bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dermatopathology in sub‐Saharan Africa: a systematic 5‐year analysis of all histopathological diagnoses from the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania
Authors: Beltraminelli H. , Kiprono S. , Zuriel D. , Swai B. , Giabbani E. , Grossmann H. , Masenga J.E. 
Published: December 2014

AbstractBackgroundProper diagnosis of skin diseases relies on dermatopathology, the most important diagnostic technique in dermatology. Unfortunately, there are few dermatopathology institutions in sub‐Saharan Africa, where little is known about the spectrum of histopathological features observed.ObjectivesTo investigate the spectrum of dermatopathological diagnoses made in a sub‐Saharan African reference centre of a large, mainly rural area.Patients/MethodsTo retrospectively evaluate all dermatopathological diagnoses made over a period of 5 years at the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania.ResultsThere were a total of 1554 skin biopsy specimens. In 45% of cases, there were inflammatory diseases, most frequently lichenoid conditions. Cutaneous neoplasms represented 30.4% of all diagnoses, with Kaposi's sarcoma (KS) and, less frequently, squamous cell carcinoma (SCC) being the two most common neoplastic conditions. The latter also reflected the intensive management of persons with albinism in the RDTC. The distribution of histological diagnoses seemed to correlate with the overall clinical spectrum of cutaneous diseases managed in the RDTC.ConclusionsIn this African study inflammatory conditions are the main burden of skin diseases leading to a diagnostic biopsy. Our findings provide further evidence that KS, primarily related to the high prevalence of HIV infection is an epidemiological problem. Both SCC and basal cell carcinoma represent another relatively common malignant cutaneous neoplasms, reflecting the presence of specific populations at risk. The challenging spectrum of histological diagnoses observed in this specific African setting with basic working conditions shows that development of laboratory services of good standards and specific training in dermatopathology are urgently needed.
Within‐population genetic effects of mtDNA on metabolic rate in Drosophila subobscura
Authors: Kurbalija Novičić Z. , Immonen E. , Jelić M. , AnÐelković M. , Stamenković‐Radak M. , Arnqvist G. 
Published: December 2014

AbstractA growing body of research supports the view that within‐species sequence variation in the mitochondrial genome (mtDNA) is functional, in the sense that it has important phenotypic effects. However, most of this empirical foundation is based on comparisons across populations, and few studies have addressed the functional significance of mtDNA polymorphism within populations. Here, using mitonuclear introgression lines, we assess differences in whole‐organism metabolic rate of adult Drosophila subobscura fruit flies carrying either of three different sympatric mtDNA haplotypes. We document sizeable, up to 20%, differences in metabolic rate across these mtDNA haplotypes. Further, these mtDNA effects are to some extent sex specific. We found no significant nuclear or mitonuclear genetic effects on metabolic rate, consistent with a low degree of linkage disequilibrium between mitochondrial and nuclear genes within populations. The fact that mtDNA haplotype variation within a natural population affects metabolic rate, which is a key physiological trait with important effects on life‐history traits, adds weight to the emergent view that mtDNA haplotype variation is under natural selection and it revitalizes the question as to what processes act to maintain functional mtDNA polymorphism within populations.
Relaxant and Antioxidant Capacity of the Red Wine Polyphenols, Resveratrol and Quercetin, on Isolated Mice Corpora Cavernosa
Authors: Boydens Charlotte , Pauwels Bart , Decaluwé Kelly , Brouckaert Peter , Van de Voorde Johan 
Published: December 2014

