bluuebunny/crossref_metadata_2025_split huggingface dataset:
Covariate effects and population pharmacokinetic analysis of the anti-FGFR2b antibody bemarituzumab in patients from phase 1 to phase 2 trials
Authors: Xiang Hong , Liu Lucy , Gao Yuying , Ahene Ago , Collins Helen 
Published: August 2021

Abstract
Purpose
A population pharmacokinetic (PK) analysis of the anti-fibroblast growth factor receptor 2b antibody, bemarituzumab, was performed to evaluate the impact of covariates on the PK and assess whether dose adjustment is necessary for a future phase 3 trial.

Methods
Serum concentration data were obtained from three clinical trials, with 1552 bemarituzumab serum samples from 173 patients, and were analyzed using nonlinear mixed-effects modeling.

Results
A two-compartment model with parallel linear and nonlinear (Michaelis–Menten) elimination from the central compartment best described the bemarituzumab serum concentration data. The final model estimated a typical linear clearance (CL) of 0.311 L/day, volume of distribution in the central compartment (Vc) of 3.58 L, distribution clearance (Q) of 0.952 L/day, volume of distribution in the peripheral compartment (Vp) of 2.71 L, maximum drug elimination by nonlinear clearance (Vmax) of 2.80 μg/day, and Michaelis–Menten constant (Km) of 4.45 μg/mL. Baseline body weight, baseline albumin, gender, and chemotherapy were identified as statistically significant covariates on the PK of bemarituzumab. Given the low interindividual variability of bemarituzumab key PK parameters (CL and Vc) and the small or modest effect of all statistically significant covariates on bemarituzumab exposure at steady-state, no covariate is expected to have clinically meaningful effects on bemarituzumab exposure.

Conclusion
No covariate had a clinically meaningful impact on bemarituzumab exposure. These results indicate that dose adjustment of bemarituzumab is not necessary, based on the aforementioned covariates, for a future phase 3 trial in gastric and gastroesophageal junction adenocarcinoma population with FGFR2b overexpression in combination with mFOLFOX6.
Diversification and distribution of gall crabs (Brachyura: Cryptochiridae: Opecarcinus) associated with Agariciidae corals
Authors: Xu Tao , Bravo Henrique , Paulay Gustav , van der Meij Sancia E. T. 
Published: August 2021

AbstractCoral reefs are home to the greatest diversity of marine life, and many species on reefs live in symbiotic associations. Studying the historical biogeography of symbiotic species is key to unravelling (potential) coevolutionary processes and explaining species richness patterns. Coral-dwelling gall crabs (Cryptochiridae) live in obligate symbiosis with a scleractinian host, and are ideally suited to study the evolutionary history between heterogeneous taxa involved in a symbiotic relationship. The genus Opecarcinus Kropp and Manning, 1987, like its host coral family Agariciidae, occurs in both Indo-Pacific and Caribbean seas, and is the only cryptochirid genus with a circumtropical distribution. Here, we use mitochondrial and nuclear DNA gene fragments of Opecarcinus specimens sampled from 21 Indo-Pacific localities and one Atlantic (Caribbean) locality. We applied several species delimitation tests to characterise species diversity, inferred a Bayesian molecular-clock time-calibrated phylogeny to estimate divergence times and performed an ancestral area reconstruction. Time to the most recent common ancestor (tMRCA) of Opecarcinus is estimated at 15−6 Mya (middle Miocene—late Miocene). The genus harbours ~ 15 undescribed species as well as several potential species complexes. There are indications of strict host-specificity patterns in certain Opecarcinus species in the Indo-Pacific and Atlantic, however, a robust phylogeny reconstruction of Agariciidae corals—needed to test this further—is currently lacking. The Indo-West Pacific was inferred to be the most probable ancestral area, from where the Opecarcinus lineage colonised the Western Atlantic and subsequently speciated into O. hypostegus. Opecarcinus likely invaded from the Indo-West Pacific across the East Pacific Barrier to the Atlantic, before the full closure of the Isthmus of Panama. The subsequent speciation of O. hypostegus, is possibly associated with newly available niches in the Caribbean, in combination with genetic isolation following the closure of the Panama Isthmus.
Viscoelastic behaviour of highly filled polypropylene with solid and liquid Tin microparticles: influence of the stearic acid additive
Authors: Patti Antonella , Acierno Domenico , Lecocq Hubert , Serghei Anatoli , Cassagnau Philippe 
Published: August 2021

