bluuebunny/crossref_metadata_2025_split huggingface dataset:
RANKL+ senescent cells under mechanical stress: a therapeutic target for orthodontic root resorption using senolytics
Authors: Zhou Yue , Nishiura Aki , Morikuni Hidetoshi , Deng Wenqi , Tsujibayashi Toru , Momota Yoshihiro , Azetsu Yuki , Takami Masamichi , Honda Yoshitomo , Matsumoto Naoyuki 
Published: May 2023

AbstractIn dentistry, orthodontic root resorption is a long-lasting issue with no effective treatment strategy, and its mechanisms, especially those related to senescent cells, remain largely unknown. Here, we used an orthodontic intrusion tooth movement model with an L-loop in rats to demonstrate that mechanical stress-induced senescent cells aggravate apical root resorption, which was prevented by administering senolytics (a dasatinib and quercetin cocktail). Our results indicated that cementoblasts and periodontal ligament cells underwent cellular senescence (p21+ or p16+) and strongly expressed receptor activator of nuclear factor-kappa B (RANKL) from day three, subsequently inducing tartrate-resistant acid phosphatase (TRAP)-positive odontoclasts and provoking apical root resorption. More p21+ senescent cells expressed RANKL than p16+ senescent cells. We observed only minor changes in the number of RANKL+ non-senescent cells, whereas RANKL+ senescent cells markedly increased from day seven. Intriguingly, we also found cathepsin K+p21+p16+ cells in the root resorption fossa, suggesting senescent odontoclasts. Oral administration of dasatinib and quercetin markedly reduced these senescent cells and TRAP+ cells, eventually alleviating root resorption. Altogether, these results unveil those aberrant stimuli in orthodontic intrusive tooth movement induced RANKL+ early senescent cells, which have a pivotal role in odontoclastogenesis and subsequent root resorption. These findings offer a new therapeutic target to prevent root resorption during orthodontic tooth movement.
Design of bacteriophage T4-based artificial viral vectors for human genome remodeling
Authors: Zhu Jingen , Batra Himanshu , Ananthaswamy Neeti , Mahalingam Marthandan , Tao Pan , Wu Xiaorong , Guo Wenzheng , Fokine Andrei , Rao Venigalla B. 
Published: May 2023

AbstractDesigning artificial viral vectors (AVVs) programmed with biomolecules that can enter human cells and carry out molecular repairs will have broad applications. Here, we describe an assembly-line approach to build AVVs by engineering the well-characterized structural components of bacteriophage T4. Starting with a 120 × 86 nm capsid shell that can accommodate 171-Kbp DNA and thousands of protein copies, various combinations of biomolecules, including DNAs, proteins, RNAs, and ribonucleoproteins, are externally and internally incorporated. The nanoparticles are then coated with cationic lipid to enable efficient entry into human cells. As proof of concept, we assemble a series of AVVs designed to deliver full-length dystrophin gene or perform various molecular operations to remodel human genome, including genome editing, gene recombination, gene replacement, gene expression, and gene silencing. These large capacity, customizable, multiplex, and all-in-one phage-based AVVs represent an additional category of nanomaterial that could potentially transform gene therapies and personalized medicine.
A mutation in switch I alters the load-dependent kinetics of myosin Va
Authors: Marang Christopher , Scott Brent , Chambers James , Gunther Laura K. , Yengo Christopher M. , Debold Edward P. 
Published: May 2023

AbstractMyosin Va is the molecular motor that drives intracellular vesicular transport, powered by the transduction of chemical energy from ATP into mechanical work. The coupling of the powerstroke and phosphate (Pi) release is key to understanding the transduction process, and crucial details of this process remain unclear. Therefore, we determined the effect of elevated Pi on the force-generating capacity of a mini-ensemble of myosin Va S1 (WT) in a laser trap assay. By increasing the stiffness of the laser trap we determined the effect of increasing resistive loads on the rate of Pi-induced detachment from actin, and quantified this effect using the Bell approximation. We observed that WT myosin generated higher forces and larger displacements at the higher laser trap stiffnesses in the presence of 30 mM Pi, but binding event lifetimes decreased dramatically, which is most consistent with the powerstroke preceding the release of Pi from the active site. Repeating these experiments using a construct with a mutation in switch I of the active site (S217A) caused a seven-fold increase in the load-dependence of the Pi-induced detachment rate, suggesting that the S217A region of switch I may help mediate the load-dependence of Pi-rebinding.
Trust within human-machine collectives depends on the perceived consensus about cooperative norms
Authors: Makovi Kinga , Sargsyan Anahit , Li Wendi , Bonnefon Jean-François , Rahwan Talal 
Published: May 2023

