bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flucloxacillin decreases tacrolimus blood trough levels: a single-center retrospective cohort study
Authors: Veenhof Herman , Schouw Hugo M. , Besouw Martine T. P. , Touw Daan J. , Gracchi Valentina 
Published: July 2020

Abstract
Purpose
Tacrolimus and everolimus are widely used to prevent allograft rejection. Both are metabolized by the hepatic cytochrome P450 (CYP) enzyme CYP3A4 and are substrate for P-glycoprotein (P-gp). Drugs influencing the activity or expression of CYP enzymes and P-gp can cause clinically relevant changes in the metabolism of immunosuppressants. Several case reports have reported that flucloxacillin appeared to decrease levels of drugs metabolized by CYP3A4 and P-gp. The magnitude of this decrease has not been reported yet.

Methods
In this single-center retrospective cohort study, we compared the tacrolimus and everolimus blood trough levels (corrected for the dose) before, during, and after flucloxacillin treatment in eleven transplant patients (tacrolimus n = 11 patients, everolimus n = 1 patient, flucloxacillin n = 11 patients).

Results
The median tacrolimus blood trough level decreased by 37.5% (interquartile range, IQR 26.4–49.7%) during flucloxacillin treatment. After discontinuation of flucloxacillin, the tacrolimus blood trough levels increased by a median of 33.7% (IQR 22.5–51.4%). A Wilcoxon signed-rank test showed statistically significantly lower tacrolimus trough levels during treatment with flucloxacillin compared with before (p = 0.009) and after flucloxacillin treatment (p = 0.010). In the only available case with concomitant everolimus and flucloxacillin treatment, the same pattern was observed.

Conclusions
Flucloxacillin decreases tacrolimus trough levels, possibly through a CYP3A4 and/or P-gp-inducing effect. It is strongly recommended to closely monitor tacrolimus and everolimus trough levels during flucloxacillin treatment and up to 2 weeks after discontinuation of flucloxacillin.
Disease management of patients with immune thrombocytopenia—results of a representative retrospective survey in Germany
Authors: Kubasch Anne Sophie , Kisro Jens , Heßling Jörg , Schulz Holger , Hurtz Hans-Jürgen , Klausmann Martine , Ehrnsperger Achim , Willy Claudia , Platzbecker Uwe 
Published: July 2020

AbstractClinical research has resulted in an improvement of treatment options for patients with immune thrombocytopenia (ITP) over the last years. However, only few data exist on the real-life management of patients with ITP. To expand the knowledge, a multicenter, national survey was undertaken in 26 hematology practices distributed all over Germany. All patients with a diagnosis of ITP were documented using questionnaires, irrespective of the diagnosis date over a period of 2 years. Overall, data of 1023 patients were evaluated with 56% of patients being older than 60 years. Seventy-nine percent of the patients had chronic (> 12 months), 16% persistent (> 3–12 months), and 5% newly diagnosed (0–3 months) ITP. In 61% of cases, the disease lasted 3 or more years before survey documentation started. Main strategies applied as first-line therapy consisted of steroids in 45% and a “watch and wait” approach in 41% of patients. During second- and third-line strategies, treatment with steroids decreased (36% and 28%, respectively), while treatment modalities such as TPO-RAs increased (19% and 26%, respectively). As expected, patients with a low platelet count and thus a higher risk for bleeding and mortality received treatment (esp. steroids) more frequently during first line than those with a higher platelet count. Up to a third of patients were treated with steroids for more than a year. Overall, our study provides a cross-section overview about the current therapeutic treatment landscape in German ITP patients. The results will help to improve therapeutic management of ITP patients.
Strategyproof auction mechanisms for network procurement
Authors: Bichler Martin , Hao Zhen , Littmann Richard , Waldherr Stefan 
Published: July 2020

AbstractDeferred-acceptance auctions can be seen as heuristic algorithms to solve $${{\mathcal {N}}}{{\mathcal {P}}}$$

