bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using a neonatal rat model to explore the therapeutic potential of coenzyme Q10 in prematurity under hyperoxia
Authors: Lee Cheng‐Han , Lee Ming‐Sheng , Yang Rei‐Cheng , Hsu Chien‐Sheng , Su Tzu‐Cheng , Chang Po‐Sheng , Lin Ping‐Ting , Kao Jun‐Kai 
Published: February 2022

AbstractHyperoxia, is often used in preterm supportive care, leading to high oxygen exposure in neonates. Coenzyme Q10 (CoQ10) is a free radical scavenger that has been studied in older children but never be investigated for its role in preterm care. We hypothesize that the administration of exogenous CoQ10 would raise serum concentrations of CoQ10 and mitigate the adverse effects of hyperoxia on the organs by reducing oxygen‐free radicals and inflammation. The aim of this study was to evaluate the effects of oxidative stress, inflammatory response, and survival in neonatal rats after CoQ10 treatment. Neonatal rats delivered from four pregnant Wistar rats were randomly divided into four groups: (a) control, (b) CoQ10, (c) hyperoxia (O2 group), and (d) treatment (CoQ10 + O2) groups. The dose of CoQ10 injected was 30 mg/kg. The CoQ9, CoQ10, cytokines, oxidative stress, and antioxidant enzyme activity were measured. Tissue samples were histologically examined and mortality was monitored for 16 days. The level of CoQ9 significantly increased in the liver, kidney, and plasma, while the level of CoQ10 significantly increased in most organ tissues in the CoQ10 + O2 group. Additionally, CoQ10 decrease oxidative stress in the liver, increase antioxidant enzyme activity in the heart, kidney, and brain, and reverse an inclined level of hematopoietic growth factors. However, CoQ10 had no effect on inflammation, organ damage, or mortality. Therefore, the use of CoQ10 in potential adjuvant therapy for neonatal hyperoxia requires further research.
LncRNA PVT1 contributes to invasion and doxorubicin resistance of bladder cancer cells through promoting MDM2 expression and AURKB‐mediated p53 ubiquitination
Authors: Jiang Xiaoqin , Li Huizhen , Fang Yu , Xu Chuanliang 
Published: February 2022

AbstractIn most bladder cancer (BC) patients, cancer cells will eventually develop chemical resistance causing increased mortality. This study aimed to explore the mechanism of lncRNA plasmacytoma variant translocation 1 (PVT1) in regulating doxorubicin (ADM) resistance of BC cells. We observed that PVT1 expression was upregulated in ADM‐resistant BC cells compared with ADM‐sensitive BC cells. Downregulation of PVT1 suppressed ADM‐resistant BC cell proliferation and invasion, promoted apoptosis, and increased sensitivity to ADM, while PVT1 overexpression promoted ADM‐sensitive BC cell growth and their resistance to ADM. Further study uncovered that PVT1 could interact with and promote mouse double minute 2 (MDM2) expression, and upregulated MDM2‐mediated Aurora kinase B (AURKB). Furthermore, Nutlin‐3, an inhibitor of MDM2, could counteract the promotive effects of PVT1 overexpression on ADM resistance of ADM‐sensitive BC cell, the expression of multidrug‐resistance‐related proteins, and the inhibition of p53‐mediated tumor suppressor genes. And, overexpression of MDM2 or AURKB reversed the promotive effects of PVT1 silence on the ADM sensitivity of ADM‐resistant BC cell, and the inhibitory effect on expression multidrug resistance proteins. Mechanically, AURKB increased MDM2‐mediated p53 ubiquitination. Taken together, PVT1 promoted BC cell proliferation and drug resistance via elevating MDM2 expression and AURKB‐mediated p53 ubiquitination.
Introduction and History of the Chemistry of Nucleic Acids Therapeutics
Authors: Gait Michael J. , Agrawal Sudhir 
Published: February 2022

AbstractThis introduction charts the history of the development of the major chemical modifications that have influenced the development of nucleic acids therapeutics focusing in particular on antisense oligonucleotide analogues carrying modifications in the backbone and sugar. Brief mention is made of siRNA development and other applications that have by and large utilized the same modifications. We also point out the pitfalls of the use of nucleic acids as drugs, such as their unwanted interactions with pattern recognition receptors, which can be mitigated by chemical modification or used as immunotherapeutic agents.
In Vivo Models for the Evaluation of Antisense Oligonucleotides in Skin
Authors: Bremer Jeroen , van den Akker Peter C. 
Published: February 2022

