bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of 12‐Years Chinese Regional Reanalysis (1998–2009): Comparison of Dynamical Downscaling Methods With/Without Local Data
Authors: Lu Yutong , Fang Juan , Pan Yinong , Wang Shuyu , Zhou Peifeng , Yang Yi , Shao Min , Tang Jianping 
Published: May 2021

AbstractHigh‐resolution regional reanalysis is one of the most powerful tool to study local and regional high‐impact weather events, climate extremes and climate change impact. In this study, two high‐resolution Chinese Regional Reanalysis (CNRR) datasets with a resolution of 18 km over 1998–2009, which are produced using the Gridpoint Statistical Interpolation (GSI) data assimilation system and spectral nudging (SN) technique, were assessed. The reliability of the surface and upper air variables of the CNRR datasets was evaluated by comparing with in situ observations and the European Centre for Medium‐Range Forecasts (ECMWF) ERA‐Interim (ERAIN) and ERA5 global reanalysis dataset. The evaluation of climatological and seasonal spatial distribution of near‐surface variables shows that the CNRR can provide more accurate near‐surface variables than the driving ERAIN global reanalysis, and CNRR‐GSI shows advantages against ERA5 in representing near‐surface atmosphere during cold season especially for daily maximum temperature. However, care should be taken when using the CNRR precipitation dataset, especially for heavy rainfall cases. CNRR datasets are also able to generate high‐quality upper atmospheric products especially in CNRR‐GSI experiment, which assimilates long time series of local observations. CNRR‐GSI can better represent the lower‐level horizontal wind and temperature than ERA5. By using the three‐dimensional variational data assimilation (3D‐Var) method, CNRR‐GSI outperforms the CNRR‐SN and the driving global reanalyzes. With the increase of the computing resources, the potential opportunities for improving CNRR can be expected by applying more advanced methods.
Pore‐Scale Modeling of Spontaneous Imbibition in Porous Media Using the Lattice Boltzmann Method
Authors: Liu Haihu , Sun Shilin , Wu Rui , Wei Bei , Hou Jian 
Published: May 2021

AbstractA new color‐gradient lattice Boltzmann model is developed to simulate spontaneous imbibition in a porous media micromodel, which needs only two‐dimensional computational cost but considers essential three‐dimensional effects. A modified periodic boundary condition is introduced to deal with inlet and outlet boundaries with great ease and effectiveness. This model is first validated against analytical solutions and micromodel experiment. It is then used to study the spontaneous imbibition process in a homogeneous micromodel for varying viscosity ratios and contact angles. Depending on the viscosity ratio (λ) of wetting to nonwetting fluids, three different imbibition patterns are observed, namely unstable displacement (UD), stable displacement (SD), and crossover from UD to SD, which occur at , , and , respectively. When the crossover occurs, the wetting fluid saturation at breakthrough increases between two plateaus corresponding to UD and SD, respectively. Consistent with theoretical predictions from a single capillary, the wetting fluid saturation versus time follows the relation of for , and for . Due to the increased capillary valve resistance, increasing wetting phase contact angle is found to promote the flow instability, resulting in the development of preferential flow paths and thus some nonwetting fluid trapped in the flow direction. In addition, it is theoretically and numerically demonstrated that the effect of contact angle cannot be properly described by the theoretical equations derived from a single capillary because of the presence of capillary valve effect, which can be suppressed by decreasing contact angle or micromodel depth.
Effects of Tibetan Plateau Growth, Paratethys Sea Retreat and Global Cooling on the East Asian Climate by the Early Miocene
Authors: Zhang Ran , Jiang Dabang , Zhang Zhongshi , Zhang Chunxia 
Published: May 2021

