bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Scintillation Events With Basis on L1 Transmissions From Geostationary SBAS Satellites
Authors: Moraes Alison , Sousasantos Jonas , Costa Emanoel , Pereira Bruno Augusto , Rodrigues Fabiano , Galera Monico João Francisco 
Published: January 2024

AbstractSignals recorded by two stations in the Brazilian region: [Fortaleza (3.74°S, 38.57°W) and Inconfidentes (22.31°S, 46.32°W)], receiving L1 transmissions from different geostationary satellites, were used to evaluate the amplitude scintillation index S4 and several characteristics of scintillation events (continuous record with S4 > 0.2) during nighttime hours (18:00 LT–02:00 LT) in the years 2014–2016. The effects from solar activity, season, and local time on the number of scintillation events per night, maximum scintillation, scintillation event duration, and spacing between consecutive events will be discussed. The results indicate that: (a) scintillation occurs from September to March in both links; (b) the most likely numbers of observed scintillation events per night were two or three, particularly during the first 2 years; (c) on average, the first scintillation event usually had larger maximum S4 values when compared to those of the later ones along the night; (d) the first scintillation event had a longer mean duration than the succeeding ones in a given night; (e) the durations of scintillation events, regardless of their numbers per night and the location, decreased with local time; (f) the opposite dependence of spacings between consecutive events on local time was observed; (g) the cumulative distribution functions of the scintillation onset time indicated a strong dependence on the dip latitude of the station; and (h) early occurrences of onset times are directly related to the increased probability of the occurrence of multiple scintillation events.
Abnormal developmental of structural covariance networks in young adults with heavy cannabis use: a 3-year follow-up study
Authors: Xu Hui , Li Jiahao , Huang Huan , Yin Bo , Li Dan-Dong 
Published: January 2024

AbstractHeavy cannabis use (HCU) exerts adverse effects on the brain. Structural covariance networks (SCNs) that illustrate coordinated regional maturation patterns are extensively employed to examine abnormalities in brain structure. Nevertheless, the unexplored aspect remains the developmental alterations of SCNs in young adults with HCU for three years, from the baseline (BL) to the 3-year follow-up (FU). These changes demonstrate dynamic development and hold potential as biomarkers. A total of 20 young adults with HCU and 22 matched controls were recruited. All participants underwent magnetic resonance imaging (MRI) scans at both the BL and FU and were evaluated using clinical measures. Both groups used cortical thickness (CT) and cortical surface area (CSA) to construct structural covariance matrices. Subsequently, global and nodal network measures of SCNs were computed based on these matrices. Regarding global network measures, the BL assessment revealed significant deviations in small-worldness and local efficiency of CT and CSA in young adults with HCU compared to controls. However, no significant differences between the two groups were observed at the FU evaluation. Young adults with HCU displayed changes in nodal network measures across various brain regions during the transition from BL to FU. These alterations included abnormal nodal degree, nodal efficiency, and nodal betweenness in widespread areas such as the entorhinal cortex, superior frontal gyrus, and parahippocampal cortex. These findings suggest that the topography of CT and CSA plays a role in the typical structural covariance topology of the brain. Furthermore, these results indicate the effect of HCU on the developmental changes of SCNs in young adults.
Results of a randomised Phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer
Authors: Nicum Shibani , McGregor Naomi , Austin Rachel , Collins Linda , Dutton Susan , McNeish Iain , Glasspool Rosalind , Hall Marcia , Roux Rene , Michael Agnieszka , Clamp Andrew , Jayson Gordon , Kristeleit Rebecca , Banerjee Susana , Mansouri Anita 
Published: January 2024

Abstract
Background
OCTOVA compared the efficacy of olaparib (O) versus weekly paclitaxel (wP) or olaparib + cediranib (O + C) in recurrent ovarian cancer (OC).

Aims
The main aim of the OCTOVA trial was to determine the progression-free survival (PFS) of olaparib (O) versus the oral combination of olaparib plus cediranib (O + C) and weekly paclitaxel (wP) in recurrent ovarian cancer (OC).

Methods
In total, 139 participants who had relapsed within 12 months of platinum therapy were randomised to O (300 mg twice daily), wP (80 mg/m2 d1,8,15, q28) or O + C (300 mg twice daily/20 mg daily, respectively). The primary endpoint was progression-free survival (PFS) of olaparib (O) versus olaparib plus cediranib (O + C) or weekly paclitaxel (wP). The sample size was calculated to observe a PFS hazard ratio (HR) 0.64 in favour of O + C compared to O (20% one-sided type I error, 80% power).

