bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional POR A503V is associated with the risk of bladder cancer in a Chinese population
Authors: Xiao Xue , Ma Gaoxiang , Li Shushu , Wang Meilin , Liu Nian , Ma Lan , Zhang Zhan , Chu Haiyan , Zhang Zhengdong , Wang Shou-Lin 
Published: June 2015

AbstractHuman cytochrome P450 oxidoreductase (POR) plays important roles in the metabolism of exogenous carcinogens and endogenous sterol hormones. However, few studies have explored the association between POR variants and the risk of bladder cancer. In this study, we first sequenced all 16 POR exons among 50 randomly selected controls and found three variants, rs1135612, rs1057868 (A503V) and rs2228104, which were then assessed the relation to risk of bladder cancer in a case-control study of 1,050 bladder cancer cases and 1,404 cancer-free controls in a Chinese population. People with A503V TT genotype have a decreased risk of bladder cancer in a recessive model (TT vs. CC/CT, OR = 0.73, 95% CI = 0.57–0.93), which was more pronounced among elderly male, non-smoking, subjects. Especially, A503V TT genotype showed a protective effect in the invasive tumor stage. Functional analysis revealed that A503V activity decreased in cytochrome c reduction (50.5 units/mg vs. 135.4 units/mg), mitomycin C clearance (38.3% vs. 96.8%) and mitomycin C-induced colony formation (78.0 vs 34.3 colonies per dish). The results suggested that POR A503V might decrease the risk of bladder cancer by reducing its metabolic activity and should be a potential biomarker for predicting the susceptibility to human bladder cancer.
SPECT/CT Imaging of High-Risk Atherosclerotic Plaques using Integrin-Binding RGD Dimer Peptides
Authors: Sun Yoo Jung , Lee Jonghwan , Ho Jung Jae , Seok Moon Byung , Kim Soonhag , Chul Lee Byung , Eun Kim Sang 
Published: June 2015

AbstractVulnerable atherosclerotic plaques with unique biological signatures are responsible for most major cardiovascular events including acute myocardial infarction and stroke. However, current clinical diagnostic approaches for atherosclerosis focus on anatomical measurements such as the degree of luminal stenosis and wall thickness. An abundance of neovessels with elevated expression of integrin αvβ3 is closely associated with an increased risk of plaque rupture. Herein we evaluated the potential of an αvβ3 integrin-targeting radiotracer, 99mTc-IDA-D-[c(RGDfK)]2, for SPECT/CT imaging of high-risk plaque in murine atherosclerosis models. In vivo uptake of 99mTc-IDA-D-[c(RGDfK)]2 was significantly higher in atherosclerotic aortas than in relatively normal aortas. Comparison with the negative-control peptide, 99mTc-IDA-D-[c(RADfK)]2, proved specific binding of 99mTc-IDA-D-[c(RGDfK)]2 for plaque lesions in in vivo SPECT/CT and ex vivo autoradiographic imaging. Histopathological characterization revealed that a prominent SPECT signal of 99mTc-IDA-D-[c(RGDfK)]2 corresponded to the presence of high-risk plaques with a large necrotic core, a thin fibrous cap and vibrant neoangiogenic events. Notably, the RGD dimer based 99mTc-IDA-D-[c(RGDfK)]2 showed better imaging performance in comparison with the common monomeric RGD peptide probe 123I-c(RGDyV) and fluorescence tissue assay corroborated this. Our preclinical data demonstrated that 99mTc-IDA-D-[c(RGDfK)]2 SPECT/CT is a sensitive tool to noninvasively gauge atherosclerosis beyond vascular anatomy by assessing culprit plaque neovascularization.
Long noncoding RNA expression profiles in gut tissues constitute molecular signatures that reflect the types of microbes
Authors: Liang Lunxi , Ai Luoyan , Qian Jin , Fang Jing-Yuan , Xu Jie 
Published: June 2015

