bluuebunny/crossref_metadata_2025 huggingface dataset:
The positive allosteric modulator of NMDA receptors, GNE‐9278, blocks the ethanol‐induced decrease of excitability in developing retrosplenial cortex neurons from mice
Authors: Bird Clark W. , Valenzuela Carlos F.
Published: December 2022

Binge‐like exposure to ethanol during the brain growth spurt triggers apoptotic neurodegeneration in multiple brain regions, including the retrosplenial cortex, a brain region that is part of the hippocampal‐diencephalic‐cingulate memory network. This is mediated, in part, by reduced Ca2+ influx through N‐methyl‐d‐aspartate (NMDA) receptors followed by a decrease in the activation of pro‐survival genes. Here, we tested whether a positive allosteric modulator of NMDA receptors could counteract the inhibitory effect of ethanol on developing retrosplenial cortex pyramidal neurons. We used patch‐clamp electrophysiological techniques in acute slices from postnatal day 6–8 mice to test the effect of the positive allosteric modulator GNE‐9278 on ethanol‐induced inhibition of NMDA receptor function. GNE‐9278 dose‐dependently increased the amplitude, decay time, and total charge of NMDA excitatory postsynaptic currents. At a concentration of 5 μmol L−1, GNE‐9278 significantly reduced the 90 mmol L−1 ethanol‐induced inhibition of NMDA excitatory postsynaptic current amplitude, decay time, and total charge. Current‐clamp experiments showed that 5 μmol L−1 GNE‐9278 ameliorated the 90 mmol L−1 ethanol‐induced inhibition of synaptically‐evoked action potential firing and compound excitatory postsynaptic potential amplitude. These findings indicate that positive allosteric modulators mitigate ethanol‐induced hypofunction of NMDA receptors in developing cerebral cortex neurons, an effect that could ameliorate its pro‐apoptotic effects during the late stages of fetal development.
Health state utilities associated with hyperphagia: Data for use in cost‐utility models
Authors: Howell Timothy A. , Matza Louis S. , Mallya Usha G. , Goldstone Anthony P. , Butsch W. Scott , Lazarus Ethan
Published: December 2022

Objective

Rare genetic diseases of obesity typically present with hyperphagia, a pathologic desire to consume food. Cost‐utility models assessing the value of treatments for these rare diseases will require health state utilities representing hyperphagia. This study estimated utilities associated with various hyperphagia severity levels.

Methods

Four health state vignettes were developed using published literature and clinician input to represent various severity levels of hyperphagia. Utilities were estimated for these health states in a time trade‐off elicitation study in a UK general population sample.

Results

In total, 215 participants completed interviews (39.5% male; mean age 39.1 years). Mean (SD) utilities were 0.98 (0.02) for no hyperphagia, 0.91 (0.10) for mild hyperphagia, 0.70 (0.30) for moderate hyperphagia, and 0.22 (0.59) for severe hyperphagia. Mean (SD) disutilities were −0.08 (0.10) for mild, −0.28 (0.30) for moderate, and −0.77 (0.58) for severe hyperphagia.

Conclusions

These data show increasing severity of hyperphagia is associated with decreased utility. Utilities associated with severe hyperphagia are similar to those of other health conditions severely impacting quality of life (QoL). These findings highlight that treatments addressing substantial QoL impacts of severe hyperphagia are needed. Utilities estimated here may be useful in cost‐utility models of treatments for rare genetic diseases of obesity.
Methods to refine and extend a Pregnancy Register in the UK Clinical Practice Research Datalink primary care databases
Authors: Campbell Jennifer , Shepherd Hilary , Welburn Stephen , Barnett Rhys , Oyinlola Jessie , Oues Namir , Williams Rachael
Published: December 2022

Purpose

Real‐world data represents a valuable tool for pregnancy research. However, an algorithmic approach is needed to ascertain pregnancy timings from this complex data. The Clinical Practice Research Datalink (CPRD) GOLD Pregnancy Register, based on UK Primary care data, has therefore proven to be a valuable research tool. The same algorithmic approach was applied to the CPRD Aurum data to generate an equivalent register in the larger database.

Methods

Records of female patients registered with a CPRD Aurum contributing practice between the 1st of January 1987 and the 30th of April 2021 were searched for evidence of pregnancy. The algorithm used to generate the CPRD GOLD Pregnancy Register was redeveloped and applied first to CPRD GOLD and then to CPRD Aurum. The resulting CPRD Aurum Pregnancy Register was validated against the CPRD GOLD register, linked Hospital Episode Statistics (HES) and the Office of National Statistics (ONS) live birth data.

Results

There are 16 833 427 pregnancy episodes in the CPRD Aurum Pregnancy Register from 6 724 615 women, more than double the number in CPRD GOLD. The distribution of pregnancy outcome types was comparable between the registers. Across the whole register, there was good concordance between pregnancy episodes found in CPRD Aurum and linked HES. However, both CPRD registers saw a declining number of pregnancy episodes from 2007 onwards, steeper than in HES or the ONS birth data.

Conclusions

A pregnancy register has been created in CPRD Aurum. Changes in antenatal care policies in the UK have led to declining numbers of pregnancies in EHR primary care data. However, the creation of this pregnancy register has tripled the number of patients in the CPRD Pregnancy Registers and will increase the capacity to study pregnancy in CPRD data, particularly rare or emerging exposures, and outcomes.
Tacrolimus in the treatment of childhood nephrotic syndrome: Machine learning detects novel biomarkers and predicts efficacy
Authors: Mo Xiaolan , Chen Xiujuan , Zeng Huasong , Zheng Wei , Ieong Chifong , Li Huixian , Huang Qiongbo , Xu Zichuan , Yang Jinlian , Liang Qianying , Liang Huiying , Gao Xia , Huang Min , Li Jiali
Published: December 2022

Study Objective

The pharmacokinetics and pharmacodynamics of tacrolimus (TAC) vary greatly among individuals, hindering its precise utilization. Moreover, effective models for the early prediction of TAC efficacy in patients with nephrotic syndrome (NS) are lacking. We aimed to identify key factors affecting TAC efficacy and develop efficacy prediction models for childhood NS using machine learning algorithms.

