bluuebunny/crossref_metadata_2025 huggingface dataset:
The stereotypicality of symptomatic and pragmatic argumentation in consultations about palliative systemic treatment for advanced cancer
Authors: Akkermans Aranka , Snoeck Henkemans Francisca , Labrie Nanon , Henselmans Inge , van Laarhoven Hanneke
Published: October 2018

A recent line of argumentation research has focused on the examination of prototypical argumentative patterns – patterns that can
be theoretically expected in view of the type of standpoint defended, the institutional aim, and the conventions and constraints
of the context (Van Eemeren 2016: 13–15). This paper aims to add a new dimension to
both this line of research and research on health communication by determining whether the prototypical types of argumentation in
consultations about palliative systemic treatment for advanced cancer are stereotypical as well, that is, whether they are
dominant in a quantitative sense (van Eemeren 2016: 16). For this purpose, a valid and
reliable measurement instrument is developed and used in a content analysis of the transcripts of 49 consultations. On the basis
of the results of this analysis, it can be concluded that the use of symptomatic and pragmatic argumentation is stereotypical in
this type of consultations.
Donald Trump’s rhetoric
Authors: Kayam Orly
Published: October 2018

The paper explores the rhetorical strategies Donald Trump employed during the 2016 U.S. presidential primary campaign. The study shows that Trump aimed at garnering public support by defining himself as an anti-politician or anti-political establishment candidate. His rhetorical strategies were aimed at building the depiction of his character as a successful businessman who came from outside the political realm to save America and restore it to its former greatness. He denounced the traditional rules of politics, avoided calculated, logical and politically correct utterances, and modeled himself as the only candidate who was fit for the presidency. The analysis reveals Trump’s prominent rhetorical strategies, and shows how each one of them fulfilled what I refer to as the ultimate “Anti-Political Rhetorical Strategy”, from ananti-politically correctstrategy, which is by nature anti-political, to more common strategies such asnegativity,simplicity, repetitionandhyperbole.
Foreign language teachers’ intercultural competence and legitimacy during an international teaching experience
Authors: Bournot-Trites Monique , Zappa-Hollman Sandra , Spiliotopoulos Valia
Published: October 2018

Given the increase in international mobility opportunities for educators, analyzing how the experience of studying and teaching abroad benefits teachers is of utmost importance in a globalized educational system. UsingDeardorff’s (2009)model of intercultural competence (IC), this study explores how a group of recently graduated Canadian foreign language teachers benefitted from a four-month international teaching experience (ITE). The following questions guided this investigation: In which ways did the ITE contribute to the participants’ IC development? How did the ITE affect the participants’ professional identity and sense of legitimacy? Data were collected, triangulated, and interpreted using thematic content data analysis. This study provides illustrations of the participants’ IC development across all components on Deardorff’s IC model, showing that properly scaffolded ITEs afforded the participants opportunities to develop their IC. The findings also show that the ITE of living and teaching abroad positively impacted their professional identity and feeling of legitimacy.
Acquisition of formulaic sequences in a study abroad context
Authors: Quan Tracy
Published: October 2018

Research (e.g.,Wood, 2010a) suggests that study abroad (SA) and the use of formulaic language (FL), or sequences of words that tend to go together, aid L2 oral fluency. Nonetheless, there is conflicting evidence regarding whether quantity of L2 use abroad is a predictor of language outcomes. This article examines the acquisition of FL by US L2 learners of Spanish (n = 11) who studied abroad in Spain. The study measures the temporal fluency variables and the formula/run ratio of narrative retell tasks pre- and post-SA by L2 learners and native Spanish speakers. The findings indicate that regardless of program type and length, learners produce more FL post-SA, but they are still far from target-like usage. Moreover, participants’ mean length of run is directly related to the formula/run ratio. Lastly, an analysis of language use shows no direct relationship between L2 use abroad and oral fluency outcomes.
Interpreter-mediated investigative interviews with minors
Authors: Böser Ursula , LaRooy David
Published: October 2018

When information is elicited from children in a criminal context, both their ability and willingness to disclose is at stake. In
law, the communicative vulnerability of children is manifest in forensic protocols for interviewing children. These are designed
to retrieve information in a child-aware fashion, as well as to produce evidence with sufficient integrity to stand up under the
scrutiny of the criminal process. This article will consider some of the added challenges of interpreter-mediated interviews for
minors. Drawing on research into monolingual child interviewing, the article proposes how some of the interpreting related aspects
of this challenge may be addressed through the adaptation of elements of reflexive coordination in the widely used NICHD child
interviewing protocol. The authors call for the data-based testing of these adaptations and suggests that modifications of
institutional speech genres for bilingual use may be a component of mainstreaming public service interpreting.
ParGenes: a tool for massively parallel model selection and phylogenetic tree inference on thousands of genes
Authors: Morel Benoit , Kozlov Alexey M , Stamatakis Alexandros
Published: October 2018

Motivation

Coalescent- and reconciliation-based methods are now widely used to infer species phylogenies from genomic data. They typically use per-gene phylogenies as input, which requires conducting multiple individual tree inferences on a large set of multiple sequence alignments (MSAs). At present, no easy-to-use parallel tool for this task exists. Ad hoc scripts for this purpose do not only induce additional implementation overhead, but can also lead to poor resource utilization and long times-to-solution. We present ParGenes, a tool for simultaneously determining the best-fit model and inferring maximum likelihood (ML) phylogenies on thousands of independent MSAs using supercomputers.

