bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of apoptosis in B16‐BL6 melanoma cells following exposure to electromagnetic fields modeled after intercellular calcium waves
Authors: Rain Benjamin D. , Plourde‐Kelly Adam D. , Lafrenie Robert M. , Dotta Blake T.
Published: December 2023

Exposure to time‐varying electromagnetic fields (EMF) has the capacity to influence biological systems. Our results demonstrate that exposure to time‐varying EMF modeled after the physiological firing frequency of intercellular calcium waves can inhibit proliferation and induce apoptosis in malignant cells. Single exposure of B16‐BL6 cells to a Ca2+ EMF for 40 min reduced the number of viable cells by 50.3%. Cell imaging with acridine orange and ethidium bromide dye revealed substantial cellular apoptosis, preapoptotic cells, nuclear fragmentation, and large spacing between cells in the Ca2+ EMF condition when compared to the control condition. The ability of Ca2+ EMF to influence the proliferation and survival of malignant cells suggests that exposure to specific EMF may function as a potential anticancer therapy.
Protective Effect of Compound Tongluo Decoction on Brain Vascular Endothelial Cells after Ischemia‐Reperfusion by Inhibition of Ferroptosis Through Regulating Nrf2/ARE/SLC7A11 Signaling Pathway
Authors: Li Peiyi , Wang Zhongda , Zhao Tong , Cheng Xiaolan , Zhang Zhennian , Wang Jingqing , Wang Sulei , Huang Ruiou , Hui Zhen
Published: December 2023

Cerebral infarction is one of the most common diseases for aged people. Compound Tongluo Decoction (CTLD), a classic traditional Chinese Medicine prescription, has been widely used in the treatment of ischemic cerebral infarction. Transient middle cerebral artery occlusion (tMCAO) rat model is established for the animal experiment and oxygen‐glucose deprivation and reperfusion (OGD/R) human umbilical vein endothelial cells (HUVECs) model are established for the cell experiment. This also use Nrf2‐/‐ rats to detect the role of nuclear factor erythroid 2‐related factor 2 (Nrf2). Longa score, Evans blue staining, brain water content measurement, and histological observation are done. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and other ferroptosis‐related components are detected respectively. In the vivo experiment, CTLD relieved ischemia‐reperfusion (IR) injury symptoms and attenuated IR injury in brain tissues of tMCAO rats by relieving peroxidation injury in brain tissues and inhibiting ferroptosis in tMCAO rats. Moreover, CTLD reversed OGD/R‐induced oxidative damage of endothelial cells via suppressing ferroptosis. After knocking out the Nrf2 gene, the protective effect of CTLD is sharply reduced. This study put forward that CTLD can inhibit ferroptosis in I/R‐injured vascular endothelium by regulating Nrf2/ARE/SLC7A11 signaling to improve the relative symptoms of rats after cerebral I/R injury, thus providing a viable treatment option for cerebrovascular disease.
The Effect of Parent Cell Type on Small Extracellular Vesicle‐Derived Vehicle Functionality
Authors: Bheri Sruti , Park Hyun‐Ji , Hoffman Jessica R. , Takaesu Felipe , Davis Michael E.
Published: December 2023

Cell therapies involving c‐kit+ progenitor cells (CPCs) and mesenchymal stem cells (MSCs) have been actively studied for cardiac repair. The benefits of such therapies have more recently been attributed to the release of small extracellular vesicles (sEVs) from the parent cells. These sEVs are 30−180 nm vesicles containing protein/nucleic acid cargo encapsulated within an amphiphilic bilayer membrane. Despite their pro‐reparative effects, sEV composition and cargo loading is highly variable, making it challenging to develop robust therapies with sEVs. Synthetic alternatives have been developed to allow cargo modulation, including prior work from the laboratory, to design sEV‐like vehicles (ELVs). ELVs are synthesized from the sEV membrane but allow controlled cargo loading. It is previously shown that loading pro‐angiogenic miR‐126 into CPC‐derived ELVs significantly increases endothelial cell angiogenesis compared to CPC‐sEVs alone. Here, they expand on this work to design MSC‐derived ELVs  and study the role of the parent cell type on ELV composition and function. It is found that ELV origin does affect the ELV potency and that ELV membrane composition can affect outcomes. This study showcases the versatility of ELVs to be synthesized from different parent cells and highlights the importance of selecting ELV source cells based on the desired functional outcomes.
The Role of the Organic Cation in Developing Efficient Green Perovskite LEDs Based on Quasi‐2D Perovskite Heterostructures
Authors: Ramadan Alexandra J. , Jeong Woo Hyeon , Oliver Robert D. J. , Jiang Junke , Dasgupta Akash , Yuan Zhongcheng , Smith Joel , Lee Jae Eun , Motti Silvia G. , Gough Olivia , Li Zhenlong , Herz Laura M. , Johnston Michael B. , Choi Hyosung , Even Jacky , Katan Claudine , Lee Bo Ram , Snaith Henry J.
Published: December 2023

Two dimensional/three‐dimensional (2D/3D) metal halide perovskite heterostructures have attracted great interest in photovoltaic and light‐emitting diode (LEDs) applications. In both, their implementation results in an improvement in device efficiency yet the understanding of these heterostructures remains incomplete. In this work the role of organic cations, essential for the formation of 2D perovskite structures is unraveled, in a range of metal halide perovskite heterostructures. These heterostructures are used to fabricate efficient green perovskite LEDs and a strong dependence between cation content and device performance is shown. The crystal structure, charge‐carrier transport and dynamics, and the electronic structure of these heterostructures are studied and it is shown that the presence of crystalline 2D perovskite inhibits electron injection and ultimately lowers device performance. This work highlights the importance of optimizing the composition of these heterostructures in ensuring optimal device performance across all parameters and suggests that developing routes to inject charge‐carriers directly into 2D perovskite structures will be important in ensuring the continued development of perovskite LEDs based on these heterostructures.
Mechanistic Insights of Zn‐Ion Storage in Synergistic Vanadium‐Based Composites
Authors: Xing Lingli , Zhang Xinyu , Xu Nuo , Hu Ping , Wang Kun , An Qinyou
Published: December 2023