Design

This was an observational cohort study of patients with pediatric refractory NS.

Setting

Guangzhou Women and Children's Medical Center between June 2013 and December 2018.

Patients

203 patients with pediatric refractory NS were used for model generation and 35 patients were used for model validation.

Intervention

All patients regularly received double immunosuppressive therapy comprising TAC and low‐dose prednisone or methylprednisolone. In this observational cohort study of 203 pediatric patients with refractory NS, clinical and genetic variables, including single‐nucleotide polymorphism (SNPs), were identified. TAC efficacy was evaluated 3 months after administration according to two different evaluation criteria: response or non‐response (Group 1) and complete remission, partial remission, or non‐remission (Group 2).

Measurements

Logistic regression, extremely random trees, gradient boosting decision trees, random forest, and extreme gradient boosting algorithms were used to develop and validate the models. Prediction models were validated among a cohort of 35 patients with NS.

Main Results

The random forest models performed best in both groups, and the area under the receiver operating characteristics curve of these two models was 80.7% (Group 1) and 80.3% (Group 2). These prediction models included urine erythrocyte count before administration, steroid types, and eight SNPs (ITGB4 rs2290460, TRPC6 rs3824934, CTGF rs9399005, IL13 rs20541, NFKBIA rs8904, NFKBIA rs8016947, MAP3K11 rs7946115, and SMARCAL1 rs11886806).

Conclusions

Two pre‐administration models with good predictive performance for TAC response of patients with NS were developed and validated using machine learning algorithms. These accurate models could assist clinicians in predicting TAC efficacy in pediatric patients with NS before utilization to avoid treatment failure or adverse effects.
Cook‐Off Characteristics of NTO/HMX‐Based Plastic‐Bonded Explosives in a Shaped Charge
Authors: Wang Xinyu , Wang Zaicheng , Fang Yuande
Published: December 2022

In this paper, the cook‐off characteristics of NTO/HMX‐based plastic‐bonded explosives, here after referred to as JEO, with confined and pressure‐relief structures are investigated. Firstly, a pre‐ignition thermal decomposition model and a post‐ignition combustion model of the explosives were established. The chemical reaction kinetics and combustion reaction parameters in the numerical model were calibrated according to a small closed‐bomb experiment. The cook‐off process of the explosives was then studied by numerical simulation, determining the influence of different structures on the ignition time, ignition position, and reaction intensity of a JEO charge. The cook‐off of NTO/HMX‐based plastic‐bonded explosives with different structures was then experimentally studied, obtaining the temperature curve of each explosive, the deformation of the shell and liner, the macro‐reaction phenomena when the charge was ignited and the residue state after the reaction, which verified the validity of the numerical simulation.
Design and Comparison of Diamond‐ and Sapphire‐Based NbN KIDs for Fusion Plasma Polarimetric Diagnostics
Authors: Mazzocchi Francesco , Ilin Konstantin , Kempf Sebastian , Kuzmin Artem , Strauß Dirk , Scherer Theo
Published: December 2022

Design and characterization measurements performed on kinetic inductance detectors (KIDs) produced on sapphire and polycrystalline diamond substrates are presented. Designed as part of a nuclear fusion polarimetric diagnostic, the foreseen plasma‐probing frequency of the final devices is 1.3 THz with a maximum response time under 10 ms and cross‐polarization target accuracy of 1%. These detectors are based on superconducting micro‐resonators that undergo de‐tuning upon absorption of radiation. The main characteristics of the devices include polarization sensitiveness and lumped‐elements multi‐pixel configuration produced from photo‐lithographed niobium nitride (NbN) thin films. The direct current (DC) and microwave characterization measurements highlight large differences in the thin film quality, with the superconductor deposited on diamond showing reduced critical temperature, lower critical current density, and increased values of the kinetic inductance. This difference is likely due to the higher lattice constant and thermal expansion coefficient mismatch between film and substrate in the case of diamond, with the different surface finish quality of the crystalline samples available also playing a role. The devices on both substrates show a bolometric response to THz radiation that fulfills the requirement guidelines and represent a good starting point to optimize the design for the application at hand.
Effect of Strain in Channel on Electron Transport Properties of Ga1−xInxSb High Electron Mobility Transistor Structures with Strained‐Al0.40In0.60Sb/Al0.25In0.75Sb Stepped Buffer
Authors: Endoh Akira , Hatori Koharu , Kishimoto Naoyuki , Hiraoka Mizuho , Kemmochi Yuta , Endoh Yuki , Osawa Koki , Hayashi Takuya , Machida Ryuto , Watanabe Issei , Yamashita Yoshimi , Hara Shinsuke , Kasamatsu Akifumi , Fujishiro Hiroki I.
Published: December 2022

