bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olaparib in an ovarian cancer patient with end-stage renal disease and hemodialysis
Authors: Baum Joanna , Zickler Daniel , Bolbrinker Juliane , Richter Rolf , Braicu Elena Ioana , Grabowski Jacek , Sehouli Jalid 
Published: March 2023

Abstract
Purpose
For patients with severe renal impairment (CrCl ≤ 30 ml/min) or end-stage renal disease (ESRD), olaparib intake is not recommended as the pharmacokinetics and safety of olaparib have not been evaluated in this patient group. Therefore, this valuable patient group is generally excluded from poly(ADP-ribose) polymerase inhibitor (PARPi) therapy. Here we report the pharmacokinetics (PK), efficacy, safety and tolerability of olaparib capsules 200 mg BID in a patient with recurrent epithelial ovarian cancer (EOC) and ESRD requiring hemodialysis.

Methods
Blood and dialysate samples of the patient were collected on a dialysis and non-dialysis day. Olaparib total plasma concentrations were determined through high-performance liquid chromatography with tandem mass spectrometric detection. Actual scheduled sample times were used in the PK analysis to determine multiple dose PK parameters at steady state.

Results
Maximum concentration was achieved 1.5 h after drug administration on non- dialysis and after 1 h on dialysis day. The steady-state trough concentration and the maximal plasma concentration were similar on dialysis and non- dialysis day. On non-dialysis day, the AUCss was 30% higher (24.0 µg.h/mL vs. 16.9 µg.h/ml) than on dialysis day. The plasma clearance CLss/F was lower on non-dialysis day. Olaparib was not detectable in the dialysate samples.

Conclusion
A total dose of olaparib 200 mg BID capsule formulation was well tolerated by our patient with ESRD and hemodialysis. Moreover, this maintenance therapy led to 16 months of progression free survival. Further trials on PARPi therapy in patients with hemodialysis are warranted.
How well do high-resolution Global Climate Models (GCMs) simulate tropical cyclones in the Bay of Bengal?
Authors: Akhter Shammi , Holloway Christopher E. , Hodges Kevin , Vanniere Benoit 
Published: March 2023

AbstractUsing six HighResMIP multi-ensemble GCMs (both the atmosphere-only and coupled versions) at 25 km resolution, the Tropical Cyclone (TC) activity over the Bay of Bengal (BoB) is examined in the present (1950–2014) climate. We use the Genesis Potential Index (GPI) to study the large-scale environmental conditions associated with the TC frequency in the models. Although the models struggle to reproduce the observed frequency and intensity of TCs, most models can capture the bimodal characteristics of the seasonal cycle of cyclones over the BoB (with fewer TCs during the pre-monsoon [April–May] than the post-monsoon [October–November] season). We find that GPI can capture the seasonal variation of the TC frequency over the BoB in both the observations and models. After calibrating the maximum sustained windspeeds in the models with IBTrACS, we find that like the observations the proportion of strong cyclones is also higher in the pre-monsoon than the post-monsoon. However, the inter-seasonal contrast of the proportion of strong cyclones between the pre-monsoon and post-monsoon seasons is reduced in almost all the models compared to the observations. The windshear term in GPI contributes the most to the model biases in all models during the post-monsoon season. This bias is caused by weakening of upper-level (200 hPa) easterlies in analysed models. During the pre-monsoon season, the environmental term in GPI dominating the model biases varies from model to model. When comparing the atmosphere-only and coupled versions of the models, a reduction of 0.5 °C in the sea surface temperature (SST) and a lowering of TC frequency occur in almost all the coupled models compared to their atmosphere-only counterparts.
Impacts of a weakened AMOC on precipitation over the Euro-Atlantic region in the EC-Earth3 climate model
Authors: Bellomo Katinka , Meccia Virna L. , D’Agostino Roberta , Fabiano Federico , Larson Sarah M. , von Hardenberg Jost , Corti Susanna 
Published: March 2023

