bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fiber Sensor for Long‐Term Monitoring of Extracellular Potassium Ion Fluctuations in Chronic Neuropsychiatric Diseases
Authors: Wang Jiajia , Wang Liyuan , Yang Yiqing , Li HongJian , Huang Xinlin , Liu Ziwei , Yu Sihui , Tang Chengqiang , Chen Jiawei , Shi Xiang , Li Wenjun , Chen Peining , Tong Qi , Yu Hongbo , Sun Xuemei , Peng Huisheng
Published: December 2023

The extracellular potassium ion concentration in the brain exerts a significant influence on cellular excitability and intercellular communication. Perturbations in the extracellular potassium ion level are closely correlated with various chronic neuropsychiatric disorders including depression. However, a critical gap persists in performing real‐time and long‐term monitoring of extracellular potassium ions, which is necessary for comprehensive profiling of chronic neuropsychiatric diseases. Here, a fiber potassium ion sensor (FKS) that consists of a soft conductive fiber with a rough surface and a hydrophobic‐treated transduction layer interfaced with a potassium ion‐selective membrane is found to solve this problem. The FKS demonstrates stable interfaces between its distinct functional layers in an aqueous environment, conferring an exceptional stability of 6 months in vivo, in stark contrast to previous reports with working durations from hours to days. Upon implantation into the mouse brain, the FKS enables effective monitoring of extracellular potassium ion dynamics under diverse physiological states including anesthesia, forced swimming, and tail suspension. Using this FKS, tracking of extracellular potassium ion fluctuations that align with behaviors associated with the progression of depression over months is achieved, demonstrating its usability in studying chronic neuropsychiatric disorders from a new biochemical perspective.
Skin‐Interfaced Bifluidic Paper‐Based Device for Quantitative Sweat Analysis
Authors: Deng Muhan , Li Xiaofeng , Song Kui , Yang Hanlin , Wei Wenkui , Duan Xiaojun , Ouyang Xiaoping , Cheng Huanyu , Wang Xiufeng
Published: December 2023

The erratic, intermittent, and unpredictable nature of sweat production, resulting from physiological or psychological fluctuations, poses intricacies to consistently and accurately sample and evaluate sweat biomarkers. Skin‐interfaced microfluidic devices that rely on colorimetric mechanisms for semi‐quantitative detection are particularly susceptible to these inaccuracies due to variations in sweat secretion rate or instantaneous volume. This work introduces a skin‐interfaced colorimetric bifluidic sweat device with two synchronous channels to quantify sweat rate and biomarkers in real‐time, even during uncertain sweat activities. In the proposed bifluidic‐distance metric approach, with one channel to measure sweat rate and quantify collected sweat volume, the other channel can provide an accurate analysis of the biomarkers based on the collected sweat volume. The closed channel design also reduces evaporation and resists contamination from the external environment. The feasibility of the device is highlighted in a proof‐of‐the‐concept demonstration to analyze sweat chloride for evaluating hydration status and sweat glucose for assessing glucose levels. The low‐cost yet highly accurate device provides opportunities for clinical sweat analysis and disease screening in remote and low‐resource settings. The developed device platform can be facilely adapted for the other biomarkers when corresponding colorimetric reagents are exploited.
Sex differences in brain atrophy in dementia with Lewy bodies
Authors: Oltra Javier , Habich Annegret , Schwarz Christopher G. , Nedelska Zuzana , Przybelski Scott A. , Inguanzo Anna , Diaz‐Galvan Patricia , Lowe Val J. , Oppedal Ketil , Gonzalez Maria C. , Philippi Nathalie , Blanc Frederic , Barkhof Frederik , Lemstra Afina W. , Hort Jakub , Padovani Alessandro , Rektorova Irena , Bonanni Laura , Massa Federico , Kramberger Milica G. , Taylor John‐Paul , Snædal Jon G. , Walker Zuzana , Antonini Angelo , Dierks Thomas , Segura Barbara , Junque Carme , Westman Eric , Boeve Bradley F. , Aarsland Dag , Kantarci Kejal , Ferreira Daniel
Published: December 2023

INTRODUCTION

Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI).

METHODS

We included 436 patients from the European‐DLB consortium and the Mayo Clinic. Sex differences and sex‐by‐age interactions were assessed through visual atrophy rating scales (n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness (n = 165; 69 ± 9 years, 72% males).

RESULTS

We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex‐by‐age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex.

DISCUSSION

We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75.

Highlights

Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales.

Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods.

Sex differences in gray matter measures in DLB tended to disappear with increasing age.
Uniformly Distributed Mixed Matrix Membranes via a Solution Processable Strategy for Propylene/Propane Separation
Authors: Su Yafei , Li Dongyang , Shan Meixia , Feng Xiaoquan , Gascon Jorge , Wang Yong , Zhang Yatao
Published: December 2023

Aggregation of filler particles during the formation of mixed matrix membranes is difficult to avoid when filler loadings exceed a 10–15 wt %. Such agglomeration usually leads to poor membrane performance. In this work, using a ZIF‐67 metal–organic framework (MOF) as filler along with surface modification of Ag4tz4 to improve processability and selective olefin adsorption, we demonstrate that highly loaded with a very low agglomeration degree membranes can be synthesized displaying unmatched separation selectivity (39) for C3H6/C3H8 mixtures and high permeability rates (99 Barrer), far surpassing previous reports in the literature. Through molecular dynamics simulation, the enhanced compatibility between ZIF‐67 and polymer matrix with adding Ag4tz4 was proven and the tendency in gas permeability and C3H6 selectivity in the mixed matrix membranes (MMMs) were well explained. More importantly, the membrane showed a wide range of pressure and temperature resistance, together with remarkable long‐term stability (>900 h). The modification method might help solve interface issues in MMMs and can be extended to the fabrication of other fillers to achieve high performance MMMs for gas separation.
Enantioselective Hydrophosphination of Terminal Alkenyl Aza‐Heteroarenes
Authors: Sinnema Esther G. , Ramspoth Tizian‐Frank , Bouma Reinder H. , Ge Luo , Harutyunyan Syuzanna R.
Published: December 2023

