bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic Review: Components of a Comprehensive Geriatric Assessment in Inflammatory Bowel Disease—A Potentially Promising but Often Neglected Risk Stratification
Authors: Asscher Vera E R , Lee-Kong Felicia V Y , Kort Esther D , van Deudekom Floor J , Mooijaart Simon P , Maljaars P W Jeroen
Published: April 2019

Background

The population of older patients with inflammatory bowel disease [IBD] is increasing. Patient age does not fully account for poor outcomes and its clinical utility for risk stratification is limited. Comprehensive geriatric assessment [CGA], comprising a somatic, functional, mental, and social assessment or frailty, could be a predictor tool.

Aims

To systematically review literature on the kind of components of a CGA being used in adult IBD patients and the association of these components with adverse health outcomes.

Methods

An electronic literature search was performed on January 16, 2018, using PubMed, Embase, Web of Science, the Cochrane Library, CENTRAL, Emcare, and PsycINFO. Longitudinal studies relating somatic, functional, mental, and social assessment or frailty to adverse health outcomes during follow-up in IBD patients were included. The Newcastle-Ottawa scale was used to assess individual study quality.

Results

Of 4080 identified citations, 27 studies were included, reporting 169 associations. Median sample size was 108 patients (interquartile range [IQR] 60–704). No studies performed subgroup analyses on older patients, and the highest mean age reported was 52.7 years. Somatic and functional assessments were used in three studies, mental in 24, and social in five. No study assessed cognitive status, functional performance, or frailty. In 62 associations [36.7%], components of a CGA were significantly associated with adverse health outcome measurements.

Conclusions

Components of a CGA were associated with adverse health outcomes in IBD patients, but older patients were under-represented. More studies among older patients with IBD are warranted to further establish the clinical impact of a CGA.
Labour Market Returns to Graduates’ International Experience: Exploring Cross-Country Variation in Europe
Authors: Jacob Marita , Kühhirt Michael , Rodrigues Margarida
Published: April 2019

The potential benefits of increased international experience abound, ranging from enriching cultural understanding to an improvement of language skills and intercultural competence. At the same time, empirical evidence is mixed, particularly with regards to how well international experience translates into individual returns on the labour market. This article examines the association between studying abroad and early labour market outcomes in a comparative perspective aiming to shed light on why labour market returns differ across countries. We expect labour market returns to vary with specific country characteristics such as demand for international experience and competition among graduates at labour market entry. In our empirical analyses, we use data from 13 European countries that provide information on graduates’ early labour market outcomes. We find a large variation in the impact of studying abroad on both wages and attaining a higher service class position. Generally, the labour market returns to international experience are larger in countries in Eastern and Southern Europe with poorer university quality, higher graduate unemployment, and fewer students abroad.
Close cousins in protection: the evolution of two norms
Authors: Rhoads Emily Paddon , Welsh Jennifer
Published: April 2019

The Protection of Civilians (PoC) in peacekeeping and the Responsibility to Protect (R2P) populations from atrocity crimes are two norms that emerged at the turn of the new millennium with the aim of protecting vulnerable peoples from mass violence and/or systematic and widespread violations of human rights. To date, most scholars have analysed the discourses over the status, strength and robustness of both norms separately. And yet, the distinction between the two has at times been exceptionally fine. In this article, we analyse the constitutive relationship between PoC and R2P, and the impact of discursive and behavioural contestation on their joint evolution within the UN system and state practice over three phases (1999–2005; 2006–10; 2011–18). In so doing, we contribute to the International Relations literature on norms by illuminating ideational interplay in the dynamics of norm evolution and contestation. More specifically, we illustrate how actors may seek to strengthen support for one norm, or dimension of a norm, by contrasting it or linking it with another. Our analysis also reveals that while the two norms of R2P and PoC were initially debated and implemented through different institutional paths and policy frameworks, discursive and behavioural contestation has in more recent years brought them closer together in one important respect. The meaning ascribed to both norms—by representatives of states and institutions such as the United Nations—has become more state-centric, with an emphasis on building and strengthening the capacity of national authorities to protect populations. This meaning contrasts with the more cosmopolitan origins of R2P and PoC, and arguably limits possibilities for the external enforcement of both norms through any form of international authority that stands above or outside sovereign states. This article forms part of the special section of the May 2019 issue of International Affairs on ‘The dynamics of dissent’, guest-edited by Anette Stimmer and Lea Wisken.
Increased Healthcare Utilization by Patients With Inflammatory Bowel Disease Covered by Medicaid at a Tertiary Care Center
Authors: Axelrad Jordan E , Sharma Rajani , Laszkowska Monika , Packey Christopher , Rosenberg Richard , Lebwohl Benjamin
Published: April 2019

Background

Low socioeconomic status has been linked with numerous poor health outcomes, but data are limited regarding the impact of insurance status on inflammatory bowel disease (IBD) outcomes. We aimed to characterize utilization of healthcare resources by IBD patients based on health insurance status, using Medicaid enrollment as a proxy for low socioeconomic status.

Methods

We retrospectively identified adult patients with IBD engaged in a colorectal cancer surveillance colonoscopy program from July 2007 to June 2017. Our primary outcomes included emergency department (ED) visits, inpatient hospitalizations, biologic infusions, and steroid exposure, stratified by insurance status. We compared patients who had ever been enrolled in Medicaid with all other patients.

