bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics
Authors: Duan Yajun , Gong Ke , Xu Suowen , Zhang Feng , Meng Xianshe , Han Jihong 
Published: August 2022

AbstractDisturbed cholesterol homeostasis plays critical roles in the development of multiple diseases, such as cardiovascular diseases (CVD), neurodegenerative diseases and cancers, particularly the CVD in which the accumulation of lipids (mainly the cholesteryl esters) within macrophage/foam cells underneath the endothelial layer drives the formation of atherosclerotic lesions eventually. More and more studies have shown that lowering cholesterol level, especially low-density lipoprotein cholesterol level, protects cardiovascular system and prevents cardiovascular events effectively. Maintaining cholesterol homeostasis is determined by cholesterol biosynthesis, uptake, efflux, transport, storage, utilization, and/or excretion. All the processes should be precisely controlled by the multiple regulatory pathways. Based on the regulation of cholesterol homeostasis, many interventions have been developed to lower cholesterol by inhibiting cholesterol biosynthesis and uptake or enhancing cholesterol utilization and excretion. Herein, we summarize the historical review and research events, the current understandings of the molecular pathways playing key roles in regulating cholesterol homeostasis, and the cholesterol-lowering interventions in clinics or in preclinical studies as well as new cholesterol-lowering targets and their clinical advances. More importantly, we review and discuss the benefits of those interventions for the treatment of multiple diseases including atherosclerotic cardiovascular diseases, obesity, diabetes, nonalcoholic fatty liver disease, cancer, neurodegenerative diseases, osteoporosis and virus infection.
Acute orexin antagonism selectively modulates anticipatory anxiety in humans: implications for addiction and anxiety
Authors: Gorka Stephanie M. , Khorrami Kia J. , Manzler Charles A. , Phan K. Luan 
Published: August 2022

AbstractResearch indicates that heightened anticipatory anxiety underlies several forms of psychopathology. Anticipatory anxiety can be reliably and objectively measured in the laboratory using the No-Predictable-Unpredictable (NPU) threat paradigm. The NPU paradigm is an ideal research tool for the NIH ‘Fast-Fail’ approach of screening promising compounds and testing human target engagement. Evidence from preclinical studies suggests that the hypocretin/orexin (ORX) hypothalamic neuropeptide system is a potential means for modulating anticipatory anxiety and disrupting stress-related alcohol use. The current study tested this question using a psychophysiological probe of the ORX system in humans. We examined whether a single dose of suvorexant (SUV; 10 mg; dual ORX receptor antagonist) can effectively and selectively target a well-validated human laboratory index of exaggerated anticipatory anxiety using a within-subjects placebo-controlled design. A total of twenty-one volunteers completed two laboratory sessions during acute administration of 10 mg SUV or placebo. Across sessions, we administered the NPU paradigm probing sustained anticipatory anxiety and fear while startle eyeblink was recorded as an index of aversive reactivity. Questionnaires assessing mood states and subjective drug effects were also collected. Results indicated SUV was well-tolerated. Compared with placebo, SUV was associated with decreased startle reactivity during anticipatory anxiety but not fear or no-threat conditions. Therefore, SUV selectively and effectively reduced objective indicators of anticipatory anxiety in humans and engaged our laboratory target of psychopathology. ORX antagonism may be a promising strategy for modulating human anxiety and potentially, stress-related alcohol use.
Spatiotemporal control of engineered bacteria to express interferon-γ by focused ultrasound for tumor immunotherapy
Authors: Chen Yuhao , Du Meng , Yuan Zhen , Chen Zhiyi , Yan Fei 
Published: August 2022