Results

ParGenes executes common phylogenetic pipeline steps such as model-testing, ML inference(s), bootstrapping and computation of branch support values via a single parallel program invocation. We evaluated ParGenes by inferring > 20 000 phylogenetic gene trees with bootstrap support values from Ensembl Compara and VectorBase alignments in 28 h on a cluster with 1024 nodes.

Availability and implementation

GNU GPL at https://github.com/BenoitMorel/ParGenes.

Supplementary information

Supplementary material is available at Bioinformatics online.
PopLDdecay: a fast and effective tool for linkage disequilibrium decay analysis based on variant call format files
Authors: Zhang Chi , Dong Shan-Shan , Xu Jun-Yang , He Wei-Ming , Yang Tie-Lin
Published: October 2018

Motivation

Linkage disequilibrium (LD) decay is of great interest in population genetic studies. However, no tool is available now to do LD decay analysis from variant call format (VCF) files directly. In addition, generation of pair-wise LD measurements for whole genome SNPs usually resulting in large storage wasting files.

Results

We developed PopLDdecay, an open source software, for LD decay analysis from VCF files. It is fast and is able to handle large number of variants from sequencing data. It is also storage saving by avoiding exporting pair-wise results of LD measurements. Subgroup analyses are also supported.

Availability and implementation

PopLDdecay is freely available at https://github.com/BGI-shenzhen/PopLDdecay.
Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants
Authors: Graspeuntner S , Waschina S , Künzel S , Twisselmann N , Rausch T K , Cloppenborg-Schmidt K , Zimmermann J , Viemann D , Herting E , Göpel W , Baines J F , Kaleta C , Rupp J , Härtel C , Pagel J
Published: October 2018

Background

Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS.

Methods

In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics.

Results

We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease.

Conclusions

Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.
Declining Incident Dementia Rates Across Four Population-Based Birth Cohorts
Authors: Sullivan Kevin J , Dodge Hiroko H , Hughes Tiffany F , Chang Chung-Chou H , Zhu Xinmei , Liu Anran , Ganguli Mary
Published: October 2018

Background

Incidence rates of dementia appear to be declining in high-income countries according to several large epidemiological studies. We aimed to describe declining incident dementia rates across successive birth cohorts in a U.S. population-based sample and to explore the influences of sex and education on these trends.

Methods

We pooled data from two community-sampled prospective cohort studies with similar study aims and contiguous sampling regions: the Monongahela Valley Independent Elders Survey (1987–2001) and the Monongahela-Youghiogheny Healthy Aging Team (2006–Ongoing). We identified four decade-long birth cohorts spanning birth years 1902–1941. In an analysis sample of 3,010 participants (61% women, mean baseline age = 75.7 years, mean follow-up = 7.1 years), we identified 257 cases of incident dementia indicated by a Clinical Dementia Rating of 1.0 or higher. We used Poisson regression to model incident dementia rates by birth cohort, age, sex, education, and interactions of Sex × Cohort and Sex × Education. We further examined whether cohort effects varied by education, testing a Cohort × Education interaction and stratifying the models by education.

Results

Compared to the earliest birth cohort (1902–1911), each subsequent cohort had a significantly lower incident dementia rate (1912–1921: incidence rate ratio [IRR] = 0.655, 95% confidence interval [95% CI] = 0.477–0.899; 1922–1931: IRR = 0.387, 95% CI = 0.265–0.564; 1932–1941: IRR = 0.233, 95% CI = 0.121–0.449). We observed no significant interactions of either sex or education with birth cohort.

Conclusions

A decline in incident dementia rates was observed across successive birth cohorts independent of sex, education, and age.
Space astrometry of the very massive ∼150 M⊙ candidate runaway star VFTS682
Authors: Renzo M , de Mink S E , Lennon D J , Platais I , van der Marel R P , Laplace E , Bestenlehner J M , Evans C J , Hénault-Brunet V , Justham S , de Koter A , Langer N , Najarro F , Schneider F R N , Vink J S
Published: October 2018

