bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lucae's Springy Pressure Probe to Mobilize the Ossicular Chain: Rise and Fall of an Ingenious Instrument
Authors: Tange Rinze Anthony , Mudry Albert 
Published: January 2017

Objectives/Hypotheses:
In 1884, Johann Constantin August Lucae (1835–1911), a German otologist from Berlin, introduced a new “method to mechanically treat chronic troubles of the mobility of the hearing organ transmission apparatus.” It consisted in the use of a springy pressure probe to directly mobilize the handle of the malleus. The aim of this study is to trace the invention, clinical use, technological modifications, and ultimate extinction of this instrument.

Method:
Review of Lucae's publications, comments by his colleagues, and trade catalogues published between 1880 and 1940.

Results:
Lucae presented at least six different models of his springy pressure probe during his career. Some of his colleagues modified it. The success rate was much disputed, and the instrument died with Lucae.

Conclusion:
Lucae's spring pressure probe is another example of the ingenuity of man to try to find a solution when confronted with an unclear and unresolved otological problem.
Effect of threatening life experiences and adverse family relations in ulcerative colitis: analysis using structural equation modeling and comparison with Crohn’s disease
Authors: Slonim-Nevo Vered , Sarid Orly , Friger Michael , Schwartz Doron , Sergienko Ruslan , Pereg Avihu , Vardi Hillel , Singer Terri , Chernin Elena , Greenberg Dan , Odes Shmuel 
Published: January 2017

Background and aims
We published that threatening life experiences and adverse family relations impact Crohn’s disease (CD) adversely. In this study, we examine the influence of these stressors in ulcerative colitis (UC).

Patients and methods
Patients completed demography, economic status (ES), the Patient-Simple Clinical Colitis Activity Index (P-SCCAI), the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Short-Form Health Survey (SF-36), the Brief Symptom Inventory (BSI), the Family Assessment Device (FAD), and the List of Threatening Life Experiences (LTE). Analysis included multiple linear and quantile regressions and structural equation modeling, comparing CD.

Results
UC patients (N=148, age 47.55±16.04 years, 50.6% women) had scores [median (interquartile range)] as follows: SCAAI, 2 (0.3–4.8); FAD, 1.8 (1.3–2.2); LTE, 1.0 (0–2.0); SF-36 Physical Health, 49.4 (36.8–55.1); SF-36 Mental Health, 45 (33.6–54.5); Brief Symptom Inventory-Global Severity Index (GSI), 0.5 (0.2–1.0). SIBDQ was 49.76±14.91. There were significant positive associations for LTE and SCAAI (25, 50, 75% quantiles), FAD and SF-36 Mental Health, FAD and LTE with GSI (50, 75, 90% quantiles), and ES with SF-36 and SIBDQ. The negative associations were as follows: LTE with SF-36 Physical/Mental Health, SIBDQ with FAD and LTE, ES with GSI (all quantiles), and P-SCCAI (75, 90% quantiles). In structural equation modeling analysis, LTE impacted ES negatively and ES impacted GSI negatively; LTE impacted GSI positively and GSI impacted P-SCCAI positively. In a split model, ES had a greater effect on GSI in UC than CD, whereas other path magnitudes were similar.

Conclusion
Threatening life experiences, adverse family relations, and poor ES make UC patients less healthy both physically and mentally. The impact of ES is worse in UC than CD.
Lipoprotein(a): new insights from modern genomics
Authors: Afshar Mehdi , Thanassoulis George 
Published: January 2017

Purpose of review
Lipoprotein(a) [Lp(a)] is the strongest independent genetic risk factor for both myocardial infarction and aortic stenosis. It has also been associated with other forms of atherosclerotic cardiovascular disease (CVD) including ischemic stroke. Its levels are genetically determined and remain fairly stable throughout life. Elevated Lp(a), above 50 mg/dl, affects one in five individuals worldwide.

Recent findings
Herein, we review the recent epidemiologic and genetic evidence supporting the causal role of Lp(a) in CVD, highlight recommendations made by European and Canadian guidelines regarding Lp(a) and summarize the rapidly evolving field of Lp(a)-lowering therapies including antisense therapies and Proprotein Convertase Subtilisin/Kexin Type 9 inhibitors.

Summary
With novel therapies on the horizon, Lp(a) is poised to gain significant clinical relevance and its lowering could have a significant impact on the burden of CVD.

