bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone health in spacefaring rodents and primates: systematic review and meta-analysis
Authors: Fu Jingyan , Goldsmith Matthew , Crooks Sequoia D. , Condon Sean F. , Morris Martin , Komarova Svetlana V. 
Published: June 2021

AbstractAnimals in space exploration studies serve both as a model for human physiology and as a means to understand the physiological effects of microgravity. To quantify the microgravity-induced changes to bone health in animals, we systematically searched Medline, Embase, Web of Science, BIOSIS, and NASA Technical reports. We selected 40 papers focusing on the bone health of 95 rats, 61 mice, and 9 rhesus monkeys from 22 space missions. The percentage difference from ground control in rodents was –24.1% [Confidence interval: −43.4, −4.9] for trabecular bone volume fraction and –5.9% [−8.0, −3.8] for the cortical area. In primates, trabecular bone volume fraction was lower by –25.2% [−35.6, −14.7] in spaceflight animals compared to GC. Bone formation indices in rodent trabecular and cortical bone were significantly lower in microgravity. In contrast, osteoclast numbers were not affected in rats and were variably affected in mice. Thus, microgravity induces bone deficits in rodents and primates likely through the suppression of bone formation.
3D cell culture using a clinostat reproduces microgravity-induced skin changes
Authors: Choi Dong Hyun , Jeon Byoungjun , Lim Min Hyuk , Lee Dong Hun , Ye Sang-Kyu , Jeong Seung-Yong , Kim Sungwan 
Published: June 2021

AbstractExposure to microgravity affects human physiology in various ways, and astronauts frequently report skin-related problems. Skin rash and irritation are frequent complaints during space missions, and skin thinning has also been reported after returning to Earth. However, spaceflight missions for studying the physiological changes in microgravity are impractical. Thus, we used a previously developed 3D clinostat to simulate a microgravity environment and investigate whether physiological changes of the skin can be reproduced in a 3D in vitro setting. Our results showed that under time-averaged simulated microgravity (taSMG), the thickness of the endothelial cell arrangement increased by up to 59.75%, indicating skin irritation due to vasodilation, and that the diameter of keratinocytes and fibroblast co-cultured spheroids decreased by 6.66%, representing skin thinning. The α1 chain of type I collagen was upregulated, while the connective tissue growth factor was downregulated under taSMG. Cytokeratin-10 expression was significantly increased in the taSMG environment. The clinostat-based 3D culture system can reproduce physiological changes in the skin similar to those under microgravity, providing insight for understanding the effects of microgravity on human health before space exploration.
Phenotype and management of chronic obstructive pulmonary disease patients in general population in China: a nationally cross-sectional study
Authors: Bao Heling , Jia Guohua , Cong Shu , Sun Wanlu , Fan Jing , Wang Ning , Feng Yajing , Wang Baohua , Curtis Jeffrey L. , Wang Linhong , Fang Liwen , Chen Yahong 
Published: June 2021

AbstractThis study aims to investigate the characteristics of the phenotype and management of chronic obstructive pulmonary disease (COPD) patients in the general population in China. We analyzed spirometry-confirmed COPD patients who were identified from a population-based, nationally representative sample in China. All participants were measured with airflow limitation severity based on post-bronchodilator FEV1 percent predicted, bronchodilator responsiveness, exacerbation history, and respiratory symptoms. Among a total of 9134 COPD patients, 90.3% were non-exacerbators, 2.9% were frequent exacerbators without chronic bronchitis, 2.0% were frequent exacerbators with chronic bronchitis, and 4.8% were asthma-COPD overlap. Less than 5% of non-exacerbators ever had pulmonary function testing performed. The utilization rate of inhaled medication in non-exacerbators, exacerbators without chronic bronchitis, exacerbators with chronic bronchitis, and asthma-COPD overlap was 1.4, 23.5, 29.5, and 19.4%, respectively. A comprehensive strategy for the management of COPD patients based on phenotype in primary care is urgently needed.
Next generation of heart regenerative therapies: progress and promise of cardiac tissue engineering
Authors: Tenreiro Miguel F. , Louro Ana F. , Alves Paula M. , Serra Margarida 
Published: June 2021

