bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare providers' expected barriers and facilitators to the implementation of person‐centered long‐term follow‐up care for childhood cancer survivors: A PanCareFollowUp study
Authors: Breij Dionne , Hjorth Lars , Bouwman Eline , Walraven Iris , Kepak Tomas , Kepakova Katerina , Haupt Riccardo , Muraca Monica , Göttgens Irene , Stollman Iridi , Winther Jeanette Falck , Kienesberger Anita , Gsell Hannah , Michel Gisela , Blijlevens Nicole , Pluijm Saskia M. F. , Roser Katharina , Skinner Roderick , Renard Marleen , Uyttebroeck Anne , Follin Cecilia , van der Pal Helena J. H. , Kremer Leontien C. M. , Loonen Jaqueline , Hermens Rosella ,   the PanCareFollowUp Consortium
Published: October 2024

Background

Childhood cancer survivors face high risks of adverse late health effects. Long‐term follow‐up care for childhood cancer survivors is crucial to improve their health and quality of life. However, implementation remains a challenge. To support implementation of high‐quality long‐term follow‐up care, we explored expected barriers and facilitators for establishing this follow‐up care among healthcare providers from four European clinics.

Methods

A qualitative study was conducted using four focus groups comprising 30 healthcare providers in total. The semi‐structured interview guide was developed based on the Grol and Wensing framework. Data was analyzed following a thematic analysis, combining both inductive and deductive approaches to identify barriers and facilitators across the six levels of Grol and Wensing: innovation, professional, patient, social, organizational and economic and political.

Results

Most barriers were identified on the organizational level, including insufficient staff, time, capacity and psychosocial support. Other main barriers included limited knowledge of late effects among healthcare providers outside the long‐term follow‐up care team, inability of some survivors to complete the survivor questionnaire and financial resources. Main facilitators included motivated healthcare providers and survivors, a skilled hospital team, collaborations with important stakeholders like general practitioners, and psychosocial care facilities, utilization of the international collaboration and reporting long‐term follow‐up care results to convince hospital managers.

Conclusion

This study identified several factors for successful implementation of long‐term follow‐up care for childhood cancer survivors. Our findings showed that specific attention should be given to knowledge, capacity, and financial issues, along with addressing psychosocial issues of survivors.
Global Trend in Pancreatic Cancer Prevalence Rates Through 2040: An Illness‐Death Modeling Study
Authors: Hesami Zeinab , Olfatifar Meysam , Sadeghi Amir , Zali Mohammad Reza , Mohammadi‐Yeganeh Samira , Habibi Mohammad Amin , Ghadir Mohammad Reza , Houri Hamidreza
Published: October 2024

Background

Despite remarkable progress in contemporary medical technology and enhanced survival outcomes for various cancer types, pancreatic cancer (PC) continues to stand out as a particularly deadly gastrointestinal malignancy. Given a persistent rise in both incidence and the corresponding mortality rates of PC globally, evaluations of PC burden by sex are of great importance. Here, we used the illness‐death multi‐state model (IDM) to forecast the prevalence of PC through the year 2040.

Methods

IDM was established based on obtainable data to predict the future prevalence of PC on global, regional, and national scales from 2019 to 2040. Analyses were also performed regarding sex and 95% confidence intervals (CIs) are presented for all estimates.

Results

The projected prevalence rate for 2040 is anticipated to be 6.093 ([95% CI 5.47–6.786] per 100,000) worldwide, indicating a significant increase of 31.45% since 1990, and a 12.29% increase since 2019. The estimated average annual increase since 2020 was 0.5%. Considering sex differences, females are expected to have a steeper slope in prevalence rate than males. Intriguingly, when considering the percentage changes between the periods of 2019–2040 and 1990–2019 for both sexes, females exhibited 29% and 11% increase relative to males (2.6‐fold greater increase).

Conclusions

By 2040, it is predicted that the prevalence of PC will increase globally, with women being at higher risk of developing the disease. Considering the percentage changes, regions with lower socioeconomic status are anticipated to face a greater risk of experiencing PC compared to other geographical areas.
Design, Synthesis, Biological Evaluation and Molecular Docking Studies of New Thiazolidinone Derivatives as NNRTIs and SARS‐CoV‐2 Main Protease Inhibitors
Authors: Fesatidou Maria , Petrou Anthi , Geronikaki Athina
Published: October 2024

HIV‐1 remains a major health problem worldwide since the virus has developed drug‐resistant strains, so, the need for novel agents is urgent. The protein reverse transcriptase plays fundamental role in the viruses’ replication cycle. FDA approved Delavirdine bearing a sulfonamide moiety, while thiazolidinone has demonstrated significant anti‐HIV activity as a core heterocycle or derivative of substituted heterocycles. In this study, thirty new thiazolidinone derivatives (series A, B and C) bearing sulfonamide group were designed, synthesized and evaluated for their HIV‐1 RT inhibition activity predicted by computer program PASS taking into account the best features of available NNRTIs as well as against SARS‐COV‐2 main protease. Seven compounds showed good anti‐HIV inhibitory activity, with two of them, C1 and C2 being better (IC50 0.18 μΜ & 0.12 μΜ respectively) than the reference drug nevirapine (IC50 0.31 μΜ). The evaluation of molecules to inhibit the main protease revealed that 6 of the synthesized compounds exhibited excellent to moderate activity with two of them (B4 and B10) having better IC50 values (0.15 & 0.19 μΜ respectively) than the reference inhibitor GC376 (IC50 0.439 μΜ). The docking studies is coincides with experimental results, showing good binding mode to both enzymes.
Synthesis of Sulfonamide‐Based Schiff Bases as Potent Anticancer Agents: Spectral Analyses, Biological Activity, Molecular Docking, ADME, DFT, and Pharmacophore Modelling Studies
Authors: Başaran Eyüp , Çakmak Reşit , Türkmenoğlu Burçin , Akkoc Senem , Köprü Semiha
Published: October 2024

