bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost of Delivering 12-Dose Isoniazid and Rifapentine Versus 6 Months of Isoniazid for Tuberculosis Infection in a High-Burden Setting
Authors: Yuen Courtney M , Majidulla Arman , Jaswal Maria , Safdar Nauman , Malik Amyn A , Khan Aamir J , Becerra Mercedes C , Keshavjee Salmaan , Lu Chunling , Hussain Hamidah
Published: December 2020

Background

Successful delivery and completion of tuberculosis preventive treatment are necessary for tuberculosis elimination. Shorter preventive treatment regimens currently have higher medication costs, but patients spend less time in care and are more likely to complete treatment. It is unknown how economic costs of successful delivery differ between longer and shorter regimens in high-tuberculosis-burden settings.

Methods

We developed survey instruments to collect costs from program and patient sources, considering costs incurred from when household contacts first entered the health system. We compared the cost per completed course of preventive treatment with either 6 months of daily isoniazid (6H) or 3 months of weekly isoniazid and rifapentine (3HP), delivered by the Indus Health Network tuberculosis program in Karachi, Pakistan, between October 2016 and February 2018.

Results

During this period, 459 individuals initiated 6H and 643 initiated 3HP; 39% and 61% completed treatment, respectively. Considering costs to both the program and care recipients, the cost per completed course was 394 US dollars (USD) for 6H and 333 USD for 3HP. Using a new 2020 price for rifapentine reduced the cost per completed course of 3HP to 290 USD. Under varying assumptions about drug prices and costs incurred by care recipients, the cost per completed course was lower for 3HP in all scenarios, and the largest cost drivers were the salaries of clinical staff.

Conclusions

In a high-burden setting, the cost of successful delivery of 3HP was lower than that of 6H, driven by higher completion.
Molecular Techniques for Genus and Species Determination of Fungi From Fresh and Paraffin-Embedded Formalin-Fixed Tissue in the Revised EORTC/MSGERC Definitions of Invasive Fungal Infection
Authors: Lockhart Shawn R , Bialek Ralf , Kibbler Christopher C , Cuenca-Estrella Manuel , Jensen Henrik E , Kontoyiannis Dimitrios P
Published: December 2020

The EORTC/MSGERC have revised the definitions for proven, probable, and possible fungal diseases. The tissue diagnosis subcommittee was tasked with determining how and when species can be determined from tissue in the absence of culture. The subcommittee reached a consensus decision that polymerase chain reaction (PCR) from tissue, but not immunohistochemistry or in situ hybridization, can be used for genus or species determination under the new EORTC/MSGERC guidelines, but only when fungal elements are identified by histology. Fungal elements seen in tissue samples by histopathology and identified by PCR followed by sequencing should fulfill the definition of a proven fungal infection, identified to genus/species, even in the absence of culture. This summary discusses the issues that were deliberated by the subcommittee to reach the consensus decision and outlines the criteria a laboratory should follow in order to produce data that meet the EORTC/MSGERC definitions.
The complexity of sleep disorders in dialysis patients
Authors: Eloot Sunny , Holvoet Els , Dequidt Clement , Maertens Sarah-Jane , Vanommeslaeghe Floris , Van Biesen Wim
Published: December 2020

Background

Dialysis patients experience a high burden of physical and emotional symptoms directly affecting their sleep and quality of life. In this study, objective and subjective measurements to quantify sleep were performed, compared with those of healthy controls, and associated with burden of comorbidity and uraemic toxicity.

Methods

A total of 64 dialysis patients were included—10 peritoneal dialysis, 42 in-centre daytime haemodialysis (HD) and 12 in-centre nocturnal HD patients—as well as one-to-one age- and gender-matched healthy controls. Assumed and actual sleep time, sleep efficiency and fragmentation index were measured by actigraphy for at least two consecutive nights. Patients and controls also completed Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) questionnaires. The patients’ blood was sampled to determine concentrations of a representative series of uraemic toxins and the Davies–Stoke comorbidity index was derived from medical records.

Results

Apart from the assumed sleep time, all objectively and subjectively measured sleep parameters were worse in the dialysis group compared with the healthy controls. No differences were seen in any of the measured sleep parameters among the different dialysis groups. None of the objectively measured sleep parameters were associated with ISI or PSQI scores in dialysis patients, while sleep times were related to the subjective scores in the healthy cohort. Objectively assessed sleep parameters were associated to neither the uraemic toxicity load nor the Davies–Stoke score.

Conclusions

Independent of the modality, dialysis patients have sleep quality much worse than age- and gender-matched healthy controls. The objectively measured sleep parameters could not be associated to the subjective score, uraemic toxicity or comorbidity score, highlighting the need for objective measurements of sleep and clinical guidelines to aid patient management.
Founding mutations explains hotspots of polycystic kidney disease in Southern Spain
Authors: García Rabaneda Carmen , Perea Francisco , Bellido Díaz María Luz , Morales García Ana I , Martínez Atienza Margarita , Sousa Silva Lisbeth , González Miguel Ángel García , Ruiz-Cabello Francisco , Esteban de la Rosa Rafael J
Published: December 2020