AbstractGiven paleoclimatic evidence that the Atlantic Meridional Overturning Circulation (AMOC) may affect the global climate system, we conduct model experiments with EC-Earth3, a state-of-the-art GCM, to specifically investigate, for the first time, mechanisms of precipitation change over the Euro-Atlantic sector induced by a weakened AMOC. We artificially weaken the strength of the AMOC in the model through the release of a freshwater anomaly into the Northern Hemisphere high latitude ocean, thereby obtaining a ~ 57% weaker AMOC with respect to its preindustrial strength for 60 model years. Similar to prior studies, we find that Northern Hemisphere precipitation decreases in response to a weakened AMOC. However, we also find that the frequency of wet days increases in some regions. By computing the atmospheric moisture budget, we find that intensified but drier storms cause less precipitation over land. Nevertheless, changes in the jet stream tend to enhance precipitation over northwestern Europe. We further investigate the association of precipitation anomalies with large-scale atmospheric circulations by computing weather regimes through clustering of geopotential height daily anomalies. We find an increase in the frequency of the positive phase of the North Atlantic Oscillation (NAO+), which is associated with an increase in the occurrence of wet days over northern Europe and drier conditions over southern Europe. Since a ~ 57% reduction in the AMOC strength is within the inter-model range of projected AMOC declines by the end of the twenty-first century, our results have implications for understanding the role of AMOC in future hydrological changes.
Indirect epigenetic testing identifies a diagnostic signature of cardiomyocyte DNA methylation in heart failure
Authors: Oeing Christian U. , Pepin Mark E. , Saul Kerstin B. , Agircan Ayça Seyhan , Assenov Yassen , Merkel Tobias S. , Sedaghat-Hamedani Farbod , Weis Tanja , Meder Benjamin , Guan Kaomei , Plass Christoph , Weichenhan Dieter , Siede Dominik , Backs Johannes 
Published: March 2023

AbstractPrecision-based molecular phenotyping of heart failure must overcome limited access to cardiac tissue. Although epigenetic alterations have been found to underlie pathological cardiac gene dysregulation, the clinical utility of myocardial epigenomics remains narrow owing to limited clinical access to tissue. Therefore, the current study determined whether patient plasma confers indirect phenotypic, transcriptional, and/or epigenetic alterations to ex vivo cardiomyocytes to mirror the failing human myocardium. Neonatal rat ventricular myocytes (NRVMs) and single-origin human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and were treated with blood plasma samples from patients with dilated cardiomyopathy (DCM) and donor subjects lacking history of cardiovascular disease. Following plasma treatments, NRVMs and hiPSC-CMs underwent significant hypertrophy relative to non-failing controls, as determined via automated high-content screening. Array-based DNA methylation analysis of plasma-treated hiPSC-CMs and cardiac biopsies uncovered robust, and conserved, alterations in cardiac DNA methylation, from which 100 sites were validated using an independent cohort. Among the CpG sites identified, hypo-methylation of the ATG promoter was identified as a diagnostic marker of HF, wherein cg03800765 methylation (AUC = 0.986, P < 0.0001) was found to out-perform circulating NT-proBNP levels in differentiating heart failure. Taken together, these findings support a novel approach of indirect epigenetic testing in human HF.
Development of the novel GlyT1 inhibitor, iclepertin (BI 425809), for the treatment of cognitive impairment associated with schizophrenia
Authors: Rosenbrock Holger , Desch Michael , Wunderlich Glen 
Published: March 2023

AbstractSchizophrenia is a psychiatric disorder characterised by symptoms in three domains: positive (e.g. delusions, hallucinations), negative (e.g. social withdrawal, lack of motivation) and cognitive (e.g. working memory and executive function impairment). Cognitive impairment associated with schizophrenia (CIAS) is a major burden for patients and negatively impacts many aspects of a patient’s life. Antipsychotics are the standard-of-care treatment for schizophrenia but only address positive symptoms. So far there are no approved pharmacotherapies for the treatment of CIAS. Iclepertin (BI 425809) is a novel, potent and selective glycine transporter 1 (GlyT1) inhibitor, under development by Boehringer Ingelheim for the treatment of CIAS. Phase I studies have shown it to be safe and well tolerated in healthy volunteers, and central target engagement (inhibition of GlyT1) was achieved in a dose-dependent manner from 5 to 50 mg in healthy volunteers. A Phase II study has demonstrated that iclepertin is safe and well tolerated in patients with schizophrenia and improves cognition at doses of 10 mg and 25 mg. Phase III studies are ongoing to confirm these initial positive safety and efficacy findings with the 10 mg dose, and if successful, iclepertin could become the first approved pharmacotherapy used to treat CIAS.
Baseline brain imaging signs in patients with ischaemic stroke by the presence of atrial fibrillation: the ENCHANTED trial
Authors: Wang Xia , You Shoujiang , Zhou Zien , Delcourt Candice , Wardlaw Joanna , Mair Grant , Robinson Thompson , Chen Xiaoying , Yoshimura Sohei , Torii-Yoshimura Takako , Carcel Cheryl , Malavera Alejandra , Anderson Craig , Lindley Richard I. 
Published: March 2023