GaInSb is one of the attractive Sb‐based channel materials for high electron mobility transistors (HEMTs) that can operate in the terahertz band. The effect of strain in the channel on the electron transport properties of Ga1−xInxSb channel HEMT structures (x = 0.60, 0.78, 0.85, 0.90, and 0.94) with the strained‐Al0.40In0.60Sb/Al0.25In0.75Sb stepped buffer is investigated. The strain in the Ga1−xInxSb channel layer is determined by the lattice constant of Al0.25In0.75Sb lower buffer layer. The electron mobility (μ) shows the maximum value of 15 100 cm2 V−1s−1atx = 0.78 (unstrained), which has the minimum threading dislocation density (TDD). The value for sheet electron density (Ns) increases with decreasingx, and saturates at about 2.1 × 1012 cm−2when unstrained or tensile strained. The minimum sheet resistance (Rs) is 202 Ω/□ for the unstrained Ga0.22In0.78Sb channel.
Ge‐ and Ge1−zSnz‐Based Gate‐Underlap Dual Material Double Gate Tunnel Field Effect Transistor: Modeling, Optimization, and its Application to Biosensors
Authors: Shaw Namrata , Mukhopadhyay Bratati
Published: December 2022

Herein, an n‐channel dual material double gate tunnel field effect transistor (DMDG‐TFET) with a gate–drain underlap using Ge and Ge1−zSnzis proposed. An analytical model has been developed to optimize the length of the underlap region for Ge and Ge–Sn alloy as the channel material. The ambipolarity shown by TFET has been utilized to perform a label‐free biosensing in response to the change of permittivity of the biomaterials used in the gate–drain underlap region. The use of Ge–Sn alloy as a channel material results in a lower ambipolar current but higher sensitivity to the presence of biomolecules. DMDG with workfunction (4 and 4.4 eV) is used to optimize the device performance. The analytical results have been validated by the results obtained using commercial software (Silvaco TCAD). A high sensitivity of the biosensor device is obtained by utilizing the tunnel FET ambipolar current with optimized gate underlap ofLUD = 55 nm (for Ge) andLUD = 38 nm (for Ge–Sn alloy).
Oxygen‐Induced Phase Separation in Sputtered Cu–Sn–I–O Thin Films
Authors: Zollner Eva M. , Selle Susanne , Yang Chang , Ritter Konrad , Eckner Stefanie , Welter Edmund , Grundmann Marius , Schnohr Claudia S.
Published: December 2022

Amorphous Cu–Sn–I is a promising p‐type transparent semiconductor. Therefore, herein, composition and structure of sputtered Cu–Sn–I thin films with varying thickness and Sn content are investigated by different electron microscopy techniques, energy‐dispersive X‐ray spectroscopy, and X‐ray absorption spectroscopy at the Cu, Sn, and I K‐edge. After exposure to air, the sputtered films are found to contain significant amounts of oxygen, leading to a complete phase separation of the resulting Cu–Sn–I–O films. Spatially‐resolved compositional analysis and high‐resolution transmission electron microscopy reveal that one phase consists of crystalline γ‐CuI while the other phase is composed of amorphous Cu–Sn–O, most likely a mixture of SnO2 and Cu2O/CuO. X‐ray absorption spectroscopy confirms that the local structural environment of the Sn and I atoms is similar to that in amorphous SnO2 and crystalline CuI, respectively. In contrast, the X‐ray absorption near edge structure and the extended X‐ray absorption fine structure of the Cu K‐edge both demonstrate that Cu atoms are not only bonded to I but also to O atoms. The incorporation of oxygen into the sputtered films thus completely alters the material and therefore clearly needs to be inhibited.
Inherent Redox Activity of Titania Support Enhances Catalytic Activity of Highly Dispersed Cu Catalyst
Authors: Sanders Lindsey M. , Nguyen Sorenson Anh H. T. , Sultan Jack A. , Hall Seth B. , Anderson Hans C. , Asplund Matthew C. , Stowers Kara J.
Published: December 2022

Modifying active species loading, particle size, and distribution on a support is an effective method for tuning catalyst activity. In this work, a copper catalyst anchored on titania was synthesized using the deposition‐precipitation method at low weight % in order to obtain a highly dispersed catalyst (1‐Cu/TiO2). The interactions between the copper and TiO2 support contribute to the physical and chemical properties of the catalyst. Transmission electron micrographs indicate copper nanoparticles with ∼2 nm diameter with a fairly uniform distribution across the TiO2 particles. This synthetic approach yields a catalyst that is more active than similar precious metal catalysts, and therefore is a possible approach for creating highly efficient catalysts from economic materials.
Modeling the Interaction of Anticancer Protein Azurin with the Nanosheets for Medical Applications
Authors: Atabay Maryam , Sardroodi Jaber Jahanbin , Ebrahimzadeh Alireza Rastkar , Avestan Mohammad Sadegh
Published: December 2022

Azurin as an electron transfer protein plays a vital role in the degradation of cancerous cells, but due to the destruction of its structure by stomach acid, finding safe and efficient techniques such as nano material to protect Azurin for drug delivery purposes is in high demand. In the present study, molecular dynamics techniques are exploited to examine the interaction and immobilization of Azurin on the surface of nanosheets such as graphene monoxide, silicon carbide and boron nitride at 310 K. To analyze the simulation results, structural parameters such as root mean square fluctuation (RMSF), root mean square deviation (RMSD), radius of gyration (Rg), the distance between the center of mass of immobilized protein and surface of the considered nanosheets, and surface accessible solvent area (SASA) are measured. Additionally, the interaction energy of the protein with the nanosheet surface is investigated using structural and energetic parameters of the protein and nanosheets including residue polarity, charge density, hydrophilicity, and hydrophobicity. The simulation results exhibit the adsorption and immobilization of Azurin on the targeted surfaces while maintaining its native structure. As an initial step, these results reveal a promising potential application of studied nanosheets in aqueous condition for the smart delivery, medicine and cancer therapy of Azurin.
Plasma Spraying of Kaolinite for Preparing Reactive Alumino‐Silicate Glass Coatings
Authors: Warr Laurence N. , Wolff Thorben , Testrich Holger , Grathoff Georg , Kruth Angela , Foest Rüdiger
Published: December 2022