AbstractIn this work, highly filled composites made of a commercial polypropylene resin and low melting point Tin particles, up to 50 vol.% in loadings, have been prepared by melt blending process. The introduction of stearic acid (SA), a common dispersant, was investigated in compositions. The developed systems were characterized in terms of dynamic rheological testing. Final results confirmed a reduction of linear viscoelastic domain, by increasing filler loadings, with an effect more emphasized in the presence of SA. Contrary to literature studies, at equal filler content (50%), both moduli resulted to be superior for formulations containing the dispersing agent. A further rheological characterization continued on systems at 30 vol.% of particle loadings for highlighting differences depending on the SA addition. Specific tests were also performed at temperatures above the melting of Tin particles. Finally, optical microscopic analyses were carried out for gaining insight on sample microstructure, in controlled conditions of temperature and shear rate.
Balanced truncation for model reduction of biological oscillators
Authors: Padoan Alberto , Forni Fulvio , Sepulchre Rodolphe 
Published: August 2021

AbstractModel reduction is a central problem in mathematical biology. Reduced order models enable modeling of a biological system at different levels of complexity and the quantitative analysis of its properties, like sensitivity to parameter variations and resilience to exogenous perturbations. However, available model reduction methods often fail to capture a diverse range of nonlinear behaviors observed in biology, such as multistability and limit cycle oscillations. The paper addresses this need using differential analysis. This approach leads to a nonlinear enhancement of classical balanced truncation for biological systems whose behavior is not restricted to the stability of a single equilibrium. Numerical results suggest that the proposed framework may be relevant to the approximation of classical models of biological systems.
Systematic review on outcomes used in clinical research on autosomal recessive polycystic kidney disease—are patient-centered outcomes our blind spot?
Authors: Gimpel Charlotte , Liebau Max Christoph , Schaefer Franz 
Published: August 2021

Abstract
Background
Autosomal recessive polycystic kidney disease (ARPKD) is a rare severe hepatorenal disease. Survivors of pulmonary hypoplasia and patients with milder presentations often achieve long-term survival but frequently require kidney and/or liver transplantation.

Objective
To examine the use of clinical, surrogate and patient-centered outcomes in studies on ARPKD with special attention to core outcomes of the Standardized Outcomes in NephroloGy project for children with chronic kidney disease (SONG-Kids).

Data sources and study eligibility criteria
A systematic MEDLINE literature search identified 367 ARPKD studies published since 1990; however, of these 134 were excluded because they did not report any clinical outcomes (e.g. only histopathological, genetic, protein structure or radiological markers), 19 studies because they only included prenatal patients and 138 because they were case reports with ≤ 3 patients.

Study appraisal
Seventy-six eligible studies were examined for study type, size, intervention, and reported outcomes by organ system and type, including all SONG-kids tier 1–3 outcomes.

Participants
There were 3231 patient-reports of children and adults with ARPKD.

Results
The overwhelming majority of studies reported clinical and surrogate outcomes (75/76 (98%) and 73/76 (96%)), but only 11/76 (14%) examined patient-centered outcomes and only 2/76 (3%) used validated instruments to capture them. Of the SONG-Kids core outcomes, kidney function was reported almost universally (70/76 (92%), infection and survival in three quarters (57/76 (75%), 55/76 (72%)) and measures of life participation (including neurological impairment) only rarely and inconsistently (16/76 (21%)).

Limitations
Thirty studies (39%) were of low quality as they were either narrative case reports (n = 14, 18%) and/or patients with ARPKD were an indistinguishable subgroup (n = 18, 24%). Only 28 trials compared interventions, but none were randomized.

Conclusions and implications
Studies that reported clinical outcomes in ARPKD usually covered the core outcome domains of kidney function, infections, and survival, but measures of life participation and patient-centered outcomes are distinctly lacking and require more attention in future trials.

