bluuebunny/crossref_metadata_2025 huggingface dataset:
Stepwise Tailoring of Perovskite Nucleation Dynamics and Defect Formation Using a Supersaturation‐Suppression Layer for Developing Efficient and Stable Perovskite Solar Cells
Authors: Jeong Gyujeong , Choi Yunseong , Kim Yujin , Jung Seungon , Koo Donghwan , Son Eunbin , Jeong Seulgi , Choi Kyoung‐Jin , Park Hyesung
Published: January 2024

Tailoring crystal growth and defects in perovskites, a viable strategy for suppressing non‐radiative recombination, is widely employed for developing efficient and stable perovskite solar cells (PSCs). However, simultaneous tailoring of crystal growth and defects in PSCs is challenging owing to several limitations; for example, excessive interactions between additives and perovskite precursors impede crystallization, and additive‐induced impurity phases can substantially increase the defect density in perovskite films. In this study, we introduced a metal‐induced supersaturation‐suppression layer (SSL) as a pseudo‐additive interfacial layer to tailor the crystallization dynamics and defect formation in perovskite crystals in steps. The proposed perovskite modification process involves an SSL‐induced metal–halide ion reaction, which modulates the crystallization kinetics for grain growth and enables the formation of metal–halide complex anion adducts that can reduce crystalline defects and suppress non‐radiative recombination while facilitating preferential perovskite crystal growth by alleviating residual strains. Because of these stepwise synergistic effects, the SSL‐based PSCs exhibited significantly improved device performances (23.4%), low hysteresis losses, and enhanced atmospheric operational stability.
Analytical quality by design aided stability indicating a robust ultra‐performance liquid chromatographic technique for the quantification of sonidegib and its organic impurities in bulk drug substance
Authors: Rajashekhar Kasturi , Naidu Challa Gangu , Kumar Chebolu Naga Sesha Sai Pavan , Ramachandra Bondigalla , Padiya Raju
Published: January 2024

A simple quality by design aided stability indicating method was developed for quantification of sonidegib (SONI) and its process related impurities using on ultra‐performance liquid chromatography in bulk drug substance. AutoChrom and Design‐Expert software were used to predict physicochemical properties, draw Ionization graphs, and generate analytical target profile. SONI was subjected to forced degradation conditions, such as oxidative, acid hydrolysis, base hydrolysis, hydrolytic, thermal, and photolytic hydrolysis. All degradation products and process contaminants were separated using an Acquity Ethylene Bridged Hybrid C18 column in gradient elution mode with a mobile phase containing 0.02 M ammonium acetate buffer and acetonitrile: methanol (80:20 v/v). The predicted physicochemical properties are accurate and they facilitated for selection of robust conditions in development of chromatographic method with minimal trials. The developed method can be used for quantification of drug and its process related impurities in bulk drugs.
Delayed deformation of confinement buildings: 30‐Year in situ measured data and prediction with the next‐generation Eurocode‐2
Authors: Aili Abudushalamu , Torrenti Jean‐Michel , Barre Francis , Caba Ludovic
Published: January 2024

Biaxially prestressed large concrete structures of the confinement building in nuclear power plants (NPPs) should meet the safety requirement for the extension of the service time. Long‐term delayed strains of concrete are one of the key factors determining the safety factor in these structures. This article presents 30‐year long in situ measurement results of strain evolution of confinement buildings in four different NPPs. The delayed strains are predicted at a material level using the next‐generation Eurocode‐2, and the influence of temperature as proposed by thefibmodel code 2010, making use of delayed strain characteristics of the corresponding concrete from a previous study. We found that the default law given in Eurocode underestimates the delayed strain. However, with the possibility of adjusting the shrinkage and creep laws, the prediction results fit with a good accuracy for the in situ measurement.
Fetal and neonatal neuroimaging in twin–twin transfusion syndrome
Authors: Spruijt M. S. , van Klink J. M. M. , de Vries L. S. , Slaghekke F. , Middeldorp J. M. , Lopriore E. , Tan R. N. G. B. , Toirkens J. P. , Steggerda S. J.
Published: January 2024

Objectives

To describe the types of brain injury and subsequent neurodevelopmental outcome in fetuses and neonates from pregnancies with twin–twin transfusion syndrome (TTTS). Additionally, to determine risk factors for brain injury and to review the use of neuroimaging modalities in these cases.

Methods

This was a retrospective cohort study of consecutive TTTS pregnancies treated with laser surgery in a single fetal therapy center between January 2010 and January 2020. The primary outcome was the incidence of brain injury, classified into predefined groups. Secondary outcomes included adverse outcome (perinatal mortality or neurodevelopmental impairment), risk factors for brain injury and the number of magnetic resonance imaging (MRI) scans.

Results

Cranial ultrasound was performed in all 466 TTTS pregnancies and in 685/749 (91%) liveborn neonates. MRI was performed in 3% of pregnancies and 4% of neonates. Brain injury was diagnosed in 16/935 (2%) fetuses and 37/685 (5%) neonates and all predefined injury groups were represented. Four fetal and four neonatal cases of cerebellar hemorrhage were detected. Among those with brain injury, perinatal mortality occurred in 11/16 (69%) fetuses and 8/37 (22%) neonates. Follow‐up was available for 29/34 (85%) long‐term survivors with brain injury and the mean age at follow‐up was 46 months. Neurodevelopmental impairment was present in 9/29 (31%) survivors with brain injury. Adverse outcome occurred in 28/53 (53%) TTTS individuals with brain injury. The risk of brain injury was increased after recurrent TTTS/post‐laser twin anemia–polycythemia sequence (TAPS) (odds ratio (OR), 3.095 (95% CI, 1.581–6.059); P = 0.001) and lower gestational age at birth (OR per 1‐week decrease in gestational age, 1.381 (95% CI, 1.238–1.541); P < 0.001).

