bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bendamustine in multiple myeloma
Authors: Gentile Massimo , Vigna Ernesto , Recchia Anna Grazia , Morabito Lucio , Mendicino Francesco , Giagnuolo Giovanna , Morabito Fortunato 
Published: June 2015

AbstractThe advent of high‐dose melphalan with autologous stem‐cell transplantation (ASCT), the availability of novel agents such as thalidomide, lenalidomide (immunomodulatory drugs or IMiDs) and bortezomib (proteasome inhibitor) and improvements in supportive care have allowed to increase overall survival in multiple myeloma (MM) patients; nevertheless, MM remains an incurable pathology. For this reason, newer agents are required for continued disease control. Bendamustine is an old drug rediscovered in the last decade. In fact, its unique mechanism of action with structural similarities to both alkylating agents and antimetabolities, but which is not cross‐resistant to alkylating agents, has reawakened interest in the use of this drug in the treatment of MM. Studies have proven the safety and efficacy of bendamustine administered alone or in combination with new drugs in both upfront and relapse/refractory settings of MM patients, including those with renal impairment. Moreover, bendamustine has been successfully used as conditioning for autologous stem‐cell transplantation. Finally, the use of bendamustine does not compromise peripheral blood stem‐cell collection. This drug is generally well tolerated, with the majority of adverse events being due to myelosuppression. Non‐haematological adverse events are infrequent and usually mild.
Antimicrobial resistance in bacteria from horses: Epidemiology of antimicrobial resistance
Authors: Maddox T. W. , Clegg P. D. , Williams N. J. , Pinchbeck G. L. 
Published: June 2015

SummaryAntimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections. While the epidemiology of antimicrobial resistance in bacteria from man has been studied extensively, less work has been undertaken in companion animals, particularly horses. Methicillin‐resistantStaphylococcus aureushas been identified as a cause of infections, with a low prevalence of nasal carriage by horses in the community but higher for hospitalised horses. Molecular characterisation has shown methicillin‐resistantStaphylococcus aureusstrains either to be predominantly of types associated with horses or of sequence typeST398. Antimicrobial‐resistantEscherichia coli(including multidrug‐resistant and extended spectrum β‐lactamase‐producing isolates) have caused infections and been documented in faecal carriage by horses, with many significant resistance mechanisms identified. More sporadic reports and molecular characterisation exist for resistance in other bacteria such as enterococci,Salmonella,AcinetobacterandPseudomonasspecies. Limited work has been undertaken evaluating risk factors and much of the epidemiology of antimicrobial resistance in bacteria from horses remains to be determined.
Abnormal Connectivity Within Executive Resting‐State Network in Migraine With Aura
Authors: Tessitore Alessandro , Russo Antonio , Conte Francesca , Giordano Alfonso , De Stefano Manuela , Lavorgna Luigi , Corbo Daniele , Caiazzo Giuseppina , Esposito Fabrizio , Tedeschi Gioacchino 
Published: June 2015

ObjectiveTo evaluate the executive control network connectivity integrity in patients with migraine with aura, in the interictal period, in comparison to patients with migraine without aura and healthy controls.MethodsUsing resting‐state functional magnetic resonance imaging, we compared executive control network functional connectivity in 20 patients with migraine with aura vs 20 sex and age‐matched patients with migraine without aura and 20 healthy controls, and assessed the correlation between executive control network functional connectivity and clinical features of patients with migraine. We used voxel‐based morphometry and diffusion tensor imaging to investigate potential structural or microstructural changes.ResultsNeuropsychological data revealed no significant executive dysfunction in patients with migraine. Resting‐state functional magnetic resonance imaging showed significant group differences in right middle frontal gyrus (Talairach coordinates x, y, z: +26, +2, +48) and dorsal anterior cingulate cortex (Talairach coordinates x, y, z: +6, +13, +49), indicating that these areas had a decreased component activity in both patients with migraine with and without aura when compared with healthy controls. Conversely, there were no significant differences in the executive control network functional connectivity between patients with migraine with and without aura (P < .05, cluster‐level corrected). These functional abnormalities are independent of structural and microstructural changes and did not significantly correlate with clinical parameters.ConclusionsOur data demonstrate a disrupted executive control network functional connectivity in patients with migraine with and without aura, in the interictal period. Although this functional phenomenon is present in the absence of clinically relevant executive deficits, it may reflect a vulnerability to executive high‐demanding conditions of daily living activities in patients with migraine.
The protein arginine methyltransferase PRMT5 regulates Aβ‐induced toxicity in human cells and Caenorhabditis elegans models of Alzheimer's disease
Authors: Quan Xin , Yue Wenhui , Luo Yunfeng , Cao Jianwei , Wang Hongyun , Wang Yue , Lu Zhongbing 
Published: June 2015