Graphical abstract
Two-phase late Paleozoic magmatism (~ 313–312 and ~ 299–298 Ma) in the Lusatian Block and its relation to large scale NW striking fault zones: evidence from zircon U–Pb CA–ID–TIMS geochronology, bulk rock- and zircon chemistry
Authors: Käßner A. , Tichomirowa M. , Lapp M. , Leonhardt D. , Whitehouse M. , Gerdes A. 
Published: August 2021

AbstractLate Paleozoic (Variscan) magmatism is widespread in Central Europe. The Lusatian Block is located in the NE Bohemian Massif and it is part of the Saxothuringian Zone of the Variscan orogen. It is bordered by two major NW-trending shear zones, the Intra-Sudetic Fault Zone towards NE and the Elbe Fault Zone towards SW. The scarce Variscan igneous rocks of the Lusatian Block are situated close to these faults. We investigated 19 samples from Variscan plutonic and volcanic rocks of the Lusatian Block, considering all petrological varieties (biotite-bearing granites from the Koenigshain and Stolpen plutons, amphibole-bearing granites from three boreholes, several volcanic dykes, and two volcanites from the intramontane Weissig basin). We applied whole-rock geochemistry (18 samples) and zircon evaporation dating (19 samples). From the evaporation data, we selected six representative samples for additional zircon SHRIMP and CA–ID–TIMS dating. For the Koenigshain pluton, possible protoliths were identified using whole-rock Nd-isotopes, and zircon Hf- and O-isotopes. The new age data allow a subdivision of Variscan igneous rocks in the Lusatian Block into two distinct magmatic episodes. The spatial relation of the two age groups to either the Elbe Fault Zone (298–299 Ma) or the Intra-Sudetic Fault Zone (312–313 Ma) together with reports on the fault-bound character of the dated intrusions suggests an interpretation as two major post-collisional faulting episodes. This assumption of two distinct magmatic periods is confirmed by a compilation of recently published zircon U–Pb CA–ID–TIMS data on further Variscan igneous rocks from the Saxothuringian Zone. New geochemical data allow us to exclude a dominant sedimentary protolith for the Koenigshain pluton as supposed by previous investigations. This conclusion is mainly based on new O- and Hf-isotope data on zircon and the scarcity of inherited zircons. Instead, acid or intermediate igneous rocks are supposed as the main source for these I-type granitoids from the Koenigshain pluton.
Characterizing SPASM/twitch Domain-Containing Radical SAM Enzymes by EPR Spectroscopy
Authors: Balo Aidin R. , Tao Lizhi , Britt R. David 
Published: August 2021

AbstractOwing to their importance, diversity and abundance of generated paramagnetic species, radical S-adenosylmethionine (rSAM) enzymes have become popular targets for electron paramagnetic resonance (EPR) spectroscopic studies. In contrast to prototypic single-domain and thus single-[4Fe–4S]-containing rSAM enzymes, there is a large subfamily of rSAM enzymes with multiple domains and one or two additional iron–sulfur cluster(s) called the SPASM/twitch domain-containing rSAM enzymes. EPR spectroscopy is a powerful tool that allows for the observation of the iron–sulfur clusters as well as potentially trappable paramagnetic reaction intermediates. Here, we review continuous-wave and pulse EPR spectroscopic studies of SPASM/twitch domain-containing rSAM enzymes. Among these enzymes, we will review in greater depth four well-studied enzymes, BtrN, MoaA, PqqE, and SuiB. Towards establishing a functional consensus of the additional architecture in these enzymes, we describe the commonalities between these enzymes as observed by EPR spectroscopy.
Expression of inflammatory mediators in biofilm samples and clinical association in inflammatory bowel disease patients—a preliminary study
Authors: Buchbender Mayte , Fehlhofer Jakob , Proff Peter , Möst Tobias , Ries Jutta , Hannig Matthias , Neurath Markus F. , Gund Madline , Atreya Raja , Kesting Marco 
Published: August 2021

