bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotype–genotype correlations of facial width and height proportions in patients with Class II malocclusion
Authors: Moreno Uribe L. M. , Ray A. , Blanchette D. R. , Dawson D. V. , Southard T. E. 
Published: April 2015

Structured AbstractObjectivesTo characterize soft‐tissue facial height and width variation in Class II malocclusion and test for correlations with genes HMGA2, AJUBA, and ADK.Setting and sample populationNine facial proportions were estimated from 2D frontal repose photographs of 330 Caucasian adults with Class II malocclusion.Material and methodsAfter adjustments for age and gender, the facial proportions were submitted to a principal component analyses (PCA). The most meaningful phenotypic variations were correlated with SNPs rs7924176 (ADK), rs17101923 (HMGA2), and rs997154 (AJUBA) genotyped in 106 individuals.ResultsPrincipal component analyses resulted in four principal components (PCs), which explained 75% of total variation. PC1 captured variation in the intercanthus distance and explained 28% of total variation. PC2 explained 21% of the variations in facial taper and facial index. PC3 explained 14% and reflected variations in the vertical dimension of the lower face. PC4 explained 12% and captured variations in distance between the eyes, width of the commissures, and the length of the superior aspect of the lower face height corresponding to the vertical dimension of the philtrum of the upper lip. A suggestive association (p < 0.05) was observed between PC4 and rs997154 corroborating the role of AJUBA in variation of facial dimensions.Conclusion2D frontal photographs can be used to derive quantitative measures of soft‐tissue phenotypes that are of clinical relevance. The methods described are suitable for discovery and replication of associations between genotypes and malocclusion phenotypes.
A pilot study of ambulatory masticatory muscle activities in temporomandibular joint disorders diagnostic groups
Authors: Iwasaki L. R. , Gonzalez Y. M. , Liu H. , Marx D. B. , Gallo L. M. , Nickel J. C. 
Published: April 2015

Structured AbstractObjectiveTo determine differences in masticatory muscle usage between temporomandibular joint disorders diagnostic groups.Setting and sample populationSeventy‐one informed and consented subjects (27 men; 44 women) participated at the University at Buffalo.Material and methodsResearch diagnostic criteria and imaging data were used to categorize subjects according to the presence/absence (+/−) of TMJ disc placement (DD) and chronic pain (P) (+DD+P, n = 18; +DD−P, n = 14; −DD−P, n = 39). Electromyographic (EMG)/bite‐force calibrations determined subject‐specific masseter and temporalis muscle activities per 20 N bite‐force (T20N, μV). Over 3 days and nights, subjects collected EMG recordings. Duty factors (DFs, % of recording time) were determined based on threshold intervals (5–9, 10–24, 25–49, 50–79, ≥80% T20N). anova and Tukey–Kramer post hoc tests identified 1) diagnostic group differences in T20N and 2) the effects of diagnostic group, gender, time and interval on muscle DFs.ResultsMean (± SE) temporalis T20N in +DD+P subjects was significantly higher (71.4 ± 8.8 μV) than masseter T20N in these subjects (19.6 ± 8.8 μV; p = 0.001) and in −DD−P subjects (25.3 ± 6.0 μV, p = 0.0007). Masseter DFs at 5–9% T20N were significantly higher in +DD−P women (3.48%) than +DD−P men (0.85%) and women and men in both other diagnostic groups (all p < 0.03), and in +DD+P women (2.00%) compared to −DD−P men (0.83%; p = 0.029). Night‐time DFs at 5–9% T20N in +DD−P women (1.97%) were significantly higher than in −DD−P men (0.47%) and women (0.24%; all p < 0.01).ConclusionsBetween‐group differences were found in masticatory muscle activities in both laboratory and natural environmental settings.
Prehospital Pain and Analgesic Therapy in Elderly Patients with Hip Fractures
Authors: Oberkircher Ludwig , Schubert Natalie , Eschbach Daphne‐Asimenia , Bliemel Christopher , Krueger Antonio , Ruchholtz Steffen , Buecking Benjamin 
Published: April 2015

