bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psilocin acutely alters sleep-wake architecture and cortical brain activity in laboratory mice
Authors: Thomas Christopher W. , Blanco-Duque Cristina , Bréant Benjamin J. , Goodwin Guy M. , Sharp Trevor , Bannerman David M. , Vyazovskiy Vladyslav V. 
Published: February 2022

AbstractSerotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the homeostatic regulation of neuronal activity and synaptic plasticity. However, it remains largely unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 h after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow-wave activity. However, psilocin decreased the recovery rate of sleep slow-wave activity following sleep deprivation in the local field potentials of electrodes targeting the medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.
SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7
Authors: Zhang Zi-Mu , Cao Hai-Bo , Li Zhi-Heng , Zhuo Ran , Tao Yan-Fang , Li Xiao-Lu , Li Gen , Liao Xin-Mei , Fang Fang , Xie Yi , Wu Di , Wang Hai-Rong , Wang Jian-Wei , Chen Yan-Ling , Yu Juan-Juan , Jia Si-Qi , Yang Ran-Dong , Guo Xin-Yi , Yang Yang , Feng Chen-Xi , Xu Yun-Yun , Qian Guang-Hui , Pan Jian 
Published: February 2022

AbstractRecent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.
Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications
Authors: Xia Xiang , Zhang Zizhen , Zhu Chunchao , Ni Bo , Wang Shuchang , Yang Shuofei , Yu Fengrong , Zhao Enhao , Li Qing , Zhao Gang 
Published: February 2022

AbstractPostoperative abdominal infectious complication (AIC) is associated with metastasis in locally advanced gastric cancer (GC) patients after radical gastrectomy. However, the underlying mechanism remains unclear. Herein, we report that neutrophil extracellular traps (NETs), the DNA meshes released by neutrophils in response to infection, could promote GC cells proliferation, invasion, migration and epithelial–mesenchymal transition dependent on TGF-β signaling. Then we model nude mice with cecal puncture without ligation to simulate postoperative AIC and find that NETs in peripheral blood and ascites fluid facilitate GC cells extravasation and implantation into liver and peritoneum for proliferation and metastasis. Notably, TGF-β signaling inhibitor LY 2157299 could effectively impede liver and peritoneal metastasis but not concurrently aggravate sepsis in those AIC-bearing nude mice. These findings implicate that targeting downstream effectors of NETs such as TGF-β signaling might provide potential therapeutic prospect to reduce the risk of GC metastasis.
Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma
Authors: Ng Yuen Lam Dora , Ramberger Evelyn , Bohl Stephan R. , Dolnik Anna , Steinebach Christian , Conrad Theresia , Müller Sina , Popp Oliver , Kull Miriam , Haji Mohamed , Gütschow Michael , Döhner Hartmut , Walther Wolfgang , Keller Ulrich , Bullinger Lars , Mertins Philipp , Krönke Jan 
Published: February 2022

AbstractThe immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are highly effective treatments for multiple myeloma. However, virtually all patients eventually relapse due to acquired drug resistance with resistance-causing genetic alterations being found only in a small subset of cases. To identify non-genetic mechanisms of drug resistance, we here perform integrated global quantitative tandem mass tag (TMT)-based proteomic and phosphoproteomic analyses and RNA sequencing in five paired pre-treatment and relapse samples from multiple myeloma patients. These analyses reveal a CDK6-governed protein resistance signature that includes myeloma high-risk factors such as TRIP13 and RRM1. Overexpression of CDK6 in multiple myeloma cell lines reduces sensitivity to IMiDs while CDK6 inhibition by palbociclib or CDK6 degradation by proteolysis targeting chimeras (PROTACs) is highly synergistic with IMiDs in vitro and in vivo. This work identifies CDK6 upregulation as a druggable target in IMiD-resistant multiple myeloma and highlights the use of proteomic studies to uncover non-genetic resistance mechanisms in cancer.
Comparison of temperature and doping dependence of elastoresistivity near a putative nematic quantum critical point
Authors: Palmstrom J. C. , Walmsley P. , Straquadine J. A. W. , Sorensen M. E. , Hannahs S. T. , Burns D. H. , Fisher I. R. 
Published: February 2022

