bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lateral plate mesoderm cell-based organoid system for NK cell regeneration from human pluripotent stem cells
Authors: Huang Dehao , Li Jianhuan , Hu Fangxiao , Xia Chengxiang , Weng Qitong , Wang Tongjie , Peng Huan , Wu Bingyan , Wu Hongling , Xiong Jiapin , Lin Yunqing , Wang Yao , Zhang Qi , Liu Xiaofei , Liu Lijuan , Zheng Xiujuan , Geng Yang , Du Xin , Zhu Xiaofan , Wang Lei , Hao Jie , Wang Jinyong 
Published: November 2022

AbstractHuman pluripotent stem cell (hPSC)-induced NK (iNK) cells are a source of off-the-shelf cell products for universal immune therapy. Conventional methods for iNK cell regeneration from hPSCs include embryoid body (EB) formation and feeder-based expansion steps, which are time-consuming and cause instability and high costs of manufacturing. Here, we develop an EB-free, organoid aggregate method for NK cell regeneration from hPSCs. In a short time-window of 27-day induction, millions of hPSC input can output over billions of iNK cells without the necessity of NK cell expansion feeders. The iNK cells highly express classical toxic granule proteins, apoptosis-inducing ligands, as well as abundant activating and inhibitory receptors. Functionally, the iNK cells eradicate human tumor cells via mechanisms of direct cytotoxicity, apoptosis, and antibody-dependent cellular cytotoxicity. This study provides a reliable scale-up method for regenerating human NK cells from hPSCs, which promotes the universal availability of NK cell products for immune therapy.
Investigation of the urinary sodium-to-potassium ratio target level based on the recommended dietary intake goals for the Japanese population: The INTERMAP Japan
Authors: Salman Ebtehal , Kadota Aya , Okami Yukiko , Kondo Keiko , Yoshita Katsushi , Okuda Nagako , Nakagawa Hideaki , Saitoh Shigeyuki , Sakata Kiyomi , Okayama Akira , Chan Queenie , Elliott Paul , Stamler Jeremiah , Ueshima Hirotsugu , Miura Katsuyuki ,   for the INTERMAP Research Group
Published: November 2022

AbstractGrowing epidemiological evidence has shown an association of the urinary sodium (Na) to potassium (K) ratio (Na/K ratio) with blood pressure and cardiovascular diseases. However, no clear cutoff level has been defined. We investigated the cutoff level of the urinary Na/K ratio under different dietary guidelines for Japanese individuals, especially that endorsed by the 2020 revised Japanese Dietary Reference Intakes (DRIs). A population of 1145 Japanese men and women aged 40 to 59 years from the INTERMAP study was examined. Using high-quality standardized data, the averages of two 24 h urinary collections and four 24 h dietary recalls were used to calculate the 24 h urinary and dietary Na/K ratios, respectively. Associations between the urinary and dietary Na/K ratios were tested by sex- and age-adjusted partial correlation. The optimal urinary Na/K ratio cutoff level was determined by receiver operating characteristic (ROC) curves and sex-specific cross tables for recommended dietary K and salt. Overall, the average molar ratio of 24 h urinary Na/K was 4.3. We found moderate correlations (P < 0.001) of the 24 h urinary Na/K ratio with 24 h urinary Na and K excretion (r = 0.52, r = −0.49, respectively) and the dietary Na/K ratio (r = 0.53). ROC curves showed that a 24 h urinary Na/K ratio of approximately 2 predicted Na and K intake that meets the dietary goals of the Japanese DRIs. The range of urinary Na/K ratios meeting the dietary goals of the Japanese DRIs for both Na and K was 1.6‒2.2 for men and 1.7‒1.9 for women. Accomplishing a urinary Na/K ratio of 2 would be desirable to achieve the DRIs dietary goals for both Na and K simultaneously in middle-aged Japanese men and women accustomed to Japanese dietary habits. This observational study is registered at www.clinicaltrials.gov as NCT00005271.
Generalizable spelling using a speech neuroprosthesis in an individual with severe limb and vocal paralysis
Authors: Metzger Sean L. , Liu Jessie R. , Moses David A. , Dougherty Maximilian E. , Seaton Margaret P. , Littlejohn Kaylo T. , Chartier Josh , Anumanchipalli Gopala K. , Tu-Chan Adelyn , Ganguly Karunesh , Chang Edward F. 
Published: November 2022