AbstractThe gut microbiota is commonly referred to as a hidden organ due to its pivotal effects on host physiology, metabolism, nutrition and immunity. The gut microbes may be shaped by environmental and host genetic factors and previous studies have focused on the roles of protein-coding genes. Here we show a link between long non-coding RNA (lncRNA) expression and gut microbes. By repurposing exon microarrays and comparing the lncRNA expression profiles between germ-free, conventional and different gnotobiotic mice, we revealed subgroups of lncRNAs that were specifically enriched in each condition. A nearest shrunken centroid methodology was applied to obtain lncRNA-based signatures to identify mice in different conditions. The lncRNA-based prediction model successfully identified different gnotobiotic mice from conventional and germ-free mice and also discriminated mice harboring transplanted microbes from fecal samples of mice or zebra fishes. To achieve optimal prediction accuracy, fewer lncRNAs were required in the prediction model than protein-coding genes. Taken together, our study demonstrated the effecacy of lncRNA expression profiles in discriminating the types of microbes in the gut. These results also provide a resource of gut microbe-associated lncRNAs for the development of lncRNA biomarkers and the identification of functional lncRNAs in host-microbes interactions.
Successful treatment of Batrachochytrium salamandrivorans infections in salamanders requires synergy between voriconazole, polymyxin E and temperature
Authors: Blooi M. , Pasmans F. , Rouffaer L. , Haesebrouck F. , Vercammen F. , Martel A. 
Published: June 2015

AbstractChytridiomycosis caused by the chytrid fungus Batrachochytrium salamandrivorans (Bsal) poses a serious threat to urodelan diversity worldwide. Antimycotic treatment of this disease using protocols developed for the related fungus Batrachochytrium dendrobatidis (Bd), results in therapeutic failure. Here, we reveal that this therapeutic failure is partly due to different minimum inhibitory concentrations (MICs) of antimycotics against Bsal and Bd. In vitro growth inhibition of Bsal occurs after exposure to voriconazole, polymyxin E, itraconazole and terbinafine but not to florfenicol. Synergistic effects between polymyxin E and voriconazole or itraconazole significantly decreased the combined MICs necessary to inhibit Bsal growth. Topical treatment of infected fire salamanders (Salamandra salamandra), with voriconazole or itraconazole alone (12.5 μg/ml and 0.6 μg/ml respectively) or in combination with polymyxin E (2000 IU/ml) at an ambient temperature of 15 °C during 10 days decreased fungal loads but did not clear Bsal infections. However, topical treatment of Bsal infected animals with a combination of polymyxin E (2000 IU/ml) and voriconazole (12.5 μg/ml) at an ambient temperature of 20 °C resulted in clearance of Bsal infections. This treatment protocol was validated in 12 fire salamanders infected with Bsal during a field outbreak and resulted in clearance of infection in all animals.
Acceleration of protein folding by four orders of magnitude through a single amino acid substitution
Authors: Roderer Daniel J. A. , Schärer Martin A. , Rubini Marina , Glockshuber Rudi 
Published: June 2015

AbstractCis prolyl peptide bonds are conserved structural elements in numerous protein families, although their formation is energetically unfavorable, intrinsically slow and often rate-limiting for folding. Here we investigate the reasons underlying the conservation of the cis proline that is diagnostic for the fold of thioredoxin-like thiol-disulfide oxidoreductases. We show that replacement of the conserved cis proline in thioredoxin by alanine can accelerate spontaneous folding to the native, thermodynamically most stable state by more than four orders of magnitude. However, the resulting trans alanine bond leads to small structural rearrangements around the active site that impair the function of thioredoxin as catalyst of electron transfer reactions by more than 100-fold. Our data provide evidence for the absence of a strong evolutionary pressure to achieve intrinsically fast folding rates, which is most likely a consequence of proline isomerases and molecular chaperones that guarantee high in vivo folding rates and yields.
The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function
Authors: Ward D D , Summers M J , Saunders N L , Ritchie K , Summers J J , Vickers J C 
Published: June 2015

AbstractThe concept of cognitive reserve (CR) has been proposed to account for observed discrepancies between pathology and its clinical manifestation due to underlying differences in brain structure and function. In 433 healthy older adults participating in the Tasmanian Healthy Brain Project, we investigated whether common polymorphic variations in apolipoprotein E (APOE) or brain-derived neurotrophic factor (BDNF)influenced the association between CR contributors and cognitive function in older adults. We show thatBDNFVal66Met moderates the association between CR and executive function. CR accounted for 8.5% of the variance in executive function inBDNFVal homozygotes, but CR was a nonsignificant predictor inBDNFMet carriers.APOEpolymorphisms were not linked to the influence of CR on cognitive function. This result implicatesBDNFin having an important role in capacity for building or accessing CR.
Increased anterior insula activity in anxious individuals is linked to diminished perceived control
Authors: Alvarez R P , Kirlic N , Misaki M , Bodurka J , Rhudy J L , Paulus M P , Drevets W C 
Published: June 2015