Our group identified two pathogenic variants on the PKD1 gene, c.10527_10528delGA and c.7292T>A, from unrelated families. They came from two small counties in Granada, with 61 and 26 autosomal dominant polycystic kidney disease (ADPKD) individuals affected. To determine a common ancestor, healthy and ADPKD individuals from these families were genotyped by analysing four microsatellites located on chromosome 16. Our study identified a common haplotype in all ADPKD individuals. These findings underpin our hypothesis of the founder effect and explain why there is a high frequency of ADPKD in small regions. Determining hotspots of ADPKD will help to better plan healthcare in the future.
Helping English language teachers become gender aware
Authors: Mojica Claudia P , Castañeda-Peña Harold
Published: December 2020

This article describes some insights gained as a result of a pedagogical experience designed for Colombian ELT teachers with the objective of raising gender awareness in their teaching practices. Such experience derives from a gender-based graduate course offered in a master’s programme in Applied Linguistics to the teaching of English at a Colombian university. During the implementation of this course there were important reflections and insights that could be used for other English language teachers who are interested in adopting a gender view within their teaching practices. This article positions the practical learning of this experience as transformative practices, which aim at supporting in-service English language teachers within their learning process of this perspective. It is hoped that these practices will challenge traditional understandings of English language teacher education drawing on critical pedagogy to build a more explicit gender awareness in the ELT field.
Learning whether to subtract beta-blockers: it’s about time
Authors: van Diepen Sean , Armstrong Paul W
Published: December 2020

Graphical Abstract

Proposed framework for foundational and provisional secondary prevention therapy over time in low-risk post-MI patients. Foundational therapies should be considered in all patients without contraindications, while provisional therapies should be considered in selected patients with comorbidities or post-infarction complications. The horizontal time axis proposes duration of therapies and timeframes for pharmacotherapeutic re-assessment, and should be responsive to the temporal evolution of post-MI risk and events. ADP, adenosine diphosphate receptor inhibitors; ASA, acetylsalicylic acid; CKD, chronic kidney disease; DM, diabetes mellitus; HTN, hypertension; RAAS, renin–angiotensin–aldosterone system; RCT, randomized controlled trials; TG, triglyceride. *Pending guideline recommendations.
The neutrophil–lymphocyte ratio and incident atherosclerotic events: analyses from five contemporary randomized trials
Authors: Adamstein Nicholas H , MacFadyen Jean G , Rose Lynda M , Glynn Robert J , Dey Amit K , Libby Peter , Tabas Ira A , Mehta Nehal N , Ridker Paul M
Published: December 2020

Aims

The neutrophil–lymphocyte ratio (NLR) is a readily available inflammatory biomarker that may associate with atherosclerosis and predict cardiovascular (CV) events. The aims of this study are to determine whether the NLR predicts incident major adverse cardiovascular events (MACE) and is modified by anti-inflammatory therapy.

Methods and results

Baseline and on-treatment NLRs were calculated from complete blood counts among 60 087 participants randomized in the CANTOS, JUPITER, SPIRE-1, SPIRE-2, and CIRT trials to receive placebo or canakinumab, rosuvastatin, bococizumab, or methotrexate, respectively, and followed up for MACE. All analyses were performed first in CANTOS, and then externally validated in the other four trials. For the five trials, hazard ratios for major CV events and mortality comparing NLR quartiles were computed using Cox proportional hazards models, and the effect of each randomized intervention on the NLR was evaluated in comparison to placebo. The NLR modestly correlated with interleukin-6, C-reactive protein, and fibrinogen levels but minimally with lipids. In all five randomized trials, baseline NLR predicted incident CV events and death; the per-quartile increase in risk of MACE was 20% in CANTOS [95% confidence interval (CI) 14–25%, P < 0.0001], 31% in SPIRE-1 (95% CI 14–49%, P = 0.00007), 27% in SPIRE-2 (95% CI 12–43%, P = 0.0002), 9% in CIRT (95% CI 0.2–20%, P = 0.045), and 11% in JUPITER (95% CI 1–22%, P = 0.03). While lipid-lowering agents had no significant impact on the NLR, anti-inflammatory therapy with canakinumab lowered the NLR (P < 0.0001).

Conclusion

The NLR, an easily obtained inflammatory biomarker, independently predicts CV risk and all-cause mortality, and is reduced by interleukin-1β blockade with canakinumab.
Both beat-to-beat changes in RR-interval and left ventricular filling time determine ventricular function during atrial fibrillation
Authors: Lyon Aurore , van Mourik Manouk , Cruts Laura , Heijman Jordi , Bekkers Sebastiaan C A M , Schotten Ulrich , Crijns Harry J G M , Linz Dominik , Lumens Joost
Published: December 2020

Aims

The irregular atrial electrical activity during atrial fibrillation (AF) is associated with a variable left ventricular (LV) systolic function. The mechanisms determining LV function during AF remain incompletely understood. We aimed at elucidating how changes in RR-interval and LV preload affect LV function during AF.

Methods and results

Beat-to-beat speckle-tracking echocardiography was performed in 10 persistent AF patients. We evaluated the relation between longitudinal LV peak strain and preceding RR-interval during AF. We used the CircAdapt computational model to evaluate beat-to-beat preload and peak strain during AF for each patient by imposing the patient-specific RR-interval sequences and a non-contractile atrial myocardium. Generic simulations with artificial RR-interval sequences quantified the haemodynamic changes induced by sudden irregular beats. Clinical data and simulations both showed a larger sensitivity of peak strain to changes in preceding RR-interval at slow heart rate (HR) (cycle length, CL <750 ms) than at faster HR. Simulations explained this by a difference in preload of the current beat. Generic simulations confirmed a larger sensitivity of peak strain to preceding RR-interval at fast HR (CL = 600 ms: Δ peak strain = 3.7% vs. 900 ms: Δ peak strain = 0.3%) as in the patients. They suggested that longer LV activation with respect to preceding RR-interval is determinant for this sensitivity.

