bluuebunny/crossref_metadata_2025 huggingface dataset:
Maltodextrin as a Commercial‐Grade Electrolyte Additive Against Dendrite Formation and Side Reactions for Aqueous Zinc‐Ion Batteries
Authors: Du Weidong , Jiang Xiaoping , Li Shiteng , Cao Piting , Li Linjie , Feng Deshi , Huang Xiaojie , Xu Fengzhao , Ye Chuangen , Liang Xiu , Zhang Jing , Gao Meng , Li Yong
Published: April 2024

Aqueous zinc‐ion batteries (AZIBs) directly using zinc metal anodes are promising candidates for grid‐scale energy storage systems due to their intrinsic high theoretical capacity, high safety, and environmental friendliness. However, the uncontrolled dendrite growth and water‐triggered side reactions seriously plague its practical application. Herein, a cost‐effective and green additive, maltodextrin (MD) is presented, to simultaneously guide the smooth Zn deposition and inhibit the occurrence of water‐related side reactions. Combing experimental characterizations and theoretical calculations shows that the MD molecules could reconstruct the Helmholtz plane, induces a preferential growth of zinc along the (002) plane, and the optimized regulation of the Zn2+ diffusion path and deposition location also results in the formation of fine‐grained Zn deposition layers, thereby inhibiting dendrite growth. In addition, MD molecules readily adsorb to the zinc anode surface, which isolates water molecules from direct contact with the zinc metal, reducing hydrogen precipitation reactions and inhibiting the formation of by‐products. Consequently, the Zn||Zn symmetric cell with MD achieves ultra‐long stable cycles of up to 5430 h at 1 mA cm−2 and 1 mA h cm−2, and the Cu||Zn asymmetric cell can stable cycle 1000 cycles with an average coulomb efficiency of 99.78%.
Solution‐Processed Sb2(S,Se)3 Seed‐Assisted Sb2Se3 Thin Film Growth for High Efficiency Solar Cell
Authors: Amin Al , Duan Xiaomeng , Zhao Kaiji , Khawaja Kausar , Xiang Wenjun , Qian Xiaofeng , Yan Feng
Published: April 2024

Antimony selenide (Sb2Se3) emerges as a promising sunlight absorber in thin film photovoltaic applications due to its excellent light absorption properties and carrier transport behavior, attributed to the quasi‐one‐dimensional Sb4Se6‐nanoribbon crystal structure. Overcoming the challenge of aligning Sb2Se3‐nanoribbons normal to substrates for efficient photogenerated carrier extraction, a solution‐processed nanocrystalline Sb2(S,Se)3‐seeds are employed on the CdS buffer layer. These seeds facilitate superstrated Sb2Se3 thin film solar cell growth through a close‐space sublimation approach. The Sb2(S,Se)3‐seeds guided the Sb2Se3 absorber growth along a [002]‐preferred crystal orientation, ensuring a smoother interface with the CdS window layer. Remarkably, Sb2(S,Se)3‐seeds improve carrier transport, reduce series resistance, and increase charge recombination resistance, resulting in an enhanced power conversion efficiency of 7.52%. This cost‐effective solution‐processed seeds planting approach holds promise for advancing chalcogenide‐based thin film solar cells in large‐scale manufacturing.
Fluoroethylene Carbonate: Bis(2,2,2,) Trifluoroethyl Carbonate as High Performance Electrolyte Solvent Blend for High Voltage Application in NMC811|| Silicon Oxide‐Graphite Lithium Ion Cells
Authors: Demelash Feleke , Gomez‐Martin Aurora , Heidrich Bastian , Adhitama Egy , Harte Patrick , Javed Atif , Arifiadi Anindityo , Bela Marlena M. , Yan Peng , Harte Patrick , Diddens Diddo , Winter Martin , Niehoff Philip
Published: April 2024

LiNixMnyCozO2 cathode materials combined with Si‐based anode materials are current state‐of‐the‐art high energy density chemistries for lithium ion batteries. Increasing the upper cut‐off voltage is an intriguing approach to achieve even higher energy density in lithium ion batteries. However, poor oxidation stability of the state‐of‐the‐art electrolytes leads to transition metal dissolution (TMD), migration, and deposition (TMDMD) on the negative electrode, followed by sudden and rapid capacity fade. Furthermore, the chemical instability of the lithium hexafluorophosphate causes hydro‐fluoric acid to develop, which targets the native SiOx layers on silicon anodes and breaks the chemical bond to the carboxymethylcellulose sodium salt binder. Herein, a fluorine‐rich electrolyte formulation consisting of lithium‐bis(fluorsulfonyl)imide with fluoroethylene carbonate (FEC): bis(2,2,2,) trifluoroethyl carbonate (BFEC) was applied in NMC811||10%SiOx‐90%graphite cells to achieve high oxidation stability and prevent TMD and deposition. Up‐to‐date, this is the premier electrochemical performance reported in literature with a capacity retention of 94.5% and 92.2% with 0.5 °C and 4.5 V upper cut‐off voltage cycling at 20 and 40 °C after 100 cycles, respectively. The post mortem analysis showed that stabilization is achieved by forming inorganic‐ and salt‐rich interphases that protect the electrolyte versus decomposition at the electrode.
The data science discovery program: A model for data science consulting in higher education
Authors: Brown C. Taylor , Mehta Megan , Ryali Mahathi , Dong Xiaoran , Shadfar Iliya , Dominquez Davalos Jacqueline , Culich Aaron , Suen Anthony
Published: April 2024