How very massive stars form is still an open question in astrophysics. VFTS682 is among the most massive stars known, with an inferred initial mass of ≳$150\,\text{M}_\odot$. It is located in 30 Doradus at a projected distance of 29 pc from the central cluster R136. Its apparent isolation led to two hypotheses: either it formed in relative isolation or it was ejected dynamically from the cluster. We investigate the kinematics of VFTS682 as obtained by Gaia and Hubble Space Telescope astrometry. We derive a projected velocity relative to the cluster of $38\pm 17{\, \mathrm{km\ s^{-1}}}$ (1σ confidence interval). Although the error bars are substantial, two independent measures suggest that VFTS682 is a runaway ejected from the central cluster. This hypothesis is further supported by a variety of circumstantial clues. The central cluster is known to harbour other stars more massive than $150\, \text{M}_\odot$ of similar spectral type and recent astrometric studies on VFTS16 and VFTS72 provide direct evidence that the cluster can eject some of its most massive members, in agreement with theoretical predictions. If future data confirm the runaway nature, this would make VFTS682 the most massive runaway star known to date.
Emergence of Kaposi’s Sarcoma Herpesvirus-Associated Complications Following Corticosteroid Use in TB-IRIS
Authors: Manion Maura , Uldrick Thomas , Polizzotto Mark N , Sheikh Virginia , Roby Gregg , Lurain Kathryn , Metzger Dorinda , Mican JoAnn M , Pau Alice , Lisco Andrea , Laidlaw Elizabeth , Hammoud Dima A , Whitby Denise , Yarchoan Robert , Sereti Irini
Published: October 2018

Corticosteroid use was associated with development of Kaposi’s sarcoma or multicentric Castleman disease in 3 patients with mycobacterial immune reconstitution inflammatory syndrome (IRIS) treated with corticosteroids. Monitoring for development of Kaposi’s sarcoma and alternative treatment may be beneficial for patients with IRIS, especially in the presence of preexisting co-infection with Kaposi’s sarcoma–associated herpesvirus.
Clinical Validation of a Commercial LAMP Test for Ruling out Malaria in Returning Travelers: A Prospective Diagnostic Trial
Authors: Cheaveau James , Nguyen Hong , Chow Barbara , Marasinghe Dewdunee , Mohon Abu Naser , Yuan Hong , Viana Gisele , van Schalkwyk Donelly , Church Deirdre , Chan Wilson , Pillai Dylan R
Published: October 2018

The mainstay of malaria diagnosis relies on rapid diagnostic tests (RDTs) and microscopy, both of which lack analytical sensitivity. This leads to repeat testing to rule out malaria. A prospective diagnostic trial of the Meridian illumigene Malaria assay (loop-mediated isothermal amplification [LAMP]) was conducted comparing it with reference microscopy and RDTs (BinaxNOW Malaria) in returning travelers between June 2017 and January 2018. Returning travelers with signs and symptoms of malaria were enrolled in the study. RDTs, microscopy, and LAMP assays were performed simultaneously. A total of 298 patients (50.7% male; mean age, 32.5 years) were enrolled, most visiting friends and relatives (43.3%), presenting with fever (88.9%), not taking prophylaxis (82.9%), and treated as outpatients (84.1%). In the prospective arm (n = 348), LAMP had a sensitivity of 98.1% (95% confidence interval [CI], 90.0%–100%) and a specificity of 97.6% (95% CI, 95.2%–99.1%) vs microscopy. After discrepant resolution with real-time polymerase chain reaction, LAMP had a sensitivity of 100% (95% CI, 93.7%–100%) and a specificity of 100% (95% CI, 98.7%–100%) vs microscopy. After discrepant resolution, RDTs had a sensitivity of 83.3% (95% CI, 58.6%–96.4%) and a specificity of 96.2% (95% CI, 93.2%–98.1%) vs microscopy. When including retrospective specimens (n = 377), LAMP had a sensitivity of 98.8% (95% CI, 93.2%–100%) and a specificity of 97.6% (95% CI, 95.2%–99.1%) vs microscopy, and after discrepant resolution of this set, LAMP had a sensitivity of 100% (95% CI, 95.8%–100%) and a specificity of 100% (95% CI, 98.7%–100%). A cost-benefit analysis of reagents and labor suggests savings of up to USD$13 per specimen using a novel algorithm with LAMP screening.
Ulrich modules over Cohen–Macaulay local rings with minimal multiplicity
Authors: Kobayashi Toshinori , Takahashi Ryo
Published: October 2018

Let R be a Cohen–Macaulay local ring. In this paper, we study the structure of Ulrich R-modules mainly in the case where R has minimal multiplicity. We explore generation of Ulrich R-modules and clarify when the Ulrich R-modules are precisely the syzygies of maximal Cohen–Macaulay R-modules. We also investigate the structure of Ulrich R-modules as an exact category.
Left Ventricular Assist Devices: How Do We Define Success?
Authors: Anwer Lucman A. , Poddi Salvatore , Tchantchaleishvili Vakhtang , Daly Richard C. , Toeg Hadi , Strand Jacob J. , Stulak John M. , Maltais Simon
Published: October 2018

