bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promotion of stem cell-like phenotype of lung adenocarcinoma by FAM83A via stabilization of ErbB2
Authors: Yuan Ye , Hao Liang , Huang Jing-Shan , Zhao Fu-Ying , Ju Ying-Hua , Wang Jia-Mei , Zhang Ting , Li Bai-Qiang , Yu Zhan-Wu 
Published: June 2024

AbstractLung cancer stands as the leading cause of mortality among all types of tumors, with over 40% of cases being lung adenocarcinoma (LUAD). Family with sequence similarity 83 member A (FAM83A) emerges as a notable focus due to its frequent overexpression in LUAD. Despite this, the precise role of FAM83A remains elusive. This study addresses this gap by unveiling the crucial involvement of FAM83A in maintaining the cancer stem cell-like (CSC-like) phenotype of LUAD. Through a global proteomics analysis, the study identifies human epidermal growth factor receptor 2 (HER2 or ErbB2) as a crucial target of FAM83A. Mechanistically, FAM83A facilitated ErbB2 expression at the posttranslational modification level via the E3 ubiquitin ligase STUB1 (STIP1-homologous U-Box containing protein 1). More importantly, the interaction between FAM83A and ErbB2 at Arg241 promotes calcineurin (CALN)-mediated dephosphorylation of ErbB2, followed by inhibition of STUB1-mediated ubiquitin-proteasomal ErbB2 degradation. The maintenance of the CSC-like phenotype by FAM83A, achieved through the posttranslational regulation of ErbB2, offers valuable insights for identifying potential therapeutic targets for LUAD.
Oligomerization regulates the interaction of Gemin5 with members of the SMN complex and the translation machinery
Authors: Francisco-Velilla Rosario , Abellan Salvador , Embarc-Buh Azman , Martinez-Salas Encarnacion 
Published: June 2024

AbstractRNA-binding proteins are multifunctional molecules impacting on multiple steps of gene regulation. Gemin5 was initially identified as a member of the survival of motor neurons (SMN) complex. The protein is organized in structural and functional domains, including a WD40 repeats domain at the N-terminal region, a tetratricopeptide repeat (TPR) dimerization module at the central region, and a non-canonical RNA-binding site at the C-terminal end. The TPR module allows the recruitment of the endogenous Gemin5 protein in living cells and the assembly of a dimer in vitro. However, the biological relevance of Gemin5 oligomerization is not known. Here we interrogated the Gemin5 interactome focusing on oligomerization-dependent or independent regions. We show that the interactors associated with oligomerization-proficient domains were primarily annotated to ribosome, splicing, translation regulation, SMN complex, and RNA stability. The presence of distinct Gemin5 protein regions in polysomes highlighted differences in translation regulation based on their oligomerization capacity. Furthermore, the association with native ribosomes and negative regulation of translation was strictly dependent on both the WD40 repeats domain and the TPR dimerization moiety, while binding with the majority of the interacting proteins, including SMN, Gemin2, and Gemin4, was determined by the dimerization module. The loss of oligomerization did not perturb the predominant cytoplasmic localization of Gemin5, reinforcing the cytoplasmic functions of this essential protein. Our work highlights a distinctive role of the Gemin5 domains for its functions in the interaction with members of the SMN complex, ribosome association, and RBP interactome.
A pan-KRAS degrader for the treatment of KRAS-mutant cancers
Authors: Yang Jie , Wang Qiao-Li , Wang Guan-Nan , Ye Jia-Cong , Li Zi-Qian , Wang Jing-Yun , Liang Zhao-Hui , Li Shu-Xin , Sun Cong , Liao Wen-Ting , Gao Yi-Jun , Wang Jing , Mao Yong , Yu Chunjing , Feng Guo-Kai , Zeng Mu-Sheng 
Published: June 2024

AbstractKRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting “undruggable” proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.
BAG6 restricts pancreatic cancer progression by suppressing the release of IL33-presenting extracellular vesicles and the activation of mast cells
Authors: Alashkar Alhamwe Bilal , Ponath Viviane , Alhamdan Fahd , Dörsam Bastian , Landwehr Clara , Linder Manuel , Pauck Kim , Miethe Sarah , Garn Holger , Finkernagel Florian , Brichkina Anna , Lauth Matthias , Tiwari Dinesh Kumar , Buchholz Malte , Bachurski Daniel , Elmshäuser Sabrina , Nist Andrea , Stiewe Thorsten , Pogge von Strandmann Lisa , Szymański Witold , Beutgen Vanessa , Graumann Johannes , Teply-Szymanski Julia , Keber Corinna , Denkert Carsten , Jacob Ralf , Preußer Christian , Pogge von Strandmann Elke 
Published: June 2024