Video abstract

http://links.lww.com/COL/A14
Variation in Transfusion Requirements Among Children With Thalassemia on Regular Transfusion Programs: Which Formula Closely Predicts the Actual Requirements?
Authors: Cornell Nikki , Eisenhut Michael , Ramprakash Stalin 
Published: January 2017

Background:
Various different formulae are used to calculate blood transfusion volumes in thalassemia. Using the right formula will avoid iron overload and complications of undertransfusion.

Observations:
Five years of transfusion data in 11 children with thalassemia showed that no single formula-calculated transfusion volumes accurately. The formula used in the United Kingdom with a hematocrit of the transfused blood of 0.6: (0.4×body weight×desired raise in hemoglobin [g/L]) yielded a volume closest to empirically determined requirements on average. Transfusion factors ranging from 0.3 to 0.48 were calculated as necessary to achieve the required volume for the individual patient.

Conclusions:
To meet transfusion requirements, individualization of formulas by establishment of the transfusion factor for each patient is helpful.
Iron Overload in the Liver of 2 Children: Nonalcoholic Steatohepatitis and Juvenile Hemochromatosis
Authors: Ünlüsoy Aksu Aysel , Caleffi Angela , Pietrangelo Antonello , Sari Sinan , Eğritaş Gürkan Ödül , Demirtaş Zeliha , Yilmaz Güldal , Dalgiç Buket 
Published: January 2017

Background:
Iron overload disorders are hereditary hemochromatosis and secondary etiologies other than hereditary hemochromatosis. We describe 2 boys presenting with iron overload. Juvenile hemochromatosis and nonalcoholic steatohepatitis (NASH) related iron overload are the genetic and secondary causes, respectively.

Observations:
Both patients benefited from phlebotomy even if they had different etiologies.

Conclusions:
In childhood, the diagnosis of iron overload syndromes is crucial because they do not confront us with obvious symptoms and findings. Early initiation of a phlebotomy program can prevent mortality. NASH might lead to iron overload and iron overload might aggravate the clinical course of NASH.
The Symptom Experience of Patients With Advanced Pancreatic Cancer
Authors: Tang Chia-Chun , Von Ah Diane , Fulton Janet S. 
Published: January 2017

Background:
Pancreatic cancer is a devastating disease with limited treatment options. More than 80% of pancreatic cancers are diagnosed in advanced stages and often have debilitating symptoms, making symptom management paramount, yet the symptom experience of patients with advanced pancreatic cancer (APC) is not well understood.

Objective:
The purpose of this integrative review is to synthesize the current evidence regarding the symptom experience of patients with APC.

Method:
An integrative literature review was conducted to identify the patient symptom experience in studies published from 2005 to 2015.

Results:
Sixteen studies met the inclusion criteria. All studies used a quantitative approach; 44% were quasi-experimental, 31% were descriptive, and 25% were correlational. Physical symptoms, especially pain, were the primary focus in most studies. Fatigue, loss of appetite, and impaired sense of well-being were prevalent and reported by patients to be of high intensity. Few studies examined psychological symptoms in patients with APC, although anxiety and depression were noted.

Conclusion:
Findings suggest that physical and psychological symptoms are prevalent, some with high intensity. Preselection of symptom inventories limits our ability to fully understand the symptom experience of patients with APC. Future qualitative work is needed to provide a more in-depth understanding of symptoms, especially symptom quality and distress level, from patients’ perspectives. More studies are needed to explore psychological symptoms and the interaction of physical and psychological symptoms.

Implications for Practice:
Findings help healthcare givers to better understand the symptom experience of their APC patients.
Brief Report: Association Between Menopause and Unprotected Sex in High-Risk HIV-Positive Women in Mombasa, Kenya
Authors: Goyette Marielle S. , Wilson Kate S. , Deya Ruth , Masese Linnet N. , Shafi Juma , Richardson Barbra A. , Mandaliya Kishorchandra , Jaoko Walter , McClelland R. Scott 
Published: January 2017

Objective:
Many HIV-positive women now live well beyond menopause. Postmenopausal women are no longer at risk for pregnancy, and some studies suggest that they may use condoms less often than premenopausal women. This study tests the hypothesis that, in HIV-positive women who report trading sex for cash or in-kind payment, unprotected sex is more common at postmenopausal visits compared with premenopausal visits.