Despite the growing acceptance of left ventricular assist device (LVAD) therapy to improve survival and quality of life in heart failure (HF) patients, uncertainties persist regarding the definition of a successful implant. We sought to define an innovative approach to assess success and subsequently compare preoperative variables affecting outcomes. From January 2007 to 2015, 278 patients underwent LVAD implantation. Median age at implant was 62 years and 81% patients were males. Indication for support was bridge-to-transplantation in 36% patients and the etiology of HF was ischemic in 49% patients. Based on clinically relevant and accepted standards, we defined successful LVAD implant as someone who was alive or transplanted at 2 years, had two or less readmissions in the first year, had no major adverse events in the first year, and had a New York Heart Association class of ≤ II at 6 months. Follow-up was obtained for a median of 1.7 years for a total of 605 patient-years-of-support. Based on our criteria, 81/278 (29%) patients were defined as having a successful implant. Univariate predictors of LVAD failure included destination therapy indication (hazard ratio [HR] = 2.11 [1.24, 3.58]), ischemic cardiomyopathy (HR = 1.73 [1.02, 2.94]), and a higher left ventricular ejection fraction (HR = 1.54 [1.07, 2.22]). After multivariable analysis, only destination therapy indication (HR = 2.2 [1.28, 3.78]) was found to be independently predictive of success failure. Despite an overall trend toward improved outcomes on device therapy, our criteria classified only one-third of patients as successful. Continued improvements in adverse event profiles, appropriate patient selection, and optimal time of implantation, together hold the key to improve outcomes after LVAD therapy.
Oral midodrine is comparable to albumin infusion in cirrhotic patients with refractory ascites undergoing large-volume paracentesis: results of a pilot study
Authors: Yosry Ayman , Soliman Zeinab A. , Eletreby Rasha , Hamza Iman , Ismail Alaa , Elkady Mohammad A.
Published: October 2018

Background and aims

Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites compared with no treatment. Less costly treatment alternatives such as vasoconstrictors have been investigated, but the results are controversial. Midodrine, an oral α1-adrenergic agonist, increases effective circulating blood volume and renal perfusion by increasing systemic and splanchnic blood pressure. Our aim is to assess whether or not morbidity in terms of renal dysfunction, hyponatremia, systemic, or portal hemodynamics derangement or mortality differed in patients receiving albumin versus midodrine.

Patients and methods

Seventy-five patients with cirrhosis and refractory ascites were randomized to receive albumin infusion, oral midodrine for 2 days, or oral midodrine for 30 days after therapeutic large volume paracentesis (LVP). The primary endpoints were development of renal impairment or hyponatremia, change in systemic and portal hemodynamics, cost, and mortality in the short-term and long-term follow-up.

Results

No significant difference was found between groups in the development of renal impairment, hyponatremia, or mortality 6 and 30 days after LVP. A significant increase in 24-h urine sodium excretion was noted in the midodrine 30-day group. Renal perfusion improved significantly with the midodrine intake for 30 days only. The cost of midodrine therapy was significantly lower than albumin.

Conclusion

Midodrine is as effective as albumin in reducing morbidity and mortality among patients with refractory ascites undergoing LVP at a significantly lower cost. Long-duration midodrine intake can be more useful than shorter duration intake in terms of improvement of renal perfusion and sodium excretion.
Implications for Breast Cancer Restaging Based on the 8th Edition AJCC Staging Manual
Authors: Plichta Jennifer K. , Ren Yi , Thomas Samantha M. , Greenup Rachel A. , Fayanju Oluwadamilola M. , Rosenberger Laura H. , Hyslop Terry , Hwang E. Shelley
Published: October 2018

Objective:

We assessed the changes that have resulted from the latest breast cancer staging guidelines and the potential impact on prognosis.

Background:

Contemporary data suggest that combining anatomic staging and tumor biology yields a predictive synergy for determining breast cancer prognosis. This forms the basis for the American Joint Committee on Cancer's (AJCC) Staging Manual, 8th edition. We assessed the changes that have resulted from the new staging guidelines and the potential impact on prognosis.

Methods:

Women with stages I to III breast cancer from 2010 to 2014 in the National Cancer Data Base were pathologically staged according to the 7th and 8th editions of the AJCC Staging Manual. Patient characteristics and restaging outcomes were summarized. Unadjusted overall survival (OS) was estimated, and differences were assessed. Cox proportional-hazards models were utilized to estimate the adjusted association of stage with OS.

Results:

After restaging the 493,854 women identified, 6.8% were upstaged and 29.7% were downstaged. The stage changes varied by tumor histology, receptor status, tumor grade, and Oncotype DX scores (all P < 0.0001). Applying the 8th edition criteria yielded an incremental reduction in survival for each increase in stage, which was not consistently seen in the 7th edition. In a subgroup analysis based on hormone receptor (HR) status, those with stages II and III, and HR− disease had a worse OS than those with HR+ disease.

Conclusions:

Applying the 8th edition staging criteria resulted in a stage change for >35% of patients diagnosed with invasive breast cancer and refined OS estimates. Overall, the transition to the 8th edition is expected to better drive clinical care, treatment recommendations, and future research.
Alcohol Use Thresholds for Identifying Alcohol-related Problems Before and Following Roux-en-Y Gastric Bypass
Authors: White Gretchen E. , Courcoulas Anita P. , Richardson Gale A. , Mair Christina , King Wendy C.
Published: October 2018

Objective:

The aim of this study was to determine the sensitivity and specificity of potential thresholds of alcohol use for identifying alcohol-related problems in women post-Roux-en-Y gastric bypass (RYGB).

Background:

Despite evidence that RYGB alters alcohol pharmacokinetics and is associated with an increased risk for alcohol-related problems, the level of alcohol use that should prompt further screening for alcohol-related problems following RYGB is unclear.