Results
The majority had platinum-resistant disease (90%), 22% prior PARPi, 34% prior anti-angiogenic therapy, 30% germline BRCA1/2 mutations. The PFS was increased for O + C vs O (O + C 5.4 mo (2.3, 9.6): O 3.7 mo (1.8, 7.6) HR = 0.73; 60% CI: 0.59, 0.89; P = 0.1) and no different between wP and O (wP 3.9 m (1.9, 9.1); O 3.7 mo (1.8, 7.6) HR = 0.89, 60% CI: 0.72, 1.09; P = 0.69). The main treatment-related adverse events included manageable diarrhoea (4% Grade 3) and hypertension (4% Grade 3) in the O + C arm.

Discussion
OCTOVA demonstrated the activity of O + C in women with recurrent disease, offering a potential non-chemotherapy option.

Trial registration
ISRCTN14784018, registered on 19th January 2018 http://www.isrctn.com/ISRCTN14784018.
The LKB1–TSSK1B axis controls YAP phosphorylation to regulate the Hippo–YAP pathway
Authors: Kim Cho-Long , Lim Su-Bin , Choi Sue-Hee , Kim Dong Hyun , Sim Ye Eun , Jo Eun-Hye , Kim Keeeun , Lee Keesook , Park Hee-Sae , Lim Su Bin , Kang Li-Jung , Jeong Han-Sol , Lee Youngsoo , Hansen Carsten G. , Mo Jung-Soon 
Published: January 2024

AbstractThe Hippo pathway’s main effector, Yes-associated protein (YAP), plays a crucial role in tumorigenesis as a transcriptional coactivator. YAP’s phosphorylation by core upstream components of the Hippo pathway, such as mammalian Ste20 kinase 1/2 (MST1/2), mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), and their substrate, large tumor suppressor 1/2 (LATS1/2), influences YAP’s subcellular localization, stability, and transcriptional activity. However, recent research suggests the existence of alternative pathways that phosphorylate YAP, independent of these core upstream Hippo pathway components, raising questions about additional means to inactivate YAP. In this study, we present evidence demonstrating that TSSK1B, a calcium/calmodulin-dependent protein kinase (CAMK) superfamily member, is a negative regulator of YAP, suppressing cellular proliferation and oncogenic transformation. Mechanistically, TSSK1B inhibits YAP through two distinct pathways. Firstly, the LKB1–TSSK1B axis directly phosphorylates YAP at Ser94, inhibiting the YAP–TEAD complex’s formation and suppressing its target genes’ expression. Secondly, the TSSK1B–LATS1/2 axis inhibits YAP via phosphorylation at Ser127. Our findings reveal the involvement of TSSK1B-mediated molecular mechanisms in the Hippo–YAP pathway, emphasizing the importance of multilevel regulation in critical cellular decision-making processes.
Fatty acid metabolism of immune cells: a new target of tumour immunotherapy
Authors: Zhang Sheng , Lv Kebing , Liu Zhen , Zhao Ran , Li Fei 
Published: January 2024

AbstractMetabolic competition between tumour cells and immune cells for limited nutrients is an important feature of the tumour microenvironment (TME) and is closely related to the outcome of tumour immune escape. A large number of studies have proven that tumour cells need metabolic reprogramming to cope with acidification and hypoxia in the TME while increasing energy uptake to support their survival. Among them, synthesis, oxidation and uptake of fatty acids (FAs) in the TME are important manifestations of lipid metabolic adaptation. Although different immune cell subsets often show different metabolic characteristics, various immune cell functions are closely related to fatty acids, including providing energy, providing synthetic materials and transmitting signals. In the face of the current situation of poor therapeutic effects of tumour immunotherapy, combined application of targeted immune cell fatty acid metabolism seems to have good therapeutic potential, which is blocked at immune checkpoints. Combined application of adoptive cell therapy and cancer vaccines is reflected. Therefore, it is of great interest to explore the role of fatty acid metabolism in immune cells to discover new strategies for tumour immunotherapy and improve anti-tumour immunity.
Breakthrough of solid tumor treatment: CAR-NK immunotherapy
Authors: Wang Wenkang , Liu Yang , He Zhen , Li Lifeng , Liu Senbo , Jiang Mingqiang , Zhao Bing , Deng Meng , Wang Wendong , Mi Xuefang , Sun Zhenqiang , Ge Xin 
Published: January 2024

