bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Affecting Pre-Travel Health Seeking Behaviour and Adherence to Pre-Travel Health Advice: A Systematic Review
Authors: Kain Dylan , Findlater Aidan , Lightfoot David , Maxim Timea , Kraemer Moritz U G , Brady Oliver J , Watts Alexander , Khan Kamran , Bogoch Isaac I
Published: August 2019

Background

Recent years have seen unprecedented growth in international travel. Travellers are at high risk for acquiring infections while abroad and potentially bringing these infections back to their home country. There are many ways to mitigate this risk by seeking pre-travel advice (PTA), including receiving recommended vaccinations and chemoprophylaxis, however many travellers do not seek or adhere to PTA. We conducted a systematic review to further understand PTA-seeking behaviour with an ultimate aim to implement interventions that improve adherence to PTA and reduce morbidity and mortality in travellers.

Methods

We conducted a systematic review of published medical literature selecting studies that examined reasons for not seeking PTA and non-adherence to PTA over the last ten years. 4484 articles were screened of which 56 studies met our search criteria after full text review.

Results

The major reason for not seeking or non-adherence to PTA was perceived low risk of infection while travelling. Side effects played a significant role for lack of adherence specific to malaria prophylaxis.

Conclusions

These data may help clinicians and public health providers to better understand reasons for non-adherence to PTA and target interventions to improve travellers understanding of potential and modifiable risks. Additionally, we discuss specific recommendations to increase public health education that may enable travellers to seek PTA.
Chagas disease: comments on the 2018 PAHO Guidelines for diagnosis and management
Authors: Norman Francesca F , López-Vélez Rogelio
Published: August 2019

Background

Chagas disease, or American trypanosomiasis, is a protozoan infectious disease endemic throughout most of the Americas, caused by the trypanosome, Trypanosoma cruzi, and mainly transmitted to humans by reduviid or kissing bugs. Some progress has been achieved in control of the disease mainly in endemic areas, but migration flows have acted as drivers for the emergence of the disease mainly in non-endemic areas of Europe and North America. Most imported cases of Chagas disease in Europe are reported in migrants from highly endemic areas of countries such as Bolivia and Paraguay, and reports of Chagas disease in travellers are extremely rare.

Methods

Pan American Health Organization (PAHO) recently updated their guidelines on the diagnosis and management of Chagas. These guidelines and their applicability to migrants and travellers are reviewed.

Results

PAHO recommends the use of two serological tests for diagnosis of chronic infection (allowing for the use of a single sensitive test followed by confirmation in special settings such as the screening of potential blood donors). The indication for specific trypanocidal treatment of acute infections, children and women of child-bearing age remains as before, with either benznidazole or nifurtimox being the treatment of choice. For chronic infection with/without organ damage, treatment recommendations are less well defined. Although treatment is generally not recommended in patients with visceral involvement, decisions regarding treatment need to be tailored to the individual. Either benznidazole or nifurtimox may be used for initial treatment.

Conclusions

The recent PAHO Guidelines provide a framework to aid the diagnosis and management of this infection, but several aspects such as the underdiagnosis of infections, the multidisciplinary approach to patient management, the investigation of novel biomarkers of disease progression/response to treatment and the development of new treatment strategies are areas which should be further strengthened.
The clustering of typical Ly α emitters from z ∼ 2.5–6: host halo masses depend on Ly α and UV luminosities
Authors: Khostovan A A , Sobral D , Mobasher B , Matthee J , Cochrane R K , Chartab N , Jafariyazani M , Paulino-Afonso A , Santos S , Calhau J
Published: August 2019

We investigate the clustering and halo properties of ∼5000 Ly α-selected emission-line galaxies (LAEs) from the Slicing COSMOS 4K (SC4K) and from archival NB497 imaging of SA22 split in 15 discrete redshift slices between z ∼ 2.5 and 6. We measure clustering lengths of r0 ∼ 3–6 h−1 Mpc and typical halo masses of ∼1011 M⊙ for our narrowband-selected LAEs with typical LLy α ∼ 1042–43 erg s−1. The intermediate-band-selected LAEs are observed to have r0 ∼ 3.5–15 h−1 Mpc with typical halo masses of ∼1011–12 M⊙ and typical LLy α ∼ 1043–43.6 erg s−1. We find a strong, redshift-independent correlation between halo mass and Ly α luminosity normalized by the characteristic Ly α luminosity, L⋆(z). The faintest LAEs (L ∼ 0.1 L⋆(z)) typically identified by deep narrowband surveys are found in 1010 M⊙ haloes and the brightest LAEs (L ∼ 7 L⋆(z)) are found in ∼5 × 1012 M⊙ haloes. A dependency on the rest-frame 1500 Å UV luminosity, MUV, is also observed where the halo masses increase from 1011 to 1013 M⊙ for MUV ∼ −19 to −23.5 mag. Halo mass is also observed to increase from 109.8 to 1012 M⊙ for dust-corrected UV star formation rates from ∼0.6 to 10 M⊙ yr−1 and continues to increase up to 1013 M⊙ in halo mass, where the majority of those sources are active galactic nuclei. All the trends we observe are found to be redshift independent. Our results reveal that LAEs are the likely progenitors of a wide range of galaxies depending on their luminosity, from dwarf-like, to Milky Way-type, to bright cluster galaxies. LAEs therefore provide unique insight into the early formation and evolution of the galaxies we observe in the local Universe.
The self-similarity of weak lensing peaks
Authors: Davies Christopher T , Cautun Marius , Li Baojiu
Published: August 2019