Conclusions

Based on dedicated neurosonography and limited use of MRI, brain injury was diagnosed in 2% of fetuses and 5% of neonates with TTTS. Adverse outcome was seen in over half of cases with brain injury. Brain injury was related to recurrent TTTS/post‐laser TAPS and a lower gestational age at birth. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
A French bulldog with rectal bleeding, anaemia and left hindlimb oedema due to arteriovenous malformations
Authors: Letwin Laura , Hanot Emilie Marine , Murgia Daniela , Taeymans Olivier , Tappin Simon , Sanchez Ferran Valls
Published: January 2024

A 2‐year‐10‐month‐old, male, neutered French bulldog presented with a rectal prolapse, rectal bleeding, weight loss and anaemia with left hindlimb oedema. Biopsies of the recto‐anal junction identified moderate neutrophilic and lymphoplasmacytic erosive proctitis, with moderate vascular hyperaemia and moderately ectatic vessels in the rectal submucosa. Abdominal computed tomography identified intra‐abdominal arteriovenous malformations involving the mesenteric arteries, colic arteries, the vertebral venous plexus and femoral veins causing concurrent left hindlimb oedema. The malformations were too extensive to allow for surgical resection of the affected area of intestine. The patient's clinical signs initially responded to immunosuppressive therapy with corticosteroids. However, the patient's clinical signs progressed, and the dog was euthanased 4 months after initial presentation. To the authors’ knowledge, this is the first report of such extensive arteriovenous anomalies also involving rectal prolapse and suspected colonic ectasia in a dog.
Functional magnetic resonance imaging in schizophrenia: current evidence, methodological advances, limitations and future directions
Authors: Voineskos Aristotle N. , Hawco Colin , Neufeld Nicholas H. , Turner Jessica A. , Ameis Stephanie H. , Anticevic Alan , Buchanan Robert W. , Cadenhead Kristin , Dazzan Paola , Dickie Erin W. , Gallucci Julia , Lahti Adrienne C. , Malhotra Anil K. , Öngür Dost , Lencz Todd , Sarpal Deepak K. , Oliver Lindsay D.
Published: January 2024

Functional neuroimaging emerged with great promise and has provided fundamental insights into the neurobiology of schizophrenia. However, it has faced challenges and criticisms, most notably a lack of clinical translation. This paper provides a comprehensive review and critical summary of the literature on functional neuroimaging, in particular functional magnetic resonance imaging (fMRI), in schizophrenia. We begin by reviewing research on fMRI biomarkers in schizophrenia and the clinical high risk phase through a historical lens, moving from case‐control regional brain activation to global connectivity and advanced analytical approaches, and more recent machine learning algorithms to identify predictive neuroimaging features. Findings from fMRI studies of negative symptoms as well as of neurocognitive and social cognitive deficits are then reviewed. Functional neural markers of these symptoms and deficits may represent promising treatment targets in schizophrenia. Next, we summarize fMRI research related to antipsychotic medication, psychotherapy and psychosocial interventions, and neurostimulation, including treatment response and resistance, therapeutic mechanisms, and treatment targeting. We also review the utility of fMRI and data‐driven approaches to dissect the heterogeneity of schizophrenia, moving beyond case‐control comparisons, as well as methodological considerations and advances, including consortia and precision fMRI. Lastly, limitations and future directions of research in the field are discussed. Our comprehensive review suggests that, in order for fMRI to be clinically useful in the care of patients with schizophrenia, research should address potentially actionable clinical decisions that are routine in schizophrenia treatment, such as which antipsychotic should be prescribed or whether a given patient is likely to have persistent functional impairment. The potential clinical utility of fMRI is influenced by and must be weighed against cost and accessibility factors. Future evaluations of the utility of fMRI in prognostic and treatment response studies may consider including a health economics analysis.
Singular integral method based closed form solution for moving EMPS model in semipermeable two‐equal‐collinear cracked MEE material
Authors: Kumar Ashish , Sharma Kuldeep , Bui Tinh Quoc
Published: January 2024

This paper presents the analytical closed‐form solutions of moving two equal collinear semipermeable cracks in magneto‐electro‐elastic material considering the strip electric‐magnetic polarization saturation (EMPS) model. To simulate the dynamic/moving cracks problem, two equal collinear Yoffe type cracks moving with a constant subsonic velocity along the plane of the cracks is considered. The problem is solved by considering semipermeable crack face conditions and under the in‐plane electro‐magnetic‐mechanical loading. Applying distributed dislocation technique and symmetry of the collinear cracks, the problem is reduced into simultaneous singular integral equations which have been solved in closed form expressions using finite Hilbert approach. The explicit expressions for dynamic distributed dislocation densities, crack opening displacement (COD), crack opening potential (COP), crack opening induction (COI), and local stress intensity factors (LSIFs) are evaluated for both the cases of the EMPS model (magnetic zone is smaller or greater than electric zone). For evaluation of inner and outer electric and magnetic zone lengths (MZLs), an iterative approach is applied to solve the developed two non‐linear equations. Also, to implement the semipermeable crack‐face conditions, a bisection iterative method has been applied. Based on the developed closed form solutions, numerical studies are presented for standard fracture parameters with respect to crack propagation velocity, electrical loading and inter‐crack space distance. This study shows that electric displacement and magnetic induction defined over the crack‐surface for semipermeable conditions decrease whereas the numerical values of saturated zone lengths, COD, COP, COI, and LSIFs increase with increasing crack propagation velocity. Moreover, for both static and dynamic cracks problems, the significant crack‐interaction effects have been observed on all the studied fracture parameters except the crack‐face conditions.
Porous Heterogeneous Sulfide Nickel/Nickel Iron Alloy Catalysts for Oxygen Evolution Reaction of Alkaline Water Electrolysis at High Current Density
Authors: Bi Songhu , Geng Zhen , Jin Liming , Xue Mingzhe , Zhang Cunman
Published: January 2024

