bluuebunny/crossref_metadata_2025 huggingface dataset:
Attosecond pulse generation at ELI-ALPS 100 kHz repetition rate beamline
Authors: Ye Peng , Csizmadia Tamás , Oldal Lénárd Gulyás , Gopalakrishna Harshitha Nandiga , Füle Miklós , Filus Zoltán , Nagyillés Balázs , Divéki Zsolt , Grósz Tímea , Dumergue Mathieu , Jójárt Péter , Seres Imre , Bengery Zsolt , Zuba Viktor , Várallyay Zoltán , Major Balázs , Frassetto Fabio , Devetta Michele , Lucarelli Giacinto Davide , Lucchini Matteo , Moio Bruno , Stagira Salvatore , Vozzi Caterina , Poletto Luca , Nisoli Mauro , Charalambidis Dimitris , Kahaly Subhendu , Zaïr Amelle , Varjú Katalin
Published: May 2020

We generate attosecond pulse train (APT) in argon driven by the high repetition rate (HR) laser of the extreme light infrastructure-attosecond light pulse source (ELI-ALPS), providing 100 kHz, 80 W, 1030 nm, 40 fs pulses from a fiber chirped-pulse amplification (fiber-CPA) laser system. Under the current operating conditions of the high harmonic generation beamline (HR-GHHG), we observed the average pulse duration to be 395 as measured using the technique of reconstruction of attosecond beating by interference of two-photon transitions. The beamline uses an annular-shape laser beam so that the main part of the driving laser co-propagating with the APT can be eliminated by reflection on a holey mirror. An additional 100 nm aluminum foil is used to filter out the remaining laser and the low order harmonics, allowing 2 pJ APT with a bandwidth from 25 eV to 50 eV to be transported to the target position where the APT interacts with matter. The implementation of the HR-GHHG beamline in ELI-ALPS delivering attosecond pulse trains at 100 kHz paves the way for time-resolved experiments in the infrastructure, especially those that involve rare events and coincidence analysis, both of which need high statistics.
Field-induced interactions in magneto-active elastomers - A comparison of experiments and simulations
Authors: Metsch P , Schmidt H , Sindersberger D , A Kalina K , Brummund J , K Auernhammer G , Monkman G J , Kästner M
Published: May 2020

In this contribution, field-induced interactions of magnetizable particles embedded into a soft elastomer matrix are analyzed with regard to the resulting mechanical deformations. By comparing experiments for two-, three- and four-particle systems with the results of finite element simulations, a fully coupled continuum model for magneto-active elastomers is validated with the help of real data for the first time. The model under consideration permits the investigation of magneto-active elastomers with arbitrary particle distances, shapes and volume fractions as well as magnetic and mechanical properties of the individual constituents. It thus represents a basis for future studies on more complex, realistic systems. Our results show a very good agreement between experiments and numerical simulations—the deformation behavior of all systems is captured by the model qualitatively as well as quantitatively. Within a sensitivity analysis, the influence of the initial particle positions on the systems’ response is examined. Furthermore, a comparison of the full three-dimensional model with the often used, simplified two-dimensional approach shows the typical overestimation of resulting interactions in magneto-active elastomers.
Lambert W function methods in double square well and waveguide problems
Authors: Bharatbhai Narola Harsh , Deshmukh P C , Scott Robert B , Roberts Ken , Valluri S R
Published: May 2020

Using methods related to the Lambert W function, we present solutions of two apparently different problems: (1) The one-dimensional double square well potential in quantum mechanics and (2) The transverse electric and magnetic modes for a step-index electromagnetic waveguide. The solution techniques provide insight into the bound energy states for the single and double square well problems and the allowed modes of propagation in a waveguide with varying refractive indices. The solutions can be viewed in either of two related complex plane representations. Comparison of the solution geometries suggests that interesting applications may be possible in nanostructures and devices which are designed to be sensitive to small changes in their environment.
Frailty, a multisystem ageing syndrome
Authors: Thillainadesan Janani , Scott Ian A , Le Couteur David G
Published: May 2020

The management of frail older people is a key component of aged care. There has been a plethora of tools developed for the diagnosis and screening of frailty. Some of these tools are entering routine clinical practice at a time when the higher healthcare costs involved in caring for older people who are frail have become a potential target for cost-cutting. Yet there is still only limited evidence to support the widespread adoption of frailty tools, and foundational factors impact on their accuracy and validity. Despite the acceptance of frailty as a valid term in research and clinical practice, older people believe the term carries stigma. Such issues indicate that there may be a need to reconsider current approaches to frailty. Recent advances in the science of ageing biology can provide a new framework for reconfiguring how we screen, diagnose, treat and prevent frailty. Frailty can be considered to be a multisystem ageing syndrome of decreased physiological and functional reserve, where the biological changes of ageing are seen in most tissues and organs and are the pathogenic mechanism for frailty. Likewise age-related chronic disease and multimorbidity are syndromes where ageing changes occur in one or multiple systems, respectively. This model focusses diagnostic criteria for frailty onto the biomarkers of ageing and generates new targets for the prevention and treatment of frailty based on interventions that influence ageing biology.
GREMA: modelling of emulated gene regulatory networks with confidence levels based on evolutionary intelligence to cope with the underdetermined problem
Authors: Tsai Ming-Ju , Wang Jyun-Rong , Ho Shinn-Jang , Shu Li-Sun , Huang Wen-Lin , Ho Shinn-Ying
Published: May 2020

Motivation

Non-linear ordinary differential equation (ODE) models that contain numerous parameters are suitable for inferring an emulated gene regulatory network (eGRN). However, the number of experimental measurements is usually far smaller than the number of parameters of the eGRN model that leads to an underdetermined problem. There is no unique solution to the inference problem for an eGRN using insufficient measurements.