We study the statistics of weak lensing convergence peaks, such as their abundance and two-point correlation function (2PCF), for a wide range of cosmological parameters Ωm and σ8 within the standard ΛCDM paradigm, focusing on intermediate-height peaks with signal-to-noise ratio (SNR) of 1.5–3.5. We find that the cosmology dependence of the peak abundance can be described by a one-parameter fitting formula that is accurate to within $\sim 3{{\ \rm per\ cent}}$. The peak 2PCFs are shown to feature a self-similar behaviour: if the peak separation is rescaled by the mean interpeak distance, catalogues with different minimum peak SNR values have identical clustering, which suggests that the peak abundance and clustering are closely interconnected. A simple fitting model for the rescaled 2PCF is given, which together with the peak abundance model above can predict peak 2PCFs with an accuracy better than $\sim 5{{\ \rm per\ cent}}$. The abundance and 2PCFs for intermediate peaks have very different dependencies on Ωm and σ8, implying that their combination can be used to break the degeneracy between these two parameters.
Amylopectin Chain Length Dynamics and Activity Signatures of Key Carbon Metabolic Enzymes Highlight Early Maturation as Culprit for Yield Reduction of Barley Endosperm Starch after Heat Stress
Authors: Cuesta-Seijo Jose Antonio , De Porcellinis Alice Jara , Valente Angela H�rdum , Striebeck Alexander , Voss Cynthia , Marri Lucia , Hansson Andreas , Jansson Anita M , Dinesen Malene Hessellund , Fangel Jonatan Ulrik , Harholt Jesper , Popovic Milan , Thieme Mercedes , Hochmuth Anton , Zeeman Samuel C , Mikkelsen Teis N�rgaard , J�rgensen Rikke Bagger , Roitsch Thomas Georg , M�ller Birger Lindberg , Braumann Ilka
Published: August 2019

Abiotic environmental stresses have a negative impact on the yield and quality of crops. Understanding these stresses is an essential enabler for mitigating breeding strategies and it becomes more important as the frequency of extreme weather conditions increases due to climate change. This study analyses the response of barley (Hordeum vulgare L.) to a heat wave during grain filling in three distinct stages: the heat wave itself, the return to a normal temperature regime, and the process of maturation and desiccation. The properties and structure of the starch produced were followed throughout the maturational stages. Furthermore, the key enzymes involved in the carbohydrate supply to the grain were monitored. We observed differences in starch structure with well-separated effects because of heat stress and during senescence. Heat stress produced marked effects on sucrolytic enzymes in source and sink tissues. Early cessation of plant development as an indirect consequence of the heat wave was identified as the major contributor to final yield loss from the stress, highlighting the importance for functional stay-green traits for the development of heat-resistant cereals.
Frailty and hospital outcomes within a low socioeconomic population
Authors: Clark S , Shaw C , Padayachee A , Howard S , Hay K , Frakking T T
Published: August 2019

Background

Clinical frailty scales (CFS) predict hospital-related outcomes. Frailty is more common in areas of higher socioeconomic disadvantage, but no studies exclusively report on the impact of CFS on hospital-related outcomes in areas of known socioeconomic disadvantage.

Aims

To evaluate the association of the CFS with hospital-related outcomes.

Design

Retrospective observational study in a community hospital within a disadvantaged area in Australia (Social Economic Index for Areas = 0.1%).

Methods

The CFS was used in the emergency department (ED) for people aged ≥ 75 years. Frailty was defined as a score of ≥4. Associations between the CFS and mortality, admission rates, ED presentations and length of stay (LOS) were analysed using regression analyses.

Results

Between 11 July 2017 and 31 March 2018, there were 5151 ED presentations involving 3258 patients aged ≥ 75 years. Frail persons were significantly more likely to be older, represent to the ED and have delirium compared with non-frail persons. CFS was independently associated with 28-day mortality, with odds of mortality increasing by 1.5 times per unit increase in CFS (95% CI: 1.3–1.7). Frail persons with CFS 4–6 were more likely to be admitted (OR: 1.2; 95% CI: 1.0–1.5), have higher geometric mean LOS (1.43; 95% CI 1.15-1.77 days) and higher rates of ED presentations (IRR: 1.12; 95% CI 1.04–1.21) compared with non-frail persons.

Conclusions

The CFS predicts community hospital-related outcomes in frail persons within a socioeconomic disadvantage area. Future intervention and allocation of resources could consider focusing on CFS 4–6 as a priority for frail persons within a community hospital setting.
Epigenetic Memory Is Involved in the Persistent Alterations of Drug-Processing Genes in Adult Mice Due to PCN-Activated PXR During Early Life
Authors: Wang Pei , Liu Guangming , Nie Yali , Han Shengna , Li Jiangfeng , Zhong Xiao-Bo , Zhang Lirong
Published: August 2019