AbstractPaleobotanical and sedimentological records indicate that marked climatic and environmental transitions had taken place in East China by the early Miocene. These transitions were driven by paleogeographic and global climatic shifts, but the respective roles of these shifts in the Asian climate remain unclear. Here, we use the low‐resolution Norwegian Earth System Model and Community Atmosphere Model version 4 to compare the effects of Tibetan Plateau (TP) growth, Paratethys Sea retreat and global cooling on the East Asian climate change that occurred by the early Miocene. The modeling results indicate that these three factors had clearly different climatic effects in East China. In particular, TP growth increased annual precipitation in East China, while Paratethys Sea retreat and global cooling generally decreased annual precipitation in East China. In addition, the three factors studied all drove aridification in inland Asia. Considering the increased precipitation, arid/semiarid‐to‐humid shift in vegetation and high plant diversity present in East China by the early Miocene, as shown in geological records, TP growth thus played a major role in these respects.
Atmospheric Blocking Drives Recent Albedo Change Across the Western Greenland Ice Sheet Percolation Zone
Authors: Lewis Gabriel , Osterberg Erich , Hawley Robert , Marshall Hans Peter , Meehan Tate , Graeter Karina , McCarthy Forrest , Overly Thomas , Thundercloud Zayta , Ferris David , Koffman Bess G. , Dibb Jack 
Published: May 2021

AbstractGreenland Ice Sheet (GrIS) albedo has decreased over recent decades, contributing to enhanced surface melt and mass loss. However, it remains unclear whether GrIS darkening is due to snow grain size increases, higher concentrations of light‐absorbing impurities (LAIs), or a combination. Here, we assess albedo controls in the western GrIS percolation zone using in situ albedo, LAI, and grain size measurements. We find a significant correlation between albedo and snow grain size (p < 0.01), but not with LAIs. Modeling corroborates that LAI concentrations are too low to significantly reduce albedo, but larger grain sizes could reduce albedo by at least ∼3%. Strong atmospheric blocking increases grain sizes and reduces albedo through increased surface temperature, fewer storms, and higher incoming shortwave radiation. These findings clarify the mechanisms by which anomalously strong blocking contributed to recent GrIS albedo decline and mass loss, highlighting the importance of improving projections of future blocking.
Preconceptional smoking alters spermatozoal miRNAs of murine fathers and affects offspring’s body weight
Authors: Hammer Barbara , Kadalayil Latha , Boateng Eistine , Buschmann Dominik , Rezwan Faisal I. , Wolff Martin , Reuter Sebastian , Bartel Sabine , Knudsen Toril Mørkve , Svanes Cecilie , Holloway John W. , Krauss-Etschmann Susanne 
Published: May 2021

Abstract
Background
Active smoking has been reported among 7% of teenagers worldwide, with ages ranging from 13 to 15 years. An epidemiological study suggested that preconceptional paternal smoking is associated with adolescent obesity in boys. We developed a murine adolescent smoking model before conception to investigate the paternal molecular causes of changes in offspring’s phenotype.

Method
Male and female C57BL/6J mice were exposed to increasing doses of mainstream cigarette smoke (CS) from onset of puberty for 6 weeks and mated with room air (RA) controls.

Results
Thirteen miRNAs were upregulated and 32 downregulated in the spermatozoa of CS-exposed fathers, while there were no significant differences in the count and morphological integrity of spermatozoa, as well as the proliferation of spermatogonia between CS- and RA-exposed fathers. Offspring from preconceptional CS-exposed mothers had lower body weights (p = 0.007). Moreover, data from offspring from CS-exposed fathers suggested a potential increase in body weight (p = 0.062).

Conclusion
We showed that preconceptional paternal CS exposure regulates spermatozoal miRNAs, and possibly influences the body weight of F1 progeny in early life. The regulated miRNAs may modulate transmittable epigenetic changes to offspring, thus influence the development of respiratory- and metabolic-related diseases such as obesity, a mechanism that warrants further studies for elaborate explanations.
Serum IGF1 and linear growth in children with congenital leptin deficiency before and after leptin substitution
Authors: Beghini Marianna , Brandt Stephanie , Körber Ingrid , Kohlsdorf Katja , Vollbach Heike , Lennerz Belinda , Denzer Christian , Shalitin Shlomit , Santini Ferruccio , Blum Werner F. , von Schnurbein Julia , Wabitsch Martin 
Published: May 2021

Abstract
Background
Evidence from in vitro and rodent studies suggests that leptin, a key signal of long-term energy reserves, promotes IGF1 synthesis and linear growth. This effect of leptin has not been fully investigated in humans. The aim of our study was to investigate the effect of leptin substitution on growth factors and linear growth in children with congenital leptin deficiency (CLD).