A novel composite material Na2V6O16·3H2O‐AlxV2O5 (NVO‐AVO) is designed and synthesized for the first time in aqueous zinc ion battery cathode. The electrochemical behavior is elucidated in detail using in situ and ex situ techniques. The NVO‐AVO is simple, inexpensive, and safe to fabricate and contributes to the synergistic effect of orthorhombic AlxV2O5 (AVO) and monoclinic Na2V6O16·3H2O (NVO), the NVO‐AVO composites have fast Zn2+ kinetics and exhibit good electrochemical properties. At 300 mA g−1, the specific capacity is as high as 392.5 mA h g−1, and even more excitingly, NVO‐AVO remains a specific capacity of 160.6 mA h g−1 even after 18 300 cycles at 5000 mA g−1, which is significantly better than the stability of both NVO and AVO. The distinctive V3O8 layered structure in Na2V6O16·3H2O facilitates the diffusion of Zn2+, and structural water located between the V3O8 layers facilitates rapid charge transfer by widening the gallery spacing and supposing more storage sites for Zn2+. In addition, AlxV2O5 forms [AlO6] octahedral units that enhance structural stability and play a crucial role in maintaining long‐term cycling stability. This work supports the theoretical basis and technical support for the development and extension studies of new vanadium‐based electrode materials.
Enhanced Electron Delocalization within Coherent Nano‐Heterocrystal Ensembles for Optimizing Polysulfide Conversion in High‐Energy‐Density Li‐S Batteries
Authors: Zhao Zhiqiang , Pan Yukun , Yi Shan , Su Zhe , Chen Hongli , Huang Yanan , Niu Bo , Long Donghui , Zhang Yayun
Published: December 2023

Commercialization of high energy density Lithium‐Sulfur (Li‐S) batteries is impeded by challenges such as polysulfide shuttling, sluggish reaction kinetics, and limited Li+ transport. Herein, a jigsaw‐inspired catalyst design strategy that involves in situ assembly of coherent nano‐heterocrystal ensembles (CNEs) to stabilize high‐activity crystal facets, enhance electron delocalization, and reduce associated energy barriers is proposed. On the catalyst surface, the stabilized high‐activity facets induce polysulfide aggregation. Simultaneously, the surrounded surface facets with enhanced activity promote Li2S deposition and Li+ diffusion, synergistically facilitating continuous and efficient sulfur redox. Experimental and DFT computations results reveal that the dual‐component hetero‐facet design alters the coordination of Nb atoms, enabling the redistribution of 3D orbital electrons at the Nb center and promoting d‐p hybridization with sulfur. The CNE, based on energy level gradient and lattice matching, endows maximum electron transfer to catalysts and establishes smooth pathways for ion diffusion. Encouragingly, the NbN‐NbC‐based pouch battery delivers a Weight energy density of 357 Wh kg−1, thereby demonstrating the practical application value of CNEs. This work unveils a novel paradigm for designing high‐performance catalysts, which has the potential to shape future research on electrocatalysts for energy storage applications.
Temperature‐Dependent Excitonic Band Gap in Lead‐Free Bismuth Halide Low‐Dimensional Perovskite Single Crystals
Authors: Valastro Salvatore , Gavranovic Stevan , Deretzis Ioannis , Vala Martin , Smecca Emanuele , La Magna Antonino , Alberti Alessandra , Castkova Klara , Mannino Giovanni
Published: December 2023

In this study, the optical behavior of lead‐free Bi‐based low‐dimensional perovskite single crystals (Cs3Bi2Cl9, Cs3Bi2Br9, Cs3Bi2I9, and MA3Bi2I9) is investigated by spectroscopic ellipsometry, supported by X‐ray diffraction and density functional theory calculations. All materials exhibit a strong excitonic peak resulting from photogenerated electron–hole Coulomb interactions, whereas the threshold of continuous absorption is found at higher energies. The resonances of the excitonic and continuous bands, along with exciton binding energies, are extracted through Critical Point Analysis of the ellipsometric data over a wide temperature range (from −90 °C to 90 °C), revealing subtle variations in the optical characteristics for each single crystal. These materials can be applied in optoelectronics as photodetectors because of their high stability and lower toxicity compared to their Pb‐based perovskites.
Long‐Lived UV‐Rewritable Luminescent Memory in a Fluoroperovskite Crystal
Authors: Schuyt Joseph J. , Williams Grant V. M. , Chong Shen V.
Published: December 2023

Photostimulated luminescence phosphors are promising candidates for next‐generation optical data storage devices. Herein, optically‐reversible luminescence modulation is demonstrated using UV wavelengths in the fluoroperovskite RbCdF3:Mn, where the modulation is mediated by photostimulated luminescence processes. UV‐C stimulation enhances the luminescence from Mn2+ centers and simultaneously fills electron traps. This charging process occurs via electron transfer from Mn2+ ions to fluorine vacancies, yielding Mn3+ ions and F‐centers, and is mediated by conduction band transport. UV‐A stimulation restores the material to the initial state. This discharging process occurs via electron transfer from F‐centers to Mn3+ ions and is similarly mediated by conduction band transport. Moreover, the discharging process manifests Mn2+ photostimulated luminescence. The primary trap state has activation energies in the range 1.46 to 1.73 eV and has room temperature lifetimes exceeding 40 000 years. A kinetic model is presented and evaluated that accurately describes the charge transport and luminescence properties of the material. Thus, a material is presented via which ultra‐long term, multi‐level luminescent data storage can be realized, and a model via which precise control over the luminescence modulation and photostimulated luminescence intensities can be achieved.
Two‐Chromatic Printing Creates Skin‐Inspired Geminate Patterns Featuring Crosstalk‐Free Chemical and Physical Colors
Authors: Liu Xiaojun , Cui Shuzhen , Qin Lang , Yu Yanlei
Published: December 2023