AbstractIntroductionThe red wine polyphenols resveratrol and quercetin are known for their vasorelaxant and antioxidant capacity, which is assumed to rely on the activation of the nitric oxide (NO)/soluble guanylyl cyclase (sGC) pathway. Vasodilators as well as antioxidants can regulate penile erection and be beneficial for the treatment of erectile dysfunction (ED).AimsThe goal of this study was to evaluate the NO/sGC dependency of the relaxant effect of resveratrol and quercetin on mice aorta and corpora cavernosa (CC), as well as to explore their influence on oxidative stress-induced ED.MethodsIsolated mice aorta and CC were mounted for isometric tension recordings into organ baths. Cumulative concentration-response curves were constructed for resveratrol and quercetin in the absence/presence of inhibitors of the NO/sGC pathway. In addition, in CC the effect of resveratrol and quercetin was studied on NO-mediated relaxations using acetylcholine (Ach), sodium nitroprusside (SNP), and electrical field stimulation (EFS). In certain experiments, corporal tissues were exposed to oxidative stress using palmitic acid (PA, 0.5 mM).Main Outcome MeasuresCorporal responses to resveratrol and quercetin were measured in the presence/absence of inhibitors of different molecular pathways. The effect of resveratrol and quercetin incubation on Ach-, SNP-, or EFS-mediated responses was explored in the presence/absence of PA.ResultsWhile both polyphenols are potent vasodilators of mice aorta, only resveratrol relaxes mice CC. The relaxation response to resveratrol on aorta was diminished in sGCα1−/− mice, but not on CC. The polyphenols did not influence Ach-, SNP-, or EFS-mediated relaxations as such. Resveratrol, but not quercetin, was able to significantly reverse PA-induced decrease of EFS relaxations.ConclusionThe red wine compound resveratrol, but not quercetin, relaxes isolated mice CC concentration-dependently through mechanisms independent of the NO/sGC pathway. Resveratrol is a more potent antioxidant than quercetin, being able to restore decreased neuronal NO responses in mice CC.
A new point mutation in the iron–sulfur subunit of succinate dehydrogenase confers resistance to boscalid in Sclerotinia sclerotiorum
Authors: Wang Yong , Duan Yabing , Wang Jianxin , Zhou Mingguo 
Published: December 2014

SummaryResearch has established that mutations in highly conserved amino acids of the succinate dehydrogenase (SDH) complex in various fungi confer SDH inhibitor (SDHI) resistance. For Sclerotinia sclerotiorum (Lib.) de Bary, a necrotrophic fungus with a broad host range and a worldwide distribution, boscalid resistance has been attributed to the mutation H132R in the highly conserved SdhD subunit protein of the SDH complex. In our previous study, however, only one point mutation, A11V in SdhB (GCA to GTA change in SdhB), was detected in S. sclerotiorum boscalid‐resistant (BR) mutants. In the current study, replacement of the SdhB gene in a boscalid‐sensitive (BS) S. sclerotiorum strain with the mutant SdhB gene conferred resistance. Compared with wild‐type strains, BR and GSM (SdhB gene in the wild‐type strain replaced by the mutant SdhB gene) mutants were more sensitive to osmotic stress, lacked the ability to produce sclerotia and exhibited lower expression of the pac1 gene. Importantly, the point mutation was not located in the highly conserved sequence of the iron–sulfur subunit of SDH. These results suggest that resistance based on non‐conserved vs. conserved protein domains differs in mechanism. In addition to increasing our understanding of boscalid resistance in S. sclerotiorum, the new information will be useful for the development of alternative antifungal drugs.
Native and denatured egg white protein IgE tests discriminate hen's egg allergic from egg‐tolerant children
Authors: Benhamou Senouf Avigael H. , Borres Magnus P. , Eigenmann Philippe A. 
Published: December 2014

AbstractBackgroundAccurate diagnosis of egg allergy by IgE testing is challenged by a large number of atopic subjects sensitized, but clinically tolerant to eggs. In addition, discrimination between allergy to raw only, or raw and cooked egg allergy is important. In this study, we investigate the diagnostic performance of IgE tests to native and denatured egg proteins.MethodsAccording to food challenges and clinical tolerance, study subjects were randomized to the following groups: (Group A) sensitized but clinically tolerant to egg, (Group B) allergic to raw egg only, or (Group C) allergic to raw and cooked egg. Serum‐specific IgE to native or reduced and oxidized egg white, ovomucoid, and ovalbumin were measured.ResultsIncreasing titers of specific IgE to the various proteins were found according to the degree of the egg allergy. Cut‐off values for IgE testing to native egg could be determined to distinguish between raw egg allergic and egg‐tolerant subjects (1.6 kU/l), as well as raw and cooked egg allergic and egg‐tolerant subjects (4.1 kU/l). ROC curves analysis showed that native ovalbumin was the best test for the diagnosis of allergy to raw and cooked egg, and native ovomucoid was best to distinguish between allergy to raw only, and allergy to raw and cooked egg. Sequential testing improved the diagnosis, when in addition to IgE to native egg white, IgE to native ovalbumin was tested for the diagnosis of raw and cooked egg allergy, and IgE to native ovomucoid for the discrimination between allergy to raw only, or to raw and cooked eggs.ConclusionThe diagnosis of egg allergy can be significantly improved using a panel of IgE tests to egg proteins in the native or denatured form. The accuracy can be improved using combined IgE testing.
Lichen Nitidus Presenting with Nail Changes—Case Report and Review of the Literature
Authors: Tay Evelyn Yuxin , Ho Madeline Sheun Ling , Chandran Nisha Suyien , Lee Joyce Siong‐See , Heng Yee Kiat 
Published: December 2014