AbstractThe adult heart is a vital and highly specialized organ of the human body, with limited capability of self-repair and regeneration in case of injury or disease. Engineering biomimetic cardiac tissue to regenerate the heart has been an ambition in the field of tissue engineering, tracing back to the 1990s. Increased understanding of human stem cell biology and advances in process engineering have provided an unlimited source of cells, particularly cardiomyocytes, for the development of functional cardiac muscle, even though pluripotent stem cell-derived cardiomyocytes poorly resemble those of the adult heart. This review outlines key biology-inspired strategies reported to improve cardiomyocyte maturation features and current biofabrication approaches developed to engineer clinically relevant cardiac tissues. It also highlights the potential use of this technology in drug discovery science and disease modeling as well as the current efforts to translate it into effective therapies that improve heart function and promote regeneration.
Engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns
Authors: Batalov Ivan , Jallerat Quentin , Kim Sean , Bliley Jacqueline , Feinberg Adam W. 
Published: June 2021

AbstractCardiac two-dimensional tissues were engineered using biomimetic micropatterns based on the fibronectin-rich extracellular matrix (ECM) of the embryonic heart. The goal of this developmentally-inspired, in vitro approach was to identify cell–cell and cell-ECM interactions in the microenvironment of the early 4-chambered vertebrate heart that drive cardiomyocyte organization and alignment. To test this, biomimetic micropatterns based on confocal imaging of fibronectin in embryonic chick myocardium were created and compared to control micropatterns designed with 2 or 20 µm wide fibronectin lines. Results show that embryonic chick cardiomyocytes have a unique density-dependent alignment on the biomimetic micropattern that is mediated in part by N-cadherin, suggesting that both cell–cell and cell-ECM interactions play an important role in the formation of aligned myocardium. Human induced pluripotent stem cell-derived cardiomyocytes also showed density-dependent alignment on the biomimetic micropattern but were overall less well organized. Interestingly, the addition of human adult cardiac fibroblasts and conditioning with T3 hormone were both shown to increase human cardiomyocyte alignment. In total, these results show that cardiomyocyte maturation state, cardiomyocyte-cardiomyocyte and cardiomyocyte-fibroblast interactions, and cardiomyocyte-ECM interactions can all play a role when engineering anisotropic cardiac tissues in vitro and provides insight as to how these factors may influence cardiogenesis in vivo.
Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa
Authors: Ganzen Logan , Ko Mee Jung , Zhang Mengrui , Xie Rui , Chen Yongkai , Zhang Liyun , James Rebecca , Mumm Jeff , van Rijn Richard M. , Zhong Wenxuan , Pang Chi Pui , Zhang Mingzhi , Tsujikawa Motokazu , Leung Yuk Fai 
Published: June 2021

AbstractRetinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients.
Monitoring of transfer and internalization of Escherichia coli from inoculated knives to fresh cut cucumbers (Cucumis sativus L.) using bioluminescence imaging
Authors: Sun Yeting , Zhao Xiaoyan , Xu Xiulan , Ma Yue , Guan Hongyang , Liang Hao , Wang Dan 
Published: June 2021

AbstractSlicing may cause the risk of cross-contamination in cucumber. In this study, knife inoculated with Escherichia coli (E. coli) was used to cut cucumbers, bioluminescence imaging (BLI) was used to visualize the possible distribution and internalization of E. coli during cutting and storage. Results showed that the initial two slices resulted in greater bacterial transfer. The bacterial transfer exhibited a fluctuating decay trend, E. coli was most distributed at the initial cutting site. The contaminated area on the surface of cucumber slices decreased during the storage period, which can be attributed to the death and internalization of E. coli. The maximum internalization distance of E. coli was about 2–3 mm, and did not further spread after 30 min from inoculation. Hence, our results provide useful information for risk management in both home and industrial environment.
Comparative transcriptome analysis reveals key genes associated with pigmentation in radish (Raphanus sativus L.) skin and flesh
Authors: Zhang Jifang , Zhao Jian , Tan Qunyun , Qiu Xiaojun , Mei Shiyong 
Published: June 2021