Conclusions

During AF, longitudinal LV peak strain is highly variable, particularly at fast HR. Beat-to-beat changes in preload explain the differences in LV systolic function. Simulations revealed that a reduced diastolic LV filling time can explain the increased variability at fast HR.
Rabies virus matrix protein targets host actin cytoskeleton: a protein–protein interaction analysis
Authors: Zandi Fatemeh , Khalaj Vahid , Goshadrou Fatemeh , Meyfour Anna , Gholami Alireza , Enayati Somayeh , Mehranfar Mahsa , Rahmati Saman , Kheiri Elmira Vadaye , Badie Hamid Gholamipour , Vaziri Behrouz
Published: December 2020

Multifunctional matrix protein (M) of rabies virus (RABV) plays essential roles in the pathogenesis of rabies infection. Identification of M protein interacting partners in target hosts could help to elucidate the biological pathways and molecular mechanisms involved in the pathogenesis of this virus. In this study, two-dimensional Far-western blotting (2D-Far-WB) technique was applied to find possible matrix protein partners in the rat brainstem. Recombinant RABV M was expressed in Pichia pastoris and was partially purified. Subsequently, 2D-Far-WB-determined six rat brainstem proteins interacted with recombinant M proteins that were identified by mass spectrometry. Functional annotation by gene ontology analysis determined these proteins were involved in the regulation of synaptic transmission processes, metabolic process and cell morphogenesis–cytoskeleton organization. The interaction of viral M protein with selected host proteins in mouse Neuro-2a cells infected with RABV was verified by super-resolution confocal microscopy. Molecular docking simulations also demonstrated the formation of RABV M complexes. However, further confirmation with co-immunoprecipitation was only successful for M-actin cytoplasmic 1 interaction. Our study revealed actin cytoplasmic 1 as a binding partner of M protein, which might have important role(s) in rabies pathogenesis.
Interkingdom Communication and Regulation of Mucosal Immunity by the Microbiome
Authors: Ethridge Alexander D , Bazzi Malak H , Lukacs Nicholas W , Huffnagle Gary B
Published: December 2020

Intercellular communication and environmental sensing are most often mediated through ligand-receptor binding and signaling. This is true for both host cells and microbial cells. The ligands can be proteins (cytokines, growth factors, and peptides), modified lipids, nucleic acid derivatives and small molecules generated from metabolic pathways. These latter nonprotein metabolites play a much greater role in the overall function of mucosal immunity than previously recognized, and the list of potential immunomodulatory molecules derived from the microbiome is growing. The most well-studied microbial signals are the nonmetabolite microbe-associated molecular pattern molecules, such as lipopolysaccharide and teichoic acid, that bind to host pattern recognition receptors. Here, we will highlight the immunomodulatory activities of other microbiome-derived molecules, such as short-chain fatty acids, bile acids, uric acid, prostaglandins, histamine, catecholamines, aryl hydrocarbon receptor ligands, and 12,13-diHOME.
The Exemplary in Transnational Social Movements: The Legacies of the Alterglobalization Movement
Authors: Perea Ozerin Iratxe
Published: December 2020

Revolutionary theorists have pointed to the “exemplary” in revolutions as the main aspect explaining the power of these phenomena to shape the international system. As a result of their internationalist commitment and their capacity to set revolutionary models, revolutions have a long-term impact not anticipated by even the revolutionaries themselves. Even though they might be overthrown or socialized, the ideas and the internationalist practice exercised by revolutionary movements continue affecting subsequent dynamics of contestation and thus defining world politics. In this article, I argue that the impact of Transnational Social Movements (TSM) can be analyzed in this light. To the extent that they aim to transform the international order, TSMs’ interaction with the international might be deeper than is normally assumed. In order to illustrate this, the article focuses on the Alterglobalization Movement (AGM) as a case study. This approach allows an assessment of the potential of the AGM to shape international politics beyond more immediate victories at the beginning of the millennium.
Integrative Taxonomy of Australian Metopia (Sarcophagidae: Miltogramminae) Reveals a New Species and Challenges Traditional Phylogeny
Authors: Johnston Nikolas P , Wallman James F , Pape Thomas
Published: December 2020

A taxonomic revision of all Australian species of Metopia Meigen (Sarcophagidae: Miltogramminae) is completed using an integrated approach combining molecular and morphological data. Metopia nudibasis (Malloch) is redescribed as a species complex and a new endemic Australian species, Metopia sputnik sp. n., is described. Evidence is presented that Metopia sauteri (Townsend) is absent from Australia and this species is therefore removed from the known Australian fauna. Molecular phylogenetics is used to reconstruct interspecific and generic relationships and support morphology-based species hypotheses. Phylogenetic analysis splits Metopia Meigen into two clades, separated by Aenigmetopia Malloch, rendering the former genus nonmonophyletic. The implications of this are discussed.
A retrospective look at the predictions and recommendations from the 2009 AMIA policy meeting: did we see EHR-related clinician burnout coming?
Authors: Starren Justin B , Tierney William M , Williams Marc S , Tang Paul , Weir Charlene , Koppel Ross , Payne Philip , Hripcsak George , Detmer Don E
Published: December 2020