Skin‐inspired optical materials that combine both chemical and physical colors provide enhanced information capacity for potential applications in optical multiplexing and anti‐counterfeiting technologies. However, the existing materials suffer from the limitations of an extremely narrow gamut and incompatibility with universal patterning methods to program dual‐mode images. Here, novel two‐chromatic printing technology is proposed to create full‐color, high‐resolution, and geminate patterns by newly designed fluorescent liquid crystal nanocomposites. Such nanocomposites consist of porous cholesteric liquid crystal networks embedded with core–shell CdSe/ZnS quantum dots to produce extended wide color palettes of both photoluminescence and Bragg reflection. The drop‐on‐demand two‐chromatic printing technology simultaneously enables the construction and patterning of the nanocomposites in a high‐precision way, orthogonally tuning the hues of two color palettes according to Grassmann's and Bragg's law. Therefore, the combination of different color generation mechanisms offers a versatile toolbox, which can be generalized to pigmentary, photonic, and even dynamic optical materials.
A Hierarchical Mechanotransduction System: From Macro to Micro
Authors: Cao Rong , Tian Huimin , Tian Yan , Fu Xianghui
Published: December 2023

Mechanotransduction is a strictly regulated process whereby mechanical stimuli, including mechanical forces and properties, are sensed and translated into biochemical signals. Increasing data demonstrate that mechanotransduction is crucial for regulating macroscopic and microscopic dynamics and functionalities. However, the actions and mechanisms of mechanotransduction across multiple hierarchies, from molecules, subcellular structures, cells, tissues/organs, to the whole‐body level, have not been yet comprehensively documented. Herein, the biological roles and operational mechanisms of mechanotransduction from macro to micro are revisited, with a focus on the orchestrations across diverse hierarchies. The implications, applications, and challenges of mechanotransduction in human diseases are also summarized and discussed. Together, this knowledge from a hierarchical perspective has the potential to refresh insights into mechanotransduction regulation and disease pathogenesis and therapy, and ultimately revolutionize the prevention, diagnosis, and treatment of human diseases.
Mapping Cell Atlases at the Single‐Cell Level
Authors: Ye Fang , Wang Jingjing , Li Jiaqi , Mei Yuqing , Guo Guoji
Published: December 2023

Recent advancements in single‐cell technologies have led to rapid developments in the construction of cell atlases. These atlases have the potential to provide detailed information about every cell type in different organisms, enabling the characterization of cellular diversity at the single‐cell level. Global efforts in developing comprehensive cell atlases have profound implications for both basic research and clinical applications. This review provides a broad overview of the cellular diversity and dynamics across various biological systems. In addition, the incorporation of machine learning techniques into cell atlas analyses opens up exciting prospects for the field of integrative biology.
Extracellular Vesicles: The Invisible Heroes and Villains of COVID‐19 Central Neuropathology
Authors: Chang Haiqing , Chen Erya , Hu Yi , Wu Lining , Deng Liyun , Ye‐Lehmann Shixin , Mao Xiaobo , Zhu Tao , Liu Jin , Chen Chan
Published: December 2023

Acknowledging the neurological symptoms of COVID‐19 and the long‐lasting neurological damage even after the epidemic ends are common, necessitating ongoing vigilance. Initial investigations suggest that extracellular vesicles (EVs), which assist in the evasion of the host's immune response and achieve immune evasion in SARS‐CoV‐2 systemic spreading, contribute to the virus's attack on the central nervous system (CNS). The pro‐inflammatory, pro‐coagulant, and immunomodulatory properties of EVs contents may directly drive neuroinflammation and cerebral thrombosis in COVID‐19. Additionally, EVs have attracted attention as potential candidates for targeted therapy in COVID‐19 due to their innate homing properties, low immunogenicity, and ability to cross the blood‐brain barrier (BBB) freely. Mesenchymal stromal/stem cell (MSCs) secreted EVs are widely applied and evaluated in patients with COVID‐19 for their therapeutic effect, considering the limited antiviral treatment. This review summarizes the involvement of EVs in COVID‐19 neuropathology as carriers of SARS‐CoV‐2 or other pathogenic contents, as predictors of COVID‐19 neuropathology by transporting brain‐derived substances, and as therapeutic agents by delivering biotherapeutic substances or drugs. Understanding the diverse roles of EVs in the neuropathological aspects of COVID‐19 provides a comprehensive framework for developing, treating, and preventing central neuropathology and the severe consequences associated with the disease.
ClAg14(C≡CtBu)12 Nanoclusters as Efficient and Selective Electrocatalysts Toward Industrially Relevant CO2 Conversion
Authors: Seong Hoeun , Chang Kiyoung , Sun Fang , Lee Sojung , Han Sang Myeong , Kim Yujin , Choi Chang Hyuck , Tang Qing , Lee Dongil
Published: December 2023