Results

This work proposes an evolutionary modelling algorithm (EMA) that is based on evolutionary intelligence to cope with the underdetermined problem. EMA uses an intelligent genetic algorithm to solve the large-scale parameter optimization problem. An EMA-based method, GREMA, infers a novel type of gene regulatory network with confidence levels for every inferred regulation. The higher the confidence level is, the more accurate the inferred regulation is. GREMA gradually determines the regulations of an eGRN with confidence levels in descending order using either an S-system or a Hill function-based ODE model. The experimental results showed that the regulations with high-confidence levels are more accurate and robust than regulations with low-confidence levels. Evolutionary intelligence enhanced the mean accuracy of GREMA by 19.2% when using the S-system model with benchmark datasets. An increase in the number of experimental measurements may increase the mean confidence level of the inferred regulations. GREMA performed well compared with existing methods that have been previously applied to the same S-system, DREAM4 challenge and SOS DNA repair benchmark datasets.

Availability and implementation

All of the datasets that were used and the GREMA-based tool are freely available at https://nctuiclab.github.io/GREMA.

Supplementary information

Supplementary data are available at Bioinformatics online.
TopicNet: a framework for measuring transcriptional regulatory network change
Authors: Lou Shaoke , Li Tianxiao , Kong Xiangmeng , Zhang Jing , Liu Jason , Lee Donghoon , Gerstein Mark
Published: May 2020

Motivation

Recently, many chromatin immunoprecipitation sequencing experiments have been carried out for a diverse group of transcription factors (TFs) in many different types of human cells. These experiments manifest large-scale and dynamic changes in regulatory network connectivity (i.e. network ‘rewiring’), highlighting the different regulatory programs operating in disparate cellular states. However, due to the dense and noisy nature of current regulatory networks, directly comparing the gains and losses of targets of key TFs across cell states is often not informative. Thus, here, we seek an abstracted, low-dimensional representation to understand the main features of network change.

Results

We propose a method called TopicNet that applies latent Dirichlet allocation to extract functional topics for a collection of genes regulated by a given TF. We then define a rewiring score to quantify regulatory-network changes in terms of the topic changes for this TF. Using this framework, we can pinpoint particular TFs that change greatly in network connectivity between different cellular states (such as observed in oncogenesis). Also, incorporating gene expression data, we define a topic activity score that measures the degree to which a given topic is active in a particular cellular state. And we show how activity differences can indicate differential survival in various cancers.

Availability and Implementation

The TopicNet framework and related analysis were implemented using R and all codes are available at https://github.com/gersteinlab/topicnet.

Supplementary information

Supplementary data are available at Bioinformatics online.
MutCombinator: identification of mutated peptides allowing combinatorial mutations using nucleotide-based graph search
Authors: Choi Seunghyuk , Paek Eunok
Published: May 2020

Motivation

Proteogenomics has proven its utility by integrating genomics and proteomics. Typical approaches use data from next-generation sequencing to infer proteins expressed. A sample-specific protein sequence database is often adopted to identify novel peptides from matched mass spectrometry-based proteomics; nevertheless, there is no software that can practically identify all possible forms of mutated peptides suggested by various genomic information sources.

Results

We propose MutCombinator, which enables us to practically identify mutated peptides from tandem mass spectra allowing combinatorial mutations during the database search. It uses an upgraded version of a variant graph, keeping track of frame information. The variant graph is indexed by nine nucleotides for fast access. Using MutCombinator, we could identify more mutated peptides than previous methods, because combinations of point mutations are considered and also because it can be practically applied together with a large mutation database such as COSMIC. Furthermore, MutCombinator supports in-frame search for coding regions and three-frame search for non-coding regions.

Availability and implementation

https://prix.hanyang.ac.kr/download/mutcombinator.jsp.

Supplementary information

Supplementary data are available at Bioinformatics online.
Primary Drivers of Reptile Overwintering Habitat Suitability: Integrating Wetland Ecohydrology and Spatial Complexity
Authors: Markle Chantel E , Moore Paul A , Waddington James M
Published: May 2020

Identifying ecosystems resilient to climate and land-use changes is recognized as essential for conservation strategies. However, wetland ecosystems may respond differently to stressors depending on their successional state and the strength of ecohydrological feedbacks resulting in fluctuations in habitat availability and suitability. Long-term habitat suitability is necessary for the persistence of wetland-dependent species and a key characteristic of climatic refugia. In the present article, we review and synthesize biogeochemical, thermal, ecological, and hydrological feedbacks and interactions that operate within wetlands and, consequently, regulate overwintering suitability for many freshwater turtles and snakes. We propose that understanding the breadth and interconnected nature of processes controlling temperature, dissolved oxygen, and water table position are vital for the conservation of northern reptile populations that depend on wetlands to survive winter conditions. Finally, we suggest that our integrated framework can guide future research and the management of wetland ecosystems in an era of unprecedented change.
Effect of additives on mercury partitioning in wet-limestone flue-gas desulfurization
Authors: Masoomi Ida , Heidel Barna , Schmid Marc Oliver , Scheffknecht Günter
Published: May 2020