Clinicians often attribute much of their burnout experience to use of the electronic health record, the adoption of which was greatly accelerated by the Health Information Technology for Economic and Clinical Health Act of 2009. That same year, AMIA’s Policy Meeting focused on possible unintended consequences associated with rapid implementation of electronic health records, generating 17 potential consequences and 15 recommendations to address them. At the 2020 annual meeting of the American College of Medical Informatics (ACMI), ACMI fellows participated in a modified Delphi process to assess the accuracy of the 2009 predictions and the response to the recommendations. Among the findings, the fellows concluded that the degree of clinician burnout and its contributing factors, such as increased documentation requirements, were significantly underestimated. Conversely, problems related to identify theft and fraud were overestimated. Only 3 of the 15 recommendations were adjudged more than half-addressed.
Measurement of clinical documentation burden among physicians and nurses using electronic health records: a scoping review
Authors: Moy Amanda J , Schwartz Jessica M , Chen RuiJun , Sadri Shirin , Lucas Eugene , Cato Kenrick D , Rossetti Sarah Collins
Published: December 2020

Background

 

Objective

Electronic health records (EHRs) are linked with documentation burden resulting in clinician burnout. While clear classifications and validated measures of burnout exist, documentation burden remains ill-defined and inconsistently measured. We aim to conduct a scoping review focused on identifying approaches to documentation burden measurement and their characteristics.

Materials and Methods

Based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews (ScR) guidelines, we conducted a scoping review assessing MEDLINE, Embase, Web of Science, and CINAHL from inception to April 2020 for studies investigating documentation burden among physicians and nurses in ambulatory or inpatient settings. Two reviewers evaluated each potentially relevant study for inclusion/exclusion criteria.

Results

Of the 3482 articles retrieved, 35 studies met inclusion criteria. We identified 15 measurement characteristics, including 7 effort constructs: EHR usage and workload, clinical documentation/review, EHR work after hours and remotely, administrative tasks, cognitively cumbersome work, fragmentation of workflow, and patient interaction. We uncovered 4 time constructs: average time, proportion of time, timeliness of completion, activity rate, and 11 units of analysis. Only 45.0% of studies assessed the impact of EHRs on clinicians and/or patients and 40.0% mentioned clinician burnout.

Discussion

Standard and validated measures of documentation burden are lacking. While time and effort were the core concepts measured, there appears to be no consensus on the best approach nor degree of rigor to study documentation burden.

Conclusion

Further research is needed to reliably operationalize the concept of documentation burden, explore best practices for measurement, and standardize its use.
Quantification of Losartan Potassium Polymorphs Using Powder X-Ray Diffraction
Authors: Lou Yongjun , Zuo Lili
Published: December 2020

Background

Losartan potassium, a common antihypertensive drug on the market, has multiple polymorphs, of which form I is used as a pharmaceutical crystal form. Form I can be partially converted to form III under some circumstances. The quantification of losartan potassium polymorphs is important to control the quality of pharmaceuticals.

Objective

To establish a method to determine the contents of losartan potassium polymorphs.

Methods

Pure form I and form III of losartan potassium were obtained by recrystallization, and characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy, Raman spectroscopy, and thermal analysis. A powder X-ray diffraction method was developed to characterize form I and form III of losartan potassium. Peak area and weight percentage were used to establish calibration curve.

Results

The calibration curve was linear over the range of 1–50% (w/w), using the characteristic peak area ratio of form I at 11.13° 2θ and form III at 5.64° 2θ as the quantitative parameter. The precisions were excellent between 0.6–4.9%, and the limit of quantification was 2.02% (w/w).

Conclusions

This PXRD method can be used to analyze mixtures of losartan potassium polymorphs (forms I and III) quantitatively and control the quality of bulk drug.

Highlights

This is a new method of quantifying the amount of form III in polymorphic forms of losartan potassium using data obtained by PXRD. It is consistent, sensitive, and accurate.
Oviposition-Site Selection of Phlebotomus papatasi (Diptera: Psychodidae) Sand Flies: Attraction to Bacterial Isolates From an Attractive Rearing Medium
Authors: Kakumanu Madhavi L , Marayati Bahjat F , Schal Coby , Apperson Charles S , Wasserberg Gideon , Ponnusamy Loganathan
Published: December 2020