The current study focuses on the synthesis and characterization of six benzenesulfonamide‐based Schiff base derivatives (7–12) with various electron‐withdrawing and electron‐donating substituents (−F, ‐CI, ‐Br, −CH3, and −OCH3) and the assessment of their antiproliferative activities against human lung (A549) and liver (HepG2) cancer cell lines using in vitro and in silico approaches. The structures of the synthesized compounds (7–12) were elucidated by elemental analysis and FT‐IR, 1D (1H, 13C, APT, and DEPT‐135), and 2D (HMQC and HMBC) NMR spectroscopies. The cytotoxic activities of the targeted compounds were determined at various concentrations against these cancer cell lines for 72 h, using the MTT method. The targeted molecules (7–12) demonstrated remarkable antiproliferative activities, with IC50 values ranging from 6.032–9.533 μM against the A549 cell line and 5.244–9.629 μM against the HepG2 cell line. These compounds showed activities at lower or very similar concentrations to cisplatin against the A549 cell line and at much lower concentrations than cisplatin against the HepG2 cell line. Among them, compounds 10 and 12 were found to be more effective against A549 and HepG2 cells, respectively, than cisplatin. These compounds were analyzed by interacting with the 1BNA, 4HJO, and 4ASD crystal structures in molecular docking studies. The docking score of 4ASD‐compound 12 interaction was calculated as −4.045 kcal/mol, 4HJO‐compound 10 interaction was calculated as −5.179 kcal/mol and 1BNA‐compound 10 interaction was calculated as −8.571 kcal/mol and it was determined that these compounds were theoretically better than Cisplatin. In the present study, ADME data were estimated using the web tool SwissADME. With ADME, it was calculated that the logP value of compounds 7–12 was less than 5, the HBD number was 1, the HBA number was 7 or 8, and the molecular weight was less than 500. Properties such as the electrophilic index and chemical hardness of the designed compounds were examined by density functional theory (DFT) using B3LYP/6‐311G**. In conclusion, these compounds have emerged as promising new anti‐cancer drug candidates.
Chemical Composition, Anti‐Microbial, and Cytotoxic Activities of Essential Oil From Magnolia bidoupensis Q. N. Vu Leaves, an Endemic Species to the Central Highlands of Vietnam
Authors: Van Ngoc Nguyen , Ngoc Uyen Nhi Tran , Thi Binh Hoang
Published: October 2024

An analysis was conducted on the essential oil extracted from the leaves of Magnolia bidoupensis utilizing GC‐MS, revealing thirty‐three constituents that account for 98.9 % of the essential oil. The main components included pogostol (22.4 %), δ‐selinene (16.2 %), and α‐amorphene (14.7 %). Bioassays were then performed to evaluate the oil's biological activity. The essential oil exhibited antimicrobial activity against all tested microorganisms (six bacterial strains and one fungal strain) using the minimum inhibitory concentration (MIC) method. Additional cytotoxicity tests were conducted on KB, HepG2, MCF‐7, and A549 cancer cell lines using the MTT method. The essential oil exhibited strong cytotoxic effects on all four cell lines, with IC50 values ranging from 1.37±0.05 μg/mL (KB) to 2.40±0.06 μg/mL (A549).
Suicide and self‐harm in prisons: The challenge of service evaluation and prevention
Authors: Challinor Alexander , Rafferty Joe , Thomas Noir , Pilling Sarah , Bhandari Sahil , Ibrahim Saied , Kapur Nav
Published: October 2024

Very high rates of suicide and self‐harm in prisons worldwide emphasise the need for evidence‐based approaches to prevention. Real world evaluations of organisational changes and service developments within prisons could yield important insights, but there are challenges to achieving this, as we found from an evaluation in a single UK institution.
NTF2‐Like Enzymes as Versatile Biocatalysts in Fungal Natural Product Biosynthesis
Authors: Li Yanqin , Wang Junfeng , Yan Yan
Published: October 2024

Fungal natural products (NPs), known for their potent bioactivities, can be utilized as human therapeutics and agrochemicals. These bioactive and structurally complex compounds are biosynthesized through condensation of monomeric building blocks to construct core scaffolds, followed by various modification steps. Recent studies have revealed that a unique class of enzymes from the NTF2‐like protein family plays important roles in the biosynthesis of complex fungal NPs. These NTF2‐like enzymes belong to a large group of related proteins that share a common fold with nuclear transport factor 2, and are capable of catalyzing various reactions. In this study, we summarize the recent progress in discovering and characterizing the catalytic functions of fungal‐derived NTF2‐like enzymes, including dehydratases, epimerases, isomerases, semipinacolases, pericyclases, and aldolases. These findings not only provide valuable insights into new catalytic reactions and mechanisms, but also offer opportunities to discover novel NPs and biocatalysts through genome mining.
Dynamic Processes at the Electrode‐Electrolyte Interface: Implications for Lithium Deposition Stability
Authors: Dutta Arghya
Published: October 2024