Pregnane X receptor (PXR), which can be activated by xenobiotic chemicals (including pediatric drugs), plays a key role in the regulation of drug-processing genes (DPGs). The induction of DPGs due to PXR activation may reduce therapeutic efficacy or cause toxicity. This work aims to demonstrate the impact of pregnenolone 16α-carbonitrile (PCN)-mediated PXR activation during early life on DPGs expression and drug sensitivity in adulthood, as well as the underlying mechanism. In this study, mice were sacrificed at postnatal day 60 to detect the hepatic expression of selected DPGs and histone modifications in the Cyp3a11 promoter. We found that all doses of PCN treatment (50–200 mg/kg/day) at postnatal days 5–8 resulted in persistently increased CYP2B10 expression, whereas only high doses of PCN treatment (150 and 200 mg/kg/day) persistently induced the expression of CYP3A11, 1A2, and UGT1A1. We also demonstrated that PCN treatment before postnatal day 15 had a long-term impact on the expression of CYP3A11, 2B10, ABCC4, and PAPSS2. Additionally, elevated expression of CYP3A11, SULT2A1, UGT1A1, and PAPSS2 was observed in PCN-treated groups at days 25–28. Attenuated inducibility of CYP3A11 by PCN was seen in the primary hepatocytes derived from PCN-pretreated mice. Moreover, enhanced H3K4me3 level and reduced H3K27me3 level in the PXR response elements (PXREs) of the Cyp3a11 promoter may contribute to the persistent upregulation of CYP3A11 by neonatal PCN treatment. Overall, our study suggests that PXR activation during early life could persistently alter the hepatic expression of DPGs and epigenetic memory may be an underlying mechanism in mice.
Contrasting selective patterns across the segmented genome of bluetongue virus in a global reassortment hotspot
Authors: Jacquot Maude , Rao Pavuluri P , Yadav Sarita , Nomikou Kyriaki , Maan Sushila , Jyothi Y Krishna , Reddy Narasimha , Putty Kalyani , Hemadri Divakar , Singh Karam P , Maan Narender Singh , Hegde Nagendra R , Mertens Peter , Biek Roman
Published: August 2019

For segmented viruses, rapid genomic and phenotypic changes can occur through the process of reassortment, whereby co-infecting strains exchange entire segments creating novel progeny virus genotypes. However, for many viruses with segmented genomes, this process and its effect on transmission dynamics remain poorly understood. Here, we assessed the consequences of reassortment for selection on viral diversity through time using bluetongue virus (BTV), a segmented arbovirus that is the causative agent of a major disease of ruminants. We analysed ninety-two BTV genomes isolated across four decades from India, where BTV diversity, and thus opportunities for reassortment, are among the highest in the world. Our results point to frequent reassortment and segment turnover, some of which appear to be driven by selective sweeps and serial hitchhiking. Particularly, we found evidence for a recent selective sweep affecting segment 5 and its encoded NS1 protein that has allowed a single variant to essentially invade the full range of BTV genomic backgrounds and serotypes currently circulating in India. In contrast, diversifying selection was found to play an important role in maintaining genetic diversity in genes encoding outer surface proteins involved in virus interactions (VP2 and VP5, encoded by segments 2 and 6, respectively). Our results support the role of reassortment in driving rapid phenotypic change in segmented viruses and generate testable hypotheses for in vitro experiments aiming at understanding the specific mechanisms underlying differences in fitness and selection across viral genomes.
Modelling and in vitro testing of the HIV-1 Nef fitness landscape
Authors: Barton John P , Rajkoomar Erasha , Mann Jaclyn K , Murakowski Dariusz K , Toyoda Mako , Mahiti Macdonald , Mwimanzi Phillip , Ueno Takamasa , Chakraborty Arup K , Ndung’u Thumbi
Published: August 2019

An effective vaccine is urgently required to curb the HIV-1 epidemic. We have previously described an approach to model the fitness landscape of several HIV-1 proteins, and have validated the results against experimental and clinical data. The fitness landscape may be used to identify mutation patterns harmful to virus viability, and consequently inform the design of immunogens that can target such regions for immunological control. Here we apply such an analysis and complementary experiments to HIV-1 Nef, a multifunctional protein which plays a key role in HIV-1 pathogenesis. We measured Nef-driven replication capacities as well as Nef-mediated CD4 and HLA-I down-modulation capacities of thirty-two different Nef mutants, and tested model predictions against these results. Furthermore, we evaluated the models using 448 patient-derived Nef sequences for which several Nef activities were previously measured. Model predictions correlated significantly with Nef-driven replication and CD4 down-modulation capacities, but not HLA-I down-modulation capacities, of the various Nef mutants. Similarly, in our analysis of patient-derived Nef sequences, CD4 down-modulation capacity correlated the most significantly with model predictions, suggesting that of the tested Nef functions, this is the most important in vivo. Overall, our results highlight how the fitness landscape inferred from patient-derived sequences captures, at least in part, the in vivo functional effects of mutations to Nef. However, the correlation between predictions of the fitness landscape and measured parameters of Nef function is not as accurate as the correlation observed in past studies for other proteins. This may be because of the additional complexity associated with inferring the cost of mutations on the diverse functions of Nef.
Maristella, a new bioluminescent ostracod genus in the Myodocopida (Cypridinidae)
Authors: Reda Nicholas J , Morin James G , Torres Elizabeth , Cohen Anne C , Schawaroch Valerie , Gerrish Gretchen A
Published: August 2019

One new species from Belize and six described species from Panama of bioluminescent ostracods (Myodocopida: Cypridinidae) are compared and placed in the new genus, Maristellagen. nov.. Maristella belongs to a diverse Caribbean clade of bioluminescent ostracods in which males perform species-specific luminescent courtship displays. Other genera of the clade include Enewton, Photeros, Konickeria and, nominally, Vargula.Maristella is likely the most species-rich genus in the clade. Maristella chicoi sp. nov., from Belize, is described as the type species. Species from Panama reassigned to Maristella are Vargula ignitula, V. lucidella, V. micamacula, V. noropsela, V. psammobia, V. scintilla. New information is presented on the sixth and eighth limbs of the species from Panama, providing additional characters for distinguishing taxa. Maristella is the only genus that contains species with lateral or diagonal luminescent courtship displays. Maristella chicoi has male displays oriented horizontal to the substrate and showing high levels of entrainment. The displays run in near-parallel bifurcations resulting in spectacular fan-like radiations of light pulse trains. The description of Maristella advances the taxonomy of the highly diverse Caribbean clade that has become a model system for studying the evolution of bioluminescence and the role of luminescent displays in speciation.
Etiology of Branch Dieback and Shoot Blight of English Walnut Caused by Botryosphaeriaceae andDiaportheSpecies in Southern Spain
Authors: López-Moral Ana , Lovera María , Raya María del Carmen , Cortés-Cosano Nerea , Arquero Octavio , Trapero Antonio , Agustí-Brisach Carlos
Published: August 2019