The wet-flue-gas desulfurization (FGD) process plays an important role in removing water-soluble flue-gas components such as sulphur dioxide (SO2) and oxidized mercury compounds. Under the reducing environment of the FGD, there is the possibility of re-emission of the already absorbed mercury (Hg) to the gas phase, which may be diminished by the utilization of specific additives. In this study, the effect of two different additives on Hg re-emission from the aqueous phase and Hg partitioning in gypsum and filtrate of a lab-scale wet-limestone FGD is investigated. Furthermore, the behaviour of additives in the presence of different halides is studied. The studied additives are TMT 15® as a sulphidic precipitating agent, which forms non-soluble mercury compounds, and activated lignite (AL) as a carbon-based sorbent, which adsorbs Hg compounds from the aqueous phase. TMT 15® has no significant effect on SO2 absorption; on the other hand, addition of AL improves the SO2-removal efficiency by up to 30%. Using both additives, Hg re-emission is suppressed in all the experimented cases except for AL in the absence of halides, in which Hg re-emission shows no change. Thus, the need to form nucleophilic oxidized mercury compounds in the slurry for the adsorption of oxidized mercury on AL can be concluded. Usage of both additives improves Hg retention in the slurry to different extents. It is shown that, for the additive-free slurries, the Hg-adsorption capacity of the solid fraction of the slurry is the limiting parameter. Moreover, the utilization of both additives results in a significant increase in the Hg concentration of solid fraction. The correlation between redox potential and partitioning of Hg in the slurry is presented by comparing the change in the redox potential of slurries when additives are used.
The IBIS-Q [IBd Identification of Spondyloarthritis Questionnaire]: A Novel Tool to Detect Both Axial and Peripheral Arthritis in Inflammatory Bowel Disease Patients
Authors: Variola Angela , Zanolin Maria Elisabetta , Cipriano Giovanni , Macchioni Pierluigi , Martinis Federica , Pasetti Annalisa , Grassi Mario , Geccherle Andrea , Marchetta Antonio , McGonagle Dennis , Tinazzi Ilaria
Published: May 2020

Background and Aims

Both peripheral and axial spondyloarthritis [SpA] occur in inflammatory bowel disease [IBD] and represent the commonest extra-intestinal manifestation. We aimed to develop an easy and quick questionnaire through psychometric analysis, to identify peripheral and axial SpA in IBD patients within an integrated combined multidisciplinary rheumatological-gastroenterology clinic.

Methods

Initially, SpA-IBD experts generated a 42-item list covering SpA manifestations including spinal, articular, and entheseal involvement. The new questionnaire was administered before routine clinical IBD assessment. On the same day, rheumatological assessment, blinded to both history and questionnaire results, was performed to explore the presence of the Assessment of SpondyloArthritis International Society [ASAS] criteria for SpA, diagnostic criteria for fibromyalgia [FM], and non-specific low back pain [NSLB]. Factorial analysis of questionnaire items to identify the main factors—receiver operating characteristic [ROC] curves for sensitivity/specificity and Youden index for cut-off—were performed.

Results

Of the 181 consecutive patients, 56 met the ASAS SpA criteria [prevalence of 30%] with 10 new cases detected [5.5%: seven peripheral and three axial]. Through the psychometric and factorial analysis, we selected 14 items for the final questionnaire [named IBIS-Q]. The IBIS-Q was quick and performed well for detection of axial SpA and peripheral SpA (area under the curve [AUC] 0.88 with 95% confidence interval [CI] 0.830.93). A cut-off of three positive questions had a sensitivity 93% and specificity 77% for SpA patient identification.

Conclusions

The IBIS-Q is a useful and simple tool to use in IBD clinics for SpA detection, with a good statistical performance. Further studies are needed to validate it.
Tests for nonlinear restrictions under misspecified alternatives with an application to testing rational expectation hypotheses
Authors: Bera Anil , Montes-Rojas Gabriel , Sosa-Escudero Walter , Alejo Javier
Published: May 2020

This paper develops generalized method of moments-based (GMM-based) Lagrange multiplier tests for nonlinear hypotheses that are robust to locally misspecified possibly nonlinear alternatives. The procedure is based on an initial consistent GMM estimator of the parameters under a given set of nonlinear restrictions. The new test for one particular set of nonlinear hypotheses is consistent and has correct asymptotic size independently of whether the other, also nonlinear hypotheses, are correct or locally misspecified. To illustrate the usefulness of our proposed tests we consider testing rational expectations hypotheses using U.S. data.
Pollinator Specific Richness and Their Interactions With Local Plant Species: 10 Years of Sampling in Mediterranean Habitats
Authors: Ropars Lise , Affre Laurence , Aubert Matthieu , Fernandez Catherine , Flacher Floriane , Genoud David , Guiter Frédéric , Jaworski Coline , Lair Xavier , Mutillod Clémentine , Nève Gabriel , Schurr Lucie , Geslin Benoît
Published: May 2020

