bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden of disease among patients with prevalent Crohn’s disease: results from a large German sickness fund
Authors: Zhuleku Evi , Antolin-Fontes Beatriz , Borsi Andras , Nissinen Riikka , Bravatà Ivana , Barthelmes Jennifer Norma , Lee Jennifer , Passey Alun , Wirth Daniel , Maywald Ulf , Bokemeyer Bernd , Wilke Thomas , Ghiani Marco 
Published: March 2023

Abstract

Purpose
The aim of this study was to investigate the burden of disease among a real-world cohort of patients with prevalent Crohn’s disease (CD) in Germany.

Methods
We conducted a retrospective cohort analysis using administrative claims data from the German AOK PLUS health insurance fund. Continuously insured patients with a CD diagnosis between 01 October 2014 and 31 December 2018 were selected and followed for at least 12 months or longer until death or end of data availability on 31 December 2019. Medication use (biologics, immunosuppressants (IMS), steroids, 5-aminosalicylic acid) was assessed sequentially in the follow-up period. Among patients with no IMS or biologics (advanced therapy), we investigated indicators of active disease and corticosteroid use.

Results
Overall, 9284 prevalent CD patients were identified. Within the study period, 14.7% of CD patients were treated with biologics and 11.6% received IMS. Approximately 47% of all prevalent CD patients had mild disease, defined as no advanced therapy and signs of disease activity. Of 6836 (73.6%) patients who did not receive advanced therapy in the follow-up period, 36.3% showed signs of active disease; 40.1% used corticosteroids (including oral budesonide), with 9.9% exhibiting steroid dependency (≥ 1 prescription every 3 months for at least 12 months) in the available follow-up.

Conclusions
This study suggests that there remains a large burden of disease among patients who do not receive IMS or biologics in the real world in Germany. A revision of treatment algorithms of patients in this setting according to the latest guidelines may improve patient outcomes.
Amnio acid substitution at position 298 of human glucose-6 phosphatase-α significantly impacts its stability in mammalian cells
Authors: Cao Jingsong , Markel Arianna , Hanahoe Erin , Ketova Tatiana , Mihai Cosmin , Zalinger Zach , Marquardt David , Amato Nicholas J. , Cheng Yi Min , Reid David W. , Dousis Athanasios , Giangrande Paloma H. , Schultz Joshua R. , Martini Paolo G. V. , Finn Patrick F. 
Published: March 2023

AbstractGlucose-6-phosphatase-α (G6Pase-α) catalyzes the hydrolysis of glucose-6-phosphate to glucose and functions as a key regulator in maintaining blood glucose homeostasis. Deficiency in G6Pase-α causes glycogen storage disease 1a (GSD1a), an inherited disorder characterized by life-threatening hypoglycemia and other long-term complications. We have developed a potential mRNA-based therapy for GSD1a and demonstrated that a human G6Pase-α (hG6Pase-α) variant harboring a single serine (S) to cysteine (C) substitution at the amino acid site 298 (S298C) had > twofold increase in protein expression, resulting in improved in vivo efficacy. Here, we sought to investigate the mechanisms contributing to the increased expression of the S298C variant. Mutagenesis of hG6Pase-α identified distinct protein variants at the 298 amino acid position with substantial reduction in protein expression in cultured cells. Kinetic analysis of expression and subcellular localization in mammalian cells, combined with cell-free in vitro translation assays, revealed that altered protein expression stemmed from differences in cellular protein stability rather than biosynthetic rates. Site-specific mutagenesis studies targeting other cysteines of the hG6Pase-α S298C variant suggest the observed improvements in stability are not due to additional disulfide bond formation. The glycosylation at Asparagine (N)-96 is critical in maintaining enzymatic activity and mutations at position 298 mainly affected glycosylated forms of hG6Pase-α. Finally, proteasome inhibition by lactacystin improved expression levels of unstable hG6Pase-α variants. Taken together, these data uncover a critical role for a single amino acid substitution impacting the stability of G6Pase-α and provide insights into the molecular genetics of GSD1a and protein engineering for therapeutic development.
On identifying possible artificial intelligence applications in requirements engineering processes
Authors: Dehn Simon , Jacobs Georg , Zerwas Thilo , Berroth Joerg , Hötter Matthis , Korten Matthias , Müller Marvin , Gossen Nico , Striegel Serena , Fleischer Dirk 
Published: March 2023