Lithium (Li) metal is a promising negative electrode material for high‐energy‐density rechargeable batteries, owing to its exceptional specific capacity, low electrochemical potential, and low density. However, challenges such as dendritic Li deposits, leading to internal short‐circuits, and low Coulombic efficiency hinder the widespread adoption of lithium‐metal batteries (LMBs). These issues stem from the morphological instability of Li deposition, influenced by dynamic processes at the electrolyte|Li interface. Understanding the interplay between electrolyte properties, interfacial kinetics, and Li deposition stability is crucial yet challenging due to their simultaneous occurrence and the complexity of the solid electrolyte interphase (SEI) layer. This review discusses three key dynamic processes influencing Li deposition: desolvation of Li+ ions, transport through the SEI, and electrochemical reduction. The effects of electrolyte properties on these processes and their interplay with electroplating stability are discussed, highlighting contradictions in the literature and proposing explanations for the discrepancies. Despite numerous reviews on SEI structure and composition effects, this article emphasizes the kinetic aspects at interfaces, aiming to provide clarity and direction for future research in achieving stable Li deposition in LMBs.
Recent Progresses and Challenges to Determine Properties of Sulfonated Polyether Ether Ketone Based Electrolytes for Direct Methanol Fuel Cell Applications
Authors: Tamer Murat , Akyalçın Sema , Akyalçın Levent
Published: October 2024

This review focuses on fillers, modifications, and methods used in the preparation and development of sulfonated poly(ether ether ketone) (sPEEK) membranes, specifically for direct methanol fuel cell (DMFC) applications as proton exchange membranes in recent years. The primary objective is to evaluate recent advancements by emphasizing key characteristics such as water uptake and swelling capacity, ionic conductivity, methanol permeability, and single cell polarization tests. Additionally, the review aims to provide insights for future researchers by discussing the preparation processes of electrolytes. It presents basic characterizations of membrane electrolytes, including evaluations of the sulfonation degree and ion exchange capacities of sPEEK. High performance of membrane electrolytes is essential for commercialization and to compete with established membranes like Nafion®, which has a perfluorosulfonic acid structure. Therefore, the review also covers detailed characterization methods for assessing long‐term stability when available in the related studies. Numerical results and indicators are categorized and tabulated for easy interpretation and comparative analysis.
Effect of SiO2 on the Performance of Cellulose/Poly(Vinylidene Fluoride) Films as Polymer Electrolytes for Lithium Ion Battery
Authors: Mohamadzade Shirin , Safavi‐Mirmahalleh Seyedeh‐Arefeh , Roghani‐Mamaqani Hossein , Salami‐Kalajahi Mehdi
Published: October 2024

Polymer electrolytes serve as highly efficient alternatives to liquid electrolytes, especially in terms of safety in lithium ion batteries. Among various polymers, Cellulose contains electron‐donating atoms which can coordinate with lithium salts and be used as polymer electrolyte. Also, cellulose can be blended with other polymers to improve their properties. Polymer electrolytes suffer from poor mechanical properties. Adding nanoparticles not only surmounts the drawback of poor mechanical properties but also improves physical and electrochemical properties. In this study, different weight ratios of PVDF/cellulose blend films containing silicon dioxide (SiO2) are prepared via solution casting method. The results explored ionic conductivity in order of 10−4 S cm−1. In addition, high transfer numbers (0.74<t+<0.98), wide electrochemical window (up to 6 V), acceptable charge capacity, and long cycle stability are attained. In details, for 90/10 (wt./wt.) cellulose/PVDF, the ionic conductivity reached 4.4×10−⁴ S cm−1, and the ion transfer number was obtained 0.98. Additionally, the electrochemical stability window for these gel polymer electrolytes exceeded 5 V. The sample containing 90 % cellulose achieved an optimal charge capacity of 225.3, with 93.4 % capacity retention after 200 cycles at 0.2 C.
Understanding the Relation Between Intrinsic Parameters of Substituents and Physical‐Chemical Properties of NVP
Authors: Baiju S. , Guillon O. , Kaghazchi P.
Published: October 2024

NASICON‐type Na3V2(PO4)3 (NVP) is regarded as an intriguing cathode material choice for sodium ion batteries (SIBs) due to its cycling stability and relatively high capacity. However, its voltage and electronic conductivity still need to be improved for larger‐scale fast‐charging applications (e.g. electric vehicles and mobile phones). In this work, we investigate the influence of Vanadium (V) substitution by other environmentally friendly, cheap, and/or high‐valent transition metal (TM) elements on the electrochemical performance of NVP. Density functional theory calculation was used to study the volume change, voltage, conductivity, and redox mechanism during charge/discharge of different compositions. It is found that a substitution of 50% of V by Mn, Mo or W ions resulting in Na3VMn(PO4)3 (NVMnP), Na3VMo(PO4)3 (NVMoP), and Na3VW(PO4)3 (NVWP) significantly alters the cathode materials’ physical and chemical properties, notably decreasing the band gap. In particular, NVMnP has lesser than 1 eV theoretical band gap and provides a higher voltage, while NVWP a much lower voltage in comparison to NVP. This means that NVMnP and NVWP can be promising cathode and anode materials respectively. This work also establishes a relation between fundamental properties of substituents (i.e. ionization energy and ionic size) and the overall performance of NVP.
Effect of Oriented External Electric Field in Altering Magnetic Exchange and Magnetic Anisotropy in Lanthanide‐Radical Complexes
Authors: Sharma Tanu , Singh Ananya , Rajaraman Gopalan
Published: October 2024

