bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foxp3 inhibitory peptide encapsulated in a novel CD25-targeted nanoliposome promotes efficient tumor regression in mice
Authors: Serrano Alejandro , Casares Noelia , Trocóniz Iñaki F. , Lozano Teresa , Lasarte Juan J. , Zalba Sara , Garrido María J. 
Published: July 2024

AbstractP60, a Foxp3 inhibitory peptide, can hinder the regulatory T cell (Treg) activity and impair tumor proliferation. However, low systemic stability and poor specificity have led to daily dosing to achieve therapeutic effect. Therefore, this study aims to improve P60 stability and specific delivery through its encapsulation in liposomes targeting CD25, constitutively expressed in Tregs. P60 liposomes formulated with DSPE-PEG750 or DSPE-PEG2000 were incubated with DSPE-PEG2000-Maleimide micelles conjugated to Fab’ fragments of anti-CD25 to develop two targeted formulations or immunoliposomes (IL): IL-P602000 (DSPE-PEG2000 only) and IL-P60750 (combining DSPE-PEG750 and DSPE-PEG2000). P60 encapsulation efficiency was 50%–60% irrespective of PEG chain length. Treg uptake was 2.5 and 14 times higher for IL-PEG750 compared with IL-PEG2000 and non-targeted liposomes, respectively, in in-vitro assays. In fact, IL-P60750 allowed CD8+  T cells ex-vivo proliferation in presence of Treg at doses 10–20 times lower than for free P60. Antitumor response of P60 and IL-P60750 in monotherapy and combined with anti-PD-1 was evaluated in MC38 and LLCOVA tumor bearing mice. In MC38 model, IL-P60750 monotherapy induced total tumor regression in 40% of mice reaching 100% for anti-PD-1 combination. This effect was associated with a significant increase in activated CD8+ T cells in tumors. Notably, IL-P60750 also inhibited human Treg in ex-vivo assay, showing the translational capability of this formulation. In conclusion, IL-P60750 formulated with different PEG chain lengths, has demonstrated antitumor efficacy by selective inhibition of Treg activity and enhances the effect of anti-PD1. Altogether, this novel IL represents a promising nanoplatform for cancer immunotherapies.
Cell fate decision by a morphogen-transcription factor-chromatin modifier axis
Authors: Ming Jin , Lin Lihui , Li Jiajun , Wu Linlin , Fang Shicai , Huang Tao , Fu Yu , Liu Dong , Zhang Wenhui , Li Chen , Yang Yongzheng , Huang Yi , Qin Yue , Kuang Junqi , Huang Xingnan , Guo Liman , Zhang Xiaofei , Liu Jing , Chen Jiekai , Zhao Chengchen , Wang Bo , Pei Duanqing 
Published: July 2024

AbstractCell fate decisions remain poorly understood at the molecular level. Embryogenesis provides a unique opportunity to analyze molecular details associated with cell fate decisions. Works based on model organisms have provided a conceptual framework of genes that specify cell fate control, for example, transcription factors (TFs) controlling processes from pluripotency to immunity1. How TFs specify cell fate remains poorly understood. Here we report that SALL4 relies on NuRD (nucleosome-remodeling and deacetylase complex) to interpret BMP4 signal and decide cell fate in a well-controlled in vitro system. While NuRD complex cooperates with SALL4 to convert mouse embryonic fibroblasts or MEFs to pluripotency, BMP4 diverts the same process to an alternative fate, PrE (primitive endoderm). Mechanistically, BMP4 signals the dissociation of SALL4 from NuRD physically to establish a gene regulatory network for PrE. Our results provide a conceptual framework to explore the rich landscapes of cell fate choices intrinsic to development in higher organisms involving morphogen-TF-chromatin modifier pathways.
Efficient reduction-oxidation coupling degradation of nitroaromatic compounds in continuous flow processes
Authors: Mao Yueshuang , Yu Bingnan , Wang Pengfei , Yue Shuai , Zhan Sihui 
Published: July 2024

