bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial
Authors: Sha Huizi , Tong Fan , Ni Jiayao , Sun Yi , Zhu Yahui , Qi Liang , Li Xiaoqin , Li Wei , Yang Yan , Gu Qing , Zhang Xing , Wang Xiaoxuan , Zhu Chan , Chen Dongsheng , Liu Baorui , Du Juan 
Published: June 2024

AbstractMetastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4–62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3–99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1–11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.
General and anxiety-linked influences of acute serotonin reuptake inhibition on neural responses associated with attended visceral sensation
Authors: Livermore James J. A. , Skora Lina I. , Adamatzky Kristian , Garfinkel Sarah N. , Critchley Hugo D. , Campbell-Meiklejohn Daniel 
Published: June 2024

AbstractOrdinary sensations from inside the body are important causes and consequences of our affective states and behaviour, yet the roles of neurotransmitters in interoceptive processing have been unclear. With a within-subjects design, this experiment tested the impacts of acute increases of endogenous extracellular serotonin on the neural processing of attended internal sensations and the links of these effects to anxiety using a selective serotonin reuptake inhibitor (SSRI) (20 mg citalopram) and a placebo. Twenty-one healthy volunteers (fourteen female, mean age 23.9) completed the Visceral Interoceptive Attention (VIA) task while undergoing functional magnetic resonance imaging (fMRI) with each treatment. The VIA task required focused attention on the heart, stomach, or visual sensation. The relative neural interoceptive responses to heart sensation [heart minus visual attention] (heart-IR) and stomach sensation [stomach minus visual attention] (stomach-IR) were compared between treatments. Visual attention subtraction controlled for the general effects of citalopram on sensory processing. Citalopram was associated with lower interoceptive processing in viscerosensory (the stomach-IR of bilateral posterior insular cortex) and integrative/affective (the stomach-IR and heart-IR of bilateral amygdala) components of interoceptive neural pathways. In anterior insular cortex, citalopram reductions of heart-IR depended on anxiety levels, removing a previously known association between anxiety and the region’s response to attended heart sensation observed with placebo. Preliminary post hoc analysis indicated that citalopram effects on the stomach-IR of the amygdalae corresponded to acute anxiety changes. This direct evidence of general and anxiety-linked serotonergic influence on neural interoceptive processes advances our understanding of interoception, its regulation, and anxiety.
Knockout of integrin αvβ6 protects against renal inflammation in chronic kidney disease by reduction of pro-inflammatory macrophages
Authors: Zhu Changjian , Zheng Ruilin , Han Xu , Tang Ziwen , Li Feng , Hu Xinrong , Lin Ruoni , Shen Jiani , Pei Qiaoqiao , Wang Rong , Wei Guangyan , Peng Zhenwei , Chen Wei , Liang Zhou , Zhou Yi 
Published: June 2024