AbstractNeuroprostheses have the potential to restore communication to people who cannot speak or type due to paralysis. However, it is unclear if silent attempts to speak can be used to control a communication neuroprosthesis. Here, we translated direct cortical signals in a clinical-trial participant (ClinicalTrials.gov; NCT03698149) with severe limb and vocal-tract paralysis into single letters to spell out full sentences in real time. We used deep-learning and language-modeling techniques to decode letter sequences as the participant attempted to silently spell using code words that represented the 26 English letters (e.g. “alpha” for “a”). We leveraged broad electrode coverage beyond speech-motor cortex to include supplemental control signals from hand cortex and complementary information from low- and high-frequency signal components to improve decoding accuracy. We decoded sentences using words from a 1,152-word vocabulary at a median character error rate of 6.13% and speed of 29.4 characters per minute. In offline simulations, we showed that our approach generalized to large vocabularies containing over 9,000 words (median character error rate of 8.23%). These results illustrate the clinical viability of a silently controlled speech neuroprosthesis to generate sentences from a large vocabulary through a spelling-based approach, complementing previous demonstrations of direct full-word decoding.
Cell division drives DNA methylation loss in late-replicating domains in primary human cells
Authors: Endicott Jamie L. , Nolte Paula A. , Shen Hui , Laird Peter W. 
Published: November 2022

AbstractDNA methylation undergoes dramatic age-related changes, first described more than four decades ago. Loss of DNA methylation within partially methylated domains (PMDs), late-replicating regions of the genome attached to the nuclear lamina, advances with age in normal tissues, and is further exacerbated in cancer. We present here experimental evidence that this DNA hypomethylation is directly driven by proliferation-associated DNA replication. Within PMDs, loss of DNA methylation at low-density CpGs in A:T-rich immediate context (PMD solo-WCGWs) tracks cumulative population doublings in primary cell culture. Cell cycle deceleration results in a proportional decrease in the rate of DNA hypomethylation. Blocking DNA replication via Mitomycin C treatment halts methylation loss. Loss of methylation continues unabated after TERT immortalization until finally reaching a severely hypomethylated equilibrium. Ambient oxygen culture conditions increases the rate of methylation loss compared to low-oxygen conditions, suggesting that some methylation loss may occur during unscheduled, oxidative damage repair-associated DNA synthesis. Finally, we present and validate a model to estimate the relative cumulative replicative histories of human cells, which we call “RepliTali” (Replication Times Accumulated in Lifetime).
Multimodal collective swimming of magnetically articulated modular nanocomposite robots
Authors: Won Sukyoung , Lee Hee Eun , Cho Young Shik , Yang Kijun , Park Jeong Eun , Yang Seung Jae , Wie Jeong Jae 
Published: November 2022

AbstractMagnetically responsive composites can impart maneuverability to miniaturized robots. However, collective actuation of these composite robots has rarely been achieved, although conducting cooperative tasks is a promising strategy for accomplishing difficult missions with a single robot. Here, we report multimodal collective swimming of ternary-nanocomposite-based magnetic robots capable of on-demand switching between rectilinear translational swimming and rotational swimming. The nanocomposite robots comprise a stiff yet lightweight carbon nanotube yarn (CNTY) framework surrounded by a magnetic polymer composite, which mimics the hierarchical architecture of musculoskeletal systems, yielding magnetically articulated multiple robots with an agile above-water swimmability (~180 body lengths per second) and modularity. The multiple robots with multimodal swimming facilitate the generation and regulation of vortices, enabling novel vortex-induced transportation of thousands of floating microparticles and heavy semi-submerged cargos. The controllable collective actuation of these biomimetic nanocomposite robots can lead to versatile robotic functions, including microplastic removal, microfluidic vortex control, and transportation of pharmaceuticals.
CDKN1A is a target for phagocytosis-mediated cellular immunotherapy in acute leukemia
Authors: Allouch Awatef , Voisin Laurent , Zhang Yanyan , Raza Syed Qasim , Lecluse Yann , Calvo Julien , Selimoglu-Buet Dorothée , de Botton Stéphane , Louache Fawzia , Pflumio Françoise , Solary Eric , Perfettini Jean-Luc 
Published: November 2022