This paper presents a Mn(I)‐catalysed methodology for the enantioselective hydrophosphination of terminal alkenyl aza‐heteroarenes. The catalyst operates through H−P bond activation, enabling successful hydrophosphination of a diverse range of alkenyl‐heteroarenes with high enantioselectivity. The presented protocol addresses the inherently low reactivity and the commonly encountered suboptimal enantioselectivities of these challenging substrates. As an important application we show that this method facilitates the synthesis of a non‐symmetric tridentate P,N,P‐containing ligand like structure in just two synthetic steps using a single catalytic system.
Origin of Stability and Activity Enhancements in Pt‐based Oxygen Reduction Reaction Catalysts via Defect‐Mediated Dopant Adsorption
Authors: Sawant Kaustubh J. , Zeng Zhenhua , Greeley Jeffrey P.
Published: December 2023

Platinum alloys are highly efficient electrocatalysts for the oxygen reduction reaction (ORR) in acidic conditions. However, these alloys are susceptible to metal loss through leaching and degradation, leading to reduced catalyst stability and activity. Recently, it has been shown that doping with oxophilic elements can significantly alleviate these problems, with a prominent example being Mo‐doped Pt alloys. Here, to achieve atomic scale understanding of the exceptional activity and stability of these alloys, we present a detailed density functional theory description of the dopants’ structures and impact on electrocatalyst properties. Beginning with the Mo/Pt system, we demonstrate that Mo can be stabilized in the form of low‐dimensional oxyhydroxide moieties on Pt defects. The resulting structures enhance stability and activity via distinct physical processes, with the Mo moieties both directly inhibiting Pt dissolution at defects and indirectly enhancing ORR activity by generation of strain fields on surrounding Pt terraces. We then generalize these analyses to other metal dopant elements, and we demonstrate that similar low‐dimensional oxyhydroxide structures control the electrocatalytic properties through an intricate interplay of the structures’ acid stability, intrinsic activity for the ORR, and ability to induce ORR‐promoting strain fields on Pt.
Metal‐Free Activation of Molecular Oxygen by 9‐Fluorenone‐Based Porous Organic Polymers for Selective Aerobic Oxidation
Authors: Wang Yinwei , Feng Xiao , Cao Jieqi , Zheng Xiaoxia , Gong Xinbin , Yu Weiqiang , Wang Min , Shi Song
Published: December 2023

Oxygen activation is a critical step in heterogeneous oxidative processes, particularly in catalytic, electrolytic, and pharmaceutical applications. Among the various catalysts available for photocatalytic O2 activation, homogeneous aryl ketones are at the forefront. To avoid the degradation and deactivation of aryl ketones, 9‐fluorenone‐based porous organic polymers were designed and regulated by doping them with co‐monomers. The obtained heterogeneous photocatalyst showed good performance in O2 activation, and its performance was better than that of homogeneous 9‐fluorenone. The obtained heterogeneous photocatalyst showed good reusability. We believe that the presented method and findings represent an important step toward designing catalysts tailored for specific tasks.
Effect of molecular structure on ethylene‐vinyl alcohol copolymer thermal degradation and stability
Authors: Da Xiaoling , Deng Zhaoyi , Wu Tong , Cao Ya , Xiang Ming , Yang Feng
Published: December 2023

To study the effect of molecular structure on ethylene‐vinyl alcohol copolymer (EVOH) thermal stability during processing, EVOH samples with different molecular weights and comonomer distributions were prepared by solubility fractionation from two different commercial materials, and then, the structure features of samples were characterized by 1H‐NMR, viscometry, differential scanning calorimetry, and, especially, successive self‐nucleation and annealing. Their thermal stabilities were further analyzed by isothermal oxygen treatment and thermogravimetry. Attenuated total internal reflectance Fourier transform infrared spectroscopy and UV were used to obverse the structural changes in samples (the formation of chromogenic groups: CO and CC). According to the results of isothermal oxygen treatment at 200°C, at the same ethylene content, low‐molecular‐weight samples have worse thermal stability, which were extremely easy to yellowing and form insoluble gel. To investigate the structure differences between the low‐molecular‐weight samples, it was found that long vinyl alcohol segments may not worsen the thermal stability in the conditions of the same ethylene content. But samples with a uniform distribution of ethylene segments and a certain length of ethylene segments will have better thermal stability, which makes it more difficult to form carbonyl even diketene conjugation structure.
An Open‐Air Palladium‐Catalyzed Stereoselective O‐Glycosylation of Glycals via in‐situ Generation of gem‐Disubstituted Methanols from p‐Quinone Methides
Authors: Azeem Ms. Zanjila , Dubey Ms. Shashiprabha , Islam Mr. Sk Areful , Mandal Pintu Kumar
Published: December 2023