AbstractWith the progress of artificial intelligence and the emergence of global online communities, humans and machines are increasingly participating in mixed collectives in which they can help or hinder each other. Human societies have had thousands of years to consolidate the social norms that promote cooperation; but mixed collectives often struggle to articulate the norms which hold when humans coexist with machines. In five studies involving 7917 individuals, we document the way people treat machines differently than humans in a stylized society of beneficiaries, helpers, punishers, and trustors. We show that a different amount of trust is gained by helpers and punishers when they follow norms over not doing so. We also demonstrate that the trust-gain of norm-followers is associated with trustors’ assessment about the consensual nature of cooperative norms over helping and punishing. Lastly, we establish that, under certain conditions, informing trustors about the norm-consensus over helping tends to decrease the differential treatment of both machines and people interacting with them. These results allow us to anticipate how humans may develop cooperative norms for human-machine collectives, specifically, by relying on already extant norms in human-only groups. We also demonstrate that this evolution may be accelerated by making people aware of their emerging consensus.
Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations
Authors: Feofanova Elena V. , Brown Michael R. , Alkis Taryn , Manuel Astrid M. , Li Xihao , Tahir Usman A. , Li Zilin , Mendez Kevin M. , Kelly Rachel S. , Qi Qibin , Chen Han , Larson Martin G. , Lemaitre Rozenn N. , Morrison Alanna C. , Grieser Charles , Wong Kari E. , Gerszten Robert E. , Zhao Zhongming , Lasky-Su Jessica ,   NHLBI Trans-Omics for Precision Medicine (TOPMed), Lin Honghuang , Haessler Jeffrey , Brody Jennifer A. , North Kari E. , Taylor Kent D. , Clish Clary B. , Wilson James G. , Lin Xihong , Kaplan Robert C. , Kooperberg Charles , Psaty Bruce M. , Rich Stephen S. , Rotter Jerome I. , Vasan Ramachandran S. , Boerwinkle Eric , Yu Bing 
Published: May 2023

AbstractCirculating metabolite levels may reflect the state of the human organism in health and disease, however, the genetic architecture of metabolites is not fully understood. We have performed a whole-genome sequencing association analysis of both common and rare variants in up to 11,840 multi-ethnic participants from five studies with up to 1666 circulating metabolites. We have discovered 1985 novel variant-metabolite associations, and validated 761 locus-metabolite associations reported previously. Seventy-nine novel variant-metabolite associations have been replicated, including three genetic loci located on the X chromosome that have demonstrated its involvement in metabolic regulation. Gene-based analysis have provided further support for seven metabolite-replicated loci pairs and their biologically plausible genes. Among those novel replicated variant-metabolite pairs, follow-up analyses have revealed that 26 metabolites have colocalized with 21 tissues, seven metabolite-disease outcome associations have been putatively causal, and 7 metabolites might be regulated by plasma protein levels. Our results have depicted the genetic contribution to circulating metabolite levels, providing additional insights into understanding human disease.
Superior zero thermal expansion dual-phase alloy via boron-migration mediated solid-state reaction
Authors: Yu Chengyi , Lin Kun , Chen Xin , Jiang Suihe , Cao Yili , Li Wenjie , Chen Liang , An Ke , Chen Yan , Yu Dunji , Kato Kenichi , Zhang Qinghua , Gu Lin , You Li , Kuang Xiaojun , Wu Hui , Li Qiang , Deng Jinxia , Xing Xianran 
Published: May 2023

