bluuebunny/crossref_metadata_2025 huggingface dataset:
SV2A PET shows hippocampal synaptic loss in cognitively unimpaired APOE ε4/ε4 homozygotes
Authors: Snellman Anniina , Tuisku Jouni , Koivumäki Mikko , Wahlroos Saara , Aarnio Richard , Rajander Johan , Karrasch Mira , Ekblad Laura L. , Rinne Juha O.
Published: October 2024

INTRODUCTION

We investigated hippocampal synaptic density using synaptic vesicle 2A positron emission tomography (PET), and its association with amyloid beta (Aβ) and cognitive performance in healthy apolipoprotein E (APOE) ε4 carriers.

METHODS

Synaptic density was assessed in 46 individuals (APOE ε4/ε4 n = 14; APOE ε3/ε4 n = 16; APOE ε3/ε3 n = 16) with [11C]UCB‐J‐PET standardized uptake value ratios (SUVRs), by using the centrum semiovale as a reference region. Differences in hippocampal [11C]UCB‐J SUVRs were analyzed with analysis of variance (ANOVA) and linear models. Associations among [11C]UCB‐J SUVR, Aβ, hippocampal volume, and cognitive variables were analyzed with Spearman correlation.

RESULTS

Hippocampal synaptic density was different among the APOE groups (PANOVA = 0.016): APOE ε4/ε4 carriers had lower [11C]UCB‐J SUVRs compared to APOE ε3/ε3 (p = 0.013). Hippocampal synaptic density did not correlate with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score (rho = −0.052, p = 0.74), Alzheimer's Prevention Initiative Preclinical Cognitive Composite (APCC) score (rho = 0.17, p = 0.28), or [11C]PiB uptake (rho = −0.10, p = 0.50).

DISCUSSION

Hippocampal synaptic loss emerges early in the AD continuum and is measurable in vivo in cognitively unimpaired high‐risk individuals.

Highlights

Synaptic density was studied in vivo in healthy older adults using [11C]UCB‐J positron emission tomography.

Apolipoprotein E (APOE) ε4/ε4 carriers had lower hippocampal synaptic density compared to APOE ε3/ε3.

Synaptic density was not associated with cognitive performance in this population.

Hippocampal synaptic alterations occur before clinical symptoms in APOE ε4/ε4 carriers.
Directional Subthalamic Deep Brain Stimulation Better Improves Gait and Balance Disorders in Parkinson's Disease Patients: A Randomized Controlled Study
Authors: Cherif Saoussen , Tempier Nicolas , Yeche Mathieu , Temiz Gizem , Perrière Julia , Romanato Marco , Ziri Déborah , Fernandez‐Vidal Sara , Hainque Elodie , Maltête David , Derrey Stéphane , Bardinet Eric , Lau Brian , Karachi Carine , Welter Marie‐Laure
Published: October 2024

Objective

To investigate the effects of directional subthalamic deep brain stimulation (STN‐dDBS) on gait and balance disorders, including freezing of gait (FOG), in patients with advanced Parkinson's disease (PD).

Methods

We included 10 participants who underwent STN‐DBS and presented severe preoperative FOG, in a randomized, double‐blind, crossover study. We used segmented DBS electrodes to investigate whether directing the predicted volume of tissue activated (VTA) to overlap the central STN preferentially improved gait and balance disorders compared to directional DBS applied in the more posterior STN (sensorimotor). We also assessed non‐directional (ring‐mode) STN‐DBS. Our primary outcome was gait and balance control measured using instrumented gait recordings. Each patient had a pre‐operative structural and diffusion‐weighted imaging to model individual VTAs and to examine cortico‐subthalamic connectivity. We used linear mixed‐effects models to contrast the effects of central STN‐dDBS, posterior STN‐dDBS, and ring‐mode STN‐DBS.

Results

Central STN‐dDBS produced significantly better improvement in gait and balance control compared to posterior STN‐dDBS (p = 0.027), with fewer FOG episodes (p < 0.001). Conversely, ring‐mode STN‐DBS resulted in worsened postural control compared to central STN‐dDBS (p = 0.009). The cortico‐subthalamic connectivity with the STN VTAs involved mostly primary sensorimotor, premotor, and medial frontal cortices, with a higher overall cortico‐STN connectivity with ring‐mode STN‐DBS.

Interpretation

Central STN‐dDBS represents the best option to improve gait and balance disorders in PD patients, including FOG. Our findings raise the possibility of reprogramming STN‐DBS toward the central area in selected patients with disabling FOG and/or postural instability after surgery. ANN NEUROL 2025;97:149–162
Association of Seizure Control with Mortality, Cognition, and Function in People With Dementia
Authors: Zawar Ifrah , Quigg Mark , Ghosal Soutik , Punia Vineet , Calle‐Lopez Yamile , Manning Carol , Kapur Jaideep
Published: October 2024

Objectives

The effects of seizure control on outcomes in persons with dementia (PWD) remain unclear. Our study aimed to investigate the impact of seizure control on mortality, function, cognition, and mood among PWD.

Methods

This longitudinal, multicenter study is based on 39 Alzheimer's disease centers (ADCs) in the United States from September 2005 to December 2021. PWD were grouped by seizure status into recurrent (seizures in the past year), remote (prior seizures but none in the past year), and no seizures (controls). The primary outcome was all‐cause mortality among seizure groups. We used Weibull survival analysis to assess the mortality risks by seizure status after adjusting for age, sex, education, race, ethnicity, hypertension, diabetes, hyperlipidemia, degree of cognitive impairment, dominant Alzheimer's disease (AD) mutation, brain trauma, stroke, Parkinson's disease, alcohol abuse, and depression. Cognition (Clinical Dementia Rating), function (physical dependence and nursing home residence), day‐to‐day activities (Functional Assessment Scores), and mood (Geriatric Depression Scale) were compared among seizure groups after adjusting for dementia duration and age.