Abstract
Background
We aimed to assess the association of atrial fibrillation (AF) on outcomes in a post hoc analysis of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) and how this association is modified by baseline imaging features.

Methods
Inverse probability of treatment weight was used to remove baseline imbalances between those with and without AF. The primary outcome was the modified Rankin Scale (mRS) scores at 90 days. Secondary outcomes were symptomatic intracerebral haemorrhage (sICH), early neurological deterioration or death within 24 h, and death at 90 days. The logistic regression model was used to determine the associations.

Results
Of the 3285 patients included in this analysis, 636 (19%) had AF at baseline. Compared with non-AF, AF was not significantly associated with an unfavourable shift of mRS (odds ratio 1.09; 95% confidence interval, 0.96–1.24), but with sICH (2.82; 1.78-4.48; IST-3 criteria), early neurological deterioration or death within 24 h (1.31; 1.01-1.70), and death (1.42; 1.12-1.79). Among patients with acute ischaemic signs (presence, extent, swelling and attenuation of acute lesions), AF was associated with the increased risk of all the poor outcomes (all P < 0.04 for interaction).

Conclusions
We found AF increased risk of sICH, early neurological deterioration or death and death, but not unfavourable functional recovery at day 90 after thrombolysis in patients with AIS. The presence of acute ischaemic brain imaging signs at stroke presentation could be used to improve risk stratification in the presence of AF.

Trial registration
The trial is registered at ClinicalTrials.gov (NCT01422616).
Remote effects of a 7-week combined stretching and foam rolling training intervention of the plantar foot sole on the function and structure of the triceps surae
Authors: Konrad Andreas , Reiner Marina Maren , Gabriel Anna , Warneke Konstantin , Nakamura Masatoshi , Tilp Markus 
Published: March 2023

AbstractIt is known that a single bout of foam rolling (FR) or stretching can induce changes in range of motion (ROM) and performance in non-directly adjoining areas of the dorsal chain (i.e., remote effects). However, to date, it is not known if such effects exist following long-term interventions. Thus, the purpose of this study was to investigate the remote effects of a 7-week combined stretching and FR training intervention of the plantar foot sole. Thirty-eight recreational athletes were randomly assigned to either an intervention (n = 20) or control (n = 18) group. The intervention group performed stretching and FR exercises of the plantar foot sole for 7 weeks. Before and after the intervention, the dorsiflexion ankle ROM, passive resistive torque at maximum angle (PRTmax) and at a fixed angle, as well as maximum voluntary isometric contraction (MVIC) torque, were measured with a dynamometer. Gastrocnemius medialis and lateralis stiffness was assessed with shear wave elastography. The results showed no interaction effect for any of the parameters. There was a time effect indicating an increase in MVIC and PRTmax, which was more pronounced in the intervention group (+ 7.4 (95% CI 2.5–12.4),  + 4.5 (95% CI − 0.2–9.2)) than the control group (+ 3.6 (95% CI − 1.4–8.6),  + 4.0 (95% CI − 2.2 to 10.2)). The results indicate no or minor remote effects of combined stretching and FR of the foot sole in the ankle joint. Potential non-significant changes in ROM were accompanied with an increase in stretch tolerance, but not with changes in muscle structure.
Tutte Embeddings of Tetrahedral Meshes
Authors: Alexa Marc 
Published: March 2023

AbstractTutte’s embedding theorem states that every 3-connected graph without a $$K_5$$