AbstractIntroductionAs a part of aging, hip fractures are becoming more common. The connection between increased pain and a poor outcome has previously been shown. Therefore, even in prehospital situations, analgesic therapy appears to be reasonable. We established a prospective study with 153 patients to evaluate the patients' pain levels during the prehospital phase of treatment and prehospital analgesic therapy.MethodsWe performed a prospective study on 153 patients the age of 60 years or older in a University hospital setting between 2010 and 2011 who suffered hip fracture. Analgesics given and the type of medical staff that was involved were documented. Pain was measured using the NRS upon initial contact of the medical staff and upon admission to our emergency department.ResultsInitial pain level evaluated by EMS (emergency medical service) was 6.8 (SD = 2.7). Twenty‐two percent of the patients reported an NRS of 10 as the highest value following their injury. Forty‐three of 153 patients (28%) received analgesics. The mean initial pain score for those 43 patients who did receive pain medication was 7.0 (SD = 2.6). However, this score dropped to a mean of 2.8 (SD = 1.4) upon hospital arrival (P < 0.001). The patients who did not receive pain medication had an initial pain score of 4.5 (SD = 1.9). Upon admission to the hospital, this score decreased to a mean of 4.0 (SD = 1.7, P = 0.092).ConclusionOnly a minority of patients with hip fractures received prehospital analgesia. The administration of prehospital analgesia was associated with significant pain relief.
Laryngoplasty in Standing Horses
Authors: Rossignol Fabrice , Vitte Amélie , Boening Josef , Maher Michael , Lechartier Antoine , Brandenberger Olivier , Martin‐Flores Manuel , Lang Hayley , Walker Wade , Ducharme Norm G. 
Published: April 2015

ObjectiveTo describe the clinical experience with standing laryngoplasty in a series of horses mostly nonracing.Study DesignCase series.AnimalsSeventy‐one client‐owned horses.MethodsMedical records (April 2008–February 2014) of horses treated by standing laryngoplasty for abnormal respiratory noise and or poor performance were reviewed. Horses were included if they had a diagnosis of idiopathic right or left recurrent laryngeal neuropathy confirmed by videoendoscopy. All horses underwent a unilateral laryngoplasty with a unilateral or bilateral ventriculectomy or ventriculocordectomy. Follow‐up endoscopy was performed in all horses within 24 hours postoperative, in 24 horses at 2‐weeks, and in 65 horses at 6 weeks. Late follow‐up was obtained from the trainer, owner, or referring veterinarian by telephone.ResultsLaryngoplasty was performed under endoscopic guidance with the horses sedated, and the surgical site was desensitized with local anesthetic solution. Laryngoplasty was completed in all horses and was well tolerated. No hyperabduction was observed. Two horses developed incisional swelling that resolved with drainage only. Late follow‐up reported satisfactory improvement in respiration in all but 3 horses.ConclusionsLaryngoplasty performed with the horse standing avoids risks associated with general anesthesia and recovery and yields comparable results in nonracing horses, to laryngoplasty performed with the horse anesthetized. This technique reduces cost and allows accurate intraoperative adjustment of the degree of arytenoid abduction.
Robust optimization methods for cardiac sparing in tangential breast IMRT
Authors: Mahmoudzadeh Houra , Lee Jenny , Chan Timothy C. Y. , Purdie Thomas G. 
Published: April 2015

Purpose:In left‐sided tangential breast intensity modulated radiation therapy (IMRT), the heart may enter the radiation field and receive excessive radiation while the patient is breathing. The patient's breathing pattern is often irregular and unpredictable. We verify the clinical applicability of a heart‐sparing robust optimization approach for breast IMRT. We compare robust optimized plans with clinical plans at free‐breathing and clinical plans at deep inspiration breath‐hold (DIBH) using active breathing control (ABC).Methods:Eight patients were included in the study with each patient simulated using 4D‐CT. The 4D‐CT image acquisition generated ten breathing phase datasets. An average scan was constructed using all the phase datasets. Two of the eight patients were also imaged at breath‐hold using ABC. The 4D‐CT datasets were used to calculate the accumulated dose for robust optimized and clinical plans based on deformable registration. We generated a set of simulated breathing probability mass functions, which represent the fraction of time patients spend in different breathing phases. The robust optimization method was applied to each patient using a set of dose‐influence matrices extracted from the 4D‐CT data and a model of the breathing motion uncertainty. The goal of the optimization models was to minimize the dose to the heart while ensuring dose constraints on the target were achieved under breathing motion uncertainty.Results:Robust optimized plans were improved or equivalent to the clinical plans in terms of heart sparing for all patients studied. The robust method reduced the accumulated heart dose (D10cc) by up to 801 cGy compared to the clinical method while also improving the coverage of the accumulated whole breast target volume. On average, the robust method reduced the heart dose (D10cc) by 364 cGy and improved the optBreast dose (D99%) by 477 cGy. In addition, the robust method had smaller deviations from the planned dose to the accumulated dose. The deviation of the accumulated dose from the planned dose for the optBreast (D99%) was 12 cGy for robust versus 445 cGy for clinical. The deviation for the heart (D10cc) was 41 cGy for robust and 320 cGy for clinical.Conclusions:The robust optimization approach can reduce heart dose compared to the clinical method at free‐breathing and can potentially reduce the need for breath‐hold techniques.
Reducing the effects of acoustic heterogeneity with an iterative reconstruction method from experimental data in microwave induced thermoacoustic tomography
Authors: Wang Jinguo , Zhao Zhiqin , Song Jian , Chen Guoping , Nie Zaiping , Liu Qing‐Huo 
Published: April 2015