English walnut (Juglans regia L.) is considered an economically important fruit crop worldwide. In Spain, little attention has been given to walnut diseases owing to the minor economic importance of the walnut crop in the country until recently. In 2017, typical symptoms of branch dieback and shoot blight of English walnut were observed in southern Spain. From 2017 to 2018, 10 commercial walnut orchards showing disease symptoms were surveyed. Botryosphaeriaceae and Diaporthe fungi were consistently isolated from affected shoots. Cytospora isolates were also recovered with minor relevance. Representative isolates of each fungal group were characterized based on colony and conidial morphology, optimum growth temperature, and comparison of DNA sequence data from the internal transcribed spacer, elongation factor 1-α, and β-tubulin genomic areas. Pathogenicity tests were performed on detached and attached shoots and on detached fruit by inoculating them with mycelial plugs. Botryosphaeriaceae and Diaporthe isolates had higher optimum growth temperatures (≈25 to 27°C) than Cytospora sp. (19.5°C). The following species were identified: Botryosphaeriaceae: Botryosphaeria dothidea, Diplodia seriata, Dothiorella sarmentorum, Dothiorella sp., Neofusicoccum mediterraneum, and N. parvum; Diaporthe: Diaporthe neotheicola, Dia. rhusicola, Diaporthe sp., and Phomopsis amygdali; and Cytospora sp. Botryosphaeriaceae isolates were the most aggressive fungi to walnut in all tissues evaluated, followed by Diaporthe isolates and Cytospora sp. N. parvum was the most virulent among the remaining species tested in any of the tissues evaluated, followed by B. dothidea or N. mediterraneum. This work is the first report to identify the fungal species causing this complex disease of English walnut in Spain and Europe.
Meprin β induces activities of A disintegrin and metalloproteinases 9, 10, and 17 by specific prodomain cleavage
Authors: Wichert Rielana , Scharfenberg Franka , Colmorgen Cynthia , Koudelka Tomas , Schwarz Jeanette , Wetzel Sebastian , Potempa Barbara , Potempa Jan , Bartsch Jörg W. , Sagi Irit , Tholey Andreas , Saftig Paul , Rose‐John Stefan , Becker‐Pauly Christoph
Published: August 2019

Meprin β is a membrane‐bound metalloprotease involved in extracellular matrix assembly and inflammatory processes in health and disease. A disintegrin and metalloproteinase (ADAM)10 and ADAM17 are physiologic relevant sheddases of inactive promeprin β, which influences its substrate repertoire and subsequent biologic functions. Proteomic analysis also revealed several ADAMs as putative meprin β substrates. Here, we demonstrate specific N‐terminal processing of ADAM9, 10, and 17 by meprin β and identify cleavage sites within their prodomains. Because ADAM prodomains can act as specific inhibitors, we postulate a role for meprin β in the regulation of ADAM activities. Indeed, prodomain cleavage by meprin β caused increased ADAM protease activities, as observed by peptide‐based cleavage assays and demonstrated by increased ectodomain shedding activity. Direct interaction of meprin β and ADAM proteases could be shown by immunofluorescence microscopy and immunoprecipitation experiments. As demonstrated by a bacterial activator of meprin β and additional measurement of TNF‐α shedding on bone marrow‐derived macrophages, meprin β/ADAM protease interactions likely influence inflammatory conditions. Thus, we identified a novel proteolytic pathway of meprin β with ADAM proteases to control protease activities at the cell surface as part of the protease web.—Wichert, R., Scharfenberg, F., Colmorgen, C., Koudelka, T., Schwarz, J., Wetzel, S., Potempa, B., Potempa, J., Bartsch, J. W., Sagi, I., Tholey, A., Saftig, P., Rose‐John, S., Becker‐Pauly, C. Meprin β induces activities of A disintegrin and metalloproteinases 9, 10, and 17 by specific prodomain cleavage. FASEB J. 33, 11925‐11940 (2019). www.fasebj.org
Patient and Physician Perspectives on Treating Tobacco Dependence in Hospitalized Smokers With Substance Use Disorders: A Mixed Methods Study
Authors: Kathuria Hasmeena , Seibert Ryan G. , Cobb Vinson , Weinstein Zoe M. , Gowarty Minda , Helm Eric D. , Wiener Renda Soylemez
Published: August 2019

Objective:

Individuals with substance use disorders have a high prevalence of smoking cigarettes. Hospitalization represents an opportunity to deliver concurrent treatment for tobacco and other substances. Using a sequential explanatory mixed methods design, we characterized practices and perspectives of patients and physicians about smoking cessation counseling during inpatient addiction medicine consultations.