AbstractStrong electronic nematic fluctuations have been discovered near optimal doping for several families of Fe-based superconductors, motivating the search for a possible link between these fluctuations, nematic quantum criticality, and high temperature superconductivity. Here we probe a key prediction of quantum criticality, namely power-law dependence of the associated nematic susceptibility as a function of composition and temperature approaching the compositionally tuned putative quantum critical point. To probe the ‘bare’ quantum critical point requires suppression of the superconducting state, which we achieve by using large magnetic fields, up to 45 T, while performing elastoresistivity measurements to follow the nematic susceptibility. We performed these measurements for the prototypical electron-doped pnictide, Ba(Fe1−xCox)2As2, over a dense comb of dopings. We find that close to the putative quantum critical point, the elastoresistivity appears to obey power-law behavior as a function of composition over almost a decade of variation in composition. Paradoxically, however, we also find that the temperature dependence for compositions close to the critical value cannot be described by a single power law.
Assembling covalent organic framework membranes with superior ion exchange capacity
Authors: Wang Xiaoyao , Shi Benbing , Yang Hao , Guan Jingyuan , Liang Xu , Fan Chunyang , You Xinda , Wang Yanan , Zhang Zhe , Wu Hong , Cheng Tao , Zhang Runnan , Jiang Zhongyi 
Published: February 2022

AbstractIonic covalent organic framework membranes (iCOFMs) hold great promise in ion conduction-relevant applications because the high content and monodispersed ionic groups could afford superior ion conduction. The key to push the upper limit of ion conductivity is to maximize the ion exchange capacity (IEC). Here, we explore iCOFMs with a superhigh ion exchange capacity of 4.6 mmol g−1, using a dual-activation interfacial polymerization strategy. Fukui function is employed as a descriptor of monomer reactivity. We use Brønsted acid to activate aldehyde monomers in organic phase and Brønsted base to activate ionic amine monomers in water phase. After the dual-activation, the reaction between aldehyde monomer and amine monomer at the water-organic interface is significantly accelerated, leading to iCOFMs with high crystallinity. The resultant iCOFMs display a prominent proton conductivity up to 0.66 S cm−1, holding great promise in ion transport and ionic separation applications.
Effect of HO-1-modified BMMSCs on immune function in liver transplantation
Authors: Li Peng , Zhang Yuyi , Li Qiongxia , Zhang Yubo 
Published: February 2022

AbstractWe examined whether haem oxygenase-1 (HO-1) could enhance the immunosuppressive effects of bone marrow mesenchymal stem cells (BMMSCs) on the rejection of transplanted liver allografts in rats. The animals were divided into three groups: the normal saline (NS) group, BMMSC group and HO-1/BMMSCs group. In vitro, the extraction, culture and HO-1 transfection of BMMSCs were performed. Mixed lymphocyte response (MLR) analysis of HO-1/BMMSCs efficacy was performed. The rejection model of orthotopic liver transplantation in rats was established when BMMSCs and HO-1/BMMSCs were transfused via the portal vein. To reduce research bias, we established an isogenic Liver transplantation model of (LEW → LEW) and (BN → BN), which can achieve tolerance. Changes in histopathology and liver function in the transplanted liver and changes in regulatory T cell (Tregs), natural killer (NK) cells and cytokines after transplantation were observed in the different groups. The severe acute rejection after liver transplantation on postoperative Day 10 was observed in the NS group. The BMMSC group showed strong protective effects against rejection within the first 10 days after transplantation, while HO-1/BMMSCs showed stronger effects on rejection than BMMSCs alone. In addition, the activity of natural killer (NK) cells decreased significantly, the levels of regulatory T cells (Tregs), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) increased significantly and the levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17 (IL-17), interleukin-23 (IL-23), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) decreased significantly in the HO-1/BMMSC group compared with the BMMSC group. HO-1/BMMSCs showed better immunosuppressive effects after liver transplantation than the other treatments. Our findings reveal that HO-1 can enhance the effects of BMMSCs on inhibiting acute rejection in orthotopic liver transplantation in rats.
The fliR gene contributes to the virulence of S. marcescens in a Drosophila intestinal infection model
Authors: Sina Rahme Bechara , Lestradet Matthieu , Di Venanzio Gisela , Ayyaz Arshad , Yamba Miriam Wennida , Lazzaro Martina , Liégeois Samuel , Garcia Véscovi Eleonora , Ferrandon Dominique 
Published: February 2022