As one of the largest data science research incubator initiatives in the country, the University of California, Berkeley's Data Science Discovery Program serves as a case study for a scalable and sustainable model of data science consulting in higher education. This case contributes to the broader literature on data science consulting in higher education by analysing the programme's development, institutional influences; staffing and structural model; and defining features, which may prove instructive to similar programmes at other institutions. The programme is characterised by a unique structure of undergraduate consultations led by graduate student mentorship and governance; a streamlined, multidepartmental model that facilitates scalability and sustainability; and diverse modes for undergraduate consulting—including one‐on‐one ad‐hoc data science consultations, extended data science project development and management, peer mentorship and data science workshop instruction. This case demonstrates that universities may be able to initiate a low‐stakes, small‐scale data science consulting initiative and then progressively scale up the project in collaboration with multiple departments and organisations across campus.
Self‐discharge in supercapacitors. Part I: Conway's diagnostics
Authors: Nimmakayala Deeksha , Srivastava Shaswat , Kumar Sanjeev
Published: April 2024

Supercapacitors have emerged as drivers for the advancement of green energy technologies in energy storage systems and energy‐efficient devices. Their ability to rapidly acquire and deliver charge at high current densities and long cycle life is key. However, their high self‐discharge rates prevent their potential use in a wide range of applications, especially when utilizing commonly available activated carbon electrodes. Addressing this bottleneck is hindered by the lack of a comprehensive understanding of the self‐discharge processes. In this article, we provide a concise overview of various types of supercapacitors, followed by an exploration of self‐discharge phenomena within electrochemical systems. Recognizing the limited understanding at a molecular level, this article focuses on characterizing self‐discharge through the nature of the gradual decline in cell potential. We then survey the use of diagnostic methods in the literature to elucidate one or more controlling mechanisms operating during self‐discharge, facilitating a rational search for mitigation. We conclude by emphasizing the need for caution when interpreting controlling mechanisms solely based on cell potential measurements over time.

This article is categorized under:

Emerging Technologies > Energy Storage
A comprehensive review of solar cooking systems
Authors: Ceviz Mehmet Akif , Muratçobanoğlu Burak , Mandev Emre , Afshari Faraz
Published: April 2024

This work presents an extensive and thorough examination of solar cooking systems, offering a comprehensive overview of their design, functionality, and practical implications. Through a comprehensive review of existing literature and technological advancements, the paper highlights the various types of solar cooking methods and their respective benefits. The study delves into the environmental, social, and economic advantages of solar cooking systems, presenting their potential to reduce energy demands and cooking‐related challenges in diverse regions. By synthesizing a wide range of research, this review serves as a valuable resource for researchers, policymakers, and individuals interested in harnessing solar energy for sustainable and efficient cooking solutions. Additionally, this study contributes to the understanding and promotion of solar cooking as a viable and environmentally friendly alternative. It also analyzes why solar cooking systems have not become widespread and reveals the obstacles facing them.

This article is categorized under:

Sustainable Energy > Solar Energy
The “energy rebound effect” within the framework of environmental sustainability
Authors: Özsoy Tufan
Published: April 2024

The energy rebound effect, characterized by increasing energy use despite enhanced efficiency, has emerged as a complex interdisciplinary topic in the literature, reflecting its significance in both production and consumption sustainability. Recognizing the pivotal role of academic research in shaping energy management strategies and policies, this study conducted a comprehensive bibliometric review, accessing 530 articles from major citation indexes. This analysis provides insights into the evolution of the energy rebound field and potential future directions. Understanding the existing literature on the rebound effect serves as a valuable foundation for forthcoming research endeavors, addressing the intricate challenge of reconciling energy efficiency with sustainable energy consumption and production. The review explores the extensive literature on the energy rebound effect, highlighting a predominant focus on residential (e.g., cooling, heating, lighting, transportation) and industrial energy consumption in the majority of studies. Empirical applications primarily emphasize the measurement of the energy rebound effect, with a notable trend of increasing research concentration in China in recent years. Additionally, there is a growing body of economy‐wide analyses in this field. However, the literature exhibits complexity in both the analyses conducted and the methods employed for measuring the rebound effect. Research gaps are apparent, numerous studies tend to concentrate solely on the rebound effect at the overall energy consumption level, neglecting variations in energy types and the behavioral patterns of economic actors. Furthermore, despite consistent findings of a higher rebound effect in developing nations, there is a noticeable lack of scholarly literature addressing this issue about these countries.

This article is categorized under:

Sustainable Energy > Energy Efficiency

Human and Social Dimensions > Behavioral Science

Policy and Economics > Governance and Regulation
The noncanonical NFκB pathway: Regulatory mechanisms in health and disease
Authors: Rodriguez Benancio N. , Huang Helen , Chia Jennifer J. , Hoffmann Alexander
Published: April 2024

The noncanonical NFκB signaling pathway mediates the biological functions of diverse cell survival, growth, maturation, and differentiation factors that are important for the development and maintenance of hematopoietic cells and immune organs. Its dysregulation is associated with a number of immune pathologies and malignancies. Originally described as the signaling pathway that controls the NFκB family member RelB, we now know that noncanonical signaling also controls NFκB RelA and cRel. Here, we aim to clarify our understanding of the molecular network that mediates noncanonical NFκB signaling and review the human diseases that result from a deficient or hyper‐active noncanonical NFκB pathway. It turns out that dysregulation of RelA and cRel, not RelB, is often implicated in mediating the resulting pathology.