AbstractHere, we describe an in vivo model in which antisense oligonucleotides were preclinically evaluated in reconstituted patient and healthy control skin. The aim was to investigate the effect of antisense oligonucleotides upon local or systemic administration. This allows for clinically relevant evaluation of antisense oligonucleotides in an in vivo setting. In this model, primary human keratinocytes and fibroblasts were placed into silicone grafting chambers, implanted onto the back of athymic nude mice. After sufficient cells were expanded, within a few weeks, human skin grafts were generated with a high success rate. These mice bearing grafts were subsequently treated with antisense oligonucleotides targeting exon 105 of the COL7A1 gene which encodes type VII collagen. Patients completely lacking expression of type VII collagen develop severe blistering of skin and mucosa, i.e., recessive dystrophic epidermolysis bullosa. In this chapter, we describe the in vivo model used for the preclinical evaluation of antisense oligonucleotides as therapeutic approach for recessive dystrophic epidermolysis bullosa.
How to Design U1 snRNA Molecules for Splicing Rescue
Authors: Matos Liliana , Santos Juliana I. , Coutinho Mª. Francisca , Alves Sandra 
Published: February 2022

AbstractMutations affecting constitutive splice donor sites (5′ss) are among the most frequent genetic defects that disrupt the normal splicing process. Pre-mRNAsplicing requires the correct identification of a number of cis-acting elements in an ordered fashion. By disrupting the complementarity of the 5′ss with the endogenous small nuclear RNA U1 (U1 snRNA), the key component of the spliceosomal U1 ribonucleoprotein, 5′ss mutations may result in exon skipping, intron retention or activation of cryptic splice sites. Engineered modification of the U1 snRNA seemed to be a logical method to overcome the effect of those mutations. In fact, over the last years, a number of in vitro studies on the use of those modified U1 snRNAs to correct a variety of splicing defects have demonstrated the feasibility of this approach. Furthermore, recent reports on its applicability in vivo are adding up to the principle that engineered modification of U1 snRNAs represents a valuable approach and prompting further studies to demonstrate the clinical translatability of this strategy.Here, we outline the design and generation of U1 snRNAs with different degrees of complementarity to mutated 5′ss. Using the HGSNAT gene as an example, we describe the methods for a proper evaluation of their efficacyin vitro, taking advantage of our experience to share a number of tips on how to design U1 snRNA molecules for splicing rescue.
Generation of Protein-Phosphorodiamidate Morpholino Oligomer Conjugates for Efficient Cellular Delivery via Anthrax Protective Antigen
Authors: Palacio-Castañeda Valentina , Brock Roland , Verdurmen Wouter P. R. 
Published: February 2022

AbstractPhosphorodiamidate morpholino oligomers (PMOs) offer great promise as therapeutic agents for translation blocking or splice modulation due to their high stability and affinity for target sequences. However, in spite of their neutral charge as compared to natural oligonucleotides or phosphorothioate analogs, they still show little permeability for cellular membranes, highlighting the need for effective cytosolic delivery strategies. In addition, the implementation of strategies for efficient cellular targeting is highly desirable to minimize side effects and maximize the drug dose at its site of action. Anthrax toxin is a three-protein toxin of which the pore-forming protein anthrax protective antigen (PA) can be redirected to a receptor of choice and lethal factor (LF), one of the two substrate proteins, can be coupled to various cargoes for efficient cytosolic cargo delivery. In this protocol, we describe the steps to produce the proteins and protein conjugates required for cytosolic delivery of PMOs through the cation-selective pore generated by anthrax protective antigen. The method relies on the introduction of a unique cysteine at the C-terminal end of a truncated LF (aa 1–254), high-yield expression of the (truncated) toxin proteins in E. coli, functionalization of a PMO with a maleimide group and coupling of the maleimide-functionalized PMO to the unique cysteine on LF by maleimide-thiol conjugation chemistry. Through co-administration of PA with LF-PMO conjugates, an efficient cytosolic delivery of PMOs can be obtained.
Arguing About “COVID”: Metalinguistic Arguments on What Counts as a “COVID-19 Death”
Authors: Lewiński Marcin , Abreu Pedro 
Published: February 2022

AbstractIn this contribution, we explore the plausibility and consequences of treating arguments over what counts as a COVID-19 death as metalinguistic arguments. While unquestionably related to the epidemiological and public health issues, these arguments are also arguments about how a term should be used. As such, they touch upon some of the foundational issues in meta-semantics, discussed in the recent literature on metalinguistic negotiations, conceptual ethics, and conceptual engineering. Against this background, we study official statements (of WHO, governments) and media reports to critically reconstruct the metalinguistic elements of the dispute over what a COVID-19 death is. We analyze in particular how epistemic and practical reasons are intertwined in nuanced and complex ways to produce an interesting type of metalinguistic interventions.
How to Handle Reasonable Scientific Disagreement: The Case of COVID-19
Authors: Antiochou Konstantina , Psillos Stathis 
Published: February 2022