Atomically precise metal nanoclusters (NCs) have emerged as a promising frontier in the field of electrochemical CO2 reduction reactions (CO2RR) because of their distinctive catalytic properties. Although numerous metal NCs are developed for CO2RR, their use in practical applications has suffered from their low‐yield synthesis and insufficient catalytic activity. In this study, the large‐scale synthesis and electrocatalytic performance of ClAg14(C≡CtBu)12+ NCs, which exhibit remarkable efficiency in catalyzing CO2‐to‐CO electroreduction with a CO selectivity of over 99% are reported. The underlying mechanisms behind this extraordinary CO2RR activity of ClAg14(C≡CtBu)12+ NCs are investigated by a combination of electrokinetic and theoretical studies. These analyses reveal that different active sites, generated through electrochemical activation, have unique adsorption properties for the reaction intermediates, leading to enhanced CO2RR and suppressed hydrogen production. Furthermore, industrially relevant CO2‐to‐CO electroreduction using ClAg14(C≡CtBu)12+ NCs in a zero‐gap CO2 electrolyzer, achieving high energy efficiency of 51% and catalyst activity of over 1400 A g−1 at a current density of 400 mA cm−2 is demonstrated.
Revealing The Morphology of Ink and Aerosol Jet Printed Palladium‐Silver Alloys Fabricated from Metal Organic Decomposition Inks
Authors: Farr Nicholas T.H , Davies Matthew , Nohl James , Abrams Kerry J. , Schäfer Jan , Lai Yufeng , Gerling Torsten , Stehling Nicola , Mehta Danielle , Zhang Jingqiong , Mihaylova Lyudmila , Willmott Jon R. , Black Kate , Rodenburg Cornelia
Published: December 2023

Palladium films hold signicance due to their remarkable affinity for hydrogen diffusion, rendering them valauble for the seperation and purification of hydrogen in membrane reactors. However, palladium is expensive, and its films can become brittle after only a few cycles of hydrogen separation. Alloying with silver has been shown to overcome the problem of palladium embrittlement. Palladium‐silver films have been produced via several methods but all have drawbacks, such as difficulties controlling the alloy composition. This study explores two promising jet printing methods: Inkjet and Aerosoljet. Both methods offer potential advantages such as direct patterning, which reduces waste, enables thin film production, and allows for the control of alloy composition. For the first time, palladium‐silver alloys have been produced via inkjet printing using a palladium‐silver metal organic decomposition (MOD) ink, which alloys at a temperature of 300 °C with nitrogen. Similarly, this study also demonstrates a pioneering approach for Aerosol Jet printing, showing the potential of a novel room‐temperature method, for the deposition of palladium‐silver MOD inks. This low temperature approach is considered an important development as palladium‐silver MOD inks are originally designed for deposition on heated substrates.
A Horizontally Transferred Plant Fatty Acid Desaturase Gene Steers Whitefly Reproduction
Authors: Gong Cheng , Guo Zhaojiang , Hu Yuan , Yang Zezhong , Xia Jixing , Yang Xin , Xie Wen , Wang Shaoli , Wu Qingjun , Ye Wenfeng , Zhou Xuguo , Turlings Ted C. J. , Zhang Youjun
Published: December 2023

Polyunsaturated fatty acids (PUFAs) are essential nutrients for all living organisms. PUFA synthesis is mediated by Δ12 desaturases in plants and microorganisms, whereas animals usually obtain PUFAs through their diet. The whitefly Bemisia tabaci is an extremely polyphagous agricultural pest that feeds on phloem sap of many plants that do not always provide them with sufficient PUFAs. Here, a plant‐derived Δ12 desaturase gene family BtFAD2 is characterized in B. tabaci and it shows that the BtFAD2‐9 gene enables the pest to synthesize PUFAs, thereby significantly enhancing its fecundity. The role of BtFAD2‐9 in reproduction is further confirmed by transferring the gene to Drosophila melanogaster, which also increases the fruit fly's reproduction. These findings reveal an extraordinary evolutionary scenario whereby a phytophagous insect acquired a family of plant genes that enables it to synthesize essential nutrients, thereby lessening its nutritional dependency and allowing it to feed and reproduce on many host plants.
BioinspiredLLM: Conversational Large Language Model for the Mechanics of Biological and Bio‐Inspired Materials
Authors: Luu Rachel K. , Buehler Markus J.
Published: December 2023

The study of biological materials and bio‐inspired materials science is well established; however, surprisingly little knowledge is systematically translated to engineering solutions. To accelerate discovery and guide insights, an open‐source autoregressive transformer large language model (LLM), BioinspiredLLM, is reported. The model is finetuned with a corpus of over a thousand peer‐reviewed articles in the field of structural biological and bio‐inspired materials and can be prompted to recall information, assist with research tasks, and function as an engine for creativity. The model has proven that it is able to accurately recall information about biological materials and is further strengthened with enhanced reasoning ability, as well as with Retrieval‐Augmented Generation (RAG) to incorporate new data during generation that can also help to traceback sources, update the knowledge base, and connect knowledge domains. BioinspiredLLM also has shown to develop sound hypotheses regarding biological materials design and remarkably so for materials that have never been explicitly studied before. Lastly, the model shows impressive promise in collaborating with other generative artificial intelligence models in a workflow that can reshape the traditional materials design process. This collaborative generative artificial intelligence method can stimulate and enhance bio‐inspired materials design workflows. Biological materials are at a critical intersection of multiple scientific fields and models like BioinspiredLLM help to connect knowledge domains.
Intense Broadband Emission in the Unconventional 3D Hybrid Metal Halide via High‐Pressure Engineering
Authors: Sun Xuening , Wu Min , Yu Xihan , Li Qian , Xiao Guanjun , Wang Kai , Zou Bo
Published: December 2023