AbstractTargeting the reprogramming and phagocytic capacities of tumor-associated macrophages (TAMs) has emerged as a therapeutic opportunity for cancer treatment. Here, we demonstrate that tumor cell phagocytosis drives the pro-inflammatory activation of TAMs and identify a key role for the cyclin-dependent kinase inhibitor CDKN1A (p21). Through the transcriptional repression of Signal-Regularity Protein α (SIRPα), p21 promotes leukemia cell phagocytosis and, subsequently, the pro-inflammatory reprogramming of phagocytic macrophages that extends to surrounding macrophages through Interferon γ. In mouse models of human T-cell acute lymphoblastic leukemia (T-ALL), infusion of human monocytes (Mos) engineered to overexpress p21 (p21TD-Mos) leads to Mo differentiation into phagocytosis-proficient TAMs that, after leukemia cell engulfment, undergo pro-inflammatory activation and trigger the reprogramming of bystander TAMs, reducing the leukemic burden and substantially prolonging survival in mice. These results reveal p21 as a trigger of phagocytosis-guided pro-inflammatory TAM reprogramming and highlight the potential for p21TD-Mo-based cellular therapy as a cancer immunotherapy.
Pharmacological blockade of TEAD–YAP reveals its therapeutic limitation in cancer cells
Authors: Sun Yang , Hu Lu , Tao Zhipeng , Jarugumilli Gopala K. , Erb Hannah , Singh Alka , Li Qi , Cotton Jennifer L. , Greninger Patricia , Egan Regina K. , Tony Ip Y. , Benes Cyril H. , Che Jianwei , Mao Junhao , Wu Xu 
Published: November 2022

AbstractTargeting TEAD autopalmitoylation has been proposed as a therapeutic approach for YAP-dependent cancers. Here we show that TEAD palmitoylation inhibitor MGH-CP1 and analogues block cancer cell “stemness”, organ overgrowth and tumor initiation in vitro and in vivo. MGH-CP1 sensitivity correlates significantly with YAP-dependency in a large panel of cancer cell lines. However, TEAD inhibition or YAP/TAZ knockdown leads to transient inhibition of cell cycle progression without inducing cell death, undermining their potential therapeutic utilities. We further reveal that TEAD inhibition or YAP/TAZ silencing leads to VGLL3-mediated transcriptional activation of SOX4/PI3K/AKT signaling axis, which contributes to cancer cell survival and confers therapeutic resistance to TEAD inhibitors. Consistently, combination of TEAD and AKT inhibitors exhibits strong synergy in inducing cancer cell death. Our work characterizes the therapeutic opportunities and limitations of TEAD palmitoylation inhibitors in cancers, and uncovers an intrinsic molecular mechanism, which confers potential therapeutic resistance.
Simultaneously tuning interlayer spacing and termination of MXenes by Lewis-basic halides
Authors: Zhang Tianze , Chang Libo , Zhang Xiaofeng , Wan Hujie , Liu Na , Zhou Liujiang , Xiao Xu 
Published: November 2022

AbstractThe surface and interface chemistry are of significance on controlling the properties of two-dimensional transition metal carbides and nitrides (MXenes). Numerous efforts have been devoted to the regulation of Ti3C2Tx MXene, however, tuning interlayer spacing and surface halogen termination of other MXenes (besides Ti3C2Tx) is rarely reported while demanded. Here we propose a Lewis-basic halides treatment, which is capable of simultaneously engineering the interlayer spacing and surface termination of various MXenes. Benefited from the abundant desolvated halogen anions and cations in molten state Lewis-basic halides, the -F termination was substituted by nucleophilic reaction and the interlayer spacing was enlarged. Ti3C2Tx MXene treated by this method showed a high specific capacity of 229 mAh g−1 for Li+ storage, which is almost 2 times higher than pristine one. Considering the universality, our method provides an approach to regulating the properties of MXenes, which may expand their potential applications in energy storage, optoelectronics and beyond.
Phosphate limitation intensifies negative effects of ocean acidification on globally important nitrogen fixing cyanobacterium
Authors: Zhang Futing , Wen Zuozhu , Wang Shanlin , Tang Weiyi , Luo Ya-Wei , Kranz Sven A. , Hong Haizheng , Shi Dalin 
Published: November 2022

AbstractGrowth of the prominent nitrogen-fixing cyanobacterium Trichodesmium is often limited by phosphorus availability in the ocean. How nitrogen fixation by phosphorus-limited Trichodesmium may respond to ocean acidification remains poorly understood. Here, we use phosphate-limited chemostat experiments to show that acidification enhanced phosphorus demands and decreased phosphorus-specific nitrogen fixation rates in Trichodesmium. The increased phosphorus requirements were attributed primarily to elevated cellular polyphosphate contents, likely for maintaining cytosolic pH homeostasis in response to acidification. Alongside the accumulation of polyphosphate, decreased NADP(H):NAD(H) ratios and impaired chlorophyll synthesis and energy production were observed under acidified conditions. Consequently, the negative effects of acidification were amplified compared to those demonstrated previously under phosphorus sufficiency. Estimating the potential implications of this finding, using outputs from the Community Earth System Model, predicts that acidification and dissolved inorganic and organic phosphorus stress could synergistically cause an appreciable decrease in global Trichodesmium nitrogen fixation by 2100.
Correlation-induced magnetism in substrate-supported 2D metal-organic frameworks
Authors: Field Bernard , Schiffrin Agustin , Medhekar Nikhil V. 
Published: November 2022