AbstractRapid progress in modern technologies demands zero thermal expansion (ZTE) materials with multi-property profiles to withstand harsh service conditions. Thus far, the majority of documented ZTE materials have shortcomings in different aspects that limit their practical utilization. Here, we report on a superior isotropic ZTE alloy with collective properties regarding wide operating temperature windows, high strength-stiffness, and cyclic thermal stability. A boron-migration-mediated solid-state reaction (BMSR) constructs a salient “plum pudding” structure in a dual-phase Er-Fe-B alloy, where the precursor ErFe10 phase reacts with the migrated boron and transforms into the target Er2Fe14B (pudding) and α-Fe phases (plum). The formation of such microstructure helps to eliminate apparent crystallographic texture, tailor and form isotropic ZTE, and simultaneously enhance the strength and toughness of the alloy. These findings suggest a promising design paradigm for comprehensive performance ZTE alloys.
Cerebral organoids transplantation repairs infarcted cortex and restores impaired function after stroke
Authors: Cao Shi-Ying , Yang Di , Huang Zhen-Quan , Lin Yu-Hui , Wu Hai-Yin , Chang Lei , Luo Chun-Xia , Xu Yun , Liu Yan , Zhu Dong-Ya 
Published: May 2023

AbstractStroke usually causes prolonged or lifelong disability, owing to the permanent loss of infarcted tissue. Although a variety of stem cell transplantation has been explored to improve neuronal defect behavior by enhancing neuroplasticity, it remains unknown whether the infarcted tissue can be reconstructed. We here cultured human cerebral organoids derived from human pluripotent stem cells (hPSCs) and transplanted them into the junction of the infarct core and the peri-infarct zone of NOD-SCID mice subjected to stroke. Months later, we found that the grafted organoids survived well in the infarcted core, differentiated into target neurons, repaired infarcted tissue, sent axons to distant brain targets, and integrated into the host neural circuit and thereby eliminated sensorimotor defect behaviors of stroke mice, whereas transplantation of dissociated single cells from organoids failed to repair the infarcted tissue. Our study offers a new strategy for reconstructing infarcted tissue via organoids transplantation thereby reversing stroke-induced disability.
Employing active learning in the optimization of culture medium for mammalian cells
Authors: Hashizume Takamasa , Ozawa Yuki , Ying Bei-Wen 
Published: May 2023

AbstractMedium optimization is a crucial step during cell culture for biopharmaceutics and regenerative medicine; however, this step remains challenging, as both media and cells are highly complex systems. Here, we addressed this issue by employing active learning. Specifically, we introduced machine learning to cell culture experiments to optimize culture medium. The cell line HeLa-S3 and the gradient-boosting decision tree algorithm were used to find optimized media as pilot studies. To acquire the training data, cell culture was performed in a large variety of medium combinations. The cellular NAD(P)H abundance, represented as A450, was used to indicate the goodness of culture media. In active learning, regular and time-saving modes were developed using culture data at 168 h and 96 h, respectively. Both modes successfully fine-tuned 29 components to generate a medium for improved cell culture. Intriguingly, the two modes provided different predictions for the concentrations of vitamins and amino acids, and a significant decrease was commonly predicted for fetal bovine serum (FBS) compared to the commercial medium. In addition, active learning-assisted medium optimization significantly increased the cellular concentration of NAD(P)H, an active chemical with a constant abundance in living cells. Our study demonstrated the efficiency and practicality of active learning for medium optimization and provided valuable information for employing machine learning technology in cell biology experiments.
Contribution of local and surrounding anthropogenic emissions to a particulate matter pollution episode in Zhengzhou, Henan, China
Authors: Wang Yaobin , Wang Feng , Min Ruiqi , Song Genxin , Song Hongquan , Zhai Shiyan , Xia Haoming , Zhang Haopeng , Ru Xutong 
Published: May 2023