Phlebotomine sand flies are worldwide vectors of Leishmania parasites as well as other bacterial and viral pathogens. Due to the variable impact of traditional vector control practices, a more ecologically based approach is needed. The goal of this study was to isolate bacteria from the most attractive substrate to gravid Phlebotomus papatasi Scopoli sand flies and determine the role of bacterial volatiles in the oviposition attractancy of P. papatasi using behavioral assays. We hypothesized that gravid sand flies are attracted to bacterially derived semiochemical cues associated with breeding sites. Bacteria were isolated from a larvae-conditioned rearing medium, previously shown to be highly attractive to sand flies. The isolated bacteria were identified by amplifying and sequencing 16S rDNA gene fragments, and 12 distinct bacterial species were selected for two-choice olfactometer bioassays. The mix of 12 bacterial isolates elicited strong attraction at the lower concentration of 107 cells per ml and significant repellence at a high concentration of 109 cells per ml. Three individual isolates (SSI-2, SSI-9, and SSI-11) were particularly attractive at low doses. In general, we observed dose-related effects, with some bacterial isolates stimulating negative and some positive dose–response curves in sand fly attraction. Our study confirms the important role of saprophytic bacteria, gut bacteria, or both, in guiding the oviposition-site selection behavior of sand flies. Identifying the specific attractive semiochemical cues that they produce could lead to development of an attractive lure for surveillance and control of sand flies.
Iron–sulfur proteins in plant mitochondria: roles and maturation
Authors: Przybyla-Toscano Jonathan , Christ Loïck , Keech Olivier , Rouhier Nicolas
Published: December 2020

Iron–sulfur (Fe–S) clusters are prosthetic groups ensuring electron transfer reactions, activating substrates for catalytic reactions, providing sulfur atoms for the biosynthesis of vitamins or other cofactors, or having protein-stabilizing effects. Hence, metalloproteins containing these cofactors are essential for numerous and diverse metabolic pathways and cellular processes occurring in the cytoplasm. Mitochondria are organelles where the Fe–S cluster demand is high, notably because the activity of the respiratory chain complexes I, II, and III relies on the correct assembly and functioning of Fe–S proteins. Several other proteins or complexes present in the matrix require Fe–S clusters as well, or depend either on Fe–S proteins such as ferredoxins or on cofactors such as lipoic acid or biotin whose synthesis relies on Fe–S proteins. In this review, we have listed and discussed the Fe–S-dependent enzymes or pathways in plant mitochondria including some potentially novel Fe–S proteins identified based on in silico analysis or on recent evidence obtained in non-plant organisms. We also provide information about recent developments concerning the molecular mechanisms involved in Fe–S cluster synthesis and trafficking steps of these cofactors from maturation factors to client apoproteins.
Ambiguity and context learning in signalling games
Authors: Tang Liping
Published: December 2020

Lexical ambiguity is present in many natural languages, but ambiguous words and phrases do not seem to be advantageous. Therefore, the presence of ambiguous words in natural language warrants explanation. We justify the existence of ambiguity from the perspective of context dependence. The main contribution of the paper is that we constructed a context learning process such that each interlocutor can infer their opponent’s private belief from the conversation. A sufficient condition for successful learning is provided. Furthermore, for cases in which learning fails, we investigate how the interlocutors choose among degrees of ambiguous expressions through an adaptive learning process. Lastly, we apply our model in the lattice network, demonstrating that structural evolution favours ambiguity as well.
On the correspondence between nested calculi and semantic systems for intuitionistic logics
Authors: Lyon Tim
Published: December 2020

This paper studies the relationship between labelled and nested calculi for propositional intuitionistic logic, first-order intuitionistic logic with non-constant domains and first-order intuitionistic logic with constant domains. It is shown that Fitting’s nested calculi naturally arise from their corresponding labelled calculi—for each of the aforementioned logics—via the elimination of structural rules in labelled derivations. The translational correspondence between the two types of systems is leveraged to show that the nested calculi inherit proof-theoretic properties from their associated labelled calculi, such as completeness, invertibility of rules and cut admissibility. Since labelled calculi are easily obtained via a logic’s semantics, the method presented in this paper can be seen as one whereby refined versions of labelled calculi (containing nested calculi as fragments) with favourable properties are derived directly from a logic’s semantics.
Early Childhood Outcomes Among Infants Born by Vaginal Birth After Cesarean and Repeat Cesarean Delivery in the Military Health System
Authors: Kikuchi Jacqueline , Ranjit Anju , Jiang Wei , Witkop Catherine , Hamlin Lynette , Koehlmoos Tracey Perez
Published: December 2020

Objective

This study examines whether children delivered by repeat cesarean section experience higher incidences of otitis media, respiratory infections, and allergic diseases than children delivered by vaginal birth after cesarean section (VBAC) in the Military Health System.

Study Design

This is a retrospective cohort study from the Military Health System Data Repository of women who underwent repeat cesarean section or VBAC between 2006 and 2012 and their offspring through 2014.

Results

About 11,659 infants with 2 years of follow-up were identified. Infants delivered by VBAC had lower odds of developing respiratory illness (P < .000), otitis media (P < .001), and allergies (P = .022) compared with infants born by repeat cesarean section. There were no differences in the development of food allergies.

Conclusion

Emerging data regarding early childhood health are additional factors that can influence the mother’s decision on mode of birth after a primary cesarean section.
Hydrogen and helium escape on Venus via energy transfer from hot oxygen atoms
Authors: Gu Hao , Cui Jun , Niu Dandan , Yu Jiang
Published: December 2020