Methods:

The Longitudinal Assessment of Bariatric Surgery-2 is a prospective cohort study. Before surgery and annually for ≤7 years following surgery, participants completed the 10-item Alcohol Use Disorder Identification Test (AUDIT), which assesses past-year frequency and quantity of alcohol, frequency of consuming ≥6 drinks, and alcohol-related problems (ie, symptoms of alcohol dependence and/or alcohol-related harm). The AUDIT-Consumption (AUDIT-C) score was determined from the first 3 AUDIT items.

Results:

Post-RYGB, 835 women reported current drinking at 1 or more annual assessment(s). Compared with higher frequency thresholds, drinking ≥2 times/month had the highest combined sensitivity (85.3%) and specificity (61.4%) for identifying alcohol-related problems. Compared with higher quantity thresholds, drinking ≥3 drinks/drinking day had the highest combined sensitivity (64.2%) and specificity (87.2%). An AUDIT-C score ≥3, versus other thresholds, had the highest combined sensitivity (76.4%) and specificity (81.6%).

Conclusion:

The sensitivity and specificity of these thresholds indicate assessment of alcohol consumption alone may be inadequate for identifying women at risk for alcohol-related problems post-RYGB. Additional screening tools for alcohol-related problems, which assess symptoms of alcohol-related problems, should be conducted in this population.
Classifying cold stress responses of inbred maize seedlings using RGB imaging
Authors: Enders Tara A. , St. Dennis Susan , Oakland Justin , Callen Steven T. , Gehan Malia A. , Miller Nathan D. , Spalding Edgar P. , Springer Nathan M. , Hirsch Cory D.
Published: October 2018

Increasing the tolerance of maize seedlings to low temperature episodes could mitigate the effects of increasing climate variability on yield. To aid progress toward this goal, we established a growth chamber-based system for subjecting seedlings of 40 maize inbred genotypes to a defined, temporary cold stress while collecting digital profile images over a 9-day time course. Image analysis performed with PlantCV software quantified shoot height, shoot area, 14 other morphological traits, and necrosis identified by color analysis. Hierarchical clustering of changes in growth rates of morphological traits and quantification of leaf necrosis over two time intervals resulted in three clusters of genotypes, which are characterized by unique responses to cold stress. For any given genotype, the set of traits with similar growth rates is unique. However, the patterns among traits are different between genotypes. Cold sensitivity was not correlated with the latitude where the inbred varieties were released suggesting potential further improvement for this trait. This work will serve as the basis for future experiments investigating the genetic basis of recovery to cold stress in maize seedlings.
Gini coefficients for measuring the distribution of sexually transmitted infections among individuals with different levels of sexual activity
Authors: Gsteiger Sandro , Low Nicola , Sonnenberg Pam , Mercer Catherine H , Althaus Christian L
Published: October 2018

Objectives

Gini coefficients have been used to describe the distribution of Chlamydia trachomatis (CT) infections among individuals with different levels of sexual activity. The objectives of this study were to investigate Gini coefficients for different sexually transmitted infections (STIs), and to determine how STI control interventions might affect the Gini coefficient over time.

Methods

We used population-based data for sexually experienced women from two British National Surveys of Sexual Attitudes and Lifestyles (Natsal-2: 1999-2001; Natsal-3: 2010-2012) to calculate Gini coefficients for CT, Mycoplasma genitalium (MG), and human papillomavirus (HPV) types 6, 11, 16 and 18. We applied bootstrap methods to assess uncertainty and to compare Gini coefficients for different STIs. We then used a mathematical model of STI transmission to study how control interventions affect Gini coefficients.

Results

Gini coefficients for CT and MG were 0.33 (95% confidence interval (CI): 0.18-0.49) and 0.16 (95% CI: 0.02-0.36), respectively. The relatively small coefficient for MG suggests a longer infectious duration compared with CT. The coefficients for HPV types 6, 11, 16 and 18 ranged from 0.15-0.38. During the decade between Natsal-2 and Natsal-3, the Gini coefficient for CT did not change. The transmission model shows that higher STI treatment rates are expected to reduce prevalence and increase the Gini coefficient of STIs. In contrast, increased condom use reduces STI prevalence but does not affect the Gini coefficient.

Conclusions

Gini coefficients for STIs can help us to understand the distribution of STIs in the population, according to level of sexual activity, and could be used to inform STI prevention and treatment strategies.

Key messages

The Gini coefficient can be used to describe the distribution of STIs in a population, according to different levels of sexual activity.

Gini coefficients for Chlamydia trachomatis (CT) and human papillomavirus (HPV) type 18 appear to be higher than for Mycoplasma genitalium and HPV 6, 11 and 16.

Mathematical modelling suggests that CT screening interventions should reduce prevalence and increase the Gini coefficient, whilst condom use reduces prevalence without affecting the Gini coefficient.