Methods
In this cohort study we included eight pediatric patients (six males), age 0.9–14.8 years, who were diagnosed with CLD and received leptin substitution at our University Medical Center. We calculated standard deviation scores (SDS) for serum levels of IGF1 and IGFBP3, IGF1/IGFBP3 molar ratio, and height at baseline (T0) and 12 months (T12) after the initiation of substitution with metreleptin.

Results
All patients had severe obesity (BMI-SDS mean ± SD: 4.14 ± 1.51) at T0 and significant BMI-SDS reduction to 2.47 ± 1.05 at T12. At T0, all patients were taller than the mid-parental median, yet had low IGF1 and IGF1/IGFBP3 molar ratios (IGF1-SDS$$\overline x$$

x

¯

T0: −1.58 ± 0.92, IGF1/IGFBP3 molar ratio-SDS$$\overline x$$

x

¯

T0: −1.58 ± 0.88). At T12, IGF1-SDS increased significantly (∆T0–12: 1.63 ± 1.40, p = 0.01), and IGFBP3-SDS and IGF1/IGFBP3 molar ratio-SDS showed a trend toward an increase. In the three children within the childhood growth period (post-infancy, pre-puberty) height-SDS increased (∆height-SDST0–12: 0.57 ± 0.06, p = 0.003) despite substantial weight loss.

Conclusions
These results in CLD patients are contrary to observations in children with idiopathic obesity who typically have above-mean IGF1 levels that decrease with weight loss, and therefore suggest that leptin increases IGF1 levels and promotes linear growth.
Sexual dimorphism in adipose tissue mitochondrial function and metabolic flexibility in obesity
Authors: MacCannell Amanda D. V. , Futers T. Simon , Whitehead Anna , Moran Amy , Witte Klaus K. , Roberts Lee D. 
Published: May 2021

Abstract
Objective
The prevalence of obesity is growing globally. Adiposity increases the risk for metabolic syndrome, type 2 diabetes and cardiovascular disease. Adipose tissue distribution influences systemic metabolism and impacts metabolic disease risk. The link between sexual dimorphisms of adiposity and metabolism is poorly defined. We hypothesise that depot-specific adipose tissue mitochondrial function contributes to the sexual dimorphism of metabolic flexibility in obesity.

Methods
Male and female mice fed high fat diet (HFD) or standard diet (STD) from 8–18 weeks of age underwent whole animal calorimetry and high-resolution mitochondrial respirometry analysis on adipose tissue depots. To determine translatability we used RT-qPCR to examine key brown adipocyte-associated gene expression: peroxisome proliferator-activated receptor co-activator 1α, Uncoupling protein 1 and cell death inducing DFFA like effector a in brown adipose tissue (BAT) and subcutaneous adipose tissue (sWAT) of 18-week-old mice and sWAT from human volunteers.

Results
Male mice exhibited greater weight gain compared to female mice when challenged with HFD. Relative to increased body mass, the adipose to body weight ratio for BAT and sWAT depots was increased in HFD-fed males compared to female HFD-fed mice. Oxygen consumption, energy expenditure, respiratory exchange ratio and food consumption did not differ between males and females fed HFD. BAT mitochondria from obese females showed increased Complex I & II respiration and maximal respiration compared to lean females whereas obese males did not exhibit adaptive mitochondrial BAT respiration. Sexual dimorphism in BAT-associated gene expression in sWAT was also associated with Body Mass Index in humans.

Conclusions
We show that sexual dimorphism of weight gain is reflected in mitochondrial respiration analysis. Female mice have increased metabolic flexibility to adapt to changes in energy intake by regulating energy expenditure through increased complex II and maximal mitochondrial respiration within BAT when HFD challenged and increased proton leak in sWAT mitochondria.
Environmental exposures associated with elevated risk for autism spectrum disorder may augment the burden of deleterious de novo mutations among probands
Authors: Pugsley Kealan , Scherer Stephen W. , Bellgrove Mark A. , Hawi Ziarih 
Published: May 2021