AbstractRadish (Raphanus sativus) is an important vegetable worldwide that exhibits different flesh and skin colors. The anthocyanins responsible for the red and purple coloring in radishes possess nutritional value and pharmaceutical potential. To explore the structural and regulatory networks related to anthocyanin biosynthesis and identify key genes, we performed comparative transcriptome analyses of the skin and flesh of six colored radish accessions. The transcript profiles showed that each accession had a species-specific transcript profile. For radish pigmentation accumulation, the expression levels of anthocyanin biosynthetic genes (RsTT4, RsC4H, RsTT7, RsCCOAMT, RsDFR, and RsLDOX) were significantly upregulated in the red- and purple-colored accessions, but were downregulated or absent in the white and black accessions. The correlation test, combined with metabolome (PCC > 0.95), revealed five structural genes (RsTT4, RsDFR, RsCCOAMT, RsF3H, and RsBG8L) and three transcription factors (RsTT8-1, RsTT8-2, and RsPAR1) to be significantly correlated with flavonoids in the skin of the taproot. Four structural genes (RsBG8L, RsDFR, RsCCOAMT, and RsLDOX) and nine transcription factors (RsTT8-1, RsTT8-2, RsMYB24L, RsbHLH57, RsPAR2L, RsbHLH113L, RsOGR3L, RsMYB24, and RsMYB34L) were found to be significantly correlated with metabolites in the flesh of the taproot. This study provides a foundation for future studies on the gene functions and genetic diversity of radish pigmentation and should aid in the cultivation of new valuable radish varieties.
Comprehensive machine learning based study of the chemical space of herbicides
Authors: Oršolić Davor , Pehar Vesna , Šmuc Tomislav , Stepanić Višnja 
Published: June 2021

AbstractWidespread use of herbicides results in the global increase in weed resistance. The rotational use of herbicides according to their modes of action (MoAs) and discovery of novel phytotoxic molecules are the two strategies used against the weed resistance. Herein, Random Forest modeling was used to build predictive models and establish comprehensive characterization of structure–activity relationships underlying herbicide classifications according to their MoAs and weed selectivity. By combining the predictive models with herbicide-likeness rules defined by selected molecular features (numbers of H-bond acceptors and donors, logP, topological and relative polar surface area, and net charge), the virtual stepwise screening platform is proposed for characterization of small weight molecules for their phytotoxic properties. The screening cascade was applied on the data set of phytotoxic natural products. The obtained results may be valuable for refinement of herbicide rotational program as well as for discovery of novel herbicides primarily among natural products as a source for molecules of novel structures and novel modes of action and translocation profiles as compared with the synthetic compounds.
Directional changes in Levallois core technologies between Eastern Africa, Arabia, and the Levant during MIS 5
Authors: Blinkhorn James , Groucutt Huw S. , Scerri Eleanor M. L. , Petraglia Michael D. , Blockley Simon 
Published: June 2021

AbstractMarine Isotope Stage (MIS) 5, ~ 130 to 71 thousand years ago, was a key period for the geographic expansion of Homo sapiens, including engagement with new landscapes within Africa and dispersal into Asia. Occupation of the Levant by Homo sapiens in MIS 5 is well established, while recent research has documented complementary evidence in Arabia. Here, we undertake the first detailed comparison of Levallois core technology from eastern Africa, Arabia, and the Levant during MIS 5, including multiple sites associated with Homo sapiens fossils. We employ quantitative comparisons of individual artefacts that provides a detailed appraisal of Levallois reduction activity in MIS 5, thereby enabling assessment of intra- and inter-assemblage variability for the first time. Our results demonstrate a pattern of geographically structured variability embedded within a shared focus on centripetal Levallois reduction schemes and overlapping core morphologies. We reveal directional changes in core shaping and flake production from eastern Africa to Arabia and the Levant that are independent of differences in geographic or environmental parameters. These results are consistent with a common cultural inheritance between these regions, potentially stemming from a shared late Middle Pleistocene source in eastern Africa.
Estimating cardiac output based on gas exchange during veno-arterial extracorporeal membrane oxygenation in a simulation study using paediatric oxygenators
Authors: Bachmann Kaspar Felix , Vasireddy Rakesh , Heinisch Paul Philipp , Jenni Hansjörg , Vogt Andreas , Berger David 
Published: June 2021

AbstractVeno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy is a rescue strategy for severe cardiopulmonary failure. The estimation of cardiac output during VA-ECMO is challenging. A lung circuit ($${\dot{\text{Q}}}$$