AbstractThe protein arginine methyltransferase 5 (PRMT5) controls cell growth and apoptosis by catalyzing mono and symmetric dimethylation of arginine residues. In human brain tissue, PRMT5 is predominantly expressed in neuronal cells. There is evidence that PRMT5 provides protection against cell death, but the impact of PRMT5 on neuronal apoptosis during the evolution of Alzheimer's disease has not been tested. In the present study, we show that PRMT5 is down‐regulated by β‐amyloid (Aβ) in primary neurons and SH‐SY5Y cells, and this is associated with the up‐regulation of the PRMT5 target protein E2F‐1. Furthermore, knockdown of PRMT5 in SH‐SY5Y cells over‐expressing the Swedish mutant form of human amyloid‐β precursor protein caused activation of E2F‐1/p53/Bax, NF‐κB, and GSK‐3β pathways, which coincided with increased apoptosis. Co‐depletion of E2F‐1 reduced the activation of p53/Bax, NF‐κB, and GSK‐3β, and limited cell apoptosis. In addition, inhibiting NF‐κB and GSK‐3β activity by specific inhibitors also attenuated cell apoptosis, suggesting that E2F‐1/NF‐κB/GSK‐3β pathways mediate for apoptosis induced by PRMT5 depletion. More importantly, knockdown of PRMT5 resulted in more paralysis in a transgenic Caenorhabditis elegans strain CL2006, indicating that PRMT5 provides protection against Aβ toxicity in vivo. Collectively, our findings identify PRMT5 as a novel regulator of Aβ toxicity and suggest that strategies aimed at activating PRMT5 in the neuron may represent a potential therapeutic approach for the prevention of Alzheimer's disease.
imageWe propose the following cascade for protein arginine methyltransferase 5 (PRMT5)‐mediated neuronal death: amyloid beta (Aβ) deposition decreases PRMT5 expression in neurons, which increases E2F‐1 expression – a PRMT5 target protein – and subsequently activates GSK‐3β and NF‐κB to induce caspase‐3‐dependent neuronal apoptosis. These findings might provide a strategy for the treatment of Alzheimer's disease.
Symmetry matters
Authors: Moubayidin Laila , Østergaard Lars 
Published: June 2015

SummaryThe development of multicellular organisms depends on correct establishment of symmetry both at the whole‐body scale and within individual tissues and organs. Setting up planes of symmetry must rely on communication between cells that are located at a distance from each other within the organism, presumably via mobile morphogenic signals. Although symmetry in nature has fascinated scientists for centuries, it is only now that molecular data to unravel mechanisms of symmetry establishment are beginning to emerge. As an example we describe the genetic and hormonal interactions leading to an unusual bilateral‐to‐radial symmetry transition of an organ in order to promote reproduction.

Contents

Summary
985

I.
Introduction
985

II.
Bilateral and radial symmetries
986

III.
Symmetry breaking
987

IV.
Symmetry transitions
988

V.
Conclusions
989

Acknowledgements
989

References
989
The effect of lichen‐dominated biological soil crusts on growth and physiological characteristics of three plant species in a temperate desert of northwest China
Authors: Zhuang W. W. , Serpe M. , Zhang Y. M. 
Published: June 2015

AbstractBiocrusts (biological soil crusts) cover open spaces between vascular plants in most arid and semi‐arid areas. Information on effects of biocrusts on seedling growth is controversial, and there is little information on their effects on plant growth and physiology. We examined impacts of biocrusts on growth and physiological characteristics of three habitat‐typical plants, Erodium oxyrhynchum, Alyssum linifolium and Hyalea pulchella, growing in the Gurbantunggut Desert, northwest China. The influence of biocrusts on plant biomass, leaf area, leaf relative water content, photosynthesis, maximum quantum efficiency of PSII (Fv/Fm), chlorophyll, osmotic solutes (soluble sugars, protein, proline) and antioxidant enzymes (superoxide dismutase, catalase, peroxidase) was investigated on sites with or without biocrust cover. Biomass, leaf area, leaf water content, photosynthesis, Fv/Fm and chlorophyll content in crusted soils were higher than in uncrusted soils during early growth and lower later in the growth period. Soluble sugars, proline and antioxidant enzyme activity were always higher in crusted than in uncrusted soils, while soluble protein content was always lower. These findings indicate that biocrusts have different effects on these three ephemeral species during growth in this desert, primarily via effects on soil moisture, and possibly on soil nutrients. The influence of biocrusts changes during plant development: in early plant growth, biocrusts had either positive or no effect on growth and physiological parameters. However, biocrusts tended to negatively influence plants during later growth. Our results provide insights to explain why previous studies have found different effects of biocrusts on vascular plant growth.
A randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats
Authors: Peacock Rachel E. , Hosgood Giselle , Swindells Katrin L. , Smart Lisa 
Published: June 2015