Due to the relatively strong gravity on Venus, heavy atmospheric neutrals are difficult to accelerate to the escape velocity. However, a variety of processes, such as the dissociative recombination of ionospheric O$_2^+$, are able to produce hot atoms which could deliver a significant amount of energy to light neutrals and drive their escape. In this study, we construct a Monte Carlo model to simulate atmospheric escape of three light species, H, H2, and He, on Venus via such a knock-on process. Two Venusian background atmosphere models are adopted, appropriate for solar minimum and maximum conditions. Various energy-dependent and species-dependent cross-sections, along with a common strongly forward scattering angle distribution, are used in our calculations. Our model results suggest that knock-on by hot O likely plays the dominant role in driving total atmospheric hydrogen and helium escape on Venus at the present epoch, with a significant portion contributed from regions below the exobase. Substantial variations are also revealed by our calculations. Of special interest is the modelled reduction in escape flux at high solar activities for all species, mainly associated with the enhancement in thermal O concentration near the exobase at high solar activities which hinders escape. Finally, model uncertainties due to several controlling factors, including the distribution of relevant light species in the background atmosphere, the plane-parallel approximation, and the finite O energy distribution, are evaluated.
Spatially resolved direct method metallicity in a high-redshift analogue local galaxy: temperature structure impact on metallicity gradients
Authors: Cameron Alex J , Yuan Tiantian , Trenti Michele , Nicholls David C , Kewley Lisa J
Published: December 2020

We investigate how H ii region temperature structure assumptions affect “direct-method” spatially-resolved metallicity observations using multispecies auroral lines in a galaxy from the SAMI Galaxy Survey. SAMI609396B, at redshift z = 0.018, is a low-mass galaxy in a minor merger with intense star formation, analogous to conditions at high redshifts. We use three methods to derive direct metallicities and compare with strong-line diagnostics. The spatial metallicity trends show significant differences among the three direct methods. Our first method is based on the commonly used electron temperature Te([O iii]) from the [O iii]λ4363 auroral line and a traditional Te([O ii]) – Te([O iii]) calibration. The second method applies a recent empirical correction to the O+ abundance from the [O iii]/[O ii] strong-line ratio. The third method infers the Te([O ii]) from the [S ii]λλ4069,76 auroral lines. The first method favours a positive metallicity gradient along SAMI609396B, whereas the second and third methods yield flattened gradients. Strong-line diagnostics produce mostly flat gradients, albeit with unquantified contamination from shocked regions. We conclude that overlooked assumptions about the internal temperature structure of H ii regions in the direct method can lead to large discrepancies in metallicity gradient studies. Our detailed analysis of SAMI609396B underlines that high-accuracy metallicity gradient measurements require a wide array of emission lines and improved spatial resolutions in order to properly constrain excitation sources, physical conditions, and temperature structures of the emitting gas. Integral-field spectroscopic studies with future facilities such as JWST/NIRSpec and ground-based ELTs will be crucial in minimising systematic effects on measured gradients in distant galaxies.
Non-thermal filaments from the tidal destruction of clouds in the Galactic centre
Authors: Coughlin Eric R , Nixon C J , Ginsburg Adam
Published: December 2020

Synchrotron-emitting, non-thermal filaments (NTFs) have been observed near the Galactic centre for nearly four decades, yet their physical origin remains unclear. Here we investigate the possibility that NTFs are produced by the destruction of molecular clouds by the gravitational potential of the Galactic centre. We show that this model predicts the formation of a filamentary structure with length on the order of tens to hundreds of pc, a highly ordered magnetic field along the axis of the filament, and conditions conducive to magnetic reconnection that result in particle acceleration. This model therefore yields the observed magnetic properties of NTFs and a population of relativistic electrons, without the need to appeal to a dipolar, ∼mG, Galactic magnetic field. As the clouds can be both completely or partially disrupted, this model provides a means of establishing the connection between filamentary structures and molecular clouds that is observed in some, but not all, cases.
Giant planet scatterings and collisions: hydrodynamics, merger-ejection branching ratio, and properties of the remnants
Authors: Li Jiaru , Lai Dong , Anderson Kassandra R , Pu Bonan
Published: December 2020

Planetary systems with sufficiently small orbital spacings can experience planetary mergers and ejections. The branching ratio of mergers versus ejections depends sensitively on the treatment of planetary close encounters. Previous works have adopted a simple ‘sticky-sphere’ prescription, whose validity is questionable. We apply both smoothed particle hydrodynamics and N-body integrations to investigate the fluid effects in close encounters between gas giants and the long-term evolution of closely packed planetary systems. Focusing on parabolic encounters between Jupiter-like planets with MJ and 2MJ, we find that quick mergers occur when the impact parameter rp (the pericentre separation between the planets) is less than 2RJ, and the merger conserved at least 97 per cent of the initial mass. Strong tidal effects can affect the ‘binary-planet’ orbit when rp is between 2RJ and 4RJ. We quantify these effects using a set of fitting formulae that can be implemented in N-body codes. We run a suite of N-body simulations with and without the formulae for systems of two giant planets initially in unstable, nearly circular and coplanar orbits. The fluid (tidal) effects significantly increase the branching ratio of planetary mergers relative to ejections by doubling the effective collision radius. While the fluid effects do not change the distributions of semimajor axis and eccentricity of each type of remnant planets (mergers versus surviving planets in ejections), the overall orbital properties of planet scattering remnants are strongly affected due to the branching ratio change. We also find that the merger products have broad distributions of spin magnitudes and obliquities.
Measuring the evolution of intergalactic gas from z = 0 to 5 using the kinematic Sunyaev–Zel’dovich effect
Authors: Chaves-Montero Jonás , Hernández-Monteagudo Carlos , Angulo Raúl E , Emberson J D
Published: December 2020