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Lung) and an ECMO circuit ($${\dot{\text{Q}}}$$

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ECMO) with oxygenators for CO2 removal ($$\mathop {\text{V}}\limits^{.}$$

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CO2) and O2 uptake ($$\mathop {\text{V}}\limits^{.}$$

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O2) simulated the setting of VA-ECMO with varying ventilation/perfusion ($$\mathop {\text{V}}\limits^{.}$$

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/$${\dot{\text{Q}}}$$

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) ratios and shunt. A metabolic chamber with a CO2/N2 blend simulated $$\mathop {\text{V}}\limits^{.}$$

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CO2 and $$\mathop {\text{V}}\limits^{.}$$

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O2. $${\dot{\text{Q}}}$$

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Lung was estimated with a modified Fick principle: $${\dot{\text{Q}}}$$

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Lung = $${\dot{\text{Q}}}$$

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ECMO × ($$\mathop {\text{V}}\limits^{.}$$

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CO2 or $$\mathop {\text{V}}\limits^{.}$$

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O2Lung)/($$\mathop {\text{V}}\limits^{.}$$

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CO2 or $$\mathop {\text{V}}\limits^{.}$$

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O2ECMO). A normalization procedure corrected $$\mathop {\text{V}}\limits^{.}$$

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CO2 values for a $$\mathop {\text{V}}\limits^{.}$$

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/$${\dot{\text{Q}}}$$

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of 1. Method agreement was evaluated by Bland–Altman analysis. Calculated $${\dot{\text{Q}}}$$

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Lung using gaseous $$\mathop {\text{V}}\limits^{.}$$

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CO2 and $$\mathop {\text{V}}\limits^{.}$$

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O2 correlated well with measured $${\dot{\text{Q}}}$$

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Lung with a bias of 103 ml/min [− 268 to 185] ml/min; Limits of Agreement: − 306 ml/min [− 241 to − 877 ml/min] to 512 ml/min [447 to 610 ml/min], r2 0.85 [0.79–0.88]). Blood measurements of $$\mathop {\text{V}}\limits^{.}$$

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CO2 showed an increased bias (− 260 ml/min [− 1503 to 982] ml/min), clinically not applicable. Shunt and $$\mathop {\text{V}}\limits^{.}$$

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/$${\dot{\text{Q}}}$$

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mismatch decreased the agreement of methods significantly. This in-vitro simulation shows that $$\mathop {\text{V}}\limits^{.}$$

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CO2 and $$\mathop {\text{V}}\limits^{.}$$

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O2 in steady-state conditions allow for clinically applicable calculations of $${\dot{\text{Q}}}$$

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Lung during VA-ECMO therapy.
Controls of a superconducting quantum parametron under a strong pump field
Authors: Masuda Shumpei , Ishikawa Toyofumi , Matsuzaki Yuichiro , Kawabata Shiro 
Published: June 2021

AbstractPumped at approximately twice the natural frequency, a Josephson parametric oscillator called parametron or Kerr parametric oscillator shows self-oscillation. Quantum annealing and universal quantum computation using self-oscillating parametrons as qubits were proposed. However, controls of parametrons under the pump field are degraded by unwanted rapidly oscillating terms in the Hamiltonian, which we call non-resonant rapidly oscillating terms (NROTs) coming from the violation of the rotating wave approximation. Therefore, the pump field can be an intrinsic origin of the imperfection of controls of parametrons. Here, we theoretically study the influence of the NROTs on the accuracy of controls of a parametron: a cat-state creation and a single-qubit gate. It is shown that there is a trade-off relationship between the suppression of the nonadiabatic transitions and the validity of the rotating wave approximation in a conventional approach. We also show that the tailored time dependence of the detuning of the pump field can suppress both of the nonadiabatic transitions and the disturbance of the state of the parametron due to the NROTs.
The association between implicit and explicit affective inhibitory control, rumination and depressive symptoms
Authors: Shimony Orly , Einav Noam , Bonne Omer , Jordan Joshua T. , Van Vleet Thomas M. , Nahum Mor 
Published: June 2021

