bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Composition on the Compressibility and Shear Strength of Dredged Cohesive Sediment
Authors: Barciela-Rial Maria , Vardon Philip J. , Van Kessel Thijs , Griffioen Jasper , Winterwerp Johan C.
Published: February 2022

Progressively, more dredged sediments are being reused for engineering projects. For example, the Marker Wadden is a new wetland constructed in lake Markermeer, the Netherlands, with dredged cohesive sediments originating from the bed of the lake. Such dredged sediments are often dominated by cohesive sediment particles with varying amounts of sand and organic matter. In addition, during and after the construction process, the material consolidates and is often compressed from a very loose state into a significantly denser condition. To assess the mechanical behavior of this material, the compressibility of the Markermeer dredged sediment samples with various sand and organic matter contents was analyzed with incremental loading oedometer tests, whereas the undrained shear strength was studied using the fall cone test. The behavior was theoretically analyzed assuming a fractal structure of the sediment and applying power law constitutive equations for effective stress, hydraulic conductivity, and undrained shear strength. These constitutive equations, usually used at low initial sediment densities, worked well at the relatively high initial densities studied and proved to be a useful tool to identify the transition fines content TFC. The constitutive equations were put in context with indicators traditionally used in soil mechanics. Samples, each with an identical composition of the fines fraction (particles< 63 μm), but with a sand content varying from 9 to 40%, showed the same compressibility and undrained shear strength behavior when considering the sand a filler material. For a natural sand content of 70%, the behavior was dominated by sand. The organic matter oxidation was observed to drastically decrease the compressibility and the shear strength, and even to decrease the amount of sand needed to exhibit sand-dominated behavior, showing the importance of the reactivity or state of organic matter on the TFC.
Contained-Reflected Megaturbidites of the Marnoso-arenacea Formation (Contessa Key Bed) and Helminthoid Flysches (Northern Apennines, Italy) and Hecho Group (South-Western Pyrenees)
Authors: Tinterri Roberto , Mazza Tommaso , Magalhaes Pierre Muzzi
Published: February 2022

Contained-reflected beds deposited by fully-ponded or partially-reflected turbidity currents are important because their correct evaluation can give important indications on the degree of basin confinement and on the type, size and orientation of the morphological obstacle. Through a detailed facies analysis of various significant megabeds in the Marnoso-arenacea Formation, including the Contessa key bed, in the helminthoid flysches in the northern Apennines (Italy) and in the Pyrenees (megaturbidite MT5), this work proposes a depositional model that is well consistent with the recent experimental data available in the literature, discussing their strengths and limits. The Contessa and flysch megabeds fit very well with the experimental conditions because they are deposited in narrow and elongated confined basins characterized by axial flows. Indeed, in the proposed model, it is possible to recognize facies deposited by: 1) a basal underflow directed towards the bounding slope (Facies A), 2) an intermediate part of the flow characterized by lateral deflections (facies B1), 3) an upper well-developed reversing flow (facies B2) and 4) an uppermost residual reversing flow recording the final collapse of the fine-grained suspended load forming a poorly-sorted slurry facies C and a very thick mudstone unit D. Facies A, B1 and B2 are usually separated by very thin fine-grained muddy drapes rich in carbonaceous matter, which can be traced throughout the basin. These drapes - very common in contained and confined beds in these settings - can be related to internal density surfaces, along which decoupling processes, separating underflows from reversing overflows, can easily occur. Conversely, as the MT5 is characterized by a source transversal to an elongated narrow basin, the large flow volume versus basin capacity hinders the generation of reversing flows and rebound layers favoring the formation of fully-ponded pulsating overflows able to deposit alternations of laminated and massive units. This facies type can be observed in the basins that are characterized by axial flows only near the basin margins where the pulsating collapse of the reversing flow can dominate. This study shows that the integration of detailed field studies are essential to validate experimental data from an applicative point of view.
DriftScalarDyFoam: An OpenFOAM-Based Multistage Solver for Drifting Snow and Its Distribution Around Buildings
Authors: Chen Xiaoxiao , Yu Zhixiang
Published: February 2022