Magnetic exchange coupling (J) is one of the important spin Hamiltonian parameters that control the magnetic characteristics of single‐molecule magnets (SMMs). While numerous chemical methodologies have been proposed to modify ligands and control the J value, and magneto‐structural correlations have been developed accordingly, altering this parameter through non‐chemical means remains a challenging task. This study explores the impact of an Oriented‐External Electric Field (OEEF) on over twenty lanthanide‐radical complexes using Density Functional Theory (DFT) and ab initio Complete Active Space Self‐Consistent Field (CASSCF) methods. Five complexes – [{(Me3Si)2N]2Gd(THF)}2(μ‐η2:η2‐N2)] (1), [Gd(Hbpz3)2(dtbsq)] (2), [Gd(hfac)3(IM‐2py)] (3), [Gd(hfac)3(NITBzImH)] (4), and [Gd(hfac)3{2Py‐NO}(H2O)] (5) – were selected for detailed analysis, revealing significant OEEF effects on magnetic exchange interactions and structural parameters. Various parameters such as bond distances, bond angles, and torsional angles were examined as a function of OEEF to establish guiding principles for molecule selection. In complexes 1, 2, and 3, OEEF influenced torsional angles and altered exchange interactions. Complex 4 demonstrated enhanced ferromagnetic coupling under OEEF, reaching a maximum J value of +5.3 cm−1. Complex 5 reveals switching the sign of JGd‐rad exchange interaction from antiferromagnetic to ferromagnetic under OEEF, highlighting the potential of electric fields in designing materials with tuneable magnetic properties. These findings offer valuable insights for future research and applications in advanced materials and molecular electronics.
An Ultrahigh Affinity DNA Aptamer for Quinine and Its Intrinsic Fluorescence Based Label‐Free Detection
Authors: Datta Meheta , Kaiyum Yunus A. , Johnson Philip E. , Liu Juewen
Published: October 2024

Measuring quinine is critical for the detection of its overdose, understanding its pharmacological and toxicological effects, and monitoring its pollution. While a previously reported aptamer named MN4 can bind quinine, it was not selected for it, leading to compromised binding affinity and specificity. In this work, a new quinine aptamer was isolated using the library immobilization capture‐SELEX technique. The Q1 aptamer has a Kd value of 10 nM determined by an isothermal titration calorimetry experiment and 45 nM in a fluorescence binding assay. A 3.5 nM quinine limit of detection was obtained based on the aptamer binding‐induced quenching of the intrinsic fluorescence of quinine. A large blue shift in fluorescence was observed for quinine upon binding to Q1, whereas binding to MN4 led to a very small red shift, indicating different ways of quinine binding by these two aptamers. Q1 did not bind cocaine based on NMR spectroscopy and fluorescence assays also indicated excellent selectivity against other tested molecules. This work has supplied a high affinity aptamer for quinine that can be useful for its detection and fundamental aptamer binding studies. It also highlights the advantages of using capture‐SELEX to isolate aptamers for small molecules.
Psychometric Evaluation of the Traumatic Grief Inventory‐Self Report Plus (TGI‐SR+) in Chinese Bereaved People
Authors: Tang Suqin , Chen Zhiwei , Boelen Paul A. , Eisma Maarten C. , Lenferink Lonneke I. M.
Published: October 2024

Objective

The Traumatic Grief Inventory‐Self Report Plus (TGI‐SR+) measures the most recent prolonged grief disorder (PGD) symptom sets defined in the 11th edition of the International Statistical of Diseases and Related Health Problems (ICD‐11) and the text revision of the fifth edition of the Diagnostical and Statistical Manual of Mental Disorders (DSM‐5‐TR). However, the TGI‐SR+ has not yet been translated and validated in Chinese. This study aims to evaluate the psychometric properties of the Chinese translation of the TGI‐SR+.

Methods

We examined the Chinese TGI‐SR+'s factor structure, internal consistency, convergent validity, discriminant validity, known‐groups validity, and optimal clinical cut‐off scores in 443 Chinese bereaved adults.

Results

Confirmatory factor analyses showed that the two‐factor models showed the best fit for the Chinese TGI‐SR+ items assessing ICD‐11 and DSM‐5‐TR prolonged grief symptoms. Items assessing ICD‐11 and DSM‐5‐TR prolonged grief symptoms demonstrated good internal consistency. Associations of TGI‐SR+ scores with symptom levels of prolonged grief (assessed by the International Prolonged Grief Disorder Scale), posttraumatic stress, anxiety, and depression supported convergent and discriminant validity. Associations with background/loss‐related variables provided evidence for known‐groups validity. Cut‐off points for probable ICD‐11 PGD (liberal scoring rule), probable ICD‐11 PGD (conservative scoring rule), and probable DSM‐5‐TR PGD were ≥67, ≥75, and ≥68, respectively.

Discussion

The Chinese TGI‐SR+ appears to be a reliable and valid measure to assess prolonged grief symptoms per ICD‐11 and DSM‐5‐TR among Chinese bereaved adults.
An IQ Industry Perspective on Informing Dosing Recommendations in Patients With Renal Impairment
Authors: Sharma Ashish , Younis Islam R. , Kanodia Jitendra , Sahasrabudhe Vaishali
Published: October 2024

The IQ CPLG Organ Impairment WG conducted a survey to understand how various IQ member companies develop dosing recommendations for patients with renal impairment. Eighteen IQ member companies participated in the survey. The survey results were summarized by the working group in light of the regulatory renal impairment guidance documents as well as recent publications from the pharmaceutical industry and nephrology community. There were two important learnings from the survey: (i) pharmaceutical companies do not use a consistent methodology to assess renal function in their drug development programs. (ii) there has been significant improvement in predicting how kidney function affects drug pharmacokinetics (PK) and thus dose recommendations. Applying model‐based methods such as population PK, physiologically‐based PK (PBPK), and virtual controls has enabled earlier prediction of how kidney function influences PK, leading to the participation of more patients with impaired kidney function in Phase 2 and 3 trials.
Advances in Two‐Electron Water Oxidation Reaction for Hydrogen Peroxide Production: Catalyst Design and Interface Engineering
Authors: Cao Huixuan , Chen Ge , Yan Yong , Wang Dong
Published: October 2024