AbstractIntegrin αvβ6 holds promise as a therapeutic target for organ fibrosis, yet targeted therapies are hampered by concerns over inflammatory-related side effects. The role of αvβ6 in renal inflammation remains unknown, and clarifying this issue is crucial for αvβ6-targeted treatment of chronic kidney disease (CKD). Here, we revealed a remarkable positive correlation between overexpressed αvβ6 in proximal tubule cells (PTCs) and renal inflammation in CKD patients and mouse models. Notably, knockout of αvβ6 not only significantly alleviated renal fibrosis but also reduced inflammatory responses in mice, especially the infiltration of pro-inflammatory macrophages. Furthermore, conditional knockout of αvβ6 in PTCs in vivo and co-culture of PTCs with macrophages in vitro showed that depleting αvβ6 in PTCs suppressed the migration and pro-inflammatory differentiation of macrophages. Screening of macrophage activators showed that αvβ6 in PTCs activates macrophages via secreting IL-34. IL-34 produced by PTCs was significantly diminished by αvβ6 silencing, and reintroduction of IL-34 restored macrophage activities, while anti-IL-34 antibody restrained macrophage activities enhanced by αvβ6 overexpression. Moreover, RNA-sequencing of PTCs and verification experiments demonstrated that silencing αvβ6 in PTCs blocked hypoxia-stimulated IL-34 upregulation and secretion by inhibiting YAP expression, dephosphorylation, and nuclear translocation, which resulted in the activation of Hippo signaling. While application of a YAP agonist effectively recurred IL-34 production by PTCs, enhancing the subsequent macrophage migration and activation. Besides, reduced IL-34 expression and YAP activation were also observed in global or PTCs-specific αvβ6-deficient injured kidneys. Collectively, our research elucidates the pro-inflammatory function and YAP/IL-34/macrophage axis-mediated mechanism of αvβ6 in renal inflammation, providing a solid rationale for the use of αvβ6 inhibition to treat kidney inflammation and fibrosis.
Stabilizing persistent currents in an atomtronic Josephson junction necklace
Authors: Pezzè Luca , Xhani Klejdja , Daix Cyprien , Grani Nicola , Donelli Beatrice , Scazza Francesco , Hernandez-Rajkov Diego , Kwon Woo Jin , Del Pace Giulia , Roati Giacomo 
Published: June 2024

AbstractArrays of Josephson junctions are at the forefront of research on quantum circuitry for quantum computing, simulation, and metrology. They provide a testing bed for exploring a variety of fundamental physical effects where macroscopic phase coherence, nonlinearities, and dissipative mechanisms compete. Here we realize finite-circulation states in an atomtronic Josephson junction necklace, consisting of a tunable array of tunneling links in a ring-shaped superfluid. We study the stability diagram of the atomic flow by tuning both the circulation and the number of junctions. We predict theoretically and demonstrate experimentally that the atomic circuit withstands higher circulations (corresponding to higher critical currents) by increasing the number of Josephson links. The increased stability contrasts with the trend of the superfluid fraction – quantified by Leggett’s criterion – which instead decreases with the number of junctions and the corresponding density depletion. Our results demonstrate atomic superfluids in mesoscopic structured ring potentials as excellent candidates for atomtronics applications, with prospects towards the observation of non-trivial macroscopic superpositions of current states.
Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas
Authors: Arrieta Víctor A. , Gould Andrew , Kim Kwang-Soo , Habashy Karl J. , Dmello Crismita , Vázquez-Cervantes Gustavo I. , Palacín-Aliana Irina , McManus Graysen , Amidei Christina , Gomez Cristal , Dhiantravan Silpol , Chen Li , Zhang Daniel Y. , Saganty Ruth , Cholak Meghan E. , Pandey Surya , McCord Matthew , McCortney Kathleen , Castro Brandyn , Ward Rachel , Muzzio Miguel , Bouchoux Guillaume , Desseaux Carole , Canney Michael , Carpentier Alexandre , Zhang Bin , Miska Jason M. , Lesniak Maciej S. , Horbinski Craig M. , Lukas Rimas V. , Stupp Roger , Lee-Chang Catalina , Sonabend Adam M. 
Published: June 2024

AbstractGiven the marginal penetration of most drugs across the blood-brain barrier, the efficacy of various agents remains limited for glioblastoma (GBM). Here we employ low-intensity pulsed ultrasound (LIPU) and intravenously administered microbubbles (MB) to open the blood-brain barrier and increase the concentration of liposomal doxorubicin and PD-1 blocking antibodies (aPD-1). We report results on a cohort of 4 GBM patients and preclinical models treated with this approach. LIPU/MB increases the concentration of doxorubicin by 2-fold and 3.9-fold in the human and murine brains two days after sonication, respectively. Similarly, LIPU/MB-mediated blood-brain barrier disruption leads to a 6-fold and a 2-fold increase in aPD-1 concentrations in murine brains and peritumoral brain regions from GBM patients treated with pembrolizumab, respectively. Doxorubicin and aPD-1 delivered with LIPU/MB upregulate major histocompatibility complex (MHC) class I and II in tumor cells. Increased brain concentrations of doxorubicin achieved by LIPU/MB elicit IFN-γ and MHC class I expression in microglia and macrophages. Doxorubicin and aPD-1 delivered with LIPU/MB results in the long-term survival of most glioma-bearing mice, which rely on myeloid cells and lymphocytes for their efficacy. Overall, this translational study supports the utility of LIPU/MB to potentiate the antitumoral activities of doxorubicin and aPD-1 for GBM.
Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging
Authors: Diez Ibai , Ortiz-Terán Laura , Ng Thomas S. C. , Albers Mark W. , Marshall Gad , Orwig William , Kim Chan-mi , Bueichekú Elisenda , Montal Victor , Olofsson Jonas , Vannini Patrizia , El Fahkri Georges , Sperling Reisa , Johnson Keith , Jacobs Heidi I. L. , Sepulcre Jorge 
Published: June 2024