Thermally treated kaolinite is used to develop a range of alumino‐silicate‐based precursor materials but its behavior during plasma spraying has not been well‐researched. In this study, two types of kaolinite samples were investigated in the form of low defect (KGa‐1b) and high defect (KGa‐2) varieties. The extreme temperatures of the plasma stream (up to 20 000 K) induced flash melting to produce a highly porous alumino‐silicate glass without any crystallization of new Al−Si oxide minerals. The glass is comprised largely of intact or deformed spheres (average diameters 1.14–1.44 μm), which indicates rapid quenching and solidification before impact. The subspherical structures contain up to 40 % closed pore space caused by the rapid escape of water during melting. The low‐density, porous alumino‐silicate glass coatings with predicted specific surface areas (>0.95 m2/g) and hardnesses >1.8 GPa represent a potentially reactive but physically stable substrate ideal for further chemical functionalization.
Applications of Bond Energy‐Based Thermodynamic Analysis to the Feasibility of Unfunctionalized C−C Cross‐Coupling Reactions
Authors: Dixit Vaibhav A. , Kulkarni Aniket
Published: December 2022

Carbon‐Carbon bond forming reactions are ubiquitous in nature and important for chemical and drug synthesis. Modern methods mostly utilize activated reactants, and despite recent developments in organic synthesis, and theoretical understanding, these have had limited success with unactivated C−H bonds. Here we apply a simple yet powerful Bond Dissociation Energy (BDE)‐based Reaction Enthalpy (BDERE) analysis to model C−C cross‐coupling reactions. BDERE appears in classical textbooks (halogenation of alkanes) but has not been applied to cross‐coupling reactions. BDERE allows one to rationalize the ease of coupling reactions for both homolytic and heterolytic mechanisms for all six C−C bond hybridization types. It facilitates the identification of a simple but unexplored reaction for ethane synthesis. BDERE values give valuable insights into recent advancements in C−C cross‐couplings of fully unfunctionalized (UFCC) and semi‐functionalized (SFCC) reactants that utilize metal, photoredox, organo, and biocatalysis. BDERE analysis may enable others to investigate and design novel cross‐coupling reactions.
Synthesis, Anticancer Activity and Molecular Docking Studies of Hybrid Molecules Containing Indole‐Thiazolidinedione‐Triazole Moieties
Authors: Perike Nagaraju , Edigi Praveen Kumar , Nirmala Gurrapu , Thumma Vishnu , Bujji Sushmitha , Naikal Prameela Subhashini
Published: December 2022

A library of twelve hybrid molecules containing Indole‐Thiazolidinedione‐Triazole moieties were synthesized by following a series of N‐benzylation, Knoevenagel condensation and click chemistry reactions. The structure of novel molecules confirmed by spectral analysis data of 1H‐NMR, 13C‐NMR and LC–MS. All the compounds screened for their anticancer activity against the human liver cancer HePG‐2, human colorectal cancer HCT‐116, human prostate cancer PC‐3, and human breast cancer MCF7 cell lines. MTT assay protocol was employed and calculated IC50 value of all compounds. Doxorubicin was used as standard drug. m‐acetylphenyl substituted compound 9 i specified outstanding activity against four cell lines compared to doxorubicin. The p‐acetylphenyl and p‐nitrophenyl substituted compounds showed moderate activity against the same. Molecular docking studies were performed on EGFR, CDK2 and sorcin using Autodock Vina of PyRx tool. The binding energies and interactions acquired from docking results of compounds supported the investigational data.
Shape‐Tunable BaTiO3 Crystals Presenting Facet‐Dependent Optical and Piezoelectric Properties
Authors: Chen Jing‐Wei , Pal Arnab , Chen Bo‐Hao , Kumar Gautam , Chatterjee Subhodeep , Peringeth Kiran , Lin Zong‐Hong , Huang Michael H.
Published: December 2022

BaTiO3 octahedra, edge‐, and corner‐truncated cubes, and cubes with four tunable sizes from 132 to 438 nm are synthesized by a solvothermal growth approach. Acetic acid treatment can cleanly remove BaCO3 impurity. Rietveld refinement of X‐ray diffraction patterns and Raman spectra help to confirm the particles have a tetragonal crystal structure. The crystals also exhibit size‐ and facet‐dependent bandgap shifts. BaTiO3 octahedra show larger piezoelectric, ferroelectric, and pyroelectric effects than truncated cubes and cubes. The measured dielectric constant differences should be associated with their various facet‐dependent behaviors. Piezoelectric nanogenerators fabricated from BaTiO3 octahedra consistently show the best performance than those containing truncated cubes and cubes. In particular, a nanogenerator with 30 wt.%‐incorporated octahedra displays an open‐circuit voltage of 23 V and short‐circuit current of 324 nA. The device performance is also highly stable. The maximum output power reaches 3.9 µW at 60 MΩ. The fabricated nanogenerator can provide sufficient electricity to power light‐emitting diodes. This work further demonstrates that various physical properties of semiconductor crystals show surface dependence.
Celery‐derived scaffolds with liver lobule‐mimicking structures for tissue engineering transplantation
Authors: Wang Jinglin , Qin Xueqian , Kong Bin , Ren Haozhen
Published: December 2022