In the context of global pollinator decline, little is known about the protection status and ecology of many species. This lack of knowledge is particularly important for Mediterranean protected areas that harbor diverse pollinator communities and are subject to considerable anthropogenic pressures. Calanques National Park (85 km2), which is located near Marseille (France), is dominated by Mediterranean low-vegetation habitats, such as phrygana and scrublands. These habitats offer favorable conditions for pollinator species due to the important amount of floral resources. Within a 10-yr period, we recorded bee (Hymenoptera: Apoidea: Anthophila), hover fly (Diptera: Syrphidae), and bee fly (Diptera: Bombyliidae) species and their interactions with the local flora through 10 field campaigns. We caught 250 pollinator species, including 192 bees, 38 hover flies, and 20 bee flies, for a total of 2,770 specimens. We recorded seven threatened bees (six near threatened and one endangered). Among the bee species, 47.9% were below-ground nesting species, and 54.7% were generalist species. Analysis of the pollination network showed that generalist and specialist pollinators do not share the same floral resources. The Cistaceae plant family (Malvales: Cistaceae) acted as a central node in the plant–pollinator network, interacting with 52 different pollinator species, which shows the importance of large open flowers that could be easily visited by both short and long-tongued pollinators in Mediterranean habitats. The occurrence of pollinator species and their ecological traits should strongly contribute to reinforcing the available information to provide or ameliorate the conservation statuses determined by IUCN Red List.
Parental Photoperiod Affects Egg Diapause in a Montane Population of Mormon Crickets (Orthoptera: Tettigoniidae)
Authors: Srygley Robert B
Published: May 2020

Insect diapause is a state of arrested development persisting when conditions are favorable for growth. Prolonged diapause, which occurs when insects remain in diapause for multiple years, is uncommon. Mormon crickets Anabrus simplex Haldane, a katydid and pest of rangeland forage and crops, were thought to be biennial in the Bighorn Mountains of Wyoming, but they are able to prolong diapause in the egg stage for multiple years. To test whether parental photoperiod serves as a cue to prolong diapause, mating pairs from the Bighorn Mountains were set in the same daily temperature and humidity profiles with 20 pairs on short daylength (12:12 [L:D] h) and 20 on long daylength (15:9 [L:D] h). Almost every parental pair had some undeveloped eggs after two warm periods. Females in short daylength were not more likely to have eggs with a biennial life cycle, but they were more likely than those in long daylength to lay eggs with multi-annual life cycles. Parents on short daylength were more likely to lay inviable eggs. Other fitness measures, such as hatchling mass, nymphal survivorship, and adult mass were not different between parental treatments. Diapause termination distributed over multiple years probably constitutes a bet-hedging strategy in an unpredictable environment.
Publicising Malfeasance: When the Local Media Structure Facilitates Electoral Accountability in Mexico
Authors: Larreguy Horacio , Marshall John , Snyder James M
Published: May 2020

Malfeasance in local governments is common in developing democracies. Electoral accountability could mitigate such malfeasance, but may require media market structures that incentivise profit-maximising local media to report on incumbent malfeasance. We test this claim in Mexico, leveraging plausibly exogenous variation in the pre-election release of municipal audits revealing misallocated spending and access to broadcast media. We find that each additional local media station amplifies voter punishment (rewards) of high (zero) malfeasance by up to 1 percentage point. Local media’s accountability-enhancing effects are greater when there are fewer non-local competitors and where local outlets’ audiences principally reside within their municipality.
The contribution of female health to economic development
Authors: Bloom David E , Kuhn Michael , Prettner Klaus
Published: May 2020

We analyse the economic consequences for poor countries of investing in female health within a unified growth model featuring health-related gender differences in productivity. Better female health accelerates the demographic transition and thereby the take-off towards sustained economic growth. By contrast, male health improvements delay the transition and take-off because they tend to raise fertility. However, households tend to prefer male health improvements over female health improvements because they imply a larger static utility gain. This highlights the existence of a dynamic trade-off between the short-run interests of households and long-run development goals.
Biomarkers Associated with Physical Resilience After Hip Fracture
Authors: Parker Daniel C , Colόn-Emeric Cathleen , Huebner Janet L , Chou Ching-Heng , Kraus Virginia Byers , Pieper Carl F , Sloane Richard , Whitson Heather E , Orwig Denise , Crabtree Donna M , Magaziner Jay , Bain James R , Muehlbauer Michael , Ilkayeva Olga R , Huffman Kim M
Published: May 2020

Background

Clinically similar older adults demonstrate variable responses to health stressors, heterogeneity attributable to differences in physical resilience. However, molecular mechanisms underlying physical resilience are unknown. We previously derived a measure of physical resilience after hip fracture—the expected recovery differential (ERD)—that captures the difference between actual recovery and predicted recovery. Starting with biomarkers associated with physical performance, morbidity, mortality, and hip fracture, we evaluated associations with the ERD to identify biomarkers of physical resilience after hip fracture.

Methods

In the Baltimore Hip Studies (N = 304) sera, we quantified biomarkers of inflammation (TNFR-I, TNFR-II, sVCAM-1, and IL-6), metabolic and mitochondrial function (non-esterified fatty acids, lactate, ketones, acylcarnitines, free amino acids, and IGF-1), and epigenetic dysregulation (circulating microRNAs). We used principal component analysis, canonical correlation, and least absolute shrinkage and selection operator regression (LASSO) to identify biomarker associations with better-than-expected recovery (greater ERD) after hip fracture.