Methods:

We abstracted data from 694 consecutive inpatient addiction consult notes to quantify how often physicians addressed tobacco dependence using the guideline-recommended 5As framework. We conducted semi-structured interviews with 9 addiction medicine physicians and 20 hospitalized smokers with substance use disorders. We analyzed transcripts to explore physicians’ and patients’ perspectives on smoking cessation conversations during inpatient addiction consultations, physician-perceived barriers and facilitators to engaging inpatients in tobacco treatment, and strategies to improve tobacco treatment in this context.

Results:

75.5% (522/694) of hospitalized substance use disorder patients were current smokers. Among smokers, 20.9% (109/522) were offered nicotine replacement while hospitalized, but only 5.4% (28/522) received the full guideline-recommended 5As. Patients and physicians reported minimal discussion about tobacco addiction during hospitalization. Physicians cited tobacco not being an immediate health threat and the perception that quitting tobacco is not a priority to patients as barriers, often limiting thorough counseling to patients with smoking-related admissions. Physicians and patients offered strategies to integrate treatment of tobacco dependence and other substances.

Conclusions:

Inpatient addiction consultations represent a missed opportunity to counsel patients with substance use disorders to quit smoking. System-level changes are needed to coordinate treatment of tobacco and other drug dependence in hospitalized smokers.
REAL-WORLD EFFECTIVENESS AND SAFETY OF RANIBIZUMAB TREATMENT IN PATIENTS WITH AND WITHOUT POLYPOIDAL CHOROIDAL VASCULOPATHY
Authors: Koh Adrian , Lai Timothy Y.Y. , Wei Wen Bin , Mori Ryusaburo , Wakiyama Harumi , Park Kyu Hyung , Ngah Fariza , Macfadden Wayne , Dunger-Baldauf Cornelia , Parikh Soumil ,   on behalf of the LUMINOUS study steering committee
Published: August 2019

Purpose:

To evaluate the real-world effectiveness and safety of intravitreal ranibizumab 0.5 mg in treatment-naive patients with and without polypoidal choroidal vasculopathy (PCV).

Methods:

Assessment of neovascular age-related macular degeneration patients with or without PCV after 12 months of ranibizumab treatment during the LUMINOUS study. Outcome measures were visual acuity and central retinal thickness changes from baseline and the rate of ocular adverse events.

Results:

At baseline, 572 and 5,644 patients were diagnosed with and without PCV, respectively. The mean visual acuity gain from baseline at Month 12 in the PCV and non-PCV groups was +5.0 and +3.0 letters, respectively; these gains were achieved with a mean of 4.4 and 5.1 ranibizumab injections. Eighty percent of PCV patients and 72.2% of non-PCV patients who had baseline visual acuity ≥73 letters maintained this level of vision at Month 12; 20.6% and 17.9% of patients with baseline visual acuity <73 letters achieved visual acuity ≥73 letters in these groups. Greater reductions in central retinal thickness from baseline were also observed for the PCV group versus the non-PCV group. The rate of serious ocular adverse events was 0.7% (PCV group) and 0.9% (non-PCV group).

Conclusion:

LUMINOUS confirms the effectiveness and safety of ranibizumab in treatment-naive patients with PCV.
Understanding the genetics of asthma and implications for clinical practice
Authors: Mammen Jennifer R. , Arcoleo Kimberly
Published: August 2019

Asthma is one of the most common heritable diseases globally, with variable clinical expression and response to treatment that is attributed to underlying genetic differences. Hundreds of loci on multiple chromosomes are associated with asthma. Although routine genetic screening is not recommended, testing for medication responsiveness might soon play a role in clinical management. Pharmacogenetic research remains early stage but has demonstrated potential for both clinical and cost effectiveness. Furthermore, recognition of clinically apparent asthma phenotypes, the result of genetic and environmental interactions, can help to inform treatment decisions. Phenotypes are divided into two broad categories of atopic and nonatopic disease, with further subdivisions that are associated with clinical presentation patterns and responsiveness to treatment. In general, earlier onset and allergic disease will respond well to traditional therapy with inhaled corticosteroids (ICSs) and leukotrienes because these medications target inflammatory pathways for allergic disease. However, patients with late-onset, symptom predominant (lacking inflammation), and obese asthma might be resistant to standard therapy and may require treatment modification. These patients are at risk for overuse of ICSs with poor response and may benefit more by use of long-acting beta agonists, long-acting muscarinic agonists, weight reduction, and exercise.
Supporting program rigor in newly developed specialty academic programs: Use of a self-evaluation reporting tool for emergency nurse practitioner academic programs
Authors: Wilbeck Jennifer , Evans Dian Dowling , Hummer Kirk , Staebler Suzanne
Published: August 2019

The emergency nurse practitioner (ENP) specialty has grown rapidly, responding and adapting to changes in emergency care. Designation and advancement of nurse practitioner (NP) specialties follows a systematic process as defined by the profession. This includes establishment of scope and standards of practice, educational standards, and policy initiatives to ensure quality and safety within the profession. This article serves to detail a process of self-evaluation for newly developed ENP academic programs, including resources and key documents to be considered in the development of NP specialty programs. A transformative tool is included that serves as a model for use in development and self-evaluation of other emerging graduate academic NP specialty programs.
Long-term Outcomes of Balloon Dilation for Persistent Eustachian Tube Dysfunction
Authors: Cutler Jeffrey L. , Meyer Ted A. , Nguyen Shaun A. , O’Malley Ellen M. , Thackeray Lisa , Slater Patrick W.
Published: August 2019

Objective:

To gather long-term follow-up data on the efficacy of balloon dilation for treating patients with persistent Eustachian tube dysfunction (ETD).