This article is categorized under:

Immune System Diseases > Molecular and Cellular Physiology

Cancer > Molecular and Cellular Physiology

Immune System Diseases > Stem Cells and Development
Examination of kt-factorization in a Yukawa theory
Authors: Guiot B. , van Hameren A.
Published: April 2024

Abstract

We discuss the upper limit, kmax, of the transverse-momentum integration performed in the kt-factorization formula. Based on explicit calculations in the Yukawa theory and the study of seminal papers, we argue that kmax is equal to the factorization scale μF used to factorize the cross section into an off-shell hard coefficient and a universal factor. There is consequently a relation between kmax and the definition of unintegrated parton densities (UPDFs). The use of an inconsistent relation leads potentially to the overestimation of the cross section, which has been observed, e.g., in D-meson production [1]. One of our conclusions is that UPDFs related to collinear PDFs by an integration up to μ ∼ Q, where Q is the hard scale and μ the scale in the collinear PDFs, imply that $$ {k}_{\textrm{max}}^2 $$

k
max
2

∼ Q2. Integrating the transverse-momentum significantly above may result in the overestimation of the cross section. On the opposite, for UPDFs related to the collinear ones by an integration of the transverse momentum up to infinity, any $$ {k}_{\textrm{max}}^2 $$

k
max
2

> Q2 is fine.
Effective dynamics of quantum fluctuations in field theory: with applications to cosmology
Authors: Ding Ding , Zhao Yu , Wan Yidun
Published: April 2024

Abstract

We develop a novel framework for describing quantum fluctuations in field theory, with a focus on cosmological applications. Our method uniquely circumvents the use of operator/Hilbert-space formalism, instead relying on a systematic treatment of classical variables, quantum fluctuations, and an effective Hamiltonian. Our framework not only aligns with standard formalisms in flat and de Sitter spacetimes, which assumes no backreaction, demonstrated through the φ3-model, but also adeptly handles time-dependent backreaction in more general cases. The uncertainty principle and spatial symmetry emerge as critical tools for selecting initial conditions and understanding effective potentials. We discover that modes inside the Hubble horizon do not necessarily feel an initial Minkowski vacuum, as is commonly assumed. Our findings offer fresh insights into the early universe’s quantum fluctuations and potential explanations to large-scale CMB anomalies.
Double parton distributions with flavor interference from lattice QCD
Authors: Reitinger Daniel , Zimmermann Christian , Diehl Markus , Schäfer Andreas
Published: April 2024

Abstract

We study double parton distributions with flavor interference in the nucleon and compare them with previous results for the flavor diagonal case. We investigate both unpolarized and polarized partons. We compare our lattice results with those obtained from the simple description of the proton in terms of an SU(6) symmetric three-quark wave function and find that this description fails for both flavor and polarization dependence. We also derive and test a factorization ansatz for the unpolarized flavor interference distribution in terms of single-parton distributions and find that this ansatz fails to a large extent.
Gravitational radiations of Kerr black hole from warped symmetries
Authors: Xu Jianfei
Published: April 2024

Abstract

The warped conformal symmetries have been found in the covariant phase space of a set of non-trivial diffeomorphism near the Kerr black hole horizon. In this paper, we consider the retarded Green’s function and the absorption probability for the scalar and higher spin perturbations on a generic non-extreme Kerr black hole background, and perform their holographic calculations in terms of the warped CFT. This provide further evidence on the conjecture that the warped CFT is relevant to the microstate description of the Kerr black hole.
Domain walls in the Two-Higgs-Doublet Model and their charge and CP-violating interactions with Standard Model fermions
Authors: Sassi Mohamed Younes , Moortgat-Pick Gudrid
Published: April 2024

Abstract

Discrete symmetries play an important role in several extensions of the Standard Model (SM) of particle physics. For instance, in order to avoid flavor changing neutral currents, a discrete Z2 symmetry is imposed on the Two-Higgs-Doublet Model (2HDM). This can lead to the formation of domain walls (DW) as the Z2 symmetry gets spontaneously broken during electroweak symmetry breaking in the early universe and domain walls form between regions whose vacua are related by the discrete symmetry. Due to this simultaneous spontaneous breaking of both the discrete symmetry and the electroweak symmetry, the vacuum manifold consists of two disconnected 3-spheres. Such a non-trivial disconnected vacuum manifold leads to several choices for the vacua at two adjacent regions, in contrast to models where only the discrete symmetry gets spontaneously broken and the vacuum manifold consists of several disconnected points. Due to this, we end up with several classes of DW solutions having different properties localized inside the wall, such as electric charge and/or CP violating vacua. We discuss the properties of these different classes of DW solutions as well as the interaction of SM fermions with such topological defects leading to different exotic phenomena such as, for example, the top quark being transmitted or reflected off the wall as a bottom quark.
Role of transient receptor potential ankyrin 1 in idiopathic pulmonary fibrosis: modulation of M2 macrophage polarization
Authors: Yang Yi , Xiao Zhenyu , Yang Weijie , Sun Yangyang , Sui Xin , Lin Xueyang , Yang Xinyi , Bao Zhenghao , Cui Ziqi , Ma Yingkai , Li Weidong , Wang Shengran , Yang Jun , Wang Yongan , Luo Yuan
Published: April 2024