Results

Of 947 patients with IBD, 221 (23%) had been enrolled in Medicaid. Compared with patients with other insurance types, patients with Medicaid had higher rates of ever being admitted to the hospital (77.6% vs 42.6%, P < 0.0001) or visiting the ED (90.5% vs 38.4%, P < 0.0001). When adjusted for sex, age at first colonoscopy, and ethnicity, patients with Medicaid had a higher rate of inpatient hospitalizations (Rate ratio [RR] 2.95; 95% CI 2.59–3.36) and ED visits (RR 4.24; 95% CI 3.82–4.70) compared to patients with other insurance. Patients with Medicaid had significantly higher prevalence of requiring steroids (62.4% vs 37.7%, P < 0.0001), and after adjusting for the same factors, the odds of requiring steroids in the patients with Medicaid was increased (OR 3.77; 95% CI 2.53–5.62).

Conclusions

Medicaid insurance was a significant predictor of IBD care and outcomes. Patients with Medicaid may have less engagement in IBD care and seek emergency care more often.
Early-life exposure to ambient fine particulate air pollution and infant mortality: pooled evidence from 43 low- and middle-income countries
Authors: Goyal Nihit , Karra Mahesh , Canning David
Published: April 2019

Background

Many low- and middle-income countries are experiencing high and increasing exposure to ambient fine particulate air pollution (PM2.5). The effect of PM2.5 on infant and child mortality is usually modelled using concentration response curves extrapolated from studies conducted in settings with low ambient air pollution, which may not capture its full effect.

Methods

We pool data on more than half a million births from 69 nationally representative Demographic and Health Surveys that were conducted in 43 low- and middle-income countries between 1998 and 2014, and we calculate early-life exposure (exposure in utero and post partum) to ambient PM2.5 using high-resolution calibrated satellite data matched to the child’s place of residence. We estimate the association between the log of early-life PM2.5 exposure, both overall and separated by type, and the odds of neonatal and infant mortality, adjusting for child-level, parent-level and household-level characteristics.

Results

We find little evidence that early-life exposure to overall PM2.5 is associated with higher odds of mortality relative to low exposure to PM2.5. However, about half of PM2.5 is naturally occurring dust and sea-salt whereas half is from other sources, comprising mainly carbon-based compounds, which are mostly due to human activity. We find a very strong association between exposure to carbonaceous PM2.5 and infant mortality, particularly neonatal mortality, i.e. mortality in the first 28 days after birth. We estimate that, at the mean level of exposure in the sample to carbonaceous PM2.5—10.9 µg/m3—the odds of neonatal mortality are over 50% higher than in the absence of pollution.

Conclusion

Our results suggest that the current World Health Organization guideline of limiting the overall ambient PM2.5 level to less than 10 µg/m³ should be augmented with a lower limit for harmful carbonaceous PM2.5.
Antiviral-resistant cytomegalovirus infections in solid organ transplantation in the Netherlands
Authors: Van Leer Buter Coretta C , de Voogd Danielle W K , Blokzijl Hans , de Joode Anoek A E , Berger Stefan P , Verschuuren Erik A M , Niesters Hubert G M
Published: April 2019

Objectives

Antiviral resistance in cytomegalovirus (CMV) may result from mutations in the molecular targets of antiviral agents. The aim of this study was to investigate both the prevalence of resistance-associated mutations and the factors associated with antiviral resistance in solid organ transplant (SOT) patients with repeated high CMV loads during antiviral treatment.

Methods

SOT patients were selected retrospectively, based on CMV loads of >30000 IU/mL at least twice in a period during which treatment was given. Patient samples were tested for antiviral resistance by Sanger sequencing the UL97 and UL54 genes of CMV, which code for the viral kinase and polymerase. Factors predisposing to and resulting from the development of antiviral resistance mutations were analysed.

Results

Multiple samples from 113 SOT patients were tested, showing resistance-associated mutations in 25 patients (22%). A further 20 (18%) patients showed mutations that were not known to be associated with antiviral resistance. Several factors were associated with development of resistance-associated mutations in UL97 as well as UL54, including human leucocyte antigen (HLA) mismatch, which occurred more frequently in the group of patients with resistance mutations. High-level resistance mutations were most frequently seen in UL97.

Conclusions

This study shows that by selecting patients solely on the basis of virological response to treatment, more patients with antiviral resistance mutations are identified. In this study we confirm findings by other groups that primary infections are associated with resistance development. Moreover, we show that HLA mismatch is associated with the development of antiviral resistance, which suggests a role for host immunity in the development of resistance.
Urban Frostbite: Strategies for Limb Salvage
Authors: Shenaq Deana S , Beederman Maureen , O’Connor Annemarie , Teele Megan , Robinson Marla R , Gottlieb Lawrence J
Published: April 2019