Results

Among 26,501 participants, 374 (1.4%) had recurrent seizures and 510 (1.9%) had remote seizures. In multivariable survival analysis, recurrent seizures were associated with a higher mortality risk than remote and no seizures (adjusted hazard ratio [aHR], 95% confidence interval [95% CI]; recurrent aHR = 1.79, 95% CI = 1.51 to 2.12; remote aHR = 1.17, 95% CI = 0.98 to 1.38). Median time‐to‐death for recurrent, remote, and no seizures was 2.4, 4.0, and 4.7 years, respectively. People with recurrent seizures had worse cognition, day‐to‐day function, and physical dependence than those with remote seizures and controls.

Interpretation

PWD with poorly controlled recurrent seizures have worse mortality, functional, and cognitive outcomes than PWD with remote and no seizures. These findings underscore the need for timely identification and management of ongoing seizures in PWD. ANN NEUROL 2025;97:358–368
Calcium Carbonate as an Ionic Molecular Lock for Ultrastrong Fluorescence of Single Organic Molecules
Authors: Zhang Jian , Xu Hengyue , Fang Weifeng , Liu Xin , Zhang Haoke , Tang Ruikang , Liu Zhaoming
Published: October 2024

Locking molecular conformation are widely applied in molecular engineering for improved performance. However, locking via organic functional groups often changes the original molecular properties. Following the rigidity and stability of ionic interaction in ionic compounds, we suggested the use of a molecular‐scale ionic compound, calcium carbonate oligomer, as a robust molecular segment to functionalize organic molecules. The rigid structure of the ionic molecular segments locked the organic molecules, which could remarkably limit the intramolecular motion and intermolecular interactions. This ensured a stable and ultrastrong fluorescence of the single organic molecule while preserving its original maximum emission wavelength. The locking strategy was general and extendable to multiple organic molecules. Additionally, the ultrastrong single‐molecular fluorescence can be maintained in inorganic solids with even higher quantum yields and almost unchanged maximum emission wavelength. The highest quantum yield of the investigated molecules reached 99.9 %, superior to all reported organic‐inorganic fluorescent composite under air conditions. This work demonstrates a general strategy to restrict intramolecular motion and intermolecular interactions by using ionic oligomers as molecular locks, providing an alternative method for realizing ultraemissive molecules. This further demonstrates a fascinating example of molecular engineering in the presence of inorganic ionic molecules.
Polar Order in a Fluid Like Ferroelectric with a Tilted Lamellar Structure – Observation of a Polar Smectic C (SmCP) Phase
Authors: Hobbs Jordan , Gibb Calum J. , Pociecha Damian , Szydłowska Jadwiga , Górecka Ewa , Mandle Richard J.
Published: October 2024

The discovery of fluid states of matter with spontaneous bulk polar order is appreciated as a major discovery in the fields of soft matter and liquid crystals. Typically, this manifests as polar order superimposed atop conventional phase structures and is thus far limited to orthogonal phase types. Here we report a family of materials which exhibit a previously unseen state of matter which we conclude is a polar smectic C phase, and so we term it SmCP. The spontaneous polarisation of the SmCP phase is over two orders of magnitude larger than that found in conventional ferroelectric SmC phase of chiral materials used in some LCD devices. Fully atomistic molecular dynamics simulations faithfully and spontaneously reproduce the proposed structure and associated bulk properties; comparison of experimental and simulated X‐ray scattering patterns shows excellent agreement. The materials disclosed here have significantly smaller dipole moments than typical polar liquid crystals such as RM734 which suggests the role of molecular electrical polarity in generating polar order is perhaps overstated, a view supported by consideration of other molecular systems.
Interweavable Metalloporphyrin‐Based Fibers for Indirect Electrocatalysis
Authors: Yao Xiaoman , Liu Gang , Huang Yingying , Huang Caier , Chen Xuanxu , Xuan Zhe , Shi Mingjin , Yang Yiwen , Huang Xianqiang , Chen Yifa , Lan Ya‐Qian
Published: October 2024

The applications of indirect electrocatalysis toward potential industrial processes are drastically limited by the utilization or processing forms of electrocatalysts. The remaining challenges of electrocatalysts like the recycling in homogeneous systems or pulverization in heterogeneous systems call for advanced processing forms to meet the desired requirements. Here, we report a series of metalloporphyrin‐based polymer fibers (M−PF, M=Ni, Cu and Zn) through a rigid‐flexible polymerization strategy based on rigid metalloporphyrin and flexible thiourea units that can be applied as heterogeneous redox‐mediators in indirect electrocatalysis. These functional fibers with high strength and flexibility exhibit interweavable and designable functions that can be processed into different fiber‐forms like knotted, two‐spiral, three‐ply, five‐ply fibers or even interweaved networks. Interestingly, they can be readily applied in S−S bond cleaving/cyclization reaction or extended oxidative self‐coupling reaction of thiols with high efficiency. Remarkably, it enables the scale‐up production (1.25 g in a batch‐experiment) under laboratory conditions.
Sulfur‐Rich Norbornadiene‐Derived Infrared Transparent Polymers by Inverse Vulcanization
Authors: Wuliu Yishun , Dong Weiliang , Huang Guohua , Xie Hui , Yao Pingping , Tan Jiji , Mu Kexin , Zhang Zhili , Chen Yinan , Wang Mingliang , Tian Lei , Zhu Caizhen , Xu Jian
Published: October 2024