AbstractManaging an ever-growing number of requirements is a time consuming and highly complex activity in product development projects. With the rise of Artificial Intelligence (AI) in the last decades, algorithms are now capable of supporting Requirements Engineering (RE) tasks. The algorithm’s ability to intelligently process natural language data as well as the application in RE have been published extensively. In established RE processes however, it is often unclear, where AI algorithms can be utilized. The result is a significant imbalance between state-of-the-art AI algorithms and their application rates in real RE processes. One of the reasons is, that current models of RE processes aren’t able to convey the needed information for the identification of suitable tasks. Therefore, this paper aims to provide a framework of finite and standardized process steps with a data processing-oriented perspective, that can be used to systematically identify the points in the RE processes where AI algorithms can be applied. With the standardized process steps of this framework, established RE processes can be abstracted and expressed in a way that is compatible with the scope of AI algorithms. Due to the finite number of standardized process steps, libraries of suitable AI algorithms for the defined process steps can be built, so that their applicability can be efficiently assessed. The presented framework was developed collaboratively during a research project with industry participation.
Assessing fluid volume and determining outcomes of acute heart failure using plasma human atrial natriuretic peptide
Authors: Suzuki Yuya , Otsuka Tadashi , Yoshioka Yuki , Iida Tomomichi , Maruyama Shingo , Watanabe Hirofumi , Kaseda Ryohei , Yamamoto Suguru , Kaneko Yoshikatsu , Goto Shin , Aoyagi Ryuji , Narita Ichiei 
Published: March 2023

Abstract
Background
The post-dialysis plasma level of human atrial natriuretic peptide (hANP) reflects the fluid volume in patients on hemodialysis. The threshold hANP level is reportedly 100 pg/mL; however, the clinical usefulness of the threshold hANP level for volume control has not been sufficiently studied.

Methods
We conducted a single-center, retrospective, observational study that included 156 hemodialysis patients without atrial fibrillation. First, we examined the usefulness of the threshold hANP level (100 pg/mL) for predicting hypoxemia due to congestion in a short-term observational study from December 30, 2015 to January 5, 2016. Subsequently, we conducted a 5-year follow-up study wherein the outcomes were hospitalization due to acute heart failure (AHF), development of cardiovascular diseases (CVD), and all-cause death. Finally, we collected echocardiography data to investigate the relationship between cardiac function and hANP.

Results
Our short-term observational study showed that patients with an hANP level ≥ 100 pg/mL developed hypoxemia due to congestion (odds ratio, 3.52; 95% confidence interval, 1.06–11.71; P = 0.040). At the 5-year follow-up, patients with an hANP level ≥ 100 pg/mL had significantly higher rates of hospitalization due to AHF, CVD, and all-cause death based on the log-rank test (P = 0.003, P = 0.019, P < 0.001, respectively). Cardiac disfunctions were significantly associated with the high hANP level.

Conclusions
The hANP level is indicative of both fluid volume and cardiac dysfunction. A threshold hANP level of 100 pg/mL can serve as a predictive marker for AHF and a practical indicator for volume control.
Urethane-acrylate-based photo-inks for digital light processing of flexible materials
Authors: Kuang Guanxing , Bakhshi Hadi , Meyer Wolfdietrich 
Published: March 2023

AbstractUrethane–acrylate-based photo-inks containing various concentrations (0.1–1.5 wt.%) of two photo-initiators, namely ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate (TPOL) or diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (BPO), for digital light processing (DLP) were developed. According to photo-DSC kinetics investigations, no significant difference was detected between the photo-activity of formulations containing BPO or TPOL at various concentrations. BPO (1.0 wt.%) with a high molar extinction coefficient (500 L/mol·cm at 365 nm) resulted in higher controllability on the layer thickness (100 µm) during the 3D printing process. The surface cracks that appeared during the post-curing process could be avoided by splitting the exposure time (5 min) into short intervals (5 × 1 min) without affecting double bond conversion (DBC). Several flexible objects were successfully 3D printed in good quality and their thermomechanical properties and layer-by-layer morphology were investigated.
Floral enhancement of turfgrass lawns benefits wild bees and honey bees (Apis mellifera)
Authors: Wolfin James , Watkins Eric , Lane Ian , Portman Zachary M. , Spivak Marla 
Published: March 2023