Under ideal circumstances, severely frostbitten extremities are rapidly rewarmed and treated with thrombolytic therapy within 6 to 24 hours. In an “inner city,” urban environment, most patients who suffer frostbite injuries present in a delayed fashion, sustain repeated injuries further complicated by psychological issues or intoxication, and are rarely ideal candidates for thrombolytic therapy within the prescribed timeframe. We describe our experience with the treatment of urban frostbite injuries. A retrospective review of patients with cold injuries sustained between November 2013 and March 2014 treated at a verified burn center in an urban setting was performed. Fifty-three patients were treated (42 males, 11 females). Average patient age was 41.8 years (range 2–84 years). No patients met criteria for thrombolytic therapy due to multiple freeze-thaw cycles or presentation greater than 24 hours after rewarming. Deep frostbite was seen in 10 patients. Of these patients, nine underwent debridement, resulting in partial limb amputations at levels guided by Tri-phasic technetium (Tc-99m) bone scans. Wound closure and limb-length salvage was then achieved by: free flap coverage (n = 2), local flaps (n = 8), split-thickness skin grafting (n = 22), and secondary intention healing (n = 6). While tissue plasminogen activator has been successful in reducing the need for digital amputation following frostbite injuries, in our experience, this treatment modality is not applicable to the urban patient population who often present late and after cycles of reinjury. Therefore, our approach focused on salvaging limb length with durable coverage, as the injuries were unable to be reversed.
Insulin Resistance and Cancer-Specific and All-Cause Mortality in Postmenopausal Women: The Women’s Health Initiative
Authors: Pan Kathy , Nelson Rebecca A , Wactawski-Wende Jean , Lee Delphine J , Manson JoAnn E , Aragaki Aaron K , Mortimer Joanne E , Phillips Lawrence S , Rohan Thomas , Ho Gloria Y F , Saquib Nazmus , Shadyab Aladdin H , Nassir Rami , Rhee Jinnie J , Hurria Arti , Chlebowski Rowan T
Published: April 2019

Background

Insulin resistance has been proposed as a mediator of the increased cancer incidence and mortality associated with obesity. However, prior studies included limited cancer deaths and had inconsistent findings. Therefore, we evaluated insulin resistance and cancer-specific and all-cause mortality in postmenopausal women participating in the Women’s Health Initiative (WHI).

Methods

Eligible were a subsample of 22 837 WHI participants aged 50–79 years enrolled at 40 US clinical centers from 1993 to 1998 who had baseline fasting glucose and insulin levels. Baseline insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Cancers were verified by central medical record review and deaths verified by medical record and death certificate review enhanced by National Death Index queries. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific and all-cause mortality. All statistical tests were two-sided.

Results

During a median of 18.9 years of follow-up, 1820 cancer deaths and 7415 total deaths occurred. Higher HOMA-IR quartile was associated with higher cancer-specific mortality (Q4 vs Q1, HR = 1.26, 95% CI = 1.09 to 1.47; Ptrend = .003) and all-cause mortality (Q4 vs Q1, HR = 1.63, 95% CI = 1.51 to 1.76; Ptrend < .001). A sensitivity analysis for diabetes status did not change findings. Among women with body mass index less than 25 kg/m2, higher HOMA-IR quartile was associated with higher cancer mortality (Fine and Gray, P = .004).

Conclusions

High insulin resistance, as measured by HOMA-IR, identifies postmenopausal women at higher risk for cancer-specific and all-cause mortality who could potentially benefit from early intervention.
Technical and methodological foundations of digital indexing of medieval and early modern court books
Authors: Borek Arkadiusz , Związek Tomasz , Słomski Michał , Gochna Michał , Myrda Grzegorz , Słoń Marek
Published: April 2019

Ever since the beginnings of the modern historiography, the court books have posed a challenge for editors in Poland, both due to their number and variety. They constitute one of the richest sources enabling a variety of historical research. The publication of the sources’ content can be shared owing to new approaches stemming from constant development of IT tools and their application in the humanities. The solution proposed in our article is a digital indexing based on a relational database enabling access to the sources’ scans. The characterization of the method is preceded by a description of the theoretical foundations of the presented method. The assumed principals are implemented by the use of a dedicated to this project online INDXR application which functionalities is thoroughly described. Using the INDXR application, the data acquired from the sources are collected and stored in the database which structure is also illustrated along with its theoretical foundations. The database is established in order to better reflect the typical elements comprising the court books as well as to store the acquired information. The issues stemming from the process of indexing the court books, such as categorizing of the entries, their spatial context, and the problem of how to describe the persons appearing in the manuscript are also presented.
Dating medieval texts by classification with flexible time intervals
Authors: Toner Gregory , Han Xiwu
Published: April 2019

Determining the date of writing is a practical problem often encountered in the study of ancient and medieval texts. The problem is compounded by differences in genre, register and style, but in particular by our frequent dependence on much later copies of lost originals. This article examines how a method of classification with flexible time intervals has been developed for a corpus of medieval Irish annals (c.700–c.1600). It is shown that the method can deal successfully with an unparsed, complex corpus containing contaminated data. A method of extending the model from good quality, uncontaminated data to more complex texts is also demonstrated by identifying temporal characteristics and typical entries in the high-quality source.
Toward a virtual research environment for the spatial humanities: heiMAP
Authors: Pfeiffer Michelle , Eller Dirk , Carré Cyril
Published: April 2019