A complete census of baryons in the late Universe is a long-standing challenge due to the intermediate temperate and rarefied character of the majority of cosmic gas. To gain insight into this problem, we extract measurements of the kinematic Sunyaev–Zel’dovich (kSZ) effect from the cross-correlation of angular redshift fluctuations maps, which contain precise information about the cosmic density and velocity fields, and cosmic microwave background maps high-pass filtered using aperture photometry; we refer to this technique as angular redshift fluctuations (ARF)–kSZ tomography. Remarkably, we detect significant cross-correlation for a wide range of redshifts and filter apertures using 6dF galaxies, BOSS galaxies, and SDSS quasars as tracers, yielding a 11σ detection of the kSZ effect. We then leverage these measurements to set constraints on the location, density, and abundance of gas inducing the kSZ effect, finding that this gas resides outside dark matter haloes, presents densities ranging from 10 to 250 times the cosmic average, and comprises half of cosmic baryons. Taken together, these findings indicate that ARF–kSZ tomography provides a nearly complete census of intergalactic gas from z = 0 to 5.
Chemical abundances in Seyfert galaxies – V. The discovery of shocked emission outside the AGN ionization axis
Authors: Riffel R A , Dors O L , Armah M , Storchi-Bergmann T , Feltre A , Hägele G F , Cardaci M V , Ruschel-Dutra D , Krabbe A C , Pérez-Montero E , Zakamska N L , Freitas I C
Published: December 2020

We present maps for the electron temperature in the inner kpc of three luminous Seyfert galaxies: Mrk 79, Mrk 348, and Mrk 607 obtained from Gemini Multi-Object Spectrograph-integral field unit observations at spatial resolutions of ∼110–280 pc. We study the distributions of electron temperature in active galaxies and find temperatures varying in the range from ∼8000 to $\gtrsim 30\, 000\,$K. Shocks due to gas outflows play an important role in the observed temperature distributions of Mrk 79 and Mrk 348, while standard photoionization models reproduce the derived temperature values for Mrk 607. In Mrk 79 and Mrk 348, we find direct evidence for shock ionization with overall orientation orthogonal to the ionization axis, where shocks can be easily observed as the active galactic nuclei radiation field is shielded by the nuclear dusty torus. This also indicates that even when the ionization cones are narrow, the shocks can be much wider angle.
A pan-cancer atlas of somatic mutations in miRNA biogenesis genes
Authors: Galka-Marciniak Paulina , Urbanek-Trzeciak Martyna Olga , Nawrocka Paulina Maria , Kozlowski Piotr
Published: December 2020

It is a well-known and intensively studied phenomenon that the levels of many miRNAs are differentiated in cancer. miRNA biogenesis and functional expression are complex processes orchestrated by many proteins cumulatively called miRNA biogenesis proteins. To characterize cancer somatic mutations in the miRNA biogenesis genes and investigate their potential impact on the levels of miRNAs, we analyzed whole-exome sequencing datasets of over 10 000 cancer/normal sample pairs deposited within the TCGA repository. We identified and characterized over 3600 somatic mutations in 29 miRNA biogenesis genes and showed that some of the genes are overmutated in specific cancers and/or have recurrent hotspot mutations (e.g. SMAD4 in PAAD, COAD and READ; DICER1 in UCEC; PRKRA in OV and LIN28B in SKCM). We identified a list of miRNAs whose level is affected by particular types of mutations in either SMAD4, SMAD2 or DICER1 and showed that hotspot mutations in the RNase domains in DICER1 not only decrease the level of 5p-miRNAs but also increase the level of 3p-miRNAs, including many well-known cancer-related miRNAs. We also showed an association of the mutations with patient survival. Eventually, we created an atlas/compendium of miRNA biogenesis alterations providing a useful resource for different aspects of biomedical research.
A ubiquitin switch controls autocatalytic inactivation of the DNA–protein crosslink repair protease SPRTN
Authors: Zhao Shubo , Kieser Anja , Li Hao-Yi , Reinking Hannah K , Weickert Pedro , Euteneuer Simon , Yaneva Denitsa , Acampora Aleida C , Götz Maximilian J , Feederle Regina , Stingele Julian
Published: December 2020

Repair of covalent DNA–protein crosslinks (DPCs) by the metalloprotease SPRTN prevents genome instability, premature aging and carcinogenesis. SPRTN is specifically activated by DNA structures containing single- and double-stranded features, but degrades the protein components of DPCs promiscuously and independent of amino acid sequence. This lack of specificity is useful to target diverse protein adducts, however, it requires tight control in return, in order to prohibit uncontrolled proteolysis of chromatin proteins. Here, we discover the components and principles of a ubiquitin switch, which negatively regulates SPRTN. We demonstrate that monoubiquitylation is induced in an E3 ligase-independent manner and, in contrast to previous assumptions, does not control chromatin access of the enzyme. Data obtained in cells and in vitro reveal that monoubiquitylation induces inactivation of the enzyme by triggering autocatalytic cleavage in trans while also priming SPRTN for proteasomal degradation in cis. Finally, we show that the deubiquitylating enzyme USP7 antagonizes this negative control of SPRTN in the presence of DPCs.
Intestinal differentiation involves cleavage of histone H3 N-terminal tails by multiple proteases
Authors: Ferrari Karin Johanna , Amato Simona , Noberini Roberta , Toscani Cecilia , Fernández-Pérez Daniel , Rossi Alessandra , Conforti Pasquale , Zanotti Marika , Bonaldi Tiziana , Tamburri Simone , Pasini Diego
Published: December 2020