Decellularized scaffolds have a demonstrated value in liver tissue engineering. Challenges in this area are focused on effectively eliminating the biological rejection of scaffolds and finding a suitable liver cell source. Here, inspired by the natural microstructure of hepatic lobules, we present a novel decellularized celery‐derived scaffold cultured with human‐induced pluripotent stem cell‐derived hepatocytes (hiPSC‐Heps) bioengineering liver tissue construction. Because of the natural hollow channels, interconnected porous structures, and excellent physicochemical characterization of the decellularized celery‐derived scaffold, the resultant bioengineering liver tissue can maintain the hiPSC‐Heps viability and the hepatic functions in the in vitro cultures. Based on this bioengineering liver tissue, we have demonstrated its good biocompatibility and the significantly higher expressions of albumin (ALB) and periodic acid‐schiff stain (PAS) when it was implanted in nude mice. These remarkable properties endow the hiPSC‐Heps integrated decellularized celery scaffolds system with promising prospects in the field of liver transplantation and other regeneration medicine.
The gift of giving
Authors: Read Claire
Published: December 2022

Being kind, and reflecting on that kindness, can offer real benefits to both giver and receiver. Laura Woodward, vet and counsellor to the vet profession, tells Claire Read more.
Multielectron ionization contributions in valence‐to‐core x‐ray emission spectra of third‐row elements
Authors: Kavčič Matjaž , Petric Marko
Published: December 2022

The valence‐to‐core (VtC) K x‐ray emission spectroscopy (XES) in the tender x‐ray range is emerging as a powerful analytical technique used to study the electronic structure of third‐row elements within complex bulk materials. With dedicated tender x‐ray emission spectrometer coupled with laboratory excitation source, such analysis can be successfully performed also in a smaller lab. In this work, we have gathered VtC x‐ray emission spectra of several sulfur and chlorine compounds measured previously in our home lab using Johansson type tender x‐ray emission spectrometer and MeV proton excitation. Measured spectra are compared to the results of one‐electron density functional theory (DFT) calculations. Theoretical spectra were found in good agreement with the experimental data with few exceptions where systematic discrepancies were observed. The latter was attributed to the simultaneous K and M shell ionization induced by MeV protons, which is not included in the one‐electron DFT theoretical framework. In order to confirm this also experimentally, VtC x‐ray emission spectra of few selected S and Cl compounds induced with three different proton energies were recorded yielding characteristic KM ionization satellite lines, confirmed by their emission energies as well as the dependence of their relative intensity on proton energy.
Hierarchy of RG flows in 6d (1, 0) orbi-instantons
Authors: Fazzi Marco , Giri Suvendu
Published: December 2022

Abstract

N M5-branes probing the intersection between the orbifold ℂ2/ΓADE and an E8 wall give rise to 6d (1, 0) SCFTs known as ADE-type orbi-instantons. At fixed N and order of the orbifold, each element of Hom(ΓADE, E8) defines a different SCFT. The SCFTs are connected by Higgs branch RG flows, which generically reduce the flavor symmetry of the UV fixed point. We determine the full hierarchy of these RG flows for type A, i.e. ℂ2/ℤk, for any value of N and k. The hierarchy takes the form of an intricate Hasse diagram: each node represents an IR orbi-instanton (homomorphism), and each edge an allowed flow, compatibly with the 6d a-theorem. The partial order is defined via quiver subtraction of the 3d magnetic quivers associated with the 6d SCFTs, which is equivalent to performing a so-called Kraft-Procesi transition between homomorphisms.
Deep Grey Matter Volume is Reduced in Amateur Boxers as Compared to Healthy Age-matched Controls
Authors: Zidan Mousa , Jesser Jessica , Herweh Christian , Jost Joachim , Heiland Sabine , Meyding-Lamadé Uta , Bendszus Martin , Haehnel Stefan
Published: December 2022

Purpose

Mild traumatic brain injuries (mTBI) sustained during contact sports like amateur boxing are found to have long-term sequelae, being linked to an increased risk of developing neurological conditions like Parkinson’s disease. The aim of this study was to assess differences in volume of anatomical brain structures between amateur boxers and control subjects with a special interest in the affection of deep grey matter structures.

Methods

A total of 19 amateur boxers and 19 healthy controls (HC), matched for age and intelligence quotient (IQ), underwent 3T magnetic resonance imaging (MRI) as well as neuropsychological testing. Body mass index (BMI) was evaluated for every subject and data about years of boxing training and number of fights were collected for each boxer. The acquired 3D high resolution T1 weighted MR images were analyzed to measure the volumes of cortical grey matter (GM), white matter (WM), cerebrospinal fluid (CSF) and deep grey matter structures. Multivariate analysis was applied to reveal differences between groups referencing deep grey matter structures to normalized brain volume (NBV) to adjust for differences in head size and brain volume as well as adding BMI as cofactor.

Results

Total intracranial volume (TIV), comprising GM, WM and CSF, was lower in boxers compared to controls (by 7.1%, P = 0.009). Accordingly, GM (by 5.5%, P = 0.038) and WM (by 8.4%, P = 0.009) were reduced in boxers. Deep grey matter showed statistically lower volumes of the thalamus (by 8.1%, P = 0.006), caudate nucleus (by 11.1%, P = 0.004), putamen (by 8.1%, P = 0.011), globus pallidus (by 9.6%, P = 0.017) and nucleus accumbens (by 13.9%, P = 0.007) but not the amygdala (by 5.5%, P = 0.221), in boxers compared to HC.