Alkaline water electrolysis is the important pathway for the green hydrogen production, where oxygen evolution reaction (OER) is the rate-limiting step due to the sluggish reaction kinetics. Transition metal heterogeneous catalyst is the kind of important OER catalyst for alkaline water electrolysis due to its good performance, low price and environmental friendliness. In this work, the porous sulfide nickel@nickel iron alloy catalyst (i.e. NM/NS@Ni3Fe) is prepared by the designed high-temperature vulcanization and multi-step electrodeposition method. The NM/NS@Ni3Fe catalyst exhibits an outstanding OER performance in an alkaline environment, with a low potential of 1.53 V at high current density of 1000 mA cm−2 and a low Tafel slope of 89 mV dec−1. The excellent OER performance is attributed to the unique electronic structure of Ni3S2/Ni3Fe heterogeneous interface and the catalyst layer with porous structure. The results indicate that Ni3S2 provides good electronic conductivity and the low electronegativity S atoms increase the formation of oxygen vacancies, which effectively improves the OER performance. In addition, the hydrophilic and porous structure of the electrode facilitates bubbles release and electrolyte flow at high current density. It provides the guidance for the design of porous heterogeneous OER catalysts with good-performance.
Coupled Heat Transfer Characteristics of SiC High Temperature Heat Exchanger in Solid Oxide Fuel Cell
Authors: Song Jia-Liang , Chen Hua , Chen Yong-Dong , Yu Gai-Ge , Zou Hong-Wei , Han Bing-Chuan
Published: January 2024

High temperature heat exchanger is a crucial equipment in the BOP of SOFC. Replacing the commonly used metal materials with high-temperature resistant SiC ceramic materials for the manufacturing of SOFC high-temperature heat exchanger is a revolutionary technology with great application potential. This paper focused on SiC-based cathodic air preheater which is a novel SOFC high temperature heat exchanger, and firstly investigated the coupled radiation-conduction-convection heat transfer characteristics between flue gas and air at extremely high temperature conditions. The DO model in ANSYS Fluent was utilized to analyze the radiation heat transfer characteristics of high-temperature flue gas and the effect of gas absorption coefficient, and the simulation results were compared with the S2S model and non-radiation model. The results showed that radiation heat transfer cannot be ignored at high flue gas inlet temperature. With flue gas inlet temperature in the range of 800–1100 °C and low air/flue gas flow rate ratio, the gas radiation heat transfer and the effect of flue gas absorption coefficient can be ignored.
Numerical Investigation of Combustion Characteristics of the Port Fuel Injection Hydrogen-Oxygen Internal Combustion Engine Under the Low-Temperature Intake Condition
Authors: Ji Changwei , Shen Jianpu , Wang Shuofeng
Published: January 2024

The flammability limits of the hydrogen-oxygen mixture are extremely wide, and the ignition energy is low. Due to its excellent combustion properties, the hydrogen-oxygen mixture can be used as fuel in internal combustion engines (ICEs). However, the combustion of hydrogen-oxygen mixture is too intense, which results in limited research on its application in ICEs and is limited to low-temperature conditions in aerospace. This research aims to numerically discuss the coupling effects of equivalence ratio and ignition timing on the port fuel injection hydrogen-oxygen ICE under the low-temperature intake condition. The three-dimensional geometric model of a single-cylinder ICE was established using the CONVERGE software and validated against the mean in-cylinder pressure and reaction mechanism. The results indicate that adjusting equivalence ratio and ignition timing operating parameters is beneficial for controlling the temperature and pressure in the cylinder within a reasonable range during the total combustion process. In general, under the low-temperature intake condition, adopting a high equivalence ratio and optimal ignition timing strategy improve the combustion process and power performance of the port fuel injection hydrogen-oxygen ICE.
Compatibilization of Carbon/Polymer Composites: Molecular Dynamics Simulation
Authors: Yao Dongmei , Feng Cong , Pan Xiangmin , Fan Runlin , Zhan Zize , Chen Jing , Zheng Junsheng , Ming Pingwen
Published: January 2024

