bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying Uncertainties in the Quiet‐Time Ionosphere‐Thermosphere Using WAM‐IPE
Authors: Zhan Weijia , Doostan Alireza , Sutton Eric , Fang Tzu‐Wei 
Published: February 2024

AbstractThis study presents a data‐driven approach to quantify uncertainties in the ionosphere‐thermosphere (IT) system due to varying solar wind parameters (drivers) during quiet conditions (Kp < 4) and fixed solar radiation and lower atmospheric conditions representative of 16 March 2013. Ensemble simulations of the coupled Whole Atmosphere Model with Ionosphere Plasmasphere Electrodynamics (WAM‐IPE) driven by synthetic solar wind drivers generated through a multi‐channel variational autoencoder (MCVAE) model are obtained. Applying the polynomial chaos expansion (PCE) technique, it is possible to estimate the means and variances of the QoIs as well as the sensitivities of the QoIs with regard to the drivers. Our results highlight unique features of the IT system's uncertainty: (a) the uncertainty of the IT system is larger during nighttime; (b) the spatial distributions of the uncertainty for electron density and zonal drift at fixed local times present 4 peaks in the evening sector, which are associated with the low‐density regions of longitude structure of electron density; (c) the uncertainty of the equatorial electron density is highly correlated with the uncertainty of the zonal drift, especially in the evening sector, while it is weakly correlated with the vertical drift. A variance‐based global sensitivity analysis suggests that the IMF Bz plays a dominant role in the uncertainty of electron density. A further discussion shows that the uncertainty of the IT system is determined by the magnitudes and universal time variations of solar wind drivers. Its temporal and spatial distribution can be modulated by the average state of the IT system.
Physical and mental health in adolescence: novel insights from a transdiagnostic examination of FitBit data in the ABCD study
Authors: Damme Katherine S. F. , Vargas Teresa G. , Walther Sebastian , Shankman Stewart A. , Mittal Vijay A. 
Published: February 2024

AbstractAdolescence is among the most vulnerable period for the emergence of serious mental illnesses. Addressing this vulnerability has generated interest in identifying markers of risk for symptoms and opportunities for early intervention. Physical fitness has been linked to psychopathology and may be a useful risk marker and target for early intervention. New wearable technology has made assessing fitness behavior more practical while avoiding recall and self-report bias. Still, questions remain regarding the clinical utility of physical fitness metrics for mental health, both transdiagnostically and along specific symptom dimensions. The current study includes 5007 adolescents (ages 10–13) who participated in the Adolescent Brain Cognitive Development (ABCD) study and additional sub-study that collected fitness data from wearable technology and clinical symptom measures. Physical fitness metrics included resting heart rate (RHR- an index of cardiovascular health), time spent sedentary (associated with increased inflammation and cardiovascular disease), and time spent in moderate physical activity (associated with increased neurogenesis, neuroplasticity, and healthy neurodevelopment). Self-report clinical symptoms included measures of psychosis-like experiences (PLE), internalizing symptoms, and externalizing symptoms. Increased RHR- lower cardiovascular fitness- related only to greater internalizing symptoms (t = 3.63). More sedentary behavior related to elevated PLE severity (t = 5.49). More moderate activity related to lower PLE (t = −2.69) and internalizing (t = −6.29) symptom severity. Wearable technology fitness metrics linked physical health to specific mental health dimensions, which emphasizes the utility of detailed digital health data as a marker for risk and the need for precision in targeting physical health behaviors to benefit symptoms of psychopathology.
Machine learning classification of autism spectrum disorder based on reciprocity in naturalistic social interactions
Authors: Koehler Jana Christina , Dong Mark Sen , Bierlich Afton M. , Fischer Stefanie , Späth Johanna , Plank Irene Sophia , Koutsouleris Nikolaos , Falter-Wagner Christine M. 
Published: February 2024