AbstractSerratia marcescens is an opportunistic bacterium that infects a wide range of hosts including humans. It is a potent pathogen in a septic injury model of Drosophila melanogaster since a few bacteria directly injected in the body cavity kill the insect within a day. In contrast, flies do not succumb to ingested bacteria for days even though some bacteria cross the intestinal barrier into the hemolymph within hours. The mechanisms by which S. marcescens attacks enterocytes and damages the intestinal epithelium remain uncharacterized. To better understand intestinal infections, we performed a genetic screen for loss of virulence of ingested S. marcescens and identified FliR, a structural component of the flagellum, as a virulence factor. Next, we compared the virulence of two flagellum mutants fliR and flhD in two distinct S. marcescens strains. Both genes are required for S. marcescens to escape the gut lumen into the hemocoel, indicating that the flagellum plays an important role for the passage of bacteria through the intestinal barrier. Unexpectedly, fliR but not flhD is involved in S. marcescens-mediated damages of the intestinal epithelium that ultimately contribute to the demise of the host. Our results therefore suggest a flagellum-independent role for fliR in bacterial virulence.
Kinematics and kinetics comparison of ultra-congruent versus medial-pivot designs for total knee arthroplasty by multibody analysis
Authors: Putame Giovanni , Terzini Mara , Rivera Fabrizio , Kebbach Maeruan , Bader Rainer , Bignardi Cristina 
Published: February 2022

AbstractNowadays, several configurations of total knee arthroplasty (TKA) implants are commercially available whose designs resulted from clinical and biomechanical considerations. Previous research activities led to the development of the so-called medial-pivot (MP) design. However, the actual benefits of the MP, with respect to other prosthesis designs, are still not well understood. The present work compares the impact of two insert geometries, namely the ultra-congruent (UC) and medial-pivot (MP), on the biomechanical behaviour of a bicondylar total knee endoprosthesis. For this purpose, a multibody model of a lower limb was created alternatively integrating the two implants having the insert geometry discretized. Joint dynamics and contact pressure distributions were evaluated by simulating a squat motion. Results showed a similar tibial internal rotation range of about 3.5°, but an early rotation occurs for the MP design. Furthermore, the discretization of the insert geometry allowed to efficiently derive the contact pressure distributions, directly within the multibody simulation framework, reporting peak pressure values of 33 MPa and 20 MPa for the UC and MP, respectively. Clinically, the presented findings confirm the possibility, through a MP design, to achieve a more natural joint kinematics, consequently improving the post-operative patient satisfaction and potentially reducing the occurrence of phenomena leading to the insert loosening.
Risk factor targeting for vaccine prioritization during the COVID-19 pandemic
Authors: Chapman Lloyd A. C. , Shukla Poojan , Rodríguez-Barraquer Isabel , Shete Priya B. , León Tomás M. , Bibbins-Domingo Kirsten , Rutherford George W. , Schechter Robert , Lo Nathan C. 
Published: February 2022