Infrared (IR) transparent polymer materials prepared by inverse vulcanization, as a promising candidate to replace inorganic materials, are new materials for constructing key devices in IR optics. However, it is difficult to achieve a balance between infrared optical and thermal properties in polymers due to the intrinsic infrared absorption of organic materials. Herein, our strategy is to construct a high boiling point symmetrical molecular norbornadiene derivative cross‐linking agent (DMMD) which can be inverse vulcanized with molten sulfur, and obtain Poly (S‐r‐DMMD) with different sulfur content by controlling the feed ratio of sulfur. With the rigid core and low IR activity in DMMD, the prepared polymers exhibit tunable thermal properties (Tg: 98.3–119.8 °C) and high IR transmittance (medium‐wave infrared region (MWIR): 42.9–52.6 %; long‐wave infrared region (LWIR): 1.5–5.29 %). In addition, Poly (S‐r‐DMMD) can be used to prepare large‐size free‐standing Fresnel lenses for IR imaging by simple hot‐pressing, which provides flexibility in the design and production of IR fine lenses. This study provides a novel strategy for balancing the thermal and optical properties of IR transparent polymer materials, while providing relevant references for balancing the IR optical and thermal properties of polymer materials.
Enhanced Quantum Efficiency via Co‐Substitution in Red‐Emitting Phosphor Sr2[MgAl5N7] : Eu2+ for Advanced Spectroscopic Applications Including Laser Displays with Ultra‐High Luminescence Saturation Threshold
Authors: Li Zebin , Wang Haoyang , Su Zhezhe , Kang Runtian , Seto Takatoshi , Wang Yuhua
Published: October 2024

In order to obtain novel and more efficient red light‐emitting materials, a series of Sr2[Mg1−xLixAl5−xSixN7] : 0.01Eu2+ (SMAN‐xLS, 0≤x≤0.5) red phosphors were devised and successfully synthesized via the high temperature solid state reaction and the effects of the co‐substitution of [Mg−Al]5+ by [Li−Si]5+ on structural and luminescence properties is investigated in detail. A series of powder XRD data and Rietveld refinement indicate that [Li−Si]5+ co‐substitution can successfully enter the Sr2[MgAl5N7] : 0.01Eu2+ (SMAN) lattice. With the entry of [Li−Si]5+ into the lattice, the substitution of Al3+ by Si4+ leads to the weakening of the nephelauxetic effect of the 5d level of Eu2+, which shifts the emission peak from 657 nm to 647 nm and reduces the excitation in the green region, i.e., lowers the absorption of green light. When the amount of [Li−Si]5+ co‐substitution is x=0.1, the luminescence intensity and thermal stability of the sample are enhanced, in which the external quantum efficiency (EQE), reflecting the luminescence intensity, is elevated by 49.6 %. The increase in lattice rigidity gives rise to higher luminescence intensity, and the introduced trap levels for the compensation of luminescence enhances the thermal stability. Under blue laser excitation, the SMAN‐0.1LS can achieve an ultra‐high luminescence saturation threshold of 52.22 W/mm2, which is remarkably superior to other existing red phosphors, a breakthrough performance that has enormous potential for application in high‐power laser display light sources. Cathodoluminescence (CL) characterization and measurements attest to the favorable CL properties of SMAN‐0.1LS. By measuring the pressure‐dependent luminescence of SMAN‐0.1LS, the emission peak can be shifted from 650 nm to 702 nm with the increase of pressure, and the sensitivity dλ/dP is 5.07 nm/GPa, which is indicative of the potential application of this system as an optical pressure sensor.
Stabilization of Ethane‐Like Dianionic Diborane(6) in Monometallic Titanium Complexes and its Subsequent B(sp3)−B(sp3) Bond Cleavage
Authors: Bairagi Subhash , Giri Soumen , Joshi Gaurav , Jemmis Eluvathingal D. , Ghosh Sundargopal
Published: October 2024

Treatment of [Cp*TiCl3] with [LiBH4 ⋅ THF] followed by thermolysis with [Ph2E2] (E=S or Se) resulted in the formation of classical diborane(6) complexes, [(Cp*Ti)(η4‐B2H4LL′)] (L=C6H4E; L′=C6H5E; 1 a: E=S, 1 b: E=Se), stabilized at titanium template. To the best of our knowledge, they are the first examples of mono‐metallic classical diborane(6) complexes. The bonding analysis and theoretical studies suggest that the stabilization of these diborane(6) species is due to the presence of four bridging ligands in ĸ4‐fashion, where two of them are phenyl thiolates/selenolates that provide more electrons to the electron‐deficient titanium center. Reactions of these diborane(6) species with [M(CO)5 ⋅ THF] (M=Mo, W) led to the cleavage of the electron‐precise B(sp3)−B(sp3) bond that yielded ĸ3‐hydridoborato complexes [(Cp*Ti)(ĸ3‐BH3R)(μ‐EPh)2{M(CO)4}] (2 a–c: R=H, 3 a–c: R=Ph). In an attempt to isolate the Te‐analogue of 1 a–b, a similar reaction was performed; however, the complex was too unstable to be isolated. Interestingly, the treatment of this unstable intermediate with [W(CO)5 ⋅ THF] yielded [(Cp*Ti)(ĸ3‐BH3R)(μ‐TePh)2{W(CO)4}] (2 d: R=H, 3 d: R=Ph) that are analogues of 2 a–c and 3 a–c, respectively. Formation of these species provide indirect evidence for the existence of unstable [(Cp*Ti)(η4‐B2H4LL′)] (L=C6H4Te; L′=C6H5Te; 1 c).
Multidentate Chelating Ligands Enable High‐Performance Zinc‐Bromine Flow Batteries
Authors: Xia Weicheng , Xie Kunchi , Gao Shang , Song Zhen , Chen Long , Li Chunzhong
Published: October 2024