AbstractAutism spectrum disorder is characterized by impaired social communication and interaction. As a neurodevelopmental disorder typically diagnosed during childhood, diagnosis in adulthood is preceded by a resource-heavy clinical assessment period. The ongoing developments in digital phenotyping give rise to novel opportunities within the screening and diagnostic process. Our aim was to quantify multiple non-verbal social interaction characteristics in autism and build diagnostic classification models independent of clinical ratings. We analyzed videos of naturalistic social interactions in a sample including 28 autistic and 60 non-autistic adults paired in dyads and engaging in two conversational tasks. We used existing open-source computer vision algorithms for objective annotation to extract information based on the synchrony of movement and facial expression. These were subsequently used as features in a support vector machine learning model to predict whether an individual was part of an autistic or non-autistic interaction dyad. The two prediction models based on reciprocal adaptation in facial movements, as well as individual amounts of head and body motion and facial expressiveness showed the highest precision (balanced accuracies: 79.5% and 68.8%, respectively), followed by models based on reciprocal coordination of head (balanced accuracy: 62.1%) and body (balanced accuracy: 56.7%) motion, as well as intrapersonal coordination processes (balanced accuracy: 44.2%). Combinations of these models did not increase overall predictive performance. Our work highlights the distinctive nature of non-verbal behavior in autism and its utility for digital phenotyping-based classification. Future research needs to both explore the performance of different prediction algorithms to reveal underlying mechanisms and interactions, as well as investigate the prospective generalizability and robustness of these algorithms in routine clinical care.
Targeting AXL induces tumor-intrinsic immunogenic response in tyrosine kinase inhibitor-resistant liver cancer
Authors: Xie Yunong , Wu Haofeng , He Yimiao , Liu Linglin , Huang Ianto Bosheng , Zhou Lei , Lin Cheuk-Yin , Leung Rainbow Wing-Hei , Loh Jia-Jian , Lee Terence Kin-Wah , Ding Jin , Man Kwan , Ma Stephanie , Tong Man 
Published: February 2024

AbstractHepatocellular carcinoma (HCC) is an aggressive malignancy without effective therapeutic approaches. Here, we evaluate the tumor-intrinsic mechanisms that attenuate the efficacy of immune checkpoint inhibitor (ICI) that is observed in patients with advanced HCC who progress on first-line tyrosine kinase inhibitor (TKI) therapy. Upregulation of AXL observed in sorafenib- and lenvatinib-resistant HCCs is correlated with poor response towards TKI and ICI treatments. AXL upregulation protects sorafenib-resistant HCC cells from oxidative stress, mitochondrial damage, and accompanying immunogenic cell death through suppressed tumor necrosis factor-α (TNF-α) and STING-type I interferon pathways. Pharmacological inhibition of AXL abrogates the protective effect and re-sensitizes TKI-resistant HCC tumors to anti-PD-1 treatment. We suggest that targeting AXL in combination with anti-PD-1 may provide an alternative treatment scheme for HCC patients who progress on TKI treatment.
Programmed microalgae-gel promotes chronic wound healing in diabetes
Authors: Kang Yong , Xu Lingling , Dong Jinrui , Yuan Xue , Ye Jiamin , Fan Yueyue , Liu Bing , Xie Julin , Ji Xiaoyuan 
Published: February 2024

AbstractChronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm2), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm2), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice.
Camrelizumab and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma: a phase 2 clinical trial
Authors: Liang Hu , Jiang Yao-Fei , Liu Guo-Ying , Wang Lin , Wang Jian-Wei , Lu Nian , Xia Wei-Xiong , Ke Liang-Ru , Ye Yan-Fang , Duan Jin-Lin , Bei Wei-Xin , Dong Shu-Hui , Li Wang-Zhong , Liu Li-Ting , Zhao Chong , Xie Changqing , Xiang Yan-Qun 
Published: February 2024

AbstractThe antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.
The anti-PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel in first-line treatment of metastatic triple-negative breast cancer: a multicenter phase II trial
Authors: Li Qiao , Liu Jiaxuan , Zhang Qingyuan , Ouyang Quchang , Zhang Yang , Liu Qiang , Sun Tao , Ye Feng , Zhang Baochun , Xia Summer , Zhang Bangyong , Xu Binghe 
Published: February 2024

AbstractThis multicenter, phase II study (NCT03872791) aims to evaluate the efficacy and safety of the anti-PD-L1/CTLA-4 bispecific antibody KN046 combined with nab-paclitaxel in the first-line treatment of patients with metastatic triple-negative breast cancer (TNBC). The primary endpoints included objective response rate (ORR) and duration of response (DoR), and secondary endpoints included progression-free survival (PFS), overall survival (OS) rate, safety, and the correlation of PD-L1 status with clinical efficacy. This trial met pre-specified endpoints. 27 female patients were enrolled sequentially to receive KN046 in two dose levels (3 mg/kg or 5 mg/kg). Among the 25 evaluable patients, the ORR achieved 44.0% (95% CI, 24.4% − 65.1%), and the median DoR was not mature. The median PFS reached 7.33 months (95%CI, 3.68 − 11.07 months), and the median OS was 30.92 months (95%CI, 14.75 - NE months). In PD-L1 positive patients, PFS was 8.61 months (versus 4.73 months) and the 2-year OS rate was 62.5% (versus 57.1%) compared to PD-L1 negative patients. Patients tolerated well the combination therapy. In general, KN046 combined with nab-paclitaxel showed favorable efficacy and survival benefits with tolerable toxicity in the first-line treatment of metastatic TNBC, especially PD-L1 positive, which is worth further investigation.
Determining intrinsic potentials and validating optical binding forces between colloidal particles using optical tweezers
Authors: Zhang Chi , Muñetón Díaz José , Muster Augustin , Abujetas Diego R. , Froufe-Pérez Luis S. , Scheffold Frank 
Published: February 2024