AbstractRecent studies reveal a critical role of tumor cell-released extracellular vesicles (EVs) in pancreatic cancer (PC) progression. However, driver genes that direct EV function, the EV-recipient cells, and their cellular response to EV uptake remain to be identified. Therefore, we studied the role of Bcl-2-associated-anthanogene 6 (BAG6), a regulator of EV biogenesis for cancer progression. We used a Cre recombinase/LoxP-based reporter system in combination with single-cell RNA sequencing to monitor in vivo EV uptake and tumor microenvironment (TME) changes in mouse models for pancreatic ductal adenocarcinoma (PDAC) in a Bag6 pro- or deficient background. In vivo data were validated using mouse and human organoids and patient samples. Our data demonstrated that Bag6-deficient subcutaneous and orthotopic PDAC tumors accelerated tumor growth dependent on EV release. Mechanistically, this was attributed to mast cell (MC) activation via EV-associated IL33. Activated MCs promoted tumor cell proliferation and altered the composition of the TME affecting fibroblast polarization and immune cell infiltration. Tumor cell proliferation and fibroblast polarization were mediated via the MC secretome containing high levels of PDGF and CD73. Patients with high BAG6 gene expression and high protein plasma level have a longer overall survival indicating clinical relevance. The current study revealed a so far unknown tumor-suppressing activity of BAG6 in PDAC. Bag6-deficiency allowed the release of EV-associated IL33 which modulate the TME via MC activation promoting aggressive tumor growth. MC depletion using imatinib diminished tumor growth providing a scientific rationale to consider imatinib for patients stratified with low BAG6 expression and high MC infiltration.
Can traditional oral hygiene methods compete with conventional toothbrushes in effectiveness?
Authors: Almutairi Waleed , Duane Brett 
Published: June 2024

Abstract
Design
The study was designed as a single-blinded, parallel, randomized controlled trial to compare the effectiveness of the Salvadora persica toothbrush (MTB), Salvadora persica chewing stick (MCS), and a standard toothbrush (STB) in controlling plaque and gingivitis. A total of 78 participants were randomly divided into three groups and instructed to use their assigned oral hygiene tool in a standardized manner for three.

Case selection
Participants were non-dental students and staff of Universiti Kebangsaan Malaysia, Kuala Lumpur Campus, selected through convenience sampling. They met specific inclusion criteria, such as being systemically healthy, having ≥20 teeth, and having a Basic Periodontal Examination score of 0, 1, or 2, with no periodontal pockets greater than 5.5 mm.

Data analysis
Clinical outcomes were measured using the Plaque Index (PI) and Periodontal Inflamed Surface Area (PISA) at baseline, one-, and three-weeks post-intervention. Data analysis was performed using mixed-model analysis of variance for continuous variables and Fisher’s exact test for categorical variables.

Results
All three groups showed significant improvements in plaque levels and severity of gingivitis from baseline to three weeks post-intervention. The MCS group demonstrated a significant improvement in mean PISA values of the anterior teeth compared to the MTB and STB groups. However, there was no significant difference in plaque level reduction or overall gingivitis severity among the three groups. This indicates that when used correctly, Salvadora persica toothbrushes and chewing sticks are as effective as standard toothbrushes in plaque control and gingival health.