AbstractThe COVID-19 pandemic has been accompanied by an overabundance of information about the new coronavirus and the disease it causes, which is often false or misleading. Science communication can play a key role in the fight against mis- and disinformation. However, the attempt to separate facts from fiction and control the flow of information is hindered by the uncertainties surrounding the scientific understanding of SARS-CoV-2. In this chapter we discuss the recent debate between John Ioannidis and Nassim Taleb about the COVID-19 forecasts and the measures that should be taken to prevent SARS-CoV-2 transmission. Our aim is to explain what distinguishes a ‘reasonable disagreement’ that may arise within science from misinformation or dissemination of false news. The Ioannidis-Taleb debate is susceptible to two readings: it can be seen as a methodological debate between scientists or as a debate about the values that can appropriately influence science policy making. This suggests a difficulty to say which is the basis of the disagreement. We show, however, that these two readings are equally supported under uncertainty and in particular that the second reading relates to the issue of how much transparency is needed to ensure the legitimacy of the values involved in decision-making.
Introduction
Authors: Mardal Kent-André , Rognes Marie E. , Thompson Travis B. , Valnes Lars Magnus 
Published: February 2022

AbstractOur brain is our most precious yet most mysterious organ. It consists of nearly 100 billion neurons, of which typically has 10,000 connections that extend up to a meter. As such, it is an intricate web that enable us to experience the world. In addition to neurons, the brain consists of about the same number of glial cells, around 700 kilometers of blood vessels, the extracellular matrix, and is surrounded by clear water-like cerebrospinal fluid, which together all work to maintain the delicate neurons' environment in a healthy state. At the whole-organ level, this is already incredibly complex, yet this is only part of the story; at any given time, various processes are happening in the brain, such as the electrical impulses between neurons and the complex chemical signaling that helps to maintain homeostasis. Due to the innate micro-scale complexity of the brain, a natural approach, in attempting to understand the brain's physiology and function, is offered by homogenized, continuum-based modeling; here, the focus is on modeling the large-scale behavior arising from the aggregate of small-scale contributions.
Getting started: from T1 images to simulation
Authors: Mardal Kent-André , Rognes Marie E. , Thompson Travis B. , Valnes Lars Magnus 
Published: February 2022

AbstractThe goal of this chapter is to outline how to perform a numerical simulation of a brain region defined from structural MR images. To address this challenge, we first demonstrate how to generate a high quality mesh of a brain hemisphere from T1-weighted MR images using the tools introduced in Chapter 2. Next, we show how to define a finite element discretization of the diffusion equation (1.1) over this mesh to simulate the influx of an injected tracer.
Introducing Heterogeneities
Authors: Mardal Kent-André , Rognes Marie E. , Thompson Travis B. , Valnes Lars Magnus 
Published: February 2022

AbstractIn this chapter, we will consider how to mark, remove, and mesh different regions of the brain and its environment based on FreeSurfer segmentations. We will

create hemisphere meshes differentiating between gray and white matter,

create hemisphere meshes without ventricles,

create brain meshes by combining the two hemispheres,

map parcellations onto brain meshes, and

locally refine parcellated brain meshes.
The Compressor: Gas Turbine Engine Keystone
Authors: Decher Reiner 
Published: February 2022

AbstractAll engines involve the raising of pressure in the engine’s medium, be it liquid compression of water, piston-cylinder compression of air or compression by aerodynamic forces. The last is the hardest because it is required to be efficient and stable. An aerodynamic air compressor works by slowing velocities to raise pressure. The airfoil has a difficult time doing this reliably and well and so does the compressor. When it does, it allows for amazing performance of the engine in terms of power and efficiency.
Spin Matrix Theory in near $$ \frac{1}{8} $$-BPS corners of $$ \mathcal{N} $$ = 4 super-Yang-Mills
Authors: Baiguera Stefano , Harmark Troels , Lei Yang 
Published: February 2022

