bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure–response analyses of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma
Authors: Dosne Anne-Gaëlle , Valade Elodie , Goeyvaerts Nele , De Porre Peter , Avadhani Anjali , O’Hagan Anne , Li Lilian Y. , Ouellet Daniele , Perez Ruixo Juan Jose 
Published: January 2022

Abstract
Background
Exposure–response analyses were conducted to explore the relationship between selected efficacy and safety endpoints and serum phosphate (PO4) concentrations, a potential biomarker of efficacy and safety, in locally advanced or metastatic urothelial carcinoma patients with FGFR alterations treated with erdafitinib.

Methods
Data from two dosing regimens of erdafitinib in a phase 2 study (NCT02365597), 6 and 8-mg/day with provision for pharmacodynamically guided titration per serum PO4 levels, were analyzed using Cox proportional hazard or logistic regression models. Efficacy endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Safety endpoints were adverse events typical for FGFR inhibitors.

Results
Exposure-efficacy analyses on 156 patients (6-mg = 68; 8-mg = 88) showed that patients with higher serum PO4 levels within the first 6 weeks showed better OS (hazard ratio 0.57 [95% CI 0.46–0.72] per mg/dL of PO4; p = 0.01), PFS (hazard ratio 0.80 [0.67–0.94] per mg/dL of PO4; p = 0.01), and ORR (odds ratio 1.38 [1.02–1.86] per mg/dL of PO4; p = 0.04). Exposure-safety analyses on 177 patients (6-mg = 78; 8-mg = 99) showed that the incidence of selected adverse events associated with on-target off-tumor effects significantly rose with higher PO4.

Conclusions
The exploratory relationship between serum PO4 levels and efficacy/safety outcomes supported the use of pharmacodynamically guided dose titration to optimize erdafitinib’s therapeutic benefit/risk ratio.

Clinical trial registration number
NCT02365597.
Zystische Fibrose und Schmerzen – ein unterschätztes Problem
Authors: Hoffmann Anna Teresa , Dillenhöfer Stefanie , Lücke Thomas , Maier Christoph , Brinkmann Folke 
Published: January 2022

Zusammenfassung
Hintergrund
Zystische Fibrose (CF) ist eine der häufigsten vererbbaren Stoffwechselerkrankungen in Deutschland. Sie betrifft verschiedene Organsysteme und führt häufig zu Schmerzen, die meist unterschätzt werden. Im deutschsprachigen Raum existieren bis dato keinerlei Leitlinien zu diesem relevanten Thema.

Methoden
Es erfolgte eine systematische Literaturrecherche in PubMed sowie der deutschsprachigen Leitlinien und Fachliteratur zum Thema CF und Schmerzen. Als relevant wurden Arbeiten gewertet, die Daten zu CF, zu Schmerzen oder deren Behandlung bei der CF enthielten. Insgesamt fanden sich 1690 Artikel, von denen 41 Arbeiten unsererseits aufgenommen wurden.

Ergebnisse
Die Recherche ergab, dass Schmerzen unterschiedlichster Art aufgrund der diversen Organbeteiligungen weit verbreitet sind. Zur Diagnostik und Therapie von Schmerzen bei CF existieren aber keine deutschsprachigen Leitlinien oder Konsenspapiere. In europäischen und amerikanischen Studien spiegelt sich die klinische Relevanz und Bandbreite des Themas wider, Daten zur Effektivität der Schmerztherapie enthalten diese jedoch nicht. Neben einer klassischen Schmerzmedikation mit Analgetika setzen viele Patienten auch auf alternative Heilversuche wie physikalische Therapien, Akupunktur oder Tetrahydrocannabinol (THC). Angesichts der multiplen Organdysfunktionen ist der Einsatz von Analgetika mit besonderen Risiken verbunden.