Zinc bromine flow battery (ZBFB) is a promising battery technology for stationary energy storage. However, challenges specific to zinc anodes must be resolved, including zinc dendritic growth, hydrogen evolution reaction, and the occurrence of “dead zinc”. Traditional additives suppress side reactions and zinc dendrite formation by altering the solvation structure of Zn2+ and adsorbing onto the zinc surface through only a limited number of zincophilic sites, resulting in weak adsorption on zinc metal and potential inability to simultaneously optimize the solvation structure of zinc ions. Obviously, increasing the number of potential zincophilic sites in the additive can significantly enhance the interaction with zinc. Herein, we propose a strong chelate, ethylenediamine tetramethylene phosphonic acid (EDTMPA) as the additive, which boasts six potent zincophilic sites, not only promotes the formation of the water‐deficient inner Helmholtz plane but also plays a crucial role in restructuring the solvation environment of Zn2+. As a result, the zinc symmetric flow battery with EDTMPA exhibited exceptional coulombic efficiency of 99.4 % over 800 cycles, surpassing the previous studies by a significant margin. Furthermore, the assembled ZBFB has showcased a dendrite‐free and enduring cycling over 400 cycles at 80 mA cm−2.
Study on flame retardant and smoke suppression of EPDM by sepiolite expansion flame retardant system
Authors: Li Song , Dong Lingbo , Jia Jinyi , Jiang Licong , Xin Zhenxiang , Liu Wei , Li Lin
Published: October 2024

A large amount of smoke will be produced during the combustion of ethylene propylene diene monomer(EPDM), which seriously endangers the environment and personal safety. In this study, K‐SEP was obtained by modifying sepiolite with KH550, and two bio‐based flame retardant and smoke suppression systems AEGS and PEGS were prepared by combining ammonium polyphosphate intumescent flame retardant system (AEG) and piperazine pyrophosphate intumescent flame retardant system (PEG), respectively. The flame retardant and smoke suppression properties of AEGS and PEGS on EPDM matrix composites were investigated. The experimental results show that the LOI values of EPDM/AEGS3 and EPDM/PEGS3 composites with 3 phr K‐SEP are 8.1% and 5.5% higher than those of the blank samples without sepiolite. TSP decreased by 26.3% and 14.3% respectively, which proved that sepiolite has important research value in the field of flame retardant and smoke suppression of polymer materials.
Modification of opto‐electrical behavior of polyvinyl chloride by infusion of SrTiO3 nanofiller synthesized via green route
Authors: Arun K. J. , Muthukrishnan Meena , Manikanda Prabu V. , Thiagamani Senthil Muthu Kumar , Mahmoud Mohamed H.
Published: October 2024

Enhancing the opto‐electrical properties of polymer is crucial for optoelectronic devices. This study emphasis the synthesis of strontium titanate (SrTiO3) nanoparticles using a green sol–gel method and incorporates them into polyvinyl chloride (PVC) to create nanocomposite films via solution casting. The structural, optical, thermal, and electrical properties of PVC with SrTiO3 at concentrations of 1, 3, and 5 wt.% were examined. Better crystallinity was obtained with filler incorporation. Fourier transform infrared shows the physical interaction between nanofiller and the matrix. SEM results suggested that SrTiO3 nanofiller are well distributed in PVC surface. UV–Vis spectroscopy was used to study optical behavior of the nanocomposites. Optical bandgap energy decreased from 3.2 to 2.5 eV with increased concentration of SrTiO3 in PVC matrix. Photoluminescence results show the reduction of electron hole recombination rate. The integration of SrTiO3 nanofiller into the PVC matrix improved the thermal stability, dielectric constant, and the overall performance of the prepared nanocomposite films, making them suitable for high‐temperature optoelectronic and energy storage applications. The green synthesis of SrTiO3 nanofiller also ensures the environmental benefits, high purity, and homogeneity, leading to consistent enhancements in the PVC/SrTiO3 composites. These improvements highlight their potential for advanced optoelectronic devices requiring efficient and durable materials.
Dual drug delivery systems based on natural and synthetic polymer particles for isoniazid and rifampicin vehiculization
Authors: Peverengo María Rocío , Ferrero Francisco J. , Turino Ludmila N. , Karp Federico , López Marcela A. , Luna Julio A. , Mengatto Luciano N.
Published: October 2024

The purpose of this work is the design and characterization of novel systems based on micro and nanoparticles prepared from poly(lactic‐co‐glycolic) acid (PLGA), chitosan (CHT) and gelatin (GEL) for compartmentalization and dual release of rifampicin and isoniazid. The emulsion/evaporation method is employed for the preparation of PLGA based microparticles and nanoparticles. CHT and GEL are used for the preparation of microparticles by spray‐drying. Entrapment efficiencies are in the range of 35%–73% and 5%–29% for rifampicin and isoniazid in PLGA microparticles, respectively. For isoniazid GEL:CHT particles the entrapment efficiencies are within 82%–100%. Isoniazid shows a complete release at acid condition from GEL:CHT particles, while rifampicin release is maintained from GEL:CHT particles or displays an slightly increase from PLGA particles during buffer conditions. Antimycobacterial activity experiments show that the formulations present the ability to inhibit the bacterial growth in comparison with a control culture without treatment. Rifampicin PLGA and isoniazid GEL:CHT microparticles could be used for the preparation of a dual drug delivery system with each antibiotic in a single particulate compartment. GEL:CHT microparticles containing free isoniazid and rifampicin PLGA nanoparticles are a novel two compartment delivery system.
Higher Incidence of Common Polymorphisms in the Genes of Folate and Methionine Cycles in Children With Orofacial Clefs and Congenital Heart Defects Compared to their Unaffected Siblings
Authors: Karas Kuželički Nataša , Šmid Alenka , Vidmar Golja Maša , Kek Tina , Eberlinc Andreja , Geršak Borut , Mazič Uroš , Mlinarič‐Raščan Irena , Geršak Ksenija
Published: October 2024

Background

Uninterrupted folate metabolism plays a vital role in embryonic development, ensuring a supply of one‐carbon‐activated folate cofactors for essential processes. Folate deficiency has been implicated in the development of orofacial clefts (OFC) and congenital heart disease (CHD). Although both malformations have been extensively studied in lieu of folate deficiency, the results of corresponding studies are ambiguous due to the interplay of maternal and fetal genomes controlling folate metabolism in the developing fetus.