Abstract
We consider limits of $$ \mathcal{N} $$
N
= 4 super-Yang-Mills (SYM) theory that approach BPS bounds. These limits result in non-relativistic theories that describe the effective dynamics near the BPS bounds and upon quantization are known as Spin Matrix Theories. The near-BPS theories can be obtained by reducing $$ \mathcal{N} $$
N
= 4 SYM on a three-sphere and integrating out the fields that become non-dynamical in the limits. In the previous works [1–3] we have considered various SU(1,1) and SU(1,2) types of subsectors in this limit. In the current work, we will construct the remaining Spin Matrix Theories defined near the $$ \frac{1}{8} $$

1
8

-BPS subsectors, which include the PSU(1,1|2) and SU(2|3) cases. We derive the Hamiltonians by applying the spherical reduction algorithm and show that they match with the spin chain result, coming from the loop corrections to the dilatation operator. In the PSU(1,1|2) case, we prove the positivity of the spectrum by constructing cubic supercharges using the enhanced PSU(1|1)2 symmetry and show that they close to the interacting Hamiltonian. We finally analyse the symmetry structure of the sectors in view of an interpretation of the interactions in terms of fundamental blocks.
Characterization of a hybrid scanning system comprising acousto-optical deflectors and galvanometer scanners
Authors: Franz Daniel , Häfner Tom , Kunz Tim , Roth Gian-Luca , Rung Stefan , Esen Cemal , Hellmann Ralf 
Published: February 2022

AbstractWe report on the characterization of a hybrid laser scanning system using acousto-optical deflectors in combination with galvanometer scanners for ultra-short pulse laser material processing. The hybrid scanning system is characterized by the roundness of static pulsed ablations of metal thin film on a transparent substrate within the acousto-optical scanning field at different galvanometer scanner deflection angles and laser focal positions. An ablation roundness of more than 90% is reached in a defocusing range of 200 $$\upmu \text{m}$$

μ
m

within a galvanometer scanfield of 900 $$\text{mm}^2$$

mm
2

, corresponding to approximately 74% of the usable scan area of the f-theta lens. A high maximum positioning speed of 843 m/s is pointed out within an acousto-optical scanfield of 0.4 $$\text{mm}^{2}$$

mm
2

by applying positioning frequencies of up to 1 MHz across a distance of 843 $$\upmu \text{m}$$

μ
m

. Consequently, the hybrid scanning system combines the advantages of optical and mirror-based scanners, enabling a highly dynamic and extremely precise laser beam positioning in a large processing area.
Age-dependent perturbation of the perceptual and postural vertical by visual roll vection and susceptibility to motion sickness in children
Authors: Schnabel Lutz , Wuehr Max , Huppert Anna , Bardins Stanislav , Brandt Thomas , Huppert Doreen 
Published: February 2022

Abstract
Background
The visual contribution to the perceptual and postural vertical is mediated by a multisensory integration process and may relate to children’s susceptibility to motion sickness that is hypothesized to arise from intersensory conflicts.

Objective
To analyze the maturation of visual contribution to the perceptual and postural vertical in conjunction with the motion sickness susceptibility in childhood.

Methods
In 81 healthy children (aged 2–17 years; 57 females), adjustments of the subjective visual vertical and posturographically tested mediolateral displacements of body sway were measured during free upright stance and large-field visual motion stimulation in the roll plane (roll vection). Motion sickness susceptibility was assessed by taking the history of parents and children.

Results
Vection-induced tilts of the visual vertical showed a linear age-dependent decrease with largest tilts in the youngest (2–7 years; median of 20°) and smallest tilts in the oldest age group (13–17 years; median of 9–10°). Analogously, postural tilts as measured by mediolateral body sway were greatest in the youngest and smallest in the oldest age group. In contrast, motion sickness susceptibility was lowest in the youngest and highest in the oldest age group and exhibited an inverse correlation with vection-induced tilts of the visual vertical.

Conclusion
Roll vection-induced tilts of the visual and postural vertical exhibited a similar age-dependent course with the greatest effects in the youngest and the least effects in the oldest age group, the latter of which exhibited the highest susceptibility to motion sickness.
The preoperative G8 geriatric screening tool independently predicts survival in older patients with endometrial cancer: results of a retrospective single-institution cohort study
Authors: Anic Katharina , Altehoefer Christin , Krajnak Slavomir , Schmidt Mona Wanda , Schwab Roxana , Linz Valerie Catherine , Schmidt Marcus , Westphalen Christiane , Hartmann Erik Kristoffer , Hasenburg Annette , Battista Marco Johannes 
Published: February 2022

Abstract
Purpose
The aim of this retrospective study was to evaluate the prognostic impact of global health status assessment tools in elderly patients with endometrial cancer (EC) on survival.

