bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glass Microneedles: A Case Study for Regulatory Approval Using a Quality by Design Approach
Authors: Sartawi Ziad , Blackshields Caroline , Ariamanesh Arefe , Farag Fatma Fawzy , Griffin Brendan , Crean Abina , Devine Ken , Elkhashab Mohamed , Aldejohann Alexander Maximilian , Kurzai Oliver , Faisal Waleed 
Published: November 2023

AbstractIn this paper, a roadmap is provided for the regulatory approval of one of the exciting and dynamic drug delivery fields, microneedles, by using a Quality by Design approach to pharmaceutical product development. In this regard, a quality target product profile (QTPP) and the critical quality attributes (CQA) of microneedles are identified. A case study of the recently patented method of fabricating glass microneedles entirely from a therapeutic agent, thus eliminating the requirement for additional excipients is discussed. The glass microneedle, ArrayPatch, is a propriety wearable device with platform potential consisting of an array of sharp, but painless, dissolvable microneedles manufactured with 100% drug. The microneedles penetrate the skin on application and dissolve to deliver a locally effective dose. The in vitro characterization of the microneedle CQAs under WHO‐guided stability conditions will be described to assess the manufacturing readiness of ArrayPatch. A live technical video is also provided, presenting a unique procedure of jugular vein cannulation through the ear vein of a pig animal model to study the in vivo pharmacokinetics of ArrayPatch compared to standard‐of‐care marketed products.
Laser‐Activatable In Situ Vaccine Enhances Cancer‐Immunity Cycle
Authors: Wang Zhenyu , You Tingting , Su Qianyi , Deng Wenjia , Li JiaBao , Hu Saixiang , Shi Shengjun , Zou Zhaowei , Xiao Jisheng , Duan Xiaopin 
Published: November 2023

AbstractThe immune response in cancer reflects a series of carefully regulated events; however, current tumor immunotherapies typically address a single key aspect to enhance anti‐tumor immunity. In the present study, a nanoplatform (Fe3O4@IR820@CpG)‐based immunotherapy strategy that targets the multiple key steps in cancer‐immunity cycle is developed: 1) promotes the release of tumor‐derived proteins (TDPs), including tumor‐associated antigens and pro‐immunostimulatory factors), in addition to the direct killing effect, by photothermal (PTT) and photodynamic therapy (PDT); 2) captures the released TDPs and delivers them, together with CpG (a Toll‐like receptor 9 agonist) to antigen‐presenting cells (APCs) to promote antigen presentation and T cell activation; 3) enhances the tumor‐killing ability of T cells by combining with anti‐programmed death ligand 1 antibody (α‐PD‐L1), which collectively advances the outstanding of the anti‐tumor effects on colorectal, liver and breast cancers. The broad‐spectrum anti‐tumor activity of Fe3O4@IR820@CpG with α‐PD‐L1 demonstrates that optimally manipulating anti‐cancer immunity not singly but as a group provides promising clinical strategies.
Transferrin Receptor‐Targeted Nonspherical Microbubbles for Blood–Brain Barrier Sonopermeation
Authors: Dasgupta Anshuman , Sun Tao , Rama Elena , Motta Alessandro , Zhang Yongzhi , Power Chanikarn , Moeckel Diana , Fletcher Stecia‐Marie , Moosavifar Mirjavad , Barmin Roman , Porte Céline , Buhl Eva Miriam , Bastard Céline , Pallares Roger M. , Kiessling Fabian , McDannold Nathan , Mitragotri Samir , Lammers Twan 
Published: November 2023