AbstractLichen nitidus of the nail is rare and can precede the onset of skin lesions. Delayed diagnosis is common. We present an unusual case of lichen nitidus–associated nail changes that preceded the onset of skin lesions in a 4‐year‐old Indian girl. We also conduct a review of six other cases of lichen nitidus with nail involvement from the English‐language literature. Clues to the diagnosis of lichen nitidus include violaceous or pigmentary changes of the nail fold and subtle lichenoid papules on the affected digits. Lichen nitidus of the nails appears to be less severe than nail changes of lichen planus and is generally self‐limiting. Understanding the natural history of lichen nitidus of the nails will help physicians better counsel patients and their families.
Ulcerated Spitz Nevus Masquerading as a Juvenile Xanthogranuloma
Authors: Ghahramani Grant K. , Swick Brian L. , Ciliberto Heather 
Published: December 2014

AbstractWe report a case of ulcerated atypical Spitz nevi that demonstrated a yellow to light orange background under dermoscopy, which can be seen in juvenile xanthogranuloma (JXG) and is referred to as the “setting sun” appearance. This yellow to orange appearance was due to serous crusting and not histiocytic infiltration, which is seen in JXG. This case highlights overlapping dermatoscopic features between the two skin lesions and polymorphous vascular structures, which are unique to atypical Spitz nevi.
Tallgrass prairie restoration: implications of increased atmospheric nitrogen deposition when site preparation minimizes adventive grasses
Authors: McPhee Jennifer , Borden Laura , Bowles Jane , Henry Hugh A. L. 
Published: December 2014

AbstractSite preparation designed to exhaust the soil seedbank of adventive species can improve the success of tallgrass prairie restoration. Despite these efforts, increased rates of atmospheric nitrogen (N) deposition over the next century could potentially promote the growth of nitrophilic, adventive species in tallgrass restoration projects. We used a field experiment to examine how N addition affected species composition and plant productivity over the first 3 years of a tallgrass prairie restoration that was preceded by the planting of glyphosate‐resistant crops and multiple applications of glyphosate to exhaust the pre‐existing seedbank. We predicted that N addition would increase the percent cover of adventive plant species not included in the original seeding. Contrary to our prediction, only the cover of native species increased with N addition; native non‐leguminous forbs increased substantially, with Conyza canadensis (a weedy native species not part of the restoration seed mix) exploiting the combination of high N and bare ground in the first year, and non‐leguminous forbs (in particular Monarda fistulosa) and native C3 grasses, all of which were seeded, increasing with N addition by the third year. Native legumes was the only functional group that exhibited lower cover in N addition plots than in control plots. There was no significant response by native C4 grasses to N addition, and adventive grasses remained mostly absent from the plots. Overall, our results suggest that site pre‐treatment with herbicide may continue to be effective in minimizing adventive grasses in restored tallgrass prairie, despite future increases in atmospheric N deposition.
Clinical use of microRNAs as potential non‐invasive biomarkers for detecting non‐small cell lung cancer: A meta‐analysis
Authors: Wang Huoqiang , Wu Songnian , Zhao Long , Zhao Juan , Liu Jinjun , Wang Zhihao 
Published: December 2014