AbstractIndividuals with high-trait anxiety frequently report decreased perceived control. However, it is unclear how these processes are instantiated at a neural level. Prior research suggests that individuals prone to anxiety may have exaggerated activity in the anterior insula and altered activity in the cingulate cortex during anticipation of aversive events. Thus, we hypothesized that anxiety proneness influences anterior insula activation during anticipation of unpredictable threat through decreased perceived control. Forty physically healthy adults underwent neuroimaging while they explored computer-simulated contexts associated either with or without the threat of an unpredictable shock. Skin conductance, anxiety ratings and blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging were used to assess responses to threat versus no threat. Perceived control was measured using the Anxiety Control Questionnaire-Revised. Mediation analysis examined how anxiety proneness influenced BOLD activity. Anticipation of unpredictable threat resulted in increased skin conductance responses, anxiety ratings and enhanced activation in bilateral insula, anterior midcingulate cortex (aMCC) and bed nucleus of the stria terminalis. Individuals with greater anxiety proneness and less perceived control showed greater activity in dorsal anterior insula (dAI). Perceived control mediated the relationship between anxiety proneness and dAI activity. Increased dAI activity was associated with increased activity in aMCC, which correlated with increased exploratory behavior. Results provide evidence that exaggerated insula activation during the threat of unpredictable shock is directly related to low perceived control in anxiety-prone individuals. Perceived control thus may constitute an important treatment target to modulate insula activity during anxious anticipation in anxiety-disordered individuals.
Psychometric precision in phenotype definition is a useful step in molecular genetic investigation of psychiatric disorders
Authors: Xu M K , Gaysina D , Barnett J H , Scoriels L , van de Lagemaat L N , Wong A , Richards M , Croudace T J , Jones P B ,   the LHA genetics group
Published: June 2015

AbstractAffective disorders are highly heritable, but few genetic risk variants have been consistently replicated in molecular genetic association studies. The common method of defining psychiatric phenotypes in molecular genetic research is either a summation of symptom scores or binary threshold score representing the risk of diagnosis. Psychometric latent variable methods can improve the precision of psychiatric phenotypes, especially when the data structure is not straightforward. Using data from the British 1946 birth cohort, we compared summary scores with psychometric modeling based on the General Health Questionnaire (GHQ-28) scale for affective symptoms in an association analysis of 27 candidate genes (249 single-nucleotide polymorphisms (SNPs)). The psychometric method utilized a bi-factor model that partitioned the phenotype variances into five orthogonal latent variable factors, in accordance with the multidimensional data structure of the GHQ-28 involving somatic, social, anxiety and depression domains. Results showed that, compared with the summation approach, the affective symptoms defined by the bi-factor psychometric model had a higher number of associated SNPs of larger effect sizes. These results suggest that psychometrically defined mental health phenotypes can reflect the dimensions of complex phenotypes better than summation scores, and therefore offer a useful approach in genetic association investigations.
Acquisition of Consonant Clusters and Acceptable Variants in Chinese-Influenced Malaysian English-Speaking Children
Authors: Phoon Hooi San , Maclagan Margaret , Abdullah Anna Christina 
Published: June 2015

Purpose
This study investigated consonant cluster acquisition in Chinese-influenced Malaysian English (ChME)-speaking children.

Method
This cross-sectional study involved 262 typically developing ChME-speaking children (138 girls, 124 boys) ages 3 to 7 years old. A single-word picture-naming task, which contained 66 words and targeted 32 syllable-initial (SI) and 14 syllable-final (SF) consonant clusters, was administered.

Results
Older children produced more correct productions than younger children, and there was no sex effect for consonant cluster production. SF consonant clusters were more accurate than SI consonant clusters among the younger children. The overall sequence of SI consonant cluster accuracy based on cluster categories from most to least accurate was /s/ + C, C + /w/, C + /j/, C + /l/, and C + /r/, whereas for SF consonant clusters, the order was C + stop, C + /s/, nasal + C, and /l/ + C. Two-element clusters consistently had higher accuracy in comparison to three-element clusters across the age groups. The overall consonant cluster accuracy of the present study showed similar patterns to those found in previous studies of Standard English.