There is a complex coupling relationship between the airflow and snow cover. In a period of hours or even days, the airflow will cause the redistribution of snow, and the redistribution of snow will cause the airflow to change. This study develops a dynamic mesh technology applied in snow drifting simulation through a real-time dynamic mesh update to depict the snow surface evolution process under long-period snow drifting, and a solver application named driftScalarDyFoam based on OpenFOAM is implemented. This solver divides the long-period snow drifting process into several stages, in each of which a snow transport equation is applied to predict the spatial distribution of snow, and finally, the snow surface evolves according to the erosion–deposition model. This method that we have proposed has been validated for several measured cases, including snow distribution on a flat roof and snow distribution around a building.
Transforming Curricula in Higher Education: Description of Two Perspectives From the Global South and the Global North
Authors: Mpofu-Hamadziripi Nomalanga , Rauch Franz , Dulle Mira
Published: February 2022

The paper is part of the broader narrative of transforming curricula in universities in Zimbabwe and Austria. The landscape in higher education globally is inexorably shifting as a result of major global forces of change. For that reason, higher education cannot remain immune to these global challenges and changes. Rather, universities should be the agents of change. Higher education in Austria and Zimbabwe, in response to these global challenges and imperatives, has begun the process of transforming curricula to educate graduates for the future. The paper explores the strategies that universities in Zimbabwe and Austria have initiated to be able to support students to make meaningful contributions to the global learning and sustainability narrative. The two central questions that this paper seeks to answer are: Which additional innovations in curricula and new epistemologies should universities in Zimbabwe and Austria implement in order to educate graduates for a sustainable future? What can universities in the South and in the North learn from each other? In attempting to reflect on these questions, pertinent lessons will be drawn from initiatives in Austria and Zimbabwe to build capacity to achieve the Education for Sustainable Development (ESD) agenda through various strategies.
Motivation and Technology Acceptance in a Neuroscience Student Lab—An Empirical Comparison Between Virtual Experiments With and Without Hands-on Elements
Authors: Formella-Zimmermann Sandra , Kleespies Matthias Winfried , Dierkes Paul Wilhelm
Published: February 2022

Out-of-school laboratories, also called student labs, are an advantageous opportunity to teach biological subjects. Particularly in the case of complex fields such as neurobiology, student labs offer the opportunity to learn about difficult topics in a practical way. Due to numerous advantages, digital student labs are becoming increasingly popular nowadays. In this study, we investigated the effect of an electrophysiological setup for a virtual experiment with and without hands-on elements on participant motivation and technology acceptance. For this purpose, 235 students were questioned during a student laboratory day. The surveyed students showed high motivation and technology acceptance for the virtual experiment. In the comparison, the electrophysiological setup with hands-on elements performs better in the intrinsic components than the setup without hands-on elements: Thus, the hands-on approach is rated as more interesting and the perceived enjoyment scores higher. Nevertheless, both experimental groups show high values, so that the results of the study support the positive influence of digital laboratory as well as a positive influence of hands-on elements.
Congenital Adrenal Hyperplasia and Ehlers-Danlos Syndrome
Authors: Marino Roxana , Moresco Angélica , Perez Garrido Natalia , Ramirez Pablo , Belgorosky Alicia
Published: February 2022

Congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency is an autosomal recessive disorder. The 21-hydroxylase enzyme P450c21 is encoded by the CYP21A2 gene located on chromosome 6p21.33 within the HLA major histocompatibility complex. This locus also contains the CYP21A1P, a non-functional pseudogene, that is highly homologous to the CYP21A2 gene. Other duplicated genes are C4A and C4B, that encode two isoforms of complement factor C4, the RP1 gene that encodes a serine/threonine protein kinase, and the TNXB gene that, encodes the extracellular matrix glycoprotein tenascin-X (TNX). TNX plays a role in collagen deposition by dermal fibroblasts and is expressed in the dermis of the skin and the connective tissue of the heart and skeletal muscle. During meiosis, misalignment may occur producing large gene deletions or gene conversion events resulting in chimeric genes. Chimeric recombination may occur between TNXB and TNXA. Three TNXA/TNXB chimeras have been described that differ in the junction site (CH1 to CH3) and result in a contiguous CYP21A2 and TNXB gene deletion, causing CAH-X syndrome. TNXB deficiency is associated with Ehlers Danlos syndrome (EDS). EDS comprises a clinically and genetically heterogeneous group of connective tissue disorders. As molecular analysis of the TNXB gene is challenging, the TNX-deficient type EDS is probably underdiagnosed. In this minireview, we will address the different strategies of molecular analysis of the TNXB-gene, as well as copy number variations and genetic status of TNXB in different cohorts. Furthermore, clinical features of EDS and clinical recommendations for long-term follow-up are discussed.
A Randomized Cohort Study: Is It Worth the Time to Receive Antiandrogenic Pretreatment Before Ovulation Induction for Women With Polycystic Ovary Syndrome?
Authors: Chen Zhiyan , Tan Jichun , Wang Huichun , Zheng Beihong , Liu Jian , Hao Guimin , Guo Zaixin , Sun Zhengyi , Yu Qi
Published: February 2022

Objective

To assess the effect of antiandrogenic pretreatment using combined oral contraceptives (COCs) before ovulation induction in infertile patients with polycystic ovary syndrome (PCOS) with hyperandrogenism.

Design

Prospective, randomized open-labeled cohort study

Setting

Multicenter

Patients

PCOS patients with hyperandrogenism and requiring infertility treatments

Interventions

Randomization to direct ovulation induction of letrozole (letrozole group) or ethinylestradiol/cyproterone acetate (EE/CPA) for 3 months and subsequent letrozole-induced ovulation (EE/CPA+ letrozole group). The maximum number of ovulation induction cycle was three to four.

Main Outcome Measures

Ovulation rate, conception rate, ongoing pregnancy rate, and live birth rate were the main outcomes of the study.

Results

There were no significant differences in the cumulative ovulation, conception, ongoing pregnancy, and live birth rates between the letrozole and EE/CPA+ letrozole groups (cumulative ovulation: 206/254 [81.10%] vs. 169/205 [82.44%], risk ratio [RR]= 1.09 [0.68,1.76], P=0.713; conception: 44/90 [48.89%] vs. 42/76 [55.26%], RR= 1.29 [0.70,2.38], P=0.413; ongoing pregnancy: 33/90 [36.67%] vs. 33/76 [43.42%], RR=1.33 [0.71,2.47], P=0.376; and live birth: 32/90 [35.56%] vs. 31/76 [40.79%], RR=1.25 [0.67, 2.34], P=0.489).

Conclusions

The results of this study showed that COC pretreatment was not superior to direct letrozole-induced ovulation therapy in improving ovulation and pregnancy results in women with PCOS. There is no benefit to perform antiandrogenic therapy before ovulation induction in patients with PCOS in clinical practice.

Clinical Trial Registration

www.clinicaltrials.gov, identifier ChiCTR1900022839
Identifying Non-Linear Association Between Maternal Free Thyroxine and Risk of Preterm Delivery by a Machine Learning Model
Authors: Zhou Yulai , Liu Yindi , Zhang Yuan , Zhang Yong , Wu Weibin , Fan Jianxia
Published: February 2022

Objective

Preterm delivery (PTD) is the primary cause of mortality in infants. Mounting evidence indicates that thyroid dysfunction might be associated with an increased risk of PTD, but the dose-dependent association between the continuous spectrum maternal free thyroxine (FT4) and PTD is still not well-defined. This study aimed to further investigate this relationship using a machine learning-based model.

Methods

A hospital-based cohort study was conducted from January 2014 to December 2018 in Shanghai, China. Pregnant women who delivered singleton live births and had first-trimester thyroid function data available were included. The generalized additive models with penalized cubic regression spline were applied to explore the non-linear association between maternal FT4 and risk of PTD and also subtypes of PTD. The time-to-event method and multivariable Cox proportional hazard model were further applied to analyze the association of abnormally high and low maternal FT4 concentrations with the timing of PTD.