The compatibilization of graphene/epoxy resin composites and carbon nanotube CNT/epoxy resin composite were studied based on the crystallized models with the molecular dynamics simulation in this paper. The effect of resin formula on compatibility parameter of carbon matrix was studied, and the combination of diglycidyl ether of bisphenol A (E51) resin with isophorone diamine (IPD) as the hardener achieved the best result. Further, the graphene/epoxy resin composite were constructed to investigate the effect of functional groups on components compatibility, conclude hydroxyl, carboxyl and amino. It was found that the functional groups had strong impact on compatibility parameter of graphene and CNT, whereas carboxylated graphene exhibits the best compatibility with the resin. This is due to the strong electronegativity of the carboxyl group, which induces a molecular interaction with the epoxy groups at the end of E51. The present study is expected to provide significant molecular insight into the relationship of compatibility between carbon matrix and epoxy resin for fuel cell composite bipolar plates.
Study on Configuration and Control Strategy of Electrolyzers in Off-Grid Wind Hydrogen System
Authors: Zhang Tao , Song Lingjun , Yang Fuyuan , Li Yangyang
Published: January 2024

Multi-electrolyzers system is an effective method to address the problem that the lowest operating point of the alkaline water electrolyzer still is high when the water electrolysis system is coupled with renewable energy. This work proposed different configurations of nominal power and operating strategies of electrolyzers for an off-grid isolated stand-alone wind hydrogen system. The configurations contain different nominal power of electrolyzers rather than the same nominal power. An equal load strategy is proposed and simulated based on the operation characteristics of the alkaline electrolyzer. This strategy could reach the 99% of energy absorption rate.
Modeling and Simulation of PEMFC Supply System with Oxygen and Air Mixing
Authors: Tong Guangyao , Chen Fengxiang , Li Tao , Xu Shuo , Shen Wei , Zhou Su
Published: January 2024

With the growing energy crisis and environmental problems in recent years, the green energy technology represented by fuel cell technology has been developing rapidly. Since air contains a large amount of nitrogen that does not participate in the reaction, the circulation of nitrogen in the cathode gas supply system will increase the power consumption of the air compressor, resulting in a lower net power output of the fuel cell system. In order to improve the output performance of the fuel cell system, a new fuel cell cathode gas supply system with oxygen and air mixing is proposed in this paper, and the research results show that this topology can effectively increase the output power of the stack and reduce the power consumption of the air compressor, which can eventually increase the net power of the system to more than 10%. This study provides an effective theoretical guide for the design of fuel cell system and the optimal matching of cathode gas supply system.
Effect of Fan Parameters on Forced-Convection Open-Cathode Proton Exchange Membrane Fuel Cells
Authors: Zhou Jiaxu , Fang Zhifei , Deng Huichao
Published: January 2024

Forced-convection open-cathode proton exchange membrane fuel cells have attracted much attention due to simple structure. The fan, as an important component of the stack, significantly influences the mass density and performance of the stack. Therefore, it is crucial to select the appropriate fan. In this study, the performance of stacks with different fans is compared and the optimal duty ratio and temperature of stacks under different load currents are determined. The experimental results show that excessive air volume reduces the performance of the stack, and the parasitic power should be taken into consideration. Additionally, the weight of the fan is is a significant factor that needs to be considered. Furthermore, the experimental results show that under the condition of sufficient air supply, the appropriate temperature rise is conducive to the improvement of stack performance. In order to reduce the weight of the stack, it is necessary to choose a reasonable fan.
Study on Optimization Operation of Micro-energy Network Considering Electro-ammonia Conversion
Authors: Ruijing Shi , Peng Ren , Xiaochao Fan , Jianglei Wang
Published: January 2024

Micro energy networks are an important way to achieve the “carbon neutrality” goal. To further explore the potential of energy conversion in reducing carbon emissions, this article proposes an optimized operation model for micro energy networks with refined power-to-ammonia conversion. Based on the operation model considering carbon trading and comprehensive demand response, an optimization model for micro energy networks with refined power-to-ammonia conversion is established, with the objective of minimizing the system’s operating cost and carbon emissions. Utilizing examples, various micro-source energy dispatch conditions are analyzed and the carbon emission costs, as well as the overall operating costs of the micro energy network, are calculated. The results show that compared with power-to-hydrogen conversion, using power-to-ammonia conversion in micro energy networks can effectively reduce system carbon emissions, with a decrease of 7.88% and a total operating cost reduction of 5.36%. This verifies the feasibility of the model and demonstrates that improving energy utilization can achieve the synergistic operation of the system’s economy and low-carbon emissions.
Extremal surfaces in glue-on AdS/$$ T\overline{T} $$ holography
Authors: Apolo Luis , Hao Peng-Xiang , Lai Wen-Xin , Song Wei
Published: January 2024

Abstract

$$ T\overline{T} $$
T

T
¯

deformed CFTs with positive deformation parameter have been proposed to be holographically dual to Einstein gravity in a glue-on AdS3 spacetime [1]. The latter is constructed from AdS3 by gluing a patch of an auxiliary $$ {\textrm{AdS}}_3^{\ast } $$

AdS
3
∗

spacetime to its asymptotic boundary. In this work, we propose a glue-on version of the Ryu-Takayanagi formula, which is given by the signed area of an extremal surface. The extremal surface is anchored at the endpoints of an interval on a cutoff surface in the glue-on geometry. It consists of an RT surface lying in the AdS3 part of the spacetime and its extension to the $$ {\textrm{AdS}}_3^{\ast } $$

AdS
3
∗

region. The signed area is the length of the RT surface minus the length of the segments in $$ {\textrm{AdS}}_3^{\ast } $$

AdS
3
∗

. We find that the Ryu-Takayanagi formula with the signed area reproduces the entanglement entropy of a half interval for $$ T\overline{T} $$
T