AbstractAs the latest and most anticipated method of tumor immunotherapy, CAR-NK therapy has received increasing attention in recent years, and its safety and high efficiency have irreplaceable advantages over CAR-T. Current research focuses on the application of CAR-NK in hematological tumors, while there are fewer studies on solid tumor. This article reviews the process of constructing CAR-NK, the effects of hypoxia and metabolic factors, NK cell surface receptors, cytokines, and exosomes on the efficacy of CAR-NK in solid tumor, and the role of CAR-NK in various solid tumor. The mechanism of action and the research status of the potential of CAR-NK in the treatment of solid tumor in clinical practice, and put forward the advantages, limitations and future problems of CAR-NK in the treatment of solid tumor.
Ramping dynamics and theta oscillations reflect dissociable signatures during rule-guided human behavior
Authors: Weber Jan , Solbakk Anne-Kristin , Blenkmann Alejandro O. , Llorens Anais , Funderud Ingrid , Leske Sabine , Larsson Pål Gunnar , Ivanovic Jugoslav , Knight Robert T. , Endestad Tor , Helfrich Randolph F. 
Published: January 2024

AbstractContextual cues and prior evidence guide human goal-directed behavior. The neurophysiological mechanisms that implement contextual priors to guide subsequent actions in the human brain remain unclear. Using intracranial electroencephalography (iEEG), we demonstrate that increasing uncertainty introduces a shift from a purely oscillatory to a mixed processing regime with an additional ramping component. Oscillatory and ramping dynamics reflect dissociable signatures, which likely differentially contribute to the encoding and transfer of different cognitive variables in a cue-guided motor task. The results support the idea that prefrontal activity encodes rules and ensuing actions in distinct coding subspaces, while theta oscillations synchronize the prefrontal-motor network, possibly to guide action execution. Collectively, our results reveal how two key features of large-scale neural population activity, namely continuous ramping dynamics and oscillatory synchrony, jointly support rule-guided human behavior.
Interindividual- and blood-correlated sweat phenylalanine multimodal analytical biochips for tracking exercise metabolism
Authors: Zhong Bowen , Qin Xiaokun , Xu Hao , Liu Lingchen , Li Linlin , Li Zhexin , Cao Limin , Lou Zheng , Jackman Joshua A. , Cho Nam-Joon , Wang Lili 
Published: January 2024

AbstractIn situ monitoring of endogenous amino acid loss through sweat can provide physiological insights into health and metabolism. However, existing amino acid biosensors are unable to quantitatively assess metabolic status during exercise and are rarely used to establish blood-sweat correlations because they only detect a single concentration indicator and disregard sweat rate. Here, we present a wearable multimodal biochip integrated with advanced electrochemical electrodes and multipurpose microfluidic channels that enables simultaneous quantification of multiple sweat indicators, including phenylalanine and chloride, as well as sweat rate. This combined measurement approach reveals a negative correlation between sweat phenylalanine levels and sweat rates among individuals, which further enables identification of individuals at high metabolic risk. By tracking phenylalanine fluctuations induced by protein intake during exercise and normalizing the concentration indicator by sweat rates to reduce interindividual variability, we demonstrate a reliable method to correlate and analyze sweat-blood phenylalanine levels for personal health monitoring.
Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia
Authors: Gurbatri Candice R. , Radford Georgette A. , Vrbanac Laura , Im Jongwon , Thomas Elaine M. , Coker Courtney , Taylor Samuel R. , Jang YoungUk , Sivan Ayelet , Rhee Kyu , Saleh Anas A. , Chien Tiffany , Zandkarimi Fereshteh , Lia Ioana , Lannagan Tamsin R. M. , Wang Tongtong , Wright Josephine A. , Kobayashi Hiroki , Ng Jia Q. , Lawrence Matt , Sammour Tarik , Thomas Michelle , Lewis Mark , Papanicolas Lito , Perry Joanne , Fitzsimmons Tracy , Kaazan Patricia , Lim Amanda , Stavropoulos Alexandra M. , Gouskos Dion A. , Marker Julie , Ostroff Cheri , Rogers Geraint , Arpaia Nicholas , Worthley Daniel L. , Woods Susan L. , Danino Tal 
Published: January 2024

AbstractBioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.
Cell state dependent effects of Bmal1 on melanoma immunity and tumorigenicity
Authors: Zhang Xue , Pant Shishir M. , Ritch Cecily C. , Tang Hsin-Yao , Shao Hongguang , Dweep Harsh , Gong Yao-Yu , Brooks Rebekah , Brafford Patricia , Wolpaw Adam J. , Lee Yool , Weeraratna Ashani , Sehgal Amita , Herlyn Meenhard , Kossenkov Andrew , Speicher David , Sorger Peter K. , Santagata Sandro , Dang Chi V. 
Published: January 2024

AbstractThe circadian clock regulator Bmal1 modulates tumorigenesis, but its reported effects are inconsistent. Here, we show that Bmal1 has a context-dependent role in mouse melanoma tumor growth. Loss of Bmal1 in YUMM2.1 or B16-F10 melanoma cells eliminates clock function and diminishes hypoxic gene expression and tumorigenesis, which could be rescued by ectopic expression of HIF1α in YUMM2.1 cells. By contrast, over-expressed wild-type or a transcriptionally inactive mutant Bmal1 non-canonically sequester myosin heavy chain 9 (Myh9) to increase MRTF-SRF activity and AP-1 transcriptional signature, and shift YUMM2.1 cells from a Sox10high to a Sox9high immune resistant, mesenchymal cell state that is found in human melanomas. Our work describes a link between Bmal1, Myh9, mouse melanoma cell plasticity, and tumor immunity. This connection may underlie cancer therapeutic resistance and underpin the link between the circadian clock, MRTF-SRF and the cytoskeleton.
Machine learning-based high-frequency neuronal spike reconstruction from low-frequency and low-sampling-rate recordings
Authors: Hong Nari , Kim Boil , Lee Jaewon , Choe Han Kyoung , Jin Kyong Hwan , Kang Hongki 
Published: January 2024

AbstractRecording neuronal activity using multiple electrodes has been widely used to understand the functional mechanisms of the brain. Increasing the number of electrodes allows us to decode more variety of functionalities. However, handling massive amounts of multichannel electrophysiological data is still challenging due to the limited hardware resources and unavoidable thermal tissue damage. Here, we present machine learning (ML)-based reconstruction of high-frequency neuronal spikes from subsampled low-frequency band signals. Inspired by the equivalence between high-frequency restoration and super-resolution in image processing, we applied a transformer ML model to neuronal data recorded from both in vitro cultures and in vivo male mouse brains. Even with the x8 downsampled datasets, our trained model reasonably estimated high-frequency information of spiking activity, including spike timing, waveform, and network connectivity. With our ML-based data reduction applicable to existing multichannel recording hardware while achieving neuronal signals of broad bandwidths, we expect to enable more comprehensive analysis and control of brain functions.
LDLR is used as a cell entry receptor by multiple alphaviruses
Authors: Zhai Xiaofeng , Li Xiaoling , Veit Michael , Wang Ningning , Wang Yu , Merits Andres , Jiang Zhiwen , Qin Yan , Zhang Xiaoguang , Qi Kaili , Jiao Houqi , He Wan-Ting , Chen Ye , Mao Yang , Su Shuo 
Published: January 2024

AbstractAlphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors have been identified for alphavirus entry; however, they cannot explain the broad host range and tissue tropism of certain alphaviruses, such as Getah virus (GETV), indicating the existence of additional receptors. Here we identify the evolutionarily conserved low-density lipoprotein receptor (LDLR) as a new cell entry factor for GETV, Semliki Forest virus (SFV), Ross River virus (RRV) and Bebaru virus (BEBV). Ectopic expression of LDLR facilitates cellular binding and internalization of GETV, which is mediated by the interaction between the E2-E1 spike of GETV and the ligand-binding domain (LBD) of LDLR. Antibodies against LBD block GETV infection in cultured cells. In addition, the GST-LBD fusion protein inhibits GETV infection both in vitro and in vivo. Notably, we identify the key amino acids in LDLR-LBD that played a crucial role in viral entry; specific mutations in the CR4 and CR5 domain of LDLR-LBD reduce viral entry to cells by more than 20-fold. These findings suggest that targeting the LDLR-LBD could be a potential strategy for the development of antivirals against multiple alphaviruses.
Distinguishing examples while building concepts in hippocampal and artificial networks
Authors: Kang Louis , Toyoizumi Taro 
Published: January 2024