Results

A total of 65,565 singleton pregnancies with completed medical records and no known thyroid disease before pregnancy were included for final analyses. There was a U-shaped dose-dependent relationship between maternal FT4 in the first trimester and PTD (p <0.001). Compared with the normal range of maternal FT4, increased risk of PTD was identified in both low maternal FT4 (<11.7 pmol/L; adjusted hazard ratio [HR] 1.34, 95% CI [1.13–1.59]) and high maternal FT4 (>19.7 pmol/L; HR 1.41, 95% CI [1.13–1.76]). The association between isolated hypothyroxinemia and PTD was mainly associated with spontaneous PTD (HR 1.33, 95% CI [1.11–1.59]) while overt hyperthyroidism may be attributable to iatrogenic PTD (HR 1.51, 95% CI [1.18–1.92]) when compared with euthyroid women. Additionally, mediation analysis identified that an estimated 11.80% of the association between overt hyperthyroidism and iatrogenic PTD risk was mediated via the occurrence of hypertensive disorders in pregnancy (p <0.001).

Conclusions

We revealed a U-shaped association between maternal FT4 and PTD for the first time, exceeding the clinical definition of maternal thyroid function test abnormalities. Our findings provide insights towards the need to establish optimal range of maternal FT4 concentrations for preventing adverse outcomes in pregnancy.
Superposition Effects of Zinc Smelting Atmospheric Deposition on Soil Heavy Metal Pollution Under Geochemical Anomaly
Authors: Yu Enjiang , Liu Hongyan , Tu Yu , Gu Xiaofeng , Ran Xiaozhui , Yu Zhi , Wu Pan
Published: February 2022

Guizhou Province is covered by a large area of carbonate rocks where, with a higher background of heavy metals under the geochemical anomaly, more than 3.6 × 105 ha of heavy metal–contaminated soil in the northwest area is related to historical indigenous zinc smelting. To explore the superposition effect of industrial source atmospheric deposition on soil, two watersheds were selected for study: 1) Maoshui reservoir watershed (MS), where there is a zinc smelting plant, and 2) Haishe lake watershed (HS), which was the control. We collected atmospheric depositions and soil for 3 years and analyzed Cadmium (Cd), lead (Pb), chromium (Cr), copper (Cu), nickel (Ni), and zinc (Zn) content. The results show that the heavy metals in the atmospheric deposition of the pollution watershed in MS were much higher than those in the control site, HS. The deposition fluxes of Cd, Pb, Cr, Ni, and Zn in MS were 27.8, 602, 145, 43.9, and 2,225 mg·m−2·a−1, respectively, and were 1.37–2.01 times higher than in HS. Soil heavy metals in MS were 1.01–5.69 times higher than in HS. The elevated concentrations were found focused from northeast to southwest around the plant but was distributed uniformly in HS. The average concentration of Cd, Pb, and Zn in the soil was 6.54, 67.4, and 264 mg·kg−1, respectively, in HS, which represents a high geochemical background even without pollution. After 13 years of deposition by prediction, the contribution of the atmospheric deposition on the soil in the zinc-smelting area was lowest, at 5.10%, for Ni, and highest, at 17.9%, for Cd. Principal component analysis of atmospheric deposition and soil heavy metals reflected that the pollution sources in MS were more diversification than those in HS. Zinc smelting atmospheric deposition showed superposition effects on the accumulation of heavy metals in soil under the geochemical anomaly in this region.
Senegalia senegal (L.) Britton Response to Microbial and Manure Amendments for the Rehabilitation of Waste Rock Dumps in the Essakane Gold Mining Site, Burkina Faso
Authors: Yonli Hendi Hermann , Sene Godar , Sanon Kadidia B. , Dianda Mahamadi , Khasa Damase P.
Published: February 2022