Design:
Prospective cohort study of HIV-positive women ≥16 years old in Mombasa, Kenya.

Methods:
At enrollment and monthly follow-up visits, participants completed a standardized interview. Study clinicians collected genital samples at enrollment and quarterly visits. Menopausal status was assessed annually. The primary outcome of unprotected sex was determined by detection of prostate specific antigen (PSA) in vaginal secretions.

Results:
This study followed 404 HIV-positive women who contributed 2753 quarterly examination visits. Detection of PSA was less frequent at postmenopausal visits compared with premenopausal visits [55/554, 10.5% versus 394/2199, 17.9%; relative risk (RR) 0.58, 95% confidence interval (CI): 0.39 to 0.87]. Adjusting for age diminished the association between menopause and PSA detection (adjusted RR 0.73, 95% CI: 0.47 to 1.14). At visits where women reported sexual activity in the past week, they reported similar rates of 100% condom use at postmenopausal and premenopausal visits (RR 0.99, 95% CI: 0.87 to 1.13).

Conclusions:
In this population of high-risk HIV-positive Kenyan women, postmenopausal status was not associated with a greater risk of unprotected sex. The relationship between menopause and unprotected sex is likely context specific and may differ with varying risk groups, regions, and levels of exposure to sexual health education.
Granulocytic Myeloid–Derived Suppressor Cells Increased in Early Phases of Primary HIV Infection Depending on TRAIL Plasma Level
Authors: Tumino Nicola , Bilotta Maria T. , Pinnetti Carmela , Ammassari Adriana , Antinori Andrea , Turchi Federica , Agrati Chiara , Casetti Rita , Bordoni Veronica , Cimini Eleonora , Abbate Isabella , Capobianchi Maria R. , Martini Federico , Sacchi Alessandra 
Published: January 2017

Background:
It has been demonstrated that myeloid-derived suppressor cells (MDSC) are expanded in HIV-1–infected individuals and correlated with disease progression. The phase of HIV infection during which MDSC expansion occurs, and the mechanisms that regulate this expansion remain to be established. In this study, we evaluated the frequency of MDSC in patients during primary HIV infection (PHI) and factors involved in MDSC control.

Methods:
Patients with PHI and chronic HIV infection (CHI) were enrolled. PHI staging was performed according to Fiebig classification, and circulating MDSC frequency and function were evaluated by flow cytometry. Cytokine levels were evaluated by Luminex technology.

Results:
We found that granulocytic MDSC (Gr-MDSC) frequency was higher in patients with PHI compared with healthy donors, but lower than that in patients with CHI. Interestingly, Gr-MDSC expansion was observed in the early phases of HIV infection (Fiebig II/III), but it was not associated with HIV viral load and CD4 T-cell count. Interestingly, in PHI, Gr-MDSC frequency was inversely correlated with plasmatic level of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), although a direct correlation was observed in CHI. Furthermore, lower level of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) was observed in PHI compared with that in CHI. In vitro experiments demonstrated that, differently from CHI, recombinant TRAIL–induced apoptosis of Gr-MDSC from PHI, an effect that can be abrogated by GM-CSF.

Conclusion:
We found that Gr-MDSC are expanded early during PHI and may be regulated by TRAIL and GM-CSF levels. These findings shed light on the fine mechanisms regulating the immune system during HIV infection and open new perspectives for immune-based strategies.
Glimma: interactive graphics for gene expression analysis
Authors: Su Shian , Law Charity W. , Ah-Cann Casey , Asselin-Labat Marie-Liesse , Blewitt Marnie E. , Ritchie Matthew E. 
Published: January 2017