The proteolytic cleavage of histone tails, also termed histone clipping, has been described as a mechanism for permanent removal of post-translational modifications (PTMs) from histone proteins. Such activity has been ascribed to ensure regulatory function in key cellular processes such as differentiation, senescence and transcriptional control, for which different histone-specific proteases have been described. However, all these studies were exclusively performed using cell lines cultured in vitro and no clear evidence that histone clipping is regulated in vivo has been reported. Here we show that histone H3 N-terminal tails undergo extensive cleavage in the differentiated cells of the villi in mouse intestinal epithelium. Combining biochemical methods, 3D organoid cultures and in vivo approaches, we demonstrate that intestinal H3 clipping is the result of multiple proteolytic activities. We identified Trypsins and Cathepsin L as specific H3 tail proteases active in small intestinal differentiated cells and showed that their proteolytic activity is differentially affected by the PTM pattern of histone H3 tails. Together, our findings provide in vivo evidence of H3 tail proteolysis in mammalian tissues, directly linking H3 clipping to cell differentiation.
Dynapaenia and sarcopaenia in chronic haemodialysis patients: do muscle weakness and atrophy similarly influence poor outcome?
Authors: Souweine Jean-Sébastien , Pasquier Grégoire , Kuster Nils , Rodriguez Annie , Patrier Laure , Morena Marion , Badia Eric , Raynaud Fabrice , Chalabi Lotfi , Raynal Nathalie , Ohresser Isabelle , Hayot Maurice , Mercier Jacques , Quintrec Moglie Le , Gouzi Fares , Cristol Jean-Paul
Published: December 2020

Background

Sarcopaenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in haemodialysis (HD) patients. It is generally assumed that sarcopaenia is driven by muscle atrophy related to protein-energy wasting. However, dynapaenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopaenia. The aim of this study was to compare the characteristics and prognosis of sarcopaenic and dynapaenic patients among a prospective cohort of chronic HD (CHD) patients.

Methods

Two hundred and thirty-two CHD patients were enrolled from January to July 2016 and then followed prospectively until December 2018. At inclusion, weakness and atrophy were, respectively, evaluated by maximal voluntary force (MVF) and creatinine index (CI). Sarcopaenia was defined as the association of weakness and atrophy (MVF and CI below the median) while dynapaenia was defined as weakness not related to atrophy (MVF below the median, and CI above the median).

Results

From a total of 187 prevalent CHD patients [65% of men, age 65.3 (49.7–82.0) years], 44 died during the follow-up period of 23.7 (12.4–34.9) months. Sarcopaenia and dynapaenia were observed in 33.7 and 16% of the patients, respectively. Compared with patients with sarcopaenia, patients with dynapaenia were younger and with a lower Charlson score. In contrast, mortality rate was similar in both groups (38 and 27%, respectively). After adjustment for age, sex, lean tissue index, serum albumin, high-sensitivity C-reactive protein (hs-CRP), haemoglobin (Hb), normalized protein catabolic rate (nPCR), dialysis vintage and Charlson score, only patients with dynapaenia were at increased risk of death [hazard ratio (HR) = 2.99, confidence interval 1.18–7.61; P = 0.02].

Conclusions

Screening for muscle functionality is highly warranted to identify patients with muscle functional impairment without muscle atrophy. In contrast to sarcopaenia, dynapaenia should appear as a phenotype induced by uraemic milieu, characterized by young patients with low Charlson score and poor prognosis outcome independently of serum albumin, hs-CRP, Hb, nPCR and dialysis vintage.
Home and facility haemodialysis patients: a comparison of outcomes in a matched cohort
Authors: Yeung Emily K , Polkinghorne Kevan R , Kerr Peter G
Published: December 2020

Background

Home haemodialysis (HHD) is utilized significantly less often than facility HD globally with few exceptions, despite being associated with improved survival and better quality of life. Previously HHD was exclusively offered to younger patients with a few comorbidities. However, with the increasing burden of end-stage kidney disease (ESKD) alongside an ageing population, increasing numbers of older patients are being treated with HHD. This study aims to re-evaluate survival and related outcomes in the context of this epidemiological shift.

Methods

A matched cohort design was used to compare all-cause mortality, transplantation, average biochemical values and graft survival 6 months post-transplant between HHD and facility HD patients. A total of 181 HHD patients from a major hospital network were included with 413 facility HD patients from the Australia and New Zealand Dialysis and Transplant Registry matched by age, gender and cause of ESKD. Survival analysis and competing risks analysis (for transplantation) were performed.

Results

After adjusting for body mass index, smoking status, racial group and comorbidities, HHD was associated with a significantly reduced risk of death compared with facility HD patients [hazard ratio 0.47 (95% confidence interval 0.30–0.74)]. Transplantation rates were comparable, with high rates of graft survival at 6 months in both groups. Haemoglobin, calcium and parathyroid hormone levels did not vary significantly. However, HHD patients had significantly lower phosphate levels.

Conclusions

In this study, improved survival outcomes were observed in patients on home compared with facility dialysis, with comparable rates of transplantation, graft survival and biochemical control.