AbstractEmerging studies have revealed that microRNA(miRNA) in body fluid may serve as a potential biomarker to detect non‐small cell lung cancer (NSCLC). However, the diagnostic accuracy of miRNAforNSCLCdetection is still under debate because there is inconsistency in previous studies. Hence, we conducted this meta‐analysis to comprehensively evaluate the diagnostic performance of miRNA. A systematic literature search was performed to retrieve relevant articles inPubMed and other databases, andSTATA12.0 (StataCorp, College Station, TX, USA) was used to calculate the pooled parameters. A total of 28 articles involving 2121NSCLCpatients and 1582 healthy controls were included in this meta‐analysis. The overall pooled sensitivity and specificity of miRNAwere 0.75 and 0.79, respectively. The pooled positive likelihood ratio was 3.6, negative likelihood ratio was 0.32 and diagnostic odds ratio was 12. The area under the curve (AUC) was 0.84. Subgroup and meta‐regression analyses established that miRNAassays were more accurate inCaucasian populations (AUCof 0.86, sensitivity of 0.79 and specificity of 0.82, respectively) than inAsian populations (AUC, sensitivity and specificity of 0.83, 0.72 and 0.80, respectively). In addition, the multiple miRNAassays (AUCof 0.89, sensitivity of 0.83 and specificity of 0.82, respectively) showed a higher accuracy than single miRNAassays (AUC, sensitivity and specificity of 0.81, 0.77 and 0.71, respectively) inNSCLCdetection. Subgroup analyses based on specimen types suggested that blood‐based miRNA(AUCof 0.86, sensitivity of 0.78 and specificity of 0.80, respectively) may have a higher diagnostic accuracy as biomarkers than sputum‐based miRNA(AUCof 0.81, sensitivity of 0.69 and specificity of 0.80, respectively). In conclusion, miRNAmay serve as a potential biomarker inNSCLSdetection, especially the multiple miRNAfrom blood, with a relatively high diagnostic accuracy.
Pharmacokinetics and Safety of Voriconazole Intravenous-to-Oral Switch Regimens in Immunocompromised Japanese Pediatric Patients
Authors: Mori Masaaki , Kobayashi Ryoji , Kato Koji , Maeda Naoko , Fukushima Keitaro , Goto Hiroaki , Inoue Masami , Muto Chieko , Okayama Akifumi , Watanabe Kenichi , Liu Ping 
Published: December 2014

ABSTRACT

The aim of this study was to investigate the pharmacokinetics, safety, and tolerability of voriconazole following intravenous-to-oral switch regimens used with immunocompromised Japanese pediatric subjects (age 2 to <15 years) at high risk for systemic fungal infection. Twenty-one patients received intravenous-to-oral switch regimens based on a recent population pharmacokinetic modeling; they were given 9 mg/kg of body weight followed by 8 mg/kg of intravenous (i.v.) voriconazole every 12 h (q12h), and 9 mg/kg (maximum, 350 mg) of oral voriconazole q12h (for patients age 2 to <12 or 12 to <15 years and <50 kg) or 6 mg/kg followed by 4 mg/kg of i.v. voriconazole q12h and 200 mg of oral voriconazole q12h (for patients age 12 to <15 years and ≥50 kg). The steady-state area under the curve over the 12-h dosing interval (AUC
0–12,ss
) was calculated using the noncompartmental method and compared with the predicted exposures in Western pediatric subjects based on the abovementioned modeling. The geometric mean (coefficient of variation) AUC
0–12,ss
values for the intravenous and oral regimens were 51.1 μg · h/ml (68%) and 45.8 μg · h/ml (90%), respectively; there was a high correlation between AUC
0–12,ss
and trough concentration. Although the average exposures were higher in the Japanese patients than those in the Western pediatric subjects, the overall voriconazole exposures were comparable between these two groups due to large interindividual variability. The exposures in the 2 cytochrome P450 2C19 poor metabolizers were among the highest. Voriconazole was well tolerated. The most common treatment-related adverse events were photophobia and abnormal hepatic function. These recommended doses derived from the modeling appear to be appropriate for Japanese pediatric patients, showing no additional safety risks compared to those with adult patients. (This study has been registered at
ClinicalTrials.gov
under registration no. NCT01383993.)
In Vitro
and
In Vivo
Antiviral Activity and Resistance Profile of the Hepatitis C Virus NS3/4A Protease Inhibitor ABT-450
Authors: Pilot-Matias Tami , Tripathi Rakesh , Cohen Daniel , Gaultier Isabelle , Dekhtyar Tatyana , Lu Liangjun , Reisch Thomas , Irvin Michelle , Hopkins Todd , Pithawalla Ron , Middleton Timothy , Ng Teresa , McDaniel Keith , Or Yat Sun , Menon Rajeev , Kempf Dale , Molla Akhteruzzaman , Collins Christine 
Published: December 2014