T
¯

-deformed CFTs on the sphere. We then study the properties of extremal surfaces on various glue-on geometries, including Poincaré AdS3, global AdS3, and the BTZ black hole. When anchored on multiple intervals at the boundary, the signed area of the minimal surfaces undergoes phase transitions with novel properties. In all of these examples, we find that the glue-on extremal surfaces exhibit a minimum length related to the deformation parameter of $$ T\overline{T} $$
T

T
¯

-deformed CFTs.
B-RNS-GSS type II superstring in Ramond-Ramond backgrounds
Authors: Chandia Osvaldo , Gomide João
Published: January 2024

Abstract

The B-RNS-GSS formalism containing both RNS and GS worldsheet variables is extended for the description of the Type II superstring in curved backgrounds. The BRST charge of the theory is expressed in terms of $$ \mathcal{N} $$
N
= (1, 1) superconformal generators $$ \left(T,G;\hat{T},\hat{G}\right) $$

T
G

T
̂

G
̂

, and the classical anticommutation relations {G, G} = −2T and $$ \left\{\hat{G},\hat{G}\right\}=-2\hat{T} $$

G
̂

G
̂

=
−
2

T
̂

are shown to imply the Type II supergravity equations of motion. The particular case of the Type IIB superstring in an AdS5 × S5 background is discussed and shown to be classically integrable.
Inhibition of autocrine HGF maturation overcomes cetuximab resistance in colorectal cancer
Authors: Jones Vivian Truong , Graves-Deal Ramona , Cao Zheng , Bogatcheva Galina , Ramirez Marisol A. , Harmych Sarah J. , Higginbotham James N. , Sharma Vineeta , Damalanka Vishnu C. , Wahoski Claudia C. , Joshi Neeraj , Irudayam Maria Johnson , Roland Joseph T. , Ayers Gregory D. , Liu Qi , Coffey Robert J. , Janetka James W. , Singh Bhuminder
Published: January 2024

Although amplifications and mutations in receptor tyrosine kinases (RTKs) act as bona fide oncogenes, in most cancers, RTKs maintain moderate expression and remain wild-type. Consequently, cognate ligands control many facets of tumorigenesis, including resistance to anti-RTK therapies. Herein, we show that the ligands for the RTKs MET and RON, HGF and HGFL, respectively, are synthesized as inactive precursors that are activated by cellular proteases. Our newly generated HGF/HGFL protease inhibitors could overcome both de novo and acquired cetuximab resistance in colorectal cancer (CRC). Conversely, HGF overexpression was necessary and sufficient to induce cetuximab resistance and loss of polarity. Moreover, HGF-induced cetuximab resistance could be overcome by the downstream MET inhibitor, crizotinib, and upstream protease inhibitors. Additionally, HAI-1, an endogenous inhibitor of HGF proteases, (i) was downregulated in CRC, (ii) exhibited increased genomic methylation that correlated with poor prognosis, (iii) HAI-1 expression correlated with cetuximab response in a panel of cancer cell lines, and (iv) exogenous addition of recombinant HAI-1 overcame cetuximab resistance in CC-HGF cells. Thus, we describe a targetable, autocrine HAI-1/Protease/HGF/MET axis in cetuximab resistance in CRC.
Packing a Tetrahedron by Similar Tetrahedra
Authors: Januszewski Janusz , Zielonka Łukasz
Published: January 2024

Any collection of homothetic copies of some tetrahedron $$T_r$$

T
r

, whose total volume does not exceed one quarter of the volume of $$T_r$$

T
r

, can be packed into $$T_r$$

T
r

.
Aufbau des neuen „Forschungsdatenzentrums Gesundheit“ zur Datenbereitstellung für die Wissenschaft
Authors: Ludwig Melanie , Schneider Katharina , Heß Steffen , Broich Karl
Published: January 2024

Die Analyse von Real-world-Daten (RWD) hat in der Gesundheitsforschung der vergangenen Jahre eine immer größere Bedeutung gewonnen. Mit dem im Aufbau befindlichen Forschungsdatenzentrum Gesundheit („FDZ Gesundheit“) werden Forschende künftig Zugang zu Routinedaten der gesetzlichen Krankenversicherungen von rund 74 Mio. Menschen in Deutschland erhalten können. Auch Daten aus den elektronischen Patientenakten können hier mit der Zeit für die Forschung bereitgestellt werden. Dabei gewährleistet das FDZ Gesundheit höchste Datenschutz- und IT-Sicherheitsstandards. Der digitale Antragsprozess, die Datenbereitstellungen in sicheren virtuellen Analyseräumen sowie die Features zur Unterstützung der Auswertungen, wie Kataloge von Kodiersystemen, ein Point-and-Click-Analysetool und vordefinierte Standardauswertungen, erhöhen die Nutzungsfreundlichkeit für die Forschenden. Durch die Analysen der umfangreichen im FDZ verfügbaren Gesundheitsdaten ergeben sich zukünftig vielfältige Möglichkeiten, das Gesundheitssystem und die Versorgungsqualität zu verbessern.