N
P

-hard allocation problems. Such auctions have been used in the context of the Incentive Auction by the US Federal Communications Commission in 2017, and they have remarkable incentive properties. Besides being strategyproof, they also prevent collusion among participants. Unfortunately, the worst-case approximation ratio of these algorithms is very low in general, but it was observed that they lead to near-optimal solutions in experiments on the specific allocation problem of the Incentive Auction. In this work, which is inspired by the telecommunications industry, we focus on a strategic version of the minimum Steiner tree problem, where the edges are owned by bidders with private costs. We design several deferred-acceptance auctions (DAAs) and compare their performance to the Vickrey–Clarke–Groves (VCG) mechanism as well as several other approximation mechanisms. We observe that, even for medium-sized inputs, the VCG mechanisms experiences impractical runtimes and that the DAAs match the approximation ratios of even the best strategy-proof mechanisms in the average case. We thus provide another example of an important practical mechanism design problem, where empirics suggest that carefully designed deferred-acceptance auctions with their superior incentive properties need not come at a cost in terms of allocative efficiency. Our experiments provide insights into the trade-off between solution quality and runtime and into the additional premium to be paid in DAAs to gain weak group-strategyproofness rather than just strategyproofness.
Compact mode-locked Er-doped fiber laser for broadband cavity-enhanced spectroscopy
Authors: Głuszek Aleksander , Senna Vieira Francisco , Hudzikowski Arkadiusz , Wąż Adam , Sotor Jarosław , Foltynowicz Aleksandra , Soboń Grzegorz 
Published: July 2020

AbstractWe report the design and characteristics of a simple and compact mode-locked Er-doped fiber laser and its application to broadband cavity-enhanced spectroscopy. The graphene mode-locked polarization maintaining oscillator consumes less than 5 W of power. It is thermally stabilized, enclosed in a 3D printed box, and equipped with three actuators that control the repetition rate: fast and slow fiber stretchers, and metal-coated fiber section. This allows wide tuning of the repetition rate and its stabilization to an external reference source. The applicability of the laser to molecular spectroscopy is demonstrated by detecting CO2 in air using continuous-filtering Vernier spectroscopy with absorption sensitivity of 5.5 × 10−8 cm−1 in 50 ms.
Timescales from magma mixing to eruption in alkaline volcanism in the Eifel volcanic fields, western Germany
Authors: Sundermeyer Caren , Gätjen Jochen , Weimann Lena , Wörner Gerhard 
Published: July 2020

AbstractDiffusion profiles in olivine crystals from the final mafic eruption products of the compositionally zoned Laacher See tephra deposit were measured to identify recharge and eruption-triggering events prior to the eruption of the Laacher See volcano (12.9 kyr). These products represent the hybrids of mixing between phonolite and intruding basanite at the bottom of the reservoir, which is likely related to the eruption-triggering event. Additionally, olivine crystals from ten basanitic scoria cones and maar deposits (East Eifel) and two nephelinites (West Eifel) were analyzed to constrain histories of olivine in Quaternary basanite magmas. Olivine crystals from the Laacher See hybrids vary in core composition (Fo83–89) and show reversely zoned mantles with high Fo87.8–89 compared to olivine in East Eifel basanites erupted in nearby, older scoria cones. Towards the crystal margin, olivine in the hybrids develop a normally zoned overgrowth (Fo86.5–87.5). Olivine from East Eifel basanites show similar zonation and core compositions (Fo80–88) but have less forsteritic mantles (Fo83–88) indicating that these basanites are less primitive than those recharging the Laacher See reservoir (> Fo89). Olivine in the West Eifel nephelinites show mantles similar to those from Laacher See (Fo87.5–90), but have normal zoning and high-Fo cores (Fo88–92). This indicates that olivine in the Laacher See hybrids were entrained by a near-primary basanite from older cumulates just before hybridization of the basanite with the phonolite. Diffusion modeling indicates maximum timescales between entrainment and eruption of Laacher See of 30–400 days that are comparable to those calculated for olivine from basanitic scoria cones (10–400 days).
Toxicogenetic analysis of Δ9-THC-metabolizing enzymes
Authors: Gasse Angela , Vennemann Marielle , Köhler Helga , Schürenkamp Jennifer 
Published: July 2020