AbstractObjectiveTo assess for any clinical benefit of intravenous lipid emulsion (ILE) for permethrin toxicosis in cats by comparing the progression of clinical signs of cats before and after treatment with ILE to cats treated with a saline control. To accomplish this objective, a clinical staging system for cats with permethrin toxicosis was developed and validated.DesignProspective, multicenter, randomized, controlled clinical trial.SettingUniversity veterinary teaching hospital and 12 private veterinary emergency hospitals.AnimalsThirty‐four client‐owned cats with permethrin toxicosis.InterventionsA clinical staging system was designed based on abnormalities found on physical examination of cats with permethrin toxicosis. The clinical staging system had 6 stages, ranging from Stage A for cats with no abnormalities to Stage F for cats with grand mal seizures. The system was validated for intraviewer and interviewer variability. Cats in the clinical trial were randomized to receive 15 mL/kg of either intravenous 0.9% saline (control) or 20% ILE over 60 minutes. For each cat, a clinical stage was recorded at set time points before and after the randomized treatment was administered. The distribution of clinical stage stratified over time was compared across treatment groups.Measurements and Main ResultsThe clinical staging system showed excellent repeatability (P = 1.0) and reliability (P = 1.0). In the clinical trial, there was a significant difference in the distribution of clinical stages over time (P < 0.001) and from presentation stage to Stage B (P = 0.006), with ILE‐treated cats (n = 20) having lower clinical stages earlier than control cats (n = 14). There was no significant difference in signalment, body weight, or supportive treatment between the groups.ConclusionsThe clinical staging system was repeatable and reliable. Clinical stages of permethrin toxicosis in ILE‐treated cats improved earlier compared to control cats, suggesting ILE may be a useful adjunctive therapy in the treatment of permethrin toxicosis in cats.
The TRPV1 channel in rodents is a major target for antinociceptive effect of the probiotic Lactobacillus reuteri DSM 17938
Authors: Perez‐Burgos Azucena , Wang Lu , McVey Neufeld Karen‐Anne , Mao Yu‐Kang , Ahmadzai Mustafa , Janssen Luke J. , Stanisz Andrew M. , Bienenstock John , Kunze Wolfgang A. 
Published: June 2015