Hydrogen peroxide (H2O2) is a versatile and zero‐emission material that is widely used in the industrial, domestic, and healthcare sectors. It is clear that it plays a critical role in advancing environmental sustainability, acting as a green energy source, and protecting human health. Conventional production techniques focused on anthraquinone oxidation, however, electrocatalytic synthesis has arisen as a means of utilizing renewable energy sources in conjunction with available resources like oxygen and water. These strides represent a substantial change toward more environmentally and energy‐friendly H2O2 manufacturing techniques that are in line with current environmental and energy goals. This work reviews recent advances in two‐electron water oxidation reaction (2e‐WOR) electrocatalysts, including design principles and reaction mechanisms, examines catalyst design alternatives and experimental characterization techniques, proposes standardized assessment criteria, investigates the impact of the interfacial milieu on the reaction, and discusses the value of in situ characterization and molecular dynamics simulations as a supplement to traditional experimental techniques and theoretical simulations. The review also emphasizes the importance of device design, interface, and surface engineering in improving the production of H2O2. Through adjustments to the chemical microenvironment, catalysts can demonstrate improved performance, opening the door for commercial applications that are scalable through tandem cell development.
Learning Strategies from Nature's Blueprint to Cyclic Carbonate Synthesis
Authors: Saccullo Erika , Patamia Vincenzo , Zagni Chiara , Rescifina Antonio , Floresta Giuseppe
Published: October 2024

Nature is a remarkable source of inspiration for developing sustainable and eco‐friendly synthetic procedures. In recent years, the synthesis of cyclic carbonates has garnered significant attention due to their versatile applications in various fields, including materials science, pharmaceuticals, and green chemistry. Drawing inspiration from nature, researchers have explored innovative synthetic routes that mimic biological processes to produce cyclic carbonates efficiently and sustainably. This article reviews nature‐inspired synthetic procedures for cyclic carbonate formation, highlighting the key strategies and principles employed. Through biomimicry, researchers aim to harness the efficiency and selectivity observed in biological systems to develop greener and more sustainable methods for cyclic carbonates synthesis. Integrating bio‐inspired strategies offers opportunities for improving synthetic efficiency and contributes to reducing the environmental impact associated with traditional chemical processes. This review underscores the potential of nature‐inspired approaches in advancing the field of cyclic carbonate synthesis toward more sustainable and environmentally benign practices, focusing on recent literature.
Excitatory neurons and oligodendrocyte precursor cells are vulnerable to focal cortical dysplasia type IIIa as suggested by single‐nucleus multiomics
Authors: Liu Yingying , Li Yinchao , Zhang Yaqian , Fang Yubao , Lei Lei , Yu Jiabin , Tan Hongping , Sui Lisen , Guo Qiang , Zhou Liemin
Published: October 2024

Background

Focal cortical dysplasia (FCD) is a heterogeneous group of cortical developmental malformations that constitute a common cause of medically intractable epilepsy. FCD type IIIa (FCD IIIa) refers to temporal neocortex alterations in architectural organisation or cytoarchitectural composition in the immediate vicinity of hippocampal sclerosis. Slight alterations in the temporal neocortex of FCD IIIa patients pose a challenge for the preoperative diagnosis and definition of the resection range.

Methods

We have performed multimodal integration of single‐nucleus RNA sequencing and single‐nucleus assay for transposase‐accessible chromatin sequencing in the epileptogenic cortex of four patients with FCD IIIa, and three relatively normal temporal neocortex were chosen as controls.

Results

Our study revealed that the most significant dysregulation occurred in excitatory neurons (ENs) and oligodendrocyte precursor cells (OPCs) in the epileptogenic cortex of FCD IIIa patients. In ENs, we constructed a transcription factor (TF)‐hub gene regulatory network and found DAB1high ENs subpopulation mediates neuronal immunity characteristically in FCD IIIa. Western blotting and immunofluorescence were used to validate the changes in protein expression levels caused by some of the key genes. The OPCs were activated and exhibited aberrant phenotypes in FCD IIIa, and TFs regulating reconstructed pseudotime trajectory were identified. Finally, our results revealed aberrant intercellular communication between ENs and OPCs in FCD IIIa patients.

Conclusions

Our study revealed significant and intricate alterations in the transcriptomes and epigenomes in ENs and OPCs of FCD IIIa patients, shedding light on their cell type‐specific regulation and potential pathogenic involvement in this disorder. This work will help evaluate the pathogenesis of cortical dysplasia and epilepsy and explore potential therapeutic targets.

Key points

Paired snRNA‐seq and snATAC‐seq data were intergrated and analysed to identify crucial subpopulations of ENs and OPCs in the epileptogenic cortex of FCD IIIa patients and explore their possible pathogenic role in the disease.

A TF‐hub gene regulatory network was constructed in ENs, and the DAB1high Ex‐1 mediated neuronal immunity was characterstically in FCD IIIa patients.

The OPCs were activated and exhibited aberrant phenotypes in FCD IIIa patients, and TFs regulating reconstructed pseudotime traectory were identified.