This article describes the context and design of heiMAP, a virtual research environment (VRE) currently under development at Heidelberg University. heiMAP is aimed at users from a wide spectrum of disciplines within the Humanities, allowing them to collaborate and share data using space as their common frame of reference by way of a collaborative web platform. We first set out the challenges that spatial research in the Humanities poses for such a working platform, including but not limited to reflecting the often heterogeneous and imperfect nature of Humanities data in a Geographic Information System (GIS). Next, we give an overview of some existing VREs and detail where heiMAP fits into this context and show what makes it a worthwhile addition to the existing research landscape. Finally, we revisit the initially outlined challenges and showcase heiMAP’s approaches to address them.
Logics based on linear orders of contaminating values
Authors: Ciuni Roberto , Macaulay Ferguson Thomas , Szmuc Damian
Published: April 2019

A wide family of many-valued logics—for instance, those based on the weak Kleene algebra—includes a non-classical truth-value that is ‘contaminating’ in the sense that whenever the value is assigned to a formula $\varphi $, any complex formula in which $\varphi $ appears is assigned that value as well. In such systems, the contaminating value enjoys a wide range of interpretations, suggesting scenarios in which more than one of these interpretations are called for. This calls for an evaluation of systems with multiple contaminating values. In this paper, we consider the countably infinite family of multiple-conclusion consequence relations in which classical logic is enriched with one or more contaminating values whose behaviour is determined by a linear ordering between them. We consider some motivations and applications for such systems and provide general characterizations for all consequence relations in this family. Finally, we provide sequent calculi for a pair of four-valued logics including two linearly ordered contaminating values before defining two-sided sequent calculi corresponding to each of the infinite family of many-valued logics studied in this paper.
‘Invisible existence’: Perspectives of forced migrants’ living within Zimbabwe
Authors: Benhura Abigail R , Naidu Maheshvari
Published: April 2019

Involuntary human mobility within and outside national borders continue to raise connotations of these migrants being dispossessed of more than their physical shelter. In 2005, the Zimbabwean government demolished hundreds of buildings, which it had condemned as illegal through a program code named Operation Murambatsvina. Likewise, for the people dislodged by this program, the article contends that internal displacement did not only lead to loss of shelter but also denied them their inherent dignity and rendered them ‘invisible’. In turn, this heightened their susceptibility to deprivations that are synonymous with forced migration. Therefore, this article aims to explore the forced migrants’ perspectives of the effects of displacement on their lives vis-à-vis the above contentions. It mainly seeks to address the displaced people’s perceptions and socially constructed meanings of internal displacement. This qualitative article is based on empirical data gathered from Hopley and Caledonia settlements in Zimbabwe. The essay uses purposive sampling and snowballing to capture the people living in displacement. The article’s findings indicate that displacement births adaptive preferences which are used to counter the negative effects experienced due to the conditions in their settlements. Despite the conspicuousness of Hopley and Caledonia residents’ type of shelter, the article also establishes that internal displacement has ironically increased their invisibility both within and outside Zimbabwe. The article determines that their ‘invisibility’ is manifested through waning interest by institutions mandated to safeguard their assistance and protection, which exposes them to heightened vulnerabilities.
The first 62 AGN observed with SDSS-IV MaNGA – IV. Gas excitation and star formation rate distributions
Authors: Nascimento Janaína C do , Storchi-Bergmann Thaisa , Mallmann Nícolas D , Riffel Rogério , Ilha Gabriele S , Riffel Rogemar A , Rembold Sandro B , Schimoia Jáderson , da Costa Luiz Nicolaci , Maia Marcio A G , Machado Alice D
Published: April 2019

We present maps of the ionized gas flux distributions, excitation, star formation rate (SFR), surface mass density ΣH+, and obtain total values of SFR and ionized gas masses M for 62 active galactic nuclei (AGN) observed with SDSS-IV MaNGA and compare them with those of a control sample of 112 non-active galaxies. The most luminous AGN – with $L(\rm {[O\,{\small III}]}\lambda 5007) \ge 3.8\times 10^{40}\, \mbox{erg}\, \mbox{s}^{-1}$, and those hosted by earlier type galaxies are dominated by Seyfert excitation within 0.2 effective radius Re from the nucleus, surrounded by LINER excitation or transition regions, while the less luminous and hosted by later-type galaxies show equally frequent LINER and Seyfert excitation within $0.2\, R_\mathrm{ e}$. The extent R of the region ionized by the AGN follows the relation $R\propto \, L(\rm {[O\,{\small III}]})^{0.5}$ – as in the case of the broad-line region. The SFR distribution over the region ionized by hot stars is similar for AGN and controls, while the integrated SFR – in the range 10−3–10 M⊙ yr−1 is also similar for the late-type subsample, but higher in the AGN for 75 per cent of the early-type subsample. We thus conclude that there is no signature of AGN quenching star formation in the body of the galaxy in our sample. We also find that 66 per cent of the AGN have higher ionized gas masses M than the controls – in the range 105–3 × 107 M⊙ – while 75 per cent of the AGN have higher ΣH+ within $0.2\, R_\mathrm{ e}$ than the control galaxies.
DeepStreaks: identifying fast-moving objects in the Zwicky Transient Facility data with deep learning
Authors: Duev Dmitry A , Mahabal Ashish , Ye Quanzhi , Tirumala Kushal , Belicki Justin , Dekany Richard , Frederick Sara , Graham Matthew J , Laher Russ R , Masci Frank J , Prince Thomas A , Riddle Reed , Rosnet Philippe , Soumagnac Maayane T
Published: April 2019