Methods
Preoperative frailty status was assessed by the G8 geriatric screening tool (G8 Score), Lee Schonberg prognostic index, Charlson Comorbidity index and American Society of Anesthesiologists Physical Status System in women older than 60 years with EC. Univariable and multivariable Cox-regression analyses, as well as Kaplan–Meier survival analyses were performed to determine the prognostic impact. Statistical analyses were adjusted for cancer entity-specific risk factors such as conventional histopathological tumor characteristics and relevant anamnestic life style parameters.

Results
153 patients with all stages of EC who were operated at the University Medical Center Mainz between 2008 and 2019 were included. In multivariable analyses, only the G8 Score retained independent significance as a prognostic factor for disease-specific survival (DSS) (HR:4.58; 95% CI [1.35–15.51]) and overall survival (OS) (HR:2.89; 95% CI [1.31–6.39]. 92 patients (61.3%) were classified as G8-non-frail with a significantly increased DSS and OS rate compared to the 58 G8-frail patients (DSS:93.8% vs. 60.8%; p < 0.001 and OS:88.2% vs. 49.7%; p < 0.001; respectively).

Conclusions
This is the first study demonstrates the substantial clinical and prognostic impact of the G8 Score on survival in elderly women with EC. Assessing the frailty status to estimate the individual vulnerability of elderly cancer patients could be useful in preoperative decision-making to individualize treatment plans such as the surgical radicality and to improve pre- and postoperative morbidity.
Electroconvulsive therapy and adiposity-related parameters in treatment-resistant depressed patients
Authors: Maier Hannah Benedictine , Pollak Christoph , Moschny Nicole , Toto Sermin , Schlatt Colin , Eberlein Christian K. , Sperling Wolfgang , Kornhuber Johannes , Kahl Kai G. , Bleich Stefan , Neyazi Alexandra , Frieling Helge 
Published: February 2022

AbstractObesity is often accompanied by major depressive disorder (MDD), and vice versa. Latest research findings suggest the body mass index (BMI) to play a role in antidepressant treatment response in general. Our study aims to examine whether adiposity-related parameters such as BMI, glucose homeostasis, or serum lipids are associated with remission to electroconvulsive therapy (ECT). A pilot study (PS, n = 9) and a glucose study (GS, n = 29) were conducted. Blood was withdrawn directly before and 15 min (GS) as well as 1 h (PS) after the first ECT and directly before the last one (usually an ECT series comprised up to twelve sessions). BMI was associated with remission in the PS (remitters: M = 28, SD = 2.5; non-remitters: M = 22, SD = 2.08; t(7) = 3.325, p < 0.001, d = 0.24) but not in the GS or when pooled together. Glucose and insulin levels increased significantly after a single ECT session (GS: glucose: F (2,25.66) = 39.04, p < 0.001; insulin: PS: F (2,83) = 25.8, p < 0.001; GS: F (2,25.87) = 3.97, p < 0.05) but no chronic effect was detectable. Serum lipids were neither significantly altered after a single ECT session nor during a whole course of ECT. There was no difference between remitters and non-remitters in insulin, glucose, or serum lipid levels. Our study is lacking the differentiation between abdominal and peripheral fat distribution, and the sample size is small. Unexpectedly, BMI, glucose homeostasis, and lipid serum levels did not differ in patients remitting during ECT. In contrast to recently published studies, we cannot confirm the hypothesis that BMI may have an impact on ECT response.
Simulative Untersuchungen des Einflusses elektromechanischer Belastungen an einem Axiallager auf die Glättung der Oberflächen und den Traganteil im Kugel-Laufbahnkontakt
Authors: Graf Simon , Sauer Bernd 
Published: February 2022

ZusammenfassungEs werden Ergebnisse aus einer Kontaktsimulation vorgestellt, welche die Oberflächenveränderung eines Axiallagers infolge von unerwünschtem elektrischem Stromdurchgang bei Mischreibung zeigen. Das hierzu entwickelte Modell berücksichtigt neben den Oberflächenrauheiten auch das nichtlineare Materialverhalten des Wälzlagerwerkstoffes. Im Gegensatz zu bekannten Modellierungsmethoden für ähnliche Problemstellungen, wird hier ein neuartiger Ansatz auf Basis einer gekoppelten Euler- Lagrange- Finite Element Simulation entwickelt. Das Modell liefert, mit experimentell geschädigten Oberflächen als Eingangsgröße, Erkenntnisse zum Traganteilsverhalten und weiterer mechanischer Kenngrößen infolge kombinierter mechanischer und elektrischer Belastungen.