In diesem Beitrag werden zunächst die Vorteile des FDZ Gesundheit beleuchtet und die sich durch das FDZ ergebenden Möglichkeiten für die Forschung in der Versorgung und für die Bevölkerung exemplarisch skizziert. Danach werden die Struktur und die zentralen Aspekte des FDZ Gesundheit erläutert. Ein Ausblick auf die Chancen der Verknüpfung verschiedener Daten wird gegeben. Wie die Antrags- und Datennutzungsprozesse am FDZ aussehen werden, wird dabei am Beispiel von fiktiven Möglichkeiten zur Analyse von Long COVID anhand der künftig verfügbaren Abrechnungsdaten dargestellt.
Sentience, Vulcans, and zombies: the value of phenomenal consciousness
Authors: Shepherd Joshua
Published: January 2024

Many think that a specific aspect of phenomenal consciousness—valenced or affective experience—is essential to consciousness’s moral significance (valence sentientism). They hold that valenced experience is necessary for well-being, or moral status, or psychological intrinsic value (or all three). Some think that phenomenal consciousness generally is necessary for non-derivative moral significance (broad sentientism). Few think that consciousness is unnecessary for moral significance (non-necessitarianism). In this paper, I consider the prospects for these views. I first consider the prospects for valence sentientism in light of Vulcans, beings who are conscious but without affect or valence of any sort. I think Vulcans pressure us to accept broad sentientism. But I argue that a consideration of explanations for broad sentientism opens up possible explanations for non-necessitarianism about the moral significance of consciousness. That is, once one leans away from valence sentientism because of Vulcans, one should feel pressure to accept a view on which consciousness is not necessary for well-being, moral status, or psychological intrinsic value.
Long chain capsaicin analogues synthetized by CALB-CLEAs show cytotoxicity on glioblastoma cell lines
Authors: Diaz-Vidal Tania , Armenta-Pérez Vicente Paúl , Rosales-Rivera Luis Carlos , Basulto-Padilla Georgina Cristina , Martínez-Pérez Raúl Balam , Mateos-Díaz Juan Carlos , Gutiérrez-Mercado Yanet K. , Canales-Aguirre Alejandro A. , Rodríguez Jorge A.
Published: January 2024

Glioblastoma is one of the most lethal tumors, displaying striking cellular heterogeneity and drug resistance. The prognosis of patients suffering from glioblastoma after 5 years is only 5%. In the present work, capsaicin analogues bearing modifications on the acyl chain with long-chain fatty acids showed promising anti-tumoral activity by its cytotoxicity on U-87 and U-138 glioblastoma multiforme cells. The capsaicin analogues were enzymatically synthetized with cross-linked enzyme aggregates of lipase B from Candida antarctica (CALB). The catalytic performance of recombinant CALB-CLEAs was compared to their immobilized form on a hydrophobic support. After 72 h of reaction, the synthesis of capsaicin analogues from linoleic acid, docosahexaenoic acid, and punicic acid achieved a maximum conversion of 69.7, 8.3 and 30.3% with CALB-CLEAs, respectively. Similar values were obtained with commercial CALB, with conversion yields of 58.3, 24.2 and 22% for capsaicin analogues from linoleic acid, DHA and punicic acid, respectively. Olvanil and dohevanil had a significant cytotoxic effect on both U-87 and U-138 glioblastoma cells. Irrespective of the immobilization form, CALB is an efficient biocatalyst for the synthesis of anti-tumoral capsaicin derivatives.

Key points

• This is the first report concerning the enzymatic synthesis of capsaicin analogues from docosahexaenoic acid and punicic acid with CALB-CLEAs.

• The viability U-87 and U-138 glioblastoma cells was significantly affected after incubation with olvanil and dohevanil.

• Capsaicin analogues from fatty acids obtained by CALB-CLEAs are promising candidates for therapeutic use as cytotoxic agents in glioblastoma cancer cells.
Valgus stress radiographs have a minor additional value in detecting lateral cartilage wear when selecting patients for medial partial knee replacement
Authors: van Langeveld Stephan J. , Janssen Stein J. , Oost Iris Koenraadt-van , Terra Maaike P. , van Geenen Rutger C. I.
Published: January 2024

Introduction

A valgus stress radiograph, in addition to the weight-bearing fixed flexion posteroanterior radiograph (e.g., Rosenberg), is deemed useful to assess lateral cartilage wear by measuring lateral joint space width (JSW) in patients with medial knee osteoarthritis. This study aimed to assess: (1) the difference in measured lateral JSW between the Rosenberg and the valgus stress radiograph, and (2) the ability of the valgus stress radiograph to detect lateral cartilage wear (indicated by joint space narrowing) in patients where the Rosenberg radiograph showed full thickness cartilage (i.e., the additional value).

Materials and methods

The Rosenberg and valgus stress radiographs, obtained between January 1st 2018 and December 31st 2018, of 137 patients with medial knee osteoarthritis prior to total or partial knee replacement were retrospectively collected. The lateral JSW was measured at its midpoint (midJSW) and minimum (minJSW). The differences were tested with a paired-sample t test. The valgus stress radiograph was considered to have an additional value if: (1) JSW ≥ 5 mm on the Rosenberg radiograph, (2) JSW < 5 mm on valgus stress radiograph, and (3) > 2 mm less JSW on the valgus stress than on the Rosenberg radiograph.

Results

The mean differences in lateral JSW between the Rosenberg and valgus stress radiographs were 0.53 mm (SD = 1.0 mm, p < 0.001) for midJSW and 0.66 mm (SD = 1.1 mm, p < 0.001) for minJSW with both values being lower on the valgus stress radiograph. The valgus stress radiograph was of additional value in 4–6% of the patients.