Methods

We used the innovative study design to compare affected and unaffected siblings from the same mother, thus minimizing the effect of the maternal genome. Thus, it might be possible to identify genetic markers of congenital malformations that pertain exclusively to the child. This study compared demographic and environmental factors between OFC or CHD‐affected and unaffected pregnancies as well as the presence of polymorphisms in genes of folate metabolism between OFC or CHD‐affected and unaffected siblings.

Results

Only the maternal fever in the first trimester was a risk factor for OFC, whereas the maternal advanced age, medication administration, and common polymorphism in the FPGS gene increased the risk of CHD formation. Both OFC and CHD formation were associated with a higher number of variant loci in genes of folate–methionine cycles.

Conclusions

Both OFC and CHD formation were associated with a higher number of mutated loci in genes of folate–methionine cycles, indicating polygenic and possibly multifactorial inheritance.
Chromatin Accessibility Plays an Important Epigenetic Role on Antibody Expression From CMV Promoter and DNA Elements Flanking the CHO TI Host Landing‐Pad
Authors: Ganapathy Kavya , McKay Andrew , Durinck Steffen , Shi Minyi , Dorighi Kristel , Lam Cynthia , Liang Yuxin , Shen Amy , Barnard Gavin , Misaghi Shahram
Published: October 2024

Targeted integration (TI) Chinese hamster ovary (CHO) platforms are commonly used for protein expression. However, the impact of epigenetic modifications on protein expression in TI cell lines remains elusive since almost all the epigenetic studies focus on random integration (RI) of the gene of interest and only within the promoter region. To address the impact of epigenetic modifications on TI CHO cells, we utilized a standard mAb‐1 to identify and characterize TI clones with the same transgene copy numbers but different levels of transgene transcription and titer. Surprisingly, while CMV promoters were not methylated and histone acetylation/methylation was present, these epigenetic markers did not trend with mRNA transcription and protein expression in our TI model. Instead, ATAC‐seq data analysis revealed that differences in chromatin accessibility within the TI site could be a major factor impacting these observed differences. However, neither chromatin accessibility nor histone acetylation/methylation profiles in early cultures were predictive of high‐expressing clones early during the CLD process. Finally, modulation of the histone profiles (H3K27ac and H3K4me3) at the CMV promoters within the TI integration site using dCas9 fusion proteins was not effective in further increasing mAb titers which could have been likely due to interference of the dCas9 fusion proteins with transcription from the CMV promoters. Overall, our data suggests increasing chromatin accessibility at the TI site is the most effective way to increase mRNA transcription and hence, productivity in TI cell lines.
Perceptions of Multicancer Detection Tests Among Primary Care Physicians and Laypersons: A Qualitative Study
Authors: Samimi Goli , Temkin Sarah M. , Weil Carol J. , Han Paul K. J. , LeeVan Elyse , Rubinstein Wendy S. , Swigart Tessa M. , Caban Sarah , Dent Katherine , Minasian Lori M.
Published: October 2024

Introduction

Multicancer detection tests (MCDs) are blood‐based tests designed to detect multiple cancer types. It is currently unclear whether these cancer screening tests improve mortality. To understand awareness of MCDs among providers and patients, as well as explore how they perceive the benefits, harms, and acceptability of MCDs, we have undertaken a focus group study in primary care physicians (PCPs) and laypersons to explore knowledge, attitudes, and expectations of cancer screening using MCDs.

Methods

We conducted six focus groups with 45 PCP participants and 12 focus groups with 80 layperson participants. Participants were identified via a consumer research firm and found eligible following the completion of a screener survey. Moderators used a semi‐structured guide containing open‐ended questions and prompts to facilitate the discussion. Recordings were transcribed and coded line by line using a codebook developed based on questions and emerging discussion concepts, and emergent themes were identified.

Results

Both PCP and layperson participants felt the that benefits of MCDs included ease of use and potential ability to detect cancers early. However, they felt that additional data is needed to overcome some of the concerns related to MCDs. PCP participants expressed concerns related to lack of practice guidelines, cost of diagnostic follow‐ups, privacy and insurance issues, fear/anxiety related to confirmation of MCD results, and malpractice liability related to perceived false negative test results. Layperson participants expressed concerns related to costs, insurance coverage, and privacy, as well as anxiety over the confirmation of a positive test result.

Conclusions

There is a major need for more rigorous data regarding MCDs to inform the development of guidelines for use as cancer screening tools.
The Rhizome of Atractylodes macrocephala Koidz.: A Comprehensive Review on the Traditional Uses, Phytochemistry and Pharmacology
Authors: Luo Weihong , Zhang Kexin , Wang Yali , Ye Miao , Zhang Yuqin , Xu Wei , Chen Lixia , Li Hua
Published: October 2024