AbstractAlthough the full aetiology of autism spectrum disorder (ASD) is unknown, familial and twin studies demonstrate high heritability of 60–90%, indicating a predominant role of genetics in the development of the disorder. The genetic architecture of ASD consists of a complex array of rare and common variants of all classes of genetic variation usually acting additively to augment individual risk. The relative contribution of heredity in ASD persists despite selective pressures against the classic autistic phenotype; a phenomenon thought to be explained, in part, by the incidence of spontaneous (or de novo) mutations. Notably, environmental exposures attributed as salient risk factors for ASD may play a causal role in the emergence of deleterious de novo variations, with several ASD-associated agents having significant mutagenic potential. To explore this hypothesis, this review article assesses published epidemiological data with evidence derived from assays of mutagenicity, both in vivo and in vitro, to determine the likely role such agents may play in augmenting the genetic liability in ASD. Broadly, these exposures were observed to elicit genomic alterations through one or a combination of: (1) direct interaction with genetic material; (2) impaired DNA repair; or (3) oxidative DNA damage. However, the direct contribution of these factors to the ASD phenotype cannot be determined without further analysis. The development of comprehensive prospective birth cohorts in combination with genome sequencing is essential to forming a causal, mechanistic account of de novo mutations in ASD that links exposure, genotypic alterations, and phenotypic consequences.
Endocannabinoid system mediates the association between gut-microbial diversity and anhedonia/amotivation in a general population cohort
Authors: Minichino Amedeo , Jackson Matthew A. , Francesconi Marta , Steves Claire J. , Menni Cristina , Burnet Philip W. J. , Lennox Belinda R. 
Published: May 2021

AbstractAnhedonia and amotivation are debilitating symptoms and represent unmet therapeutic needs in a range of clinical conditions. The gut-microbiome-endocannabinoid axis might represent a potential modifiable target for interventions. Based on results obtained from animal models, we tested the hypothesis that the endocannabinoid system mediates the association between gut-microbiome diversity and anhedonia/amotivation in a general population cohort. We used longitudinal data collected from 786 volunteer twins recruited as part the TwinsUK register. Our hypothesis was tested with a multilevel mediation model using family structure as random intercept. The model was set using alpha diversity (within-individual gut-microbial diversity) as predictor, serum and faecal levels of the endocannabinoid palmitoylethanolamide (PEA) as mediator, and anhedonia/amotivation as outcome. PEA is considered the endogenous equivalent of cannabidiol, with increased serum levels believed to have anti-depressive effects, while increased stool PEA levels, reflecting increased excretion, are believed to have opposite, detrimental, effects on mental health. We therefore expected that either reduced serum PEA or increased stool PEA would mediate the association between microbial diversity and anhedonia amotivation. Analyses were adjusted for obesity, diet, antidepressant use, sociodemographic and technical covariates. Data were imputed using multiple imputation by chained equations. Mean age was 65.2 ± 7.6; 93% of the sample were females. We found a direct, significant, association between alpha diversity and anhedonia/amotivation (β = −0.37; 95%CI: −0.71 to −0.03; P = 0.03). Faecal, but not serum, levels of the endocannabinoid palmitoylethanolamide (PEA) mediated this association: the indirect effect was significant (β = −0.13; 95%CI: −0.24 to −0.01; P = 0.03), as was the total effect (β = −0.38; 95%CI: −0.72 to −0.04; P = 0.03), whereas the direct effect of alpha diversity on anhedonia/amotivation was attenuated fully (β = −0.25; 95%CI: −0.60 to 0.09; P = 0.16). Our results suggest that gut-microbial diversity might contribute to anhedonia/amotivation via the endocannabinoid system. These findings shed light on the biological underpinnings of anhedonia/amotivation and suggest the gut microbiota-endocannabinoid axis as a promising therapeutic target in an area of unmet clinical need.
Protein kinase CK2: a potential therapeutic target for diverse human diseases
Authors: Borgo Christian , D’Amore Claudio , Sarno Stefania , Salvi Mauro , Ruzzene Maria 
Published: May 2021