Study Design:

Extended follow-up study of the treatment arm of a prospective, multicenter, randomized controlled trial.

Setting:

Tertiary care academic center and private practice.

Patients:

Patients diagnosed with medically refractory persistent ETD.

Interventions:

Balloon dilation of the Eustachian tube.

Main Outcome Measures:

The endpoints were the mean change from baseline in the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) score, revision dilation rate, changes in assessments of middle ear function, and patient satisfaction.

Results:

A total of 47 participants enrolled in the extended follow-up study. Mean follow-up was 29.4 months (range, 18–42 mo). There was a statistically significant mean (SD) change from baseline in the overall ETDQ-7 score (–2.5 ± 1.2; p < 0.0001). A reduction of one or more in their overall ETDQ-7 score was observed by 93.6% (44/47) participants. The revision dilation rate was 2.1% (1/47). Among participants with abnormal baseline middle ear assessments, 76.0% had normalized tympanic membrane position (p < 0.0001), 62.5% had normalization of tympanogram type (p < 0.001), and 66.7% had positive Valsalva maneuvers (p < 0.0001). Participant satisfaction was 83.0% at long-term follow-up.

Conclusions:

Balloon dilation results in durable improvements in symptoms and middle ear assessments for patients with persistent Eustachian tube dysfunction at mean follow-up of longer than 2 years.
Immune responses towards bioengineered tissues and strategies to control them
Authors: Angeletti Andrea , Cantarelli Chiara , Cravedi Paolo
Published: August 2019

Purpose of review

Research into development of artificial tissues and bioengineered organs to replace physiological functions of injured counterparts has highlighted a previously underestimated challenge for its clinical translatability: the immune response against biomaterials. Herein, we will provide an update and review current knowledge regarding this important barrier to regenerative medicine.

Recent findings

Although a clear understanding of the immune reactivity against biomaterials remains elusive, accumulating evidence indicates that innate immune cells, primarily neutrophils and macrophages, play a key role in the initial phases of the immune response. More recently, data have shown that in later phases, T and B cells are also involved. The use of physicochemical modifications of biomaterials and cell-based strategies to modulate the host inflammatory response is being actively investigated for effective biomaterial integration.

The immune response towards biomaterials and bioengineered organs plays a crucial role in determining their utility as transplantable grafts. Expanding our understanding of these responses is necessary for developing protolerogenic strategies and delivering on the ultimate promise of regenerative medicine.
Current Procedural Terminology Coding in an Academic Breast Pathology Service
Authors: Johnson Steven M. , Vanleer Jessica P. , O’Connor Siobhan M. , Maygarden Susan J.
Published: August 2019

Many physicians share the perception that the work required to evaluate breast pathology specimens is undervalued by Current Procedural Terminology (CPT) codes. To examine this issue, we compared slide volumes from an equal number of breast and nonbreast specimens assigned 88305, 88307, or 88309 CPT codes during four 2.5-week periods over 1 year. For each specimen, a number of initial hematoxylin and eosin–stained sections (H&Es), preordered additional H&E sections (levels), H&E sections ordered after initial slide review (recuts), and specimen type were recorded. Slides associated with ancillary stains were not considered. In total, 911 breast and 911 nonbreast specimens, each assigned 88305 (n=580), 88307 (n=320), and 88309 (n=11) CPT codes, were compared. Breast 88305 specimens were mainly core biopsies and margins and generated 2.3 and 6.4 times the H&Es and recuts, respectively, than did nonbreast specimens (P<0.01). Breast 88307 specimens were mainly lymph nodes and lumpectomies and generated 1.8 times the total slides than did nonbreast specimens (P<0.01). Eleven modified radical mastectomies (88309) generated 2.1 times the total slides than nonbreast 88309 specimens (P<0.01). In total (n=911 in each cohort), breast specimens generated 1.9, 4.0, and 1.7 times the H&Es, recuts, and total slides (P<0.01) than did nonbreast specimens. At our academic institution, the slide volume for breast specimens is nearly twice that of similarly coded nonbreast specimens. These results have significant implications for workload management and assessing pathologist productivity, particularly in subspecialty practices.
Treitz Hernia: Report of a Case and Review of the Literature
Authors: Cereser Teresa , Kuchen Natalie , Schöb Othmar
Published: August 2019

Introduction:

Congenital hernias are rare findings, and their diagnosis is often delayed due to an incorrect interpretation of the clinical symptoms and/or images. We present a rare case of left-sided paraduodenal hernia at the ligament of Treitz, followed by a review of the literature.

Case Presentation:

We report the case of a 20-year-old patient with unusual, recurring abdominal pain in the past 3 months. There were no previous operations or past illnesses in the patient’s history. The computed tomographic scan showed a misplacement of small bowel into the lesser sack. With high suspicion of an internal hernia, we performed a diagnostic laparoscopy, which revealed a Treitz hernia. The reduction and fixation could be carried out fully with minimally invasive surgery with an uneventful postoperative course and complete recovery.

Conclusion:

A Treitz hernia is a rare cause of unspecific abdominal pain and the clinical signs are difficult to interpret. However, its knowledge may help to avoid emergency procedures and provide quick recovery of the patients. We recommend the laparoscopic approach as the first choice of treatment in all cases of internal hernia in the absence of peritoneal irritation or severe bowel obstruction.
Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques
Authors: Alonso-Guallart Paula , Duran-Struuck Raimon , Zitsman Jonah S. , Sameroff Stephen , Pereira Marcus , Stern Jeffrey , Berglund Erik , Llore Nathaly , Pierre Genevieve , Lopes Emily , Kofman Sigal B. , Danton Makenzie , Sondermeijer Hugo P. , Woodland David , Kato Yojiro , Ekanayake-Alper Dilrukshi K. , Iuga Alina C. , Wuu Cheng-Shie , Wu Anette , Lipkin W. Ian , Tokarz Rafal , Sykes Megan , Griesemer Adam
Published: August 2019

Background.