Key points
Certain probiotic bacteria have been shown to reduce distension‐dependent gut pain, but the mechanisms involved remain obscure.
Live luminal Lactobacillus reuteri (DSM 17938) and its conditioned medium dose dependently reduced jejunal spinal nerve firing evoked by distension or capsaicin, and 80% of this response was blocked by a specific TRPV1 channel antagonist or in TRPV1 knockout mice.
The specificity of DSM action on TRPV1 was further confirmed by its inhibition of capsaicin‐induced intracellular calcium increases in dorsal root ganglion neurons. Another lactobacillus with ability to reduce gut pain did not modify this response.
Prior feeding of rats with DSM inhibited the bradycardia induced by painful gastric distension.
These results offer a system for the screening of new and improved candidate bacteria that may be useful as novel therapeutic adjuncts in gut pain.AbstractCertain bacteria exert visceral antinociceptive activity, but the mechanisms involved are not determined. Lactobacillus reuteri DSM 17938 was examined since it may be antinociceptive in children. Since transient receptor potential vanilloid 1 (TRPV1) channel activity may mediate nociceptive signals, we hypothesized that TRPV1 current is inhibited by DSM. We tested this by examining the effect of DSM on the firing frequency of spinal nerve fibres in murine jejunal mesenteric nerve bundles following serosal application of capsaicin. We also measured the effects of DSM on capsaicin‐evoked increase in intracellular Ca2+ or ionic current in dorsal root ganglion (DRG) neurons. Furthermore, we tested the in vivo antinociceptive effects of oral DSM on gastric distension in rats. Live DSM reduced the response of capsaicin‐ and distension‐evoked firing of spinal nerve action potentials (238 ± 27.5% vs. 129 ± 17%). DSM also reduced the capsaicin‐evoked TRPV1 ionic current in DRG neuronal primary culture from 83 ± 11% to 41 ± 8% of the initial response to capsaicin only. Another lactobacillus (Lactobacillus rhamnosus JB‐1) with known visceral anti‐nociceptive activity did not have these effects. DSM also inhibited capsaicin‐evoked Ca2+ increase in DRG neurons; an increase in Ca2+ fluorescence intensity ratio of 2.36 ± 0.31 evoked by capsaicin was reduced to 1.25 ± 0.04. DSM releasable products (conditioned medium) mimicked DSM inhibition of capsaicin‐evoked excitability. The TRPV1 antagonist 6‐iodonordihydrocapsaicin or the use of TRPV1 knock‐out mice revealed that TRPV1 channels mediate about 80% of the inhibitory effect of DSM on mesenteric nerve response to high intensity gut distension. Finally, feeding with DSM inhibited perception in rats of painful gastric distension. Our results identify a specific target channel for a probiotic with potential therapeutic properties.
Development of an accurate EPID‐based output measurement and dosimetric verification tool for electron beam therapy
Authors: Ding Aiping , Xing Lei , Han Bin 
Published: June 2015

Purpose:To develop an efficient and robust tool for output measurement and absolute dose verification of electron beam therapy by using a high spatial‐resolution and high frame‐rate amorphous silicon flat panel electronic portal imaging device (EPID).Methods:The dosimetric characteristics of the EPID, including saturation, linearity, and ghosting effect, were first investigated on a Varian Clinac 21EX accelerator. The response kernels of the individual pixels of the EPID to all available electron energies (6, 9, 12, 16, and 20 MeV) were calculated by using Monte Carlo (MC) simulations, which formed the basis to deconvolve an EPID raw images to the incident electron fluence map. The two‐dimensional (2D) dose distribution at reference depths in water was obtained by using the constructed fluence map with a MC simulated pencil beam kernel with consideration of the geometric and structural information of the EPID. Output factor measurements were carried out with the EPID at a nominal source–surface distance of 100 cm for 2 × 2, 3 × 3, 6 × 6, 10 × 10, and 15 × 15 cm2 fields for all available electron energies, and the results were compared with that measured in a solid water phantom using film and a Farmer‐type ion chamber. The dose distributions at a reference depth specific to each energy and the flatness and symmetry of the 10 × 10 cm2 electron beam were also measured using EPID, and the results were compared with ion chamber array and water scan measurements. Finally, three patient cases with various field sizes and irregular cutout shapes were also investigated.Results:EPID‐measured dose changed linearly with the monitor units and showed little ghosting effect for dose rate up to 600 MU/min. The flatness and symmetry measured with the EPID were found to be consistent with ion chamber array and water scan measurements. The EPID‐measured output factors for standard square fields of 2 × 2, 3 × 3, 6 × 6, 10 × 10, 15 × 15 cm2 agreed with film and ion chamber measurements. The average discrepancy between EPID and ion chamber/film measurements was 0.81% ± 0.60% (SD) and 1.34% ± 0.75%, respectively. For the three clinical cases, the difference in output between the EPID‐ and ion chamber array measured values was found to be 1.13% ± 0.11%, 0.54% ± 0.10%, and 0.74% ± 0.11%, respectively. Furthermore, the γ‐index analysis showed an excellent agreement between the EPID‐ and ion chamber array measured dose distributions: 100% of the pixels passed the criteria of 3%/3 mm. When the γ‐index was set to be 2%/2 mm, the pass rate was found to be 99.0% ± 0.07%, 98.2% ± 0.14%, and 100% for the three cases.Conclusions:The EPID dosimetry system developed in this work provides an accurate and reliable tool for routine output measurement and dosimetric verification of electron beam therapy. Coupled with its portability and ease of use, the proposed system promises to replace the current film‐based approach for fast and reliable assessment of small and irregular electron field dosimetry.
Morphological and Molecular Characterization of Exophiala polymorpha sp. nov. Isolated from Sporotrichoid Lymphocutaneous Lesions in a Patient with Myasthenia Gravis
Authors: Yong Lee K. , Wiederhold Nathan P. , Sutton Deanna A. , Sandoval-Denis Marcelo , Lindner Jonathan R. , Fan Hongxin , Sanders Carmita , Guarro Josep 
Published: June 2015