Results

Participants with greater ERD were more likely to be women and less disabled at baseline. The complete biomarker set explained 37% of the variance in ERD (p < .001) by canonical correlation. LASSO regression identified a biomarker subset that accounted for 27% of the total variance in the ERD and included a metabolic factor (aspartate/asparagine, C22, C5:1, lactate, glutamate/mine), TNFR-I, miR-376a-3p, and miR-16-5p.

Conclusions

We identified a set of biomarkers that explained 27% of the variance in ERD—a measure of physical resilience after hip fracture. These ERD-associated biomarkers may be useful in predicting physical resilience in older adults facing hip fracture and other acute health stressors.
Upper crustal structure of NW Iran revealed by regional 3-D Pg velocity tomography
Authors: Maheri-Peyrov Mehdi , Ghods Abdolreza , Donner Stefanie , Akbarzadeh-Aghdam Maryam , Sobouti Farhad , Motaghi Khalil , Hassanzadeh Mirali , Mortezanejad Gholamreza , Talebian Morteza , Chen Ling
Published: May 2020

We present the result of a 3-D Pg tomography in NW Iran to better understand the relationship between seismicity and velocity structure within the young continental collision system. In this regard, we have collected 559 07 Pg traveltime readings from 3963 well located earthquakes recorded by 353 seismic stations including 121 stations from four new temporary seismic networks. The most prominent feature of our Pg velocity model is a high correlation between the location of majority of large magnitude events and the location of low velocity regions within the seismogenic layer. The large instrumental and historical earthquakes with some limited exceptions tends to happen close to the borders of the low velocity regions. The Lorestan arc of Zagros has the thickest (∼20 km) low velocity region and Central Iran has the thinnest (less than 10 km) low velocity region where little seismicity is observed. Despite the relative increase of thickness of low velocity region in the uppermost part of the upper crust of Alborz, the average Pg velocity of the upper crust increases from Central Iran towards Alborz and reaches to its climax in the northern hills of Alborz, where the catastrophic Rudbar-Tarom 1990 event happened. The Pg velocity map shows presence of a low angle basement ramp in the Lorestan arc at the depth range of ∼10–20 km. The large low angle thrust Ezgele-Sarpolzahab 2017 earthquake and medium size high angle thrust events happened at the base and updip part of the velocity ramp, respectively. The calculated Pg velocity map shows low velocity regions at depths deeper than 11 and 20 km beneath the Sahand and Sabalan volcanoes, respectively.
Muc5ac Expression Protects the Colonic Barrier in Experimental Colitis
Authors: Olli Kristine E , Rapp Caroline , O’Connell Lauren , Collins Colm B , McNamee Eoin N , Jensen Owen , Jedlicka Paul , Allison Kristen C , Goldberg Matthew S , Gerich Mark E , Frank Daniel N , Ir Diana , Robertson Charles E , Evans Christopher M , Aherne Carol M
Published: May 2020

Background

The mucus gel layer (MGL) lining the colon is integral to exclusion of bacteria and maintaining intestinal homeostasis in health and disease. Some MGL defects allowing bacteria to directly contact the colonic surface are commonly observed in ulcerative colitis (UC). The major macromolecular component of the colonic MGL is the secreted gel-forming mucin MUC2, whose expression is essential for homeostasis in health. In UC, another gel-forming mucin, MUC5AC, is induced. In mice, Muc5ac is protective during intestinal helminth infection. Here we tested the expression and functional role of MUC5AC/Muc5ac in UC biopsies and murine colitis.

Methods

We measured MUC5AC/Muc5ac expression in UC biopsies and in dextran sulfate sodium (DSS) colitis. We performed DSS colitis in mice deficient in Muc5ac (Muc5ac-/-) to model the potential functional role of Muc5ac in colitis. To assess MGL integrity, we quantified bacterial-epithelial interaction and translocation to mesenteric lymph nodes. Antibiotic treatment and 16S rRNA gene sequencing were performed to directly investigate the role of bacteria in murine colitis.

Results

Colonic MUC5AC/Muc5ac mRNA expression increased significantly in active UC and murine colitis. Muc5ac-/- mice experienced worsened injury and inflammation in DSS colitis compared with control mice. This result was associated with increased bacterial-epithelial contact and translocation to the mesenteric lymph nodes. However, no change in microbial abundance or community composition was noted. Antibiotic treatment normalized colitis severity in Muc5ac-/- mice to that of antibiotic-treated control mice.

Conclusions

MUC5AC/Muc5ac induction in the acutely inflamed colon controls injury by reducing bacterial breach of the MGL.
Natural History of  Very Early Onset Inflammatory Bowel Disease in North America: A Retrospective Cohort Study
Authors: Kerur Basavaraj , Benchimol Eric I , Fiedler Karoline , Stahl Marisa , Hyams Jeffrey , Stephens Michael , Lu Ying , Pfefferkorn Marian , Alkhouri Raza , Strople Jennifer , Kelsen Judith , Siebold Leah , Goyal Alka , Rosh Joel R , LeLeiko Neal , Van Limbergen Johan , Guerrerio Anthony L , Maltz Ross , Karam Lina , Crowley Eileen , Griffiths Anne , Heyman Melvin B , Deneau Mark , Benkov Keith , Noe Joshua , Mouton Dedrick , Pappa Helen , Galanko Joseph A , Snapper Scott , Muise Aleixo M , Kappelman Michael D
Published: May 2020

Background

The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described.