Aberrant intercelluar communications between ENs and OPCs in FCD IIIa patients were identified.
Non‐Alzheimer's amnestic mild cognitive impairment with medial temporal hypometabolism
Authors: De Keersmaecker Sebastiaan , De Meyer Steffi , Vandenberghe Rik
Published: October 2024

INTRODUCTION

The increasing use of Alzheimer's disease (AD) biomarkers has led to the recognition of a subgroup of non‐AD amnestic mild cognitive impairment (aMCI) patients who have medial temporal hypometabolism on fluorodeoxyglucose‐positron emission tomography (FDG‐PET).

METHODS

In this academic memory‐clinic‐based consecutive series, 16 non‐AD aMCI patients and 28 AD controls matched for sex, age, and baseline Mini‐Mental State Examination (MMSE) were followed for a median duration of 4.5 years. Our primary outcome was the MMSE decline rate over the subsequent years. We also determined the final diagnosis over time.

RESULTS

FDG‐PET showed more pronounced medial temporal hypometabolism in non‐AD cases and more inferior parietal lobule hypometabolism in AD controls. MMSE decline was slower in non‐AD (β = −0.51) than in AD (β = −2.00) patients. Five non‐AD cases developed frontotemporal dementia years after symptom onset, and one developed dementia with Lewy bodies.

DISCUSSION

Non‐AD aMCI patients with medial temporal hypometabolism show slower cognitive decline.

Highlights

Non‐AD aMCI with medial temporal hypometabolism shows slower cognitive decline than AD.

FDG‐PET revealed distinct metabolic patterns between non‐AD aMCI and AD patients.

Approximately one‐third of non‐AD aMCI cases developed frontotemporal dementia.

Comprehensive diagnostic biomarkers are crucial for non‐AD aMCI characterization.
Deep Contrast Clustering Analysis to Distinguish Diabetic Complications in Elderly Chinese Patients
Authors: Wang Weihao , Wei Ran , Xiao Pei , Jiang Xun , Chen Zihao , Huang Jinghe , Ma Yanhua , Gao Danni , Shao Jian , Yu Jun , Zhou Kaixin , Chen Chen , Li Ying , Pan Ying , Pan Qi , Jia Tong , Guo Lixin
Published: October 2024

Aim

To establish an innovative clustering method for predicting variable categories of diabetic complications in Chinese ≥ 65 with diabetes.

Materials and methods

We selected and extracted data from elderly patients with diabetes (n = 4980) from a medical examination group of 51,400 people followed up annually from 2014 to date in Kunshan, China. A deep contrast clustering approach was used to cluster and predict diabetic complications. The clustering approach was further validated using data from elderly patients with diabetes (n = 397) from one medical examination cohort of 20,000 people followed up yearly from 2014 to date in Beijing Jiuhua Hospital.

Results

The patients were clustered into 6 categories by analysing 20 indicators. Cluster 1—Heavy smoking and a high cardiovascular disease (CVD) risk; Cluster 2—High alcohol consumption, high aminotransferase levels, the highest risk of stroke complications, and a high fatty liver disease (FLD) risk; Cluster 3—High blood lipid levels and a risk of FLD and stroke complications; Cluster 4—Good health indicators and a low risk of FLD, stroke, and CVD complications; Cluster 5—Older age, higher uric acid concentration and creatinine level, and the highest risk of CVD complications; Cluster 6—Large waist circumference, high BMI, high blood pressure, and the highest risk of FLD complications. The gene for nonalcoholic fatty liver disease in cluster 2 had the highest risk coefficient. This was consistent with cluster 2, which had a higher FLD prevalence.

Conclusions

A new clustering method was developed from two large Chinese cohorts of older patients with diabetes, which may effectively predict complications by clustering into different categories.
Multi‐method approach to assessing the floral‐visiting insect assemblage of rare, ambophilous plant Baccharis vanessae in Southern California
Authors: Simokat Christina , Ferguson Elizabeth L. , Keatly Jessica , Smith Tyler , Lorence Mia , O'Hara Jasmine
Published: October 2024

Insects are the major pollination vectors for angiosperms, and insects native to a given habitat can play an irreplaceable ecological role in food webs and plant reproduction. With precipitous declines in insect species over the last decades, it is urgent to document insect assemblages in native plant communities to support conservation efforts. Identifying pollinators and their pollination activity is challenging; however, emerging technological methods are providing new monitoring capabilities. In this study, we compare the accuracy of two different methods of monitoring to assess the flower‐visiting insect assemblage and likely pollinators of Encinitas baccharis (Baccharis vanessae): focal observations and video recordings from camera traps. B. vanessae is a rare, endemic species found in Coastal Sage Scrub communities in San Diego County. This federally listed species is threatened by habitat loss and fragmentation, which may also be affecting the availability of its insect pollinators. Results indicate that B. vanessae supports and is supported by a variety of flower‐visiting insect groups. The diversity of insect visitors at male and female plants were similar across all diversity measurements. The insect vectors identified were as expected given B. vanessae pollination syndrome. This syndrome also aligns with wind as a pollination vector, providing evidence of ambophily. While focal observations underreported insect activity by approximately half, the proportions of common diurnal visitors were similar with both methods. Camera traps were unable to provide sufficient detail to discern visually similar groups, but were able to record nocturnal insect activity, which was dominated by moths (Lepidoptera, 82%). While collection protocol in this study did not record the time an insect spent interacting with a flower, we anecdotally observed moths spent notably longer periods in contact with flowers than most diurnal insects. This study has implications for effective monitoring and conservation of endangered plant species and their affiliated pollinators.
Colonization of North America Boosted the Diversification of Whiptail Lizards
Authors: Nappo Humberto Coelho , Colli Guarino Rinaldi
Published: October 2024