AbstractNitroaromatic compounds (NACs) with electron-withdrawing nitro (-NO2) groups are typical refractory pollutants. Despite advanced oxidation processes (AOPs) being appealing degradation technologies, inefficient ring-opening oxidation of NACs and practical large-scale applications remain challenges. Here we tackle these challenges by designing a reduction-oxidation coupling (ROC) degradation process in LaFe0.95Cu0.05O3@carbon fiber cloth (LFCO@CFC)/PMS/Vis continuous flow system. Cu doping enhances the photoelectron transfer, thus triggering the -NO2 photoreduction and breaking the barriers in the ring opening. Also, it modulates surface electronic configuration to generate radicals and non-radicals for subsequent oxidation of reduction products. Based on this, the ROC process can effectively remove and mineralize NACs under the environmental background. More importantly, the LFCO catalyst outperformed most of the recently reported catalysts with lower cost (13.72 CNY/ton) and higher processing capacity (3600 t/month). Furthermore, the high scalability, material durability, and catalytic activity of LFCO@CFC under various realistic environmental conditions prove the potential ability for large-scale applications.
High-precision flexible sweat self-collection sensor for mental stress evaluation
Authors: Wang Chenhao , Wang Zhengyu , Wei Wei , Zhang Zhenjie , Li Anne Ailina , Huang Guanghao , Li Xian , Ge Shuzhi Sam , Zhou Lianqun , Kong Hui 
Published: July 2024

AbstractAs a stress hormone existing in the human body, cortisol can reflect the psychological stress and health status in daily life, and is a potential biomarker of the body’s stress response. To effectively collect sweat and accurately identify the target, this paper reports a flexible wearable cortisol detection device with outstanding reliability and sensitivity. Molecular imprinted polymer (MIP) ensures cortisol specificity. And carbon nanotubes (CNT) on electrodes increase sensitivity, expanding the detection range to 10−3 to 104 nM, with sensitivity at 189.2 nA/lg(nM). In addition, porous chitosan hydrogel (PCSH) collects sweat effectively, its adhesive properties and 80% swelling rate offer a low-cost alternative to microfluidics. Flexible printed circuit board (FPCB) and serpentine electrode (SE) ensure device durability. This non-invasive, highly sensitive device offers a novel method for mental stress monitoring and clinical diagnosis, advancing human physiological state monitoring.
Multiferroic quantum material Ba2Cu1−xMnxGe2O7 (0 ≤ x ≤ 1) as a potential candidate for frustrated Heisenberg antiferromagnet
Authors: Thoma Henrik , Dutta Rajesh , Hutanu Vladimir , Granata Veronica , Fittipaldi Rosalba , Zhang Qiang , Lynn Jeffrey W. , Čermák Petr , Khan Nazir , Nandi Shibabrata , Angst Manuel 
Published: July 2024

AbstractMultiferroic Ba2CuGe2O7 was anticipated as a potential member of the exciting group of materials hosting a skyrmion or vortex lattice because of its profound Dzyaloshinskii–Moriya interaction (DMI) and the absence of single ion anisotropy (SIA). This phase, however, could not be evidenced and instead, it exhibits a complex incommensurate antiferromagnetic (AFM) cycloidal structure. Its sister compound Ba2MnGe2O7, in contrast, is characterized by a relatively strong in-plane exchange interaction that competes with a non-vanishing SIA and the weak DMI, resulting in a quasi-two-dimensional commensurate AFM structure. Considering this versatility in the magnetic interactions, a mixed solid solution of Cu and Mn in Ba2Cu1−xMnxGe2O7 can hold an interesting playground for its interactive DMI and SIA depending on the mixed spin states of the transition metal ions towards the skyrmion physics. Here, we present a detailed study of the micro- and macroscopic spin structure of the Ba2Cu1−xMnxGe2O7 solid solution series using high-resolution neutron powder diffraction techniques. We have developed a remarkably rich magnetic phase diagram as a function of the applied magnetic field and x, which consists of two end-line phases separated by a potentially quantum-critical phase at x = 0.57. An AFM conical structure at zero magnetic field is demonstrated to persist up to x = 0.50. Our results provide crucial information on the spin structure and magnetic properties, which are necessary for the general understanding and theoretical developments on multiferroicity in the frame of skyrmion type or frustrated AFM lattice where DMI and SIA play an important role.
Template-assisted covalent modification underlies activity of covalent molecular glues
Authors: Li Yen-Der , Ma Michelle W. , Hassan Muhammad Murtaza , Hunkeler Moritz , Teng Mingxing , Puvar Kedar , Rutter Justine C. , Lumpkin Ryan J. , Sandoval Brittany , Jin Cyrus Y. , Schmoker Anna M. , Ficarro Scott B. , Cheong Hakyung , Metivier Rebecca J. , Wang Michelle Y. , Xu Shawn , Byun Woong Sub , Groendyke Brian J. , You Inchul , Sigua Logan H. , Tavares Isidoro , Zou Charles , Tsai Jonathan M. , Park Paul M. C. , Yoon Hojong , Majewski Felix C. , Sperling Haniya T. , Marto Jarrod A. , Qi Jun , Nowak Radosław P. , Donovan Katherine A. , Słabicki Mikołaj , Gray Nathanael S. , Fischer Eric S. , Ebert Benjamin L. 
Published: July 2024