AbstractTwo-dimensional (2D) metal-organic frameworks (MOFs) with a kagome lattice can exhibit strong electron-electron interactions, which can lead to tunable quantum phases including many exotic magnetic phases. While technological developments of 2D MOFs typically take advantage of substrates for growth, support, and electrical contacts, investigations often ignore substrates and their dramatic influence on electronic properties. Here, we show how substrates alter the correlated magnetic phases in kagome MOFs using systematic density functional theory and mean-field Hubbard calculations. We demonstrate that MOF-substrate coupling, MOF-substrate charge transfer, strain, and external electric fields are key variables, activating and deactivating magnetic phases in these materials. While we consider the example of kagome-arranged 9,10-dicyanoanthracene molecules coordinated with copper atoms, our findings should generalise to any 2D kagome material. This work offers useful predictions for tunable interaction-induced magnetism in surface-supported 2D (metal-)organic materials, opening the door to solid-state electronic and spintronic technologies based on such systems.
Remimazolam besylate for the sedation of postoperative patients undergoing invasive mechanical ventilation in the ICU: a prospective dose‒response study
Authors: Chen Xiaoyan , Zhang Jiancheng , Yuan Shiying , Huang Haiyan 
Published: November 2022

AbstractThis single-center study aimed to determine the effective dose and safety of remimazolam besylate for the sedation of postoperative patients undergoing invasive mechanical ventilation in the intensive care unit (ICU). Mechanically ventilated patients admitted to the ICU after surgery were included. The Narcotrend index (NTI) was used to assess the depth of sedation, and the Richmond Agitation-Sedation Scale (RASS) score was also recorded. Remimazolam besylate was administered initially at a loading dose of 0.02 mg/kg, followed by a gradual increase of 0.005 mg/kg each time until the targeted depth of sedation was achieved (NTI 65–94). A maintenance dose of remimazolam besylate was administered starting at 0.2 mg/kg/h, followed by increments or subtractions of 0.05 mg/kg/h each time until a satisfactory depth of sedation was achieved and maintained for at least 30 min. The demographic data, anesthesia, surgery types, hemodynamics and respiratory parameters were recorded. Adverse events and adverse drug reactions were monitored for safety. Twenty-three patients were eventually included in this study covering a period of 1 year. A satisfactory depth of sedation was achieved by a single intravenous infusion of remimazolam besylate at a loading dose of 0.02–0.05 mg/kg followed by a maintenance dose of 0.20–0.35 mg/kg/h. There were no significant changes in hemodynamic and respiratory parameters within 10 min after the administration of remimazolam besylate. In addition, a significant correlation was observed between the NTI and the RASS score for assessing sedation (r = 0.721, P < 0.001). The NTI showed a predictive probability for a RASS score of 0.817. Remimazolam besylate was effective for mild/moderate sedation of invasively mechanically ventilated postoperative patients in the ICU while maintaining excellent respiratory and hemodynamic stability. The NTI can be used as a good tool for the objective evaluation of the depth of sedation and agitation.
Evaluation of commercially available fully automated and ELISA-based assays for detecting anti-SARS-CoV-2 neutralizing antibodies
Authors: Zedan Hadeel T. , Yassine Hadi M. , Al-Sadeq Duaa W. , Liu Na , Qotba Hamda , Nicolai Eleonora , Pieri Massimo , Bernardini Sergio , Abu-Raddad Laith J. , Nasrallah Gheyath K. 
Published: November 2022