Diskussion
Eine Schmerztherapie ist bei Patienten mit zystischer Fibrose und Multiorganbeteiligung häufig erforderlich und muss der Progression der Erkrankung angepasst werden. Kontraindikationen und Nebenwirkungen der Analgetika sollten individuell ermittelt werden. Die Aufnahme der Behandlung von Schmerzen in deutschsprachige CF-Leitlinien ist dringend erforderlich.
On band gaps of nonlocal acoustic lattice metamaterials: a robust strain gradient model
Authors: Wang Binying , Liu Jinxing , Soh A. K. , Liang Naigang 
Published: January 2022

AbstractWe have proposed an “exact” strain gradient (SG) continuum model to properly predict the dispersive characteristics of diatomic lattice metamaterials with local and nonlocal interactions. The key enhancement is proposing a wavelength-dependent Taylor expansion to obtain a satisfactory accuracy when the wavelength gets close to the lattice spacing. Such a wavelength-dependent Taylor expansion is applied to the displacement field of the diatomic lattice, resulting in a novel SG model. For various kinds of diatomic lattices, the dispersion diagrams given by the proposed SG model always agree well with those given by the discrete model throughout the first Brillouin zone, manifesting the robustness of the present model. Based on this SG model, we have conducted the following discussions. (I) Both mass and stiffness ratios affect the band gap structures of diatomic lattice metamaterials, which is very helpful for the design of metamaterials. (II) The increase in the SG order can enhance the model performance if the modified Taylor expansion is adopted. Without doing so, the higher-order continuum model can suffer from a stronger instability issue and does not necessarily have a better accuracy. The proposed SG continuum model with the eighth-order truncation is found to be enough to capture the dispersion behaviors all over the first Brillouin zone. (III) The effects of the nonlocal interactions are analyzed. The nonlocal interactions reduce the workable range of the well-known long-wave approximation, causing more local extrema in the dispersive diagrams. The present model can serve as a satisfactory continuum theory when the wavelength gets close to the lattice spacing, i.e., when the long-wave approximation is no longer valid. For the convenience of band gap designs, we have also provided the design space from which one can easily obtain the proper mass and stiffness ratios corresponding to a requested band gap width.
PTEN promoter methylation predicts 10-year prognosis in hormone receptor-positive early breast cancer patients who received adjuvant tamoxifen endocrine therapy
Authors: Fan Yu , Xie Guiqin , Wang Zhu , Wang Yu , Wang Yanping , Zheng Hong , Zhong Xiaorong 
Published: January 2022

Abstract
Purpose
There remain a lack of biomarkers for endocrine therapy resistance in patients with breast cancer (BC), which is proving to be a great challenge. In vitro experiments have shown that downregulation of PTEN expression leads to resistance to tamoxifen (TAM) in BC cells. We aimed to investigate the predictive role of tumor PTEN promoter methylation and PTEN expression in long-term survival after TAM adjuvant therapy in patients with early-stage BC.

Methods
From 2001 to 2013, 105 patients with stage I–III BC who were treated with standardized adjuvant TAM for 5 years or until relapse in West China Hospital (WCH) were enrolled in this study. PTEN expression and DNA methylation of three specified sequences from the PTEN promoter in primary tumors were measured using immunohistochemistry and pyrosequencing. A cohort of 159 hormone receptor-positive patients receiving TAM treatment from The Cancer Genome Atlas (TCGA) database was used for verification.

Results
Median follow-up time for the WCH cohort was 141.7 months. The low, moderate, and high PTEN expression groups had differing 10-year disease-free survival (DFS) (42.3%, 55%, 81%, respectively, P = 0.027) and overall survival (OS) rates (65%, 84.2%, 90.5%, respectively, P = 0.027). Higher methylation levels of the second sequence (− 819 to − 787 bp), rather than the first (− 1143 to − 1107 bp) or third sequence (− 663 to − 593 bp), independently increased the risk of disease recurrence (hazard ratio = 2.60) and death (hazard ratio = 3.79) in the WCH cohort, according to multivariate Cox regression analysis. Importantly, out of the five CpG islands located within this sequence, only high methylation of the − 796 CpG island predicted shorter DFS and OS. In TCGA validation cohort, there was also a trend of higher methylation of the − 796 CpG island correlating with shorter disease-free intervals, with borderline significance (P = 0.057).