Atractylodes macrocephala Koidz. (A. macrocephala) is a perennial herb of the genus Atractylodes. The rhizome of A. macrocephala (AMR) is its medicinal part. It primarily grows in Southeast Asia and function to invigorate the spleen and qi, drying dampness and removing water. It has long been used for cancer treatment, relieving inflammation, and improving gastrointestinal function, highlighting its remarkable medicinal value. This paper focuses on recent advancements in the traditional uses, phytochemistry, and pharmacology of AMR from 2018 to the present, while exploring its therapeutic and scientific potential. In recent years, more than 120 compounds have been identified in AMR. The primary active components have been identified as sesquiterpenoids, polysaccharides and polyacetylenes. Modern pharmacological studies have demonstrated that AMR has anti‐inflammatory, anti‐tumor, immunity enhancement, gastrointestinal function improvement, and other pharmacological effects. It is mainly employed in the clinical treatment of tumors and gastrointestinal diseases, showing promising developmental potential. Its mechanism may be related to reducing oxidative stress, inhibiting the expression of inflammatory mediators and factors, and alleviating apoptosis through related signaling pathways. It is hoped that this review can provide a theoretical reference and scientific basis for further systematic research and extensive clinical application of AMR.
Annihilation Electrochemiluminescence Triggered by Bipolar Electrochemistry
Authors: Arias‐Aranda Leslie R. , Salinas Gerardo , Li Haidong , Hogan Conor F. , Kuhn Alexander , Bouffier Laurent , Sojic Neso
Published: October 2024

Bipolar electrochemistry (BE) combined with electrochemiluminescence (ECL) has gained considerable attention as a versatile and powerful analytical technique operating in a wireless manner. However, only co‐reactant ECL has been reported so far when using a BE setup. In this work, the generation of annihilation ECL at the anodic extremity of a bipolar electrode (BPE) is demonstrated in two different spatial arrangements of the electrodes. The reported approach is based on a synergetic effect between the asymmetric electroactivity induced across the BPE, which produces different redox states of [Ru(bpy)3]2+, and the electro‐migration mechanism of the formed ionic species, allowing the localization and concentration of the ECL emission. The presented approach demonstrating annihilation ECL via BE, paves the way for the design of easy and straightforward light‐emitting platforms for multiple applications.
Evaluation of Anti‐Alzheimer's Potential of Azo‐Stilbene‐Thioflavin‐T derived Multifunctional Molecules: Synthesis, Metal and Aβ Species Binding and Cholinesterase Activity
Authors: Rana Monika , Terpstra Karna , Gutierrez Citlali , Xu Kerui , Arya Hemant , Bhatt Tarun K. , Mirica Liviu M. , Sharma Anuj K.
Published: October 2024

Inhibition of amyloid β (Aβ) aggregation and cholinesterase activity are two major therapeutic targets for Alzheimer's disease (AD). Multifunctional Molecules (MFMs) specifically designed to address other contributing factors, such as metal ion induced abnormalities, oxidative stress, toxic Aβ aggregates etc. are very much required. Several multifunctional molecules have been developed using different molecular scaffolds. Reported herein is a new series of four MFMs based on ThT, Azo‐stilbene and metal ion chelating pockets. The synthesis, characterization, and metal chelation ability for [Cu2+ and Zn2+] are presented herein. Furthermore, we explored their multifunctionality w.r.t. to their (i) recognition of Aβ aggregates and monomeric form, (ii) utility in modulating the aggregation pathways of both metal‐free and metal‐bound amyloid‐β, (iii) ex‐vivo staining of amyloid plaques in 5xFAD mice brain sections, (iv) ability to scavenge free radicals and (v) ability to inhibit cholinesterase activity. Molecular docking studies were also performed with Aβ peptides and acetylcholinesterase enzyme to understand the observed inhibitory effect on activity. Overall, the studies presented here establish the multifunctional nature of these molecules and qualify them as promising candidates for furthermore investigation in the quest for finding Alzheimer's disease treatment.
Teaching green and sustainable chemistry by the example of wood biorefinery – a teaching and learning sequence for secondary education chemistry classes
Authors: Teplá Alexandra , Hettegger Hubert , Rosenau Thomas , Lembens Anja
Published: October 2024

Wir treffen täglich Wahl‐ und Konsumentscheidungen, die das Ausmaß an Umweltverschmutzungen, Treibhausgasemissionen und Ressourcenverbrauch beeinflussen. Der Umgang mit Produkten der chemischen Industrie ist dabei eine besondere Herausforderung. Verbesserungen chemischer Prozesse unter Berücksichtigung der Prinzipien der Grünen Chemie können helfen, diese Herausforderung zu bewältigen. Zum Schutz des Klimas und der Umwelt brauchen wir verantwortungsbewusste Entscheidungsträger:innen und informierte Bürger:innen gleichermaßen. Um nachhaltige Entscheidungen treffen zu können, ist naturwissenschaftliche Grundbildung notwendig, deren Grundlagen u.a. im Chemieunterricht gelegt werden müssen. In diesem Beitrag stellen wir eine Unterrichtsreihe zur Grünen und nachhaltigen Chemie am Beispiel der Holz‐Bioraffinerie für Lernende der Sek. II vor, die klassische Fachinhalte vor dem Hintergrund nachhaltiger Chemie beleuchtet und dadurch zur Förderung von Urteils‐ und Handlungskompetenz bezüglich aktueller Herausforderungen beiträgt.
Profiling Cysteine Proteases Activities in Neuroinflammatory Cells
Authors: Agost‐Beltrán Laura , Canseco‐Rodríguez Ania , Schirmeister Tanja , Rodríguez Santiago , Sánchez‐Pérez Ana María , González Florenci V.
Published: October 2024