ABSTRACT

The development of direct-acting antiviral agents is a promising therapeutic advance in the treatment of hepatitis C virus (HCV) infection. However, rapid emergence of drug resistance can limit efficacy and lead to cross-resistance among members of the same drug class. ABT-450 is an efficacious inhibitor of HCV NS3/4A protease, with 50% effective concentration values of 1.0, 0.21, 5.3, 19, 0.09, and 0.69 nM against stable HCV replicons with NS3 protease from genotypes 1a, 1b, 2a, 3a, 4a, and 6a, respectively.
In vitro
, the most common amino acid variants selected by ABT-450 in genotype 1 were located in NS3 at positions 155, 156, and 168, with the D168Y variant conferring the highest level of resistance to ABT-450 in both genotype 1a and 1b replicons (219- and 337-fold, respectively). In a 3-day monotherapy study with HCV genotype 1-infected patients, ABT-450 was coadministered with ritonavir, a cytochrome P450 3A4 inhibitor shown previously to markedly increase peak, trough, and overall drug exposures of ABT-450. A mean maximum HCV RNA decline of 4.02 log
10
was observed at the end of the 3-day dosing period across all doses. The most common variants selected in these patients were R155K and D168V in genotype 1a and D168V in genotype 1b. However, selection of resistant variants was significantly reduced at the highest ABT-450 dose compared to lower doses. These findings were informative for the subsequent evaluation of ABT-450 in combination with additional drug classes in clinical trials in HCV-infected patients. (Study M11-602 is registered at ClinicalTrials.gov under registration no. NCT01074008.)
The Novel Arylamidine T-2307 Maintains
In Vitro
and
In Vivo
Activity against Echinocandin-Resistant Candida albicans
Authors: Wiederhold Nathan P. , Najvar Laura K. , Fothergill Annette W. , Bocanegra Rosie , Olivo Marcos , McCarthy Dora I. , Kirkpatrick William R. , Fukuda Yoshiko , Mitsuyama Junichi , Patterson Thomas F. 
Published: December 2014

ABSTRACT

We evaluated the
in vitro
and
in vivo
activities of the investigational arylamidine T-2307 against echinocandin-resistant
Candida albicans
. T-2307 demonstrated potent
in vitro
activity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistant
C. albicans
infections.
Mechanism of Reduced Vancomycin Susceptibility Conferred by
walK
Mutation in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strain MW2
Authors: Hu Jinfeng , Zhang Xu , Liu Xiaoyu , Chen Chuan , Sun Baolin 
Published: December 2014

ABSTRACT

Point mutations with unclear molecular mechanisms are often associated with vancomycin resistance in
Staphylococcus aureus
. Here, we observed that the
walK
(G223D) mutation caused decreased expression of genes associated with cell wall metabolism, decreased autolytic activity, thickened cell walls, and reduced vancomycin susceptibility. A phosphorylation assay showed that WalK (G223D) exhibited reduced autophosphorylation, which led to reduced phosphorylation of WalR. An electrophoretic mobility shift assay indicated that WalK (G223D)-phosphorylated WalR had a reduced capacity to bind to the
atlA
promoter.
Analysis of Neisseria gonorrhoeae Azithromycin Susceptibility in the United States by the Gonococcal Isolate Surveillance Project, 2005 to 2013
Authors: Kirkcaldy Robert D. , Soge Olusegun , Papp John R. , Hook Edward W. , del Rio Carlos , Kubin Grace , Weinstock Hillard S. 
Published: December 2014

ABSTRACT

Azithromycin, administered with ceftriaxone, is recommended by the CDC for the treatment of gonorrhea. Many experts have expressed concern about the ease with which
Neisseria gonorrhoeae
can acquire macrolide resistance. We sought to describe gonococcal azithromycin susceptibility in the United States and to determine whether azithromycin susceptibility has changed over time. We analyzed data from 2005 to 2013 from the Gonococcal Isolate Surveillance Project, a CDC-supported sentinel surveillance network that monitors gonococcal antimicrobial susceptibility. A total of 44,144
N. gonorrhoeae
isolates were tested for azithromycin susceptibility by agar dilution methods. The overall azithromycin MIC
50
was 0.25 μg/ml, and the MIC
90
was 0.5 μg/ml. There were no overall temporal trends in geometric means. Isolates from men who had sex with men had significantly higher geometric mean MICs than isolates from men who had sex exclusively with women. The overall prevalence of reduced azithromycin susceptibility (MIC, ≥2 μg/ml) was 0.4% and varied by year from 0.3% (2006 and 2009) to 0.6% (2013). We did not find a clear temporal trend in gonococcal azithromycin MICs in the United States, and the prevalence of reduced azithromycin susceptibility remains low. These findings support the continued use of azithromycin in a combination therapy regimen for gonorrhea.