Changes in Gini coefficients over time could be used to assess the impact of STI prevention and treatment strategies.
Measures of neural similarity
Authors: Bobadilla-Suarez S. , Ahlheim C. , Mehrotra A. , Panos A. , Love B. C.
Published: October 2018

One fundamental question is what makes two brain states similar. For example, what makes the activity in visual cortex elicited from viewing a robin similar to a sparrow? One common assumption in fMRI analysis is that neural similarity is described by Pearson correlation. However, there are a host of other possibilities, including Minkowski and Mahalanobis measures, with each differing in its mathematical, theoretical, neural computational assumptions. Moreover, the operable measures may vary across brain regions and tasks. Here, we evaluated which of several competing similarity measures best captured neural similarity. Our technique uses a decoding approach to assess the information present in a brain region and the similarity measures that best correspond to the classifier’s confusion matrix are preferred. Across two published fMRI datasets, we found the preferred neural similarity measures were common across brain regions, but differed across tasks. Moreover, Pearson correlation was consistently surpassed by alternatives.
Attenuating the DNA damage response to double strand breaks restores function in models of CNS neurodegeneration
Authors: Tuxworth Richard I. , Taylor Matthew J. , Anduaga Ane Martin , Hussien-Ali Alaa , Chatzimatthaiou Sotiroula , Longland Joanne , Thompson Adam M. , Almutiri Sharif , Alifragis Pavlos , Kyriacou Charalambos P. , Kysela Boris , Ahmed Zubair
Published: October 2018

DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell cycle leading to senescence or apoptosis. Mature, non-dividing neurons may tolerate low levels of DNA damage, in which case muting the DNA damage response might be neuroprotective. Here, we show that attenuating the DNA damage response by targeting the meiotic recombination 11, Rad50, Nijmegen breakage syndrome 1 complex, which is involved in double strand break recognition, is neuroprotective in three neurodegeneration models in Drosophila and prevents Aβ1-42-induced loss of synapses in embryonic hippocampal neurons. Attenuating the DNA damage response after optic nerve injury is also neuroprotective to retinal ganglion cells and promotes dramatic regeneration of their neurites both in vitro and in vivo. Dorsal root ganglion neurons similarly regenerate when the DNA damage response is targeted in vitro and in vivo and this strategy also induces significant restoration of lost function after spinal cord injury. We conclude that muting the DNA damage response in the nervous system is neuroprotective in multiple neurological disorders. Our results point to new therapies to maintain or repair the nervous system.
Solving the riddle of the evolution of Shine-Dalgarno based translation in chloroplasts
Authors: Weiner Iddo , Shahar Noam , Marcu Pini , Yacoby Iftach , Tuller Tamir
Published: October 2018

The chloroplast, a photosynthetic organelle found in all plant and algae species, originates from an ancient event in which a cyanobacterium was engulfed by a larger eukaryote. Thus, modern chloroplasts still harbor a bacterial-like genome and carry out all stages of gene expression, including mRNA translation by a 70S ribosome. However, the Shine-Dalgarno model, which predominantly regulates translation initiation by base-pairing between the ribosomal RNA and the mRNA in model bacteria genera, was reported to have ambiguous effects on chloroplast gene expression. Here we show that while the Shine-Dalgarno motif is clearly conserved in proteobacterial mRNAs, its general absence from chloroplast mRNAs is observed in cyanobacteria as well, promoting the idea that the evolutionary process of reducing the centrality of the Shine-Dalgarno mechanism began well before plastid endosymbiosis. As plastid ribosomal RNA anti-Shine-Dalgarno elements are highly similar to their bacterial counterparts, these sites alone cannot explain the decline in plastid Shine-Dalgarno generality. However, by computational simulation we show that upstream point mutations modulate the local structure of ribosomal RNA in chloroplasts, creating significantly tighter structures around the anti-Shine-Dalgarno locus, which in-turn reduce the probability of ribosome binding via the Shine-Dalgarno mechanism. To validate our model, we expressed a mCherry gene harboring a Shine-Dalgarno motif in the Chlamydomonas reinhardtii chloroplast. We show that co-expressing it with a 16S ribosomal RNA, modified according to our model, significantly enhances its expression compared to co-expression with an endogenous 16S gene.

Significance statement

Chloroplasts are fascinating intracellular organelles which have evolved from an ancient cyanobacterium engulfed by a larger eukaryote. Surprisingly, the canonical mechanism regulating bacterial translation initiation – Shine-Dalgarno – has been shown to play a reduced role in chloroplasts. Here, we show that mutations upstream from the anti-Shine-Dalgarno element decrease the probability of spontaneous ribosome binding by modulating the secondary structure of the ribosomal RNA. These mutations constitute a regulatory step which acclimates the Shine-Dalgarno mechanism to the translational regulation regime of chloroplasts. Interestingly, we show that these chloroplast features occur in modern cyanobacteria as well, promoting the idea that they have evolved prior to endosymbiosis.
Harmonization of resting-state functional MRI data across multiple imaging sites via the separation of site differences into sampling bias and measurement bias
Authors: Yamashita Ayumu , Yahata Noriaki , Itahashi Takashi , Lisi Giuseppe , Yamada Takashi , Ichikawa Naho , Takamura Masahiro , Yoshihara Yujiro , Kunimatsu Akira , Okada Naohiro , Yamagata Hirotaka , Matsuo Koji , Hashimoto Ryuichiro , Okada Go , Sakai Yuki , Morimoto Jun , Narumoto Jin , Shimada Yasuhiro , Kasai Kiyoto , Kato Nobumasa , Takahashi Hidehiko , Okamoto Yasumasa , Tanaka Saori C , Kawato Mitsuo , Yamashita Okito , Imamizu Hiroshi
Published: October 2018