AbstractA key public health question during any disease outbreak when limited vaccine is available is who should be prioritized for early vaccination. Most vaccine prioritization analyses only consider variation in risk of infection and death by a single risk factor, such as age. We provide a more granular approach with stratification by demographics, risk factors, and location. We use this approach to compare the impact of different COVID-19 vaccine prioritization strategies on COVID-19 cases, deaths and disability-adjusted life years (DALYs) over the first 6 months of vaccine rollout, using California as a case example. We estimate the proportion of cases, deaths and DALYs averted relative to no vaccination for strategies prioritizing vaccination by a single risk factor and by multiple risk factors (e.g. age, location). When targeting by a single risk factor, we find that age-based targeting averts the most deaths (62% for 5 million individuals vaccinated) and DALYs (38%) and targeting essential workers averts the least deaths (31%) and DALYs (24%) over the first 6 months of rollout. However, targeting by two or more risk factors simultaneously averts up to 40% more DALYs. Our findings highlight the potential value of multiple-risk-factor targeting of vaccination against COVID-19 and other infectious diseases, but must be balanced with feasibility for policy.
Neural model generating klinotaxis behavior accompanied by a random walk based on C. elegans connectome
Authors: Chen Mohan , Feng Dazheng , Su Hongtao , Su Tingting , Wang Meng 
Published: February 2022

AbstractKlinotaxis is a strategy of chemotaxis behavior inCaenorhabditis elegans(C. elegans), and random walking is evident during its locomotion. As yet, the understanding of the neural mechanisms underlying these behaviors has remained limited. In this study, we present a connectome-based simulation model ofC. elegansto concurrently realize realistic klinotaxis and random walk behaviors and explore their neural mechanisms. First, input to the model is derived from an ASE sensory neuron model in which the all-or-none depolarization characteristic of ASEL neuron is incorporated for the first time. Then, the neural network is evolved by an evolutionary algorithm; klinotaxis emerged spontaneously. We identify a plausible mechanism of klinotaxis in this model. Next, we propose the liquid synapse according to the stochastic nature of biological synapses and introduce it into the model. Adopting this, the random walk is generated autonomously by the neural network, providing a new hypothesis as to the neural mechanism underlying the random walk. Finally, simulated ablation results are fairly consistent with the biological conclusion, suggesting the similarity between our model and the biological network. Our study is a useful step forward in behavioral simulation and understanding the neural mechanisms of behaviors inC. elegans.
Percutaneous coronary intervention for chronic total occlusion in octogenarians: a propensity score study
Authors: Blessing Recha R. L. , Ahoopai Majid , Geyer Martin , Brandt Moritz , Zeiher Andreas M. , Vasa-Nicotera Mariuca , Münzel Thomas , Wenzel Philip , Gori Tommaso , Dimitriadis Zisis 
Published: February 2022

AbstractFeasibility and efficacy of complex percutaneous coronary intervention (PCI) in the elderly, a more frail population due to more comorbidities is incompletely understood. We therefore set out to compare success and complication rate of PCI for chronic total occlusion (CTO) in octogenarians, in comparison to non-octogenarians. Data from 267 patients (58 patients over 80 years of age and 209 under 80 years of age) who had undergone CTO PCI were analyzed. To compare the results we calculated the propensity score and used inverse probability of treatment weighting. We evaluated demographic, clinical, angiographic, and periprocedural information. The median age of the total collective was 68 (31–90) years (octogenarian collective 82 (80–90) years vs non-octogenarians 65 (31–79) years). We observed a high success rate in both collectives (82.8% vs 90.4%, p = 0.10) and no difference in periprocedural complications or complications in the follow-up period. In our collective restenosis rate at follow-up was comparable to the propensity sore weighted population (11.3% vs 16.3%, p = 0.9). Our results show that CTO PCI in older patients is safe and feasible with comparable in-hospital and follow-up complication rates compared to a younger patient population.
Vertical oxide thin-film transistor with interfacial oxidation
Authors: Baek Yeong Jo , Kang In Hye , Hwang Sang Ho , Han Ye Lin , Kang Min Su , Kang Seok Jun , Kim Seo Gwon , Woo Jae Geun , Yu Eun Seong , Bae Byung Seong 
Published: February 2022

