bluuebunny/crossref_metadata_2025_split huggingface dataset:
P662 A retrospective claims analysis on the prevalence and incidence of ulcerative colitis in Germany and the frequency of advanced therapy use
Authors: Mueller S , Khalid M , Patel H , Wilke T , Dittmar A 
Published: May 2021

Abstract

Background
Ulcerative colitis (UC) is a chronic inflammatory bowel disease that requires continuous medical treatment. Current epidemiological data about UC in Germany are lacking, and in particular, it is unknown how many patients are treated with advanced therapies.
This study aimed to investigate the prevalence and incidence of UC in Germany and describe the frequency of advanced therapy use in this population.

Methods
We used claims data from a regional German sickness fund (AOK PLUS). Continuously insured persons from 01/01/2015 until 31/12/2019 or death with at least 2 outpatient diagnoses documented by a specialist in 2 quarters within 12 months or one inpatient diagnosis (ICD-10: K51.-) were defined to be UC prevalent. Patients were defined to be incident in 2019 if the respective selection criteria could be observed in 2019, but no UC diagnosis was documented in the previous 4 years.
Age- and gender-standardized point prevalence was calculated on 01/01/2019, cumulative incidence was evaluated for the year 2019. Standardization was based on the age/gender distribution within the entire population of the German statutory insurance (KM-6 statistic), which covers about 90% of the whole German population.
Main characteristics and comorbidity status were assessed at the index date based on diagnoses documented in the 12-month pre-index period (index: 01/01/2019 or date of incident diagnosis in 2019).
The proportion of prevalent patients receiving advanced therapies (infliximab, adalimumab, golimumab, vedolizumab, tofacitinib) was evaluated in 2019, considering both out- and inpatient treatments.

Results
The standardized incidence in 2019 was 0.36 cases/1,000 persons. Incident patients were, on average, 59.7 years old (SD: 21.6; 95% CI: 58.2–61.1), and 56.1% were females. The mean Charlson Comorbidity Index (CCI) was 2.7 (SD: 3.1; 95% CI: 2.5–2.9).
The standardized prevalence at 01/01/2019 was 5.29 cases/1,000 persons. In 2019, 12,736 prevalent patients were observed (12,510.8 person-years), with 56.2% of the patients being female. The mean age was 60.6 years (SD: 18.8; 95% CI: 60.2–60.9), and the mean CCI was 2.3 (SD: 2.8; 95% CI: 2.2–2.3). 827 patients (6.5%) were treated with advanced therapy in 2019. These patients were considerably younger (44.9 (95% CI: 43.9–46.0) versus 61.7 years (95% CI: 61.3–62.0)) and less comorbid (CCI: 1.2 (95% CI: 1.0–1.3) vs. 2.4 (95% CI: 2.3–2.4)) than patients who have not been treated with an advanced therapy.

Conclusion
Our analysis showed a considerable UC incidence and a high disease burden in Germany, with a prevalence surpassing 0.5%. Advanced therapies were prescribed only in a minority of UC patients, who were generally younger and less comorbid.
P663 Long-term follow up in IBD: 10-year observational study of a UK IBD cohort
Authors: Radhakrishnan S T , Vasireddy A , Gallagher K I , Hicks L C , Powles S T , Chong L , Peake S T , Orchard T R , Williams H R T 
Published: May 2021

Abstract

Background
Crohn’s Disease (CD) and ulcerative colitis (UC) are the two main sub-types of Inflammatory Bowel disease (IBD), which affect 300–500 per 100,000 people within Europe, with an increasing incidence. Long-term outcomes have been reported cohorts of Korean and Scandinavian populations, but long-term UK data are limited.

Methods
Data were prospectively collected from an IBD cohort over a 10-year period. 90 patients were included (47 CD, 36 UC, 7 IBD-unclassified). Phenotypic data (Montreal classification), medication and management decisions were documented. Statistical significance was determined by the Z-score for 2 population proportions.

Results
Over 10 years, the number of operations for CD significantly increased from 8 to 19 patients (p=0.03) but not significantly in UC from 1 to 4 (p=0.09). Perianal involvement in CD also increased from 15.5% to 27.7% at 10 years, but this change was non-significant (p=0.14). Within the UC cohort, a trend for aminosalicylate use was seen, increasing from 53% to 64% (p=0.34), whilst thiopurine use decreased from 44% to 28% (p=0.12). 6/36 patients with UC and 10/47 patients with CD failed thiopurine use due to intolerance or severe side-effects. Biologic use in both UC and CD significantly increased from 10 to 22 patients (p=0.013) over 10 years.