Developing hybrid metal halides with self‐trapped exciton (STE) emission is a powerful and promising approach to achieve single‐component phosphors for wide‐color‐gamut display and illumination. Nevertheless, it is difficult to generate STEs and broadband emission in the classical and widely used 3D systems, owing to the great structural connectivity of metal‐halogen networks. Here, high pressure is implemented to achieve dual emission and dramatical emission enhancement in 3D metal halide of [Pb3Br4][O2C(CH2)2CO2]. The pressure‐induced new emission is ascribed to the radiation recombination of STEs from the Pb2Br2O2 tetrahedra with the promoted distortion through the isostructural phase transition. Furthermore, the wide range of emission chromaticity can be regulated by controlling the distortion order of different polyhedral units upon compression. This work not only constructs the relationship between structure and optical behavior of [Pb3Br4][O2C(CH2)2CO2], but also provides new strategies for optimizing broadband emission toward potential applications in solid‐state lighting.
Accelerating Materials Discovery: Automated Identification of Prospects from X‐Ray Diffraction Data in Fast Screening Experiments
Authors: Schuetzke Jan , Schweidler Simon , Muenke Friedrich R. , Orth Andre , Khandelwal Anurag D. , Breitung Ben , Aghassi‐Hagmann Jasmin , Reischl Markus
Published: December 2023

New materials are frequently synthesized and optimized with the explicit intention to improve their properties to meet the ever‐increasing societal requirements for high‐performance and energy‐efficient electronics, new battery concepts, better recyclability, and low‐energy manufacturing processes. This often involves exploring vast combinations of stoichiometries and compositions, a process made more efficient by high‐throughput robotic platforms. Nonetheless, subsequent analytical methods are essential to screen the numerous samples and identify promising material candidates. X‐ray diffraction is a commonly used analysis method available in most laboratories which gives insight into the crystalline structure and reveals the presence of phases in a powder sample. Herein, a method for automating the analysis of XRD patterns, which uses a neural network model to classify samples into nondiffracting, single‐phase, and multi‐phase structures, is presented. To train neural networks for identifying materials with compositions not matching known crystallographic structures, a synthetic data generation approach is developed. The application of the neural networks on high‐entropy oxides experimental data is demonstrated, where materials frequently deviate from anticipated structures. Our approach, not limited to these materials, seamlessly integrates into high‐throughput data analysis pipelines, either filtering acquired patterns or serving as a standalone method for automated material exploration workflows.
A novel TTC26 variant in a patient with hexadactyly, pituitary stalk interruption, hepatopathy, nephropathy, and bilateral lip‐palate cleft: A case report and expansion of the phenotype
Authors: Papingi Dzhoy , Bierhals Tatjana , Volk Alexander E. , Kutsche Michael , Paul Kevin , Herget Theresia
Published: December 2023

Biallelic pathogenic variants in the TTC26 gene are known to cause BRENS (biliary, renal, neurological, skeletal) syndrome, an ultra‐rare autosomal recessive condition with only few patients published to date. BRENS syndrome is characterized by hexadactyly, severe neonatal cholestasis, and involvement of the brain, heart, and kidney, however the full phenotypic and genotypic spectrum is unknown. Here, we report on a previously undescribed homozygous intronic TTC26 variant (c.1006‐5 T > C) in a patient showing some of the known TTC26‐associated features like hexadactyly, hypopituitarism, hepatopathy, nephropathy, and congenital heart defect. Moreover, he presented with a suspected unilateral hearing loss and bilateral cleft lip‐palate. The variant is considered to affect correct splicing by the loss of the canonical acceptor splice site and activation of a cryptic acceptor splice site. Hereby, our patient represents one additional patient with BRENS syndrome carrying a previously unreported TTC26 variant. Furthermore, we confirm the involvement of the pituitary gland to be a common clinical feature of the syndrome and broaden the clinical spectrum of TTC26 ciliopathy to include facial clefts and a probable hearing involvement.
Effect of landscape attributes on the occurrence of the endangered golden‐headed lion tamarin in southern Bahia, Brazil
Authors: Teixeira Joanison Vicente dos Santos , Bonfim Fernando César Gonçalves , Vancine Maurício Humberto , Ribeiro Milton C. , Oliveira Leonardo de C.
Published: December 2023

The golden‐headed lion tamarin (Leontopithecus chrysomelas) is an endangered primate that occurs exclusively in the Atlantic Forest of southern Bahia, Brazil. Its geographic range has been severely reduced by deforestation and its populations are restricted to a human‐modified landscape consisting primarily of Atlantic forest fragments and shade cacao (Theobroma cacao) agroforestry, locally known as cabrucas. In the last 30 years, there has been a 42% reduction in the geographic range and a 60% reduction in the population size of L. chrysomelas, with only 8% of its habitat represented by protected areas. Thus, we investigated the occurrence of L. chrysomelas in forest fragments and cabrucas based on interviews and using playback census, and evaluated the influence of landscape attributes on its occurrence. The occurrence was measured using a Generalized Linear Model using a set of 12 predictor variables, including fragment size and elevation. L. chrysomelas inhabited 186 (38%) of the 495 forest fragments and cabrucas. Most inhabited habitat patches (n = 169, 91%) are in the eastern portion (ca. 70 km wide region from the Atlantic coast to inland) of its geographic range. The remaining (n = 17, 9%) are in the western portion of the distribution, between 70 and 150 km from the Atlantic coast. Our models indicate a higher occurrence of L. chrysomelas in the eastern portion of its geographic range, where the landscape exhibits lower land cover diversity, greater functional connectivity, lower altitudes (<400 m), and is primarily composed of forest fragments and cabrucas with a higher core percentage. In contrast, we observed a lower occurrence of L. chrysomelas in the western portion, where the landscape is more diverse and heterogeneous due to anthropogenic activities, such as agriculture and livestock. We urge the establishment of ecological corridors via reforestation of degraded areas in the western portion of the range. This increase in habitat availability and suitability in the west together with the protection of the forests and cabrucas in the east would increase our chances of saving L. chrysomelas from extinction.
Age‐related changes in hematological biomarkers in common marmosets
Authors: Hickmott Alexana J. , Cervantes Lidia , Arroyo Juan Pablo , Brasky Kathy , Bene Michael , Salmon Adam B. , Phillips Kimberley A. , Ross Corinna N.
Published: December 2023