Conclusion

Several deep grey matter structures were reduced in volume in the amateur boxer group. Furthermore, longitudinal studies are needed to determine the damage pattern affecting deep grey matter structures and its neuropsychological relevance.
Weil–Petersson geodesics on the modular surface
Authors: Gadre Vaibhav
Published: December 2022

We consider the Weil–Petersson (WP) metric on the modular surface. We lift WP geodesics to the universal cover of the modular surface, and analyse geometric properties of a lift as a path in the hyperbolic metric on the universal cover. For any pair of distinct points in the thick part of the universal cover, we prove that the WP and hyperbolic geodesic segments that connect the pair, fellow-travel in the thick part and all deviations between these segments arise during cusp excursions. Furthermore, we give a quantitative analysis of the deviation during an excursion. We leverage the fellow traveling to derive a correspondence between recurrent WP and hyperbolic rays from a base-point. We show that the correspondence can be promoted to a homeomorphism on the circle of directions. By analysing cuspidal winding of a typical WP geodesic ray, we show that the homeomorphism pushes forward a Lebesgue measure on the circle to a singular measure. In terms of continued fraction coefficients, the singularity boils down to a comparison that we prove, namely, the average coefficient is bounded along a typical WP ray but unbounded along a typical hyperbolic ray.
Assessment of myocardial fibrosis in patients with systemic sclerosis using [68Ga]Ga-FAPI-04-PET-CT
Authors: Treutlein Christoph , Distler Jörg H. W. , Tascilar Koray , Fakhouri Sara Chenguiti , Györfi Andrea-Hermina , Atzinger Armin , Matei Alexandru-Emil , Dees Clara , Büttner-Herold Maike , Kuwert Torsten , Prante Olaf , Bäuerle Tobias , Uder Michael , Schett Georg , Schmidkonz Christian , Bergmann Christina
Published: December 2022

Purpose

Myocardial fibrosis (MF) is a factor of poor prognosis in systemic sclerosis (SSc). Direct in-vivo visualization of fibroblast activation as early readout of MF has not been feasible to date. Here, we characterize 68Gallium-labeled-Fibroblast-Activation-Inhibitor-04 ([68Ga]Ga-FAPI-04)-PET-CT as a diagnostic tool in SSc-related MF.

Methods

In this proof-of-concept trial, six SSc patients with and eight without MF of the EUSTAR cohort Erlangen underwent [68Ga]Ga-FAPI-04-PET-CT and cardiac MRI (cMRI) and clinical and serologic investigations just before baseline and during follow-up between January 2020 and December 2020. Myocardial biopsy was performed as clinically indicated.

Results

[68Ga]Ga-FAPI-04 tracer uptake was increased in SSc-related MF with higher uptake in SSc patients with arrhythmias, elevated serum-NT-pro-BNP, and increased late gadolinium enhancement (LGE) in cMRI. Histologically, myocardial biopsies from cMRI- and [68Ga]Ga-FAPI-04-positive regions confirmed the accumulation of FAP+ fibroblasts surrounded by collagen deposits. We observed similar but not equal spatial distributions of [68Ga]Ga-FAPI-04 uptake and quantitative cMRI-based techniques. Using sequential [68Ga]Ga-FAPI-04-PET-CTs, we observed dynamic changes of [68Ga]Ga-FAPI-04 uptake associated with changes in the activity of SSc-related MF, while cMRI parameters remained stable after regression of molecular activity and rather indicated tissue damage.

Conclusions

We present first in-human evidence that [68Ga]Ga-FAPI-04 uptake visualizes fibroblast activation in SSc-related MF and may be a diagnostic option to monitor cardiac fibroblast activity in situ.
Transaneurysmal Occlusion of Complicated Common Femoral Artery Pseudoaneurysms Using the Angio-Seal Closure Device—A Promising Technique
Authors: Auer Timo A. , Fehrenbach Uli , Torsello Giovanni F. , Collettini Federico , Wieners Gero , Günther Rolf W. , Gebauer Bernhard
Published: December 2022

Purpose

Pseudoaneurysm (PSA) developing after catheter examinations is one of the most frequent vascular complications and a nonsurgical technique with utmost low risk of complications is warranted. Our aim was to investigate the technical feasibility, success, and safety of transaneurysmal occlusion of complicated post-interventional common femoral artery (CFA) PSA using the Angio-Seal Closure Device (ASCD) and a technique that we describe as the transaneurysmal (TA) maneuver.

Material and Methods

We used the Angio-Seal (Terumo, Tokyo, Japan) Closure System to manage complicated PSAs in patients who would otherwise have needed surgery after failure of all conservative therapies. The TA maneuver was performed in 14 consecutive patients from July 2021 to July 2022. After ultrasound-guided puncture of the PSA close to its neck, the CFA was entered radiographically with micro-guidewires, and the neck of the PSA was closed with the ASCD after changing the sheaths and wires. All patient had to wear a pressure dressing until the next day, when successful closure was verified by sonography.

Results

All procedures were performed with technical success and without any complications. No patient had to undergo surgery. All sonographies on the next day confirmed complete absence of perfusion within the PSA and normal flow conditions of the CFA and vessels below.

Conclusion

The TA maneuver a promising minimally invasive procedure for closing complicated PSA of the CFA after catheter examination.
Utility of [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT in the initial evaluation of gastric cancer
Authors: Miao Ying , Feng Runhua , Guo Rui , Huang Xinyun , Hai Wangxi , Li Jian , Yu Teng , Qu Qian , Zhang Min , Shangguan Chengfang , Mi Jun , Zhu Zhenggang , Li Biao
Published: December 2022

Objectives

We aimed to investigate the role of [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT for the initial assessment of gastric cancer and to explore the factors associated with their uptake.

Methods

This study enrolled 62 patients with histopathologically confirmed gastric cancer. We compared the diagnostic performance of [68Ga]FAPI-04, [18F]FDG, and combined dual-tracer PET/CT. The standardized uptake value (SUV) and tumor-to-background ratio (TBR) were also measured, and the factors that influence tracer uptake were analyzed.