AbstractThe turfgrass lawn is a common feature of urban and suburban communities, often accounting for the largest green spaces by area in these landscapes. Flowering species within turfgrass lawns have the potential to serve as a source of forage for bee pollinators in urban and suburban areas. We intentionally introduced low-growing flowers to turfgrass lawns to promote bee diversity and reduce inputs, while maintaining the traditional aesthetics and recreational uses associated with lawns. We compared bee communities on lawns with naturally-occurring blooms of Trifolium repens to bee communities on florally-enhanced lawns that contained Prunella vulgaris ssp. lanceolata and Thymus serpyllum in addition to T. repens. Trifolium repens provided forage for both wild bee communities and Apis mellifera, with A. mellifera being the most common of the 56 species of bees observed on T. repens. We found that florally-enhanced lawns supported more diverse bee communities than lawns with just T. repens. Furthermore, the bee communities supported by florally-enhanced lawns were significantly different from the bee communities supported by lawns containing just T. repens based on presence-absence data (Jaccard’s dissimilarity index). Our research indicates that A. mellifera colonies and wild bee communities can be supported by allowing T. repens to bloom in turfgrass lawns, and that land managers can support more diverse bee communities by intentionally introducing low-growing species of flowers to lawns.
Circularity indicators and added value to traditional LCA impact categories: example of pig production
Authors: Møller Hanne , Lyng Kari-Anne , Röös Elin , Samsonstuen Stine , Olsen Hanne Fjerdingby 
Published: March 2023

Abstract
Purpose
The purpose of using circularity indicators is to show the effect of changes from linear to more circular systems. This paper contributes to highlighting the importance of methodological aspects of circularity indicators in the agricultural sector when using a life cycle thinking approach. Selected circularity indicators have been explored and compared with LCA impact categories by using them to evaluate the circularity of a livestock system.

Methods
Circularity indicators were tested on a theoretical pig production system where several circularity strategies and associated mitigation actions were applied. The strategies and mitigation actions were as follows: anaerobic digestion of manure (closing resource loops), anaerobic digestion of bread waste (closing resource loops), precision fertilization (narrowing resource loops), use of cover crops in feed production (regenerating resource flows), and use of bread waste as feed (slowing resource loops). The functional unit was 1 kg pork as carcass weight, and the treatment of 1.1 kg bread waste for all impact categories and indicators. For each mitigation action, relevant circularity indicators were tested. Based on this, the functionality and suitability of these indicators were discussed.

Results and discussion
Four of the circularity indicators were based on nitrogen (N) or phosphorus (P) substances: N recycling index, partial N balance, consumption of fossil-P fertilizers, and emissions to water bodies (P). Even if the indicators do not capture the impact of emissions of N and P as the eutrophication impact categories, they provide a useful indication of the circularity of a system. The other three circularity indicators tested were as follows: renewable energy production, soil organic carbon, and land use ratio. The renewable energy production indicator is easy to understand and communicate and provides unique information. Soil organic carbon presents a potential for soil carbon sequestration. Land use ratio is based on the same data as land occupation but provides an assessment of whether feed production competes for the suitable area for food production by including production of human-digestible protein.

Conclusions
Circularity indicators provide valuable information about the circularity of an agricultural product system. The circularity indicators and LCA impact categories can be used either separately or together, or to complement each other. The choice of indicators depends on the questions raised, i.e., goals and scope, and it is therefore important to have a number of circular indicators to choose from in order to achieve a comprehensive assessment.
On the Necessity Defense in a Democratic Welfare State: Leaving Pandora’s Box Ajar
Authors: Coca-Vila Ivó 
Published: March 2023