AbstractBacteria-based tumor therapy has recently attracted wide attentions due to its unique capability in targeting tumors and preferentially colonizing the core area of the tumor. Various therapeutic genes are also harbored into these engineering bacteria to enhance their anti-tumor efficacy. However, it is difficult to spatiotemporally control the expression of these inserted genes in the tumor site. Here, we engineer an ultrasound-responsive bacterium (URB) which can induce the expression of exogenous genes in an ultrasound-controllable manner. Owing to the advantage of ultrasound in tissue penetration, an acoustic remote control of bacterial gene expression can be realized by designing a temperature-actuated genetic switch. Cytokine interferon-γ (IFN-γ), an important immune regulatory molecule that plays a significant role in tumor immunotherapy, is used to test the system. Our results show that brief hyperthermia induced by focused ultrasound promotes the expression of IFN-γ gene, improving anti-tumor efficacy of URB in vitro and in vivo. Our study provides an alternative strategy for bacteria-mediated tumor immunotherapy.
Segregated cation flux by TPC2 biases Ca2+ signaling through lysosomes
Authors: Yuan Yu , Jaślan Dawid , Rahman Taufiq , Bolsover Stephen R. , Arige Vikas , Wagner Larry E. , Abrahamian Carla , Tang Rachel , Keller Marco , Hartmann Jonas , Rosato Anna S. , Weiden Eva-Maria , Bracher Franz , Yule David I. , Grimm Christian , Patel Sandip 
Published: August 2022

AbstractTwo-pore channels are endo-lysosomal cation channels with malleable selectivity filters that drive endocytic ion flux and membrane traffic. Here we show that TPC2 can differentially regulate its cation permeability when co-activated by its endogenous ligands, NAADP and PI(3,5)P2. Whereas NAADP rendered the channel Ca2+-permeable and PI(3,5)P2 rendered the channel Na+-selective, a combination of the two increased Ca2+ but not Na+ flux. Mechanistically, this was due to an increase in Ca2+ permeability independent of changes in ion selectivity. Functionally, we show that cell permeable NAADP and PI(3,5)P2 mimetics synergistically activate native TPC2 channels in live cells, globalizing cytosolic Ca2+ signals and regulating lysosomal pH and motility. Our data reveal that flux of different ions through the same pore can be independently controlled and identify TPC2 as a likely coincidence detector that optimizes lysosomal Ca2+ signaling.
Search performance and octopamine neuronal signaling mediate parasitoid induced changes in Drosophila oviposition behavior
Authors: Pang Lan , Liu Zhiguo , Chen Jiani , Dong Zhi , Zhou Sicong , Zhang Qichao , Lu Yueqi , Sheng Yifeng , Chen Xuexin , Huang Jianhua 
Published: August 2022

AbstractMaking the appropriate responses to predation risk is essential for the survival of an organism; however, the underlying mechanisms are still largely unknown. Here, we find that Drosophila has evolved an adaptive strategy to manage the threat from its parasitoid wasp by manipulating the oviposition behavior. Through perception of the differences in host search performance of wasps, Drosophila is able to recognize younger wasps as a higher level of threat and consequently depress the oviposition. We further show that this antiparasitoid behavior is mediated by the regulation of the expression of Tdc2 and Tβh in the ventral nerve cord via LC4 visual projection neurons, which in turn leads to the dramatic reduction in octopamine and the resulting dysfunction of mature follicle trimming and rupture. Our study uncovers a detailed mechanism underlying the defensive behavior in insects that may advance our understanding of predator avoidance in animals.
Effectiveness of REGEN-COV antibody combination in preventing severe COVID-19 outcomes
Authors: Hayek Samah , Ben-shlomo Yatir , Dagan Noa , Reis Ben Y. , Barda Noam , Kepten Eldad , Roitman Alina , Shapira Shachar , Yaron Shlomit , Balicer Ran D. , Netzer Doron , Peretz Alon 
Published: August 2022

AbstractREGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, has been approved as a treatment for high-risk patients infected with SARS-CoV-2 within five days of their diagnosis. We performed a retrospective cohort study, and used data repositories of Israel’s largest healthcare organization to determine the real-world effectiveness of REGEN-COV treatment against COVID-19-related hospitalization, severe disease, and death. We compared patients infected with Delta variant and treated with REGEN-COV (n = 289) to those infected but not-treated with REGEN-COV (n = 1,296). Demographic and clinical characteristics were used to match patients and for further adjustment as part of the C0x model. Estimated treatment effectiveness was defined as one minus the hazard ratio. Treatment effectiveness of REGEN-COV was 56.4% (95% CI: 23.7–75.1%) in preventing COVID-19 hospitalization, 59.2% (95% CI: 19.9–79.2%) in preventing severe COVID-19, and 93.5% (95% CI: 52.1–99.1%) in preventing COVID-19 death in the 28 days after treatment. In conclusion, REGEN-COV was effective in reducing the risk of severe sequelae in high-risk COVID-19 patients.
1D and 3D co-simulation and self-adaptive position control of electrostatic levitation in China’s Space Station
Authors: Zhang Peng , Zhang Yang , Wang Zile , Wang Yang , Li Mao , Niu Ran , Liang Li , Yang Wenju , Gao Ming , Zhong Hongen , Li Xuzhi , Yu Jianding 
Published: August 2022

AbstractThe greatest challenge of electrostatic levitation for containerless material processing is the stable control of charged material during heating. Recently, high-precision self-adaptive control of electrostatic levitation has been achieved in China’s Space Station. Based on the 1D and 3D co-simulation analysis, an optimal scheduling of control strategies of sample release and retrieval in space is developed. Both simulation results and on-orbit experiments demonstrated that the inversion of surface charge is responsible for the heating induced material instability. On-orbit experiments indicated that under laser illuminations, the net surface charge of metal Zr changed from positive to negative at 900 K and from negative to positive at 1300 K. The possible physical mechanism of the charge inversion of heated material is discussed.
A paper-based self-inductive folding displacement sensor for human respiration and motion signals measurement
Authors: Zhu Junwen , Jia Yanshen , Li Mengmeng , Zhou Zhanxuan , Chen Yinghao , Liu Qiang , Yang Xing 
Published: August 2022

AbstractFlexible sensors have recently attracted much attention for potential applications in motion measurement and wearable health monitoring. In this paper, an environment-friendly, economic, and high-performance paper-based self-inductive folding displacement sensor (PSIFS) was proposed, with displacement resolution of 20 μm and wide measurement range of 43.2 mm. The sensor sensitivity could reach 4.44% mm−1 with the maximum deviation of 0.00904 in experiments. The sensing mechanism based on inductance variation due to three-dimensional deformation of planar inductor coil and structural design principle under two dimensions of sensitivity and size were proposed and studied. The folding method to enhance sensitivity was proposed and 3 times sensitivity enhancement could be achieved by once folding. Multiple breathing states and motion states of the human joints could be recognized. The proposed simple paper-based sensor, folding method to increase sensitivity, and structural design model may provide a way for the research of flexible sensors.
Clinical trajectories and biomarkers for weight variability in early Parkinson’s disease
Authors: Urso Daniele , van Wamelen Daniel J. , Batzu Lucia , Leta Valentina , Staunton Juliet , Pineda-Pardo José A. , Logroscino Giancarlo , Sharma Jagdish , Ray Chaudhuri K. 
Published: August 2022