We present DeepStreaks, a convolutional-neural-network, deep-learning system designed to efficiently identify streaking fast-moving near-Earth objects that are detected in the data of the Zwicky Transient Facility (ZTF), a wide-field, time-domain survey using a dedicated 47 deg2 camera attached to the Samuel Oschin 48-inch Telescope at the Palomar Observatory in California, United States. The system demonstrates a 96–98 per cent true positive rate, depending on the night, while keeping the false positive rate below 1 per cent. The sensitivity of DeepStreaks is quantified by the performance on the test data sets as well as using known near-Earth objects observed by ZTF. The system is deployed and adapted for usage within the ZTF Solar system framework and has significantly reduced human involvement in the streak identification process, from several hours to typically under 10 min per day.
The 3XMM/SDSS Stripe 82 Galaxy Cluster Survey – II. X-ray and optical properties of the cluster sample
Authors: Takey Ali , Durret Florence , Márquez Isabel , Ellien Amael , Molham Mona , Plat Adèle
Published: April 2019

We present X-ray and optical properties of the optically confirmed galaxy cluster sample from the 3XMM/SDSS Stripe 82 cluster survey. The sample includes 54 galaxy clusters in the redshift range of 0.05–1.2, with a median redshift of 0.36. We first present the X-ray temperature and luminosity measurements that are used to investigate the X-ray luminosity–temperature relation. The slope and intercept of the relation are consistent with those published in the literature. Then, we investigate the optical properties of the cluster galaxies including their morphological analysis and the galaxy luminosity functions (GLFs). The morphological content of cluster galaxies is investigated as a function of cluster mass and distance from the cluster centre. No strong variation of the fraction of early- and late-type galaxies with cluster mass is observed. The fraction of early-type galaxies as a function of cluster radius varies as expected. The individual GLFs of red sequence galaxies were studied in the five ugriz bands for 48 clusters. The GLFs were then stacked in three mass bins and two redshift bins. Twenty clusters of the present sample are studied for the first time in X-rays, and all are studied for the first time in the optical range. Altogether, our sample appears to have X-ray and optical properties typical of ‘average’ cluster properties.
Additive Traits Lead to Feeding Advantage and Reproductive Isolation, Promoting Homoploid Hybrid Speciation
Authors: Masello Juan F , Quillfeldt Petra , Sandoval-Castellanos Edson , Alderman Rachael , Calderón Luciano , Cherel Yves , Cole Theresa L , Cuthbert Richard J , Marin Manuel , Massaro Melanie , Navarro Joan , Phillips Richard A , Ryan Peter G , Shepherd Lara D , Suazo Cristián G , Weimerskirch Henri , Moodley Yoshan
Published: April 2019

Speciation through homoploid hybridization (HHS) is considered extremely rare in animals. This is mainly because the establishment of reproductive isolation as a product of hybridization is uncommon. Additionally, many traits are underpinned by polygeny and/or incomplete dominance, where the hybrid phenotype is an additive blend of parental characteristics. Phenotypically intermediate hybrids are usually at a fitness disadvantage compared with parental species and tend to vanish through backcrossing with parental population(s). It is therefore unknown whether the additive nature of hybrid traits in itself could lead successfully to HHS. Using a multi-marker genetic data set and a meta-analysis of diet and morphology, we investigated a potential case of HHS in the prions (Pachyptila spp.), seabirds distinguished by their bills, prey choice, and timing of breeding. Using approximate Bayesian computation, we show that the medium-billed Salvin’s prion (Pachyptila salvini) could be a hybrid between the narrow-billed Antarctic prion (Pachyptila desolata) and broad-billed prion (Pachyptila vittata). Remarkably, P. salvini’s intermediate bill width has given it a feeding advantage with respect to the other Pachyptila species, allowing it to consume a broader range of prey, potentially increasing its fitness. Available metadata showed that P. salvini is also intermediate in breeding phenology and, with no overlap in breeding times, it is effectively reproductively isolated from either parental species through allochrony. These results provide evidence for a case of HHS in nature, and show for the first time that additivity of divergent parental traits alone can lead directly to increased hybrid fitness and reproductive isolation.
Non-canonical translation initiation in yeast generates a cryptic pool of mitochondrial proteins
Authors: Monteuuis Geoffray , Miścicka Anna , Świrski Michał , Zenad Lounis , Niemitalo Olli , Wrobel Lidia , Alam Jahangir , Chacinska Agnieszka , Kastaniotis Alexander J , Kufel Joanna
Published: April 2019