AbstractIn this study, we simulated the spatial and temporal processes of a particulate matter (PM) pollution episode from December 10–29, 2019, in Zhengzhou, the provincial capital of Henan, China, which has a large population and severe PM pollution. As winter is the high incidence period of particulate pollution, winter statistical data were selected from the pollutant observation stations in the study area. During this period, the highest concentrations of PM2.5 (atmospheric PM with a diameter of less than 2.5 µm) and PM10 (atmospheric PM with a diameter of less than 10 µm) peaked at 283 μg m-3 and 316 μg m-3, respectively. The contribution rates of local and surrounding regional emissions within Henan (emissions from the regions to the south, northwest, and northeast of Zhengzhou) to PM concentrations in Zhengzhou were quantitatively analyzed based on the regional Weather Research and Forecasting model coupled with Chemistry (WRF/Chem). Model evaluation showed that the WRF/Chem can accurately simulate the spatial and temporal variations in the PM concentrations in Zhengzhou. We found that the anthropogenic emissions south of Zhengzhou were the main causes of high PM concentrations during the studied episode, with contribution rates of 14.39% and 16.34% to PM2.5 and PM10, respectively. The contributions of anthropogenic emissions from Zhengzhou to the PM2.5 and PM10 concentrations in Zhengzhou were 7.94% and 7.29%, respectively. The contributions of anthropogenic emissions from the area northeast of Zhengzhou to the PM2.5 and PM10 concentrations in Zhengzhou were 7.42% and 7.18%, respectively. These two areas had similar contributions to PM pollution in Zhengzhou. The area northeast of Zhengzhou had the lowest contributions to the PM2.5 and PM10 concentrations in Zhengzhou (5.96% and 5.40%, respectively).
PSO tuned interval type-2 fuzzy logic for load frequency control of two-area multi-source interconnected power system
Authors: Soliman Ahmed Mohammed Attiya , Bahaa Mostafa , Mehanna Mohammed A. 
Published: May 2023

AbstractNowadays, most of modern power systems integrate concentrated renewable energy resources power plants like solar and wind parks in addition to central conventional plants. The output power from these concentrated renewable energy resources varies continuously according to weather conditions like solar irradiance value or wind speed and direction, the variation for their output power may be in mega watts. In this work, Robust secondary load frequency controller (LFC) based on one of artificial intelligent technique which called interval type-2 fuzzy logic controller (IT2FLC) has been proposed for two-area multi-source interconnected power system with central solar park power plants in each area while considering non-linearities in the power system. IT2FLC has accommodated vagueness, distortions and imprecision for the power system input signals which caused by weather fluctuations and system non-linearities. In addition to LFC, another controller based also on IT2FLC has been proposed to control the output power from the central solar parks in each area of generation during cloudy periods instead of maximum power point tracking method (MPPT) in order to enhance the stability for the power system during disturbance periods. In order to enhance the performance of the proposed LFC, particle swarm optimization technique (PSO) has been utilized to optimize the proposed LFC gains to minimize the steady state error, over/under shooting value, settling time and system oscillation for the investigated power system frequency. The performance and the superiority of the proposed PSO tuned IT2FLC is evaluated and compared with another LFC based on PSO tuned cascaded PID controller while applying severe demand load and solar irradiance changes. the simulation has been carried out using matlab/simulink program.
Optical-referenceless optical frequency counter with twelve-digit absolute accuracy
Authors: Ishizawa Atsushi , Nishikawa Tadashi , Hitachi Kenichi , Akatsuka Tomoya , Oguri Katsuya 
Published: May 2023

AbstractA simpler and more accurate measurement of absolute optical frequencies (AOFs) is very important for optical communications and navigation systems. To date, an optical reference has been needed for measuring AOFs with twelve-digit accuracy because of the difficulty in measuring them directly. Here, we focus on an electro-optics-modulation comb that can bridge the vast frequency gap between photonics and electronics. We demonstrate an unprecedented method that can directly measure AOFs to an accuracy of twelve digits with an RF frequency counter by simply delivering a frequency-unknown laser into an optical phase modulator. This could open up a new horizon for optical-referenceless optical frequency metrology. Our method can also simultaneously achieve a 100-fold phase-noise reduction in a conventional signal generator. This corresponds to an increase in the transmission speed of wireless communications of by about seven times.
Three-month outcomes of faricimab loading therapy for wet age-related macular degeneration in Japan
Authors: Mukai Ryo , Kataoka Keiko , Tanaka Koji , Miyara Yasunori , Maruko Ichiro , Nakayama Makiko , Watanabe Yuto , Yamamoto Akiko , Wakatsuki Yu , Onoe Hajime , Wakugawa Sorako , Terao Nobuhiro , Hasegawa Taiji , Hashiya Nozomu , Kawai Moeko , Maruko Ruka , Itagaki Kanako , Honjo Jyunichiro , Okada Annabelle A. , Mori Ryusaburo , Koizumi Hideki , Iida Tomohiro , Sekiryu Tetsuju 
Published: May 2023