AbstractThe direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer’s disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.
High-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1
Authors: Cui Zhanding , Liu Jinlong , Xie Chong , Wang Tao , Sun Pu , Wang Jinlong , Li Jiaoyang , Li Guoxiu , Qiu Jicheng , Zhang Ying , Li Dengliang , Sun Ying , Yin Juanbin , Li Kun , Zhao Zhixun , Yuan Hong , Bai Xingwen , Ma Xueqing , Li Pinghua , Fu Yuanfang , Bao Huifang , Li Dong , Zhang Qiang , Liu Zaixin , Cao Yimei , Zhang Jing , Lu Zengjun 
Published: June 2024

AbstractPorcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ’s role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ’s effectiveness.
Current-induced domain wall motion in a van der Waals ferromagnet Fe3GeTe2
Authors: Zhang Wenjie , Ma Tianping , Hazra Binoy Krishna , Meyerheim Holger , Rigvedi Prajwal , Yin Zihan , Srivastava Abhay Kant , Wang Zhong , Gu Ke , Zhou Shiming , Wang Shouguo , Yang See-Hun , Guan Yicheng , Parkin Stuart S. P. 
Published: June 2024

AbstractThe manipulation of spin textures by spin currents is of fundamental and technological interest. A particularly interesting system is the 2D van der Waals ferromagnet Fe3GeTe2, in which Néel-type skyrmions have recently been observed. The origin of these chiral spin textures is of considerable interest. Recently, it was proposed that these derive from defects in the structure that lower the symmetry and allow for a bulk vector Dzyaloshinsky-Moriya interaction. Here, we demonstrate current-induced domain wall motion in Fe3GeTe2 flakes, in which the maximum domain wall velocity is an order of magnitude higher than those reported in previous studies. In heterostructures with Pt or W layers on top of the Fe3GeTe2 flakes, domain walls can be moved via a combination of spin transfer and spin-orbit torques. The competition between these torques leads to a change in the direction of domain wall motion with increasing magnitude of the injected current.
The climate benefits from cement carbonation are being overestimated
Authors: Van Roijen Elisabeth , Sethares Kati , Kendall Alissa , Miller Sabbie A. 
Published: June 2024

AbstractRapid decarbonization of the cement industry is critical to meeting climate goals. Oversimplification of direct air capture benefits from hydrated cement carbonation has skewed the ability to derive decarbonization solutions. Here, we present both global cement carbonation magnitude and its dynamic effect on cumulative radiative forcing. From 1930–2015, models suggest approximately 13.8 billion metric tons (Gt) of CO2 was re-absorbed globally. However, we show that the slow rate of carbonation leads to a climate effect that is approximately 60% smaller than these apparent benefits. Further, we show that on a per kilogram (kg) basis, demolition emissions from crushing concrete at end-of-life could roughly equal the magnitude of carbon-uptake during the demolition phase. We investigate the sensitivity of common decarbonization strategies, such as utilizing supplementary cementitious materials, on the carbonation process and highlight the importance of the timing of emissions release and uptake on influencing cumulative radiative forcing. Given the urgency of determining effective pathways for decarbonizing cement, this work provides a reference for overcoming some flawed interpretations of the benefits of carbonation.
Kagomerization of transition metal monolayers induced by two-dimensional hexagonal boron nitride
Authors: Zhou Hangyu , dos Santos Dias Manuel , Zhang Youguang , Zhao Weisheng , Lounis Samir 
Published: June 2024