AbstractMicrobubbles (MB) are widely used for ultrasound (US) imaging and drug delivery. MB are typically spherically shaped, due to surface tension. When heated above their glass transition temperature, polymer‐based MB can be mechanically stretched to obtain an anisotropic shape, endowing them with unique features for US‐mediated blood–brain barrier (BBB) permeation. It is here shown that nonspherical MB can be surface‐modified with BBB‐specific targeting ligands, thereby promoting binding to and sonopermeation of blood vessels in the brain. Actively targeted rod‐shaped MB are generated via 1D stretching of spherical poly(butyl cyanoacrylate) MB and via subsequently functionalizing their shell with antitransferrin receptor (TfR) antibodies. Using US and optical imaging, it is demonstrated that nonspherical anti‐TfR‐MB bind more efficiently to BBB endothelium than spherical anti‐TfR‐MB, both in vitro and in vivo. BBB‐associated anisotropic MB produce stronger cavitation signals and markedly enhance BBB permeation and delivery of a model drug as compared to spherical BBB‐targeted MB. These findings exemplify the potential of antibody‐modified nonspherical MB for targeted and triggered drug delivery to the brain.
Raman‐Active Interlayer Phonons and Moiré Phonons in Twisted Thin‐Layer MoTe2
Authors: Wu Youxuan , Wang Shiyuan , Chen Chuoqi , Zhou Cong , Chen Kun , Zhou Jian , Wang Zhi , Bie Ya‐Qing , Deng Shaozhi 
Published: November 2023

AbstractA wide range of artificially twist‐stacked van der Waals materials offer versatile building blocks for quantum optoelectronic devices. Among these, twisted bilayer MoTe2 has excellent optical properties in the near‐infrared range and can be integrated with silicon photonics. While recent studies mainly focus on the emission properties in twisted bilayer MoTe2, a comprehensive investigation of how Moiré superlattice affects phonon modes in twisted thin‐layer MoTe2 remains unexplored. These phonon modes can serve as indicators of stacking configuration and interface uniformity. Here, a series of twisted bilayer and tetralayer MoTe2 with precisely controlled twist angles ranging from 0° to 60° are prepared. Using polarization‐dependent low‐frequency Raman spectroscopy, the evolution of interlayer phonon modes at different twist angles is identified. Additionally, a range of acoustic phonon modes activated by Moiré potentials in both twisted bilayer MoTe2 and twisted tetralayer MoTe2 are observed and analyzed. The findings provide experimental evidence of the interlayer phonon coupling and Moiré phonons in MoTe2, offering insights for the future development of near‐infrared optoelectronic devices based on twisted thin‐layer MoTe2.
Unveiling the Potential of Sunlight‐Driven Multifunctional Blue Long Persistent Luminescent Materials via Cutting‐Edge Trap Modulation Strategies
Authors: Cao Junlong , Ding Songsong , Zhou Yunpeng , Wang Yuhua 
Published: November 2023

AbstractNumerous challenges persist in the field of long persistent luminescence (LPL) materials, including the unclear mechanism of persistent luminescence, low efficiency of sunlight excitation, and limited availability of commercial materials. To address these issues, a LPL material, SrAl2Si2O8:x% Eu2+,y% Dy3+, is synthesized for excitation by UV lamps or sunlight. Dy3+ doping remarkably extends the afterglow duration from 2 to 7 h under UV lamp excitation, exhibiting a remarkable enhancement of 350%. Notably, SrAl2Si2O8:4.0% Eu2+, 3.0% Dy3+ shows 2 h afterglow duration when exposed to sunlight, surpassing other LPL materials and expanding potential applications. XPS and XANES measurements confirm Eu2+ as the luminescent and persistent luminescent centers, while Dy3+ increases trap diversity. Through meticulous analysis of the EPR and XPS data, it is elucidated that the material encompasses two distinct types of traps, namely oxygen vacancies and may be traps. This provides a basis for subsequent trap analysis in LPL materials. Microstructural analysis examined ion coordination environment changes due to Eu2+ and Dy3+ doping. The mechanical luminescent properties are characterized, and a plausible afterglow mechanism is proposed based on the experimental results, offering insights for further research into LPL materials.
Transition‐Metal‐Catalyzed Cyclization of Alkenyl Iodide
Authors: Jia Yuwei , Liu Qing , Xie Caixia , Li Xiaowei , Liu Hui 
Published: November 2023