AbstractMolecular glues are proximity-inducing small molecules that have emerged as an attractive therapeutic approach. However, developing molecular glues remains challenging, requiring innovative mechanistic strategies to stabilize neoprotein interfaces and expedite discovery. Here we unveil a trans-labeling covalent molecular glue mechanism, termed ‘template-assisted covalent modification’. We identified a new series of BRD4 molecular glue degraders that recruit CUL4DCAF16 ligase to the second bromodomain of BRD4 (BRD4BD2). Through comprehensive biochemical, structural and mutagenesis analyses, we elucidated how pre-existing structural complementarity between DCAF16 and BRD4BD2 serves as a template to optimally orient the degrader for covalent modification of DCAF16Cys58. This process stabilizes the formation of BRD4–degrader–DCAF16 ternary complex and facilitates BRD4 degradation. Supporting generalizability, we found that a subset of degraders also induces GAK–BRD4BD2 interaction through trans-labeling of GAK. Together, our work establishes ‘template-assisted covalent modification’ as a mechanism for covalent molecular glues, which opens a new path to proximity-driven pharmacology.
Caspase-4 in glioma indicates deterioration and unfavorable prognosis by affecting tumor cell proliferation and immune cell recruitment
Authors: Di Longjiang , Li Mengyan , Lei Xianli , Xie Wenting , Liu Guoqiang , Wang Yongqing , Zhang Wenjing , Zhu Wei-Guo 
Published: July 2024

AbstractGliomas are the most common malignant tumors of the central nervous system, accounting for approximately 80% of all malignant brain tumors. Accumulating evidence suggest that pyroptosis plays an essential role in the progression of cancer. Unfortunately, the effect of the pyroptosis-related factor caspase-4 (CASP4) on immunotherapy and drug therapy for tumors has not been comprehensively investigated. In this study, we systematically screened six hub genes by pooling differential pyroptosis-related genes in The Cancer Genome Atlas (TCGA) glioma data and the degree of centrality of index-related genes in the protein–protein interaction network. We performed functional and pathway enrichment analyses of the six hub genes to explore their biological functions and potential molecular mechanisms. We then investigated the importance of CASP4 using Kaplan–Meier survival analysis of glioma patients. TCGA and the Chinese Glioma Genome Atlas (CGGA) databases showed that reduced CASP4 expression leads to the potent clinical deterioration of glioma patients. Computational analysis of the effect of CASP4 on the infiltration level and recruitment of glioma immune cells revealed that CASP4 expression was closely associated with a series of tumor-suppressive immune checkpoint molecules, chemokines, and chemokine receptors. We also found that aberrant CASP4 expression correlated with chemotherapeutic drug sensitivity. Finally, analysis at the cellular and tissue levels indicated an increase in CASP4 expression in glioma, and that CASP4 inhibition significantly inhibited the proliferation of glioma cells. Thus, CASP4 is implicated as a new prognostic biomarker for gliomas with the potential to further guide immunotherapy and chemotherapy strategies for glioma patients.
Field evaluation of a volatile pyrethroid spatial repellent and etofenprox treated clothing for outdoor protection against forest malaria vectors in Cambodia
Authors: Vajda Élodie A. , Ross Amanda , Doum Dyna , Fairbanks Emma L. , Chitnis Nakul , Hii Jeffrey , Moore Sarah J. , Richardson Jason H. , Macdonald Michael , Sovannaroth Siv , Kimheng Pen , McIver David J. , Tatarsky Allison , Lobo Neil F. 
Published: July 2024

AbstractCambodia’s goal to eliminate malaria by 2025 is challenged by persistent transmission in forest and forest fringe areas, where people are exposed to Anopheles mosquito bites during the day and night. Volatile pyrethroid spatial repellents (VPSRs) and insecticide-treated clothing (ITC) could address these gaps. This study evaluated the outdoor application of one passive transfluthrin-based VPSR, four etofenprox-ITCs paired with a picaridin topical repellent, and a combination of VPSR and ITC against wild Anopheles landing in Cambodia. A 7 × 7 Latin-square study was conducted over 49 collection nights in temporary open structures in Mondulkiri Province. All interventions substantially reduced Anopheles landing, with protective efficacy ranging from 61 to 95%. Mathematical modeling showed significant reductions in vectoral capacity, especially with the combined ITC and VPSR and VPSR alone, albeit with decreased effectiveness over time. These interventions have the potential to reduce outdoor and daytime Anopheles biting, offering valuable contributions to malaria elimination efforts in Cambodia and the Greater Mekong Subregion, contingent upon achieving effective coverage and adherence.
Joint AI-driven event prediction and longitudinal modeling in newly diagnosed and relapsed multiple myeloma
Authors: Hussain Zeshan , De Brouwer Edward , Boiarsky Rebecca , Setty Sama , Gupta Neeraj , Liu Guohui , Li Cong , Srimani Jaydeep , Zhang Jacob , Labotka Rich , Sontag David 
Published: July 2024