Conclusions

Although the valgus stress radiograph shows more lateral JSW narrowing compared to Rosenberg radiograph, it only has an additional value in 1 out of 17–25 patients with medial osteoarthritis. We, therefore, recommend a Rosenberg radiograph as routine radiographic assessment and only use an additional valgus stress radiograph in case of discrepancy between clinical and radiological findings.
pH-regulated single cell migration
Authors: Stock Christian
Published: January 2024

Over the last two decades, extra- and intracellular pH have emerged as fundamental regulators of cell motility. Fundamental physiological and pathological processes relying on appropriate cell migration, such as embryonic development, wound healing, and a proper immune defense on the one hand, and autoimmune diseases, metastatic cancer, and the progression of certain parasitic diseases on the other, depend on surrounding pH. In addition, migrating single cells create their own localized pH nanodomains at their surface and in the cytosol. By this means, the migrating cells locally modulate their adhesion to, and the re-arrangement and digestion of, the extracellular matrix. At the same time, the cytosolic nanodomains tune cytoskeletal dynamics along the direction of movement resulting in concerted lamellipodia protrusion and rear end retraction. Extracellular pH gradients as found in wounds, inflamed tissues, or the periphery of tumors stimulate directed cell migration, and long-term exposure to acidic conditions can engender a more migratory and invasive phenotype persisting for hours up to several generations of cells after they have left the acidic milieu. In the present review, the different variants of pH-dependent single cell migration are described. The underlying pH-dependent molecular mechanisms such as conformational changes of adhesion molecules, matrix protease activity, actin (de-)polymerization, and signaling events are explained, and molecular pH sensors stimulated by H+ signaling are presented.
Predicting wait time for pediatric kidney transplant: a novel index
Authors: Alvarez Alexandra , Montgomery Ashley , Galván Nhu Thao Nguyen , Brewer Eileen D. , Rana Abbas
Published: January 2024

Background

Over one thousand pediatric kidney transplant candidates are added to the waitlist annually, yet the prospective time spent waiting is unknown for many. Our study fills this gap by identifying variables that impact waitlist time and by creating an index to predict the likelihood of a pediatric candidate receiving a transplant within 1 year of listing. This index could be used to guide patient management by giving clinicians a potential timeline for each candidate’s listing based on a unique combination of risk factors.

Methods

A retrospective analysis of 3757 pediatric kidney transplant candidates from the 2014 to 2020 OPTN/UNOS database was performed. The data was randomly divided into a training set, comprising two-thirds of the data, and a testing set, comprising one-third of the data. From the training set, univariable and multivariable logistic regressions were used to identify significant predictive factors affecting wait times. A predictive index was created using variables significant in the multivariable analysis. The index’s ability to predict likelihood of transplantation within 1 year of listing was validated using ROC analysis on the training set. Validation of the index using ROC analysis was repeated on the testing set.

Results

A total of 10 variables were found to be significant. The five most significant variables include the following: blood group, B (OR 0.65); dialysis status (OR 3.67); kidney disease etiology, SLE (OR 0.38); and OPTN region, 5 (OR 0.54) and 6 (OR 0.46). ROC analysis of the index on the training set yielded a c-statistic of 0.71. ROC analysis of the index on the testing set yielded a c-statistic of 0.68.

Conclusions

This index is a modest prognostic model to assess time to pediatric kidney transplantation. It is intended as a supplementary tool to guide patient management by providing clinicians with an individualized prospective timeline for each candidate. Early identification of candidates with potential for prolonged waiting times may help encourage more living donation including paired donation chains.

Graphical Abstract
Insights into the relationship between hydraulic safety, hydraulic efficiency and tree structural complexity from terrestrial laser scanning and fractal analysis
Authors: Dorji Yonten , Isasa Emilie , Pierick Kerstin , Cabral Juliano Sarmento , Tobgay Tashi , Annighöfer Peter , Schuldt Bernhard , Seidel Dominik
Published: January 2024

Key message

This research focused on the interplay between tree structural complexity and drought tolerance, unraveling the crucial role of Db as an indicator of hydraulic efficiency and vulnerability in several tree species.

The potential of trees to adapt to drier and hotter climates will determine the future state of forests in the wake of a changing climate. Attributes connected to the hydraulic network are likely to determine a tree’s ability to endure drought. However, how a tree’s architectural attributes related to drought tolerance remains understudied. To fill this gap, we compared the structural complexity of 71 trees of 18 species obtained from terrestrial laser scanning (TLS) with key hydraulic thresholds. We used three measures of xylem safety, i.e., the water potential at 12%, 50%, and 88% loss of hydraulic conductance (P12, P50, P88) and specific hydraulic conductivity (Ks) to assess the trees’ drought tolerance. TLS data were used to generate 3D attributes of each tree and to construct quantitative structure models (QSMs) to characterize the branching patterns. Fractal analysis (box-dimension approach) was used to evaluate the overall structural complexity of the trees (Db) by integrating horizontal and vertical extent as well as internal branching patterns. Our findings revealed a significant relationship between the structural complexity (Db) and the three measures of xylem safety along with Ks. Tree species with low structural complexity developed embolism-resistant xylem at the cost of hydraulic efficiency. Our findings also revealed that the Db had a stronger and more significant relationship with branch hydraulic safety and efficiency compared to other structural attributes examined. We conclude that Db seems to be a robust descriptor of tree architecture that relates to important branch hydraulic properties of a tree.
Hydration of $$p-$$aminobenzoic acid: structures and non-covalent bondings of aminobenzoic acid-water clusters
Authors: Anni Diane , Amika Mbema Jean Claude , Malloum Alhadji , Conradie Jeanet
Published: January 2024