Conclusion
This is the first long-term observational study in IBD patients within the UK. The data show that even with an increase in biologic availability and prescribing, the overall lifetime risk of surgical management in CD does increase with time, mirroring recent publications. Studies with an increased number of IBD patients under long-term follow up are ongoing.
P664 Adherence to mesalazine and identification of patients with ulcerative colitis in healthcare administrative databases of Tuscany (Italy)
Authors: Bertani L , Bartolini C , Ferraro S , Convertino I , Giometto S , Tillati S , Valdiserra G , Cappello E , Blandizzi C , Lucenteforte E , Gini R , Tuccori M , Costa F 
Published: May 2021

Abstract

Background
Drug supply can be used to identify patients with a specific disease in healthcare administrative databases (HAD), particularly when they have a univocal indication. For drugs with multiple indications, other elements must be considered, such as dosing or scheduled regimen. This is the case of mesalazine (MZ), a drug indicated for ulcerative colitis (UC), but also for Crohn’s disease and other not classifiable inflammatory bowel diseases. The aim of the present study was to explore adherence trajectories to MZ, in the attempt of identifying variables useful to detect patients with UC in HAD

Methods
In this retrospective cohort study, data was retrieved from administrative healthcare databases in Tuscany. Patients who had at least a first MZ dispensation between 6/1/2011 and 6/30/2016 (index date, ID) were included. We performed four sub-group analyses: 1) Patients with at least 1 MZ dispensation in the follow-up (FUP); 2) Patients with at least 2 MZ dispensations in the first 3 months of FUP; 3) Patients with MZ dosage &gt;1.5 grams between the 1st and the 2nd dispensation; 4) Patients with MZ dosage &gt;2.5 grams between the 1st and the 2nd dispensation. Each sub-group was stratified by age: ≤65 and &gt;65, separately. We estimated adherence to MZ monthly, through the Medication Possession Ratio and computed adherence trajectories with a 3 step-procedure: 1) computation of 24 statistical measures; 2) factor analysis; 3) cluster analysis. We performed two sensitivity analyses: 1) Patients &gt;65 years old with UC ICD-9 code, 2) Patients ≤65 years old with the UC exemption code.

Results
The sub-groups 1, 2, 3 and 4 included 47.750, 34.037, 29.730 and 26.165 MZ users, respectively. In all the sub-groups and stratification by age, 3 clusters of adherence were identified: high, medium low and low. The high adherence trajectory showed a mean adherence over 40% in the FUP, while patients in the low and medium low trajectories discontinued MZ within 5 and 15 months, respectively. The first and second sensitivity analysis included 409 and 1514 patients, respectively. Two clusters were identified in both analyses: high, around 80%, and moderate, up to 30% at the end of FUP. No MZ discontinuation was observed in the sensitivity analyses on ascertained UC patients.

Conclusion
In the main analyses, two out of three trajectories were characterized by MZ discontinuation, while in the trajectories calculated for the patients with UC codes, no MZ use interruption was detected. This finding could help the identification of true UC patients in the overall population of MZ users.
Seismic crustal structure beneath Jeju Volcanic Island, South Korea from teleseismicP-receiver functions
Authors: Kang Hyunsun , Kim YoungHee , Rhie Junkee , Kang Tae-Seob , Brenna Marco 
Published: May 2021

SUMMARYJeju Island is an intraplate volcanic island with enigmatic origins, located on the continental shelf south of the Korean Peninsula. A dense temporary seismic array, operated on Jeju Island from 2013 to 2015, revealed several important constraints on the magma plumbing system of Jeju Island. In this study, we determined the deep crustal seismic structure beneath Jeju Island from the teleseismic P-to-S converted phases (receiver functions) recorded from 20 temporary and three permanent stations. We removed the contribution of near-surface reverberations in the resulting receiver functions by applying a resonance removal filter. We estimated crustal P-to-S velocity ratio (VP/VS) and discontinuity depth to provide teleseismic constraints on the composition and structure. We observed two major seismic discontinuities, which are the upper boundaries of a mid-to-lower crustal low-velocity zone (LVZ) and the Moho transition zone. The depth to the upper boundary of the LVZ is deep in the west and southeast (24–30 km) and shallow in the northeast (8–11 km). The LVZ can be interpreted as an extensively distributed residual magma plumbing system, with magma batches stalled at various levels and at various degrees of crystallization, consistent with the chemical diversity of Jeju magmas. The seismic characteristics of the Moho transition zone vary greatly among regions. The top interface of the Moho transition zone is at a wide range of depth (26–40 km), and is shallow at 26–29 km depths beneath central Jeju, suggesting a complex Moho topography. The presence of mafic cumulates and partially molten mushes may contribute to the observed shallow seismic discontinuity at a depth of 26–29 km. The lack of obvious crustal thickening below the shield volcano, Mt Halla, may be associated with mantle upwelling or presence of mafic underplating and cumulates below Jeju. Spatial variations of crustal VP/VS represent highly heterogeneous crustal composition, resulting from magma differentiation during the evolution of the island.
Perspectives on Individual Animal Identification from Biology and Computer Vision
Authors: Vidal Maxime , Wolf Nathan , Rosenberg Beth , Harris Bradley P , Mathis Alexander 
Published: May 2021

