decline and different final pH values. Samples from the silos were taken after 0 (not ensiled, i.e. control), 4, 8 and 16 weeks of ensiling. The silage samples were not dried, but ground‐frozen under liquid nitrogen to pass a 1‐mm sieve. The gas production technique was used to evaluate the influence of the ensiling temperature and the duration of ensiling on the degradation of the silage samples in rumen fluid. The gas production was highest when the maize was ensiled at 12 °C (p < 0.0001). An increase in ensiling duration caused a decrease in silage pH, accompanied by a decrease in gas production (p < 0.0001). The decrease in gas production was linearly related to the decrease in pH at the three temperatures. The present study shows that both ensiling temperature and ensiling duration play a significant role in the rumen degradability of maize silage.
Literacy, poverty and schooling: what matters in young people's education?
Authors: Comber Barbara
Published: September 2014

This paper draws upon several decades of literacy research in schools in high‐poverty environments to explore what matters in young people's education. In dialogue with themes from Kevin Marjoribanks' work, such as student aspirations, family environments and teacher expectations, key insights are summarised. Referring to longitudinal case studies and a current ethnographic project, the interplay between literacy, poverty and schooling, and young people's aspirations and education outcomes is explored. Although the work of educators in high‐poverty communities continues to be highly demanding, there are some schools and teachers making a durable positive difference to learner dispositions and literate repertoires. Teacher expectations and discursive practices are crucial in this process.
Bupleurum shanianum sp. nov. (Apiaceae) from China
Authors: Ma Xiang‐Guang , He Xing‐Jin
Published: September 2014

Bupleurum shanianum X. G. Ma & X. J. He, previously recognized in China as B. gracillimum, is proposed here as a new species. This new species and B. gracillimum differ in many morphological characters (flowering stem position, bract size, number of flowers per umbellule) and have non‐overlapping distribution ranges. Bupleurum shanianum is most similar to B. yunnanense Franch., but the new species has shorter cauline leaves, and umbellules usually with 4 bracteoles and 3–6(–9) flowers. Bupleurum shanianum is known from eastern Himalayas to western Sichuan.
Influence of bacteria on cell size development and morphology of cultivated diatoms
Authors: Windler Miriam , Bova Dariia , Kryvenda Anastasiia , Straile Dietmar , Gruber Ansgar , Kroth Peter G.
Published: September 2014

Vegetative cell division in diatoms often results in a decreased cell size of one of the daughter cells, which during long‐term cultivation may lead to a gradual decrease of the mean cell size of the culture. To restore the initial cell size, sexual reproduction is required, however, in many diatom cultures sexual reproduction does not occur. Such diatom cultures may lose their viability once the average size of the cells falls below a critical size. Cell size reduction therefore seriously restrains the long‐term stability of many diatom cultures. In order to study the bacterial influence on the size diminution process, we observed cell morphology and size distribution of the diatoms Achnanthidium minutissimum, Cymbella affiniformis and Nitzschia palea for more than two years in bacteria‐free conditions (axenic cultures) and in cultures that contain bacteria (xenic cultures). We found considerable morphological aberrations of frustule microstructures in A. minutissimum and C. affiniformis when cultivated under axenic conditions compared to the xenic cultures. These variations comprise significant cell length reduction, simplification and rounding of the frustule contour and deformation of the siliceous cell walls, features that are normally found in older cultures shortly before they die off. In contrast, the xenic cultures were well preserved and showed less cell length diminution. Our results show that bacteria may have a fundamental influence on the stability of long‐term cultures of diatoms.