Results

[68Ga]FAPI-04 PET/CT detected more primary lesions (90.3% vs 77.4%, p = 0.008) and peritoneal metastases (91.7% vs 41.7%, p = 0.031) and demonstrated higher SUVmax and TBR values (p < 0.001) of primary lesions compared to [18F]FDG PET/CT. Dual-tracer PET/CT significantly improved the diagnostic sensitivity for the detection of distant metastases, compared with stand-alone [18F]FDG (97.1% vs 73.5%, p = 0.008) or [68Ga]FAPI-04 (97.1% vs 76.5%, p = 0.016) PET/CT. Subsequently, treatment strategies were changed in nine patients following [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT. Nevertheless, [68Ga]FAPI-04 uptake was primarily influenced by the size and invasion depth of the tumor. Both [68Ga]FAPI-04 and [18F]FDG PET/CT showed limited sensitivity for detecting early gastric cancer (EGC) (37.5% vs 25.0%, p > 0.05).

Conclusions

In this initial study, [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT were complementary and improved sensitivity for the detection of distant metastases pre-treatment in gastric cancer and could improve treatment stratification in the future. [68Ga]FAPI-04 had limited efficacy in detecting EGC.

Key Points

•[68Ga]FAPI-04 and[18F]FDG dual-tracer PET/CT are complementary to each other for improving diagnostic sensitivity in the initial evaluation of distant metastases from gastric cancer.

•[68Ga]FAPI-04 PET/CT showed limited sensitivity in detecting EGC.

• Need for further validation in a larger multi-centre prospective study.
Estimation of parameters and quantiles of the Weibull distribution
Authors: Jokiel-Rokita Alicja , Pia̧tek Sylwester
Published: December 2022

We propose three new estimators of the Weibull distribution parameters which lead to three new plug-in estimators of quantiles. One of them is a modification of the maximum likelihood estimator and two of them are based on nonparametric estimators of the Gini coefficient. We also make some review of estimators of the Weibull distribution parameters and quantiles. We compare the small sample performance (in terms of bias and mean squared error) of the known and new estimators and extreme quantiles. Based on simulations, we obtain, among others, that the proposed modification of the maximum likelihood estimator of the shape parameter has a smaller bias and mean squared error than the maximum likelihood estimator, and is better or as good as known estimators when the sample size is not very small. Moreover, one of the proposed estimator, based on the nonparametric estimator of the Gini coefficient, leads to good extreme quantiles estimates (better than the maximum likelihood estimator) in the case of small sample sizes.
How do patients interpret and respond to a single-item global indicator of cancer treatment tolerability?
Authors: Peipert John Devin , Shaunfield Sara , Kaiser Karen , Moreno Patricia I. , Fox Rina S. , Kircher Sheetal , Mohindra Nisha , Ip Edward , Zhao Fengmin , Wagner Lynne , Cella David
Published: December 2022

Background

There is increasing interest in patient-reported measures of cancer treatment tolerability. A global measure of bother, the FACT GP5 item (“I am bothered by side effects of treatment”) is potentially useful for regulatory, research, and clinical use. To understand this item’s appropriateness for capturing treatment tolerability, we conducted cognitive interviews on this item with 3 samples of cancer patients.

Methods

Patients with ovarian cancer (Study 1: N = 21; on treatment), lymphoma (Study 2: N = 14; on treatment), and colorectal or lung cancer (Study 3: N = 16; treatment naïve) were interviewed about GP5’s understandability and relevance to their treatment side effects. What patients think about when answering GP5 was also assessed. In all studies, the interview included both structured and open-ended questions. Qualitative data were coded to extract themes and responses to structured questions were tallied.

Results

Most patients on treatment (Studies 1 and 2) reported that the GP5 item wording is appropriate (88%) and its meaning is clear (97%). They were very confident or confident in their response (97%) and stated that GP5 was relevant to their cancer experience (97%). When answering GP5, patients considered their treatment and specific side effects. A large proportion (40%) of the treatment-naïve (Study 3) patients reported that GP5 was not relevant to their cancer treatment, and the largest proportion responded to GP5 thinking of negative side effect expectancies.

Conclusion

This study provides assurance that GP5 is a useful indicator of treatment tolerability, and is meaningful to people with cancer, especially once they have started treatment.
Die jüngsten Rechtsetzungsaktivitäten auf EU- und Bundesebene zur Beschleunigung des Ausbaus der Windenergie an Land
Authors: Faßbender Dr. , Brade Alexander
Published: December 2022

Der Bundestag hat am 7.7.2022 eine Reihe von Gesetzesänderungen beschlossen, die auf eine Beschleunigung
des Ausbaus der erneuerbaren Energien abzielen. Wenige Wochen zuvor hat die EU-Kommission am 18.5.2022
einen Vorschlag vorgelegt, der Änderungen der Erneuerbare-Energien-Richtlinie vorsieht, die sich u.a.
mit der Festlegung von Gebieten für den weiteren Ausbau der erneuerbaren Energien und mit der Anwendung
des (sonstigen) europäischen Umweltrechts, v.a. des Naturschutzrechts beim Ausbau der erneuerbaren
Energien befassen. Der nachfolgende Beitrag skizziert zunächst die hierzu vorgeschlagenen Änderungen
und befasst sich sodann am Beispiel des Ausbaus der Windenergie an Land mit den Folgen für die neuen
Regelungen auf Bundesebene.
Higher order risk attitudes: new model insights and heterogeneity of preferences
Authors: Georgalos Konstantinos , Paya Ivan , Peel David
Published: December 2022