We devised a palladium‐catalyzed α‐stereoselective glycosylation that incorporates oxygen via in‐situ generation of gem‐disubstituted methanols from p‐quinone methides to access 2,3‐unsaturated gem‐diarylmethyl O‐glycosides under open‐air atmosphere at room temperature. Advantages of this environmentally friendly strategy include the absence of additives and ligands, using water as the green source of oxygen, mildest, operationally simple, exhibiting a wide functional group tolerance, and compatibility with a variety of glycal progenitors in appreciable yields. A mechanistic study has been verified via H218O labeling, which validates that water (moisture) is a sole source of oxygen.
Command filter‐based finite‐time adaptive tracking control for MIMO dynamic systems with external disturbances and prescribed performance constraints
Authors: Wang Zhechen , Jia Yingmin
Published: December 2023

This paper investigates command filter‐based finite‐time stability of multi‐input multi‐output (MIMO) dynamic systems with prescribed performance constraints and external disturbances. A novel finite‐time differentiator is introduced into command filter‐based control scheme, which improves transient performance of each subsystem. Meanwhile, disturbance observers are utilized to eliminate negative effects on control system caused by external disturbances. Furthermore, featured with a selected performance function, it can be guaranteed that tracking errors remain in prescribed performance region. Stability analysis of the proposed controller is presented by using a Lyapunov function including transformed filter errors, parameter errors of neural networks, and observed errors of lumped disturbances. Effectiveness of proposed control method is verified by a numerical example and a practical system of inverted pendulums, respectively.
Das γ‐Verfahren zur Berechnung nachgiebig verbundener Biegeträger aus beliebig vielen Einzelquerschnitten: doppelsymmetrische Querschnitte
Authors: Zhu Jianzhong
Published: December 2023

Nachgiebig verbundene Trägerquerschnitte aus beliebig vielen Einzelquerschnitten mit doppelsymmetrischem Aufbau weisen antimetrische Normalspannungsverteilung und symmetrische Schubspannungsverteilung auf. Die Symmetrieeigenschaften werden in diesem Beitrag ausgenutzt, um einfache Formeln zur Bestimmung der einzelnen γ‐Werte zu entwickeln. Für nachgiebig zusammengesetzte Biegeträger mit doppelsymmetrischen Querschnitten aus bis zu neun Einzelquerschnitten werden Formeln angegeben.
A comprehensive review of 3D cancer models for drug screening and translational research
Authors: Sharma Karthikey , Dey Sreenath , Karmakar Rounik , Rengan Aravind Kumar
Published: December 2023

The 3D cancer models fill the discovery gap of 2D cancer models and play an important role in cancer research. In addition to cancer cells, a range of other factors include the stroma, density and composition of extracellular matrix, cancer‐associated immune cells (e.g., cancer‐associated fibroblasts cancer cell‐stroma interactions and subsequent interactions, and a number of other factors (e.g., tumor vasculature and tumor‐like microenvironment in vivo) has been widely ignored in the 2D concept of culture. Despite this knowledge, the continued use of monolayer cell culture methods has led to the failure of a series of clinical trials. This review discusses the immense importance of tumor microenvironment (TME) recapitulation in cancer research, prioritizing the individual roles of TME elements in cancer histopathology. The TME provided by the 3D model fulfills the requirements of in vivo spatiotemporal arrangement, components, and is helpful in analyzing various different aspects of drug sensitivity in preclinical and clinical trials, some of which are discussed here. Furthermore, it discusses models for the co‐assembly of different TME elements in vitro and focuses on their synergistic function and responsiveness as tumors. Furthermore, this review broadly describes of a handful of recently developed 3D models whose main focus is limited to drug development and their screening and/or the impact of this approach in preclinical and translational research.
First evidence of AXL expression on circulating tumor cells in metastatic breast cancer patients: A proof‐of‐concept study
Authors: Bardol Thomas , Eslami‐S Zahra , Masmoudi Doryan , Alexandre Marie , Duboys de Labarre Marie , Bobrie Angélique , D'Hondt Véronique , Guiu Séverine , Kurma Keerthi , Cayrefourcq Laure , Jacot William , Alix‐Panabières Catherine
Published: December 2023

Background

For several years, the AXL tyrosine kinase receptor, a member of the Tyro3‐Axl‐Mer (TAM) family, has been considered a new strategic target in oncology. AXL overexpression is common in solid tumors and is associated with poor prognosis. In this context, the detection of a subset of circulating tumor cells (CTCs) that express AXL (AXL+ CTCs) could be clinically relevant.

Methods

Immunostaining was performed to assess AXL expression in human breast cancer cell lines. The optimal conditions were established using flow cytometry. Spiking experiments were carried out to optimize the parameters of the CellSearch® system detection test. CTC enumeration and AXL expression were evaluated in patients with metastatic breast cancer (mBC) before treatment initiation.

Results

An innovative AXL+ CTC detection assay to be used with the CellSearch® system was developed. In a prospective longitudinal clinical trial, blood samples from 60 patients with untreated mBC were analyzed to detect AXL+ CTCs with this new assay. CTCs were detected in 35/60 patients (58.3%) and AXL+ CTCs were identified in 7 of these 35 patients (11.7% of all patients).