Idiopathic pulmonary fibrosis (IPF) poses significant challenges due to limited treatment options despite its complex pathogenesis involving cellular and molecular mechanisms. This study investigated the role of transient receptor potential ankyrin 1 (TRPA1) channels in regulating M2 macrophage polarization in IPF progression, potentially offering novel therapeutic targets. Using a bleomycin-induced pulmonary fibrosis model in C57BL/6J mice, we assessed the therapeutic potential of the TRPA1 inhibitor HC-030031. TRPA1 upregulation was observed in fibrotic lungs, correlating with worsened lung function and reduced survival. TRPA1 inhibition mitigated fibrosis severity, evidenced by decreased collagen deposition and restored lung tissue stiffness. Furthermore, TRPA1 blockade reversed aberrant M2 macrophage polarization induced by bleomycin, associated with reduced Smad2 phosphorylation in the TGF-β1-Smad2 pathway. In vitro studies with THP-1 cells treated with bleomycin and HC-030031 corroborated these findings, highlighting TRPA1's involvement in fibrotic modulation and macrophage polarization control. Overall, targeting TRPA1 channels presents promising therapeutic potential in managing pulmonary fibrosis by reducing pro-fibrotic marker expression, inhibiting M2 macrophage polarization, and diminishing collagen deposition. This study sheds light on a novel avenue for therapeutic intervention in IPF, addressing a critical need in the management of this challenging disease.

Graphical abstract
Sections and Unirulings of Families over $\mathbb{P}^{1}$
Authors: Pieloch Alex
Published: April 2024

We consider morphisms $\pi : X \to \mathbb{P}^{1}$ of smooth projective varieties over $\mathbb{C}$. We show that if π has at most one singular fibre, then X is uniruled and π admits sections. We reach the same conclusions, but with genus zero multisections instead of sections, if π has at most two singular fibres, and the first Chern class of X is supported in a single fibre of π.

To achieve these result, we use action completed symplectic cohomology groups associated to compact subsets of convex symplectic domains. These groups are defined using Pardon’s virtual fundamental chains package for Hamiltonian Floer cohomology. In the above setting, we show that the vanishing of these groups implies the existence of unirulings and (multi)sections.
Compact Embeddings for Fractional Super and Sub Harmonic Functions with Radial Symmetry
Authors: Bellazzini Jacopo , Georgiev Vladimir
Published: April 2024

We prove compactness of the embeddings in Sobolev spaces for fractional super and sub harmonic functions with radial symmetry. The main tool is a pointwise decay for radially symmetric functions belonging to a function space defined by finite homogeneous Sobolev norm together with finite $$L^2$$

L
2

norm of the Riesz potentials. As a byproduct we prove also existence of maximizers for the interpolation inequalities in Sobolev spaces for radially symmetric fractional super and sub harmonic functions.
Genetik, Epigenetik und Umweltfaktoren der Lebenserwartung – Welche Rolle spielt Nature-versus-Nurture beim Altern?
Authors: Bierhoff Holger
Published: April 2024

In Deutschland und weltweit steigt das Durchschnittsalter der Bevölkerung immer weiter an. Mit dieser allgemeinen Zunahme des chronologischen Alters wird der Fokus auf das biologische Alter, d. h. den tatsächlichen Gesundheits- und Fitnesszustand, immer wichtiger. Hier stellt sich die zentrale Frage, inwieweit die altersbedingte Abnahme der Fitness genetisch vorbestimmt oder durch Umweltfaktoren und Lebensstil beeinflussbar ist.

Bei dieser Nature-versus-Nurture-Debatte haben viele epigenetische Studien in der Alternsforschung interessante Einblicke geliefert. In den meisten Modellorganismen geht das Altern mit bestimmten epigenetischen Veränderungen einher, denen unter anderem durch moderate Kalorienreduzierung oder vermehrte körperliche Aktivität entgegengewirkt werden kann. Da sich diese Interventionen auch positiv auf die Lebensspanne und Gesundheit auswirken, scheint die Epigenetik im Mittelpunkt zwischen Umwelteinflüssen und Alternsprozessen zu stehen. Hierfür spricht auch, dass es im Verlauf des Lebens von eineiigen Zwillingen eine epigenetische Drift gibt, die mit der unterschiedlichen Ausprägung von Alterserscheinungen zusammenhängt. Darüber hinaus lässt sich anhand von DNA-Methylierungsmustern das biologische Alter sehr präzise bestimmen, was die Bedeutung der Epigenetik für das Altern weiter untermauert.

Dieser Beitrag gibt eine Übersicht über die Bedeutung von genetischen und epigenetischen Parametern für die Lebenserwartung. Dabei wird ein Augenmerk auf den Möglichkeiten liegen, durch Lebensstil und Umweltfaktoren ein junges Epigenom zu erhalten, um so das biologische Altern zu verlangsamen.
Aktuelle Diagnostik und Behandlung der Sprunggelenks-Distorsion in Deutschland
Authors: Lichte Philipp , Weber Christian , Otto Michael , Bläsius Felix , Gutteck Natalia , Hildebrand Frank , Arbab Dariusch
Published: April 2024

Hintergrund

Die Distorsion des oberen Sprunggelenks (OSG) ist eine der häufigsten Verletzungen des Bewegungsapparates. Das Verletzungsmuster bestimmt die zu wählende Therapie und ist entscheidend für das Outcome. Die isolierte Ruptur des Außenbandapparates ist die häufigste strukturelle Verletzung. Hierfür wird leitliniengerecht eine konservative Therapie empfohlen, für Kombinationsverletzungen besteht hingegen hinsichtlich des diagnostischen und therapeutischen Vorgehens keine einheitliche Vorgehensweise. Ziel der bundesweiten Umfrage war es, einen Überblick über die aktuelle diagnostische Strategie und die gängigen therapeutischen Konzepte in Deutschland zu gewinnen.