Utilization of non-AUG alternative translation start sites is most common in bacteria and viruses, but it has been also reported in other organisms. This phenomenon increases proteome complexity by allowing expression of multiple protein isoforms from a single gene. In Saccharomyces cerevisiae, a few described cases concern proteins that are translated from upstream near-cognate start codons as N-terminally extended variants that localize to mitochondria. Using bioinformatics tools, we provide compelling evidence that in yeast the potential for producing alternative protein isoforms by non-AUG translation initiation is much more prevalent than previously anticipated and may apply to as many as a few thousand proteins. Several hundreds of candidates are predicted to gain a mitochondrial targeting signal (MTS), generating an unrecognized pool of mitochondrial proteins. We confirmed mitochondrial localization of a subset of proteins previously not identified as mitochondrial, whose standard forms do not carry an MTS. Our data highlight the potential of non-canonical translation initiation in expanding the capacity of the mitochondrial proteome and possibly also other cellular features.
Symptoms associated with inflammatory arthritis are common in the primary care population: results from the joint symptoms survey
Authors: Hider Samantha L , Muller Sara , Helliwell Toby , Prior James A , Scott Ian , Lawton Sarah A , Zwierska Irena , van Schaardenburg Dirkjan , van der Helm-van Mil Annette , Raza Karim , Mallen Christian D
Published: April 2019

Objectives

To describe the prevalence of self-reported inflammatory joint symptoms, such as joint pain, stiffness and swelling, in UK primary care patients consulting for both musculoskeletal (MSK) and non-musculoskeletal (non-MSK) complaints.

Methods

A joint symptoms questionnaire survey was sent to 10 161 individuals, of whom 5050 had consulted for MSK problems. These were matched by age, gender and general practice to non-MSK consulters. Participants provided data on relevant symptoms such as joint pain, stiffness and swelling. The prevalence of these symptoms, their severity and impact were compared between MSK and non-MSK consulters.

Results

A total of 4549 adults responded to the survey (adjusted response 45.8%) of whom 52.3% consulted for a MSK problem. The mean (s.d.) age was 61.6 (14.8) years and 58.9% were female. Persistent (on at least half of the days in the last month) inflammatory symptoms were common even in non-MSK consulters, with 42% reporting joint pain, 36% reporting joint stiffness and 18% reporting joint swelling. This is in comparison with 62% reporting joint pain, 50% stiffness and 24% swelling among MSK consulters.

Conclusions

Although symptoms such as persistent joint pain, swelling and stiffness are predictive of inflammatory arthritis, large numbers of people consulting primary care for non-MSK reasons report these symptoms when asked by questionnaire. This compounds the challenges of diagnosing inflammatory arthritis in a non-specialist setting where new approaches are needed to ensure accurate, early diagnosis, facilitating a treat-to-target approach.
Sugarcane Mosaic Distribution, Incidence, Increase, and Spatial Pattern in Louisiana
Authors: Rice J. L. , Hoy J. W. , Grisham M. P.
Published: April 2019

Sugarcane mosaic is a historically important disease in Louisiana currently caused by sorghum mosaic virus (SrMV). Successful breeding for resistance reduced the disease to low incidence in commercial cultivars. However, mosaic was detected in experimental clone evaluations at multiple locations, leading to uncertainty concerning the current distribution and incidence in the state. Field surveys were conducted from 2016 to 2018 in breeding program yield trials and experimental clone seed cane increase fields. Mosaic symptomatic plants were observed in a newly released cultivar, HoCP 09-804, in three of five production areas, with incidences ranging from 0 to 10%. Mosaic also was observed in nine additional experimental clones. Single leaf samples were tested for SrMV using reverse transcription PCR. All symptomatic samples and a low percentage (0.3%) of asymptomatic samples tested positive for SrMV, confirming that it continues to be the causal species. Runs analysis detected aggregation of infected plants within at least 70% of rows in 94% of surveyed fields. The spatial pattern and geographical distribution of disease incidence suggested that infected seed cane was the source of the disease. Surveys conducted in the same fields of HoCP 09-804 through two subsequent crops detected disease incidence increases in some fields and decreases in the others in first ratoon, but observed incidence was lower compared with plant cane in all fields in second ratoon. The results indicated that disease increase owing to aphid transmission did not occur under the prevailing conditions.
Effects of Cultivar Susceptibility, Fruit Maturity, Leaf Age, Fungal Isolate, and Temperature on Infection of Almond by Colletotrichum spp.
Authors: López-Moral Ana , Agustí-Brisach Carlos , Lovera María , Luque Francisca , Roca Luis F. , Arquero Octavio , Trapero Antonio
Published: April 2019

Almond anthracnose, caused by Colletotrichum spp., is a reemerging disease in Spain. To date, little research has been conducted on the factors affecting this disease development. In this study, the effects of cultivar, fruit wounding and maturity, leaf age, fungal isolate, and temperature on almond infection by Colletrotrichum spp. were evaluated under laboratory-controlled conditions. Inoculations were performed using conidial suspensions of Colletrotrichum acutatum or C. godetiae. Disease severity was higher in wounded than in unwounded fruit. Based on observations of inoculated fruit, Ferraduel and Nonpareil were the most tolerant cultivars, while Tarraco and Penta were the most susceptible cultivars. Four categories of susceptibility (highly susceptible, susceptible, moderately susceptible, and resistant) were distinguished by using the cluster analysis statistical approach. Differences in susceptibility between young and old leaves were observed, but Nonpareil was consistently the most tolerant cultivar. Significant differences in virulence between C. acutatum and C. godetiae were observed in inoculated fruit, with C. acutatum being the most virulent. Disease development was more severe when inoculations were performed at the fruitlet stage or when the fruit were incubated at approximately 25°C, with respect to other maturity stages and temperatures evaluated. Natural fruit infections were also assessed. Cultivar susceptibility data were compared between laboratory tests and field observations. A significant positive linear correlation was obtained between the susceptibility of the common cultivars evaluated under the two conditions.
Serum separator tube method for matrix-assisted laser desorption/ionization time-of-flight analysis
Authors: Freimann Sarit , Shapira Maanit , Athamna Abed
Published: April 2019