Purpose:An iterative reconstruction method has been previously reported by the authors of this paper. However, the iterative reconstruction method was demonstrated by solely using the numerical simulations. It is essential to apply the iterative reconstruction method to practice conditions. The objective of this work is to validate the capability of the iterative reconstruction method for reducing the effects of acoustic heterogeneity with the experimental data in microwave induced thermoacoustic tomography.Methods:Most existing reconstruction methods need to combine the ultrasonic measurement technology to quantitatively measure the velocity distribution of heterogeneity, which increases the system complexity. Different to existing reconstruction methods, the iterative reconstruction method combines time reversal mirror technique, fast marching method, and simultaneous algebraic reconstruction technique to iteratively estimate the velocity distribution of heterogeneous tissue by solely using the measured data. Then, the estimated velocity distribution is used subsequently to reconstruct the highly accurate image of microwave absorption distribution. Experiments that a target placed in an acoustic heterogeneous environment are performed to validate the iterative reconstruction method.Results:By using the estimated velocity distribution, the target in an acoustic heterogeneous environment can be reconstructed with better shape and higher image contrast than targets that are reconstructed with a homogeneous velocity distribution.Conclusions:The distortions caused by the acoustic heterogeneity can be efficiently corrected by utilizing the velocity distribution estimated by the iterative reconstruction method. The advantage of the iterative reconstruction method over the existing correction methods is that it is successful in improving the quality of the image of microwave absorption distribution without increasing the system complexity.
Genetic Diversity of the
fliC
Genes Encoding the Flagellar Antigen H19 of Escherichia coli and Application to the Specific Identification of Enterohemorrhagic E. coli O121:H19
Authors: Beutin Lothar , Delannoy Sabine , Fach Patrick 
Published: April 2015

ABSTRACT

Enterohemorrhagic
Escherichia coli
(EHEC) O121:H19 belong to a specific clonal type distinct from other classical EHEC and major enteropathogenic
E. coli
groups and is regarded as one of the major EHEC serogroups involved in severe infections in humans. Sequencing of the
fliC
genes associated with the flagellar antigen H19 (
fliC
H19
) revealed the genetic diversity of the
fliC
H19
gene sequences in
E. coli
. A cluster analysis of 12
fliC
H19
sequences, 4 from O121 and 8 from non-O121
E. coli
strains, revealed five different genotypes. All O121:H19 strains fell into one cluster, whereas a second cluster was formed by five non-O121:H19 strains. Cluster 1 and cluster 2 strains differ by 27 single nucleotide exchanges in their
fliC
H19
genes (98.5% homology). Based on allele discrimination of the
fliC
H19
genes, a real-time PCR test was designed for specific identification of EHEC O121:H19. The O121
fliC
H19
PCR tested negative in 73
E. coli
H19 strains that belonged to serogroups other than O121, including 28 different O groups, O-nontypeable H19, and O-rough:H19 strains. The O121
fliC
H19
PCR reacted with all 16 tested O121:H19 strains and 1 O-rough:H19 strain which was positive for the O121
wzx
gene. A cross-reaction was observed only with
E. coli
H32 strains which share sequence similarities in the target region of the O121
fliC
H19
PCR. The combined use of O-antigen genotyping (O121
wzx
) and the detection of O121
fliC
H19
allele type contributes to improving the identification and molecular serotyping of EHEC O121:H19 motile and nonmotile strains and variants of these strains lacking
stx
genes.
Steroid Hydroxylation by Basidiomycete Peroxygenases: a Combined Experimental and Computational Study
Authors: Babot Esteban D. , del Río José C. , Cañellas Marina , Sancho Ferran , Lucas Fátima , Guallar Víctor , Kalum Lisbeth , Lund Henrik , Gröbe Glenn , Scheibner Katrin , Ullrich René , Hofrichter Martin , Martínez Angel T. , Gutiérrez Ana 
Published: April 2015