Material und Methoden

Mitglieder der Deutschen Gesellschaft für Orthopädie und Unfallchirurgie (DGOU) wurden eingeladen, an einer online Umfrage zum diagnostischen und zum therapeutischen Vorgehen bei OSG-Distorsion mit einem Fragebogen, bestehend aus 20 Fragen, teilzunehmen. Neben Fragen zur Fachrichtung und zum Tätigkeitsfeld wurden die Teilnehmer gebeten, ihr diagnostisches und therapeutisches Vorgehen darzustellen.

Ergebnisse

Insgesamt nahmen 806 Teilnehmer an der Umfrage teil. Die Mehrzahl der Befragten waren Orthopäden und Unfallchirurgen und in der Klinik tätig. Bei der Erstvorstellung werden der Schubladen Test (89,5 %) und der Inversions‑/Eversionstest (81,6 %) am häufigsten durchgeführt. Eine Röntgenuntersuchung führen 88,1 % regelhaft bei Erstvorstellung durch, 26,5 % auch eine sonographische Untersuchung. Die isolierte Verletzung des Lig. fibulotalare anterius (LFTA) behandeln 99,7 % konservativ, in 78,8 % der Fälle mit Vollbelastung in der Orthese. Die vollständige Außenbandruptur würden 79,9 % konservativ behandeln. Eine kombinierte Außenbandruptur mit Syndesmosenverletzung würden 30,1 % der Befragten konservativ behandeln.

Diskussion

Aufgrund der Heterogenität der Verletzungsmuster nach einer OSG-Distorsion bestehen keine einheitlichen diagnostischen und therapeutischen Behandlungsempfehlungen. Die Ottawa Ankle Rules und die Sonographie werden trotz der guten Studienlage nur wenig eingesetzt. Die isolierte LFTA-Ruptur wird von einem Großteil der Befragten leitliniengerecht diagnostiziert und behandelt. Bei kombinierten Verletzungen des Innen- und Außenbandapparates entscheidet sich die Mehrheit für ein konservatives Vorgehen, was durch die Literatur bei geringer Evidenz als gerechtfertigt erscheint. Kombinierte Verletzungen der Syndesmose und des Außenbandapparates würde die Mehrzahl der Befragten operativ behandeln, was ebenfalls mit den Empfehlungen der Literatur korreliert. Der Versorgungsstandard in Deutschland entspricht somit weitgehend den Literaturempfehlungen.

Graphic abstract
Determination of aluminium concentrations in black, green, and white tea samples: effects of different infusion times and teapot species on aluminium release
Authors: Öztürk Elif , Yıldırım Sercan , Akyol Asli
Published: April 2024

Tea is the most consumed beverage in the world after water and contains heavy metals and trace elements that may cause potential negative effects on health. Aluminium (Al) concentrations in black, green, and white tea with different infusion times and teapot materials were evaluated in this study. Commercially available tea samples were brewed in 5 different teapots, consisting of aluminium, copper, glass, steel, and porcelain materials for 5, 10, and 15 min. Al concentrations in tea samples were determined by high-performance liquid chromatography with a fluorescence detector. Al concentrations in tea samples were in the range of 38.46 ± 5.08–844.75 ± 10.86 µg/L. Both teapot type (p < 0.001) and infusion time (p < 0.001) significantly influenced Al concentrations in tea samples. The interaction between tea type, teapot material, and infusion time was statistically significant (p < 0.001). The hazard ratio was less than 1 for black and white tea infusions except for one sample whereas it was greater than 1 for green tea. These data suggest that green tea consumption might be a potential risk factor for Al exposure.
Disrupting FKF1 homodimerization increases FT transcript levels in the evening by enhancing CO stabilization
Authors: Cho Sung Won , Lokhandwala Jameela , Park Jun Sang , Kang Hye Won , Choi Mingi , Yang Hong-Quan , Imaizumi Takato , Zoltowski Brian D. , Song Young Hun
Published: April 2024

Key message

FKF1 dimerization is crucial for proper FT levels to fine-tune flowering time. Attenuating FKF1 homodimerization increased CO abundance by enhancing its COP1 binding, thereby accelerating flowering under long days.

In Arabidopsis (Arabidopsis thaliana), the blue-light photoreceptor FKF1 (FLAVIN-BINDING, KELCH REPEAT, F-BOX 1) plays a key role in inducing the expression of FLOWERING LOCUS T (FT), encoding the main florigenic signal in plants, in the late afternoon under long-day conditions (LDs) by forming dimers with FT regulators. Although structural studies have unveiled a variant of FKF1 (FKF1 I160R) that disrupts homodimer formation in vitro, the mechanism by which disrupted FKF1 homodimer formation regulates flowering time remains elusive. In this study, we determined that the attenuation of FKF1 homodimer formation enhances FT expression in the evening by promoting the increased stability of CONSTANS (CO), a primary activator of FT, in the afternoon, thereby contributing to early flowering. In contrast to wild-type FKF1, introducing the FKF1 I160R variant into the fkf1 mutant led to increased FT expression under LDs. In addition, the FKF1 I160R variant exhibited diminished dimerization with FKF1, while its interaction with GIGANTEA (GI), a modulator of FKF1 function, was enhanced under LDs. Furthermore, the FKF1 I160R variant increased the level of CO in the afternoon under LDs by enhancing its binding to COP1, an E3 ubiquitin ligase responsible for CO degradation. These findings suggest that the regulation of FKF1 homodimerization and heterodimerization allows plants to finely adjust FT expression levels around dusk by modulating its interactions with GI and COP1.
Radiomics and machine learning for renal tumor subtype assessment using multiphase computed tomography in a multicenter setting
Authors: Uhlig Annemarie , Uhlig Johannes , Leha Andreas , Biggemann Lorenz , Bachanek Sophie , Stöckle Michael , Reichert Mathias , Lotz Joachim , Zeuschner Philip , Maßmann Alexander
Published: April 2024

Objectives

To distinguish histological subtypes of renal tumors using radiomic features and machine learning (ML) based on multiphase computed tomography (CT).