AbstractWhile the impact of genetic polymorphisms on the metabolism of various pharmaceuticals is well known, more data are needed to better understand the specific influence of pharmacogenetics on the metabolism of delta 9-tetrahydocannabinol (Δ9-THC). Therefore, the aim of the study was to analyze the potential impact of variations in genes coding for phase I enzymes of the Δ9-THC metabolism. First, a multiplex assay for genotyping different variants of genes coding for phase I enzymes was developed and applied to 66 Δ9-THC-positive blood samples obtained in cases of driving under the influence of drugs (DUID). Genetic and demographic data as well as plasma concentrations of Δ9-THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC), and 11-nor-9-carboxy-Δ9-THC (Δ9-THC-COOH) were combined and statistically investigated. For cytochrome P450 2C19 (CYP2C19) variants, no differences in analyzed cannabinoid concentrations were found. There were also no differences in the concentrations of Δ9-THC and 11-OH-Δ9-THC for the different allelic CPY2C9 status. We recognized significantly lower Δ9-THC-COOH concentrations for CYP2C9*3 (p = 0.001) and a trend of lower Δ9-THC-COOH concentrations for CYP2C9*2 which did not reach statistical significance (p = 0.068). In addition, this study showed significantly higher values in the ratio of Δ9-THC/Δ9-THC-COOH for the carriers of the CYP2C9 variants CYP2C9*2 and CYP2C9*3 compared with the carriers of the corresponding wild-type alleles. Therefore, an impact of variations of the CYP2C9 gene on the interpretation of cannabinoid plasma concentrations in DUID cases should be considered.
Introducing the DizzyQuest: an app-based diary for vestibular disorders
Authors: Martin E. C. , Leue C. , Delespaul P. , Peeters F. , Janssen A. M. L. , Lousberg R. , Erdkamp A. , van de Weijer S. , Widdershoven J. , Blom H. , Bruintjes T. , Zwergal A. , Grill E. , Guinand N. , Perez-Fornos A. , van de Berg M. R. , Stultiens J. J. A. , Kingma H. , van de Berg R. 
Published: July 2020

Abstract
Background
Most questionnaires currently used for assessing symptomatology of vestibular disorders are retrospective, inducing recall bias and lowering ecological validity. An app-based diary, administered multiple times in daily life, could increase the accuracy and ecological validity of symptom measurement. The objective of this study was to introduce a new experience sampling method (ESM) based vestibular diary app (DizzyQuest), evaluate response rates, and to provide examples of DizzyQuest outcome measures which can be used in future research.

Methods
Sixty-three patients diagnosed with a vestibular disorder were included. The DizzyQuest consisted of four questionnaires. The morning- and evening-questionnaires were administered once each day, the within-day-questionnaire 10 times a day using a semi-random time schedule, and the attack questionnaire could be completed after the occurrence of a vertigo or dizziness attack. Data were collected for 4 weeks. Response rates and loss-to-follow-up were determined. Reported symptoms in the within-day-questionnaire were compared within and between patients and subgroups of patients with different vestibular disorders.

Results
Fifty-one patients completed the study period. Average response rates were significantly higher than the desired response rate of > 50% (p < 0.001). The attack-questionnaire was used 159 times. A variety of neuro-otological symptoms and different disease profiles were demonstrated between patients and subgroups of patients with different vestibular disorders.

Conclusion
The DizzyQuest is able to capture vestibular symptoms within their psychosocial context in daily life, with little recall bias and high ecological validity. The DizzyQuest reached the desired response rates and showed different disease profiles between subgroups of patients with different vestibular disorders. This is the first time ESM was used to assess daily symptoms and quality of life in vestibular disorders, showing that it might be a useful tool in this population.
Focal aggregates of normal or near normal uveal melanocytes (FANNUMs) in the choroid: a distinct clinical and histopathological entity?
Authors: Augsburger James J. 
Published: July 2020

Abstract
Purpose
To define, describe, and illustrate a previously unreported category of discrete melanotic choroidal melanocytic lesion.

Methods
Prospective ophthalmoscopic study of the ocular fundi of 79 light-skinned persons 50 years of age or older not referred for any evident fundus lesion, with detection of all evident discrete melanotic choroidal lesions > 0.3 mm in largest basal diameter.

Results
One or more discrete dark-brown to gray choroidal lesions > 0.3 mm in largest basal diameter were detected in 27 of the 79 evaluated subjects (34.2%). All but four of the detected lesions were “flat” by both ophthalmoscopy and ultrasonography. A single flat lesion was present in one eye of 14 subjects whose fellow eye was normal, 2 or more flat lesions were evident in one eye of 5 subjects whose other eye was normal, and one or more lesions were evident in both eyes of 6 subjects.