Methods

We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years.

Results

The study population included 269 children (105 [39%] Crohn’s disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9–5.2). Most (94%) Crohn’s disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn’s disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis.

Conclusions

Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%–15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.
Vitamin D Therapy in Adults With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
Authors: Guzman-Prado Yuli , Samson Ondrej , Segal Jonathan P , Limdi Jimmy K , Hayee Bu’Hussain
Published: May 2020

Background

Vitamin D deficiency has been implicated in the pathogenesis of inflammatory bowel disease. Emerging literature suggests that optimization of vitamin D levels may be associated with improvements in disease activity and quality of life. We conducted a meta-analysis exploring the effect of vitamin D on serum 25-hydroxyvitamin D (s-25[OH]D) levels, clinical improvement, and biomarkers.

Methods

MEDLINE, EMBASE, the Cochrane Library, and sources for grey literature were searched from inception until September 2019. The primary outcome was s-25(OH)D mean differences. Heterogeneity was assessed using the χ 2 test and the I2 statistic. Review Manager software v. 5.3 was used.

Results

Twelve randomized controlled trials (n = 611) and 4 observational studies (n = 359) were included in the meta-analysis. On average, in the randomized controlled trials, vitamin D supplementation increased s-25(OH)D levels by 15.50 ng/mL (95% confidence interval [CI], 11.08-19.92, P ≤ 0.00001, I2 = 90%) and in observational studies they increased by 18.39 ng/mL (95% CI, 8.91-27.88, P = 0.0001, I2 = 82%). Subgroup analyses between vitamin D and placebo groups revealed that vitamin D increased s-25(OH)D by 14.85 ng/mL (95% CI, 9.96-19.73, P ≤ 0.00001, I2 = 90%) and when high doses of vitamin D were compared with low doses, high doses increased s-25(OH)D by 18.27 ng/mL (95% CI, 5.44-31.10, P = 0.005, I2 = 90%). The Harvey Bradshaw Index improved by –1.47 points (95% CI, –2.47 to –0.47, P = 0.004, I2 = 0%) and the high-sensitivity C-reactive protein decreased by –1.58 mg/L (95% CI, –2.95 to –0.21, P = 0.02, I2 = 0%).

Conclusions

Vitamin D supplementation in patients with IBD and vitamin D deficiency is effective at correcting vitamin D levels and is associated with improvement in clinical and biochemical disease activity scores.
Inflammatory Bowel Disease Through the Lens of Single-cell RNA-seq Technologies
Authors: Corridoni Daniele , Chapman Thomas , Antanaviciute Agne , Satsangi Jack , Simmons Alison
Published: May 2020

The intestinal mucosa represents a unique environment where the coordinated function of diverse epithelial, mesenchymal, and immune cells maintains a physiologically balanced environment in the presence of gut microbiota. The intestinal mucosa plays a central role in the pathogenesis of inflammatory bowel disease (IBD), yet the molecular and cellular composition of this diverse environment is poorly understood. However, the recent advent of multimodal single-cell technologies, including single-cell RNA sequencing (scRNA-seq), now provides an opportunity to accurately map the tissue architecture, characterize rare cell types that were previously overlooked, and define function at a single-cell level. In this review, we summarize key advances in single-cell technology and provide an overview of important aspects of computational analysis. We describe emerging data in the field of IBD and discuss how the characterization of novel intestinal mucosa cell populations is reshaping our understanding of this complex disease. We conclude by considering the potential clinical applications, including the definition of novel drug targets and the opportunity for personalization of care in this exciting new era of precision medicine.
Double Biologic Therapy for Refractory Stricturing Crohn’s Disease: A Successful Case of Deep Remission with Ustekinumab and Vedolizumab
Authors: Elmoursi Ahmed , Barrett Terrence A , Perry Courtney
Published: May 2020

Stricturing Crohn’s disease (CD) is a severe phenotype that presents unique challenges to therapeutic management. Emerging literature suggests that anti-TNF monoclonal antibody (mAb) therapies are inadequate for preventing progression to stricture. We hereby present a case of a patient with refractory CD who required multiple surgical resections despite several anti-TNF treatment regimens. Subsequent surgical complications were avoided after changing to combination vedolizumab and ustekinumab therapies every 4 weeks. This case argues for a tailored approach to CD therapy based on disease phenotype and demonstrates that combination therapy with ustekinumab and vedolizumab is a viable option for patients with stricturing disease.
Reversibility of Multimodal Shift: Zebrafish Shift to Olfactory Cues When the Visual Environment Changes
Authors: Suriyampola Piyumika S , Lopez Melissa , Ellsworth Brontë E , Martins Emília P
Published: May 2020