Conclusions
The study concludes that both Salvadora persica toothbrushes and chewing sticks can serve as effective alternatives to the standard toothbrush for plaque control and gingival health. This showcases the beneficial anti-plaque and anti-gingivitis properties of Salvadora persica. However, the effectiveness of these oral hygiene tools is contingent upon the correct usage techniques.
A popcorn-inspired strategy for compounding graphene@NiFe2O4 flexible films for strong electromagnetic interference shielding and absorption
Authors: Liu Mingjie , Wang Zhiyuan , Song Zhaoqiang , Wang Fangcheng , Zhao Guangyao , Zhu Haojie , Jia Zhuofei , Guo Zhenbin , Kang Feiyu , Yang Cheng 
Published: June 2024

AbstractCompounding functional nanoparticles with highly conductive and porous carbon scaffolds is a basic pathway for engineering many important functional devices. However, enabling uniform spatial distribution of functional particles within a massively conjugated, monolithic and mesoporous structure remains challenging, as the high processing temperature for graphitization can arouse nanoparticle ripening, agglomerations and compositional changes. Herein, we report a unique “popcorn-making-mimic” strategy for preparing a highly conjugated and uniformly compounded graphene@NiFe2O4 composite film through a laser-assisted instantaneous compounding method in ambient condition. It can successfully inhibit the unwanted structural disintegration and mass loss during the laser treatment by avoiding oxidation, bursting, and inhomogeneous heat accumulations, thus achieving a highly integrated composite structure with superior electrical conductivity and high saturated magnetization. Such a single-sided film exhibits an absolute shielding effectiveness of up to 20906 dB cm2 g−1 with 75% absorption rate, superior mechanical flexibility and excellent temperature/humidity aging reliability. These performance indexes signify a substantial advance in EMI absorption capability, fabrication universality, small form-factor and device reliability toward commercial applications. Our method provides a paradigm for fabricating sophisticated composite materials for versatile applications.
Immersive scene representation in human visual cortex with ultra-wide-angle neuroimaging
Authors: Park Jeongho , Soucy Edward , Segawa Jennifer , Mair Ross , Konkle Talia 
Published: June 2024

AbstractWhile human vision spans 220°, traditional functional MRI setups display images only up to central 10-15°. Thus, it remains unknown how the brain represents a scene perceived across the full visual field. Here, we introduce a method for ultra-wide angle display and probe signatures of immersive scene representation. An unobstructed view of 175° is achieved by bouncing the projected image off angled-mirrors onto a custom-built curved screen. To avoid perceptual distortion, scenes are created with wide field-of-view from custom virtual environments. We find that immersive scene representation drives medial cortex with far-peripheral preferences, but shows minimal modulation in classic scene regions. Further, scene and face-selective regions maintain their content preferences even with extreme far-periphery stimulation, highlighting that not all far-peripheral information is automatically integrated into scene regions computations. This work provides clarifying evidence on content vs. peripheral preferences in scene representation and opens new avenues to research immersive vision.
Magnon-phonon Fermi resonance in antiferromagnetic CoF2
Authors: Metzger Thomas W. J. , Grishunin Kirill A. , Reinhoffer Chris , Dubrovin Roman M. , Arshad Atiqa , Ilyakov Igor , de Oliveira Thales V. A. G. , Ponomaryov Alexey , Deinert Jan-Christoph , Kovalev Sergey , Pisarev Roman V. , Katsnelson Mikhail I. , Ivanov Boris A. , van Loosdrecht Paul H. M. , Kimel Alexey V. , Mashkovich Evgeny A. 
Published: June 2024

AbstractUnderstanding spin-lattice interactions in antiferromagnets is a critical element of the fields of antiferromagnetic spintronics and magnonics. Recently, coherent nonlinear phonon dynamics mediated by a magnon state were discovered in an antiferromagnet. Here, we suggest that a strongly coupled two-magnon-one phonon state in this prototypical system opens a novel pathway to coherently control magnon-phonon dynamics. Utilizing intense narrow-band terahertz (THz) pulses and tunable magnetic fields up to μ0Hext = 7 T, we experimentally realize the conditions of magnon-phonon Fermi resonance in antiferromagnetic CoF2. These conditions imply that both the spin and the lattice anharmonicities harvest energy from the transfer between the subsystems if the magnon eigenfrequency fm is half the frequency of the phonon 2fm = fph. Performing THz pump-infrared probe spectroscopy in conjunction with simulations, we explore the coupled magnon-phonon dynamics in the vicinity of the Fermi-resonance and reveal the corresponding fingerprints of nonlinear interaction facilitating energy exchange between these subsystems.
Variegated overexpression of chromosome 21 genes reveals molecular and immune subtypes of Down syndrome
Authors: Donovan Micah G. , Eduthan Neetha P. , Smith Keith P. , Britton Eleanor C. , Lyford Hannah R. , Araya Paula , Granrath Ross E. , Waugh Katherine A. , Enriquez Estrada Belinda , Rachubinski Angela L. , Sullivan Kelly D. , Galbraith Matthew D. , Espinosa Joaquin M. 
Published: June 2024