AbstractAlkenyl iodide, as an essential precursor and structural unit in organic synthesis, has been widely used in the synthesis of natural products, pharmaceutical pesticides and functional materials. The high reactivity of the Csp2−I bond enables the formation of a C−M bond through oxidative addition, followed by subsequent transformations of the C−M bond to create new chemical bonds. A variety of valuable scaffolds, in particular the cyclic motifs, could be achieved via designing and synthesis the corresponding alkenyl iodide, which makes this strategy to be a hot topic in synthetic chemistry. In this paper, the recent progresses of transition metal‐catalyzed cyclizationof alkenyl iodides are summarized, and the possible mechanisms for most transformations are described in detail.
Ectopic Expression of a Truncated Isoform of Hair Keratin 81 in Breast Cancer Alters Biophysical Characteristics to Promote Metastatic Propensity
Authors: Kang Diane S. , Moriarty Aidan , Wang Yiru Jess , Thomas Amal , Hao Jia , Unger Bret A. , Klotz Remi , Ahmmed Shamim , Amzaleg Yonatan , Martin Stuart , Vanapalli Siva , Xu Ke , Smith Andrew , Shen Keyue , Yu Min 
Published: November 2023

AbstractKeratins are an integral part of cell structure and function. Here, it is shown that ectopic expression of a truncated isoform of keratin 81 (tKRT81) in breast cancer is upregulated in metastatic lesions compared to primary tumors and patient‐derived circulating tumor cells, and is associated with more aggressive subtypes. tKRT81 physically interacts with keratin 18 (KRT18) and leads to changes in the cytosolic keratin intermediate filament network and desmosomal plaque formation. These structural changes are associated with a softer, more elastically deformable cancer cell with enhanced adhesion and clustering ability leading to greater in vivo lung metastatic burden. This work describes a novel biomechanical mechanism by which tKRT81 promotes metastasis, highlighting the importance of the biophysical characteristics of tumor cells.
Bone Marrow‐Derived GCA+ Immune Cells Drive Alzheimer's Disease Progression
Authors: Zhou Rui , Wang Liwen , Chen Linyun , Feng Xu , Zhou Ruoyu , Xiang Peng , Wen Jie , Huang Yan , Zhou Haiyan 
Published: November 2023

AbstractAlzheimer's disease (AD) is an age‐related degenerative disease of the central nervous system (CNS), whereas the role of bone marrow immune cells in the pathogenesis of AD remains unclear. Here, the study reveals that compared to matched healthy individuals, AD patients have higher circulating grancalcin (GCA) levels, which negatively correlate with cognitive function. Bone marrow‐derived GCA+ immune cells, which secret abundant GCA and increase during aging, preferentially invaded the hippocampus and cortex of AD mouse model in a C‐C Motif Chemokine Receptor 10 (CCR10)‐dependent manner. Transplanting GCA+ immune cells or direct stereotaxic injection of recombinant GCA protein intensified amyloid plaque load and aggravated cognitive and memory impairments. In contrast, genetic ablation of GCA in the hematopoietic compartment improves cognitive and memory function. Mechanistically, GCA competitively binds to the low‐density lipoprotein receptor‐related protein 1 (LRP1) in microglia, thus inhibiting phagocytosis and clearance of Aβ and potentiating neuropathological changes. Importantly, GCA‐neutralizing antibody treatment rejuvenated cognitive and memory function and constrained AD progression. Together, the study demonstrates a pathological role of GCA+ immune cells instigating cognitive and memory decline, suggesting that GCA+ immune cells can be a potential target for innovative therapeutic strategies in AD.
Single‐Cell Analysis Reveals Malignant Cells Reshape the Cellular Landscape and Foster an Immunosuppressive Microenvironment of Extranodal NK/T‐Cell Lymphoma
Authors: Li Yi‐Qi , Luo Chun‐Ling , Jiang Jia‐Xin , He Shuai , Liu Yang , Yan Wen‐Xin , Xia Yi , Cui Qian , Huang Ying , Lim Jing Quan , Huang Dachuan , Hussein Izzah Nabilah , Gao Yan , Lin Guo‐Wang , Ling Yi‐Hong , Ma Dong , Zhang Yue‐Tong , Chan Jason Yongsheng , Wei Pan‐Pan , Wang Xiao‐Xiao , Cheng Chee Leong , Xiong Jie , Zhao Wei‐Li , Ong Choon Kiat , Lim Soon Thye , Huang Hui‐Qiang , Peng Rou‐Jun , Bei Jin‐Xin 
Published: November 2023