Background. Without appropriate treatment, bloodstream infections have a high mortality rate. Quicker identification of the microbial pathogen allows the clinician to develop an initial strategy of antimicrobial therapy. Sample preparation protocols for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS; Bruker Daltonics for Microflex LT spectrometer) technology were evaluated in an attempt to identify pathogens directly from positive blood culture bottles and thus shorten the time to identify them. This application requires preparatory processing because blood culture bottles contain undesirable proteins. This study aimed to evaluate two methods for microbial preparation for identification by MALDI-ToF MS.

Methods. This study evaluated two methods for microbial preparation from 200 positive blood culture samples, half prepared by the differential centrifugation method and half with the serum separator tube method for identification by MALDI-ToF MS. Both methods were compared to conventional methods such as VITEK II and ChromAgar culture plates.

Results. All Gram-negative bacteria tested were identified correctly by MALDI-ToF MS compared to conventional methods, regardless of the preparation method. However, more Gram-positive bacteria were identified when the serum separator tube method was used (83.3%) compared with the differential centrifugation method (65.3  %). Moreover, the serum separator tube protocol requires 12–15 min, while the differential centrifugation protocol requires 30–45 min.

Conclusions. Sample preparation using the serum separator tube method is easy to perform, fast and reliable for accurate microbial identification by MALDI-ToF MS technology.
Application of next generation sequencing for the elucidation of genes and pathways involved in the host response to bovine respiratory syncytial virus
Authors: Johnston Dayle , Earley Bernadette , McCabe Matthew , Blackshields Gordon , Lemon Ken , Duffy Catherine , McMenamy Michael , Cosby Sara Louise , Kim Jaewoo , Taylor Jerry , Waters Sinead
Published: April 2019

High rates of calf mortality in the first 12 months of life, results in significant economic losses in Europe and the USA. Bovine respiratory disease (BRD) accounts for the largest proportion of calf mortality. There is a paucity of literature concerning the host response to BRD. In a controlled challenge study in artificially reared dairy calves [155 (S.D. 14) kg], the influence of the host response to bovine respiratory syncytial virus (BRSV) was examined. At AFBI Holstein-Friesian calves were either challenged with BRSV (n=12) or mock challenged with phosphate buffer saline (n=6). Calves were euthanised on day 7 post-challenge. Bronchial lymph nodes were collected and flash-frozen at −80 °C. RNA was extracted and sent to the University of Missouri’s DNA Core Facility for RNA-Seq library preparation and sequencing. Sequenced reads were adapter trimmed, quality assessed using FastQC and aligned to the bovine genome (UMD 3.1) using STAR. Differential gene expression analysis was performed using EdgeR, and pathway and gene ontology analyses were carried out using g:Profiler and Ingenuity Pathway Analysis (IPA). There was a clear separation between BRSV challenged and control calves based on log2 fold gene expression changes, despite an observed mild clinical manifestation of the disease. There were 934 differentially expressed genes (DEG) (P<0.05, FDR<0.1, fold change >2) between the BRSV challenged and control calves. Over-represented pathways and gene ontology terms among the DEG were associated with immune responses and included: GO:0051607 defense response to virus, the KEGG pathway Influenza A and the IPA pathway Interferon Signaling.
Isolation and characterization of Clostridioides difficile spores from contaminated single-used surgical gowns
Authors: Waterfield Shannon , Hutt Lee , Burky Robert , Joshi Lovleen Tina
Published: April 2019

Clostridium difficile is the primary cause of antibiotic associated diarrhoea globally. In the UK there has been a decline in the prevalence of C. difficile due to implementation of surveillance and infection control procedures. At Rideout Hospital, USA, however, there is a high incidence of C. difficile infection, which has been partly attributed to poor infection control measures. Other factors include the ability of spores to adhere to fomites such as surgical gowns. It has been demonstrated that the single-use polypropylene surgical gowns used at Rideout can ‘trap’ hydrophobic epidemic spores of C. difficile within the fibres, which can then be transferred to stainless steel surfaces and hospital floor vinyl; even with use of appropriate sporicides such as sodium dichloroisocyanurate. This study sought to establish the strains of C. difficile present on the gowns and thus inside the nosocomial environment. Contaminated gowns from Rideout were cultured for 5 days anaerobically in Brain –Heart Infusion broth supplemented with 0.1 % Sodium taurocholate. Broth culture was screened for the presence of C. difficile using CCFA media, C. DIFF QUIK CHEK COMPLETE®, 16 s-23s RNA analysis and toxin PCR. Once isolated, strains were sequenced and tested for biocide susceptibility to in-use concentrations of Sodium dichloroisocyanurate. In total 23 suspected C. difficile samples were isolated from the gowns; of which 8 were confirmed. Sporicide susceptibility testing is ongoing. Once infective strains have been identified measures can be taken to enforce appropriate infection control procedures in order to limit the prevalence of spores and reduce infection rates.
Risk of mitochondrial deletions is affected by the global secondary structure of the human mitochondrial genome
Authors: Shamanskiy Victor , Mikhailova Alina A. , Ushakova Kristina , Mikhailova Alina G. , Oreshkov Sergei , Knorre Dmitry , Tretiakov Evgenii O. , Ri Natalia , Overdevest Jonathan B. , Lukowski Samuel W. , Gostimskaya Irina , Yurov Valerian , Liou Chia-Wei , Lin Tsu-Kung , Kunz Wolfram S. , Reymond Alexandre , Mazunin Ilya , Bazykin Georgii A. , Gunbin Konstantin , Fellay Jacques , Tanaka Masashi , Khrapko Konstantin , Popadin Konstantin
Published: April 2019