It is now well established that higher-order risk preferences play a crucial role in determining the risky choices of decision makers in a wide range of important areas such as economics, finance and health. While influential theories of risky choice in those fields can explain attitudes to second order risk, the implications of these models for higher order risk preferences is still to be developed. This paper addresses that gap for the Markowitz (J Political Econ, 60:151–58, 1952) (M) model of utility which embodies reference-dependent utility, loss aversion and was seemingly the first model to explain the fourfold attitude to risk. In this paper, we set out new properties of the M model for higher order preferences, such as higher-order risky choice reversals, that can help explain experimental evidence not readily reconcilable with other models of risky choice. A second contribution of the paper is to empirically examine the heterogeneity of preference functionals describing second as well as higher order risky choices using hierarchical Bayesian estimation methods. Our analysis of the risky choices revealed in three prominent studies provides support for the M model as a useful complement to other leading models of risky choice such as cumulative prospect theory (CPT). In addition, we set up a new experiment whose design is shown to have satisfactory discriminatory power between the M and CPT specifications, and our results based on the Bayes factor confirm the heterogeneity of preference functionals across decision makers, and that the CPT specification is more prevalent.
Water Deficit, Nitrogen Availability, and Their Combination Differently Affect Floral Scent Emission in Three Brassicaceae Species
Authors: Höfer Rebecca J. , Ayasse Manfred , Kuppler Jonas
Published: December 2022

Floral scent plays a central role in plant-pollinator interactions, as flower visitors can discriminate between scent differences to recognize and forage on rewarding flowers. Changes in scent compositions might therefore lead to recognition mismatches between host plants and flower visitors. An understanding of the phenotypic plasticity of floral scent, especially in crop species, is becoming important because of climate change, e.g., increasing drought periods, and other anthropogenic influences, e.g., nitrogen (N) deposition. We have investigated the effects of the combination of progressive water deficits (dry-down) and N supplementation on floral scent emission in three Brassicaceae species (cultivated vs. wild). Individuals were randomly assigned to one of four treatments: (1) well-watered without N supplementation; (2) well-watered with N supplementation; (3) dry-down without N supplementation; (4) dry-down with N supplementation. We collected scent on day 0, 2, 7, and 14 after the commencement of the watering treatment. All samples were analyzed using gas chromatography coupled with mass spectrometry. We found that the highly cultivated Brassica napus had the lowest overall emission rate; its scent composition was affected by the interaction of watering treatment and N supplementation. Scent bouquets of the cultivated Sinapis alba also changed under these treatments. Scent bouquets of the common weed Sinapis arvensis were affected by watering treatment, but not by time and N supplementation. Furthermore, the influence of treatments on the emission rate of single compounds was highly compound-specific. Nonetheless, our study revealed that especially terpenes were negatively affected by drought-stress.
Radiosynthesis and Analysis of (S)-4-(3-[18F]Fluoropropyl)-L-Glutamic Acid
Authors: Brown Gavin , Soloviev Dmitry , Lewis David Y.
Published: December 2022

Purpose

(S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid ([18F]FSPG) is an L-glutamate derivative used as a PET biomarker to assess intracellular redox status in vivo through targeting of the cystine/glutamate antiporter protein, xc− transporter. In this report, we describe a radiosynthesis of [18F]FSPG for use in PET studies that address specific challenges in relation to the radiotracer purity, molar activity, and quality control testing methods.

Procedures

The radiosynthesis of [18F]FSPG was performed using a customised RNPlus Research automated radiosynthesis system (Synthra GmbH, Hamburg, Germany). [18F]FSPG was labelled in the 3-fluoropropylmoiety at the 4-position of the glutamic acid backbone with fluorine-18 via substitution of nucleophilic [18F]fluoride with a protected naphthylsulfonyloxy-propyl-L-glutamate derivative. Radiochemical purity of the final product was determined by radio HPLC using a new method of direct analysis using a Hypercarb C18 column.

Results

The average radioactivity yield of [18F]FSPG was 4.2 GBq (range, 3.4–4.8 GBq) at the end of synthesis, starting from 16 GBq of [18F]fluoride at the end of bombardment (n = 10) in a synthesis time of 50 min. The average molar activity and radioactivity volumetric concentration at the end of synthesis were 66 GBq µmol−1 (range, 48–73 GBq µmol−1) and 343–400 MBq mL−1, respectively.

Conclusion

Stability tests using a 4.6 GBq dose with a radioactivity volumetric concentration of 369 MBq mL−1 at the end of synthesis showed no observable radiolysis 3 h after production. The formulated product is of high radiochemical purity (> 95%) and higher molar activity compared to previous methods and is safe to inject into mice up to 3 h after production.
Velocity variation coefficient-based angle-dependent gradient conditioning scheme: a new strategy for an enhanced full waveform inversion
Authors: Dhubia Santosh , Routa Alok Kumar , Datta Gupta Saurabh , Mohanty Priya Ranjan
Published: December 2022

The development of an accurate velocity model is the significant target in the Full Waveform Inversion (FWI) process where the data fitting process is carried out based on an ill-posed technique. In the FWI technique optimization process plays a crucial role through which objective function minimizes, which is related to the misfit function between observed and modelled data. However, the influence of external factors such as data fitting errors (local minima) and the presence of noise in data are involved in the success of this processing technique. The artefacts that arise during gradient computation also affect this processing technique. This study presents a strategy to mitigate the influence of these local minima and other artefacts based on the velocity variation coefficient where an angle-dependent gradient conditioning approach has been proposed. It is an auto-controlled process in which the primary mechanism updates the velocity model from a large angle scale to a smaller angle scale when iteration begins. At each iteration, it preserves the previous result whereby it does not scatter or overlap with the previous one. It covers all the angles smoothly which helps in minimizing the data misfit and providing a high-resolution velocity model. The proposed conditioning approach is demonstrated by implementing the Marmousi model, and the result proves that the method provides a much-improved velocity inversion result which is attained with reasonable iterations. This study represents of a suitable procedure for the FWI processing technique where less sensitive artefacts are identified with negligible time consumption. Furthermore, it also helps to reduce the cycle skips and improve convergence in any complex scenario.