AbstractThe kagome lattice is an exciting solid state physics platform for the emergence of nontrivial quantum states driven by electronic correlations: topological effects, unconventional superconductivity, charge and spin density waves, and unusual magnetic states such as quantum spin liquids. While kagome lattices have been realized in complex multi-atomic bulk compounds, here we demonstrate from first-principles a process that we dub kagomerization, in which we fabricate a two-dimensional kagome lattice in monolayers of transition metals utilizing an hexagonal boron nitride (h-BN) overlayer. Surprisingly, h-BN induces a large rearrangement of the transition metal atoms supported on a fcc(111) heavy-metal surface. This reconstruction is found to be rather generic for this type of heterostructures and has a profound impact on the underlying magnetic properties, ultimately stabilizing various topological magnetic solitons such as skyrmions and bimerons. Our findings call for a reconsideration of h-BN as merely a passive capping layer, showing its potential for not only reconstructing the atomic structure of the underlying material, e.g. through the kagomerization of magnetic films, but also enabling electronic and magnetic phases that are highly sought for the next generation of device technologies.
Cis-regulatory evolution of the recently expanded Ly49 gene family
Authors: Fan Changxu , Xing Xiaoyun , Murphy Samuel J. H. , Poursine-Laurent Jennifer , Schmidt Heather , Parikh Bijal A. , Yoon Jeesang , Choudhary Mayank N. K. , Saligrama Naresha , Piersma Sytse J. , Yokoyama Wayne M. , Wang Ting 
Published: June 2024

AbstractComparative genomics has revealed the rapid expansion of multiple gene families involved in immunity. Members within each gene family often evolved distinct roles in immunity. However, less is known about the evolution of their epigenome and cis-regulation. Here we systematically profile the epigenome of the recently expanded murine Ly49 gene family that mainly encode either inhibitory or activating surface receptors on natural killer cells. We identify a set of cis-regulatory elements (CREs) for activating Ly49 genes. In addition, we show that in mice, inhibitory and activating Ly49 genes are regulated by two separate sets of proximal CREs, likely resulting from lineage-specific losses of CRE activity. Furthermore, we find that some Ly49 genes are cross-regulated by the CREs of other Ly49 genes, suggesting that the Ly49 family has begun to evolve a concerted cis-regulatory mechanism. Collectively, we demonstrate the different modes of cis-regulatory evolution for a rapidly expanding gene family.
Terahertz photon to dc current conversion via magnetic excitations of multiferroics
Authors: Ogino Makiko , Okamura Yoshihiro , Fujiwara Kosuke , Morimoto Takahiro , Nagaosa Naoto , Kaneko Yoshio , Tokura Yoshinori , Takahashi Youtarou 
Published: June 2024

AbstractDirect conversion from terahertz photon to charge current is a key phenomenon for terahertz photonics. Quantum geometrical description of optical processes in crystalline solids predicts existence of field-unbiased dc photocurrent arising from terahertz-light generation of magnetic excitations in multiferroics, potentially leading to fast and energy-efficient terahertz devices. Here, we demonstrate the dc charge current generation from terahertz magnetic excitations in multiferroic perovskite manganites with spin-driven ferroelectricity, while keeping an insulating state with no free carrier. It is also revealed that electromagnon, which ranges sub-terahertz to 2 THz, as well as antiferromagnetic resonance shows the giant conversion efficiency. Polar asymmetry induced by the cycloidal spin order gives rise to this terahertz-photon-induced dc photocurrent, and no external magnetic and electric bias field are required for this conversion process. The observed phenomena are beyond the conventional photovoltaics in semi-classical regime and demonstrate the essential role of quantum geometrical aspect in low-energy optical processes. Our finding establishes a paradigm of terahertz photovoltaic phenomena, paving a way for terahertz photonic devices and energy harvesting.
Global expansion of tropical cyclone precipitation footprint
Authors: Qin Lianjie , Zhu Laiyin , Liu Baoyin , Li Zixuan , Tian Yugang , Mitchell Gordon , Shen Shifei , Xu Wei , Chen Jianguo 
Published: June 2024