Aging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Deletions in mitochondrial DNA (mtDNA) are often flanked by direct nucleotide repeats, but this alone does not fully explain their distribution. Here, we hypothesized that the close proximity of direct repeats on single-stranded DNA might play a role in the formation of deletions. By analyzing human mtDNA deletions in the major arc of mtDNA, which is single-stranded during replication and is characterized by a high number of deletions, we found a non-uniform distribution with a "hot spot" where one deletion breakpoint occurred within the region of 6-9kb and another within 13-16kb of the mtDNA. This distribution was not explained by the presence of direct repeats, suggesting that other factors, such as the spatial proximity of these two regions can be the cause. In silico analyses revealed that the single-stranded major arc may be organized as a large-scale hairpin-like loop with a center close to 11kb and contacting regions between 6-9 kb and 13-16 kb, which would explain the high deletion activity in this contact zone. The direct repeats located within the contact zone, such as the well-known common repeat with a first arm at 8470-8482 bp and a second arm at 13447-13459 bp, are three times more likely to cause deletions compared to direct repeats located outside of the contact zone. An analysis of age- and disease-associated deletions demonstrated that the contact zone plays a crucial role in explaining the age-associated deletions, emphasizing its importance in the rate of healthy aging. Overall, we provide topological insights into the mechanism of age-associated deletion formation in human mtDNA, which could be used to predict somatic deletion burden and maximum lifespan in different human haplogroups and mammalian species.
High accuracy DNA sequencing on a small, scalable platform via electrical detection of single base incorporations
Authors: Esfandyarpour Hesaam , Parizi Kosar B. , Barmi Meysam R. , Rategh Hamid , Wang Lisen , Paliwal Saurabh , Golnabi HamidReza , Kenney Paul , Reel Richard , Lee Frank , Gomes Xavier , Stern Seth , Ramachandran Ashok , Sankar Subra , Doomson Solomon , Ung Rick , Jouzi Maryam , Babu Ramya Akula Suresh , Nabi Ali , Castillo Nestor , Lei Raymond , Fallahi Mohammad , LoPrete Eric , Kemper Austin , Bagchi Srijeeta , Tarbox Robert , Choudhary Pallavi , Nezamfar Hooman , Hsie Linda , Monier Nicolas , Clark Tyson A. , Spence Eric , Yang Fei , Bronson Benjamin , Sutton Gina , Schweidenback Caterina , Lundy John , Ho An , Tangprasertchai Narin , Thomas Anthony , Baxter Brian , Shastry Shankar , Barua Anooshka , Chen Yongzhi , Hashemzadeh Hamid , Shtern David , Kim Eugene , Thomas Christopher , Tanti Patrice , Mazouchi Ali , Tumurbaatar Erden , Nieboer Jordan , Knopf Christopher , Tram Hien , Sood Vipal , Stingley Sam , Cahill Megan , Roy Sid , Sha Ky , Dong Bin , Witney Frank R. , Davis Ronald W.
Published: April 2019

High throughput DNA sequencing technologies have undergone tremendous development over the past decade. Although optical detection-based sequencing has constituted the majority of data output, it requires a large capital investment and aggregation of samples to achieve optimal cost per sample. We have developed a novel electronic detection-based platform capable of accurately detecting single base incorporations. The GenapSys technology with its electronic detection modality allows the system to be compact, accessible, and affordable. We demonstrate the performance of the system by sequencing several different microbial genomes with varying GC content. The platform is capable of generating up to 2 Gb of high-quality nucleic acid sequence in a single run. We routinely generate sequence data that exceeds 99% raw accuracy with read lengths of up to 175 bp. Average quality scores remain above Q30 (99.9% raw sequencing accuracy) beyond 150 bp, with more than 85% of total bases at or above Q30. The utility of the platform is highlighted by targeted sequencing of the human genome. We show high concordance of SNP detection on the human NA12878 HapMap cell line with data generated on the Illumina sequencing platform. In addition, we sequenced a targeted panel of cancer-associated genes in a well characterized reference standard. With multiple library preparation approaches on this sample, we were able to identify low frequency mutations at expected allele frequencies.