Synopsis

Animals can shift their reliance on different sensory modalities in response to environmental conditions, and knowing the degree to which traits are reversible may help us to predict their chances of survival in a changing environment. Here, using adult zebrafish (Danio rerio), we found that 6 weeks in different light environments alone were sufficient to shift whether fish approached visual or chemical cues first, and that a subsequent reversal of lighting conditions also reversed their sensory preferences. In addition, we measured simple behavioral responses to sensory stimuli presented alone, and found that zebrafish housed in dim light for 6 weeks responded weakly to an optomotor assay, but strongly to an olfactory cue, whereas fish experiencing bright light for 6 weeks responded strongly to the visual optomotor stimulus and weakly in an olfactory assay. Visual and olfactory responses were equally reversible, and shifted to the opposite pattern when we reversed lighting conditions for 6 weeks. In contrast, we did not find a change in activity level, suggesting that changes in multiple sensory modalities can buffer animals from changes in more complex forms of behavior. This reversal of sensory response provides insight into how animals may use sensory shifts to keep up with environmental change.
Different aortic arch surgery methods for type A aortic dissection: clinical outcomes and follow-up results
Authors: Xue Yunxing , Pan Jun , Cao Hailong , Fan Fudong , Luo Xuan , Ge Min , Chen Yang , Wang Dongjin , Zhou Qing
Published: May 2020

OBJECTIVES

The aim of this study was to investigate the clinical outcomes and follow-up results among 5 main aortic arch surgery methods for type A aortic dissection in a single centre.

METHODS

From 2002 to 2018, 958 type A aortic dissection patients who received surgical repair were divided into 5 groups according to the arch surgery method: hemiarch replacement (n = 206), island arch replacement (n = 54), total arch replacement with frozen elephant trunk (n = 425), triple-branched stent (n = 39) and fenestrated stent (n = 234). The indications for the different arch methods were related to the patient’s preoperative status, the location and extent of the dissection and the surgical ability of the surgeons. A comparative study was performed to identify the differences in the perioperative data, and the Kaplan–Meier analysis was used to assess the long-term survival and reintervention rates. Thirty matched surviving patients that were included in each group completed Computed tomography angiography to determine long-term reshaping effect.

RESULTS

The 30-day mortality rate was 15.8%, and there was no difference among the 5 groups (P = 0.848). The follow-up survival rates were similar among the 5 groups (P = 0.130), and the same was true for patients without reintervention (P = 0.471). In the propensity matching study, patients with stents (frozen elephant trunk, triple-branched stent, fenestrated stent) had a slower aortic dilation rate and a higher ratio of thrombosis in the false lumen at the descending aortic and abdominal aortic levels than patients without stents.

CONCLUSIONS

No standard method is available for arch surgery, and indications and long-term effects should be identified with clinical data. In our experiences, simpler surgical procedures could reduce mortality in critically ill patients and stents in the distal aorta could improve long-term reshape effects.
On the complexity of an augmented Lagrangian method for nonconvex optimization
Authors: Grapiglia Geovani Nunes , Yuan Ya-xiang
Published: May 2020

In this paper we study the worst-case complexity of an inexact augmented Lagrangian method for nonconvex constrained problems. Assuming that the penalty parameters are bounded we prove a complexity bound of $\mathcal{O}(|\log (\epsilon )|)$ outer iterations for the referred algorithm to generate an $\epsilon$-approximate KKT point for $\epsilon \in (0,1)$. When the penalty parameters are unbounded we prove an outer iteration complexity bound of $\mathcal{O}(\epsilon ^{-2/(\alpha -1)} )$, where $\alpha>1$ controls the rate of increase of the penalty parameters. For linearly constrained problems these bounds yield to evaluation complexity bounds of $\mathcal{O}(|\log (\epsilon )|^{2}\epsilon ^{-2})$ and $\mathcal{O}(\epsilon ^{- (\frac{2(2+\alpha )}{\alpha -1}+2 )})$, respectively, when appropriate first-order methods ($p=1$) are used to approximately solve the unconstrained subproblems at each iteration. In the case of problems having only linear equality constraints the latter bounds are improved to $\mathcal{O}(|\log (\epsilon )|^{2}\epsilon ^{-(p+1)/p})$ and $\mathcal{O}(\epsilon ^{-(\frac{4}{\alpha -1}+\frac{p+1}{p})})$, respectively, when appropriate $p$-order methods ($p\geq 2$) are used as inner solvers.
China, Japan, and the Governance of Space: prospects for competition and cooperation
Authors: Pekkanen Saadia M.
Published: May 2020

China and Japan are among the world’s top space powers, with significant technical competence in both conventional and ‘newspace’ capabilities. Since the early 1990s, each country has also taken a keen interest in shaping the governance of outer space activities. But they have done so in remarkably different ways, calling into question Asian states’ supposed preferences for soft and informal institutions. Japan has led the Asia-Pacific Regional Space Agency Forum, involving both state and nonstate participants, which is guided by a set of principles. China has opted for a high-profile formal intergovernmental design, the Asia-Pacific Space Cooperation Organization, with a Convention and all the trappings of a formal organizational structure. This article assesses the activities of China and Japan in the new space race, discusses how and why the design of their space governance differs, and reflects on prospects for competition and cooperation.
Effects of source and concentration of neutral detergent fiber from roughage in beef cattle diets on feed intake, ingestive behavior, and ruminal kinetics
Authors: Goulart Rodrigo S , Vieira Ricardo A M , Daniel Joao L P , Amaral Rafael C , Santos Vanessa P , Toledo Filho Sergio G , Cabezas-Garcia Edward H , Tedeschi Luis O , Nussio Luiz G
Published: May 2020