When collecting large neuroimaging data associated with psychiatric disorders, images must be acquired from multiple sites because of the limited capacity of a single site. However, site differences represent the greatest barrier when acquiring multi-site neuroimaging data. We utilized a traveling-subject dataset in conjunction with a multi-site, multi-disorder dataset to demonstrate that site differences are composed of biological sampling bias and engineering measurement bias. Effects on resting-state functional MRI connectivity because of both bias types were greater than or equal to those because of psychiatric disorders. Furthermore, our findings indicated that each site can sample only from among a subpopulation of participants. This result suggests that it is essential to collect large neuroimaging data from as many sites as possible to appropriately estimate the distribution of the grand population. Finally, we developed a novel harmonization method that removed only the measurement bias by using traveling-subject dataset and achieved the reduction of the measurement bias by 29% and the improvement of the signal to noise ratios by 40%.
Motile curved bacteria are Pareto-optimal
Authors: Schuech Rudi , Hoehfurtner Tatjana , Smith David , Humphries Stuart
Published: October 2018

Curved-rods are a ubiquitous bacterial phenotype, but the fundamental question of why they are shaped this way remains unanswered. Throughin silicoexperiments, we assessed freely swimming straight- and curved-rod bacteria of a wide diversity of equal-volume shapes parameterized by elongation and curvature, and predicted their performances in tasks likely to strongly influence overall fitness. Performance tradeoffs between these tasks lead to a variety of shapes that are Pareto-optimal, including coccoids, all straight rods, and a range of curvatures. Comparison with an extensive morphological survey of motile curved-rod bacteria indicates that the vast majority of species fall within the Pareto-optimal region of morphospace. This result is consistent with evolutionary tradeoffs between just three tasks: efficient swimming, chemotaxis, and low cell construction cost. We thus reveal the underlying selective pressures driving morphological diversity in a wide-spread component of microbial ecosystems.

Significance Statement

Bacteria exhibit a bewildering diversity of morphologies but despite their impact on nearly all aspects of life, they are frequently classified into a few general categories, usually just ‘spheres’ and ‘rods’. Curved-rod bacteria are one simple variation and are widespread, particularly in the ocean. However, why so many species have evolved this shape is unknown. We show that curvature can increase swimming efficiency, revealing a widely-applicable selective advantage. Furthermore, we show that the distribution of cell lengths and curvatures observed across bacteria in nature are predicted by evolutionary tradeoffs between three tasks influenced by shape: efficient swimming, the ability to detect chemical gradients, and reduced cost of cell construction. We therefore reveal shape as an important component of microbial fitness.
Unraveling Tumor-Immune Heterogeneity in Advanced Ovarian Cancer Uncovers Immunogenic Effect of Chemotherapy
Authors: Jiménez-Sánchez Alejandro , Cybulska Paulina , Lavigne Katherine , Walther Tyler , Nikolovski Ines , Mazaheri Yousef , Weigelt Britta , Chi Dennis S. , Park Kay J. , Hollmann Travis , Couturier Dominique-Laurent , Vargas Alberto , Brenton James D. , Sala Evis , Snyder Alexandra , Miller Martin L.
Published: October 2018

In metastatic cancer, the role of heterogeneity at the tumor-immune microenvironment, its molecular underpinnings and clinical relevance remain largely unexplored. To understand tumor-immune dynamics at baseline and upon chemotherapy treatment, we performed unbiased pathway and cell type-specific immunogenomics analysis of treatment-naive (38 samples from 8 patients) and paired chemotherapy treated (80 paired samples from 40 patients) high-grade serous ovarian cancer (HGSOC) samples. Whole transcriptome analysis and image-based quantification of T cells from treatment-naive tumors revealed ubiquitous variability in immune signaling and distinct immune microenvironments co-existing within the same individuals and within tumor deposits at diagnosis. To systematically explore cell type composition of the tumor microenvironment using bulk mRNA, we derived consensus immune and stromal cell gene signatures by intersecting state-of-the-art deconvolution methods, providing improved accuracy and sensitivity when compared to HGSOC immunostaining and leukocyte methylation data sets. Cell-type deconvolution and pathway analyses revealed that Myc and Wnt signaling associate with immune cell exclusion in untreated HGSOC. To evaluate the effect of chemotherapy on the intrinsic tumor-immune heterogeneity, we compared site-matched and site-unmatched tumors before and after neoadjuvant chemotherapy. Transcriptomic and T-cell receptor sequencing analyses showed that site-matched samples had increased cytotoxic immune activation and oligoclonal expansion of T cells after chemotherapy, which was not seen in site-unmatched samples where heterogeneity could not be accounted for. These results demonstrate that the tumor-immune interface in advanced HGSOC is intrinsically heterogeneous, and thus requires site-specific analysis to reliably unmask the impact of therapy on the tumor-immune microenvironment.
QuBiT: A quantitative tool for epithelial tubes reveals cell dynamics and unexpected patterns of organization during Drosophila tracheal morphogenesis
Authors: Yang Ran , Li Eric , Mani Madhav , Beitel Greg J.
Published: October 2018