Conclusion

This newly established AXL+ CTC assay is a promising tool that can be used for liquid biopsy in future clinical trials to stratify and monitor patients with cancer receiving anti‐AXL therapies.
Immune cells within tertiary lymphoid structures are associated with progression‐free survival in patients with locoregional recurrent breast cancer
Authors: Gu Jinyuan , Wang Jiaming , Sun Yue , Mao Xinrui , Qian Chao , Tang Xinyu , Wang Ji , Xie Hui , Ling Lijun , Zhao Yi , Liu Xiaoan , Zhang Kai , Pan Hong , Wang Shui , Wang Cong , Zhou Wenbin
Published: December 2023

Introduction

Locoregional recurrent breast cancers have a poor prognosis. Little is known about the prognostic impact of immune microenvironment, and tertiary lymphoid structures (TLSs) in particular have not been reported. Thus, we aimed to characterize the immune microenvironment in locoregional recurrent breast tumors and to investigate its relationship with prognosis.

Methods

We retrospectively included 112 patients with locoregional recurrent breast cancer, and hematoxylin–eosin staining and immunohistochemical staining (CD3, CD4, CD8, CD19, CD38, and CD68) were performed on locoregional recurrent tumor samples. The association of immune cells and TLSs with progression‐free survival (PFS) were analyzed by survival analysis.

Results

We found more immune cells in the peritumor than stroma. After grouping according to estrogen receptor (ER) status, a low level of peritumoral CD3+ cells in ER+ subgroup (p = 0.015) and a low level of stromal CD68+ cells in ER− subgroup (p = 0.047) were both associated with longer PFS. TLSs were present in 68% of recurrent tumors, and CD68+ cells within TLSs were significantly associated with PFS as an independent prognostic factor (p = 0.035). TLSs and immune cells (CD3, CD38, and CD68) within TLSs were associated with longer PFS in ER− recurrent tumors (p = 0.044, p = 0.012, p = 0.050, p < 0.001, respectively), whereas CD38+ cells within TLSs were associated with shorter PFS in ER+ recurrent tumors (p = 0.037).

Conclusion

Our study proposes potential predictors for the clinical prognosis of patients with locoregional recurrent breast cancer, emphasizing the prognostic value of immune cells within TLSs, especially CD68+ cells.
Stability challenges and prospects for the industrial application of non‐noble catalysts for selective catalytic reduction of NOx by CO (CO‐SCR)
Authors: Li Shuhao , Wang Feng , Ng Derrick , Shen Boxiong , Xie Zongli
Published: December 2023

The selective catalytic reduction of NOx by CO (CO‐SCR) holds considerable promise as a simple and cost‐effective technology capable of concurrently removing CO and NOx from mobile and stationary sources. This is especially pertinent for industry sectors with high CO emissions, such as the iron and steel industry, making CO‐SCR an attractive solution with significant industrial applicability. However, despite the promising industrial potential of CO‐SCR technology, its widespread adoption is hindered by several factors, most notably the impacts of SO2, H2O, and O2 on catalyst performance and stability. Current research on these limiting factors is not exhaustive, posing challenges for the comprehensive industrial implementation of CO‐SCR technology. Therefore, this review paper focuses on the variables impeding the industrial utilization of CO‐SCR, summarizing existing bottlenecks and emphasizing the urgent need to address the inhibitory effects of O2 on the CO‐SCR reaction, a critical issue in contemporary research. This review aims to clearly articulate the key challenges of CO‐SCR technology and provide direction for future research.
Extending the solid solution range of sodium ferric pyrophosphate: Off‐stoichiometric Na3Fe2.5(P2O7)2 as a novel cathode for sodium‐ion batteries
Authors: Pu Xiangjun , Yang Kunran , Pan Zibing , Song Chunhua , Lai Yangyang , Li Renjie , Xu Zheng‐Long , Chen Zhongxue , Cao Yuliang
Published: December 2023

Iron‐based pyrophosphates are attractive cathodes for sodium‐ion batteries due to their large framework, cost‐effectiveness, and high energy density. However, the understanding of the crystal structure is scarce and only a limited candidates have been reported so far. In this work, we found for the first time that a continuous solid solution, Na4−αFe2+α/2(P2O7)2 (0 ≤ α ≤ 1, could be obtained by mutual substitution of cations at center‐symmetric Na3 and Na4 sites while keeping the crystal building blocks of anionic P2O7 unchanged. In particular, a novel off‐stoichiometric Na3Fe2.5(P2O7)2 is thus proposed, and its structure, energy storage mechanism, and electrochemical performance are extensively investigated to unveil the structure–function relationship. The as‐prepared off‐stoichiometric electrode delivers appealing performance with a reversible discharge capacity of 83 mAh g−1, a working voltage of 2.9 V (vs. Na+/Na), the retention of 89.2% of the initial capacity after 500 cycles, and enhanced rate capability of 51 mAh g−1 at a current density of 1600 mA g−1. This research shows that sodium ferric pyrophosphate could form extended solid solution composition and promising phase is concealed in the range of Na4−αFe2+α/2(P2O7)2, offering more chances for exploration of new cathode materials for the construction of high‐performance SIBs.
Characterization of the Ligand Properties of Donor‐stabilized Pnictogenyltrielanes
Authors: Szlosek Robert , Niefanger Amelie Sophie , Balázs Gábor , Seidl Michael , Timoshkin Alexey Y. , Scheer Manfred
Published: December 2023