AbstractUnexplained weight changes that occur in Parkinson’s disease (PD), are often neglected and remain a poorly understood non-motor feature in patients with PD. A specific ‘Park-weight’ phenotype with low body weight has been described, and our aim was to evaluate the clinical and prognostic trajectories and biomarkers of weight variability in PD. We evaluated body weight-related biomarkers in 405 de novo PD patients and 187 healthy controls (HC) over a 5-year follow-up period from the PPMI database. Body-weight variability was defined as intra-individual variability in body weight between visits. PD patients were categorized as weight losers, gainers, or patients with stable weight. The differential progression of motor and non-motor clinical variables between groups was explored using linear mixed-effects models. Finally, we estimated longitudinal changes in weight as a function of baseline and longitudinal striatal presynaptic dopaminergic transporter imaging. PD patients presented a greater weight variability compared to HC (p = 0.003). Patients who developed weight loss had lower CSF amyloid-beta 1–42 (p = 0.009) at baseline. In addition, patients with weight loss showed a faster cognitive decline (p = 0.001), whereas patients with weight gain showed a slower motor progression (p = 0.001), compared to patients with stable weight. Baseline right striatal denervation was a predictor of weight variability in both PD patients and HC (p < 0.001). Similarly, weight variability in PD patients was associated with the progression of right striatal denervation (p < 0.001). Weight variability and specifically weight loss are more frequent in PD compared to HC, and are associated with specific motor, non-motor and cognitive progression patterns. A greater CSF amyloid burden was present at baseline in patients with subsequent weight loss. Presynaptic dopaminergic imaging in the right striatum may serve as a predictor of future weight changes in PD and HC.
Compilation of longitudinal gut microbiome, serum metabolome, and clinical data in acute myeloid leukemia
Authors: Rashidi Armin , Ebadi Maryam , Rehman Tauseef Ur , Elhusseini Heba , Halaweish Hossam , Kaiser Thomas , Holtan Shernan G. , Khoruts Alexander , Weisdorf Daniel J. , Staley Christopher 
Published: August 2022

AbstractInduction chemotherapy for patients with acute myeloid leukemia (AML) is a unique clinical scenario. These patients spend several weeks in the hospital, receiving multiple antibiotics, experiencing gastrointestinal mucosal damage, and suffering severe impairments in their immune system and nutrition. These factors cause major disruptions to the gut microbiota to a level rarely seen in other clinical conditions. Thus, the study of the gut microbiota in these patients can reveal novel aspects of microbiota-host relationships. When combined with the circulating metabolome, such studies could shed light on gut microbiota contribution to circulating metabolites. Collectively, gut microbiota and circulating metabolome are known to regulate host physiology. We have previously deposited amplicon sequences from 566 fecal samples from 68 AML patients. Here, we provide sample-level details and a link, using de-identified patient IDs, to additional data including serum metabolomics (260 samples from 36 patients) and clinical metadata. The detailed information provided enables comprehensive multi-omics analysis. We validate the technical quality of these data through 3 examples and demonstrate a method for integrated analysis.
Investigation of memory-enhancing effects of Streptococcus thermophilus EG007 in mice and elucidating molecular and metagenomic characteristics using nanopore sequencing
Authors: Kim Hyaekang , Jeon Soomin , Kim Jina , Seol Donghyeok , Jo JinChul , Cho Seoae , Kim Heebal 
Published: August 2022

AbstractOver the past decades, accumulating evidences have highlighted the gut microbiota as a key player in the brain functioning via microbiota–gut–brain axis, and accordingly, the beneficial role of several probiotic strains in cognitive ability also have been actively investigated. However, the majority of the research have demonstrated the effects against age-related cognitive decline or neurological disease. To this end, we aimed to investigate lactic acid bacteria strains having beneficial effects on the cognitive function of healthy young mice and elucidate underlying characteristics by carrying out nanopore sequencing-based genomics and metagenomics analysis. 8-week consumption of Streptococcus thermophilus EG007 demonstrated marked enhancements in behavior tests assessing short-term spatial and non-spatial learning and memory. It was revealed that EG007 possessed genes encoding various metabolites beneficial for a health condition in many aspects, including gamma-aminobutyric acid producing system, a neurotransmitter associated with mood and stress response. Also, by utilizing 16S–23S rRNA operon as a taxonomic marker, we identified more accurate species-level compositional changes in gut microbiota, which was increase of certain species, previously reported to have associations with mental health or down-regulation of inflammation or infection-related species. Moreover, correlation analysis revealed that the EG007-mediated altered microbiota had a significant correlation with the memory traits.
Assessment of thermal distribution through an inclined radiative-convective porous fin of concave profile using generalized residual power series method (GRPSM)
Authors: Varun Kumar R. S. , Sowmya G. , Jayaprakash M. C. , Prasannakumara B. C. , Khan M. Ijaz , Guedri Kamel , Kumam Poom , Sitthithakerngkiet Kanokwan , Galal Ahmed M. 
Published: August 2022