AbstractUnderstanding the interactions between small, submicrometer-sized colloidal particles is crucial for numerous scientific disciplines and technological applications. In this study, we employ optical tweezers as a powerful tool to investigate these interactions. We utilize a full image reconstruction technique to achieve high precision in characterizing particle pairs that enable nanometer-scale measurement of their positions. This approach captures intricate details and provides a comprehensive understanding of the spatial arrangement between particles, overcoming previous limitations in resolution. Moreover, our research demonstrates that properly accounting for optical binding forces to determine the intrinsic interaction potential is vital. We employ a discrete dipole approximation approach to calculate optical binding potentials and achieve a good agreement between the calculated and observed binding forces. We incorporate the findings from these simulations into the assessment of the intrinsic interaction potentials and validate our methodology by using short-range depletion attraction induced by micelles as an example.
Tuning oxidant and antioxidant activities of ceria by anchoring copper single-site for antibacterial application
Authors: Jiang Peng , Zhang Ludan , Liu Xiaolong , Ye Chenliang , Zhu Peng , Tan Ting , Wang Dingsheng , Wang Yuguang 
Published: February 2024

AbstractThe reaction system of hydrogen peroxide (H2O2) catalyzed by nanozyme has a broad prospect in antibacterial treatment. However, the complex catalytic activities of nanozymes lead to multiple pathways reacting in parallel, causing uncertain antibacterial results. New approach to effectively regulate the multiple catalytic activities of nanozyme is in urgent need. Herein, Cu single site is modified on nanoceria with various catalytic activities, such as peroxidase-like activity (POD) and hydroxyl radical antioxidant capacity (HORAC). Benefiting from the interaction between coordinated Cu and CeO2 substrate, POD is enhanced while HORAC is inhibited, which is further confirmed by density functional theory (DFT) calculations. Cu-CeO2 + H2O2 system shows good antibacterial properties both in vitro and in vivo. In this work, the strategy based on the interaction between coordinated metal and carrier provides a general clue for optimizing the complex activities of nanozymes.
The liver and muscle secreted HFE2-protein maintains central nervous system blood vessel integrity
Authors: Wang Xue Fan , Vigouroux Robin , Syonov Michal , Baglaenko Yuriy , Nikolakopoulou Angeliki M. , Ringuette Dene , Rus Horea , DiStefano Peter V. , Dufour Suzie , Shabanzadeh Alireza P. , Lee Seunggi , Mueller Bernhard K. , Charish Jason , Harada Hidekiyo , Fish Jason E. , Wither Joan , Wälchli Thomas , Cloutier Jean-François , Zlokovic Berislav V. , Carlen Peter L. , Monnier Philippe P. 
Published: February 2024

AbstractLiver failure causes breakdown of the Blood CNS Barrier (BCB) leading to damages of the Central-Nervous-System (CNS), however the mechanisms whereby the liver influences BCB-integrity remain elusive. One possibility is that the liver secretes an as-yet to be identified molecule(s) that circulate in the serum to directly promote BCB-integrity. To study BCB-integrity, we developed light-sheet imaging for three-dimensional analysis. We show that liver- or muscle-specific knockout of Hfe2/Rgmc induces BCB-breakdown, leading to accumulation of toxic-blood-derived fibrinogen in the brain, lower cortical neuron numbers, and behavioral deficits in mice. Soluble HFE2 competes with its homologue RGMa for binding to Neogenin, thereby blocking RGMa-induced downregulation of PDGF-B and Claudin-5 in endothelial cells, triggering BCB-disruption. HFE2 administration in female mice with experimental autoimmune encephalomyelitis, a model for multiple sclerosis, prevented paralysis and immune cell infiltration by inhibiting RGMa-mediated BCB alteration. This study has implications for the pathogenesis and potential treatment of diseases associated with BCB-dysfunction.
ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation
Authors: Mazzeo Luigi , Ghosh Soumitra , Di Cicco Emery , Isma Jovan , Tavernari Daniele , Samarkina Anastasia , Ostano Paola , Youssef Markus K. , Simon Christian , Dotto G. Paolo 
Published: February 2024