AbstractObjectivesInflammatory bowel disease (IBD) has multiple impacts on soft and hard tissues in the oral cavity. The aim of this study was to analyze the expression of cytokines in biofilm samples from patients suffering from IBD and compare them to healthy patients. It was hypothesized that different cytokine expression levels and clinical associations might be drawn.Material and methodsA total of 56 biofilm samples from three different patient cohorts (group 0 = healthy, HCn = 30; group 1 = Crohn’s disease, CD,n = 19; group 2 = ulcerative colitis, UC,n = 7) were examined for the expression levels of the cytokine interleukins IL-2, -6, and -10; matrix metalloproteinases 7 and 9; and surface antigens CD90/CD11a by quantitative real-time PCR and according to clinical parameters (plaque index, BOP, PD, DMFT, CAL). Relative gene expression was determined using the ∆∆CT method.ResultsThe mean BOP values (p = 0.001) and PD (p = 0.000) were significantly higher in the CD group compared to controls. Expression of IL-10 was significantly higher in the CD (p = 0.004) and UC groups (p = 0.022). Expression of MMP-7 was significantly higher in the CD group (p = 0.032). IBD patients treated with TNF inhibitors (p = 0.007) or other immunosuppressants (p = 0.014) showed significant overexpression of IL-10 compared to controls.ConclusionDifferent expression levels of IL-10 and MMP-7 were detected in plaque samples from IBD patients. As only BOP was significantly increased, we conclude that no clinical impairment of periodontal tissue occurred in IBD patients.Clinical relevanceWith the worldwide increasing incidence of IBD, it is important to obtain insights into the effects of the disease on the oral cavity. The study was registered (01.09.2020) at the German clinical trial registry (DRKS00022956).Clinical trial registrationThe study is registered at the German clinical trial registry (DRKS00022956).
Characterization of the subsurface urban heat island and its sources in the Milan city area, Italy
Authors: Previati Alberto , Crosta Giovanni B. 
Published: August 2021

AbstractUrban areas are major contributors to the alteration of the local atmospheric and groundwater environment. The impact of such changes on the groundwater thermal regime is documented worldwide by elevated groundwater temperature in city centers with respect to the surrounding rural areas. This study investigates the subsurface urban heat island (SUHI) in the aquifers beneath the Milan city area in northern Italy, and assesses the natural and anthropogenic controls on groundwater temperatures within the urban area by analyzing groundwater head and temperature records acquired in the 2016–2020 period. This analysis demonstrates the occurrence of a SUHI with up to 3 °C intensity and reveals a correlation between the density of building/subsurface infrastructures and the mean annual groundwater temperature. Vertical heat fluxes to the aquifer are strongly related to the depth of the groundwater and the density of surface structures and infrastructures. The heat accumulation in the subsurface is reflected by a constant groundwater warming trend between +0.1 and + 0.4 °C/year that leads to a gain of 25 MJ/m2 of thermal energy per year in the shallow aquifer inside the SUHI area. Future monitoring of groundwater temperatures, combined with numerical modeling of coupled groundwater flow and heat transport, will be essential to reveal what this trend is controlled by and to make predictions on the lateral and vertical extent of the groundwater SUHI in the study area.
Pixel-CO2 laser for the treatment of stress urinary incontinence
Authors: Nalewczynska Agnieszka Aleksandra , Barwijuk Michael , Kolczewski Piotr , Dmoch-Gajzlerska Ewa 
Published: August 2021

Abstract
The aim of this study was to assess the safety and efficacy of a minimally invasive pixel-CO2 laser procedure for the treatment of stress urinary incontinence (SUI). This was a prospective, open-label study with a cohort of 59 women. Patients were treated intravaginally with a fractional/pixel CO2 laser every 4–6 weeks for a total of three treatments and assessed at 3, 6, and 12 months. Evaluation tools included a Sandvik severity score based on a validated questionnaire, 1-h pad test, vaginal health index score (VHIS), validated female sexual function index (FSFI), patient’s impression of disease severity (PGI-S), global impression of improvement (PGI-I), and the short-term pelvic floor impact questionnaire (PFIQ-7) to assess improvements in quality of life. Reduction in SUI severity was noticed throughout the duration of the study, as compared to the baseline in which 2% of the patients were defined as “slight,” 73% “moderate,” and 25% “severe.” Gradual improvement of symptoms resulted in redistribution of severity score and the best outcome observed between 3 and 6 months. Sanitary pad weight declined from an average of 35.45 g per day at baseline to 12.47 g at the 3rd treatment, and increased to 23.06 g at 12 months. Vaginal acidity changes showed a similar pattern. No serious adverse events were reported. Pixel-CO2 laser is safe and effective for treating SUI. Additional maintenance treatments should be considered during the 6–12-month post-treatment period in order to maintain the beneficial effects.