Synopsis
Identifying individual animals is crucial for many biological investigations. In response to some of the limitations of current identification methods, new automated computer vision approaches have emerged with strong performance. Here, we review current advances of computer vision identification techniques to provide both computer scientists and biologists with an overview of the available tools and discuss their applications. We conclude by offering recommendations for starting an animal identification project, illustrate current limitations, and propose how they might be addressed in the future.
Tails, Flails, and Sails: How Appendages Improve Terrestrial Maneuverability by Improving Stability
Authors: Shield Stacey , Jericevich Ricardo , Patel Amir , Jusufi Ardian 
Published: May 2021

Abstract
Trade-offs in maneuverability and stability are essential in ecologically relevant situations with respect to robustness of locomotion, with multiple strategies apparent in animal model systems depending on their habitat and ecology. Free appendages such as tails and ungrounded limbs may assist in navigating this trade-off by assisting with balance, thereby increasing the acceleration that can be achieved without destabilizing the body. This comparative analysis explores the inertial mechanisms and, in some cases, fluid dynamic mechanisms by which appendages contribute to the stabilization of gait and perturbation response behaviors in a wide variety of animals. Following a broad review of examples from nature and bio-inspired robotics that illustrate the importance of appendages to the control of body orientation, two specific cases are examined through preliminary experiments: the role of arm motion in bipedal gait termination is explored using trajectory optimization, and the role of the cheetah’s tail during a deceleration maneuver is analyzed based on motion capture data. In both these examples, forward rotation of the appendage in question is found to counteract the unwanted forward pitch caused by the braking forces. It is theorized that this stabilizing action may facilitate more rapid deceleration by allowing larger or longer-acting braking forces to be applied safely.
Home range variation in leopards living across the human density gradient
Authors: Snider Matthew H , Athreya Vidya R , Balme Guy A , Bidner Laura R , Farhadinia Mohammed S , Fattebert Julien , Gompper Matthew E , Gubbi Sanjay , Hunter Luke T B , Isbell Lynne A , Macdonald David W , Odden Morten , Owen Cailey R , Slotow Rob , Spalton James A , Stein Andrew B , Steyn Villiers , Vanak Abi T , Weise Florian J , Wilmers Christopher C , Kays Roland 
Published: May 2021

AbstractHome range size is a fundamental measure of animal space use, providing insight into habitat quality, animal density, and social organization. Human impacts increasingly are affecting wildlife, especially among wide-ranging species that encounter anthropogenic disturbance. Leopards (Panthera pardus) provide a useful model for studying this relationship because leopards coexist with people at high and low human densities and are sensitive to human disturbance. To compare leopard home range size across a range of human densities and other environmental conditions, we combined animal tracking data from 74 leopards in multiple studies with new analytical techniques that accommodate different sampling regimes. We predicted that home ranges would be smaller in more productive habitats and areas of higher human population density due to possible linkage with leopard prey subsidies from domestic species. We also predicted that male leopards would have larger home ranges than those of females. Home ranges varied in size from 14.5 km2 in India to 885.6 km2 in Namibia, representing a 60-fold magnitude of variation. Home range stability was evident for 95.2% of nontranslocated individuals and 38.5% of translocated individuals. Leopard home range sizes were negatively correlated with landscape productivity, and males used larger areas than females. Leopards in open habitats had a predicted negative correlation in home range size with human population density, but leopards in closed habitats used larger home ranges in areas with more people.
Advantages of an Automated Method Compared With Manual Methods for the Quantification of Intraepidermal Nerve Fiber in Skin Biopsy
Authors: Corrà Marta Francisca , Sousa Mafalda , Reis Inês , Tanganelli Fabiana , Vila-Chã Nuno , Sousa Ana Paula , Magalhães Rui , Sampaio Paula , Taipa Ricardo , Maia Luís 
Published: May 2021