Diversification is frequently associated with change—anything from colonizing a new area to evolving a new trait. Once a lineage changes, the organisms may be able to exploit previously unavailable ecological opportunities and release pressures from predators, parasites, and competitors, which may increase the speciation rate. Modern teiid lizards originated in South America but managed to colonize and diversify in North America. We assessed whether geographic distribution, body size, and body temperatures are associated with teiid diversification using GeoHiSSE and inverse equal‐splits statistics with simulation tests. We also estimated speciation rates with MiSSE to account for the effect of unmeasured variables. Moreover, we assessed the ecological niche overlap between North American (including Caribbean) teiids and their sister clade in South America. Our results indicate that only distribution range affected diversification, but we discuss that the available data might not have been enough to assess the effect of body temperatures. We also show that North American teiids have a broader ecological niche encompassing almost all environmental conditions used by their sister clade in South America but expanding mainly toward arid areas. Our results suggest that this expansion significantly impacted teiid diversification due to the seizing of ecological opportunities or ecological release, but we do not discard possible effects of phenotypic evolution.
Radical‐Driven Imine Hydrogenation Promoted by the Cooperativity of Nickel and a Redox‐Active Ligand
Authors: Bains Amreen K , Kundu Abhishek , Singh Rahul , Jain Harshit , Adhikari Debashis
Published: October 2024

In the case of N‐alkylation reaction via borrowing hydrogen (BH) methods, imine hydrogenation is one of the critical steps. Mechanistically, the majority of imine hydrogenation, either by dihydrogen gas or by alcohol in case of BH methods, follow two‐electron chemistry, where a metal‐hydride intermediate plays a pivotal role. Herein we demonstrate a completely complementary protocol, where the hydrogenation is governed by a radical pathway. Such a pathway is adopted from the redox active nature of the azophenolate ligand backbone. The facile and reversible 2e−/2H+, azo/hydrazo redox couple in a nickel catalyst helps in storing the hydrogen from alcohol dehydrogenation. An imine substrate is reduced by one‐electron from the azo motif with the assistance of the nickel center. The reduced imine drives a critical hydrogen atom transfer step from the hydrazo motif to conduct the hydrogenation. A set of kinetics experiments including Eyring analysis, radical inhibition experiment along with computational probation attest for the radical‐promoted hydrogenation mechanism.
A Separable Bootstrap Variance Estimation Algorithm for Hierarchical Model‐Based Inference of Forest Aboveground Biomass Using Data From NASA's GEDI and Landsat Missions
Authors: Saarela Svetlana , Healey Sean P. , Yang Zhiqiang , Roald Bjørn‐Eirik , Patterson Paul L. , Gobakken Terje , Næsset Erik , Hou Zhengyang , McRoberts Ronald E. , Ståhl Göran
Published: October 2024

The hierarchical model‐based (HMB) statistical method is currently applied in connection with NASA's Global Ecosystem Dynamics Investigation (GEDI) mission for assessing forest aboveground biomass (AGB) in areas lacking a sufficiently large number of GEDI footprints for employing hybrid inference. This study focuses on variance estimation using a bootstrap procedure that separates the computations into parts, thus considerably reducing the computational time required and making bootstrapping a viable option in this context. The procedure we propose uses a theoretical decomposition of the HMB variance into two parts. Through this decomposition, each variance component can be estimated separately and simultaneously. For demonstrating the proposed procedure, we applied a square‐root‐transformed ordinary least squares (OLS) model, and parametric bootstrapping, in the first modeling step of HMB. In the second step, we applied a random forest model and pairwise bootstrapping. Monte Carlo simulations showed that the proposed variance estimator is approximately unbiased. The study was performed on an artificial copula‐generated population that mimics forest conditions in Oregon, USA, using a dataset comprising AGB, GEDI, and Landsat variables.
Multi‐disciplinary team approach for pediatric hemimegalencephaly: Insights from a single institutional case series
Authors: Edmonds Benjamin , Ngo Jacqueline P. , Groves Aran , Reyes Beck , Gott Rolanda A. , Chia Dennis J. , Mirbaha Hilda , Magaki Shino , Khanlou Negar , Pineles Stacy L. , Salamon Noriko , Thompson Rachel M. , Newman Maya , Rajaraman Rajsekar R. , Hussain Shaun A. , Fallah Aria , Russell Bianca , Nariai Hiroki
Published: October 2024

Recent genetic studies have revealed that hemimegalencephaly (HME) is a multi‐system disorder associated with germline or mosaic variants within the PI3K‐mTOR‐GATOR1 signaling pathways. Patients with HME typically develop drug‐resistant epilepsy necessitating extensive evaluation, hemispherectomy, and long‐term management. We describe the role of a multidisciplinary team (MDT) for the diagnosis and management of recent patients with HME at UCLA who underwent hemispherectomy. Genetic evaluation identified nine patients with the following variants: NPRL3 x2 germline, PIK3CA mosaicism x4, MTOR mosaicism x1, AKT3 mosaicism x1, unknown x1. Each patient's MDT comprised 4–9 specialties. One child with a MTOR variant had persistent epilepsy after hemispherectomy, but addition of everolimus resulted in an 80% decrease in seizure frequency. Another child with hemihypertrophy and PIK3CA mosaic variant was offered targeted PIK3CA inhibitor treatment, alpelisib, for overgrowth. A third child with germline NPRL3 variant inherited from their unaffected mother resulted in a sibling being diagnosed with the variant who later developed seizures secondary to focal cortical dysplasia. The implementation of a MDT offers essential guidance for families affected by HME, encompassing prognostication, surveillance, and therapeutic strategies. Identifying the etiology of HME can facilitate the development of targeted treatments and enable timely genetic counseling.