AbstractMotivationSummary graphics for RNA-sequencing and microarray gene expression analyses may contain upwards of tens of thousands of points. Details about certain genes or samples of interest are easily obscured in such dense summary displays. Incorporating interactivity into summary plots would enable additional information to be displayed on demand and facilitate intuitive data exploration.ResultsThe open-sourceGlimmapackage creates interactive graphics for exploring gene expression analysis with a few simple R commands. It extends popular plots found in thelimmapackage, such as multi-dimensional scaling plots and mean-difference plots, to allow individual data points to be queried and additional annotation information to be displayed upon hovering or selecting particular points. It also offers links between plots so that more information can be revealed on demand.Glimmais widely applicable, supporting data analyses from a number of well established Bioconductor workflows(limma, edgeRandDESeq2)and uses D3/JavaScript to produce HTML pages with interactive displays that enable more effective data exploration by end-users. Results fromGlimmacan be easily shared between bioinformaticians and biologists, enhancing reporting capabilities while maintaining reproducibility.Availability and ImplementationTheGlimmaR package is available fromhttp://bioconductor.org/packages/devel/bioc/html/Glimma.html.
Evidence for Transcriptome-wide RNA Editing AmongSus scrofaPRE-1 SINE Elements
Authors: Funkhouser Scott A. , Steibel Juan P. , Bates Ronald O. , Raney Nancy E. , Schenk Darius , Ernst Catherine W. 
Published: January 2017

AbstractBackgroundRNA editing by ADAR (adenosine deaminase acting on RNA) proteins is a form of transcriptional regulation that is widespread among humans and other primates. Based on high-throughput scans used to identify putative RNA editing sites, ADAR appears to catalyze a substantial number of adenosine to inosine transitions within repetitive regions of the primate transcriptome, thereby dramatically enhancing genetic variation beyond what is encoded in the genome.ResultsHere, we demonstrate the editing potential of the pig transcriptome by utilizing DNA and RNA sequence data from the same pig. We identified a total of 8550 mismatches between DNA and RNA sequences across three tissues, with 75% of these exhibiting an A-to-G (DNA to RNA) discrepancy, indicative of a canonical ADAR-catalyzed RNA editing event. When we consider only mismatches within repetitive regions of the genome, the A-to-G percentage increases to 94%, with the majority of these located within the swine specific SINE retrotransposon PRE-1. We also observe evidence of A-to-G editing within coding regions that were previously verified in primates.ConclusionsThus, our high-throughput evidence suggests that pervasive RNA editing by ADAR can exist outside of the primate lineage to dramatically enhance genetic variation in pigs.
Allee dynamics: growth, extinction and range expansion
Authors: Bose I , Pal M , Karmakar C 
Published: January 2017

AbstractIn population biology, the Allee dynamics refer to negative growth rates below a critical population density. In this Letter, we study a reaction-diffusion (RD) model of population growth and dispersion in one dimension, which incorporates the Allee effect in both the growth and mortality rates. In the absence of diffusion, the bifurcation diagram displays regions of both finite population density and zero population density, i.e., extinction. The early signatures of the transition to extinction at a bifurcation point are computed in the presence of additive noise. For the full RD model, the existence of travelling wave solutions of the population density is demonstrated. The parameter regimes in which the travelling wave advances (range expansion) and retreats are identified. In the weak Allee regime, the transition from the pushed to the pulled wave is shown as a function of the mortality rate constant. The results obtained are in agreement with the recent experimental observations on budding yeast populations.
Egocentric and Allocentric Representations in Auditory Cortex
Authors: Town Stephen M. , Brimijoin W. Owen , Bizley Jennifer K. 
Published: January 2017

AbstractA key function of the brain is to provide a stable representation of an object’s location in the world. In hearing, sound azimuth and elevation are encoded by neurons throughout the auditory system and auditory cortex is necessary for sound localization. However the coordinate frame in which neurons represent sound space remains undefined: classical spatial receptive fields in head-fixed subjects can be explained either by sensitivity to sound source location relative to the head (egocentric) or relative to the world (allocentric encoding). This coordinate frame ambiguity can be resolved by studying freely moving subjects and here we recorded spatial receptive fields in auditory cortex freely moving ferrets. We found two distinct populations of neurons: While the majority (∼80%) of spatially tuned neurons represented sound source location relative to the head, we provide novel evidence for a group of neurons in which space was represented in an allocentric world-centered coordinate frame. We also use our ability to measure spatial tuning in moving subjects to explore the influence of sound source distance and speed of head movements on auditory cortical activity and spatial tuning. Modulation depth of spatial tuning increased with distance for egocentric but not allocentric units, whereas for both populations modulation was stronger at faster movement speeds. Our findings argue that auditory cortex is involved in the representation of both sound source location relative to ourselves and sound location in the world independent of our own position.
An overexpressedQallele leads to increased spike density and improved processing quality
Authors: Xu Bin-Jie , Chen Qing , Zheng Ting , Jiang Yun-Feng , Qiao Yuan-Yuan , Guo Zhen-Ru , Cao Yong-Li , Wang Yan , Zhang Ya-Zhou , Zong Lu-Juan , Zhu Jing , Liu Cai-Hong , Jiang Qian-Tao , Lan Xiu-Jin , Ma Jian , Wang Ji-Rui , Zheng You-Liang , Wei Yu-Ming , Qi Peng-Fei 
Published: January 2017