A general synthesis and the characterization of novel alkyl‐substituted NHC‐stabilized pnictogenylboranes NHC ⋅ BH2ER2 (NHC=N‐heterocyclic carbene, E=P, As; R2=Me2, Ph2, tBuH, Cy2, (SiMe3)2) are reported. These compounds were reacted with Ni(CO)4 to the corresponding complexes of the type [(NHC ⋅ BH2ER2)Ni(CO)3] to determine their donor strength by Tolman Electronic Parameters (TEPs) and their steric demand as ligands compared to classical phosphines, superbasic phosphines and other commonly applied donor systems. The results show that the NHC‐stabilized pnictogenyltrielanes can be considered as being highly basic, while their steric influence depends strongly on the organic residues as well as the donor attached to the {BH2} moiety. Although weaker than commonly used superbasic phosphines, the donor strength of pnictogenyltrielanes in general can be classified as of similar strength as NHCs. The steric and electronic properties can easily be modified by alkyl substitution as evident from the TEP trends.
“Buttressing Effect” in the Halogen‐Lithium Exchange in ortho‐Bromo‐N,N‐dimethylanilines and Related Naphthalenes
Authors: Meshalkin Stepan A. , Tsybulin Semyon V. , Bardakov Victor G. , Tatarinov Ilya A. , Shitov Daniil A. , Tupikina Elena Y. , Efremova Mariia M. , Antonov Alexander S.
Published: December 2023

Non‐covalent interactions such as coordination of an organolithium reagent by a directing group and steric repulsion of substituents strongly affect the halogen‐lithium exchange process. Here we present the manifestation of the “buttressing effect” – an indirect interaction between two substituents issued by the presence of a third group – and its influence on the ease and selectivity of the bromine‐lithium exchange and the reactivity of formed aryllithiums. The increase of the size of the “buttressing” substituent strongly affects the conformation of a NMe2 group, forcing it to hinder ortho‐bromine and thus slowing down the exchange. In naphthalene substrates bearing two bromines, this suppresses regioselectivity of the reaction. The “buttressing effect” forces formed aryllithiums to deaggregate, thus boosting their reactivity. This facilitates the decomposition via protolisys by ethereal solvents even at low temperatures and in some cases initiates fast Wurtz‐Fittig coupling.
Research on the working mode, working state, and control strategies of generalized electric spring
Authors: Wang Xiaohu , Chen Xinyuan , Huang Zhun , Zhao Chaohui
Published: December 2023

The advantage of a generalized electric spring (G‐ES) is that it solves the redundancy problem of a conventional electric spring (ES) in the face of critical load clusters. This paper first introduces Hamilton's principle into the G‐ES, derives the mathematical model of the G‐ES, and further introduces the topology of the G‐ES. Next, the working modes and working states of the G‐ES are defined. The working modes are used to reflect the combination of ES power inside the G‐ES, and the power conditions in specific working modes are described using a phase diagram. Then, the paper analyses the power case of the G‐ES to the external system, giving the respective working states according to their internal working modes. Finally, this paper introduces PQ control to the control strategy of the G‐ES and achieves control of the G‐ES working mode and its working state. The results of the study show that there are 100 working modes of the G‐ES, and 76 working modes have a specific working state. The correctness of the working mode and working state analysis is verified with the help of the MATLAB/Simulink simulation and experiment.
Molecular analysis of XPO1 inhibitor and gemcitabine–nab‐paclitaxel combination in KPC pancreatic cancer mouse model
Authors: Uddin Md. Hafiz , Al‐Hallak Mohammad Najeeb , Khan Husain Yar , Aboukameel Amro , Li Yiwei , Bannoura Sahar F. , Dyson Gregory , Kim Seongho , Mzannar Yosef , Azar Ibrahim , Odisho Tanya , Mohamed Amr , Landesman Yosef , Kim Steve , Beydoun Rafic , Mohammad Ramzi M. , Philip Philip A. , Shields Anthony F. , Azmi Asfar S.
Published: December 2023

Background

The majority of pancreatic ductal adenocarcinoma (PDAC) patients experience disease progression while on treatment with gemcitabine and nanoparticle albumin‐bound (nab)‐paclitaxel (GemPac) necessitating the need for a more effective treatment strategy for this refractory disease. Previously, we have demonstrated that nuclear exporter protein exportin 1 (XPO1) is a valid therapeutic target in PDAC, and the selective inhibitor of nuclear export selinexor (Sel) synergistically enhances the efficacy of GemPac in pancreatic cancer cells, spheroids and patient‐derived tumours, and had promising activity in a phase I study.

Methods

Here, we investigated the impact of selinexor–gemcitabine–nab‐paclitaxel (Sel‐GemPac) combination on LSL‐KrasG12D/+; LSL‐Trp53R172H/+; Pdx1‐Cre (KPC) mouse model utilising digital spatial profiling (DSP) and single nuclear RNA sequencing (snRNAseq).

Results

Sel‐GemPac synergistically inhibited the growth of the KPC tumour‐derived cell line. The Sel‐GemPac combination reduced the 2D colony formation and 3D spheroid formation. In the KPC mouse model, at a sub‐maximum tolerated dose (sub‐MTD) , Sel‐GemPac enhanced the survival of treated mice compared to controls (p < .05). Immunohistochemical analysis of residual KPC tumours showed re‐organisation of tumour stromal architecture, suppression of proliferation and nuclear retention of tumour suppressors, such as Forkhead Box O3a (FOXO3a). DSP revealed the downregulation of tumour promoting genes such as chitinase‐like protein 3 (CHIL3/CHI3L3/YM1) and multiple pathways including phosphatidylinositol 3'‐kinase‐Akt (PI3K‐AKT) signalling. The snRNAseq demonstrated a significant loss of cellular clusters in the Sel‐GemPac‐treated mice tumours including the CD44+ stem cell population.

Conclusion

Taken together, these results demonstrate that the Sel‐GemPac treatment caused broad perturbation of PDAC‐supporting signalling networks in the KPC mouse model.