AbstractThe necessity defense is barely accepted in contemporary Western case law. The courts, relying on the opinion held by the majority of legal scholars, have reduced its margin of application to practically zero, since in the framework of contemporary welfare states, there is almost always a “legal alternative.” The needy person who acts on their own behalf, regardless of whether they save an interest higher than the one they injure, does not show due deference to democratic legal solutions and procedural channels. This article aims to contest this abrogative interpretation of the necessity defense and to outline the limits of its legitimate scope. Even in welfare states, there are actions in a necessity scenario that neither question the legal decisions of the democratically elected legislature nor make a mockery of established procedural channels.
An Experimental, Computational, and Statistical Strategy for the Bayesian Calibration of Complex Material Models
Authors: de Pablos Juan L. , Sabirov Ilchat , Romero Ignacio 
Published: March 2023

AbstractThe study of solids and structures under extreme conditions often relies on simulations that employ complex material models. These, in turn, are formulated using analytical expressions that depend on parameters whose values need to be adjusted for optimally reproducing available experimental results and, especially, out-of-sample predictiveness. In this article we review the process required to calibrate all the parameters of the Johnson-Cook and Zerilli-Armstrong models for a nickel-based superalloy. To this end, we present in an unified fashion the thermomechanical problem, its numerical implementation, a complete experimental campaign that suffices to obtain the material constants, and a Bayesian calibration procedure that can be employed to obtain the optimal values for the model parameters as well as their uncertainty. The advocated methodology is ideally designed to calibrate strain rate-, temperature-, and age-dependent elastoplastic models. The procedure is, however, general enough to be employed as guideline for other complex calibrations.
Pulmonary thromboembolism and obesity in forensic pathologic case work
Authors: Klintschar Michael , Wöllner Kirsten , Hagemeier Lars , Engelmann Theresa A. , Mahlmann Jan , Lunow Alessia , Wolff-Maras Roman 
Published: March 2023

Abstract328 autopsy cases of fatal pulmonary thromboembolism (PE) were compared to 984 age- and sex-matched controls to evaluate the association between obesity and PE in a forensic context. Both PE and control cases had a mean age of 67,8 years (male 62,9 years, females 71,7 years). The percentage of morbidly obese persons with a body mass index (BMI) of above 40 or abdominal subcutaneous adipose tissue of above 4 cm was higher in the PE group (8,39% vs. 4,67% and 29.45% vs. 23.40%, respectively). On the other side, that of very slim persons (BMI below 18.5 or adipose tissue below 3 cm) was significantly smaller (4,27% vs. 7,52% and 47.55% vs. 56,60%). We thus found a strong association between being overweight and death from PE, while slim persons seem to be at an advantage. As the group of underweight persons includes those suffering from chronic diseases with reduced mobility or hypercoagulability (e.g. tumor kachexia or sarkopenia due to immobilisation), this finding is to some extent unexpected.
Apigenin Attenuates Hippocampal Microglial Activation and Restores Cognitive Function in Methotrexate-Treated Rats: Targeting the miR-15a/ROCK-1/ERK1/2 Pathway
Authors: Taha Mohamed , Eldemerdash Omar Mohsen , Elshaffei Ismail Mohamed , Yousef Einas Mohamed , Soliman Ayman S. , Senousy Mahmoud Ahmed 
Published: March 2023

AbstractMicroglial activation underpins the methotrexate (MTX)-induced neurotoxicity; however, the precise mechanism remains unclear. This study appraised the potential impact of apigenin (Api), a neuroprotective flavonoid, in MTX-induced neurotoxicity in rats in terms of microglial activation through targeting the miR-15a/Rho-associated protein kinase-1 (ROCK-1)/extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Male Sprague Dawley rats were randomly divided into 4 groups: Normal control (saline i.p. daily and i.v. on days 8 and 15); Api control (20 mg/kg, p.o.) daily for 30 days; MTX-alone (75 mg/kg, i.v.) on days 8 and 15, then four i.p. injections of leucovorin (LCV): 6 mg/kg after 18 h, then three doses (3 mg/kg) every 8 h post-MTX; and Api co-treated (20 mg/kg/day, p.o.) throughout the model for 30 days, with administration of MTX and LCV as in group 3. MTX administration elevated hippocampal ionized calcium-binding adaptor protein-1 (Iba-1) immunostaining, indicating microglial activation. This was accompanied by neuroinflammation, oxidative stress, and enhanced apoptosis manifested by elevated hippocampal interleukin-1β, malondialdehyde, and caspase-3, and decreased reduced glutathione levels. Concurrently, abated miR-15a expression, overexpression of its target ROCK-1, diminished downstream ERK1/2 and cAMP response element-binding protein (CREB) phosphorylation, and decreased hippocampal brain-derived neurotrophic factor (BDNF) levels were observed. Api mitigated the MTX-induced neurotoxicity by reversing the biochemical, histopathological, and behavioral derangements tested by novel object recognition and Morris water maze tests. Conclusively, Api lessens MTX-induced neuroinflammation, oxidative stress, and apoptosis and boosts cognitive function through inhibiting microglial activation via modulating the miR-15a/ROCK-1/ERK1/2/CREB/BDNF pathway.
Graphical Abstract