Senegalia senegal (L.) Britton (Fabaceae) is a widespread, multipurpose tree capable of colonizing disturbed Sub-Saharan mining sites given its adaptations to arid lands. The purpose of this study was to determine the potential of the association of microbial and/or manure amendments with S. senegal seedlings for the effective rehabilitation of the environment post mining. A multi-year factorial experiment involving this species was conducted in a nursery and on waste rock dumps (Essakane gold mine, NE Burkina Faso). Inoculation with arbuscular mycorrhizal (AM) fungi (native isolate Rhizophagus aggregatus DAOM2277128; commercial isolate Rhizophagus irregularis DAOM197198) and Mesorhizobium plurifarium strain ORS3588 was conducted on S. senegal seedlings. These were planted in black polythene bags filled with three substrate types: 100% sandy soil (substrate A); 75% sandy soil, 25% manure (substrate B); and 50% sandy soil, 50% manure (substrate C). Seedlings were then out-planted on waste rock to determine whether microbial inoculation improves their growth and survival rates. Under nursery conditions, manure-enriched substrates harboured less nodulation and AM colonization, but substantially increased plant height, and dry mass compared to un-amended substrate. Inoculation on manure-enrich substrates did not consistently increase root AM colonization and plant growth parameters among treatments. Plants that were inoculated with R. aggregatus alone or with R. irregularis or Mesorhizobium plurifarium ORS3588 showed the greatest increase in growth variables. On un-amended substrates, inoculation with R. aggregatus in combination with M. plurifarium or R. irregularis significantly enhanced root colonization rates, without altering plant growth parameters. Yet, inoculation with R. irregularis or M. plurifarium alone did not elicit increases in these parameters, although nodulation was greatly improved by the latter treatment. In field conditions, plant growth and survival were reduced under high rate manure amendments, likely due to less AM colonization and root nodulation that was observed for these treatments in nursery before out-planting. Strongly colonized plants on the un-amended substrate and moderately amended substrate showed greater survival after out-planting. Our results support the general conclusion that microbial inoculation and manure-enriched substrates are a viable option for mining site rehabilitation using S. senegal. They also suggest that manure amendments in forest nurseries should be cautiously applied given that high rates may impede establishment of plant symbioses, thereby affecting their performance on waste rock dumps following out-planting.
“Landscape of Stress” for Sheep Owners in the Swedish Wolf Region
Authors: Flykt Anders , Eklund Ann , Frank Jens , Johansson Maria
Published: February 2022

Farmers who keep livestock in large carnivore areas are exposed to threat of predation directly impacting on finances and workload as well as the associated psychological stress indirectly impacting on farmers well-being. So far, little is known about such stress responses. The concept of “stress” or “stress reaction” is often used as an undifferentiated umbrella concept for the experience of negative emotional episodes. However, the stress reactions could be divided into cognitive, physiological, and behavioural aspects. This study aimed to develop and apply a theory-based approach to identify stress responses among sheep farmers in the Swedish “wolf-region.” A thematic analysis of interviews conducted with sheep farmers showed ample support for stress responses among the informants in relation to large carnivores and their management, although the interviews were conducted with a different focal topic. The findings support the idea that stress responses could be categorised into cognitive, physiological, and behavioural aspects. This distinction would help to identify and fully understand the cumulative impact of stress from the presence of large carnivores on farmers’ well-being.
Genetic Lineage Distribution Modeling to Predict Epidemics of a Conifer Disease
Authors: Herpin-Saunier Naomie Y. H. , Sambaraju Kishan R. , Yin Xue , Feau Nicolas , Zeglen Stefan , Ritokova Gabriela , Omdal Daniel , Côté Chantal , Hamelin Richard C.
Published: February 2022