Conclusion
Low PTEN expression and high methylation of its promoter (sequence − 819 to − 787 bp) in tissue predict poor DFS and OS in hormone receptor-positive early BC patients who received adjuvant TAM.
Symptom Dimension Breakpoints for the Obsessive-Compulsive Inventory-Child Version (OCI-CV)
Authors: Cervin Matti , Garcia-Delgar Blanca , Calvo Rosa , Ortiz Ana E. , Lazaro Luisa 
Published: January 2022

AbstractPediatric obsessive-compulsive disorder (OCD) clusters around three major symptom dimensions: contamination/cleaning, symmetry/ordering, and disturbing thoughts/checking. The Obsessive-Compulsive Inventory-Child Version (OCI-CV) is a self-report questionnaire that provides scores along six theory-based OCD dimensions, but no study has evaluated how well OCI-CV identifies clinically significant symptoms within each of the three major symptom dimensions of OCD. We examined this question using data from 197 Swedish and Spanish youth with OCD. All youth completed the OCI-CV and clinically significant symptom severity within each major OCD dimension was established with a validated interview-based measure. Results showed that a score ≥ 3 on the OCI-CV washing scale excellently captured those with clinically significant contamination/cleaning symptoms (AUC = 0.85 [0.80–0.90], 79% accuracy). A score ≥ 4 on the obsessing scale adequately captured those with disturbing thoughts/checking symptoms (AUC = 0.71 [0.64–0.78], 67% accuracy) and a score ≥ 3 on the ordering scale adequately captured those with symmetry/ordering symptoms (AUC = 0.72 [0.65–0.79], 70% accuracy). Similar accuracy of the breakpoints was found in the Swedish and Spanish samples. OCI-CV works well to identify youth with pediatric OCD that have clinically significant contamination/cleaning symptoms. The measure can also with adequate precision identify those with clinically significant disturbing thoughts/checking and symmetry/ordering symptoms. The breakpoints provided in this study can be used to examine differences in clinical presentation and treatment outcome for youth with different types of OCD.
Cardiovascular risk factors, living and ageing in Halle: the CARLA study
Authors: Hassan Lamiaa , Efremov Ljupcho , Großkopf Anne , Kartschmit Nadja , Medenwald Daniel , Schott Artjom , Schmidt-Pokrzywniak Andrea , Lacruz Maria E. , Tiller Daniel , Kraus Frank Bernhard , Greiser Karin H. , Haerting Johannes , Werdan Karl , Sedding Daniel , Simm Andreas , Nuding Sebastian , Kluttig Alexander , Mikolajczyk Rafael 
Published: January 2022

AbstractThe CARLA study (Cardiovascular Disease, Living and Ageing in Halle) is a longitudinal population-based cohort study of the general population of the city of Halle (Saale), Germany. The primary aim of the cohort was to investigate risk factors for cardiovascular diseases based on comprehensive cardiological phenotyping of study participants and was extended to study factors associated with healthy ageing. In total, 1779 probands (812 women and 967 men, aged 45–83 years) were examined at baseline (2002–2005), with a first and second follow-up performed 4 and 8 years later. The response proportion at baseline was 64.1% and the reparticipation proportion for the first and second follow-up was 86% and 77% respectively. Sixty-four percent of the study participants were in retirement while 25% were full- or partially-employed and 11% were unemployed at the time of the baseline examination. The currently running third follow-up focuses on the assessment of physical and mental health, with an intensive 4 h examination program, including measurement of cardiovascular, neurocognitive, balance and gait parameters. The data collected in the CARLA Study resulted in answering various research questions in over 80 publications, of which two thirds were pooled analyses with other similar population-based studies. Due to the extensiveness of information on risk factors, subclinical conditions and evident diseases, the biobanking concept for the biosamples, the cohort representativeness of an elderly population, and the high level of quality assurance, the CARLA cohort offers a unique platform for further research on important indicators for healthy ageing.
A Critical Review on the Complex Potentials in Linear Elastic Fracture Mechanics
Authors: Scheel Johannes , Wallenta Daniel , Ricoeur Andreas 
Published: January 2022

AbstractIntroducing a crack in an elastic plate is challenging from the mathematical point of view and relevant within an engineering context of evaluating strength and reliability of structures. Accordingly, a multitude of associated works is available to date, emanating from both applied mathematics and mechanics communities. Although considering the same problem, the given complex potentials prove to be different, revealing various inconsistencies in terms of resulting stresses and displacements. Essential information on crack near-tip fields and crack opening displacements is nonetheless available, while intuitive adaption is required to obtain the full-field solutions. Investigating the cause of prevailing deficiencies inevitably leads to a critical review of classical works by Muskhelishvili or Westergaard. Complex potentials of the mixed-mode loaded Griffith crack, sparing restrictive assumptions or limitations of validity, are finally provided, allowing for rigorous mathematical treatment. The entity of stresses and displacements in the whole plate is finally illustrated and the distributions in the crack plane are given explicitly.
Greening work: labor market policies for the environment
Authors: Bohnenberger Katharina 
Published: January 2022