AbstractInhibitory control underlies one’s ability to maintain goal-directed behavior by inhibiting prepotent responses or ignoring irrelevant information. Recent models suggest that impaired inhibition of negative information may contribute to depressive symptoms, and that this association is mediated by rumination. However, the exact nature of this association, particularly in non-clinical samples, is unclear. The current study assessed the relationship between inhibitory control over emotional vs. non-emotional information, rumination and depressive symptoms. A non-clinical sample of 119 participants (mean age: 36.44 ± 11.74) with various levels of depressive symptoms completed three variations of a Go/No-Go task online; two of the task variations required either explicit or implicit processing of emotional expressions, and a third variation contained no emotional expressions (i.e., neutral condition). We found reductions in inhibitory control for participants reporting elevated symptoms of depression on all three task variations, relative to less depressed participants. However, for the task variation that required implicit emotion processing, depressive symptoms were associated with inhibitory deficits for sad and neutral, but not for happy expressions. An exploratory analysis showed that the relationship between inhibition and depressive symptoms occurs in part through trait rumination for all three tasks, regardless of emotional content. Collectively, these results indicate that elevated depressive symptoms are associated with both a general inhibitory control deficit, as well as affective interference from negative emotions, with implications for the assessment and treatment of mood disorders.
The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo
Authors: Kropp Camille , Le Corf Katy , Relizani Karima , Tambosco Kevin , Martinez Ccori , Chain Florian , Rawadi Georges , Langella Philippe , Claus Sandrine P. , Martin Rebeca 
Published: June 2021

AbstractChristensenellaceae is a family of subdominant commensal bacteria found in humans. It is thought to play an important role in gut health by maintaining microbial symbiosis. Indeed, these bacteria occur at significantly lower levels or are absent in individuals suffering from inflammatory bowel diseases (IBDs). Here, we explored if type species Christensenella minuta (strain: DSM 22607) could have the potential to help treat IBDs. We assessed key properties displayed by the bacterium using a combination of in vitro and in vivo assays. We found that while C. minuta is a strict anaerobe, it is also oxygen tolerant. Additionally, we observed that the species produces high levels of acetate and moderate levels of butyrate. We performed deep phenotyping using Biolog microarrays. Using human intestinal cell lines, we discovered that C. minuta demonstrated strong anti-inflammatory activity, resulting in reduced levels of proinflammatory IL-8 cytokines via the inhibition of the NF-κB signaling pathway. Furthermore, C. minuta protected intestinal epithelial integrity in vitro. Finally, in two distinct animal models of acute colitis, C. minuta prevented intestinal damage, reduced colonic inflammation, and promoted mucosal healing. Together, these results indicate that C. minuta has potent immunomodulatory properties, underscoring its potential use in innovative microbiome-based IBD biotherapies.
Medium-throughput zebrafish optogenetic platform identifies deficits in subsequent neural activity following brief early exposure to cannabidiol and Δ9-tetrahydrocannabinol
Authors: Kanyo Richard , Amin Md Ruhul , Locskai Laszlo F. , Bouvier Danika D. , Olthuis Alexandria M. , Allison W. Ted , Ali Declan W. 
Published: June 2021

AbstractIn light of legislative changes and the widespread use of cannabis as a recreational and medicinal drug, delayed effects of cannabis upon brief exposure during embryonic development are of high interest as early pregnancies often go undetected. Here, zebrafish embryos were exposed to cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) until the end of gastrulation (1–10 h post-fertilization) and analyzed later in development (4–5 days post-fertilization). In order to measure neural activity, we implemented Calcium-Modulated Photoactivatable Ratiometric Integrator (CaMPARI) and optimized the protocol for a 96-well format complemented by locomotor analysis. Our results revealed that neural activity was decreased by CBD more than THC. At higher doses, both cannabinoids could dramatically reduce neural activity and locomotor activity. Interestingly, the decrease was more pronounced when CBD and THC were combined. At the receptor level, CBD-mediated reduction of locomotor activity was partially prevented using cannabinoid type 1 and 2 receptor inhibitors. Overall, we report that CBD toxicity occurs via two cannabinoid receptors and is synergistically enhanced by THC exposure to negatively impact neural activity late in larval development. Future studies are warranted to reveal other cannabinoids and their receptors to understand the implications of cannabis consumption on fetal development.