Conclusion
The findings of the study will be useful in the assessment of consonant cluster production of ChME-speaking children.
Nonspeech Oral Movements and Oral Motor Disorders: A Narrative Review
Authors: Kent Ray D. 
Published: June 2015

PurposeSpeech and other oral functions such as swallowing have been compared and contrasted with oral behaviors variously labeledquasispeech, paraspeech, speechlike,andnonspeech,all of which overlap to some degree in neural control, muscles deployed, and movements performed. Efforts to understand the relationships among these behaviors are hindered by the lack of explicit and widely accepted definitions. This review article offers definitions and taxonomies for nonspeech oral movements and for diverse speaking tasks, both overt and covert.MethodReview of the literature included searches of Medline, Google Scholar, HighWire Press, and various online sources. Search terms pertained to speech, quasispeech, paraspeech, speechlike, and nonspeech oral movements. Searches also were carried out for associated terms in oral biology, craniofacial physiology, and motor control.Results and ConclusionsNonspeech movements have a broad spectrum of clinical applications, including developmental speech and language disorders, motor speech disorders, feeding and swallowing difficulties, obstructive sleep apnea syndrome, trismus, and tardive stereotypies. The role and benefit of nonspeech oral movements are controversial in many oral motor disorders. It is argued that the clinical value of these movements can be elucidated through careful definitions and task descriptions such as those proposed in this review article.
Survey of Speech-Language Pathology Graduate Program Training in Outer and Middle Ear Screening
Authors: Serpanos Yula C. , Senzer Deborah 
Published: June 2015

Purpose
The purpose of this study was to determine the national training practices of speech-language pathology graduate programs in outer and middle ear screening.

Method

Directors of all American Speech-Language-Hearing Association–accredited speech-language pathology graduate programs (
N
= 254; Council on Academic Accreditation in Audiology and Speech-Language Pathology, 2013) were surveyed on instructional formats in outer and middle ear screening.

Results

The graduate speech-language pathology program survey yielded 84 (33.1%) responses. Results indicated that some programs do not provide any training in the areas of conventional screening otoscopy using a handheld otoscope (15.5%;
n
= 13) or screening tympanometry (11.9%;
n
= 10), whereas close to one half (46.4%;
n
= 39) reported no training in screening video otoscopy. Outcomes revealed that approximately one third or more of speech-language pathology graduate programs do not provide experiential opportunities in screening handheld otoscopy (36.9%) or tympanometry (32.1%), and most (78.6%) do not provide experiential opportunities in video otoscopy.

Conclusions
The implication from the graduate speech-language pathology program survey findings is that some speech-language pathologists will graduate from academic programs without the acquired knowledge or experiential learning required to establish skill in 1 or more areas of screening otoscopy and tympanometry. Graduate speech-language pathology programs should consider appropriate training opportunities for students to acquire and demonstrate skill in outer and middle ear screening.
Characteristics of Fluency and Speech in Two Families With High Incidences of Stuttering
Authors: Stager Sheila V. , Freeman Frances J. , Braun Allen 
Published: June 2015

PurposeThis study presents data from 2 families with high incidence of stuttering, comparing methods of phenotype assignment and exploring the presence of other fluency disorders and corresponding speech characteristics.MethodThree methods for assigning phenotype of stuttering were used: self-identification, family identification, and expert identification. Agreement on which individuals were assigned by each of these methods was studied. Multiple measures of fluency and speech production were obtained.ResultsSelf-reports and descriptions of blocking rather than self-identification as a person who stutters demonstrated the best agreement with expert identification of stuttering. Family identification showed poor agreement with both expert and self-identification of stuttering. Using binary categories of fluent or stuttering, 90% of individuals in 1 family were classified by expert consensus. Only 70% of the other family could be similarly categorized. Experts required 2 other categories, cluttering and other fluency disorders, to fully characterize dysfluency within this family. These 2 families also demonstrated differences in speech production.ConclusionSome families with high incidence of stuttering may also have high incidence of other fluency disorders and other speech-production difficulties. This finding may have ramifications for genetic studies, including criteria for defining phenotype and collapsing data across multiple families.
Simultaneous Multiple Extradural Hematomas
Authors: Agarwal Parag , Roy Kaushik , Tripathy Parimal 
Published: June 2015