AbstractJobs are essential for social inclusion, raising taxes, and guaranteeing the financial resilience of (welfare) states. At the same time, the Sustainable Development Goals, the Paris Agreement, and the European Green Deal require the greening of our economies and labor markets. This paper assesses how labor market policies can green employment. The paper analyses the potential effects of eight different policy strategies on four dimensions of the Taxonomy of Sustainable Employment: conversion of plants and businesses, environmental labor law, climate decommodification, socio-ecological job guarantee, vocational guidance and retraining, distribution of employment time, alternative income sources, and equalization of income. All eight strategies have the potential of greening employment but feature different intensities in the four dimensions. In the light of environmental crises, the results suggest widening the toolbox of labor market policies for a green and just transition.
Post-conflict development, reviewing the water sector in Somalia
Authors: Mourad Khaldoon A. 
Published: January 2022

AbstractSomali post-conflict development faces many challenges that affect the sustainability of the water sector. This paper reviews and analyses the post-conflict development activities in the water sector through local communications and reviewing published materials and databases from international players in Somalia, funding agencies and financial tracking service. The paper has shown that there has been great attention and support given to the country during its post-conflict development. However, most of these initiatives and projects have focused on emerging issues such as tackling food security and water, sanitation and hygiene services. The paper also shows that the continuous funding of emerging issues in Somalia has reduced its long-term sustainability of the water sector and limited its national and long-term benefits but has increased corruption due to increase the gap between actors and local people. Therefore, new transparent cooperative initiatives are needed based on transparent involvement and coordination among donors, local authorities and implementers to improve and develop the water sector and the livelihood in Somalia through a solid water governance system.
The generic isogeny decomposition of the Prym Variety of a cyclic branched covering
Authors: Alexandrou Theodosis 
Published: January 2022

AbstractLet $$f:S'\longrightarrow S$$

f
:

S
′

⟶
S

be a cyclic branched covering of smooth projective surfaces over $${\mathbb {C}}$$
C
whose branch locus $$\Delta \subset S$$

Δ
⊂
S

is a smooth ample divisor. Pick a very ample complete linear system $$|{\mathcal {H}}|$$

|
H
|

on S, such that the polarized surface $$(S, |{\mathcal {H}}|)$$

(
S
,
|
H
|
)

is not a scroll nor has rational hyperplane sections. For the general member $$[C]\in |{\mathcal {H}}|$$

[
C
]
∈
|
H
|

consider the $$\mu _{n}$$

μ
n

-equivariant isogeny decomposition of the Prym variety $${{\,\mathrm{Prym}\,}}(C'/C)$$

Prym

(

C
′

/
C
)

of the induced covering $$f:C'{:}{=}f^{-1}(C)\longrightarrow C$$

f
:

C
′

:
=

f

-
1

(
C
)

⟶
C

: $$\begin{aligned} {{\,\mathrm{Prym}\,}}(C'/C)\sim \prod _{d|n,\ d\ne 1}{\mathcal {P}}_{d}(C'/C). \end{aligned}$$

Prym

(

C
′

/
C
)

∼

∏

d
|
n
,

d
≠
1

P
d

(

C
′

/
C
)

.

We show that for the very general member $$[C]\in |{\mathcal {H}}|$$

[
C
]
∈
|
H
|

the isogeny component $${\mathcal {P}}_{d}(C'/C)$$

P
d

(

C
′

/
C
)

is $$\mu _{d}$$

μ
d

-simple with $${{\,\mathrm{End}\,}}_{\mu _{d}}({\mathcal {P}}_{d}(C'/C))\cong {\mathbb {Z}}[\zeta _{d}]$$

End

μ
d

(

P
d

(

C
′

/
C
)

)

≅
Z

[

ζ
d

]