AbstractThe thermal distribution in a convective-radiative concave porous fin appended to an inclined surface has been examined in this research. The equation governing the temperature and heat variation in fin with internal heat generation is transformed using non-dimensional variables, and the resulting partial differential equation (PDE) is tackled using an analytical scheme, generalized residual power series method (GRPSM). Moreover, a graphical discussion is provided to examine the consequence of diverse non-dimensional variables including the parameters of convection-conduction, ambient temperature, radiation, heat generation, and porosity effect on the thermal field of the fin. Also, a graph is plotted to analyze the variations in unsteady temperature gradient using the finite difference method (FDM) and generalized residual power series method (GRPSM). The major result of this investigation unveils that as the convection-conduction parameter scale upsurges, the distribution of temperature in the fin diminishes. For the heat-generating parameter, the thermal distribution inside the fin increases.
Understanding hesitancy with revealed preferences across COVID-19 vaccine types
Authors: Kutasi Kristóf , Koltai Júlia , Szabó-Morvai Ágnes , Röst Gergely , Karsai Márton , Biró Péter , Lengyel Balázs 
Published: August 2022

AbstractMany countries have secured larger quantities of COVID-19 vaccines than their population is willing to take. The abundance and the large variety of vaccines created not only an unprecedented intensity of vaccine related public discourse, but also a historical moment to understand vaccine hesitancy better. Yet, the heterogeneity of hesitancy by vaccine types has been neglected in the existing literature so far. We address this problem by analysing the acceptance and the assessment of five vaccine types. We use information collected with a nationally representative survey at the end of the third wave of the COVID-19 pandemic in Hungary. During the vaccination campaign, individuals could reject the assigned vaccine to wait for a more preferred alternative that enables us to quantify revealed preferences across vaccine types. We find that hesitancy is heterogenous by vaccine types and is driven by individuals’ trusted source of information. Believers of conspiracy theories are more likely to evaluate the mRNA vaccines (Pfizer and Moderna) unacceptable. Those who follow the advice of politicians are more likely to evaluate vector-based (AstraZeneca and Sputnik) or whole-virus vaccines (Sinopharm) acceptable. We argue that the greater selection of available vaccine types and the free choice of the individual are desirable conditions to increase the vaccination rate in societies.
Construction of a novel signature and prediction of the immune landscape in gastric cancer based on necroptosis-related genes
Authors: Li Zhengtian , Yang Wenkang , Liu Dejun , Ye Weizheng , Du Gang , Li Xi 
Published: August 2022

AbstractNecroptosis, a type of programmed cell death, has become a potential therapeutic target for solid tumors. Nevertheless, the potential roles of necroptosis-related genes (NRGs) in gastric cancer (GC) remain unknown. The objective of the present study was to create a necroptosis-related prognostic signature that can provide more accurate assessment of prognosis in GC. Using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data, we identified differentially expressed NRGs. Univariate analysis and Lasso regression were performed to determine the prognostic signature. Risk scores were calculated and all GC patients were divided into high- and low-risk score group according to the median risk score value. The robustness of this signature was externally validated with data from GSE84437 cohort (n = 431). Survival analysis revealed high-risk score patients had a worse prognosis. Results evidenced that the signature was an independent prognosis factor for survival. Single-sample sequence set enrichment analysis (ssGSEA) exhibited different enrichment of immune cells and immune-related pathways in the two risk groups. Furthermore, a predictive nomogram was generated and showed excellent predictive performance based on discrimination and calibration. In addition, the risk score positively correlated with tumor mutational burden and was associated with sensitivity to multiple anti-cancer drugs. Overall, our work demonstrates a close relationship between necroptosis and the prognosis of GC. The signature we constructed with potential clinical application value, can be used for prognosis prediction and being a potential therapeutic responses indicator in GC patients.