Context

Micro-hydration of the aminobenzoic acid is essential to understand its interaction with surrounding water molecules. Understanding the micro-hydration of the aminobenzoic acid is also essential to study its remediation from wastewater. Therefore, we explored the potential energy surfaces (PESs) of the para-aminobenzoic acid-water clusters, $$\text {ABW}_{n}$$

ABW
n

, $$n=1-10$$

n
=
1
-
10

, to study the microsolvation of the aminobenzoic acid in water. In addition, we performed a quantum theory of atoms in molecules (QTAIM) analysis to identify the nature of non-covalent bondings in the aminobenzoic acid-water clusters. Furthermore, temperature effects on the stability of the located isomers have been examined. The located structures have been used to calculate the hydration free energy and the hydration enthalpy of the aminobenzoic acid using the cluster continuum solvation model. The hydration free energy and the hydration enthalpy of the aminobenzoic acid at room temperature are evaluated to be −7.0 kcal/mol and −18.1 kcal/mol, respectively. The hydration enthalpy is in perfect agreement with a previous experimental estimate. Besides, temperature effects on the calculated hydration enthalpy and free energy are reported. Finally, we calculated the gas phase binding energies of the most stable structures of the $$\text {ABW}_{n}$$

ABW
n

clusters using twelve functionals of density functional theory (DFT), including empirical dispersion. The DFT functionals are benchmarked against the DLPNO-CCSD(T)/CBS. We have found that the three most suitable DFT functionals are classified in the following order: PW6B95D3 > MN15 > $$\omega $$
ω
B97XD. Therefore, the PW6B95D3 functional is recommended for further study of the aminobenzoic acid-water clusters and similar systems.

Methods

The exploration started with classical molecular dynamics simulations followed by complete optimization at the PW6B95D3/def2-TZVP level of theory. Optimizations are performed using Gaussian 16 suite of codes. QTAIM analysis is performed using the AIMAll program.
Photobiomodulation increases brain metabolic activity through a combination of 810 and 660 wavelengths: a comparative study in male and female rats
Authors: Zorzo Candela , Rodríguez-Fernández Lucía , Martínez Juan A. , Arias Jorge L.
Published: January 2024

Photobiomodulation (PBM), an emerging and non-invasive intervention, has been shown to benefit the nervous system by modifying the mitochondrial cytochrome c-oxidase (CCO) enzyme, which has red (620–680 nm) or infrared (760–825 nm) spectral absorption peaks. The effect of a single 810-nm wavelength with a combination of 810 nm and 660 nm lights in the brain metabolic activity of male and female rats was compared. PBM, with a wavelength of 810 nm and a combination of 810 nm and 660 nm, was applied for 5 days on the prefrontal cortex. Then, brain metabolic activity in the prefrontal area, hippocampus, retrosplenial, and parietal cortex was explored. Sex differences were found in cortical and subcortical regions, indicating higher male brain oxidative metabolism, regardless of treatment. CCO activity in the cingulate and prelimbic area, dentate gyrus, retrosplenial and parietal cortex was enhanced in both treatments (810 + 660 nm and 810 nm). Moreover, using the combination of waves, CCO increased in the infralimbic area, and in CA1 and CA3 of the hippocampus. Thus, employment of a single NIR treatment or a combination of red to NIR treatment led to slight differences in CCO activity across the limbic system, suggesting that a combination of lights of the spectrum may be relevant.
Comparison of the removal of intracanal medicaments used in regenerative endodontics from root canal system using needle, ultrasonic, sonic, and laser-activated irrigation systems
Authors: Usta Sıla Nur , Erdem Berat Akın , Gündoğar Mustafa
Published: January 2024

This study aimed to compare the syringe-needle irrigation (SNI), passive ultrasonic irrigation (PUI), EDDY, and shock wave–enhanced emission photoacoustic streaming (SWEEPS) techniques regarding calcium hydroxide and double antibiotic paste removal from the root canal in regenerative endodontic treatments. Eighty single-rooted human teeth were decoronated and enlarged up to #100 to stimulate the immature tooth model. Root canals were irrigated with 1.5% sodium hypochlorite followed by saline solution according to the regenerative endodontic treatment protocol. Dressed teeth were divided into 2 main groups regarding the used intracanal medicaments. Calcium hydroxide and double antibiotic paste were introduced to the canals, and teeth were stored for 3 weeks. Each medicament group was divided into 4 subgroups according to the activation techniques. Medicaments were removed using a 17% EDTA solution. Teeth were split longitudinally into two parts. The remaining medicaments were evaluated under a stereo microscope with a scoring system. Data were analyzed with the Kruskal-Wallis and Mann-Whitney U tests. Regardless of the used irrigation activation systems, there was no statistically significant difference between the removal of the CH and DAP from the root canal (P>0.05). While SWEEPS had the highest ability regarding the removal of intracanal medicaments, syringe-needle irrigation had the lowest (P<0.05). There was no statistically significant difference between PUI and EDDY (P>0.05). Complete removal of intracanal medicaments could not be achieved with any techniques. SWEEPS technology was more effective in removing intracanal medicaments in regenerative endodontic treatments compared to the sonic and ultrasonic irrigation activation systems.