Highlights

The majority of pancreatic ductal adenocarcinoma (PDAC) patients experience disease progression while on treatment with gemcitabine and nanoparticle albumin‐bound (nab)‐paclitaxel (GemPac).

Exporter protein exportin 1 (XPO1) inhibitor selinexor (Sel) with GemPac synergistically inhibited the growth of LSL‐KrasG12D/+; LSL‐Trp53R172H/+; Pdx1‐Cre (KPC) mouse derived cell line and enhanced the survival of mice.

Digital spatial profiling shows that Sel‐GemPac causes broad perturbation of PDAC‐supporting signalling in the KPC model.
Beetle colony optimization algorithm‐based node clustering scheme for efficient data dissemination in vehicular ad hoc networks
Authors: Nithyanandam Gopinath , Ambayiram Chinnasamy , Natarajan Bhalaji
Published: December 2023

Vehicular ad hoc networks (VANETs) are the ultimate solution for preventing road accidents, which result in the loss of precious human life worldwide. In this context, effective communication between the vehicular nodes is essential due to the varying network topology and high vehicular mobility inherent with VANETs. Cluster‐based routing is identified to be a significant approach for achieving efficient routing and improving communication proficiency in VANETs. In this paper, a beetle colony optimization algorithm–based clustering scheme (BCOACS) is proposed for generating optimized clusters for facilitating reliable data dissemination. This BCOACS algorithm includes two vital strategies such as beetle antenna search (BAS) and swarm intelligence for attaining inter‐cluster and intra‐cluster communications. In specific, BAS strategy that includes random search attributed toward gradient direction is used for intra‐cluster communication without using the complete amount of gradient information. On the other hand, a swarm intelligence strategy that encompasses a collective approach of self‐organized and decentralized agents is used for inter‐cluster communication with the view to minimize the load on each cluster head (CH) and to extend the clusters' lifetime. The simulation outcomes of the proposed BCOACS scheme confirmed improved performance in optimizing the number of constructed clusters independent of the increase in the network grid size, transmission range, and number of vehicular nodes in the network compared to the benchmarked approaches. The results also confirmed that the proposed BCOACS scheme achieved a maximized throughput of 13.42%, with reduced delay and protocol overhead of 18.96% and 19.45%, better than the benchmarked schemes used for investigation.
Plasma p‐tau217, p‐tau181, and NfL as early indicators of dementia risk in a community cohort: The Shanghai Aging Study
Authors: Xiao Zhenxu , Wu Wanqing , Ma Xiaoxi , Wu Jie , Liang Xiaoniu , Zhou Xiaowen , Cao Yang , Zhao Qianhua , Ding Ding
Published: December 2023

INTRODUCTION

Blood biomarkers showed values for predicting future cognitive impairment. Evidence from the community‐based cohort was limited only in high‐income countries.

METHODS

This study included 1857 dementia‐free community residents recruited in 2009–2011 and followed up in waves 2014–2016 and 2019–2023 in the Shanghai Aging Study. We intended to explore the relationships of baseline plasma ALZpath phosphorylated tau 217 (p‐tau217), p‐tau181, neurofilament light chain (NfL) with follow‐up incident dementia, Alzheimer's disease (AD), and amyloidosis.

RESULTS

Higher concentrations of plasma p‐tau217, p‐tau181, and NfL were correlated to higher decline speed of Mini‐Mental State Examination score, and higher risk of incident dementia and AD. The p‐tau217 demonstrated a significant correlation with longitudinal neocortical amyloid‐beta (Aβ) deposition (r = 0.57 [0.30, 0.76]) and a high accuracy differentiating Aβ+ from Aβ‐ at follow‐ups (area under the receiver operating characteristic curve = 0.821 [0.703, 0.940]).

DISCUSSION

Plasma p‐tau217 may be an early predictive marker of AD and Aβ pathology in older community‐dwelling individuals.

Highlights

Plasma p‐tau217, p‐tau181, and NfL were positively associated with long‐term cognitive decline and risk of incident dementia.

Plasma p‐tau217 showed a better performance distinguishing Aβ+ individuals from Aβ‐ individuals at follow‐ups.

Plasma NfL may be a suitable predictor of general cognitive decline in older community‐dwelling individuals.
A preliminary site selection system for underground hydrogen storage in salt caverns and its application in Pingdingshan, China
Authors: Huang Liangchao , Fang Yanli , Hou Zhengmeng , Xie Yachen , Wu Lin , Luo Jiashun , Wang Qichen , Guo Yilin , Sun Wei
Published: December 2023

Large‐scale underground hydrogen storage (UHS) provides a promising method for increasing the role of hydrogen in the process of carbon neutrality and energy transition. Of all the existing storage deposits, salt caverns are recognized as ideal sites for pure hydrogen storage. Evaluation and optimization of site selection for hydrogen storage facilities in salt caverns have become significant issues. In this article, the software CiteSpace is used to analyze and filter hot topics in published research. Based on a detailed classification and analysis, a “four‐factor” model for the site selection of salt cavern hydrogen storage is proposed, encompassing the dynamic demands of hydrogen energy, geological, hydrological, and ground factors of salt mines. Subsequently, 20 basic indicators for comprehensive suitability grading of the target site were screened using the analytic hierarchy process and expert survey methods were adopted, which provided a preliminary site selection system for salt cavern hydrogen storage. Ultimately, the developed system was applied for the evaluation of salt cavern hydrogen storage sites in the salt mines of Pingdingshan City, Henan Province, thereby confirming its rationality and effectiveness. This research provides a feasible method and theoretical basis for the site selection of UHS in salt caverns in China.
Organised loneliness and its discontents
Authors: Sagan Olivia
Published: December 2023