Abstract
Intraepidermal nerve fiber density (IENFD) measurements in skin biopsy are performed manually by 1–3 operators. To improve diagnostic accuracy and applicability in clinical practice, we developed an automated method for fast IENFD determination with low operator-dependency. Sixty skin biopsy specimens were stained with the axonal marker PGP9.5 and imaged using a widefield fluorescence microscope. IENFD was first determined manually by 3 independent observers. Subsequently, images were processed in their Z-max projection and the intradermal line was delineated automatically. IENFD was calculated automatically (fluorescent images automated counting [FIAC]) and compared with manual counting on the same fluorescence images (fluorescent images manual counting [FIMC]), and with classical manual counting (CMC) data. A FIMC showed lower variability among observers compared with CMC (interclass correlation [ICC] = 0.996 vs 0.950). FIMC and FIAC showed high reliability (ICC = 0.999). A moderate-to-high (ICC = 0.705) was observed between CMC and FIAC counting. The algorithm process took on average 15 seconds to perform FIAC counting, compared with 10 minutes for FIMC counting. This automated method rapidly and reliably detects small nerve fibers in skin biopsies with clear advantages over the classical manual technique.
Incidence and risk factors for pneumonitis among patients with lung cancer who received immune checkpoint inhibitors after palliative thoracic radiotherapy
Authors: Saito Satoshi , Abe Takanori , Iino Misaki , Aoshika Tomomi , Ryuno Yasuhiro , Ohta Tomohiro , Igari Mitsunobu , Hirai Ryuta , Kumazaki Yu , Yamaguchi Ou , Kaira Kyoichi , Kagamu Hiroshi , Noda Shin-ei , Kato Shingo 
Published: May 2021

Abstract
The aim of this study is to analyze the incidence and risk factors for pneumonitis when immune checkpoint inhibitors (ICIs) are combined with palliative thoracic radiotherapy (RT) for lung cancer. We retrospectively evaluated 29 patients with lung cancer who received ICIs after palliative thoracic RT (30 Gy in 10 fractions). Their ICIs were pembrolizumab (n = 17), nivolumab (n = 8) and atezolizumab (n = 4). Median follow-up period was 10 months. The median interval between starting RT and starting ICI was 25 days. Pneumonitis events were grade 1 (n = 10; 34%), grade 2 (n = 4; 14%) and grade 3 (n = 3; 10%). Obstructive pneumonia was significantly associated with grade ≥ 2 pneumonitis (P = 0.036). Age, sex, ICI agent, interval between RT and ICI and history of ICI before RT were not associated with grade ≥ 2 pneumonitis. Tumor volume; Brinkman index; dosimetric factors, such as lung V5, V10, V20, V30 and mean lung dose (MLD); lactate dehydrogenase; and C-reactive protein did not significantly differ between the grade ≤ 1 and grade ≥ 2 pneumonitis groups. Levels of sialylated carbohydrate antigen KL-6 were evaluated in 27 patients before RT; they significantly differed between patients with grade ≤ 2 pneumonitis (mean: 431 U/ml) and those with grade ≥ 3 pneumonitis (mean: 958 U/ml; P &lt; 0.001). Patients who receive ICI after palliative thoracic RT should be carefully followed-up, especially those who have had obstructive pneumonia or high KL-6 levels.
Elevated CO2 modulates the effect of heat stress responses inTriticum aestivumby differential expression of anisoflavone reductase-like gene
Authors: Shokat Sajid , Novák Ondřej , Široká Jitka , Singh Sukhwinder , Gill Kulvinder Singh , Roitsch Thomas , Großkinsky Dominik K , Liu Fulai 
Published: May 2021

AbstractTwo wheat genotypes forming high and low biomass, exhibiting differential expression of an isoflavone reductase-like (IRL) gene, and resulting in contrasting grain yield under heat stress field conditions were analyzed in detail for their responses under controlled heat and elevated CO2 conditions. Significant differences in IRL expression between the two lines were hypothesized to be the basis of their differential performance under the tested conditions and their stress tolerance potential. By a holistic approach integrating advanced cell physiological phenotyping of the antioxidative and phytohormone system in spikes and leaves with measurements of ecophysiological and agronomic traits, the genetic differences of the genotypes in IRL expression were assessed. In response to heat and elevated CO2, the two genotypes showed opposite regulation of IRL expression, which was associated with cytokinin concentration, total flavonoid contents, activity of superoxide dismutase, antioxidant capacity and photosynthetic rate in leaves, and cytokinin concentration and ascorbate peroxidase activity in spikes. Our study showed that IRL expression is associated with wheat yield performance under heat stress at anthesis, mediated by diverse physiological mechanisms. Hence, based on our results, the IRL gene is a promising candidate for developing genetic markers for breeding heat-tolerant wheat.
The COS-legacy survey of C iv absorbers: properties and origins of the intervening systems
Authors: Manuwal Aditya , Narayanan Anand , Udhwani Purvi , Srianand Raghunathan , Savage Blair D , Charlton Jane C , Misawa Toru 
Published: May 2021