K
5

- or $$K_{3,3}$$

K

3
,
3

-minor (i.e., a planar graph) is embedded in the plane if the outer face is in convex position and the interior vertices are convex combinations of their neighbors. We show that this result extends to simply connected tetrahedral meshes in a natural way: for the tetrahedral mesh to be embedded if the outer polyhedron is in convex position and the interior vertices are convex combination of their neighbors it is sufficient (but not necessary) that the graph of the tetrahedral mesh contains no $$K_6$$

K
6

and no $$K_{3,3,1}$$

K

3
,
3
,
1

, and all triangles incident on three boundary vertices are boundary triangles.
Locking treatment of penalty-based gradient-enhanced damage formulation for failure of compressible and nearly incompressible hyperelastic materials
Authors: Valverde-González A. , Reinoso J. , Dortdivanlioglu B. , Paggi M. 
Published: March 2023

AbstractSoft materials are of major interest for biomechanics applications due to their high deformability and susceptibility to experience damage events under different loading scenarios. The present study is concerned with modelling damage evolution processes in these nonlinear materials whose structural responses are prone to locking when low-order kinematic interpolation is employed in the context of nonlinear Finite Element schemes. For this reason, a pair of gradient-enhanced continuum damage schemes are proposed with the aim of tackling mechanical failure problems in applications that exhibit shear and volumetric locking. In particular, we present the consistent formulation and the assessment of the corresponding performance of (i) a mixed displacement-enhanced assumed strain employing a total Lagrangian formulation, and (ii) a three-field mixed displacement-pressure-Jacobian formulation. The novel and formulations are consistently derived and numerically implemented, providing a satisfactory agreement with respect to built-in elements handling the treatment of shear and volumetric locking, respectively, in conjunction to the modelling damage phenomena via the use of a penalty-based gradient-enhanced formulation. This performance is examined via several numerical applications. Furthermore, the final example justifies the need for a formulation combining both mixed FE approaches to simulate problems encompassing both locking issues (shear and volumetric locking), which can be performed using a combination of the and herein proposed.
The decrease in diurnal oxygen production in Elodea under the influence of high geomagnetic variability: the role of light, temperature and atmospheric pressure
Authors: Davies Elizabeth 
Published: March 2023

Abstract
Epidemiological studies have indicated adverse effects of geomagnetic disturbance on human health, including increased mortality. There is evidence from plant and animal studies that help to elucidate this interaction. This study tests the hypothesis that geomagnetic disturbance affects living systems, by modifying the metabolic process of photosynthesis, in the natural environment.Continuous 24-h measurements of dissolved oxygen in flasks containing Holtfreiter’s solution and strands of healthy Elodea were recorded from May 1996, until September 1998, in an electromagnetically quiet, purpose built, garden shed environment, without mains electricity. Sensormeter recordings of oxygen, light, temperature and air pressure were uploaded weekly to a PC. The hourly total geomagnetic field measurements were obtained from the nearest observatory.Significant decrease in oxygen (diurnal volume of oxygen divided by plant mass and diurnal light), (O/WL), was found on days of high geomagnetic field variability throughout 11 recorded months of the year 1997. This result was independent of temperature and atmospheric pressure. No significant decrease in O/WL during high geomagnetic variability was found for the 7 months recorded in 1996. The 1996 and 1997 data both showed a significant decrease in the diurnal time lag between peak light and peak oxygen for diurnal high geomagnetic variability compared with low geomagnetic variability. Cross correlation analysis for 1997 and 1998 data showed a decrease in positive correlation of oxygen with light in high geomagnetic variability, compared with low geomagnetic variability, and increased positive correlation with the geomagnetic field instead. These experiments support a hypothesis of high geomagnetic field variability as a weak zeitgeber, and a metabolic depressant for photosynthetic oxygen production in plants.
Design of hairpin windings considering the transient potential distribution
Authors: Dittmann Jochen , England Marc , Ponick Bernd 
Published: March 2023