AbstractCK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (either viral and host proteins). CK2 is also considered an emerging target for neurological diseases, inflammation and autoimmune disorders, diverse ophthalmic pathologies, diabetes, and obesity. In addition, CK2 activity has been associated with cardiovascular diseases, as cardiac ischemia–reperfusion injury, atherosclerosis, and cardiac hypertrophy. The hypothesis of considering CK2 inhibition for cystic fibrosis therapies has been also entertained for many years. Moreover, psychiatric disorders and syndromes due to CK2 mutations have been recently identified. On these bases, CK2 is emerging as an increasingly attractive target in various fields of human medicine, with the advantage that several very specific and effective inhibitors are already available. Here, we review the literature on CK2 implication in different human pathologies and evaluate its potential as a pharmacological target in the light of the most recent findings.
Understanding the psychiatric symptoms of COVID-19: a meta-analysis of studies assessing psychiatric symptoms in Chinese patients with and survivors of COVID-19 and SARS by using the Symptom Checklist-90-Revised
Authors: Xie Qin , Liu Xiao-Bo , Xu Yan-Min , Zhong Bao-Liang 
Published: May 2021

AbstractUnderstanding the psychiatric symptoms of COVID-19 could facilitate the clinical management of COVID-19 patients. However, the profile of psychiatric symptoms among COVID-19 patients has been understudied. We performed a meta-analysis of studies assessing psychiatric symptoms of COVID-19 and SARS patients and survivors by using the Symptom Checklist-90-Revised (SCL-90-R), an instrument covering a wide spectrum of psychiatric symptoms. Studies reporting SCL-90-R subscale scores among patients with and survivors of COVID-19 and SARS were retrieved from major English and Chinese literature databases. Patients’ pooled SCL-90-R subscale scores were compared to the Chinese normative SCL-90-R data, and Cohen’s d values were calculated to indicate the severity of psychiatric symptoms. The Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data was used to assess the quality of the included studies. The search yielded 25 Chinese studies with 1675 acute COVID-19 and 964 acute SARS patients, 30 COVID-19 and 552 SARS survivors during very early recovery (up to 1 month since discharge), 291 SARS survivors during early recovery (1–6 months after discharge), and 48 SARS survivors during late recovery (12 months after discharge). None of the included studies were rated as good quality. The ten SCL-90-R-defined psychiatric symptoms, which were of medium-to-severe severity (d = 0.68–3.01), were all exhibited in acute COVID-19 patients, and the severity of these symptoms decreased to mild-to-medium during very early recovery (d = 0.17–0.73). SARS patients presented eight psychiatric symptoms with mild-to-severe severity during the acute stage (d =0.43–1.88), and thereafter, the severity of symptoms decreased over the follow-up period. However, somatization (d = 0.30) and anxiety (d = 0.28) remained at mild levels during late recovery. A wide variety of severe psychiatric symptoms have been reported by acute COVID-19 patients, and these symptoms, despite decreasing in severity, persist in very early recovery. The changing trajectory observed with SARS suggests that psychiatric symptoms of COVID-19 may persist for a long time after discharge, and therefore, periodic monitoring of psychiatric symptoms, psychosocial support, and psychiatric treatment (when necessary) may be necessary for COVID-19 patients from the acute to convalescent stages.
DA-DRD5 signaling controls colitis by regulating colonic M1/M2 macrophage polarization
Authors: Liu Lu , Wu Yuqing , Wang Bingwei , Jiang Yuying , Lin Lin , Li Xiaoxi , Yang Shuo 
Published: May 2021

AbstractThe decrease of neurotransmitter dopamine (DA) levels in the intestine is closely related to the development of inflammatory bowel disease (IBD). However, the functional relevance and underlying mechanistic basis of the effects of DA signaling on IBD remains unclear. Here, we observed that the DRD5 receptor is highly expressed in colonic macrophages, and the deficiency of DA-DRD5 signaling exacerbated experimental colitis. Moreover, DA-DRD5 signaling can inhibit M1 by negatively regulating NF-κB signaling but promote M2 macrophage polarization through activation of the CREB pathway, respectively. The deficiency of DRD5 signaling increased colonic M1 macrophages but reduced M2 cells during colitis. Additionally, the administration of a D1-like agonist that has a higher affinity to DRD5 can attenuate the colitogenic phenotype of mice. Collectively, these findings provide the first demonstration of DA-DRD5 signaling in colonic macrophages controlling the development of colitis by regulating M1/M2 macrophage polarization.