Plain Language Summary

Hemimegalencephaly (HME) is a complex brain disorder caused by genetic changes. It often leads to severe epilepsy that doesn't respond to standard treatments and frequently requires surgery. In this case series, nine patients with HME were identified and found to have genetic mutations in key growth‐regulating genes. A multidisciplinary team model was developed to facilitate patients' care. For example, one patient's seizures improved with surgery, another with a new targeted medication, and another received treatment for symptoms of overgrowth. This team approach provides comprehensive care for patients and can lead to efficient care coordination and implementation of novel therapies.
Improved Antioxidant, Antihypertensive, and Antidiabetic Activities and Tailored Emulsion Stability and Foaming Properties of Mixture of Corn Gluten and Soy Protein Hydrolysates Via Enzymatic Processing and Fractionation
Authors: Mirzaee Homaira , Ahmadi Gavlighi Hassan , Nikoo Mehdi , Udenigwe Chibuike C. , Rezvankhah Amir , Khodaiyan Faramarz
Published: October 2024

Bioactive peptides and protein hydrolysates have gained considerable attention in the food industry and functional food markets due to their diverse health effects, including antioxidant, antihypertensive, and antidiabetic properties. This study aimed to produce combined soy and corn protein hydrolysates using Alcalase (Al), modification of Al‐hydrolysates through sequential hydrolysis using Flavourzyme (Al‐FL), cross‐linking of Al‐hydrolysates using microbial transglutaminase (MTGase) (Al‐TG), and fractionation of Al‐hydrolysates by ultrafiltration (UF) with molecular weight (MW) cut‐off of 100 (Al‐F4), 30 (Al‐F3), 10 (Al‐F2), and 2 kDa (Al‐F1). Notably, the < 2 kDa fraction (Al‐F1) showcased exceptional biological activities, including antioxidant (81.54% DPPH, 98.02% ABTS), antihypertensive (95.45%), and antidiabetic effects (44.72% α‐glucosidase, 77.52% α‐amylase), linked to its high hydrophobic amino acid content and low molecular weights (111 and 263 Da). Conversely, the higher molecular weight fraction (Al‐TG) excelled in emulsion and foam stability, attributed to its balanced amino acid profile and larger peptides (1385–7057 Da). Our findings reveal that specific protein hydrolysate fractions, particularly Al‐F1 and Al‐TG, are promising for applications in food and pharmaceutical formulations due to their enhanced biological and functional properties.
A Multicriteria Approach for Landslide Hazard Zonation in the Lesser Kumaun Himalaya
Authors: Verma Rahul Kumar , Singh Rajesh , Sharma Prateek , Umrao Ravi Kumar , Singh T. N.
Published: October 2024

The socioeconomic prosperity of a region is intricately tied to its infrastructure development, particularly the connectivity provided by highways. Preserving the economic well‐being of an area demands meticulous planning and the execution of construction projects with minimal risk. Landslide hazard zonation (LHZ) is a crucial tool for assessing the likelihood of landslide occurrences in specific regions. This study delves into the LHZ of a 171.2 km2 area, focusing on critical causative factors such as slope inclination and aspect, slope mass material, Land Use/Land Cover (LULC), distance from fault lines, roads, and drainage systems. The classification resulted in four distinct zones along the National Highway (NH‐109) stretch from Bhowali to Almora. Notably, the moderate‐hazard zone encompasses 60.4% of the area, followed by the high‐hazard zone at 24.4%, the low‐hazard zone at 11.9%, and the very high‐hazard zone at 3.3%. To enhance the reliability of the study, 63 previously identified landslide locations were marked based on diverse sources, including field studies and landslide inventory data from the Geological Survey of India (GSI). In the validation process, 12 past landslide occurrences were situated within the very high‐hazard zone, 32 in the high‐hazard zone, 18 in the moderate‐hazard zone, and only one in the low‐hazard zone. The receiver operating characteristic (ROC) curve yielded a commendable quality with a % area under the curve (AUC) of 71.2%. In summary, this research underscores the importance of LHZ in assessing and mitigating landslide risks along a stretch of the NH‐109 corridor. The findings provide valuable insights for informed decision‐making in infrastructure development and risk management, contributing to the sustainable growth and protection of the region's livelihood.
Assessing the Influence of Zero‐Flow Threshold Choice for Characterising Intermittent Stream Hydrology
Authors: Yu Songyan , Shanafield Margaret , Kennard Mark J.
Published: October 2024

Zero‐flow recordings in gauged streamflow data are critically important for intermittent stream research. Acknowledging the high uncertainty in zero‐flow recordings, many studies pick a small number as zero‐flow threshold, below which the flow is considered to be zero. The choice of zero‐flow threshold is often arbitrary or unjustified, which leads us to wonder: would selecting a slightly different threshold change analysis result significantly? Here, we used a simple sensitivity analysis to assess how the choice of zero‐flow threshold impacts the calculated values of relevant metrics to intermittent stream research. Results show that these metrics tended to be more sensitive to lower zero‐flow thresholds, suggesting that even choosing a slightly different threshold could lead to meaningfully different results from the management perspective. This study highlights the need for reasonable justification of the choice of zero‐flow threshold and concludes with potential ways to reduce uncertainty in zero‐flow measurement.