AbstractMultiple myeloma management requires a balance between maximizing survival, minimizing adverse events to therapy, and monitoring disease progression. While previous work has proposed data-driven models for individual tasks, these approaches fail to provide a holistic view of a patient’s disease state, limiting their utility to assist physician decision-making. To address this limitation, we developed a transformer-based machine learning model that jointly (1) predicts progression-free survival (PFS), overall survival (OS), and adverse events (AE), (2) forecasts key disease biomarkers, and (3) assesses the effect of different treatment strategies, e.g., ixazomib, lenalidomide, dexamethasone (IRd) vs lenalidomide, dexamethasone (Rd). Using TOURMALINE trial data, we trained and internally validated our model on newly diagnosed myeloma patients (N = 703) and externally validated it on relapsed and refractory myeloma patients (N = 720). Our model achieved superior performance to a risk model based on the multiple myeloma international staging system (ISS) (p < 0.001, Bonferroni corrected) and comparable performance to survival models trained separately on each task, but unable to forecast biomarkers. Our approach outperformed state-of-the-art deep learning models, tailored towards forecasting, on predicting key disease biomarkers (p < 0.001, Bonferroni corrected). Finally, leveraging our model’s capacity to estimate individual-level treatment effects, we found that patients with IgA kappa myeloma appear to benefit the most from IRd. Our study suggests that a holistic assessment of a patient’s myeloma course is possible, potentially serving as the foundation for a personalized decision support system.
Asteroid (4337) Arecibo: Two ice-rich bodies forming a binary
Authors: Liu Ziyu , Hestroffer Daniel , Desmars Josselin , David Pedro 
Published: July 2024

Context. Binary asteroids are present in all populations of the Solar System, from near-Earth to trans-Neptunian regions. As is true for the small Solar System bodies (SSSBs), binary asteroids generally offer valuable insights into the formation of the Solar System, as well as its collisions and dynamic evolution. In particular, the binaries provide fundamental quantities and properties of these SSSBs, such as mass, angular momentum, and density, all of which are often hidden. The direct measurement of densities and porosities is of great value in revealing the gravitational aggregates and icy bodies that form the asteroid-comet continuum.
Aims. Several observation techniques from space and ground-based platforms have provided many results in this regard. Here we show the value of the Gaia mission and its high-precision astrometry for analysing asteroid binaries and for individually deriving the masses of the components.
Methods. We focus on the binary asteroid (4337) Arecibo, a member of the Themis family. We analysed the astrometry obtained in the Gaia FPR catalogue release, and performed orbital fitting for both the heliocentric orbit of the system and the relative orbit of the binary components.
Results. We obtain an estimation of the component masses and their flux ratio, and derive bulk densities ρ1 ≈ 1.2 and ρ2 ≈ 1.6 for the primary and the secondary, respectively. The results are consistent with an ice-rich body in the outer main belt. They also show a significantly denser secondary or a less closely packed primary. Constraints on these densities and on macroscopic porosities are nevertheless limited by our poor knowledge of the sizes of the components. Observations of future mutual events, and of stellar occultations predicted in 2024–2025, will be essential for improving our knowledge of this system and its formation.
Student Ultrasound Education, Current Views and Controversies; Who Should be Teaching?
Authors: Barth Gregor , Prosch Helmut , Blaivas Michael , Gschmack Anna Maria , Hari Roman , Hoffmann Beatrice , Jenssen Christian , Möller Kathleen , Neubauer Ricarda , Nourkami-Tutdibi Nasenien , Recker Florian , Ruppert Johannes Peter , Von Wangenheim Friederike , Weimer Johannes , Westerway Susan Campbell , Zervides Constantinos , Dietrich Christoph F. 
Published: July 2024