AbstractThere are significant commonalities among several pathologies involving fibroblasts, ranging from auto-immune diseases to fibrosis and cancer. Early steps in cancer development and progression are closely linked to fibroblast senescence and transformation into tumor-promoting cancer-associated fibroblasts (CAFs), suppressed by the androgen receptor (AR). Here, we identify ANKRD1 as a mesenchymal-specific transcriptional coregulator under direct AR negative control in human dermal fibroblasts (HDFs) and a key driver of CAF conversion, independent of cellular senescence. ANKRD1 expression in CAFs is associated with poor survival in HNSCC, lung, and cervical SCC patients, and controls a specific gene expression program of myofibroblast CAFs (my-CAFs). ANKRD1 binds to the regulatory region of my-CAF effector genes in concert with AP-1 transcription factors, and promotes c-JUN and FOS association. Targeting ANKRD1 disrupts AP-1 complex formation, reverses CAF activation, and blocks the pro-tumorigenic properties of CAFs in an orthotopic skin cancer model. ANKRD1 thus represents a target for fibroblast-directed therapy in cancer and potentially beyond.
A prefrontal-thalamic circuit encodes social information for social recognition
Authors: Chen Zihao , Han Yechao , Ma Zheng , Wang Xinnian , Xu Surui , Tang Yong , Vyssotski Alexei L. , Si Bailu , Zhan Yang 
Published: February 2024

AbstractSocial recognition encompasses encoding social information and distinguishing unfamiliar from familiar individuals to form social relationships. Although the medial prefrontal cortex (mPFC) is known to play a role in social behavior, how identity information is processed and by which route it is communicated in the brain remains unclear. Here we report that a ventral midline thalamic area, nucleus reuniens (Re) that has reciprocal connections with the mPFC, is critical for social recognition in male mice. In vivo single-unit recordings and decoding analysis reveal that neural populations in both mPFC and Re represent different social stimuli, however, mPFC coding capacity is stronger. We demonstrate that chemogenetic inhibitions of Re impair the mPFC-Re neural synchronization and the mPFC social coding. Projection pathway-specific inhibitions by optogenetics reveal that the reciprocal connectivity between the mPFC and the Re is necessary for social recognition. These results reveal an mPFC-thalamic circuit for social information processing.
Micropillar arrays, wide window acquisition and AI-based data analysis improve comprehensiveness in multiple proteomic applications
Authors: Matzinger Manuel , Schmücker Anna , Yelagandula Ramesh , Stejskal Karel , Krššáková Gabriela , Berger Frédéric , Mechtler Karl , Mayer Rupert L. 
Published: February 2024

AbstractComprehensive proteomic analysis is essential to elucidate molecular pathways and protein functions. Despite tremendous progress in proteomics, current studies still suffer from limited proteomic coverage and dynamic range. Here, we utilize micropillar array columns (µPACs) together with wide-window acquisition and the AI-based CHIMERYS search engine to achieve excellent proteomic comprehensiveness for bulk proteomics, affinity purification mass spectrometry and single cell proteomics. Our data show that µPACs identify ≤50% more peptides and ≤24% more proteins, while offering improved throughput, which is critical for large (clinical) proteomics studies. Combining wide precursor isolation widths of m/z 4–12 with the CHIMERYS search engine identified +51–74% and +59–150% more proteins and peptides, respectively, for single cell, co-immunoprecipitation, and multi-species samples over a conventional workflow at well-controlled false discovery rates. The workflow further offers excellent precision, with CVs <7% for low input bulk samples, and accuracy, with deviations <10% from expected fold changes for regular abundance two-proteome mixes. Compared to a conventional workflow, our entire optimized platform discovered 92% more potential interactors in a protein-protein interaction study on the chromatin remodeler Smarca5/Snf2h. These include previously described Smarca5 binding partners and undescribed ones including Arid1a, another chromatin remodeler with key roles in neurodevelopmental and malignant disorders.
Detection of senescence using machine learning algorithms based on nuclear features
Authors: Duran Imanol , Pombo Joaquim , Sun Bin , Gallage Suchira , Kudo Hiromi , McHugh Domhnall , Bousset Laura , Barragan Avila Jose Efren , Forlano Roberta , Manousou Pinelopi , Heikenwalder Mathias , Withers Dominic J. , Vernia Santiago , Goldin Robert D. , Gil Jesús 
Published: February 2024

AbstractCellular senescence is a stress response with broad pathophysiological implications. Senotherapies can induce senescence to treat cancer or eliminate senescent cells to ameliorate ageing and age-related pathologies. However, the success of senotherapies is limited by the lack of reliable ways to identify senescence. Here, we use nuclear morphology features of senescent cells to devise machine-learning classifiers that accurately predict senescence induced by diverse stressors in different cell types and tissues. As a proof-of-principle, we use these senescence classifiers to characterise senolytics and to screen for drugs that selectively induce senescence in cancer cells but not normal cells. Moreover, a tissue senescence score served to assess the efficacy of senolytic drugs and identified senescence in mouse models of liver cancer initiation, ageing, and fibrosis, and in patients with fatty liver disease. Thus, senescence classifiers can help to detect pathophysiological senescence and to discover and validate potential senotherapies.