AbstractWith the increasing use of novel semiconductor technologies such as SiC and GaN in inverter-fed electrical machines, the switching losses of the power electronics can be reduced. However, this leads to steeper voltage gradients, resulting in a strongly nonlinear transient potential distribution along the winding of the electrical machine. As a result, the insulation system – especially the turn-to-turn insulation – is subjected to additional voltage stress. To carry out targeted dimensioning of the insulation system, it is necessary to calculate the transient potential distribution in advance. In the design of a hairpin winding, it is possible to influence the transient potential differences by employing a method called “shifting” within the winding scheme and thus to reduce the maximum potential differences that occur. On this basis, a targeted design of winding plans with hairpins can be achieved. Here, both the transient potential differences between the conductors within a slot of the stator core and the potential differences between the conductors of different phases in the end winding region of the machine are considered. Furthermore, the voltage differences between the conductors and the stator core are determined and compared for different variants. In this way, it is possible to reduce the amount of material used in the insulation system. Finally, an advantageous winding layout plan based on reduced potential differences is compared with a reference plan.
Talar component subsidence correlates with periprosthetic osteolysis after total ankle arthroplasty
Authors: Kihara Shinsuke , Kanzaki Noriyuki , Yamashita Takahiro , Yamamoto Tetsuya , Nishida Kyohei , Nagai Kanto , Araki Daisuke , Hoshino Yuichi , Matsushita Takehiko , Kuroda Ryosuke 
Published: March 2023

Abstract
Purpose
This study aimed to investigate the relationship between periprosthetic osteolysis around the talar component and the amount of talar component subsidence after total ankle arthroplasty (TAA).

Methods
This study included forty patients who underwent TAA with a mean follow-up of 67.5 ± 17.0 months. The patients were divided into two groups based on the amount of osteolysis around the talar component, as measured by computed tomography at the latest clinic visit: none to 2 mm (N group, n = 20) and greater than or equal to 2 mm (O group, n = 20). The average amount of talar component subsidence, clinical outcomes, and complications were compared between the two groups. In the O group, the correlation between osteolysis and talar component subsidence was evaluated.

Results
The average talar component subsidence was significantly different between the N (0.22 ± 0.94 mm) and O groups (2.12 ± 2.28 mm). Five out of 20 ankles in the O group required revision surgery owing to talar component subsidence. The Japanese Society for Surgery of the Foot scores in the N and O groups were significantly different: 93.5 ± 7.7 and 85.3 ± 15.4, respectively. In the O group, we found that osteolysis tended to develop on the lateral side, and the amount of osteolysis was positively correlated with the talar component subsidence (r = 0.59, P = .007).

Conclusion
In the O group, a positive correlation between osteolysis and talar component subsidence was found, and five patients required revision surgery.
Design of colorimetric nanostructured sensor phases for simple and fast quantification of low concentrations of acid vapors
Authors: Fernández-Ramos M. D. , Bastida-Armesto M. , Blanc-García R. , Capitán-Vallvey L. F. , Medina-Castillo A. L. 
Published: March 2023

AbstractTwo colorimetric nanostructured sensor phases (Color-NSPs) for the determination of low concentrations of acid vapors in the atmosphere of paper storage rooms have been designed and characterized. The acid vapor determination is based on the color change that occurs in polyaniline (PANI) in the presence of acids when it goes from its emeraldine base form (blue) to its emeraldine salt form (green). To synthesize the Color-NSPs, two methods have been used, a one-step method performed by grafting polyaniline onto a cellulose membrane (Cellu-PANI) and a two-step method in which in the first step, polyaniline is grafted onto the surface of polymeric nanoparticles (NPs-PANI), and in a second step, NPs-PANI are immobilized into the pores of a nylon membrane (Nylon-NPs PANI). The response of the sensors versus acid vapor was measured by color coordinates with a photographic camera. A linear response range from 1 ppmv to 7 ppmv was found for both sensors, and the detection limits were 0.95 ppmv (1.2 % RSD) and 0.40 ppmv (0.8 % RSD) for Cellu-PANI and Nylon-NPs PANI, respectively. In addition, both sensors showed complete reversibility and a short exposition time (5 min). The potential applicability of the Color-NSPs in the control of the exposure of paper heritage collections to outdoor- and indoor-generated gaseous pollutants was demonstrated by determining acid vapors in museums. The method was validated with an external reference method; the paired test was applied, andp-values greater than 5% were obtained, indicating an excellent correlation and showing that the Color-NSPs reported are simple, fast, and an economical alternative to control and protect cultural heritage materials in indoor environments.Graphical Abstract