This review paper offers a critique of the discourse of loneliness both in the popular and academic imagination. It questions the stance and approach of much loneliness research and the headlines that have been extracted from it. These position loneliness as an epidemic, framing it as a global public health problem, its aetiology and management located in the individual. The paper draws attention to overlooked alternative framings of loneliness as well as to the risks of maintaining our current levels of alarm regarding it. Finally, the work of Hannah Arendt is turned to, as part of a wider academic reappreciation of her work on loneliness. The paper ends by suggesting what can be learned by loneliness researchers in the medical humanities from such political analyses.
What medical providers need to elevate outpatient care for adolescents and young adults with binge‐eating disorder: A novel protocol
Authors: Downey Amanda E. , Odette Michelle , Sanders Austin E. , Kuykendall Mikayla , Saunders Elizabeth , Nagata Jason M. , Forsberg Sarah , Buckelew Sara M. , Garber Andrea K.
Published: December 2023

Purpose

Binge‐eating disorder (BED) in adolescents and young adults is underrecognized and understudied and no standardized guidelines exist for medical providers caring for this population. To highlight the lack of extant evidence, we examine the demographic characteristics of youth with BED in an academic eating disorders (EDs) program and primary care clinic and describe the needs of their medical care providers.

Method

A retrospective chart review was conducted for patients who met criteria for BED from July 2021 to June 2022. We surveyed their medical providers to understand their needs in caring for this population. A multidisciplinary team with expertise in the care of youth with EDs amalgamated current evidence in caring for youth with BED into a protocolized care schema designed for implementation in the outpatient medical setting.

Results

Eighteen youth with BED were reviewed, 14 identified as female, 3 as male, and 1 as “Other.” Average age was 15.4 (2.7) years old, and mean body mass index was 35.90 (8.25). 33.3% (6) patients identified as White/Caucasian, followed by 22.2% (4) Hispanic/Latinx. Eleven of 18 were privately insured. The most common medical recommendations were for regular meals and snacks and for individual psychotherapy. Medical providers desired more education about identification and management of youth with BED.

Conclusions

To address the lack of medical care guidelines for youth with BED, recommendations in this Forum include: increased education for medical providers, standardized medical monitoring, an emphasis on psychotherapy, and a weight‐inclusive orientation.

Public Significance

Adolescents and young adults with BED are underrecognized and undertreated. Little is known about the characteristics of these patients and the medical care these patients receive within academic EDs program. For the first time, preliminary recommendations for medical care are provided.
Body mass index, frailty, and outcomes in heart failure with preserved ejection fraction
Authors: Li Wenjie , Wang Zhiyan , Hua Chang , Zhang Hao , Liu Xinru , Zheng Shiyue , Lv Qiang , Jiang Chao , Dong Jianzeng , Ma Changsheng , Du Xin
Published: December 2023

Aims

Relationship between body mass index (BMI), frailty, and clinical adverse events remains unclear in patients with heart failure (HF) with preserved ejection fraction (HFpEF) in different patient populations. We aimed to compare the association of BMI, frailty, and clinical adverse events between a US cohort from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study and a Chinese cohort from the Heart Failure Registry of Patient Outcomes (HERO) study.

Methods and results

We used data of 1715 participants enrolled from America in the TOPCAT study and 1487 patients with HFpEF in the Chinese registry study, the HERO. We evaluated the relationship between BMI and frailty using multivariate restricted cubic spline logistic regression. Association between frailty and BMI categories and primary outcomes including HF hospitalization, aborted sudden death, and cardiovascular death, all‐cause mortality, and HF hospitalization were analysed by Cox proportional hazards models. The patients' mean age was 72 ± 11 years for both study populations, with 50% and 46% female for the TOPCAT study and the HERO study, respectively. Patients in the TOPCAT study had a higher mean BMI (33.9 vs. 24 kg/m2), with 72.3% vs. 52.9% defined as moderately to severely frail (frailty index > 0.3). In the TOPCAT study, risk of frailty rose as BMI increased, but not in the HERO study. Patients with frailty were at significant higher risk for the primary composite outcomes [hazard ratio (HR) 1.84 (95% confidence interval: 1.46–2.32)], all‐cause mortality [HR 1.73 (1.34–2.25)], and HF hospitalization [HR 1.83 (1.40–2.40)] in the TOPCAT study. The corresponding numbers in the HERO study were 1.26 (1.01–1.57), 2.21 (1.45–3.35), and 1.15 (0.81–1.37), respectively. The association of frailty with clinical outcomes did not vary with BMI categories in the two studies.

Conclusions

BMI distribution and association between BMI and frailty risk were different between the two study populations. Frailty was associated with clinical adverse events and this association was consistent across different BMI categories in both studies.
Facile (3+2) Cycloaddition between an N‐Heterocyclic Olefin and Nitrous Oxide at Ambient Conditions
Authors: Ariai Jama , Becker Jonathan , Gellrich Urs
Published: December 2023