Material and methods

Patients who underwent surgical treatment for renal tumors at two tertiary centers from 2012 to 2022 were included retrospectively. Preoperative arterial (corticomedullary) and venous (nephrogenic) phase CT scans from these centers, as well as from external imaging facilities, were manually segmented, and standardized radiomic features were extracted. Following preprocessing and addressing the class imbalance, a ML algorithm based on extreme gradient boosting trees (XGB) was employed to predict renal tumor subtypes using 10-fold cross-validation. The evaluation was conducted using the multiclass area under the receiver operating characteristic curve (AUC). Algorithms were trained on data from one center and independently tested on data from the other center.

Results

The training cohort comprised n = 297 patients (64.3% clear cell renal cell cancer [RCC], 13.5% papillary renal cell carcinoma (pRCC), 7.4% chromophobe RCC, 9.4% oncocytomas, and 5.4% angiomyolipomas (AML)), and the testing cohort n = 121 patients (56.2%/16.5%/3.3%/21.5%/2.5%).

The XGB algorithm demonstrated a diagnostic performance of AUC = 0.81/0.64/0.8 for venous/arterial/combined contrast phase CT in the training cohort, and AUC = 0.75/0.67/0.75 in the independent testing cohort. In pairwise comparisons, the lowest diagnostic accuracy was evident for the identification of oncocytomas (AUC = 0.57–0.69), and the highest for the identification of AMLs (AUC = 0.9–0.94)

Conclusion

Radiomic feature analyses can distinguish renal tumor subtypes on routinely acquired CTs, with oncocytomas being the hardest subtype to identify.

Clinical relevance statement

Radiomic feature analyses yield robust results for renal tumor assessment on routine CTs. Although radiologists routinely rely on arterial phase CT for renal tumor assessment and operative planning, radiomic features derived from arterial phase did not improve the accuracy of renal tumor subtype identification in our cohort.
Health-related quality of life following salvage radical prostatectomy for recurrent prostate cancer after radiotherapy or focal therapy
Authors: Rodler Severin , Danninger Dina , Eismann Lennert , Kazmierczak Philipp Maximilian , Jokisch Friedrich , Li Minglun , Becker Armin , Kretschmer Alexander , Stief Christian , Westhofen Thilo
Published: April 2024

Background

Salvage radical prostatectomy (sRP) is an important treatment option for patients with recurrent prostate cancer (PCa) after radiotherapy (RT) or focal therapy (FT). However, health-related quality of life (HRQOL) after sRP depending on the primary treatment is understudied.

Methods

Patients who underwent Salvage RP for recurrent PCa were analyzed. The primary outcome of this study was HRQOL assessed by the quality-of-life questionnaire (QLQ)-C30 and its prostate specific QLQ-PR25 add-on. Secondary outcomes were functional outcome parameters (erectile function, continence) and biochemical recurrence-free survival (BRFS). Statistical analyses employed the chi-square test, Mann–Whitney U test, and Kaplan–Meier method, with a p value < 0.05 denoting significance.

Results

37 patients with RT as primary treatment (RT-sRP) and 22 patients with focal therapy prior sRP (FT-sRP) were analyzed. Mean global health score was not significantly different preoperatively (71.9 vs. 67.3, p = 0.89) as well as after a median of 32 months follow-up (54.9 vs. 50.6, p = 0.63) with impaired HRQOL after sRP in both groups. Baseline erectile dysfunction was more prevalent in the RT-sRP group (mean IIEF-5: 5.0) than in the FT-sRP group (mean IIEF-5: 8.5, p = 0.037). No differences were observed at follow-up for erectile function (IIEF-5-Score: 0.5 vs 2.5, p = 0.199) and continence (continence rate: 48.4% vs 52.9% (p = 0.763) between the RT-sRP and FT-sRP group. 5-year-BRFS was 60% (RT-sRP) and 68% (FT-sRP, p = 0.849).