AbstractExtranodal natural killer/T‐cell lymphoma (NKTCL) is an aggressive type of lymphoma associated with Epstein–Barr virus (EBV) and characterized by heterogeneous tumor behaviors. To better understand the origins of the heterogeneity, this study utilizes single‐cell RNA sequencing (scRNA‐seq) analysis to profile the tumor microenvironment (TME) of NKTCL at the single‐cell level. Together with in vitro and in vivo models, the study identifies a subset of LMP1+ malignant NK cells contributing to the tumorigenesis and development of heterogeneous malignant cells in NKTCL. Furthermore, malignant NK cells interact with various immunocytes via chemokines and their receptors, secrete substantial DPP4 that impairs the chemotaxis of immunocytes and regulates their infiltration. They also exhibit an immunosuppressive effect on T cells, which is further boosted by LMP1. Moreover, high transcription of EBV‐encoded genes and low infiltration of tumor‐associated macrophages (TAMs) are favorable prognostic indicators for NKTCL in multiple patient cohorts. This study for the first time deciphers the heterogeneous composition of NKTCL TME at single‐cell resolution, highlighting the crucial role of malignant NK cells with EBV‐encoded LMP1 in reshaping the cellular landscape and fostering an immunosuppressive microenvironment. These findings provide insights into understanding the pathogenic mechanisms of NKTCL and developing novel therapeutic strategies against NKTCL.
Radiative Cooling for Energy Sustainability: From Fundamentals to Fabrication Methods Toward Commercialization
Authors: So Sunae , Yun Jooyeong , Ko Byoungsu , Lee Dasol , Kim Minkyung , Noh Jaebum , Park Cherry , Park Junkyeong , Rho Junsuk 
Published: November 2023

AbstractRadiative cooling, a technology that lowers the temperature of terrestrial objects by dissipating heat into outer space, presents a promising ecologically‐benign solution for sustainable cooling. Recent years witness substantial progress in radiative cooling technologies, bringing them closer to commercialization. This comprehensive review provides a structured overview of radiative cooling technologies, encompassing essential principles, fabrication techniques, and practical applications, with the goal of guiding researchers toward successful commercialization. The review begins by introducing the fundamentals of radiative cooling and the associated design strategies to achieve it. Then, various fabrication methods utilized for the realization of radiative cooling devices are thoroughly discussed. This discussion includes detailed assessments of scalability, fabrication costs, and performance considerations, encompassing both structural designs and fabrication techniques. Building upon these insights, potential fabrication approaches suitable for practical applications and commercialization are proposed. Further, the recent efforts made toward the practical applications of radiative cooling technology, including its visual appearance, switching capability, and compatibility are examined. By encompassing a broad range of topics, from fundamental principles to fabrication and applications, this review aims to bridge the gap between theoretical research and real‐world implementation, fostering the advancement and widespread adoption of radiative cooling technology.
APP‐C31: An Intracellular Promoter of Both Metal‐Free and Metal‐Bound Amyloid‐β40 Aggregation and Toxicity in Alzheimer's Disease
Authors: Nam Eunju , Lin Yuxi , Park Jiyong , Do Hyunsu , Han Jiyeon , Jeong Bohyeon , Park Subin , Lee Da Yong , Kim Mingeun , Han Jinju , Baik Mu‐Hyun , Lee Young‐Ho , Lim Mi Hee 
Published: November 2023