Brief summary
Pixel-CO2 laser is a safe and effective treatment for SUI. Maintenance treatments should be considered at 6–12 months.
On augmenting database schemas by latent visual attributes
Authors: Grošup Tomáš , Peška Ladislav , Skopal Tomáš 
Published: August 2021

AbstractDecision-making in our everyday lives is surrounded by visually important information. Fashion, housing, dating, food or travel are just a few examples. At the same time, most commonly used tools for information retrieval operate on relational and text-based search models which are well understood by end users, but unable to directly cover visual information contained in images or videos. Researcher communities have been trying to reveal the semantics of multimedia in the last decades with ever-improving results, dominated by the success of deep learning. However, this does not close the gap to relational retrieval model on its own and often rather solves a very specialized task like assigning one of pre-defined classes to each object within a closed application ecosystem. Retrieval models based on these novel techniques are difficult to integrate in existing application-agnostic environments built around relational databases, and therefore, they are not so widely used in the industry. In this paper, we address the problem of closing the gap between visual information retrieval and relational database model. We propose and formalize a model for discovering candidates for new relational attributes by analysis of available visual content. We design and implement a system architecture supporting the attribute extraction, suggestion and acceptance processes. We apply the solution in the context of e-commerce and show how it can be seamlessly integrated with SQL environments widely used in the industry. At last, we evaluate the system in a user study and discuss the obtained results.
How well do neurosurgeons predict survival in patients with high-grade glioma?
Authors: Sagberg Lisa Millgård , Jakola Asgeir S. , Reinertsen Ingerid , Solheim Ole 
Published: August 2021

AbstractDue to the lack of reliable prognostic tools, prognostication and surgical decisions largely rely on the neurosurgeons’ clinical prediction skills. The aim of this study was to assess the accuracy of neurosurgeons’ prediction of survival in patients with high-grade glioma and explore factors possibly associated with accurate predictions. In a prospective single-center study, 199 patients who underwent surgery for high-grade glioma were included. After surgery, the operating surgeon predicted the patient’s survival using an ordinal prediction scale. A survival curve was used to visualize actual survival in groups based on this scale, and the accuracy of clinical prediction was assessed by comparing predicted and actual survival. To investigate factors possibly associated with accurate estimation, a binary logistic regression analysis was performed. The surgeons were able to differentiate between patients with different lengths of survival, and median survival fell within the predicted range in all groups with predicted survival < 24 months. In the group with predicted survival > 24 months, median survival was shorter than predicted. The overall accuracy of surgeons’ survival estimates was 41%, and over- and underestimations were done in 34% and 26%, respectively. Consultants were 3.4 times more likely to accurately predict survival compared to residents (p = 0.006). Our findings demonstrate that although especially experienced neurosurgeons have rather good predictive abilities when estimating survival in patients with high-grade glioma on the group level, they often miss on the individual level. Future prognostic tools should aim to beat the presented clinical prediction skills.
Reciprocal Relationships between Trajectories of Loneliness and Screen Media Use during Adolescence
Authors: Lawrence David , Hunter Simon C. , Cunneen Rebecca , Houghton Stephen J. , Zadow Corinne , Rosenberg Michael , Wood Lisa , Shilton Trevor 
Published: August 2021

AbstractAdolescence is the peak period for loneliness. Now a ubiquitous part of the adolescent landscape, electronic screens may provide avenues for ameliorating feelings of loneliness. Conversely, they may act as risk factors for the development of such feelings. Although cross-sectional studies to date have investigated the relationship between screen use and loneliness, longitudinal studies are needed if causal and directional associations are to be investigated. Utilising an accelerated longitudinal design and online survey we collected four waves of data from 1919 secondary school adolescents aged 10–15 years over two years. Random intercept cross-lagged panel models tested whether changes in five types of screen use (i.e., total screen time, social media use, gaming, passive screen use, and web use) are associated with changes in loneliness in the subsequent time-point, or changes in loneliness are associated with changes in screen use in the subsequent time-point. We found significant reciprocal associations between screen use and loneliness, with the strongest associations between social networking and electronic gaming and quality of friendships. These findings highlight that any significant increase in an adolescent’s screen use may be a potential indicator of changes in quality of friendships or feelings of isolation.