Biological tubes are essential for animal survival, and their functions are critically dependent on tube shape. Analyzing the contributions of cell shape and organization to the morphogenesis of small tubes has been hampered by the limitations of existing programs in quantifying cell geometry on highly curved tubular surfaces and calculating tube-specific parameters. We therefore developed QuBiT (QuantitativeTool forBiologicalTubes) and used it to analyze morphogenesis during embryonic Drosophila tracheal (airway) development. We find that there are previously unknown anterior-to-posterior (A-P) gradients of cell orientation and aspect ratio, and that there is periodicity in the organization of cells in the main tube. Furthermore, cell intercalation during development dampens an A-P gradient of the number of the number of cells per cross-section of the tube, but these intercalation events do not change the patterns of cell connectivity. These unexpected findings demonstrate the importance of a computational tool for analyzing the morphogenesis of small diameter biological tubes.
Galectin-1 promotes the invasion of bladder cancer urothelia through their matrix milieu
Authors: Balakrishnan A. , Pally D , Gondkar K. , Naito S. , Sidransky D. , Chatterjee A. , Kumar P. , Bhat R.
Published: October 2018

The progression of carcinoma of the urinary bladder involves migration of cancer epithelia through their surrounding tissue matrix microenvironment. This was experimentally confirmed when a gender- and grade-diverse set of bladder cancer cell lines were cultured in pathomimetic three-dimensional laminin-rich environments. The high-grade cells, particularly female, formed multicellular invasive morphologies in 3D. In comparison, low- and intermediate-grade counterparts showed growth-restricted phenotypes. A proteomic approach combining mass spectrometry and bioinformatics analysis identified the estrogen-driven lactose-binding lectin Galectin-1 (GAL-1) as a putative candidate that could drive this invasion. Expression ofLGALS1, the gene encoding GAL-1 showed an association with tumor grade progression in bladder cell lines. Immunohisto- and cyto-chemical experiments suggested greater extracellular levels of GAL-1 in 3D cultures of high-grade bladder cells and cancer tissues. High levels of GAL-1 associated with increased proliferation- and adhesion- of bladder cancer cells when grown on laminin-rich matrices. Pharmacological inhibition and Gal-1 knockdown in high-grade female cells decreased their adhesion to, and viability on, laminin-rich substrata. Higher GAL-1 also correlated with reduced E-cadherin and increased N-cadherin levels in consonance with a mesenchymal-like phenotype that we observed in 3D culture. The inhibition of GAL-1 reversed the stellate invasive phenotype to a more growth-restricted one in high-grade cells embedded within both basement-membrane-like and stromal collagenous matrix scaffolds. Finally, inhibition of GAL-1 specifically altered cell surface sialic acids, suggesting the mechanism by which the levels of GAL-1 may underlie the aggression and poor prognosis of invasive bladder cancer, especially in women.
Lmx1b influences correct post-mitotic coding of mesodiencephalic dopaminergic neurons
Authors: Wever Iris , Barrientos Pablo Largo , Hoekstra Elisa J. , Smidt Marten P.
Published: October 2018

The Lim Homeobox transcription factor 1 beta (LMX1b) has been identified as one of the transcription factors important for the development of mesodiencephalic dopaminergic (mdDA) neurons. During early development, Lmx1b is essential for induction and maintenance of the Isthmic Organizer (IsO), and genetic ablation results in the disruption of inductive activity from the IsO and loss of properly differentiated mdDA neurons.

To study the downstream targets of Lmx1b without affecting the IsO, we generated a conditional model in which Lmx1b was selectively deleted in Pitx3 expressing cells from embryonic day (E)13 onward. Supporting previous data, no significant changes could be observed in general dopamine (DA) marks, like Th, Pitx3 and Vmat2 at E14.5. However, in depth analysis by means of RNA-sequencing revealed that Lmx1b is important for the expression level of survival factors En1 and En2 and for the repression of mdDA subset mark Ahd2 during (late) development. Interestingly, the regulation of Ahd2 by Lmx1b was found to be Pitx3 independent, since Pitx3 levels were not altered in Lmx1b conditional knock-outs (cKO) and Ahd2 expression was also up-regulated in Lmx1b/Pitx3 double mutants compared to Pitx3 mutants. Further analysis of Lmx1b cKOs showed that post-mitotic deletion of Lmx1b additional leads to a loss of TH+ cells at 3 months age both in the VTA and SNc. Remarkably, different cell types were affected in the SNc and the VTA. While TH+AHD2+ cells were lost the SNc, TH+AHD2- neurons were affected in the VTA, reflected by a loss of Cck expression, indicating that Lmx1b is important for the survival of a sub-group of mdDA neurons.