Conclusion
While some of the discrete small, flat melanocytic choroidal lesions detected in this study might have been choroidal nevi, the author hypothesizes that an indeterminate proportion of them may have been focal aggregates of normal or near normal uveal melanocytes (FANNUMs).
Transport properties in CFTR−/− knockout piglets suggest normal airway surface liquid pH and enhanced amiloride-sensitive Na+ absorption
Authors: Benedetto Roberta , Centeio Raquel , Ousingsawat Jiraporn , Schreiber Rainer , Janda Melanie , Kunzelmann Karl 
Published: July 2020

AbstractPrevious analysis of CFTR-knockout (CFTR−/−) in piglets has provided important insights into the pathology of cystic fibrosis. However, controversies exist as to the true contribution of CFTR to the pH balance in airways and intestine. We therefore compared ion transport properties in newborn wild-type (CFTR+/+) and CFTR-knockout (CFTR−/− piglets). Tracheas of CFTR−/− piglets demonstrated typical cartilage malformations and muscle cell bundles. CFTR−/− airway epithelial cells showed enhanced lipid peroxidation, suggesting inflammation early in life. CFTR was mainly expressed in airway submucosal glands and was absent in lungs of CFTR−/− piglets, while expression of TMEM16A was uncompromised. mRNA levels for TMEM16A, TMEM16F, and αβγENaC were unchanged in CFTR−/− airways, while mRNA for SLC26A9 appeared reduced. CFTR was undetectable in epithelial cells of CFTR−/− airways and intestine. Small intestinal epithelium of CFTR−/− piglets showed mucus accumulation. Secretion of both electrolytes and mucus was activated by stimulation with prostaglandin E2 and ATP in the intestine of CFTR+/+, but not of CFTR−/− animals. pH was measured inside small bronchi using a pH microelectrode and revealed no difference between CFTR+/+ and CFTR−/− piglets. Intracellular pH in porcine airway epithelial cells revealed only a small contribution of CFTR to bicarbonate secretion, which was absent in cells from CFTR−/− piglets. In contrast to earlier reports, our data suggest a minor impact of CFTR on ASL pH. In contrast, enhanced amiloride-sensitive Na+ absorption may contribute to lung pathology in CFTR−/− piglets, along with a compromised CFTR- and TMEM16A-dependent Cl− transport.
Combined effects of niclosamide and temozolomide against human glioblastoma tumorspheres
Authors: Oh Hyeong-Cheol , Shim Jin-Kyoung , Park Junseong , Lee Ji-Hyun , Choi Ran Joo , Kim Nam Hee , Kim Hyun Sil , Moon Ju Hyung , Kim Eui Hyun , Chang Jong Hee , Yook Jong In , Kang Seok-Gu 
Published: July 2020

Abstract
Purpose
Glioblastoma (GBM) is the most aggressive type of brain tumor and has poor survival outcomes, even after a combination of surgery, radiotherapy, and chemotherapy. Temozolomide is the only agent that has been shown to be effective against GBM, suggesting that combination of temozolomide with other agents may be more effective. Niclosamide, an FDA approved anthelmintic agent, has shown anti-cancer effects against human colon, breast, prostate cancers as well as GBM. However, the efficacy of the combination of niclosamide with temozolomide against GBM tumorspheres (TSs) has not been determined. We hypothesized that the combined treatment could effectively suppress GBM TSs.

Methods
GBM TSs (TS15-88, GSC11) were treated with niclosamide and/or temozolomide. Combined effects of two drugs were evaluated by measuring viability, neurosphere formation, and 3D-invasion in collagen matrix. Transcriptional profiles of GBM TS were analyzed using RNA sequencing. In vivo anticancer efficacy of combined drugs was tested in a mouse orthotopic xenograft model.

Results
Combination treatment of niclosamide and temozolomide significantly inhibited the cell viability, stemness, and invasive properties of GBM TSs. This combined treatment significantly down-regulated the expression of epithelial mesenchymal transition-related markers, Zeb1, N-cadherin, and β-catenin. The combined treatment also significantly decreased tumor growth in orthotopic xenograft models.