AbstractPrecipitation from tropical cyclones (TCs) can cause massive damage from inland floods and is becoming more intense under a warming climate. However, knowledge gaps still exist in changes of spatial patterns in heavy TC precipitation. Here we define a metric, DIST30, as the mean radial distance from centers of clustered heavy rainfall cells (> 30 mm/3 h) to TC center, representing the footprint of heavy TC precipitation. There is significant global increase in DIST30 at a rate of 0.34 km/year. Increases of DIST30 cover 59.87% of total TC impact areas, with growth especially strong in the Western North Pacific, Northern Atlantic, and Southern Pacific. The XGBoost machine learning model showed that monthly DIST30 variability is majorly controlled by TC maximum wind speed, location, sea surface temperature, vertical wind shear, and total water column vapor. TC poleward migration in the Northern Hemisphere contributes substantially to the DIST30 upward trend globally.
A single-cell and spatial RNA-seq database for Alzheimer’s disease (ssREAD)
Authors: Wang Cankun , Acosta Diana , McNutt Megan , Bian Jiang , Ma Anjun , Fu Hongjun , Ma Qin 
Published: June 2024

AbstractAlzheimer’s Disease (AD) pathology has been increasingly explored through single-cell and single-nucleus RNA-sequencing (scRNA-seq & snRNA-seq) and spatial transcriptomics (ST). However, the surge in data demands a comprehensive, user-friendly repository. Addressing this, we introduce a single-cell and spatial RNA-seq database for Alzheimer’s disease (ssREAD). It offers a broader spectrum of AD-related datasets, an optimized analytical pipeline, and improved usability. The database encompasses 1,053 samples (277 integrated datasets) from 67 AD-related scRNA-seq & snRNA-seq studies, totaling 7,332,202 cells. Additionally, it archives 381 ST datasets from 18 human and mouse brain studies. Each dataset is annotated with details such as species, gender, brain region, disease/control status, age, and AD Braak stages. ssREAD also provides an analysis suite for cell clustering, identification of differentially expressed and spatially variable genes, cell-type-specific marker genes and regulons, and spot deconvolution for integrative analysis. ssREAD is freely available at https://bmblx.bmi.osumc.edu/ssread/.
m6a methylation orchestrates IMP1 regulation of microtubules during human neuronal differentiation
Authors: Klein Pierre , Petrić Howe Marija , Harley Jasmine , Crook Harry , Esteban Serna Sofia , Roumeliotis Theodoros I. , Choudhary Jyoti S. , Chakrabarti Anob M. , Luisier Raphaëlle , Patani Rickie , Ramos Andres 
Published: June 2024

AbstractNeuronal differentiation requires building a complex intracellular architecture, and therefore the coordinated regulation of defined sets of genes. RNA-binding proteins (RBPs) play a key role in this regulation. However, while their action on individual mRNAs has been explored in depth, the mechanisms used to coordinate gene expression programs shaping neuronal morphology are poorly understood. To address this, we studied how the paradigmatic RBP IMP1 (IGF2BP1), an essential developmental factor, selects and regulates its RNA targets during the human neuronal differentiation. We perform a combination of system-wide and molecular analyses, revealing that IMP1 developmentally transitions to and directly regulates the expression of mRNAs encoding essential regulators of the microtubule network, a key component of neuronal morphology. Furthermore, we show that m6A methylation drives the selection of specific IMP1 mRNA targets and their protein expression during the developmental transition from neural precursors to neurons, providing a molecular principle for the onset of target selectivity.