ABSTRACT
We present here results from a survey of intervening C iv absorbers at z &lt; 0.16 conducted using 223 sightlines from the Hubble Spectroscopic Legacy Archive. Most systems (83%) out of the total sample of 69 have simple kinematics with 1 or 2 C iv components. In the 22 C iv systems with well constrained H i column densities, the temperatures from the b-values imply predominantly photoionized plasma (T ≤ 105 K) and non-thermal dynamics. These systems also have solar or higher metallicities. We obtain a C iv line density of $\mathrm{ d}\mathcal {N}/\mathrm{ d}X = 5.1\pm 1.0$ for $\log [N(\rm {C}\, \rm {{iv}})~(\rm {cm}^{-2})]\ge 12.9$, and $\Omega _{\rm {C}\, \rm {\rm {iv}}}=(8.01\pm 1.62) \times 10^{-8}$ for $12.9 \le \log [N(\rm {C}\, \rm {{iv}})~(\rm {cm}^{-2})] \le 15.0$. The C iv bearing diffuse gas in the z &lt; 0.16 Universe has a metallicity of (2.07 ± 0.43) × 10−3 Z⊙, an order of magnitude more than the metal abundances in the IGM at high redshifts (z ≳ 5), and consistent with the slow build-up of metals in the diffuse circum/intergalactic space with cosmic time. For z &lt; 0.015 (complete above L &gt; 0.01L⋆), the Sloan Digital Sky Survey provides a tentative evidence of declining covering fraction for strong C iv (N &gt; 1013.5 cm−2) with ρ (impact parameter) and ρ/Rvir. However, the increase at high separations suggests that strong systems are not necessarily coincident with such galaxies. We also find that strong C iv absorption at z &lt; 0.051 is not coincident with galaxy overdense regions complete for L &gt; 0.13L⋆.
AniProtDB: A Collection of Consistently Generated Metazoan Proteomes for Comparative Genomics Studies
Authors: Barreira Sofia N , Nguyen Anh-Dao , Fredriksen Mark T , Wolfsberg Tyra G , Moreland R Travis , Baxevanis Andreas D 
Published: May 2021

Abstract
To address the void in the availability of high-quality proteomic data traversing the animal tree, we have implemented a pipeline for generating de novo assemblies based on publicly available data from the NCBI Sequence Read Archive, yielding a comprehensive collection of proteomes from 100 species spanning 21 animal phyla. We have also created the Animal Proteome Database (AniProtDB), a resource providing open access to this collection of high-quality metazoan proteomes, along with information on predicted proteins and protein domains for each taxonomic classification and the ability to perform sequence similarity searches against all proteomes generated using this pipeline. This solution vastly increases the utility of these data by removing the barrier to access for research groups who do not have the expertise or resources to generate these data themselves and enables the use of data from nontraditional research organisms that have the potential to address key questions in biomedicine.
Structural basis of successive adenosine modifications by the conserved ribosomal methyltransferase KsgA
Authors: Stephan Niklas C , Ries Anne B , Boehringer Daniel , Ban Nenad 
Published: May 2021

Abstract
Biogenesis of ribosomal subunits involves enzymatic modifications of rRNA that fine-tune functionally important regions. The universally conserved prokaryotic dimethyltransferase KsgA sequentially modifies two universally conserved adenosine residues in helix 45 of the small ribosomal subunit rRNA, which is in proximity of the decoding site. Here we present the cryo-EM structure of Escherichia coli KsgA bound to an E. coli 30S at a resolution of 3.1 Å. The high-resolution structure reveals how KsgA recognizes immature rRNA and binds helix 45 in a conformation where one of the substrate nucleotides is flipped-out into the active site. We suggest that successive processing of two adjacent nucleotides involves base-flipping of the rRNA, which allows modification of the second substrate nucleotide without dissociation of the enzyme. Since KsgA is homologous to the essential eukaryotic methyltransferase Dim1 involved in 40S maturation, these results have also implications for understanding eukaryotic ribosome maturation.