AbstractThe hippocampal subfield CA3 is thought to function as an auto-associative network that stores experiences as memories. Information from these experiences arrives directly from the entorhinal cortex as well as indirectly through the dentate gyrus, which performs sparsification and decorrelation. The computational purpose for these dual input pathways has not been firmly established. We model CA3 as a Hopfield-like network that stores both dense, correlated encodings and sparse, decorrelated encodings. As more memories are stored, the former merge along shared features while the latter remain distinct. We verify our model’s prediction in rat CA3 place cells, which exhibit more distinct tuning during theta phases with sparser activity. Finally, we find that neural networks trained in multitask learning benefit from a loss term that promotes both correlated and decorrelated representations. Thus, the complementary encodings we have found in CA3 can provide broad computational advantages for solving complex tasks.
Unraveling the crucial role of trace oxygen in organic semiconductors
Authors: Huang Yinan , Wu Kunjie , Sun Yajing , Hu Yongxu , Wang Zhongwu , Yuan Liqian , Wang Shuguang , Ji Deyang , Zhang Xiaotao , Dong Huanli , Gong Zhongmiao , Li Zhiyun , Weng Xuefei , Huang Rong , Cui Yi , Chen Xiaosong , Li Liqiang , Hu Wenping 
Published: January 2024

AbstractOptoelectronic properties of semiconductors are significantly modified by impurities at trace level. Oxygen, a prevalent impurity in organic semiconductors (OSCs), has long been considered charge-carrier traps, leading to mobility degradation and stability problems. However, this understanding relies on the conventional deoxygenation methods, by which oxygen residues in OSCs are inevitable. It implies that the current understanding is questionable. Here, we develop a non-destructive deoxygenation method (i.e., de-doping) for OSCs by a soft plasma treatment, and thus reveal that trace oxygen significantly pre-empties the donor-like traps in OSCs, which is the origin of p-type characteristics exhibited by the majority of these materials. This insight is completely opposite to the previously reported carrier trapping and can clarify some previously unexplained organic electronics phenomena. Furthermore, the de-doping results in the disappearance of p-type behaviors and significant increase of n-type properties, while re-doping (under light irradiation in O2) can controllably reverse the process. Benefiting from this, the key electronic characteristics (e.g., polarity, conductivity, threshold voltage, and mobility) can be precisely modulated in a nondestructive way, expanding the explorable property space for all known OSC materials.
Leukemia inhibitory factor suppresses hepatic de novo lipogenesis and induces cachexia in mice
Authors: Yang Xue , Wang Jianming , Chang Chun-Yuan , Zhou Fan , Liu Juan , Xu Huiting , Ibrahim Maria , Gomez Maria , Guo Grace L. , Liu Hao , Zong Wei-Xing , Wondisford Fredric E. , Su Xiaoyang , White Eileen , Feng Zhaohui , Hu Wenwei 
Published: January 2024

AbstractCancer cachexia is a systemic metabolic syndrome characterized by involuntary weight loss, and muscle and adipose tissue wasting. Mechanisms underlying cachexia remain poorly understood. Leukemia inhibitory factor (LIF), a multi-functional cytokine, has been suggested as a cachexia-inducing factor. In a transgenic mouse model with conditional LIF expression, systemic elevation of LIF induces cachexia. LIF overexpression decreases de novo lipogenesis and disrupts lipid homeostasis in the liver. Liver-specific LIF receptor knockout attenuates LIF-induced cachexia, suggesting that LIF-induced functional changes in the liver contribute to cachexia. Mechanistically, LIF overexpression activates STAT3 to downregulate PPARα, a master regulator of lipid metabolism, leading to the downregulation of a group of PPARα target genes involved in lipogenesis and decreased lipogenesis in the liver. Activating PPARα by fenofibrate, a PPARα agonist, restores lipid homeostasis in the liver and inhibits LIF-induced cachexia. These results provide valuable insights into cachexia, which may help develop strategies to treat cancer cachexia.