AbstractAcquiring diagnostic ultrasound competencies and skills is crucial in modern health care, and achieving the practical experience is vital in developing the necessary anatomy interpretation and scan acquisition skills. However, traditional teaching methods may not be sufficient to provide hands-on practice, which is essential for this skill acquisition. This paper explores various modalities and instructors involved in ultrasound education to identify the most effective approaches. The field of ultrasound instruction is enriched by the diverse roles of physicians, anatomists, peer tutors, and sonographers. All these healthcare professionals can inspire and empower the next generation of ultrasound practitioners with continuous training and support. Physicians bring their clinical expertise to the table, while anatomists enhance the understanding of anatomical knowledge through ultrasound integration. Peer tutors, often medical students, provide a layer of social congruence and motivation to the learning process. Sonographers provide intensive practical experience and structured learning plans to students. By combining different instructors and teaching methods, success can be achieved in ultrasound education. An ultrasound curriculum organized by experts in the field can lead to more efficient use of resources and better learning outcomes. Empowering students through peer-assisted learning can also ease the burden on faculty. Every instructor must receive comprehensive didactic training to ensure high-quality education in diagnostic ultrasound.
Pediatric Foot: Development, Variants, and Related Pathology
Authors: Morgan Daniel F. , Elangovan Stacey M. , Meyers Arthur B. 
Published: July 2024

AbstractPediatric foot development throughout childhood and adolescence can present a diagnostic dilemma for radiologists because imaging appearances may be confused with pathology. Understanding pediatric foot development and anatomical variants, such as accessory ossification centers, is essential to interpret musculoskeletal imaging in children correctly, particularly because many of these variants are incidental but others can be symptomatic. We first briefly review foot embryology. After describing common accessory ossification centers of the foot, we explain the different patterns of foot maturation with attention to irregular ossification and bone marrow development. Common pediatric foot variants and pathology are described, such as tarsal coalitions and fifth metatarsal base fractures. We also discuss pediatric foot alignment and various childhood foot alignment deformities.
The Pediatric Ankle: Normal Variations and Maturation-Dependent Pathology
Authors: Colucci Philip G. , Sofka Carolyn M. 
Published: July 2024

AbstractThe pediatric ankle can present a broad range of normal variation and pathology unique to certain stages of development. Understanding the expected age ranges of ossification and fusion about the ankle is essential to provide accurate diagnoses regarding skeletal integrity. This conclusion has been well characterized radiographically and is supported by cadaveric research.The range of appearances on magnetic resonance imaging has also been well described. Knowledge about the structure of the periosteum and perichondrium aids in image interpretation as well as explaining typical injury patterns. The expected appearance of the physis and regional bone marrow signal is also of utmost importance.Ultrasonography is a valuable tool in pediatric musculoskeletal imaging but is limited when there is concern for intra-articular pathology. Computed tomography tends to be reserved for preoperative evaluation. We describe normal variation and maturation-dependent pathology of the pediatric ankle with an emphasis on imaging considerations.
Long-Term Safety of a Four-Factor Prothrombin Complex Concentrate (Kcentra®/Beriplex® P/N): An Updated Pharmacovigilance Review
Authors: Milling Truman J. , Voronov Anna , Schmidt Dirk S. , Lindhoff-Last Edelgard 
Published: July 2024

Introduction Four-factor prothrombin complex concentrate (4F-PCC) is recommended for vitamin K antagonist reversal in patients with major bleeding or in need of surgery. The most important risk associated with the use of 4F-PCC is the occurrence of thromboembolic events (TEEs). In this review, we aim to evaluate the safety profile of a 4F-PCC (Kcentra®/Beriplex® P/N; CSL Behring, Marburg, Germany) by reviewing pharmacovigilance data.
Methods A retrospective analysis of postmarketing pharmacovigilance data of Kcentra®/Beriplex® P/N from February 1996 to April 2022 was performed and complemented by a review of clinical studies published between January 2012 and April 2022.
Results A total of 2,321,443 standard infusions of Kcentra®/Beriplex® P/N were administered during the evaluation period. Adverse drug reactions (ADRs) were reported in 614 cases (∼1 per 3,781 standard infusions) and 233 of these cases (37.9%) experienced suspected TEEs related to 4F-PCC (∼1 per 9,963 standard infusions); most of these cases had pre-existing or concomitant conditions likely to be significant risk factors for thrombosis. TEE rates were similar when 4F-PCC was used on-label or off-label for direct oral anticoagulant-associated bleeding. Thirty-six cases (5.9%) reported hypersensitivity type reactions (∼1 per 64,485 standard infusions). No confirmed case of viral transmission related to 4F-PCC use was reported. The published literature also revealed a favorable safety profile of 4F-PCC.
Conclusion Analysis of postmarketing pharmacovigilance safety reports demonstrated that treatment with 4F-PCC was associated with few ADRs and a low rate of TEEs across multiple indications and settings, thus confirming a positive safety profile of 4F-PCC.