A new activity‐based probe (ABP) of cysteine proteases (FGA139) has been designed and synthesized. The design of the ABP has been done based upon the chemical structure of an irreversible inhibitor of cysteine proteases by attaching a bodipy fluorophore at the N‐terminus of the peptide backbone. The synthetic route of the probe has a metathesis and a “click” reaction as key steps. Although some studies have been reported about the role played by cysteine proteases in neurodegenerative diseases, there are not definitive conclusions. The obtained ABP has been employed as a chemical tool to profile activities of cysteine proteases cathepsins B, L, and calpain in neurodegenerative cell models through confocal imaging. Colocalization of the probe to specific antibodies of the proteases and competitive experiments with non‐fluorescent inhibitors confirm the specificity of the ABP. From a theranostic perspective, our findings strongly suggest that FGA139 exhibits a protective role in various cell lines against oxidative stress or pro‐inflammatory toxicity and it effectively attenuates macrophage activation triggered by LPS.
Progress of Photoantibiotics in Overcoming Antibiotic Resistance
Authors: Bhunia Supriya , Box Sk Majid , Bera Satyajit , Dolai Anirban , Samanta Subhas
Published: October 2024

Antibiotic resistance has emerged as a global public health crisis in the 21st century, leading to treatment failures. To address this issue, the medical and pharmaceutical sectors are confronted with two challenges: i) finding potent new antimicrobial agents that would work against resistant‐pathogens, and ii) developing conceptually new or unconventional strategies by which a particular antibiotic would remain effective persistently. Photopharmacology with the aid of reversibly controllable light‐active antibiotics that we call “photoantibiotics” shows great promise to meet the second challenge, which has inspired many research laboratories worldwide to align their research in inventing or developing such antibiotics. In this review, we have given an overview of the progress made over the last ten years or so towards developing such photoantibiotics. Although making such antibiotics that hold high antimicrobial potency like the native drugs and subsequently maintain a significant activity difference between light‐irradiated and non‐irradiated states is very challenging, the progress being reported here demonstrates the feasibility of various approaches to engineer photoantibiotics. This review provides a future perspective on the use of such antibiotics in clinical practice with the identification of potential problems and their solutions.
Outcomes of pregnancy in patients with chronic myeloid leukemia in the era of tyrosine kinase inhibitors
Authors: Kondo Takeshi , Matsuki Eri , Takaku Tomoiku , Watanabe Naoki , Yoshida Chikashi , Okada Masaya , Murai Kazunori , Kodama Takashi , Takahashi Naoto , Kimura Shinya , Matsumura Itaru ,   Preg‐CML/Japan Study Investigators
Published: October 2024

Background

Young female patients with chronic myeloid leukemia (CML) often face challenges becoming pregnant due to the teratogenicity of tyrosine kinase inhibitors (TKIs).

Methods

The authors conducted a nationwide survey of female patients with CML who experienced pregnancy between 2002 and 2020.

Results

Information for 70 pregnancies in 49 patients was obtained. There were three types of pregnancies: CML onset during pregnancy (n = 9), unplanned pregnancy mostly during treatment with a TKI (n = 25), and planned pregnancy during treatment‐free remission (TFR) or treatment with interferon‐alpha (IFN‐α) (n = 36). The median duration from CML diagnosis to pregnancy in patients with planned pregnancy was significantly longer than that in patients with unplanned pregnancy (10.6 years vs. 4.1 years, p < .001). In 48 pregnancies that resulted in childbirth, TFR and treatment with IFN‐α were chosen in 26 and 17 pregnancies, respectively. Sustained major or deeper molecular response was observed in 18 of 26 pregnancies with TFR. The patients who fulfilled the requirements for TKI therapy discontinuation by European LeukemiaNet recommendations achieved a TFR rate of 77% in pregnancy. Treatment with IFN‐α might be effective for patients who are in complete cytogenetic response or deeper response (response rate, 76%).

Conclusion

Pregnancy by TFR or treatment with IFN‐α could be a safe and feasible way for patients with CML. However, a substantial duration of treatment with a TKI before conception may be needed for planned pregnancy. Planning and evaluation for pregnancy should be considered at the time of CML onset for female patients with childbearing potential.
A phase 2, multicenter, clinical trial of CPX‐351 in older patients with secondary or high‐risk acute myeloid leukemia: PETHEMA‐LAMVYX
Authors: Rodríguez‐Arbolí Eduardo , Rodríguez‐Veiga Rebeca , Soria‐Saldise Elena , Bergua Juan M. , Caballero‐Velázquez Teresa , Arnán Montserrat , Vives Susana , Serrano Josefina , Bernal Teresa , Martínez‐Sánchez Pilar , Tormo Mar , Rodríguez‐Medina Carlos , Herrera‐Puente Pilar , Lavilla‐Rubira Esperanza , Boluda Blanca , Acuña‐Cruz Evelyn , Cano Isabel , Cáceres Sara , Ballesteros Juan , Falantes José , Martínez‐Cuadrón David , Pérez‐Simón José A. , Montesinos Pau ,   the PETHEMA Group
Published: October 2024

Background

LAMVYX was a multicenter, single‐arm, phase 2 trial designed to validate the safety and efficacy of CPX‐351 in patients aged 60–75 years with newly diagnosed, secondary acute myeloid leukemia and to generate evidence on key issues not addressed in the preceding regulatory pivotal trial.

Methods

The primary end point of the study was the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate after induction. Eligible patients were recommended to undergo allogeneic hematopoietic stem cell transplantation after the first consolidation cycle. Alternatively, patients could undergo up to six maintenance cycles with CPX‐351.

Results

Twenty‐nine patients (49%; 95% exact confidence interval [CI], 37%–62%) patients achieved a CR/CRi after one or two cycles of induction, with a measurable residual disease negativity rate of 67% as assessed by centralized, multiparameter flow cytometry. Among patients who had serial next‐generation sequencing analyses available, clearance of somatic mutations that were present at diagnosis was achieved in 7 (35%). The median follow‐up among survivors was 16.8 months (range, 8.7–24.3 months). The median event‐free survival was 3.0 months (95% CI, 1.4–7.3 months), and the median overall survival was 7.4 months (95% CI, 3.7–12.7 months). In landmark analyses at day +100 from diagnosis, the 1‐year overall and event‐free survival rate among patients who underwent allogeneic hematopoietic stem cell transplantation was 70% (95% CI, 47%–100%) and 70% (95% CI, 47%–100%), respectively. The corresponding values were 89% (95% CI, 71%–100%) and 44% (95% CI, 21%–92%), respectively, for patients who entered the maintenance phase. No significant longitudinal changes were observed in severity index or quality‐of‐life visual analog scale scores.