Researchers and veterinarians often use hematology and clinical chemistry to evaluate animal health. These biomarkers are relatively easy to obtain, and understanding how they change across healthy aging is critical to clinical care and diagnostics for these animals. We aimed to evaluate how clinical biomarkers from a chemistry profile and complete blood count (CBC) change with age in common marmosets (Callithrix jacchus). We assessed blood samples collected during routine physical exams at the Southwest National Primate Research Center and the University of Texas Health San Antonio marmoset colonies from November 2020–November 2021. We found that chemistry and CBC profiles varied based on facility, sex, and age. Significant changes in albumin, phosphorus/creatinine ratio, albumin/globulin ratio, amylase, creatinine, lymphocyte percent, hematocrit, granulocytes percent, lymphocytes, hemoglobin, red cell distribution width, and platelet distribution width were all reported with advancing age. Aged individuals also demonstrated evidence for changes in liver, kidney, and immune system function compared with younger individuals. Our results suggest there may be regular changes associated with healthy aging in marmosets that are outside of the range typically considered as normal values for healthy young individuals, indicating the potential need for redefined healthy ranges for clinical biomarkers in aged animals. Identifying animals that exhibit values outside of this defined healthy aging reference will allow more accurate diagnostics and treatments for aging colonies.
Determining the minimal clinically important difference for the questionnaire of olfactory disorders in people with cystic fibrosis and factors associated with improvement after highly effective modulator therapy
Authors: Miller Jessa E. , Taylor‐Cousar Jennifer L. , Overdevest Jonathan B. , Khatiwada Aastha , Mace Jess C. , Alt Jeremiah A. , Bodner Todd E. , Chowdhury Naweed I. , DiMango Emily A. , Eshaghian Patricia H. , Getz Anne E. , Gudis David A. , Han Ethan J. , Hwang Peter H. , Keating Claire L. , Khanwalkar Ashoke , Kimple Adam J. , Lee Jivianne T. , Li Douglas , Markarian Karolin , Norris Meghan , Nayak Jayakar V. , Owens Cameran , Patel Zara M. , Poch Katie , Schlosser Rodney J. , Smith Kristine A. , Smith Timothy L. , Soler Zachary M. , Suh Jeffrey D. , Tervo Jeremy P. , Turner Grant A. , Wang Marilene B. , Saavedra Milene T. , Beswick Daniel M.
Published: December 2023

Introduction

Olfactory dysfunction (OD) is common among people with cystic fibrosis (PwCF). The Questionnaire of Olfactory Disorders (QOD) is a validated instrument that evaluates olfactory‐specific quality‐of‐life. The QOD minimal clinically important difference (MCID) and factors associated with olfactory improvement after elexacaftor/tezacaftor/ivacaftor have not been determined for PwCF.

Methods

Prospective observational data were pooled from three studies that enrolled adult PwCF with chronic rhinosinusitis (CRS). QOD scores and disease characteristics were assessed. To evaluate internal consistency and calculate the QOD MCID, Cronbach's alpha and four distribution‐based methods were employed. For participants who enrolled prior to elexacaftor/tezacaftor/ivacaftor, QOD scores were obtained at baseline and after elexacaftor/tezacaftor/ivacaftor initiation. Multivariable regression was used to identify factors associated with QOD improvement.

Results

Of 129 PwCF included, 65 had QOD scores before and 3–6 months after starting elexacaftor/tezacaftor/ivacaftor. Mean baseline QOD score was 6.5 ± 7.9. Mean Cronbach's alpha was ≥0.85. The MCID estimates were as follows: Cohen's effect size = 1.6, standard error of measurement = 2.5, ½ baseline standard deviation = 4.0, and minimal detectable change = 6.9. Mean MCID was 3.7. Of those with pre/post elexacaftor/tezacaftor/ivacaftor QOD scores, the mean change in QOD was −1.3 ± 5.4. After elexacaftor/tezacaftor/ivacaftor, QOD improvement surpassed the MCID in 22% of participants (14/65). Worse baseline QOD scores and nasal polyps were associated with improved QOD scores after elexacaftor/tezacaftor/ivacaftor (both p < 0.04).

Conclusion

The QOD MCID in PwCF was estimated to be 3.7. Elexacaftor/tezacaftor/ivacaftor led to qualitative but not clinically meaningful improvements in QOD score for most PwCF; PwCF with worse baseline QOD scores and nasal polyps improved in a clinically significant manner.
Human postmortem studies as a driver of biomarker development
Authors: Cobos Inma
Published: December 2023

Recent technologies utilizing human postmortem tissue from donors who died with Alzheimer’s disease (AD) and related dementias are advancing our understanding of disease pathogenesis and progression. In this perspective session, I will present recent discoveries from single‐nuclear RNA‐sequencing, spatial multiomics, and the profiling of tangle‐bearing neurons from the human AD brain and their potential and limitations for biomarker discovery.
On the role of neuropsychiatric symptoms as markers for Alzheimer´s disease in an era of disease modifying treatments
Authors: Johansson Maurits
Published: December 2023

