bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking the Surface and Subsurface in River Deltas—Part 1: Relating Surface and Subsurface Geometries
Authors: Hariharan Jayaram , Xu Zhongyuan , Michael Holly A. , Paola Chris , Steel Elisabeth , Passalacqua Paola 
Published: August 2021

AbstractRiver deltas are densely populated regions of the world with vulnerable groundwater reserves. Contamination of these groundwater aquifers via saline water intrusion and pollutant transport is a growing threat due to both anthropogenic and climate changes. The arrangement and composition of subsurface sediment is known to have a significant impact on aquifer contamination; however, developing accurate depictions of the subsurface is challenging. In this work, we explore the relationship between surface and subsurface properties and identify the metrics most sensitive to different forcing conditions. To do so, we simulate river delta evolution with the rule‐based numerical model, DeltaRCM, and test the influence of input sand fraction and steady sea level rise (SLR) on delta evolution. From the model outputs, we measure a variety of surface and subsurface metrics chosen based on their applicability to imagery and modeling results. The Kullback‐Leibler (KL) divergence is then used to quantitatively gauge which metrics are most indicative of the imposed forcings. Both qualitative observations and the KL divergence analysis suggest that estimates of subsurface connectivity can be constrained using surface information. In particular, more variable shoreline roughness values and higher surface wetted fraction values correspond to increased subsurface connectivity. These findings complement traditional methods of estimating subsurface structure in river‐dominated delta systems and represent a step toward the identification of a direct link between surface observations and subsurface form.
Native H2 Exploration in the Western Pyrenean Foothills
Authors: Lefeuvre Nicolas , Truche Laurent , Donzé Frédéric‐Victor , Ducoux Maxime , Barré Guillaume , Fakoury Rose‐Adeline , Calassou Sylvain , Gaucher Eric C. 
Published: August 2021

AbstractNative hydrogen (H2) may represent a new carbon free‐energy resource, but to date there is no specific exploration guide to target H2‐fertile geological settings. Here, we present the first soil gas survey specifically designed to explore H2 migration in a region where no surface seepage has been documented so far. We choose the Pyrenean orogenic belt and its northern foreland basin (Aquitaine, France) as a test site for our strategy. The presence of mantle rocks at shallow depth (<10 km depth) under the Mauléon Basin connected to the surface by major faults is considered as preliminary requisites for H2 generation and drainage. On this basis, more than 1,100 in situ soil gas analysis (H2, CO, CO2, CH4, H2S, and 222Rn) were performed at ∼1 m depth at the regional scale along a 10 × 10 km grid spanning over 7,500 km2. The analysis campaign reveals several areas of high occurrence to the north of the Mauléon Basin where H2, CO2, and 222Rn concentrations exceed 1,000 ppmv, 10 vol%, and 50 kBq m−3, respectively. Most of these hot spots are located along the North Pyrenean Frontal Thrust and other related faults rooted in the mantle body. These results, together with evidence from the literature of fluid migration at depth, suggest that H2 may be sourced from mantle rocks serpentinization and carried to the surface along major thrusting faults. Traps containing hydrogen remain unidentified up to now but the presence of salt‐related structures (diapirs) near these hot spots is considered encouraging.
Dynamical Variations of the Global COVID‐19 Pandemic Based on a SEICR Disease Model: A New Approach of Yi Hua Jie Mu
Authors: Wang Xia , Yin Gang , Hu Zengyun , He Daihai , Cui Qianqian , Feng Xiaomei , Teng Zhidong , Hu Qi , Li Jiansen , Zhou Qiming 
Published: August 2021

AbstractThe ongoing coronavirus disease 2019 (COVID‐19) pandemic has caused more than 150 million cases of infection to date and poses a serious threat to global public health. In this study, global COVID‐19 data were used to examine the dynamical variations from the perspectives of immunity and contact of 84 countries across the five climate regions: tropical, arid, temperate, and cold. A new approach named Yi Hua Jie Mu is proposed to obtain the transmission rates based on the COVID‐19 data between the countries with the same climate region over the Northern Hemisphere and Southern Hemisphere. Our results suggest that the COVID‐19 pandemic will persist over a long period of time or enter into regular circulation in multiple periods of 1–2 years. Moreover, based on the simulated results by the COVID‐19 data, it is found that the temperate and cold climate regions have higher infection rates than the tropical and arid climate regions, which indicates that climate may modulate the transmission of COVID‐19. The role of the climate on the COVID‐19 variations should be concluded with more data and more cautions. The non‐pharmaceutical interventions still play the key role in controlling and prevention this global pandemic.
Tumor microenvironment and immune evasion in head and neck squamous cell carcinoma
Authors: Elmusrati Areeg , Wang Justin , Wang Cun-Yu 
Published: August 2021