AbstractSpike density and processing quality are important traits during the evolution of wheat, which is controlled by multiple gene loci. The associated gene loci have been heavily studied with slow progress. A common wheat mutant with extremely compact spikes and good processing quality was isolated. The gene (Qc1) responsible for the mutant phenotype was mapped and cloned, and the cellular mechanism for the mutant phenotype was investigated.Qc1originated from a point mutation that interferes with the miR172-directed cleavage of theQgene, leading to its overexpression.Qc1reduces the longitudinal cell size of rachises, resulting in an increased spike density.Qc1increases the number of vascular bundles, which suggests a higher efficiency in the transportation of assimilates in the spikes of the mutant than in the WT. This could account for the improved processing quality. The effects ofQc1on spike density and wheat processing quality were confirmed by the identification of nine common wheat mutants having four differentQcalleles. These results deepen our understanding of the key role ofQgene, one of the most important domestication gene for wheat, and provide new insights for the potential application ofQcallele in wheat breeding.
OrthoFiller: utilising data from multiple species to improve the completeness of genome annotations
Authors: Dunne Michael P. , Kelly Steven 
Published: January 2017

AbstractBackroundComplete and accurate annotation of sequenced genomes is of paramount importance to their utility and analysis. Differences in gene prediction pipelines mean that genome sequences for a species can differ considerably in the quality and quantity of their predicted genes. Furthermore, genes that are present in genome sequences sometimes fail to be detected by computational gene prediction methods. Erroneously unannotated genes can lead to oversights and inaccurate assertions in biological investigations, especially for smaller-scale genome projects which rely heavily on computational prediction.ResultsHere we present OrthoFiller, a tool designed to address the problem of finding and adding such missing genes to genome annotations. OrthoFiller leverages information from multiple related species to identify those genes whose existence can be verified through comparison with known gene families, but which have not been predicted. By simulating missing gene annotations in real sequence datasets from both plants and fungi we demonstrate the accuracy and utility of OrthoFiller for finding missing genes and improving genome annotation. Furthermore, we show that applying OrthoFiller to existing “complete” genome annotations can identify and correct substantial numbers of erroneously missing genes in these two sets of species.ConclusionsWe show that significant improvements in the completeness of genome annotations can be made by leveraging information from multiple species.
Epistatic networks jointly influence phenotypes related to metabolic disease and gene expression in Diversity Outbred mice
Authors: Tyler Anna L. , Ji Bo , Gatti Daniel M. , Munger Steven C. , Churchill Gary A. , Svenson Karen L. , Carter Gregory W. 
Published: January 2017

ABSTRACTGenetic studies of multidimensional phenotypes can potentially link genetic variation, gene expression, and physiological data to create multi-scale models of complex traits. Multi-parent populations provide a resource for developing methods to understand these relationships. In this study, we simultaneously modeled body composition, serum biomarkers, and liver transcript abundances from 474 Diversity Outbred mice. This population contained both sexes and two dietary cohorts. Using weighted gene co-expression network analysis (WGCNA), we summarized transcript data into functional modules which we then used as summary phenotypes representing enriched biological processes. These module phenotypes were jointly analyzed with body composition and serum biomarkers in a combined analysis of pleiotropy and epistasis (CAPE), which inferred networks of epistatic interactions between quantitative trait loci that affect one or more traits. This network frequently mapped interactions between alleles of different ancestries, providing evidence of both genetic synergy and redundancy between haplotypes. Furthermore, a number of loci interacted with sex and diet to yield sex-specific genetic effects. We were also able to identify alleles that potentially protect individuals from the effects of a high-fat diet. Although the epistatic interactions explained small amounts of trait variance, the combination of directional interactions, allelic specificity, and high genomic resolution provided context to generate hypotheses for the roles of specific genes in complex traits. Our approach moves beyond the cataloging of single loci to infer genetic networks that map genetic etiology by simultaneously modeling all phenotypes.