Early and reliable detection of Alzheimer’s disease (AD) is fundamental in an era with novel disease modifying treatments on the market. Late in life emerging neuropsychiatric symptoms (NPS) (e.g., apathy, anxiety, depression) have been reported prevalent among cognitively unimpaired (CU) older adults, as well as among patients with Mild Cognitive Impairment (MCI). Findings have indicated that NPS can emerge prior to MCI in ∼50% of cases that subsequently develop a neurocognitive disorder (NCD). Additionally, ∼30% of AD patients have been reported to have received a primary psychiatric diagnosis before their final NCD diagnosis. Combined, these studies point to NPS as important early clinical manifestations of AD. NPS have furthermore been related to several clinically negative outcomes, such as reduced quality of life, increased caregiver burden and earlier institutionalization. Some reports even indicate that NPS can be stronger related to these outcomes than cognition. Importantly, several studies have demonstrated NPS to be predictive of future cognitive decline, dementia, or AD. For example, anxiety in non‐demented subjects has consistently been shown to interact with beta‐amyloid yielding accelerated cognitive decline. NPS are further demonstrated related to AD neuropathological changes including beta‐amyloid, tau, and neurodegeneration. For instance, beta‐amyloid in initially CU elderly has been demonstrated associated with steeper development of NPS over time. Intriguingly, an earlier study has reported the overall burden of NPS to precede memory deficits in its association with early tau deposition in amyloid‐beta positive CU subjects, results supportive of NPS as early markers of dementing biochemical processes. Despite this growing evidence of being both prevalent and early prognostic markers, as well as associated with AD pathology, NPS are only given diminutive consideration in contemporary clinical AD diagnostic criteria. Perhaps so since the added value of NPS in such criteria has rarely been investigated. Consequently, CU subjects with a positive NPS and biomarker status face the risk of not being eligible for a disease modifying treatment since they formally do not fulfill diagnostic criteria for AD. Hence, studies exploring the added value of NPS in clinical diagnostic criteria for AD are prompted.
Comorbid Chronic Conditions and Subjective Cognitive Decline‐ A Snap‐shot
Authors: Gupta Sangeeta
Published: December 2023

Background

Rapidly increasing aging population in Delaware forecasts not only an increased burden of Alzheimer’s disease and related dementias (ADRD) but also a sharp rise in comorbid chronic conditions. Estimating the burden and characteristics of this “dual burden” is critical. Subjective Cognitive Decline (SCD)—a population‐based measure‐ was used to measure ADRD. The primary objective was to study prevalence of selected chronic conditions among Delaware adults with SCD in order to compare the prevalence of chronic conditions among people with and without SCD.

Method

Data for Delaware were obtained from the 2020 Behavioral Risk Factor Surveillance System. Respondents aged 45 years or older who answered the SCD screening question as “yes” or “no” were included in the analyses. Participants were identified as having a diagnosed chronic disease if they had been told by a doctor or other health care provider that they ever had angina; arthritis; asthma; cancer; chronic kidney disease; chronic obstructive pulmonary disease; diabetes; heart attack; and stroke. Descriptive statistics examined sociodemographic characteristics and chronic conditions in Delawareans with and without SCD.

Result

Nearly 1 in 12 of Delaware adults reported SCD. Compared with those without SCD, Delawareans with SCD were two or three times more likely to have angina, heart attack, stroke, diabetes, asthma, COPD, cancer, arthritis, or kidney disease. Nearly eighty percent of Delawareans with SCD have at least one other chronic health condition. More than seventy ‐five percent of Delawareans with SCD were two times as likely to have any one of the selected chronic conditions as compared to those without SCD. Adults with comorbid chronic conditions and SCD were more likely to report functional limitations.

Conclusion

By 2030 the proportion of Delawareans over 60 will nearly double. Study results can facilitate timely targeted interventions to address the burden of SCD and comorbid chronic conditions in Delaware.
The Impact of a High Fat Diet on AD‐risk Associated Genes in a Mouse Model of Alzheimer’s Disease
Authors: Belanger‐Mayer Kasey M , Smith Rachel , Pumiglia Kevin , Zuloaga Kristen L
Published: December 2023

Background

Over 80% of individuals with AD have a co‐morbid metabolic disease, defined as obesity, glucose intolerance, or diabetes. Both metabolic disease and a HF diet cause the release of inflammatory factors, increases AD risk, and alters the expression of hippocampal microvascular genes. Work has increased in identifying specific networks and the genes that drive these networks in AD. We hypothesize that AD causes baseline changes in a specific cluster of genes and when a HF diet is introduced, it further drives alterations of a sub‐population of genes to drive the worsening of AD pathology.

Method

Male wild type (WT) and AppNL‐F knock‐in mice were given a low fat (LF; 10% fat) or high fat (HF; 60% fat; metabolic disease model) diet for 1 month. Weekly weights and end of study visceral fat weight were taken. The hippocampus was rapidly extracted and flash frozen for bulk RNA sequencing and differential gene expression analysis.

Result

On an LF diet, AppNL‐F mice had a greater body weight gain and greater visceral fat compared to WT controls. HF diet increased body weight and visceral fat in WT mice. There was surprisingly no difference between AppNL‐F mice on a LF diet and HF diet in body weight gain and visceral fat. There were 760 significant hippocampal gene alterations between AD and WT mice. Within the WT controls on a LF vs HF diet, there were 213 gene alterations and within the AD model on a LF vs HF diet, there were 31 gene alterations.