AbstractIndividuals with Down syndrome, the genetic condition caused by trisomy 21, exhibit strong inter-individual variability in terms of developmental phenotypes and diagnosis of co-occurring conditions. The mechanisms underlying this variable developmental and clinical presentation await elucidation. We report an investigation of human chromosome 21 gene overexpression in hundreds of research participants with Down syndrome, which led to the identification of two major subsets of co-expressed genes. Using clustering analyses, we identified three main molecular subtypes of trisomy 21, based on differential overexpression patterns of chromosome 21 genes. We subsequently performed multiomics comparative analyses among subtypes using whole blood transcriptomes, plasma proteomes and metabolomes, and immune cell profiles. These efforts revealed strong heterogeneity in dysregulation of key pathophysiological processes across the three subtypes, underscored by differential multiomics signatures related to inflammation, immunity, cell growth and proliferation, and metabolism. We also observed distinct patterns of immune cell changes across subtypes. These findings provide insights into the molecular heterogeneity of trisomy 21 and lay the foundation for the development of personalized medicine approaches for the clinical management of Down syndrome.
eReaxFF force field development for BaZr0.8Y0.2O3-δ solid oxide electrolysis cells applications
Authors: Hossain Md Jamil , Gaikwad Prashik , Shin Yun Kyung , Schulze Jessica A. , Penrod Katheryn A. , Li Meng , Lin Yuxiao , Pawar Gorakh , van Duin Adri C. T. 
Published: June 2024

AbstractThe use of solid-oxide materials in electrocatalysis applications, especially in hydrogen-evolution reactions, is promising. However, further improvements are warranted to overcome the fundamental bottlenecks to enhancing the performance of solid-oxide electrolysis cells (SOECs), which is directly linked to the more-refined fundamental understanding of complex physical and chemical phenomena and mass exchanges that take place at the surfaces and in the bulk of electrocatalysis materials. Here, we developed an eReaxFF force field for barium zirconate doped with 20 mol% of yttrium, BaZr0.8Y0.2O3-δ (BZY20) to enable a systematic, large-length-scale, and longer-timescale atomistic simulation of solid-oxide electrocatalysis for hydrogen generation. All parameters for the eReaxFF were optimized to reproduce quantum-mechanical (QM) calculations on relevant condensed phase and cluster systems describing oxygen vacancies, vacancy migrations, electron localization, water adsorption, water splitting, and hydrogen generation on the surfaces of the BZY20 solid oxide. Using the developed force field, we performed both zero-voltage (excess electrons absent) and non-zero-voltage (excess electrons present) molecular dynamics simulations to observe water adsorption, water splitting, proton migration, oxygen-vacancy migrations, and eventual hydrogen-production reactions. Based on investigations offered in the present study, we conclude that the eReaxFF force field-based approach can enable computationally efficient simulations for electron conductivity, electron leakage, and other non-zero-voltage effects on the solid oxide materials using the explicit-electron concept. Moreover, we demonstrate how the eReaxFF force field-based atomistic-simulation approach can enhance our understanding of processes in SOEC applications and potentially other renewable-energy applications.
Probing phonon focusing, thermomechanical behavior, and moiré patterns in van der Waals architectures using surface acoustic waves
Authors: Baradwaj Nitish , Aditya Anikeya , Mishra Ankit , Burns Kory , Lang Eric , Hachtel Jordan A. , Hattar Khalid , Aitkaliyeva Assel , Nakano Aiichiro , Vashishta Priya , Kalia Rajiv 
Published: June 2024