AbstractIntracellular C‐terminal cleavage of the amyloid precursor protein (APP) is elevated in the brains of Alzheimer's disease (AD) patients and produces a peptide labeled APP‐C31 that is suspected to be involved in the pathology of AD. But details about the role of APP‐C31 in the development of the disease are not known. Here, this work reports that APP‐C31 directly interacts with the N‐terminal and self‐recognition regions of amyloid‐β40 (Aβ40) to form transient adducts, which facilitates the aggregation of both metal‐free and metal‐bound Aβ40 peptides and aggravates their toxicity. Specifically, APP‐C31 increases the perinuclear and intranuclear generation of large Aβ40 deposits and, consequently, damages the nucleus leading to apoptosis. The Aβ40‐induced degeneration of neurites and inflammation are also intensified by APP‐C31 in human neurons and murine brains. This study demonstrates a new function of APP‐C31 as an intracellular promoter of Aβ40 amyloidogenesis in both metal‐free and metal‐present environments, and may offer an interesting alternative target for developing treatments for AD that have not been considered thus far.
Actin Paracrystals Display Double Schottky Diode‐Like Electrical Behavior
Authors: Cantiello Horacio F. , Gutiérrez Brenda C. , Cantero María del Rocío 
Published: November 2023

AbstractActin filaments are abundant intracellular polymers implicated in cell motility and contraction. Actin also forms paracrystalline structures under various conditions, including exposure to lanthanides and other high ionic strength conditions. Here the electrical properties of purified actin paracrystals induced by either MgCl2 or GdCl3 are tested. Tight electrically seal‐voltage‐clamped crystals display strong rectification with a nonlinear conductance under symmetrical and biionic conditions, including 20 mm GdCl3/140 mm KCl and 10 mm MgCl2/140 mm KCl. Rectification is observed in symmetrical ionic conditions with positive‐to‐negative conductance ratios ranging from 4.18 to 9.00 nS. The current‐to‐voltage relationships can be fitted with theoretical double Schottky equations and resemble the behavior of semiconducting nanotubes. The highly nonlinear electrical properties of paracrystalline actin arrays may help explain the physiology of actin‐rich cellular compartments, such as stereocilia of the cochlea and neuronal dendritic spines also suggest potentially relevant nano‐technological properties of this protein.
Incorporating radiation with anti‐CD19 chimeric antigen receptor T‐cell therapy for relapsed/refractory non‐Hodgkin lymphoma: A multicenter consensus approach
Authors: Saifi Omran , Lester Scott C. , Breen William G. , Rule William G. , Lin Yi , Bennani N. Nora , Rosenthal Allison , Munoz Javier , Murthy Hemant S. , Kharfan‐Dabaja Mohamed A. , Peterson Jennifer L. , Hoppe Bradford S. 
Published: November 2023

AbstractAnti‐CD19 chimeric antigen receptor T‐cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B‐cell non‐Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life‐threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre‐existing sites of disease present pre‐CART. Radiation therapy stands as a promising peri‐CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease‐free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post‐CART disease alters the pattern of relapse and improves local recurrence‐free and progression‐free survivals. Salvage radiotherapy for relapsed post‐CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri‐CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART.
VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management
Authors: Koster Matthew J. , Lasho Terra L. , Olteanu Horatiu , Reichard Kaaren K. , Mangaonkar Abhishek , Warrington Kenneth J. , Patnaik Mrinal M. 
Published: November 2023

AbstractVEXAS (Vacuoles, E1 enzyme, X‐linked, Autoinflammatory, Somatic) syndrome is a newly identified disease caused by somatic alterations in UBA1 which produce a recalcitrant inflammatory state along with hematologic disturbances. Patients with VEXAS can have a wide spectrum of clinical symptoms and providers should be familiar with the heterogeneity of associated clinical features. While hematologic parameters may be generally non‐specific, peripheral blood features of macrocytosis, monocytopenia, and/or thrombocytopenia coupled with bone marrow vacuolization of erythroid or myeloid precursors should raise suspicion for this condition. Due to an increased mortality, prompt recognition and accurate diagnosis is paramount. Access to testing for confirmation of UBA1 variants is not yet universally available but clinicians should understand the current available options for genetic confirmation of this disease. Treatment options are limited due to lack of prospective clinical trials but cytokine directed therapies such as interleukin‐6 inhibitors and JAK–STAT inhibitors as well as hypomethylating agents such as azacitidine have shown evidence of partial effect. Though cases are limited, allogeneic stem cell transplantation holds promise for durable response and potential cure. The intent of this review is to outline the pathophysiology of VEXAS syndrome and to provide a practical approach to diagnosis and treatment.