Conclusions

sRP impacts HRQOL in patients with PCa after RT and FT with no significant differences. Comparison with HRQOL and BRFS of treatment alternatives is paramount to counsel patients for appropriate treatments.
Characterization of NEB pathogenic variants in patients reveals novel nemaline myopathy disease mechanisms and omecamtiv mecarbil force effects
Authors: Karimi Esmat , Gohlke Jochen , van der Borgh Mila , Lindqvist Johan , Hourani Zaynab , Kolb Justin , Cossette Stacy , Lawlor Michael W. , Ottenheijm Coen , Granzier Henk
Published: April 2024

Nebulin, a critical protein of the skeletal muscle thin filament, plays important roles in physiological processes such as regulating thin filament length (TFL), cross-bridge cycling, and myofibril alignment. Pathogenic variants in the nebulin gene (NEB) cause NEB-based nemaline myopathy (NEM2), a genetically heterogeneous disorder characterized by hypotonia and muscle weakness, currently lacking curative therapies. In this study, we examined a cohort of ten NEM2 patients, each with unique pathogenic variants, aiming to understand their impact on mRNA, protein, and functional levels. Results show that pathogenic truncation variants affect NEB mRNA stability and lead to nonsense-mediated decay of the mutated transcript. Moreover, a high incidence of cryptic splice site activation was found in patients with pathogenic splicing variants that are expected to disrupt the actin-binding sites of nebulin. Determination of protein levels revealed patients with either relatively normal or markedly reduced nebulin. We observed a positive relation between the reduction in nebulin and a reduction in TFL, or reduction in tension (both maximal and submaximal tension). Interestingly, our study revealed a pathogenic duplication variant in nebulin that resulted in a four-copy gain in the triplicate region of NEB and a much larger nebulin protein and longer TFL. Additionally, we investigated the effect of Omecamtiv mecarbil (OM), a small-molecule activator of cardiac myosin, on force production of type 1 muscle fibers of NEM2 patients. OM treatment substantially increased submaximal tension across all NEM2 patients ranging from 87 to 318%, with the largest effects in patients with the lowest level of nebulin. In summary, this study indicates that post-transcriptional or post-translational mechanisms regulate nebulin expression. Moreover, we propose that the pathomechanism of NEM2 involves not only shortened but also elongated thin filaments, along with the disruption of actin-binding sites resulting from pathogenic splicing variants. Significantly, our findings highlight the potential of OM treatment to improve skeletal muscle function in NEM2 patients, especially those with large reductions in nebulin levels.
Real-world prevalence of microsatellite instability testing and related status in women with advanced endometrial cancer in Europe
Authors: Kelkar Sneha S. , Prabhu Vimalanand S. , Zhang Jingchuan , Ogando Yoscar M. , Roney Kyle , Verma Rishi P. , Miles Nicola , Marth Christian
Published: April 2024

Purpose

To assess the real-world prevalence of microsatellite instability (MSI)/mismatch repair (MMR) testing and related tumor status in recurrent/advanced endometrial cancer patients in Europe.

Methods

Data were from two multi-center, retrospective patient chart review studies conducted in the United Kingdom, Germany, Italy, France and Spain: The Endometrial Cancer Health Outcomes-Europe-First-Line (ECHO-EU-1L) study and the ECHO-EU-Second-Line (ECHO-EU-2L) study. ECHO-EU-1L included recurrent/advanced endometrial cancer patients who received first-line systemic therapy between 1/JUN/2016 and 31/MAR/2020 after recurrent/advanced diagnosis. ECHO-EU-2L included patients with recurrent/advanced endometrial cancer who progressed between 1/JUN/2016 and 30/JUN/2019 following prior first-line systemic therapy. Data collected included patient demographics, MSI/MMR tumor testing and results, and clinical/treatment characteristics.

Results

ECHO-EU-1L included 242 first-line patients and ECHO-EU-2L included 475 s-line patients. For all patients, median age at recurrent/advanced diagnosis was 69 years, roughly half had endometrioid carcinoma histology and over 75% had Stage IIIB-IV disease at initial diagnosis. The prevalence of MSI/MMR testing in the first-line and second-line cohorts was similar (36.4 and 34.9%, respectively). Among those tested, a majority had non-MSI-high/MMR proficient tumors (80.7 and 74.7% among first- and second-line patients, respectively). About 15% had MSI-high/MMR deficient tumors in both cohorts, and a few patients had discordant results (3.4 and 10.8% among first- and second-line patients, respectively).

Conclusion

Prior to the approvals of biomarker-directed therapies for recurrent/advanced endometrial cancer patients in Europe, there were low MSI/MMR testing rates for these patients of just over one-third. Given the availability of biomarker-directed therapies, increased MSI/MMR testing may help inform treatment decisions for recurrent/advanced endometrial cancer patients in Europe.
Impact of macronutrients intake on glycemic homeostasis of preterm infants: evidence from continuous glucose monitoring
Authors: Guiducci Silvia , Res Giulia , Bonadies Luca , Savio Federica , Brigadoi Sabrina , Priante Elena , Trevisanuto Daniele , Baraldi Eugenio , Galderisi Alfonso
Published: April 2024

Nutritional intake could influence the blood glucose profile during early life of preterm infants. We investigated the impact of macronutrient intake on glycemic homeostasis using continuous glucose monitoring (CGM). We analyzed macronutrient intake in infants born ≤ 32 weeks gestational age (GA) and/or with birth weight ≤ 1500 g. CGM was started within 48 h of birth and maintained for 5 days. Mild and severe hypoglycemia were defined as sensor glucose (SG) < 72 mg/dL and <47 mg/dL, respectively, while mild and severe hyperglycemia were SG > 144 mg/dL and >180 mg/dL. Data from 30 participants were included (age 29.9 weeks (29.1; 31.2), birthweight 1230.5 g (1040.0; 1458.6)). A reduced time in mild hypoglycemia was associated to higher amino acids intake (p = 0.011) while increased exposure to hyperglycemia was observed in the presence of higher lipids intake (p = 0.031). The birthweight was the strongest predictor of neonatal glucose profile with an inverse relationship between the time spent in hyperglycemia and birthweight (p = 0.007).