AbstractHead and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.
Liquid–liquid phase separation in human health and diseases
Authors: Wang Bin , Zhang Lei , Dai Tong , Qin Ziran , Lu Huasong , Zhang Long , Zhou Fangfang 
Published: August 2021

AbstractEmerging evidence suggests that liquid–liquid phase separation (LLPS) represents a vital and ubiquitous phenomenon underlying the formation of membraneless organelles in eukaryotic cells (also known as biomolecular condensates or droplets). Recent studies have revealed evidences that indicate that LLPS plays a vital role in human health and diseases. In this review, we describe our current understanding of LLPS and summarize its physiological functions. We further describe the role of LLPS in the development of human diseases. Additionally, we review the recently developed methods for studying LLPS. Although LLPS research is in its infancy—but is fast-growing—it is clear that LLPS plays an essential role in the development of pathophysiological conditions. This highlights the need for an overview of the recent advances in the field to translate our current knowledge regarding LLPS into therapeutic discoveries.
Light-driven carbon dioxide reduction to methane by Methanosarcina barkeri in an electric syntrophic coculture
Authors: Huang Lingyan , Liu Xing , Zhang Zhishuai , Ye Jie , Rensing Christopher , Zhou Shungui , Nealson Kenneth H 
Published: August 2021

Abstract
The direct conversion of CO2 to value-added chemical commodities, thereby storing solar energy, offers a promising option for alleviating both the current energy crisis and global warming. Semiconductor-biological hybrid systems are novel approaches. However, the inherent defects of photocorrosion, photodegradation, and the toxicity of the semiconductor limit the application of these biohybrid systems. We report here that Rhodopseudomonas palustris was able to directly act as a living photosensitizer to drive CO2 to CH4 conversion by Methanosarcina barkeri under illumination after coculturing. Specifically, R. palustris formed a direct electric syntrophic coculture with M. barkeri. Here, R. palustris harvested solar energy, performed anoxygenic photosynthesis using sodium thiosulfate as an electron donor, and transferred electrons extracellularly to M. barkeri to drive methane generation. The methanogenesis of M. barkeri in coculture was a light-dependent process with a production rate of 4.73 ± 0.23 μM/h under light, which is slightly higher than that of typical semiconductor-biohybrid systems (approximately 4.36 μM/h). Mechanistic and transcriptomic analyses showed that electrons were transferred either directly or indirectly (via electron shuttles), subsequently driving CH4 production. Our study suggests that R. palustris acts as a natural photosensitizer that, in coculture with M. barkeri, results in a new way to harvest solar energy that could potentially replace semiconductors in biohybrid systems.
A machine learning case–control classifier for schizophrenia based on DNA methylation in blood
Authors: Gunasekara Chathura J. , Hannon Eilis , MacKay Harry , Coarfa Cristian , McQuillin Andrew , Clair David St. , Mill Jonathan , Waterland Robert A. 
Published: August 2021

AbstractEpigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case–control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); application of SPLS-DA to HM450 data has not been previously reported. Using the first two SPLS-DA dimensions we calculated a “risk distance” to identify individuals with the highest probability of SZ. The model was then evaluated on an independent HM450 data set on 353 SZ cases and 322 non-psychiatric controls. Our CoRSIV-based model classified 303 individuals as cases with a positive predictive value (PPV) of 80%, far surpassing the performance of a model based on polygenic risk score (PRS). Importantly, risk distance (based on CoRSIV methylation) was not associated with medication use, arguing against reverse causality. Risk distance and PRS were positively correlated (Pearsonr = 0.28,P = 1.28 × 10−12), and mediational analysis suggested that genetic effects on SZ are partially mediated by altered methylation at CoRSIVs. Our results indicate two innate dimensions of SZ risk: one based on genetic, and the other on systemic epigenetic variants.
Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease
Authors: Courbon Guillaume , Francis Connor , Gerber Claire , Neuburg Samantha , Wang Xueyan , Lynch Emily , Isakova Tamara , Babitt Jodie L. , Wolf Myles , Martin Aline , David Valentin 
Published: August 2021