AbstractRapid and accurate measurement of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-specific neutralizing antibodies (nAbs) is paramount for monitoring immunity in infected and vaccinated subjects. The current gold standard relies on pseudovirus neutralization tests which require sophisticated skills and facilities. Alternatively, recent competitive immunoassays measuring anti-SARS-CoV-2 nAbs are proposed as a quick and commercially available surrogate virus neutralization test (sVNT). Here, we report the performance evaluation of three sVNTs, including two ELISA-based assays and an automated bead-based immunoassay for detecting nAbs against SARS-CoV-2. The performance of three sVNTs, including GenScript cPass, Dynamiker, and Mindray NTAb was assessed in samples collected from SARS-CoV-2 infected patients (n = 160), COVID-19 vaccinated individuals (n = 163), and pre-pandemic controls (n = 70). Samples were collected from infected patients and vaccinated individuals 2–24 weeks after symptoms onset or second dose administration. Correlation analysis with pseudovirus neutralization test (pVNT) and immunoassays detecting anti-SARS-CoV-2 binding antibodies was performed. Receiver operating characteristic (ROC) curve analysis was generated to assess the optimal threshold for detecting nAbs by each assay. All three sVNTs showed an excellent performance in terms of specificity (100%) and sensitivity (100%, 97.0%, and 97.1% for GenScript, Dynamiker, and Mindray, respectively) in samples collected from vaccinated subjects. GenScript demonstrated the strongest correlation with pVNT (r = 0.743, R2 = 0.552), followed by Mindray (r = 0.718, R2 = 0.515) and Dynamiker (r = 0.608, R2 = 0.369). Correlation with anti-SARS-CoV-2 binding antibodies was variable, but the strongest correlations were observed between anti-RBD IgG antibodies and Mindray (r = 0.952, R2 = 0.907). ROC curve analyses demonstrated excellent performance for all three sVNT assays in both groups, with an AUC ranging between 0.99 and 1.0 (p < 0.0001). Also, it was shown that the manufacturer's recommended cutoff values could be modified based on the tested cohort without significantly affecting the sVNT performance. The sVNT provides a rapid, low-cost, and scalable alternative to conventional neutralization assays for measuring and expanding nAbs testing across various research and clinical settings. Also, it could aid in evaluating actual protective immunity at the population level and assessing vaccine effectiveness to lay a foundation for boosters' requirements.
Estrogen-induced immune changes within the normal mammary gland
Authors: Tower Helen , Dall Genevieve , Davey Ashleigh , Stewart Melanie , Lanteri Patrick , Ruppert Meagan , Lambouras Maria , Nasir Ibraheem , Yeow Serene , Darcy Phillip K. , Ingman Wendy V. , Parker Belinda , Haynes Nicole M. , Britt Kara L. 
Published: November 2022

AbstractBreast cancer (BCa) incidence increases following aberrant hormone exposure, which has been linked to direct effects on estrogen receptor (ER)+mammary epithelium. While estrogen exposure during mammary involution has been shown to drive tumour growth via neutrophils, the potential for the ER + immune microenvironment to mediate part (in addition to mammary epithelial cells) of hormonally controlled BCa risk during normal development has not been assessed. We collected mammary tissue, lymph nodes and blood from tumour naïve mice treated with, oophorectomy, estrogen (17β estradiol) or Fulvestrant. Flow cytometry was used to examine the impact on the frequency of innate and adaptive immune cells. Oophorectomy and fulvestrant decreased the proportion of macrophages, particularly pro-tumour polarized M2 macrophages and neutrophils. Conversely, dendritic cells were increased by these therapies, as were eosinophils. Estrogen increased the proportion of M2 macrophages and to a lesser extent CD4-CD8- double negative and FoxP3+regulatory T cells but decreased CD8 + T cells and B cells. Excluding eosinophils, these changes were restricted to the mammary tissue. This suggests that inhibiting estrogen action lowers the immune suppressive myeloid cells, increases in antigen presentation and eosinophil-mediated direct or indirect cytotoxic effects. In contrast, estrogen exposure, which drives BCa risk, increases the suppressive myeloid cells and reduces anti-tumour cytotoxic T cells. The impact of hormonal exposure on BCa risk, may in part be linked to its immune modulatory activity.
Utilization of Galerkin finite element strategy to investigate comparison performance among two hybrid nanofluid models
Authors: Sohail Muhammad , Nazir Umar , Naz Samaira , Singh Abha , Mukdasai Kanit , Ali Mohamed R. , Khan Muhammad Jahangir , Galal Ahmed M. 
Published: November 2022

AbstractThe utilization of Fourier’s law of heat conduction provides the parabolic partial differential equation of thermal transport, which provides the information regarding thermal transport for the initial time, but during many practical applications, this theory is not applicable. Therefore, the utilization of modified heat flux model is to be used. This work discusses the utilization of non-Fourier heat flux model to investigate thermal performance of tri-hybrid nanoparticles mixture immersed in Carreau Yasuda material past over a Riga plate by using Hamilton Crosser and Yamada Ota models considering the variable thermos-physical characteristics. The phenomenon presenting the transport of momentum and energy are developed in the form of coupled partial differential equations, which are complex and then transformed into ordinary differential equations by using an appropriate transformation. The transformed equations have been tackled numerically via finite element scheme and the authenticity of obtained solution is shown with the help of comparative analysis of present results with those are available in open literature.