  Conclusions: Macronutrient intakes influence neonatal glucose profile as described by continuous glucose monitoring. CGM might contribute to adjust nutritional intakes in preterm infants.

What is Known:• Parenteral nutrition may affect glucose profile during the first days of life of preterm infants.

What is New:• Continuous glucose monitoring describes the relationship between daily parenteral nutrient intakes and time spent in hypo and hyperglycemic ranges.
Necroptosis-related lncRNA-based novel signature to predict the prognosis and immune landscape in soft tissue sarcomas
Authors: Long Qiuzhong , Li Zhengtian , Yang Wenkang , Huang Ke , Du Gang
Published: April 2024

Background

Necroptosis-related long noncoding RNAs (lncRNAs) play crucial roles in cancer initiation and progression. Nevertheless, the role and mechanism of necroptosis-related lncRNAs in soft tissue sarcomas (STS) is so far unknown and needs to be explored further.

Methods

Clinical and genomic data were obtained from the UCSC Xena database. All STS patients’ subclusters were performed by unsupervised consensus clustering method based on the prognosis-specific lncRNAs, and then assessed their survival advantage and immune infiltrates. In addition, we explored the pathways and biological processes in subclusters through gene set enrichment analysis. At last, we established the necroptosis-related lncRNA-based risk signature (NRLncSig) using the least absolute shrinkage and selection operator (LASSO) method, and explored the prediction performance and immune microenvironment of this signature in STS.

Results

A total of 911 normal soft tissue samples and 259 STS patients were included in current study. 39 prognosis-specific necroptosis-related lncRNAs were selected. Cluster 2 had a worse survival than the cluster 1 and characterized by different immune landscape in STS. A worse outcome in the high-risk group was observed by survival analysis and indicated an immunosuppressive microenvironment. The ROC curve analyses illustrated that the NRLncSig performing competitively in prediction of prognosis for STS patients. In addition, the nomogram presents excellent performance in predicting prognosis, which may be more beneficial towards STS patients’ treatment.

Conclusions

Our result indicated that the NRLncSig could be a good independent predictor of prognosis, and significantly connected with immune microenvironment, thereby providing new insights into the roles of necroptosis-related lncRNAs in STS.
Clinical and computational development of a patient-calibrated ICGFA bowel transection recommender
Authors: Dalli Jeffrey , Epperlein Jonathan P. , Hardy Niall P. , Khan Mohammad Faraz , Mac Aonghusa Pol , Cahill Ronan A.
Published: April 2024

Introduction

Intraoperative indocyanine green fluorescence angiography (ICGFA) aims to reduce colorectal anastomotic complications. However, signal interpretation is inconsistent and confounded by patient physiology and system behaviours. Here, we demonstrate a proof of concept of a novel clinical and computational method for patient calibrated quantitative ICGFA (QICGFA) bowel transection recommendation.

Methods

Patients undergoing elective colorectal resection had colonic ICGFA both immediately after operative commencement prior to any dissection and again, as usual, just before anastomotic construction. Video recordings of both ICGFA acquisitions were blindly quantified post hoc across selected colonic regions of interest (ROIs) using tracking-quantification software and computationally compared with satisfactory perfusion assumed in second time-point ROIs, demonstrating 85% agreement with baseline ICGFA. ROI quantification outputs detailing projected perfusion sufficiency-insufficiency zones were compared to the actual surgeon-selected transection/anastomotic construction site for left/right-sided resections, respectively. Anastomotic outcomes were recorded, and tissue lactate was also measured in the devascularised colonic segment in a subgroup of patients. The novel perfusion zone projections were developed as full-screen recommendations via overlay heatmaps.

Results

No patient suffered intra- or early postoperative anastomotic complications. Following computational development (n = 14) the software recommended zone (ROI) contained the expert surgical site of transection in almost all cases (Jaccard similarity index 0.91) of the nine patient validation series. Previously published ICGFA time-series milestone descriptors correlated moderately well, but lactate measurements did not. High resolution augmented reality heatmaps presenting recommendations from all pixels of the bowel ICGFA were generated for all cases.

Conclusions

By benchmarking to the patient’s own baseline perfusion, this novel QICGFA method could allow the deployment of algorithmic personalised NIR bowel transection point recommendation in a way fitting existing clinical workflow.
Is mild dehydration a risk for progression of childhood chronic kidney disease?
Authors: Le Page Amelia K. , Johnson Evan C. , Greenberg Jason H.
Published: April 2024

Children with chronic kidney disease (CKD) can have an inherent vulnerability to dehydration. Younger children are unable to freely access water, and CKD aetiology and stage can associate with reduced kidney concentrating capacity, which can also impact risk. This article aims to review the risk factors and consequences of mild dehydration and underhydration in CKD, with a particular focus on evidence for risk of CKD progression. We discuss that assessment of dehydration in the CKD population is more challenging than in the healthy population, thus complicating the definition of adequate hydration and clinical research in this field. We review pathophysiologic studies that suggest mild dehydration and underhydration may cause hyperfiltration injury and impact renal function, with arginine vasopressin as a key mediator. Randomised controlled trials in adults have not shown an impact of improved hydration in CKD outcomes, but more vulnerable populations with baseline low fluid intake or poor kidney concentrating capacity need to be studied. There is little published data on the frequency of dehydration, and risk of complications, acute or chronic, in children with CKD. Despite conflicting evidence and the need for more research, we propose that paediatric CKD management should routinely include an assessment of individual dehydration risk along with a treatment plan, and we provide a framework that could be used in outpatient settings.

Graphical Abstract