AbstractBone-produced fibroblast growth factor 23 (FGF23) increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2; LCN2 the murine homolog) is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD progression. We investigated bone FGF23 regulation by circulating LCN2. At 23 weeks, Col4a3KO mice showed impaired kidney function, increased levels of kidney and serum LCN2, increased bone and serum FGF23, anemia, and left ventricular hypertrophy (LVH). Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum FGF23. Lcn2 deletion specifically prevented FGF23 elevations in response to inflammation, but not iron deficiency or phosphate, and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone cells. These results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in CKD. LCN2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.
RASSF9 promotes NSCLC cell proliferation by activating the MEK/ERK axis
Authors: Yuan Jun , Ju Qianqian , Zhu Jun , Jiang Yun , Yang Xuechao , Liu Xiaoyu , Ma Jinyu , Sun Cheng , Shi Jiahai 
Published: August 2021

AbstractThe RAS-associated domain family 9 (RASSF9), a RAS-associated domain family gene, is expressed in a variety of tissues. However, its roles in tumorigenesis, particularly in non-small cell lung cancer (NSCLC), are still not understood well. In the present study, we aimed to examine the potential roles of RASSF9 in NSCLC and the underlying mechanisms. Our data showed that RASSF9 expression was upregulated in NSCLC tissues and cell lines. Increased expression of RASSF9 promotes NSCLC cell proliferation. On the contrary, knockdown of RASSF9 represses cell proliferation. Moreover, the effects of RASSF9 on NSCLC cell proliferation were further confirmed in vivo by using a subcutaneous tumor model. Mechanistically, pharmacological intervention studies revealed that the MEK/ERK axis is targeted by RASSF9 for transducing its regulatory roles on NSCLC cell proliferation. Collectively, our data indicate that RASSF9 plays a key role in tumorigenesis of NSCLC by stimulating tumor cell proliferation, which relies on activation of the MEK/ERK axis. Thus, RASSF9 might be a druggable target for developing novel agents for treating NSCLC.
Compounds targeting OSBPL7 increase ABCA1-dependent cholesterol efflux preserving kidney function in two models of kidney disease
Authors: Wright Matthew B. , Varona Santos Javier , Kemmer Christian , Maugeais Cyrille , Carralot Jean-Philippe , Roever Stephan , Molina Judith , Ducasa G. Michelle , Mitrofanova Alla , Sloan Alexis , Ahmad Anis , Pedigo Christopher , Ge Mengyuan , Pressly Jeffrey , Barisoni Laura , Mendez Armando , Sgrignani Jacopo , Cavalli Andrea , Merscher Sandra , Prunotto Marco , Fornoni Alessia 
Published: August 2021

AbstractImpaired cellular cholesterol efflux is a key factor in the progression of renal, cardiovascular, and autoimmune diseases. Here we describe a class of 5-arylnicotinamide compounds, identified through phenotypic drug discovery, that upregulate ABCA1-dependent cholesterol efflux by targeting Oxysterol Binding Protein Like 7 (OSBPL7). OSBPL7 was identified as the molecular target of these compounds through a chemical biology approach, employing a photoactivatable 5-arylnicotinamide derivative in a cellular cross-linking/immunoprecipitation assay. Further evaluation of two compounds (Cpd A and Cpd G) showed that they induced ABCA1 and cholesterol efflux from podocytes in vitro and normalized proteinuria and prevented renal function decline in mouse models of proteinuric kidney disease: Adriamycin-induced nephropathy and Alport Syndrome. In conclusion, we show that small molecule drugs targeting OSBPL7 reveal an alternative mechanism to upregulate ABCA1, and may represent a promising new therapeutic strategy for the treatment of renal diseases and other disorders of cellular cholesterol homeostasis.
Effective EMI shielding behaviour of thin graphene/PMMA nanolaminates in the THz range
Authors: Pavlou Christos , Pastore Carbone Maria Giovanna , Manikas Anastasios C. , Trakakis George , Koral Can , Papari Gianpaolo , Andreone Antonello , Galiotis Costas 
Published: August 2021

AbstractThe use of graphene in a form of discontinuous flakes in polymer composites limits the full exploitation of the unique properties of graphene, thus requiring high filler loadings for achieving- for example- satisfactory electrical and mechanical properties. Herein centimetre-scale CVD graphene/polymer nanolaminates have been produced by using an iterative ‘lift-off/float-on’ process and have been found to outperform, for the same graphene content, state-of-the-art flake-based graphene polymer composites in terms of mechanical reinforcement and electrical properties. Most importantly these thin laminate materials show a high electromagnetic interference (EMI) shielding effectiveness, reaching 60 dB for a small thickness of 33 μm, and an absolute EMI shielding effectiveness close to 3·105 dB cm2 g−1 which is amongst the highest values for synthetic, non-metallic materials produced to date.
Clinical classification systems and long-term outcome in mid- and late-stage Parkinson’s disease
Authors: Ygland Rödström Emil , Puschmann Andreas 
Published: August 2021