AbstractA vertical oxide thin-film transistor was developed with interfacial oxidation for low voltage operation. The gate metal was used as a spacer for the definition of the transistor’s channel as well as the gate electrode. After definition of the vertical side wall, an IGZO (In-Ga-Zn Oxide) layer was deposited, followed by the interfacial oxidation to form a thin gate insulator. Ta was used for the gate material due to the low Gibbs free energy and high dielectric constant of tantalum oxide. A 15 nm tantalum oxide layer was obtained by the interfacial oxidation of Ta at 400 °C under oxygen atmosphere. The thin gate oxide made it possible to operate the transistor under 1 V. The low operation voltage enables low power consumption, which is essential for mobile application.
A multi-sensory stimulating attention model for cities’ taxi service demand prediction
Authors: Liao Lyuchao , Wang Yongqiang , Zou Fumin , Bi Shuoben , Su Jinya , Sun Qi 
Published: February 2022

AbstractTaxi demand forecasting is crucial to building an efficient transportation system in a smart city. Accurate taxi demand forecasting could help the taxi management platform to allocate taxi resources in advance, alleviate traffic congestion, and reduce passenger waiting time. Thus, more efforts in industrial and academic circles have been directed towards the cities’ taxi service demand prediction (CTSDP). However, the complex nonlinear spatio-temporal relationship in demand data makes it challenging to construct an accurate forecasting model. There remain challenges in perceiving the micro spatial characteristics and the macro periodicity characteristics from cities’ taxi service demand data. What’s more, the existing methods are significantly insufficient for exploring the potential multi-time patterns from these demand data. To meet the above challenges, and also stimulated by the human perception mechanism, we propose a Multi-Sensory Stimulus Attention (MSSA) model for CTSDP. Specifically, the MSSA model integrates a detail perception attention and a stimulus variety attention for capturing the micro and macro characteristics from massive historical demand data, respectively. The multiple time resolution modules are employed to capture multiple potential spatio-temporal periodic features from massive historical demand data. Extensive experiments on the yellow taxi trip records data in Manhattan show that the MSSA model outperforms the state-of-the-art baselines.
Mitochondrial dysfunction associated with TANGO2 deficiency
Authors: Heiman Paige , Mohsen Al-Walid , Karunanidhi Anuradha , St Croix Claudette , Watkins Simon , Koppes Erik , Haas Richard , Vockley Jerry , Ghaloul-Gonzalez Lina 
Published: February 2022

AbstractTransport and Golgi Organization protein 2 Homolog (TANGO2)-related disease is an autosomal recessive disorder caused by mutations in the TANGO2 gene. Symptoms typically manifest in early childhood and include developmental delay, stress-induced episodic rhabdomyolysis, and cardiac arrhythmias, along with severe metabolic crises including hypoglycemia, lactic acidosis, and hyperammonemia. Severity varies among and within families. Previous studies have reported contradictory evidence of mitochondrial dysfunction. Since the clinical symptoms and metabolic abnormalities are suggestive of a broad dysfunction of mitochondrial energy metabolism, we undertook a broad examination of mitochondrial bioenergetics in TANGO2 deficient patients utilizing skin fibroblasts derived from three patients exhibiting TANGO2-related disease. Functional studies revealed that TANGO2 protein was present in mitochondrial extracts of control cells but not patient cells. Superoxide production was increased in patient cells, while oxygen consumption rate, particularly under stress, along with relative ATP levels and β-oxidation of oleate were reduced. Our findings suggest that mitochondrial function should be assessed and monitored in all patients with TANGO2 mutation as targeted treatment of the energy dysfunction could improve outcome in this condition.