ABSTRACT

Exophiala
species are capable of causing cutaneous and subcutaneous infections in immunocompromised patients. An
Exophiala
isolate was cultured from a biopsy specimen of a lesion on the forearm of a patient with myasthenia gravis. The patient also had lesions on the palm and distal aspects of the hand, which were successfully treated with a long-term course of itraconazole. A detailed morphological and molecular characterization of the isolate was undertaken. Phylogenetic analysis of the internal transcribed spacer region and portions of the β-tubulin and translation elongation factor 1-alpha genes indicated that the isolate was a novel species closely related to but genetically distinct from species within the
Exophiala spinifera
clade; the name
Exophiala polymorpha
sp. nov. is proposed. Morphologically,
E. polymorpha
most closely resembles
E. xenobiotica
but it differs in possessing phialides bearing prominent, wide collarettes, and it does not produce chlamydospores.
Fonsecaea pugnacius, a Novel Agent of Disseminated Chromoblastomycosis
Authors: de Azevedo Conceição M. P. S. , Gomes Renata R. , Vicente Vania A. , Santos Daniel W. C. L. , Marques Sirlei G. , do Nascimento Mariana M. F. , Andrade Caroline E. W. , Silva Raimunda R. , Queiroz-Telles Flávio , de Hoog G. Sybren 
Published: June 2015

ABSTRACT

We report a fatal case of a chromoblastomycosis-like infection caused by a novel species of
Fonsecaea
in a 52-year-old immunocompetent Caucasian male from an area of chromoblastomycosis endemicity in Brazil. The patient had a 30-year history of slowly evolving, verrucous lesions on the right upper arm which gradually affected the entire arm, the left hemifacial area, and the nose. Subsequent dissemination to the brain was observed, which led to death of the patient. The internal transcribed spacer (ITS) and partial large subunit (LSU),
BT2
, and
CDC42
genes of the isolates recovered from skin and brain were sequenced, confirming the novelty of the species. The species is clinically unique in causing brain abscesses secondary to chromoblastomycosis lesions despite the apparent intact immunity of the patient. Histopathologic appearances were very different, showing muriform cells in skin and hyphae in brain.
Analytical Comparison of
In Vitro
-Spiked Human Serum and Plasma for PCR-Based Detection of Aspergillus fumigatus DNA: a Study by the European Aspergillus PCR Initiative
Authors: Loeffler Juergen , Mengoli Carlo , Springer Jan , Bretagne Stéphane , Cuenca-Estrella Manuel , Klingspor Lena , Lagrou Katrien , Melchers Willem J. G. , Morton C. Oliver , Barnes Rosemary A. , Donnelly J. Peter , White P. Lewis 
Published: June 2015

ABSTRACT

The use of serum or plasma for
Aspergillus
PCR testing facilitates automated and standardized technology. Recommendations for serum testing are available, and while serum and plasma are regularly considered interchangeable for use in fungal diagnostics, differences in galactomannan enzyme immunoassay (GM-EIA) performance have been reported and are attributed to clot formation. Therefore, it is important to assess plasma PCR testing to determine if previous recommendations for serum are applicable and also to compare analytical performance with that of serum PCR. Molecular methods testing serum and plasma were compared through multicenter distribution of quality control panels, with additional studies to investigate the effect of clot formation and blood fractionation on DNA availability. Analytical sensitivity and time to positivity (TTP) were compared, and a regression analysis was performed to identify variables that enhanced plasma PCR performance. When testing plasma, sample volume, preextraction-to-postextraction volume ratio, PCR volume, duplicate testing, and the use of an internal control for PCR were positively associated with performance. When whole-blood samples were spiked and then fractionated, the analytical sensitivity and TTP were superior when testing plasma. Centrifugation had no effect on DNA availability, whereas the presence of clot material significantly lowered the concentration (
P
= 0.028). Technically, there are no major differences in the molecular processing of serum and plasma, but the formation of clot material potentially reduces available DNA in serum. During disease,
Aspergillus
DNA burdens in blood are often at the limits of PCR performance. Using plasma might improve performance while maintaining the methodological simplicity of serum testing.