AbstractParkinson’s disease shows a heterogeneous course and different clinical subtyping systems have been described. To compare the capabilities of two clinical classification systems, motor-phenotypes, and a simplified clinical motor-nonmotor subtyping system, a cohort was included at mean 7.9 ± 5.3 years of disease duration, classified using both clinical systems, and reexamined and reclassified at the end of an observation period. Time-points were retrospectively extracted for five major disease milestones: death, dementia, Hoehn and Yahr stage 5, nursing home living, and walking aid use. Eighty-nine patients were observed for 8.1 ± 2.7 years after inclusion. Dementia developed in 32.9% of the patients and 36.0–67.4% reached the other milestones. Motor-phenotypes were unable to stratify risks during this period, but the worst compared with the more favorable groups in the motor-nonmotor system conveyed hazard ratios between 2.6 and 63.6 for all milestones. A clear separation of risks for dying, living at the nursing home, and reaching motor end-stage was also shown when using only postural instability and gait disorder symptoms, without weighing them against the severity of the tremor. At reexamination, 29.4% and 64.7% of patients had changed classification groups in the motor-phenotype and motor-nonmotor systems, respectively. The motor-nonmotor system thus stratified risks of reaching crucial outcomes in mid–late Parkinson’s disease far better than the well-studied motor-phenotypes. Removing the tremor aspect of motor-phenotypes clearly improved this system, however. Classifications in both systems became unstable over time. The simplification of the motor-nonmotor system was easily applicable and showed potential as a prognostic marker during a large part of Parkinson’s disease.
The coordination of major events in C4 photosynthesis evolution in the genus Flaveria
Authors: Lyu Ming-Ju Amy , Gowik Udo , Kelly Steve , Covshoff Sarah , Hibberd Julian M. , Sage Rowan F. , Ludwig Martha , Wong Gane Ka-Shu , Westhoff Peter , Zhu Xin-Guang 
Published: August 2021

AbstractC4 photosynthesis is a remarkable complex trait, elucidations of the evolutionary trajectory of C4 photosynthesis from its ancestral C3 pathway can help us better understand the generic principles of the evolution of complex traits and guide the engineering of C3 crops for higher yields. Here, we used the genus Flaveria that contains C3, C3–C4, C4-like and C4 species as a system to study the evolution of C4 photosynthesis. We first mapped transcript abundance, protein sequence and morphological features onto the phylogenetic tree of the genus Flaveria, and calculated the evolutionary correlation of different features; we then predicted the relative changes of ancestral nodes of those features to illustrate the major events during the evolution of C4 photosynthesis. We found that gene expression and protein sequence showed consistent modification patterns in the phylogenetic tree. High correlation coefficients ranging from 0.46 to 0.9 among gene expression, protein sequence and morphology were observed. The greatest modification of those different features consistently occurred at the transition between C3-C4 species and C4-like species. Our results show highly coordinated changes in gene expression, protein sequence and morphological features, which support evolutionary major events during the evolution of C4 metabolism.
An integrative analysis uncovers a new, pseudo-cryptic species of Amazonian marmoset (Primates: Callitrichidae: Mico) from the arc of deforestation
Authors: Costa-Araújo Rodrigo , Silva- José S. , Boubli Jean P. , Rossi Rogério V. , Canale Gustavo R. , Melo Fabiano R. , Bertuol Fabrício , Silva Felipe E. , Silva Diego A. , Nash Stephen D. , Sampaio Iracilda , Farias Izeni P. , Hrbek Tomas 
Published: August 2021

AbstractAmazonia has the richest primate fauna in the world. Nonetheless, the diversity and distribution of Amazonian primates remain little known and the scarcity of baseline data challenges their conservation. These challenges are especially acute in the Amazonian arc of deforestation, the 2500 km long southern edge of the Amazonian biome that is rapidly being deforested and converted to agricultural and pastoral landscapes. Amazonian marmosets of the genusMicoare little known endemics of this region and therefore a priority for research and conservation efforts. However, even nascent conservation efforts are hampered by taxonomic uncertainties in this group, such as the existence of a potentially new species from the Juruena–Teles Pires interfluve hidden within theM. emiliaeepithet. Here we test if these marmosets belong to a distinct species using new morphological, phylogenomic, and geographic distribution data analysed within an integrative taxonomic framework. We discovered a new, pseudo-crypticMicospecies hidden within the epithetM. emiliae, here described and named after Horacio Schneider, the pioneer of molecular phylogenetics of Neotropical primates. We also clarify the distribution, evolutionary and morphological relationships of four otherMicospecies, bridging Linnean, Wallacean, and Darwinian shortfalls in the conservation of primates in the Amazonian arc of deforestation.