ABSTRACT

The goal of this study is the selective oxyfunctionalization of steroids under mild and environmentally friendly conditions using fungal enzymes. With this purpose, peroxygenases from three basidiomycete species were tested for the hydroxylation of a variety of steroidal compounds, using H
2
O
2
as the only cosubstrate. Two of them are wild-type enzymes from
Agrocybe aegerita
and
Marasmius rotula
, and the third one is a recombinant enzyme from
Coprinopsis cinerea
. The enzymatic reactions on free and esterified sterols, steroid hydrocarbons, and ketones were monitored by gas chromatography, and the products were identified by mass spectrometry. Hydroxylation at the side chain over the steroidal rings was preferred, with the 25-hydroxyderivatives predominating. Interestingly, antiviral and other biological activities of 25-hydroxycholesterol have been reported recently (M. Blanc et al., Immunity 38:106–118, 2013,
http://dx.doi.org/10.1016/j.immuni.2012.11.004
). However, hydroxylation in the ring moiety and terminal hydroxylation at the side chain also was observed in some steroids, the former favored by the absence of oxygenated groups at C-3 and by the presence of conjugated double bonds in the rings. To understand the yield and selectivity differences between the different steroids, a computational study was performed using Protein Energy Landscape Exploration (PELE) software for dynamic ligand diffusion. These simulations showed that the active-site geometry and hydrophobicity favors the entrance of the steroid side chain, while the entrance of the ring is energetically penalized. Also, a direct correlation between the conversion rate and the side chain entrance ratio could be established that explains the various reaction yields observed.
Structure and Mechanism of Ferulic Acid Decarboxylase (FDC1) from Saccharomyces cerevisiae
Authors: Bhuiya Mohammad Wadud , Lee Soon Goo , Jez Joseph M. , Yu Oliver 
Published: April 2015

ABSTRACT

The nonoxidative decarboxylation of aromatic acids occurs in a range of microbes and is of interest for bioprocessing and metabolic engineering. Although phenolic acid decarboxylases provide useful tools for bioindustrial applications, the molecular bases for how these enzymes function are only beginning to be examined. Here we present the 2.35-Å-resolution X-ray crystal structure of the ferulic acid decarboxylase (FDC1; UbiD) from
Saccharomyces cerevisiae
. FDC1 shares structural similarity with the UbiD family of enzymes that are involved in ubiquinone biosynthesis. The position of 4-vinylphenol, the product of
p
-coumaric acid decarboxylation, in the structure identifies a large hydrophobic cavity as the active site. Differences in the β2e-α5 loop of chains in the crystal structure suggest that the conformational flexibility of this loop allows access to the active site. The structure also implicates Glu285 as the general base in the nonoxidative decarboxylation reaction catalyzed by FDC1. Biochemical analysis showed a loss of enzymatic activity in the E285A mutant. Modeling of 3-methoxy-4-hydroxy-5-decaprenylbenzoate, a partial structure of the physiological UbiD substrate, in the binding site suggests that an ∼30-Å-long pocket adjacent to the catalytic site may accommodate the isoprenoid tail of the substrate needed for ubiquinone biosynthesis in yeast. The three-dimensional structure of yeast FDC1 provides a template for guiding protein engineering studies aimed at optimizing the efficiency of aromatic acid decarboxylation reactions in bioindustrial applications.
Developmental Growth Control Exerted via the Protein A Kinase Tpk2 in Ashbya gossypii
Authors: Wasserstrom Lisa , Lengeler Klaus , Walther Andrea , Wendland Jürgen 
Published: April 2015

ABSTRACT

Sporulation in
Ashbya gossypii
is induced by nutrient-limited conditions and leads to the formation of haploid spores. Using RNA-seq, we have determined a gene set induced upon sporulation, which bears considerable overlap with that of
Saccharomyces cerevisiae
but also contains
A. gossypii
-specific genes. Addition of cyclic AMP (cAMP) to nutrient-limited media blocks sporulation and represses the induction of sporulation specific genes. Deletion of the protein kinase A (PKA) catalytic subunits encoded by
TPK1
and
TPK2
showed reduced growth in
tpk1
but enhanced growth in the
tpk2
strain; however, both mutants sporulated well. Sporulation can be blocked by cAMP in
tpk1
but not in
tpk2
strains. Similarly,
TPK2
acts at a second developmental switch promoting the break in spore dormancy. In
S. cerevisiae
, PKA phosphorylates and inhibits Msn2/4. The transcript profiles of the
tpk1
and
msn2/4
mutants were very similar to that of the wild type under sporulation conditions. However, deletion of the single
A. gossypii
MSN2/4
homolog generated a specific sporulation defect. We identified a set of genes involved in spore wall assembly that was downregulated in the
msn2/4
mutant, particularly
DIT2
, suggesting that poor spore viability may be due to lysis of spores. Our results reveal specific functional differences between the two catalytic PKA subunits in
A. gossypii
and identified Tpk2 as the key A kinase that transduces developmental decisions of growth. Our data also suggest that Msn2/4 is involved only at a late step of sporulation in
A. gossypii
and is not a major regulator of
IME1
.
Genetic variation at the human connexin 43 locus but not at the connexin 40 locus is associated with left bundle branch block
Authors: Ladenvall Per , Andersson Björn , Dellborg Mikael , Hansson Per-Olof , Eriksson Henry , Thelle Dag , Eriksson Peter 
Published: April 2015