. In addition, for the non-ample case we reformulate the result by considering the identity component of the kernel of the map $${\mathcal {P}}_{d}(C'/C)\subset {{\,\mathrm{Jac}\,}}(C')\longrightarrow {{\,\mathrm{Alb}\,}}(S')$$

P
d

(

C
′

/
C
)

⊂

Jac

(

C
′

)

⟶

Alb

(

S
′

)

.
The Engagement of Complementors and the Role of Platform Boundary Resources in e-Commerce Platform Ecosystems
Authors: Engert Martin , Evers Julia , Hein Andreas , Krcmar Helmut 
Published: January 2022

AbstractThe success of digital platforms can be attributed to the engagement of autonomous complementors as exemplified by e-commerce Content Management System (CMS) platforms such as WordPress and Shopify. Platform owners provide Platform Boundary Resources (PBRs) to stimulate and control complementor engagement. Despite the increasing scholarly interest in digital platform ecosystems, their exact role in facilitating and channeling complementor engagement remains unclear. Therefore, we conducted an embedded case study on CMS platform ecosystems, comprising a total of 24 interviews with platform owners and complementors. We inductively derive five types of complementor engagement and their respective manifestations and two overarching engagement goals of complementors. Moreover, we determine the different types of PBRs utilized, including their critical effects, and distinguish between uniform and individual PBRs reflecting their respective generalizability and scalability. We discuss the findings by introducing the concepts of complementor resourcing and complementor securing and shed light on the standardization-individualization tension of PBRs faced by platform owners.
Binding site identification of G protein-coupled receptors through a 3D Zernike polynomials-based method: application to C. elegans olfactory receptors
Authors: Di Rienzo Lorenzo , De Flaviis Luca , Ruocco Giancarlo , Folli Viola , Milanetti Edoardo 
Published: January 2022

AbstractStudying the binding processes of G protein-coupled receptors (GPCRs) proteins is of particular interest both to better understand the molecular mechanisms that regulate the signaling between the extracellular and intracellular environment and for drug design purposes. In this study, we propose a new computational approach for the identification of the binding site for a specific ligand on a GPCR. The method is based on the Zernike polynomials and performs the ligand-GPCR association through a shape complementarity analysis of the local molecular surfaces. The method is parameter-free and it can distinguish, working on hundreds of experimentally GPCR-ligand complexes, binding pockets from randomly sampled regions on the receptor surface, obtaining an Area Under ROC curve of 0.77. Given its importance both as a model organism and in terms of applications, we thus investigated the olfactory receptors of the C. elegans, building a list of associations between 21 GPCRs belonging to its olfactory neurons and a set of possible ligands. Thus, we can not only carry out rapid and efficient screenings of drugs proposed for GPCRs, key targets in many pathologies, but also we laid the groundwork for computational mutagenesis processes, aimed at increasing or decreasing the binding affinity between ligands and receptors.
Improved Suzuki–Miyaura reaction conversion efficiency using magnetic nanoparticles and inductive heating
Authors: Villacampa Alejandro , Duque Luis , Juanes Olga , Palomares Francisco Javier , Herrasti Pilar , Menéndez Nieves 
Published: January 2022

AbstractThe use of magnetic nanoparticles in C–C coupling reactions enables the facile recovery of the catalyst under environmentally friendly conditions. Herein, the synthesis of Pd/Fe@Fe3O4 nanoparticles by the reduction of Pd2+ and oxidation of Fe on the surface of preformed Fe@Fe3O4 is reported. The nanoparticles were characterized using a variety of analytical techniques (transmission electron microscopy, Mössbauer spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction) to determine their size, structure, and chemical composition. The catalytic efficiency of these nanoparticles in classical Suzuki–Miyaura coupling reactions was investigated. The nanoparticles achieved high catalytic activity with the application of local heating by an alternating magnetic field. An investigation was conducted at identical temperatures to compare global heating with the application of an external magnetic field; magnetic heating demonstrated excellent substrate conversion in lesser time and at a lower temperature. The catalyst could also be recycled and reused three times, with ~ 30% decrease in the substrate conversion, which is most likely due to the agglomeration of the Pd nanoparticles or poisoning of the Pd catalyst. This approach, which takes advantage of the catalytic activity and magnetic susceptibility of magnetic nanoparticles, can be applied to several organic transformations to improve their efficiency.
Graphical abstract