A growing body of evidence suggests that climate change is altering the epidemiology of many forest diseases. Nothophaeocryptopus gaeumannii (Rhode) Petrak, an ascomycete native to the Pacific Northwest and the causal agent of the Swiss needle cast (SNC) disease of Douglas-fir [Pseudotsuga menziesii (Mirbel) Franco], is no exception. In the past few decades, changing climatic conditions have coincided with periodic epidemics of SNC in coastal forests and plantations from Southwestern British Columbia (B.C.) to Southwestern Oregon, wherein an increase in the colonization of needles by N. gaeumanii causes carbon starvation, premature needle shedding and a decline in growth. Two major sympatric genetic lineages of N. gaeumannii have been identified in the coastal Pacific Northwest. Past research on these lineages suggests they have different environmental tolerance ranges and may be responsible for some variability in disease severity. In this study, we examined the complex dynamics between biologically pertinent short- and long-term climatic and environmental factors, phylogenetic lineages of N. gaeumannii and the severity patterns of the SNC disease. Firstly, using an ensemble species distribution modeling approach using genetic lineage presences as model inputs, we predicted the probability of occurrence of each lineage throughout the native range of Douglas-fir in the present as well as in 2050 under the “business as usual” (RCP8.5) emissions scenario. Subsequently, we combined these model outputs with short-term climatic and topographic variables and colonization index measurements from monitoring networks across the SNC epidemic area to infer the impacts of climate change on the SNC epidemic. Our results suggest that the current environmental tolerance range of lineage 1 exceeds that of lineage 2, and we expect lineage 1 to expand inland in Washington and Oregon, while we expect lineage 2 will remain relatively constrained to its current range with some slight increases in suitability, particularly in coastal Washington and Oregon. We also found that disease colonization index is associated with the climatic suitability of lineage 1, and that the suitability of the different lineages could impact the vertical patterns of colonization within the crown. We conclude that unabated climate change could cause the SNC epidemic to intensify.
Fragmentation-Driven Divergent Trends in Burned Area in Amazonia and Cerrado
Authors: Rosan Thais M. , Sitch Stephen , Mercado Lina M. , Heinrich Viola , Friedlingstein Pierre , Aragão Luiz E. O. C.
Published: February 2022

The two major Brazilian biomes, the Amazonia and the Cerrado (savanna), are increasingly exposed to fires. The Amazonian Forest is a fire sensitive ecosystem where fires are a typically rare disturbance while the Cerrado is naturally fire-dependent. Human activities, such as landscape fragmentation and land-use management, have modified the fire regime of the Cerrado and introduced fire into the Amazonian Forest. There is limited understanding of the role of landscape fragmentation on fire occurrence in the Amazonia and Cerrado biomes. Due to differences in vegetation structure, composition, and land use characteristics in each biome, we hypothesize that the emerging burned area (BA) patterns will result from biome-specific fire responses to fragmentation. The aim of this study was to test the general relationship between BA, landscape fragmentation, and agricultural land in the Amazonia and the Cerrado biomes. To estimate the trends and status of landscape fragmentation a Forest Area Density (FAD) index was calculated based on the MapBiomas land cover dataset for both biomes between 2002 and 2018. BA fraction was analyzed within native vegetation against the FAD and agricultural land fraction. Our results showed an increase in landscape fragmentation across 16% of Amazonia and 15% of Cerrado. We identified an opposite relationship between BA fraction, and landscape fragmentation and agricultural fraction contrasting the two biomes. For Amazonia, both landscape fragmentation and agricultural fraction increased BA fraction due to an increase of human ignition activities. For the Cerrado, on the other hand, an increase in landscape fragmentation and agricultural fraction caused a decrease in BA fraction within the native vegetation. For both biomes, we found that during drought years BA increases whilst the divergent trends driven by fragmentation in the two contrasting global biomes is maintained. This understanding will be critical to informing the representation of fire dynamics in fire-enable Dynamic Global Vegetation Models and Earth System Models for climate projection and future ecosystem service provision.
Two Co-occurring Liana Species Strongly Differ in Their Hydraulic Traits in a Water-Limited Neotropical Forest
Authors: Coppieters Kasper , Verbeeck Hans , Dequeker Simon , Powers Jennifer S. , Vargas G. German , Smith-Martin Chris M. , Steppe Kathy , Meunier Félicien
Published: February 2022