BackgroundBundle branch block (BBB) has been regarded as a disease of the conduction system, but occurs in mice lacking connexin 40 (expressed in atria, proximal conduction system) or connexin 43 (expressed in Purkinje cells, cardiomyocytes).ObjectiveThe aim of this paper is to explore whether BBB is heritable, and whether polymorphisms at connexin 40 and connexin 43 loci are associated with BBB.MethodsTo assess BBB heritability, we screened descendants of men with BBB in the population cohort ‘The Study of Men Born 1913’. DNA samples from 80-year-old men with extreme QRS-duration phenotypes were used to search for polymorphisms at connexin 40 and 43 loci. Associations between identified polymorphisms and BBB were evaluated in an independent cohort (INTERGENE).ResultsSeventy-seven men from ‘The Study of Men Born 1913’ with BBB had 116 descendants. Among the 76 participating descendants, 2 sons (6.4%) had BBB at 54 years of age. At the same age, 0.9% of men born in 1913 had BBB. We identified 6 single nucleotide polymorphisms (SNPs) in connexin 40 and 1 polymorphism in connexin 43. In the INTERGENE cohort, the connexin 43 polymorphism was associated with left BBB (LBBB) (4 of 35 LBBB vs 16 of 232 without BBB, χ2=7.4, p=0.03), but not with right BBB (RBBB) or overall BBB. None of the connexin 40 SNPs or haplotypes were associated with LBBB or RBBB.ConclusionsThese findings indicate that conduction by connexin 43 within the ventricular muscle distal to the specialised conduction system may be important for LBBB development.
An Antibody–Drug Conjugate Directed against Lymphocyte Antigen 6 Complex, Locus E (LY6E) Provides Robust Tumor Killing in a Wide Range of Solid Tumor Malignancies
Authors: Asundi Jyoti , Crocker Lisa , Tremayne Jarrod , Chang Peter , Sakanaka Chie , Tanguay Josh , Spencer Susan , Chalasani Sreedevi , Luis Elizabeth , Gascoigne Karen , Desai Rupal , Raja Rajiv , Friedman Brad A. , Haverty Peter M. , Polakis Paul , Firestein Ron 
Published: April 2015

Abstract
Purpose: Chemotherapies are limited by a narrow therapeutic index resulting in suboptimal exposure of the tumor to the drug and acquired tumor resistance. One approach to overcome this is through antibody–drug conjugates (ADC) that facilitate greater potency via target-specific delivery of highly potent cytotoxic agents.
Experimental Design: In this study, we used a bioinformatics approach to identify the lymphocyte antigen 6 complex locus E (LY6E), an IFN-inducible glycosylphosphatidylinositol (GPI)-linked cell membrane protein as a promising ADC target. We developed a monoclonal anti-LY6E antibody and characterized in situ LY6E expression in over 750 cancer specimens and normal tissues. Target-dependent anti-LY6E ADC killing was investigated both in vitro and in vivo using patient-derived xenograft models.
Results: Using in silico approaches, we found that LY6E was significantly overexpressed and amplified in a wide array of different human solid tumors. IHC analysis revealed high LY6E protein expression in a number of tumor types, such as breast, lung, gastric, ovarian, pancreatic, kidney and head/neck carcinomas. Characterization of the endocytic pathways for LY6E revealed that the LY6E-specific antibody is internalized into cells leading to lysosomal accumulation. Consistent with this, a LY6E-specific ADC inhibited in vitro cell proliferation and produced durable tumor regression in vivo in clinically relevant LY6E-expressing xenograft models.
Conclusions: Our results identify LY6E as a highly promising molecular ADC target for a variety of solid tumor types with current unmet medical need. Clin Cancer Res; 21(14); 3252–62. ©2015 AACR.