The objectives of this research were to evaluate the effects of source and concentration of α-amylase-treated neutral detergent fiber (aNDF) from roughage on feed intake, ingestive behavior, and ruminal kinetics in beef cattle receiving high-concentrate diets. Six ruminally cannulated Nellore steers (408 ± 12 kg of body weight) were randomly assigned to a 6 × 6 Latin square design with six diets: 10% aNDF from corn silage (10CS); 20% aNDF from corn silage (20CS); or four diets containing 10% aNDF from corn silage and 10% aNDF from one of the following sources: sugarcane (SC), sugarcane bagasse (SCB), soybean hulls (SH), or low oil cottonseed hulls (LOCH). The parameters of passage and degradation kinetics were estimated based on a two-compartmental model with gamma- and exponential-distributed residence times. The nonlinear models were fitted by nonlinear least squares, and a linear mixed-effects model was fitted to all variables measured from the Latin square design that were related to intake, digestibility, digestion kinetic parameters, and residence times. Mean particle size (MPS) between roughage sources (CS, SCB, and SC) and coproducts (SH and LOCH) was affected (P < 0.05). Dry matter intake (DMI) was not affected (P > 0.05) by 20CS, SC, SH, or LOCH. Steers fed 20CS or LOCH diets had 16% and 20% greater DMI, respectively, (P < 0.05) than steers fed 10CS diet. Steers fed SCB consumed the least dry matter (DM). The SH and LOCH diets had lower MPS values (about 8.77 mm) in comparison to 20CS, SCB, and SC diets (about 13.08 mm) and, consequently, affected (P < 0.05) rumen content, ruminal in situ disappearance, nutrient digestibility, and solid fractional passage rate. Chewing time was affected (P < 0.05) by roughage sources and concentration. Lower values of distance travel inside the rumen (min/cm) were observed (P < 0.05) for the SCB and SC diets in comparison with any other diet. Except for SCB, there was no difference (P > 0.05) in rumen fill, among other treatments. Mean daily ruminal pH was not affected (P > 0.05) by 20CS, SCB, SC, and LOCH diets, and it ranged from 6.1 to 6.23. Total short-chain fatty acids concentration was affected (P < 0.05) by roughage source and concentration. Based on our results, we recommend that under Brazilian finishing diets, replacing roughage sources, except for SCB, based on aNDF concentration of the roughage in high-concentrate diets containing finely ground flint corn does not affect DMI.
The effect of reduced dietary glycine and serine and supplemental threonine on growth performance, protein deposition in carcass and viscera, and skin collagen abundance of nursery pigs fed low crude protein diets
Authors: Silva Kayla E , Huber Lee-Anne , Mansilla Wilfredo D , Shoveller Anna K , Htoo John K , Cant John P , de Lange Cornelis F M
Published: May 2020

Thirty five barrows (initial body weight [BW]: 15.1 ± 1.0 kg) were used to determine the effect of partially replacing Gly + Ser with Thr in reduced crude protein (CP) diets on growth performance, protein deposition in carcass and viscera, and skin collagen abundance during the late nursery phase to 25 kg BW. Pigs were individually fed one of five iso-nitrogenous diets (n = 7) for 21 d. The basal diet met estimated essential amino acids (AA) requirements by using all essential AA plus Gly and Ser in free form (CON; 12.1% CP; as-fed, analyzed contents). The remaining four diets were formulated by reducing total Gly and Ser concentrations to 60% or 20% of the CON diet. The N removed with Gly and Ser was replaced with either crystalline Thr or Glu. Total analyzed Thr made up either 1.59% (T1; 12.5% CP) or 2.34% (T2; 12.2% CP) of the Thr-supplemented diets, and total analyzed Glu made up either 3.47% (G1; 12.7% CP) or 4.64% (G2; 12.9% CP) of the Glu-supplemented diets. Pigs were slaughtered on day 21 to determine body composition and skin collagen abundance via bright field microscopy. Overall, average daily gain (ADG) and G:F and final carcass weights were greater for pigs fed diets supplemented with Glu (G1 + G2) vs. those fed diets supplemented with Thr (T1 + T2; P < 0.05, P = 0.060, and P = 0.050 for ADG, G:F, and final carcass weight, respectively); intermediate values were observed for CON. Nitrogen retention in carcass plus viscera and the AA profile of deposited protein in the carcass were not influenced by dietary treatment. Pigs fed the T2 and G2 diets had greater retention of Thr (vs. CON and G2) and Glu (vs. CON and T2) in the viscera protein, respectively (P < 0.05). The apparent utilization efficiency of standardized ileal digestible Thr for protein deposition in carcass plus viscera was less for pigs fed T2 (15.1%) vs. those fed CON (56.7%) or G2 (58.6% ± 2.9%) diets (P < 0.001). Only pigs fed T1 had skin collagen abundance not different from CON; pigs fed G1, G2, and T2 had reduced skin collagen abundance compared with CON and T1 (P < 0.01). Using Glu as an N source when Gly and Ser were reduced to 60% and 20% of CON in reduced CP diets maintained ADG for pigs between 15 and 25 kg BW, whereas supplying Thr as a N source reduced ADG and carcass weight. When dietary Gly and Ser were supplied at 60% of CON, only Thr supplementation rescued skin collagen abundance. Therefore, supplemental Thr at excess levels is not sufficient to replace N from Gly and Ser in reduced CP diets fed to late nursery pigs, despite supporting skin collagen abundance as a secondary indicator of Gly status.