Conclusion
The combination of niclosamide and temozolomide effectively decreased the stemness and invasive properties of GBM TSs, suggesting that this regimen may be therapeutically effective in treating patients with GBM.
Diversification of petal monoterpene profiles during floral development and senescence in wild roses: relationships among geraniol content, petal colour, and floral lifespan
Authors: Dani K. G. Srikanta , Fineschi Silvia , Michelozzi Marco , Trivellini Alice , Pollastri Susanna , Loreto Francesco 
Published: July 2020

AbstractWild roses store and emit a large array of fragrant monoterpenes from their petals. Maximisation of fragrance coincides with floral maturation in many angiosperms, which enhances pollination efficiency, reduces floral predation, and improves plant fitness. We hypothesized that petal monoterpenes serve additional lifelong functions such as limiting metabolic damage from reactive oxygen species (ROS), and altering isoprenoid hormonal abundance to increase floral lifespan. Petal monoterpenes were quantified at three floral life-stages (unopened bud, open mature, and senescent) in 57 rose species and 16 subspecies originating from Asia, America, and Europe, and relationships among monoterpene richness, petal colour, ROS, hormones, and floral lifespan were analysed within a phylogenetic context. Three distinct types of petal monoterpene profiles, revealing significant developmental and functional differences, were identified: Type A, species where monoterpene abundance peaked in open mature flowers depleting thereafter; Type B, where monoterpenes peaked in senescing flowers increasing from bud stage, and a rare Type C (8 species) where monoterpenes depleted from bud stage to senescence. Cyclic monoterpenes peaked during early floral development, whereas acyclic monoterpenes (dominated by geraniol and its derivatives, often 100-fold more abundant than other monoterpenes) peaked during floral maturation in Type A and B roses. Early-diverging roses were geraniol-poor (often Type C) and white-petalled. Lifetime changes in hydrogen peroxide (H2O2) revealed a significant negative regression with the levels of petal geraniol at all floral life-stages. Geraniol-poor Type C roses also showed higher cytokinins (in buds) and abscisic acid (in mature petals), and significantly shorter floral lifespan compared with geraniol-rich Type A and B roses. We conclude that geraniol enrichment, intensification of petal colour, and lower potential for H2O2-related oxidative damage characterise and likely contribute to longer floral lifespan in monoterpene-rich wild roses.
Parameterized Dynamic Cluster Editing
Authors: Luo Junjie , Molter Hendrik , Nichterlein André , Niedermeier Rolf 
Published: July 2020

AbstractWe introduce a dynamic version of the -hard graph modification problemCluster Editing. The essential point here is to take into account dynamically evolving input graphs: having a cluster graph (that is, a disjoint union of cliques) constituting a solution for a first input graph, can we cost-efficiently transform it into a “similar” cluster graph that is a solution for a second (“subsequent”) input graph? This model is motivated by several application scenarios, including incremental clustering, the search for compromise clusterings, or also local search in graph-based data clustering. We thoroughly study six problem variants (three modification scenarios edge editing, edge deletion, edge insertion; each combined with two distance measures between cluster graphs). We obtain both fixed-parameter tractability as well as (parameterized) hardness results, thus (except for three open questions) providing a fairly complete picture of the parameterized computational complexity landscape under the two perhaps most natural parameterizations: the distances of the new “similar” cluster graph to (1) the second input graph and to (2) the input cluster graph.
Building a Nest by an Automaton
Authors: Czyzowicz Jurek , Dereniowski Dariusz , Pelc Andrzej 
Published: July 2020

AbstractA robot modeled as a deterministic finite automaton has to build a structure from material available to it. The robot navigates in the infinite oriented grid $${\mathbb {Z}} \times {\mathbb {Z}}$$

Z
×
Z

. Some cells of the grid are full (contain a brick) and others are empty. The subgraph of the grid induced by full cells, called the shape, is initially connected. The (Manhattan) distance between the furthest cells of the shape is called its span. The robot starts at a full cell. It can carry at most one brick at a time. At each step it can pick a brick from a full cell, move to an adjacent cell and drop a brick at an empty cell. The aim of the robot is to construct the most compact possible structure composed of all bricks, i.e., a nest. That is, the robot has to move all bricks in such a way that the span of the resulting shape be the smallest. Our main result is the design of a deterministic finite automaton that accomplishes this task and subsequently stops, for every initially connected shape, in time $$O(sn)$$

O
(
s
n
)

, where s is the span of the initial shape and $$n$$
n
is the number of bricks. We show that this complexity is optimal.