We report that a gem‐dimethylated N‐heterocyclic olefin (NHO) reacts with N2O at ambient pressure and room temperature to give an imidazolone and an azine formed from intermediately generated 2‐diazopropane. The in situ formation of transient diazopropane was indirectly proven by its engagement in a facile cycloaddition with norbornene. According to our studies, the reaction sequence consists of a rate‐determining (3+2) cycloaddition between the NHO and N2O, followed by a cycloreversion that releases the diazoalkane. This mechanistic proposal is supported by DFT calculations. Eyring analysis using temperature‐variable 1H NMR spectroscopy allowed us to determine the activation parameters of the initial (3+2) cycloaddition (Δ≠H=11.2(4) kcal/mol, Δ≠S=−39.8(13) e.u., 293–308 K). Frontier molecular orbital analysis shows that the polarization of the π‐bond of the NHO decisively facilitates the cycloaddition.
The cost of participation: An analysis of the financial dimensions of participatory budgets in Portugal
Authors: Bogo Rodrigo Sartori , Falanga Roberto
Published: December 2023

Participatory budgeting (PB) is a democratic innovation that allows citizens to deliberate about a share of the public budget. Portugal was one of the most influent countries in this field in the last decade, as PB was implemented at multiple levels. However, few studies have made in‐depth research on the financial dimensions of PB, which raises interest as to whether and how citizens' voice has had a significant impact on policy‐making. To fill in this gap, this article considers the financial asset of local, regional, and national PBs in Portugal up to the disruption of the COVID‐19 pandemic. Our methodological approach relies on both quantitative data analyzed through Geographical Information Systems and descriptive statistics, and qualitative data retrieved from document analysis. Findings are discussed through four different stages of dissemination in the country, and show that despite significant advancements in this field, impacts in the financial dimensions lay behind expectations.
E = mc2: Education (E), medication (m), and conditional cash (c2) to improve uptake of antiseizure medications in a low‐resource population: Protocol for randomized trial
Authors: Rezaei Shawheen J. , Cissé Fodé Abass , Touré Mohamed Lamine , Duan Rui , Rice Dylan R. , Ham Andrew Siyoon , de Walque Damien , Mateen Farrah J.
Published: December 2023

Objective

Most people with epilepsy (PWE) could live seizure‐free if treated with one or more antiseizure medications (ASMs). The World Health Organization (WHO) estimates that 75% of PWE in low‐resource settings lack adequate antiseizure treatment. Limited education surrounding epilepsy and the out‐of‐pocket costs of ASMs in particular pose barriers to managing epilepsy in resource‐poor, low‐income settings. The aim of this study is to implement and test a novel strategy to improve outcomes across the epilepsy care cascade marked by (1) retention in epilepsy care, (2) adherence to ASMs, and (3) seizure reduction, with the measured goal of seizure freedom.

Methods

A randomized, double‐blinded clinical trial will be performed, centered at the Ignace Deen Hospital in Conakry, Republic of Guinea, in Western Sub‐Saharan Africa. Two hundred people with clinically diagnosed epilepsy, ages 18 years and above, will receive education on epilepsy and then be randomized to (i) free ASMs versus (ii) conditional cash, conditioned upon return to the epilepsy clinic. Participants will be followed for 360 days with study visits every 90 days following enrollment.

Significance

We design a randomized trial for PWE in Guinea, a low‐resource setting with a high proportion of untreated PWE and a nearly completely privatized healthcare system. The trial includes a conditional cash transfer intervention, which has yet to be tested as a targeted means to improve outcomes for people with a chronic neurological disorder. The trial aims to provide an evidence base for the treatment of epilepsy in such settings.

Plain Language Summary

We present a clinical trial protocol for a randomized, blinded study of 200 people with epilepsy in the low‐resource African Republic of Guinea, providing an educational intervention (E), and then randomizing in a 1:1 allocation to either free antiseizure medication (m) or conditional cash (c2) for 360 days. Measured outcomes include (1) returning to outpatient epilepsy care, (2) adherence to antiseizure medications (ASMs), and (3) reducing the number of seizures. This study is an initial look at giving small amounts of cash for desired results (or “nudges”) for improving epilepsy outcomes in the sub‐Saharan African and brain disorder contexts.
Joint optimization of task scheduling and computing resource allocation for VR video services in 5G‐advanced networks
Authors: Huang Zhenglei , Du Yupeng , Yang Shujie , Xiao Han , Wang Dan , Sun Tao
Published: December 2023

With the development of 5G networks and related hardware equipment, the demand for various VR video services including panoramic video live broadcast and immersive game is increasing day by day. Due to the explosive growth of data volume and the trend toward lightweight VR equipment, traditional local computing architecture faces problems of insufficient computing power and high cost. As an emerging computing paradigm, the remote computing architecture of cloud‐edge collaboration frees users from cumbersome local restrictions. However, edge computing resources are often limited, and the remote cloud has inconsistent network latency. Therefore, how to adaptively schedule and allocate computing resources is the key to determining VR service quality. Based on an in‐depth analysis of the characteristics of VR video services and network environments, this article first builds a cloud‐edge‐network coorperation computing and transmission architecture for VR video services. This architecture can adaptively offload concurrent computing tasks and allocate computing power to them in VR scenes based on network conditions provided by the 5G‐Advanced networks via network information exposure interface. This paper proposes a general optimization problem to maximize user experience. And a single‐slot delay optimization model was constructed. Combining convex optimization theory and deep learning algorithms, this paper designs a task scheduling and computing power allocation strategy based on deep reinforcement learning. The policy gradually learns optimal task scheduling and resource allocation decisions to maximize delay‐related rewards in the long run. This article further introduces the graph neural network under the attention mechanism to solve the problem of changes in the number of concurrent tasks. Finally, through Cloudsim simulation, this article verifies the superiority of task scheduling and computing power allocation strategies based on deep reinforcement learning compared to other common strategies in terms of resource utilization, client latency, scalability and decision time.