AbstractThis multicenter study aimed to assess the short-term effectiveness and safety of faricimab in treatment-naïve patients with wet age-related macular degeneration (wAMD) in Japan. We retrospectively reviewed 63 eyes of 61 patients with wAMD, including types 1, 2, and 3 macular neovascularization as well as polypoidal choroidal vasculopathy (PCV). Patients received three consecutive monthly intravitreal injections of faricimab as loading therapy. Over these 3 months, visual acuity improved gradually compared to baseline. Moreover, the central foveal thickness decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). At 3 months after initiation of faricimab therapy, a dry macula (defined as absence of intraretinal or subretinal fluid) was achieved in 82% of the eyes. Complete regression of polypoidal lesions was observed in 52% of eyes with PCV. Subfoveal choroidal thickness also decreased significantly at 1, 2, and 3 months compared to baseline (p < 0.0001). Although retinal pigment epithelium tears developed in two eyes, there were no other ocular or systemic complications observed during the 3 months of loading therapy. In conclusion, loading therapy using faricimab resulted in improved visual acuity and retinal morphology in Japanese patients with wAMD without particular safety issues.
The prevalence and burden of Rome IV bowel disorders of gut brain interaction in patients with non-alcoholic fatty liver disease: a cross-sectional study
Authors: Purssell Huw , Bennett Lucy , Street Oliver , Hanley Karen Piper , Hanley Neil , Vasant Dipesh H. , Athwal Varinder S. 
Published: May 2023

AbstractRome IV bowel disorders of gut brain interaction (DGBI) and non-alcoholic fatty liver disease (NAFLD) are highly prevalent entities with overlapping pathophysiology and risk factors. We aimed to evaluate the prevalence and burden of Rome IV irritable bowel syndrome (IBS) in patients with NAFLD. Patients diagnosed with NAFLD were recruited from a specialist liver clinic. All participants completed assessments to determine liver fibrosis severity, including liver stiffness measurement (LSM), completed the Rome IV diagnostic questionnaire for bowel disorders of gut brain interaction, the IBS symptom severity score (IBS-SSS), and the EQ-5D-5L to measure of quality-of-life (QoL). 142 patients with NAFLD (71 (50%) female, mean age 53.5 (SD ± 14.9), BMI 35.2 (SD ± 8.1) kg/M2) were recruited. 79 (55.6%) patients met criteria for a Rome IV bowel DGBI, including 50 patients (35.2%) who met the criteria for IBS (mean IBS-SSS 277.2 (SD ± 131.5)). There was no difference in liver fibrosis scores between those with and without Rome IV IBS (FIB-4 scores p = 0.14, LSM p = 0.68). Patients with NAFLD and Rome IV IBS had significantly worse QoL scores (EQ-VAS p = 0.005 and EQ-5D-5L index p = 0.0007), impairment of usual activities of daily living (p = 0.012) and were more likely to report anxiety or depression (p = 0.038). Rome IV bowel DGBI such as IBS are highly prevalent in patients with NAFLD attending liver clinics and are associated with impaired QoL and psychosocial distress.
Mathematical model analysis of effective intervention strategies on transmission dynamics of hepatitis B virus
Authors: Wodajo Firaol Asfaw , Gebru Dawit Melesse , Alemneh Haileyesus Tessema 
Published: May 2023

AbstractHepatitis B is one of the world’s most common and severe infectious diseases. Worldwide, over 350 million people are currently estimated to be persistent carriers of the hepatitis B virus (HBV), with the death of 1 million people from the chronic stage of HBV infection. In this work, developed a nonlinear mathematical model for the transmission dynamics of HBV. We constructed the mathematical model by considering vaccination, treatment, migration, and screening effects. We calculated both disease-free and endemic equilibrium points for our model. Using the next-generation matrix, an effective reproduction number for the model is calculated. We also proved the asymptotic stability of both local and global asymptotically stability of disease-free and endemic equilibrium points. By calculating the sensitivity indices, the most sensitive parameters that are most likely to affect the disease’s endemicity are identified. From the findings of this work, we recommend vaccination of the entire population and screening all the exposed and migrants. Additionally, early treatment of both the exposed class after screening and the chronically infected class is vital to decreasing the transmission of HBV in the community.