Objective Simultaneous multiple epidural hematomas (EDHs) are very rare and are associated with high mortality. The purpose of this study is to identify the clinical features, varying mechanisms that may be responsible for production of these hematomas, location of hematomas, and outcome of simultaneous multiple EDHs.
Methods Our study consisted of 528 patients who were admitted in our emergency department with diagnosis of traumatic brain injury (TBI) over a period of 14 months from September 2012 to October 2013 and retrospective analysis of all cases with EDH, particularly those with simultaneous multiple EDHs was done. All the patients were carefully examined clinically, Glasgow Coma Scale (GCS) was noted, plain computed tomographic scan (CT scan) was done and managed accordingly.
Results We came across six cases of multiple EDHs which accounted to 1.13% of all TBI. All of the cases except one were diagnosed within the first 6 hours. The GCS was used for neurological evaluations on admission and during hospital stay. A CT scan was done in all cases. Five patients underwent surgical intervention and one was managed conservatively. Two patients expired due to pre- and postoperative complications.
Conclusion EDHs are serious manifestation of TBI, of which multiple EDHs are even worse. These are life-threatening conditions. Early recognition and treatment can save a precious life. Widespread use of CT scan leads to early diagnosis before deterioration of the neurological status and affects the outcome of surgery.
Statistical universals reveal the structures and functions of human music
Authors: Savage Patrick E. , Brown Steven , Sakai Emi , Currie Thomas E. 
Published: June 2015

SignificanceWhich features of music are universal and which are culture-specific? Why? These questions are important for understanding why humans make music but have rarely been scientifically tested. We used musical classification techniques and statistical tools to analyze a global set of 304 music recordings, finding no absolute universals but dozens of statistical universals. These include not only commonly cited features related to pitch and rhythm but also domains such as social context and interrelationships between musical features. We speculate that group coordination is the common aspect unifying the cross-cultural structural regularities of human music, with implications for the study of music evolution.
Probing the structural and molecular basis of nucleotide selectivity by human mitochondrial DNA polymerase γ
Authors: Sohl Christal D. , Szymanski Michal R. , Mislak Andrea C. , Shumate Christie K. , Amiralaei Sheida , Schinazi Raymond F. , Anderson Karen S. , Yin Y. Whitney 
Published: June 2015

Significance
Nucleoside analog reverse transcriptase inhibitors (NRTIs) are the cornerstones of treatment for fighting HIV infection. Unfortunately, they also cause drug toxicity by inhibiting human mitochondrial DNA polymerase (Pol γ). Identification of structural differences between the intended target (RT) and adverse reaction target (Pol γ) will provide critical information for designing more potent drugs with lower toxicity. Here, we reveal structural and mechanistic differences between Pol γ and RT by studying NRTIs that have comparable efficacy on RT but significantly different affinities for Pol γ. We identified critical discriminator residues in Pol γ that are fully responsible for its differential response to emtricitabine. More importantly, the topological equivalent residue in RT is essential for activity, thus identifying this region as a hot-spot for inhibitor design.
MicroRNA-148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC
Authors: Joshi Pooja , Jeon Young-Jun , Laganà Alessandro , Middleton Justin , Secchiero Paola , Garofalo Michela , Croce Carlo M. 
Published: June 2015

Significance
Nonsmall cell lung cancer (NSCLC) is one of the deadliest cancers in the world. Although a very small subset of NSCLC patients respond to TNF-related apoptosis-inducing ligand (TRAIL), resistance remains a major hindrance to successful treatment. miRNAs are small noncoding RNAs of ∼24 nt that negatively regulate gene expression. Here, we show that miR-148a is significantly down-regulated in cells with acquired TRAIL resistance. Furthermore, we have determined that miR-148a can sensitize cells to TRAIL and inhibit tumorigenesis by targeting matrix metalloproteinase 15 and Rho-associated kinase 1 protein expression. Thus, miR-148a could be a promising prognostic and therapeutic tool in NSCLC treatment.