AbstractSurface acoustic waves (SAWs) propagate along solid-air, solid-liquid, and solid-solid interfaces. Their characteristics depend on the elastic properties of the solid. Combining transmission electron microscopy (TEM) experiments with molecular dynamics (MD) simulations, we probe atomic environments around intrinsic defects that generate SAWs in vertically stacked two-dimensional (2D) bilayers of MoS2. Our joint experimental-simulation study provides insights into SAW-induced structural and dynamical changes and thermomechanical responses of MoS2 bilayers. Using MD simulations, we compute mechanical properties from the SAW velocity and thermal conductivity from thermal diffusion of SAWs. The results for Young’s modulus and thermal conductivity of an MoS2 monolayer are in good agreement with experiments. The presence of defects, such as nanopores which generate SAWs, reduces the thermal conductivity of 2D-MoS2 by an order of magnitude. We also observe dramatic changes in moiré patterns, phonon focusing, and cuspidal structures on 2D-MoS2 layers.
Rare variants at KCNJ2 are associated with LDL-cholesterol levels in a cross-population study
Authors: Rossi Niccolò , Syed Najeeb , Visconti Alessia , Aliyev Elbay , Berry Sarah , Bourbon Mafalda , Spector Tim D. , Hysi Pirro G. , Fakhro Khalid A. , Falchi Mario 
Published: June 2024

AbstractLeveraging whole genome sequencing data of 1751 individuals from the UK and 2587 Qatari subjects, we suggest here an association of rare variants mapping to the sour taste-associated gene KCNJ2 with reduced low-density lipoprotein cholesterol (LDL-C, P = 2.10 × 10−12) and with a 22% decreased dietary trans-fat intake. This study identifies a novel candidate rare locus for LDL-C, adding insights into the genetic architecture of a complex trait implicated in cardiovascular disease.
Prediction model for cardiovascular disease in patients with diabetes using machine learning derived and validated in two independent Korean cohorts
Authors: Sang Hyunji , Lee Hojae , Lee Myeongcheol , Park Jaeyu , Kim Sunyoung , Woo Ho Geol , Rahmati Masoud , Koyanagi Ai , Smith Lee , Lee Sihoon , Hwang You-Cheol , Park Tae Sun , Lim Hyunjung , Yon Dong Keon , Rhee Sang Youl 
Published: June 2024

AbstractThis study aimed to develop and validate a machine learning (ML) model tailored to the Korean population with type 2 diabetes mellitus (T2DM) to provide a superior method for predicting the development of cardiovascular disease (CVD), a major chronic complication in these patients. We used data from two cohorts, namely the discovery (one hospital; n = 12,809) and validation (two hospitals; n = 2019) cohorts, recruited between 2008 and 2022. The outcome of interest was the presence or absence of CVD at 3 years. We selected various ML-based models with hyperparameter tuning in the discovery cohort and performed area under the receiver operating characteristic curve (AUROC) analysis in the validation cohort. CVD was observed in 1238 (10.2%) patients in the discovery cohort. The random forest (RF) model exhibited the best overall performance among the models, with an AUROC of 0.830 (95% confidence interval [CI] 0.818–0.842) in the discovery dataset and 0.722 (95% CI 0.660–0.783) in the validation dataset. Creatinine and glycated hemoglobin levels were the most influential factors in the RF model. This study introduces a pioneering ML-based model for predicting CVD in Korean patients with T2DM, outperforming existing prediction tools and providing a groundbreaking approach for early personalized preventive medicine.
Preparation of Erlotinib hydrochloride nanoparticles (anti-cancer drug) by RESS-C method and investigating the effective parameters
Authors: Bazaei Majid , Honarvar Bizhan , Esfandiari Nadia , Sajadian Seyed Ali , Arab Aboosadi Zahra 
Published: June 2024

AbstractThe size of the drug particles is one of the essential factors for the proper absorption of the drug compared to the dose of the drug. When particle size is decreased, drug uptake into the body increases. Recent studies have revealed that the rapid expansion of supercritical solution with cosolvent plays a significant role in preparing micron and submicron particles. This paper examines the preparation of Erlotinib hydrochloride nanoparticles using a supercritical solution through the cosolvent method for the first time. An examination of the parameters of temperature (318–338 K), pressures (15–25 MPa) and nozzle diameter (300–700 μm) was investigated by Box-Behnken design, and their respective effects on particle size revealed that the nozzle diameter has a more significant impact on particle size than the other parameters. The smallest particles were produced at temperature 338 K, pressure 20 MPa, and nozzle diameter 700 μm. Besides, the ERL nanoparticles were characterized using SEM, DLS, XRD, FTIR, and DSC analyses. Finally, the results showed that the average size of the ERL particles decreased from 31.6 μm to 200–1100 nm.