Graphical abstract showing the effects of methotrexate and apigenin co-treatment in MTX-induced neurotoxicity model.
On the left, methotrexate (MTX) administration to rats resulted in hippocampal miR-15a downregulation, which triggered an enhanced expression of its target ROCK-1, consequently inhibiting the downstream ERK1/2/CREB/BDNF pathway, instigating a state of microglial activation, neuroinflammation, oxidative stress, and apoptosis. On the other hand, apigenin (Api) co-treatment restored miR-15a, inhibited ROCK-1 expression, and activated the ERK1/2/CREB/BDNF pathway, leading to diminished hippocampal microglial activation, neuroinflammation, and apoptosis, and restoration of the redox balance, along with improvement in memory and cognitive function of the MTX-treated rats.
The Importance of Winter Dinoflagellate Blooms in Chesapeake Bay—a Missing Link in Bay Productivity
Authors: Millette Nicole C. , Clayton Sophie , Mulholland Margaret R. , Gibala-Smith Leah , Lane Michael 
Published: March 2023

AbstractIt is widely assumed that phytoplankton abundance and productivity decline during temperate winters because of low irradiance and temperatures. However, winter phytoplankton blooms commonly occur in temperate estuaries, but they are often undocumented because of reduced water quality monitoring in winter. The small body of in situ work that has been done on winter blooms suggests they can be of enormous consequence to ecosystems. However, because monitoring is often reduced or stopped altogether during winter, it is unclear how widespread these blooms are or how long they can last. We analyzed an over 30-year record of monthly phytoplankton monitoring samples along with ad hoc sampling throughout Chesapeake Bay to assess the distributions of two common winter bloom species, Heterocapsa rotundata and Heterocapsa steinii, and the environmental conditions associated with these blooms. The long-term monitoring data revealed that H. rotundata blooms occur within a narrow salinity range (7–12) and potentially have different triggers depending upon the nutrient status of waters affected. The ad hoc sampling confirmed the occurrence of H. steinii blooms in the lower Chesapeake Bay, despite the lack of evidence for them from monthly monitoring data. Together, our findings demonstrate that winter blooms routinely occur in numerous locations throughout Chesapeake Bay and can last up to a month. Our findings suggest that while winter blooms are a staple of the Bay’s annual phytoplankton community, there are major data gaps reporting their occurrence highlighting the need for more frequent monitoring to understand factors promoting these blooms and their consequences on ecosystem productivity.
Identifying activity areas in a neanderthal hunting camp (the Navalmaíllo Rock Shelter, Spain) via spatial analysis
Authors: Moclán Abel , Huguet Rosa , Márquez Belén , Álvarez-Fernández Ana , Laplana César , Arsuaga Juan Luis , Pérez-González Alfredo , Baquedano Enrique 
Published: March 2023

AbstractSpatial analysis has been much used to examine the distribution of archaeological remains at Pleistocene sites. However, little is known about the distribution patterns at sites identified as hunting camps, i.e., places occupied over multiple short periods for the capture of animals later transported to a base camp. The present work examines a Neanderthal hunting camp (the Navalmaíllo Rock Shelter in Pinilla del Valle, Madrid, Spain) to determine whether different activities were undertaken in different areas of the site. A spatial pattern was detected with a main cluster of materials (lithic tools, faunal remains, and coprolites) clearly related to the presence of nearby hearths—the backbone of the utilised space. This main cluster appears to have been related to collaborative and repetitive activities undertaken by the hunting parties that used the site. Spatial analysis also detected a small, isolated area perhaps related to carcasses processing at some point in time and another slightly altered by water.