Conclusion

AppNL‐F mice on both a LF and HF diet gained equivalent amounts of weight, displaying an altered metabolic profile due to AD alone. While AD alone caused most of the gene alterations, a HF diet further drove alterations in a subset of genes. This work increases our understanding of the contribution of a HF diet to metabolic disease and alterations in AD‐risk associated hippocampal genes to uncover potential modifiable targets. We are currently examining specific clusters of genes and how they are linked to AD pathology, increased inflammation, and vascular dysfunction, and sequencing hippocampal samples from female mice to examine sex differences.
Effects of applying virtual reality in Cognitive Stimulation Therapy (CST) on cognition and functional communication of people with concurrent dementia and visual impairment: An initial study
Authors: Wong Winsy Wing Sze , Tsang Hiu Tung , Luk Chun Lam , Chiu Armstrong Tat San
Published: December 2023

Background

Cognitive stimulation therapy (CST; Spector et al., 2003) is an evidence‐based group therapy for people with dementia. Since multi‐sensory input such as visual, auditory, and tactile stimuli is used during therapy, people with sensory deficit, e.g., visual impairment, may encounter difficulties in perceiving the stimuli presented. Meanwhile, the use of virtual reality (VR) in rehabilitation has been reported in various clinical populations, its benefits on people with concurrent visual impairment and dementia are yet to be explored. The current study aimed to investigate the effects of applying VR to CST on cognition and functional communication of individuals with concurrent visual impairment and dementia.

Method

Five and seven participants with mild to moderate visual impairment completed 14 sessions of CST adopted from Wong (2018) in VR‐CST and conventional conditions, respectively. Processed magnified visual stimuli were presented via head‐mounted displays in the VR group, while stimuli used in the conventional treatment group was displayed via tablets. Participants’ performance on general cognition, different cognitive components, language functions in word and discourse levels, and their functional communication was tapped three times within two weeks prior to/right after treatment, respectively. Tau‐U statistics were applied for pre/post comparison.

Result

No significant improvement was observed in all cognitive measures in the VR‐CST group while positive changes in measures on general cognition, short‐term and working memory, and executive functions were noted in the conventional CST group. Improvements in functional communication were observed in both treatment groups while gains in word comprehension were only seen in the conventional CST group (see Table 1).

Conclusion

This study demonstrated preliminary evidence for the application of VR in CST among people with concurrent visual impairment and dementia.

References:

Spector, A., Thorgrimsen, L., Woods, B., Royan, L., Davies, S., Butterworth, M., & Orrell, M. (2003). Efficiacy of an evidence‐based cognitive stimulation therapy programme for people with dementia. British Journal of Psychiatry, 183, 248‐254.

Wong, G. H., Yek, O. P., Zhang, A. Y., Lum, T. Y., & Spector, A. (2018). Cultural adaptation of cognitive stimulation therapy (CST) for Chinese people with dementia: Multicentre pilot study. International journal of geriatric psychiatry, 33, 841‐848.
Evaluating brain age as a marker of autosomal dominant Alzheimer disease progression
Authors: Millar Peter R , Gordon Brian A. , Benzinger Tammie L.S. , Cruchaga Carlos , Fagan Anne M. , Goate Alison , Hassenstab Jason J. , Holtzman David M. , Llibre‐Guerra Jorge J , Morris John C , Perrin Richard J. , Supnet Charlene B , Xiong Chengjie , Bateman Randall J. , Ances Beau , McDade Eric ,   the Dominantly Inherited Alzheimer Network
Published: December 2023

Background

Estimates of “brain‐predicted age” quantify apparent brain age compared to normative trajectories of neuroimaging features. Brain‐predicted age is elevated in sporadic Alzheimer disease (AD), but is underexplored in autosomal dominant AD (ADAD). We used a previously‐trained model (DeepBrainNet [DBN], Bashyam et al., 2020), which requires minimal MRI pre‐processing, to predict brain age in the Dominantly Inherited Alzheimer Network (DIAN) and evaluated brain age as a marker of ADAD progression.

Method

We used DBN to predict brain age from minimally‐processed, whole‐brain T1 structural MRI scans in 265 ADAD mutation‐carriers (MCs) and 183 non‐carrier controls (NCs). We then tested whether the brain age gap (BAG; difference between predicted and true age) differed as a function of mutation and cognitive status, or estimated years until symptom onset (EYO), and whether it was associated with established markers of amyloid (PiB PET, CSF amyloid‐β‐42/40), phosphorylated tau (CSF and plasma pTau‐181), neurodegeneration (CSF and plasma neurofilament light [NFL]), and cognition (global neuropsychological composite and CDR‐sum of boxes). Finally, we compared BAG to other MRI measures, and examined heterogeneity in BAG as a function of mutation variants (APP vs. PSEN1 before or after codon 200), APOE E4 carrier status, sex, and education.

Result

DBN accurately predicted age in DIAN (Figure 1A). BAG was elevated in symptomatic and asymptomatic MCs, compared to NCs, beginning around ‐10 EYO (Figure 1B,C). BAG, hippocampal volume, and a cortical thickness summary followed similar trajectories across EYO (Figure 1D). BAG was positively associated with PiB PET, CSF and plasma pTau, and CSF and plasma NFL, and was associated with worse cognitive scores, especially in symptomatic MCs (Figure 2). BAG was most elevated in MCs with a PSEN1 mutation before codon 200, but did not differ as a function of APOE, sex, or education (Figure 3).

Conclusion

We extend prior work using BAG from sporadic AD to ADAD, noting consistent results. BAG tracks well with markers of pTau, neurodegeneration, and cognition, but to a lesser extent, amyloid, in ADAD. BAG may capture similar signal to established MRI measures. However, DBN‐based BAG offers unique benefits in simplicity of data processing and interpretation.