Cytomegalovirus (CMV) infection is a serious complication in immunosuppressed patients, specifically transplant recipients. Here, we describe the development and use of an assay to monitor the incidence and treatment of CMV viremia in a Cynomolgus macaque model of bone marrow transplantation (BMT) for tolerance induction. We address the correlation between the course of viremia and immune reconstitution.

Methods.

Twenty-one animals received a nonmyeloablative conditioning regimen. Seven received cyclosporine A for 28 days and 14 received rapamycin. A CMV polymerase chain reaction assay was developed and run twice per week to monitor viremia. Nineteen recipients were CMV seropositive before BMT. Immune reconstitution was monitored through flow cytometry and CMV viremia was tracked via quantitative polymerase chain reaction.

Results.

Recipients developed CMV viremia during the first month post-BMT. Two animals developed uncontrollable CMV disease. CMV reactivation occurred earlier in cyclosporine A-treated animals compared with those receiving rapamycin. Post-BMT, T-cell counts remained significantly lower compared with pretransplant levels until CMV reactivation, at which point they increased during the viremic phase and approached pretransplant levels 3 months post-BMT. Management of CMV required treatment before viremia reached 10 000 copies/mL; otherwise clinical symptoms were observed. High doses of ganciclovir resolved the viremia, which could subsequently be controlled with valganciclovir.

Conclusions.

We developed an assay to monitor CMV in Cynomolgus macaques. CMV reactivation occurred in 100% of seropositive animals in this model. Rapamycin delayed CMV reactivation and ganciclovir treatment was effective at high doses. As in humans, CD8+ T cells proliferated during CMV viremia.
Neuroprotective Biomarkers and Cognitive Function in a Long-Term Prospective Population-based Study of Aging US Adults
Authors: Paulsen Adam J. , Schubert Carla R. , Pinto Alex , Carlsson Cynthia M. , Chappell Richard J. , Fischer Mary E. , Klein Barbara E.K. , Klein Ronald , Tsai Michael Y. , Cruickshanks Karen J.
Published: August 2019

Background:

Relationships between brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), aldosterone, and cognition in aging were evaluated in the population-based Epidemiology of Hearing Loss Study (1993 to present).

Methods:

Beginning in 1998 to 2000, cognitive impairment was assessed by report of physician diagnoses and the Mini-Mental State Examination. In 2009 to 2010 and 2013 to 2016, information was collected on diagnosis of mild cognitive impairment/dementia. Decline in cognitive function was assessed by principal component analysis from additional tests administered during 2009 to 2010 and 2013 to 2016. BDNF, IGF-1, and aldosterone were measured in serum collected in 1998 to 2000.

Results:

There were 1970 participants (mean age=66.9 y; 59.1% female) without cognitive impairment at baseline. Among women, low BDNF was associated with 16-year incident cognitive impairment [hazard ratio=1.76; 95% confidence interval (CI)=1.04, 2.98]. Among men, increasing IGF-1 was associated with decreased risk [per SD: relative risk (RR)=0.57; 95% CI=0.35, 0.92], whereas increasing aldosterone levels were associated with increased risk (per SD: RR=1.28; 95% CI=1.01, 1.62) for 5-year incident mild cognitive impairment/dementia. Overall, low BDNF was associated with increased risk (RR=1.52; 95% CI=1.02, 2.26) for 5-year cognitive decline.

Conclusion:

Low levels of serum BDNF and IGF-1 were associated with poorer cognition during aging. There may be differential biomarker effects by sex.
Can school children support ecological research? Lessons from the‘Oak bodyguard’citizen science project
Authors: Castagneyrol Bastien , Valdés-Correcher Elena , Bourdin Audrey , Barbaro Luc , Bouriaud Olivier , Branco Manuela , Csóka György , Duduman Mihai-Leonard , Dulaurent Anne-Maïmiti , Eötvös Csaba B. , Ferrante Marco , Fürjes-Mikó Ágnes , Galman Andrea , Gossner Martin M. , Harvey Deborah , Howe Andy G. , Kaennel-Dobbertin Michèle , Koricheva Julia , Löveï Gábor L. , Lupaștean Daniela , Milanović Slobodan , Mrazova Anna , Opgennoorth Lars , Pitkänen Juha-Matti , Popović Marija , Roslin Tomas V. , Scherer-Lorenzen Michael , Sam Katerina , Tahadlova Marketa , Thomas Rebecca , Tack Ayco J. M.
Published: August 2019

Scientific knowledge in the field of ecology is increasingly enriched by data acquired by the general public participating in citizen science (CS) programs. Yet, doubts remain about the reliability of such data, in particular when acquired by school children. We built upon an ongoing CS program -Oak bodyguards- to assess the ability of European schoolchildren to accurately estimate the strength of biotic interactions in terrestrial ecosystems. We used standardized protocols to estimate predation rates on artificial caterpillars and insect herbivory on oak leaves and compared estimates made by school children, trained and untrained professional scientists (with no or limited expertise in predation or herbivory assessment). Compared to trained scientists, both schoolchildren and untrained professional scientists overestimated predation rates, but assessments made by the latter were more consistent. School children overestimated insect herbivory, as did untrained professional scientists. Thus, raw data acquired by school children participating in CS programs cannot be used and require several quality checks. However, such data are of no less value than data collected by untrained professional scientists and can be calibrated for bias.
In Situ Transcriptome Accessibility Sequencing (INSTA-seq)
Authors: Fürth Daniel , Hatini Victor , Lee Je H.
Published: August 2019