Conclusions

The current data provide novel insights that might inform the clinical positioning and optimal use of CPX‐351, complementing previous results (ClinicalTrials.gov identifier NCT04230239).
Gold Nanoparticles Cause Radiosensitization in 4T1 Cells by Inhibiting DNA Double Strand Break Repair: Single Cell Comparisons of DSB Formation and γH2AX Expression
Authors: Atkinson Jake , Chopin Joshua , Bezak Eva , Le Hien , Kempson Ivan
Published: October 2024

Metal nanoparticles sensitize cancers to radiotherapy however their mechanisms of action are complex. The conceptual inspiration arose from theories of physical dose deposition however various chemical and biological factors have also been identified. Interpretation of data has been limited by challenges in measuring true DNA damage compared to DNA damage repair factors. Here, we applied a new assay, STRIDE, for the first time to measure DNA double strand breaks (DSBs) in 4T1 cells as a model of triple negative breast cancer exposed to gold nanoparticles and radiation, and compared this to the common γH2AX assay for DSB repair. The STRIDE assay showed no increase in DSB detection 15 mins after irradiation for cells containing nanoparticles compared to cells without. Gold nanoparticles led to prolonged detection of DSBs after irradiation and delayed the DSB repair. The data show no evidence of increased radiation dose deposition with nanoparticles, but rather enhanced radiobiological effects resulting from nanoparticles which includes disruption of the recruitment of essential DDR machinery, thereby impairing DNA repair processes.
Radiation and DNA Origami Nanotechnology: Probing Structural Integrity at the Nanoscale
Authors: Ameixa João , Sala Leo , Kocišek Jaroslav , Bald Ilko
Published: October 2024

DNA nanotechnology has emerged as a groundbreaking field, using DNA as a scaffold to create nanostructures with customizable properties. These DNA nanostructures hold potential across various domains, from biomedicine to studying ionizing radiation‐matter interactions at the nanoscale. This review explores how the various types of radiation, covering a spectrum from electrons and photons at sub‐excitation energies to ion beams with high‐linear energy transfer influence the structural integrity of DNA origami nanostructures. We discuss both direct effects and those mediated by secondary species like low‐energy electrons (LEEs) and reactive oxygen species (ROS). Further we discuss the possibilities for applying radiation in modulating and controlling structural changes. Based on experimental insights, we identify current challenges in characterizing the responses of DNA nanostructures to radiation and outline further areas for investigation. This review not only clarifies the complex dynamics between ionizing radiation and DNA origami but also suggests new strategies for designing DNA nanostructures optimized for applications exposed to various qualities of ionizing radiation and their resulting byproducts.
Impacting Non‐Covalent Interactions through Vibrational Strong Coupling
Authors: Maiti Sourav , Maheswar Kothapalli Gnana , Nagarajan Kalaivanan
Published: October 2024

Light‐matter strong coupling, especially Vibrational Strong Coupling (VSC), has become a significant research focus due to its potential to alter materials’ inherent physical and chemical properties. Remarkably, VSC operates even in the absence of light, harnessing subtle quantum fluctuations to influence material characteristics. Vibro‐polaritonic states, which are half photonic and half material, are introduced in the molecular/material energy ladder under VSC conditions. Although the underlying mechanism remains elusive, it is proposed that these hybrid states may modify chemical reactivity and other properties by altering factors such as polarity, polarizability, and Van der Waals interactions. This evolving field, vibro‐polaritonic chemistry, holds vast potential for deeper exploration, particularly within molecular sciences. This Review examines VSC's observed effects on non‐bonding interactions, including hydrogen bonding and π‐π interactions, typically governed by dispersive forces.
Quantification of Sarcoplasmic Reticulum Ca2+ Release in Primary Ventricular Cardiomyocytes
Authors: Afsar Md Nure Alam , Akter Mahmuda , Ko Christopher Y. , Sequeira Vasco , Olgar Yusuf , Johnson Christopher N.
Published: October 2024

In the heart, ion channels generate electrical currents that signal muscle contraction through changes in intracellular calcium concentration, i.e., [Ca2+]. The cardiac ryanodine receptor type 2 (RyR2) is the predominant ion channel responsible for increasing intracellular [Ca2+] by releasing Ca2+ from the sarcoplasmic reticulum (SR). Timely Ca2+ release is necessary for appropriate cardiac function, and dysfunction can cause or contribute to life‐threatening diseases such as arrhythmia. Quantification of SR‐Ca2+ release in the form of sparks and waves can provide valuable insight into RyR2 opening, and factors that influence or regulate channel function. Here, we provide a series of protocols that outline processes for (1) obtaining high‐quality isolated cardiomyocytes, (2) preparing samples for experimentally investigating factors that influence RyR2 function, and (3) data acquisition and analysis. Notably, our protocols leverage the potency of the recently developed myosin ATPase inhibitor, Mavacamten. This affords the opportunity to characterize the effects of small molecules or reconstituted proteins/enzymes on RyR2‐Ca2+ release events across a range of [Ca2+]. © 2024 Wiley Periodicals LLC.

Basic Protocol 1: Cardiomyocyte isolation from mouse

Basic Protocol 2: Preparation of cardiomyocytes for Ca2+ imaging

Basic Protocol 3: Confocal microscopy and quantitative Ca2+ analysis using SparkMaster 2