Subcellular RNA localization regulates spatially polarized cellular processes, but unbiased investigation of its control in vivo remains challenging. Current hybridization-based methods cannot differentiate small regulatory variants, while in situ sequencing is limited by short reads. We solved these problems using a bidirectional sequencing chemistry to efficiently image transcript-specific barcode in situ, which are then extracted and assembled into longer reads using NGS. In the Drosophila retina, genes regulating eye development and cytoskeletal organization were enriched compared to methods using extracted RNA. We therefore named our method In Situ Transcriptome Accessibility sequencing (INSTA-seq). Sequencing reads terminated near 3’ UTR cis-motifs (e.g. Zip48C, stau), revealing RNA-protein interactions. Additionally, Act5C polyadenylation isoforms retaining zipcode motifs were selectively localized to the optical stalk, consistent with their biology. Our platform provides a powerful way to visualize any RNA variants or protein interactions in situ to study their regulation in animal development.
Evolution of imprinting via lineage-specific insertion of retroviral promoters
Authors: Bogutz Aaron B. , Brind’Amour Julie , Kobayashi Hisato , Jensen Kristoffer N. , Nakabayashi Kazuhiko , Imai Hiroo , Lorincz Matthew C. , Lefebvre Louis
Published: August 2019

Imprinted genes are expressed from a single parental allele. In mammals, this unusual mode of transcription generally depends on the epigenetic silencing of one allele by DNA methylation (DNAme) established in the germline. While many species-specific imprinted orthologues have been documented in eutherians, the molecular mechanisms underlying the evolutionary switch from biallelic to imprinted expression are currently unknown. During mouse oogenesis, gametic differentially methylated regions (gDMRs) acquire DNAme in a process guided by transcription. Here we show that transcription initiating in proximal lineage-specific endogenous retroviruses (ERVs) is likely responsible for DNAme established in oocytes at 4/6 mouse-specific and 17/110 human-specific maternal imprinted gDMRs (igDMRs). The latter can be further divided into Catarrhini (Old World monkeys and apes)- or Hominoidea (ape)-specific igDMRs, which are embedded within transcription units initiating in ERVs specific to these primate lineages. Using CRISPR-Cas9 mutagenesis, we deleted the relevant murine-specific ERVs upstream of the maternally methylated genes Impact and Slc38a4. Strikingly, imprinting at these genes was lost in the offspring of females harboring these deletions and biallelic expression was observed. Our work reveals a novel evolutionary mechanism whereby maternally silenced genes arise from biallelically expressed progenitors.
Sequestration and functional diversification of cyanogenic glucosides in the life cycle of Heliconius melpomene
Authors: de Castro Érika C. P. , Demirtas Rojan , Orteu Anna , Olsen Carl Erik , Motawie Mohammed Saddik , Cardoso Márcio Z. , Zagrobelny Mika , Bak Søren
Published: August 2019

Heliconius butterflies are highly specialized in Passiflora, laying eggs and feeding as larvae only on these plants. Interestingly, Heliconius butterflies and Passiflora plants both contain cyanogenic glucosides (CNglcs). While feeding on specific Passiflora species, Heliconius melpomene larvae are able to sequester simple cyclopentenyl CNglcs, the most common CNglcs in this plant genus. Yet, aromatic, aliphatic, and modified CNglcs have been reported in Passiflora species and they were never tested for sequestration by heliconiine larvae. As other cyanogenic lepidopterans, H. melpomene also biosynthesize the aliphatic CNglcs linamarin and lotaustralin, and their toxicity does not rely exclusively on sequestration. Although the genes encoding the enzymes in the CNglc biosynthesis have not yet been fully biochemically characterized in butterflies, the cytochromes P450 CYP405A4, CYP405A5, CYP405A6 and CYP332A1 are hypothesized to be involved in this pathway in H. melpomene. In this study, we determine how the CNglc composition and expression of the putative P450s involved in the biosynthesis of these compounds vary at different development stages of Heliconius butterflies. We also established which kind of CNglcs H. melpomene larvae can sequestered from Passiflora. By analysing the chemical composition of the haemolymph from larvae fed with different Passiflora diets, we observed that H. melpomene is able to sequestered prunasin, an aromatic CNglcs, from P. platyloba. They were also able to sequester amygdalin, gynocardin, [C13/C14]linamarin and [C13/C14]lotaustralin painted on the plant leaves. The CNglc tetraphyllin B-sulphate from P. caerulea was not detected in the larval haemolymph, suggesting that such modified CNglcs cannot be sequestered by Heliconius. Although pupae and virgin adults contain dihydrogynocardin resulting from larval sequestration, this compound was metabolized during adulthood, and not used as nuptial gift or transferred to the offspring. Thus, we speculate that dihydrogynocardin was catabolized to recycle nitrogen and glucose, and/or to produce fitness signals during courtship and calling. Mature adults had a higher concentration of CNglcs than any other developmental stages due to intense de novo biosynthesis of linamarin and lotaustralin. All CYP405As were expressed in adults, whereas larvae mostly expressed CYP405A4. Our results shed light on the importance of CNglcs in Heliconius biology and for their coevolution with Passiflora.