Lianas are a key growth form in tropical forests. They are believed to be strong competitors for water, thanks to their presumed efficient vascular systems. However, despite being a large polyphyletic group, they are currently often considered as a functionally homogeneous entity. In this study, we challenged this assumption by estimating the variability in hydraulic traits of two common, co-occurring liana species in a water-limited environment, namely, a seasonally dry tropical forest in Costa Rica. We measured vulnerability to embolism at the leaf and branch levels using two different methods (optical and acoustic vulnerability) and found that both species had very different hydraulic properties. Compared to reported P50values in literature, we found two extreme P50values: a low value forBignonia diversifolia(−4.30 ± 0.54 MPa at the leaf level; −7.42 ± 0.54 MPa at the branch level) and a high value forCissus microcarpa(−1.07 ± 0.14 at the leaf level; −1.20 ± 0.05 MPa at the branch level). Furthermore,B. diversifoliahad a higher apparent modulus of elasticity in the radial direction (556.6 ± 401.0 MPa) and a variable midday water potential. On the other hand,C. microcarpahad a low apparent modulus of elasticity in the radial direction (37.8 ± 26.3 MPa) and a high branch water content, which enabled the species to keep its water potential stable during the dehydration experiments and during a drought period in the field. This mechanism may enable this species to coexist with species that are more resistant to drought-induced embolisms such asB. diversifolia. Although only two species were studied, considerable overlap was found between the range of hydraulic properties of trees growing in the same location and trees and lianas growing in two forests in Panama. These findings demonstrate that lianas cannot be considered as a homogeneous group and call for further research into the intra-growth form diversity of liana properties.
Pretreatment Thoracic CT Radiomic Features to Predict Brain Metastases in Patients With ALK-Rearranged Non-Small Cell Lung Cancer
Authors: Wang Hua , Chen Yong-Zi , Li Wan-Hu , Han Ying , Li Qi , Ye Zhaoxiang
Published: February 2022

Objective: To identify CT imaging biomarkers based on radiomic features for predicting brain metastases (BM) in patients with ALK-rearranged non-small cell lung cancer (NSCLC).

Methods: NSCLC patients with pathologically confirmed ALK rearrangement from January 2014 to December 2020 in our hospital were enrolled retrospectively in this study. Finally, 77 patients were included according to the inclusion and exclusion criteria. Patients were divided into two groups: BM+ were those patients who were diagnosed with BM at baseline examination (n = 16) or within 1 year’s follow-up (n = 14), and BM− were those without BM followed up for at least 1 year (n = 47). Radiomic features were extracted from the pretreatment thoracic CT images. Sequential univariate logistic regression, LASSO regression, and backward stepwise logistic regression were used to select radiomic features and develop a BM-predicting model.

Results: Five robust radiomic features were found to be independent predictors of BM. AUC for radiomics model was 0.828 (95% CI: 0.736–0.921), and when combined with clinical features, the AUC was increased (p = 0.017) to 0.909 (95% CI: 0.845–0.972). The individualized BM-predicting model incorporated with clinical features was visualized by the nomogram.

Conclusion: Radiomic features extracted from pretreatment thoracic CT images have the potential to predict BM within 1 year after detection of the primary tumor in patients with ALK-rearranged NSCLC. The radiomics model incorporated with clinical features shows improved risk stratification for such patients.
Mild Phenotype of Arthrogryposis, Renal Dysfunction, and Cholestasis Syndrome 1 Caused by a Novel VPS33B Variant
Authors: Linhares Natália Duarte , Fagundes Eleonora Druve Tavares , Ferreira Alexandre Rodrigues , Queiroz Thaís Costa Nascentes , da Silva Luiz Roberto , Pena Sergio D. J.
Published: February 2022

The arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is an autosomal recessive multisystem disease caused by variants in VPS33B or VIPAS39. The classical presentation includes congenital joint contractures, renal tubular dysfunction, cholestasis, and early death. Additional features include ichthyosis, central nervous system malformations, platelet dysfunction, and severe failure to thrive. We studied three patients with cholestasis, increased aminotransferases, normal gamma-glutamyl transferase, and developmental and language delay. Whole exome sequencing analysis identified VPS33B variants in all patients: patients 1 and 2 presented a novel homozygous variant at position c.1148T>A. p.(Ile383Asn), and patient 3 was compound heterozygous for the same c.1148T>A. variant, in addition to the c.940-2A>G. variant. ARCS is compatible with the symptomatology presented by the studied patients. However, most patients that have been described in the literature with ARCS had severe failure to thrive and died in the first 6 months of life. The three patients studied here have a mild ARCS phenotype with prolonged survival. Consequently, we believe that the molecular analysis of the VPS33B and VIPAS39 should be considered in patients with normal gamma-glutamyl transferase cholestasis.
Exploring Immune-Related Prognostic Signatures in the Tumor Microenvironment of Colon Cancer
Authors: Cao Lichao , Li Tong , Ba Ying , Chen Erfei , Yang Jin , Zhang Hezi
Published: February 2022

Background: Colon cancer is a common malignant tumor with poor prognosis. The aim of this study is to explore the immune-related prognostic signatures and the tumor immune microenvironment of colon cancer.

Methods: The mRNA expression data of TCGA-COAD from the UCSC Xena platform and the list of immune-related genes (IRGs) from the ImmPort database were used to identify immune-related differentially expressed genes (DEGs). Then, we constructed an immune-related risk score prognostic model and validated its predictive performance in the test dataset, the whole dataset, and two independent GEO datasets. In addition, we explored the differences in tumor-infiltrating immune cell types, tumor mutation burden (TMB), microsatellite status, and expression levels of immune checkpoints and their ligands between the high-risk and low-risk score groups. Moreover, the potential value of the identified immune-related signature with respect to immunotherapy was investigated based on an immunotherapeutic cohort (Imvigor210) treated with an anti-PD-L1 agent.

Results: Seven immune-related DEGs were identified as prognostic signatures. The areas under the curves (AUCs) of the constructed risk score model for overall survival (OS) were calculated (training dataset: 0.780 at 3 years, 0.801 at 4 years, and 0.766 at 5 years; test dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years; and the whole dataset: 0.642 at 3 years, 0.647 at 4 years, and 0.629 at 5 years). In the high-risk score group of the whole dataset, patients had worse OS, higher TMN stages, advanced pathological stages, and a higher TP53 mutation rate (p < 0.05). In addition, a high level of resting NK cells or M0 macrophages, and high TMB were significantly related to poor OS (p < 0.05). Also, we observed that high-risk score patients had a high expression level of PD-L1, PD-1, and CTLA-4 (p < 0.05). The patients with high-risk scores demonstrated worse prognosis than those with low-risk scores in multiple datasets (GSE39582: p = 0.0023; GSE17536: p = 0.0008; immunotherapeutic cohort without platinum treatment: p = 0.0014; immunotherapeutic cohort with platinum treatment: p = 0.0027).

Conclusion: We developed a robust immune-related prognostic signature that performed great in multiple cohorts and explored the characteristics of the tumor immune microenvironment of colon cancer patients, which may give suggestions for the prognosis and immunotherapy in the future.
KDF1 Promoted Proliferation and Metastasis of Epithelial Ovarian Cancer via Wnt/Beta-Catenin Pathway: TCGA-Based Data Mining and Experimental Validation
Authors: Zhu Changyu , Liu Yilong , Tong Rongsheng , Guan Jianmei
Published: February 2022

Objectives: It has been reported that keratinocyte differentiation factor 1 (KDF1) was related to proliferation, differentiation, and cell cycle. However, the role of KDF1 has not been reported in ovarian cancer. The present study investigated the function and the potential mechanism of KDF1 in ovarian cancer.

Methods: We evaluated the prognostic value in ovarian cancer based on data from the Cancer Genome Atlas (TCGA) database. The Kruskal–Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate the relationship between KDF1 expression and clinicopathologic features. The Cox regression and the Kaplan–Meier method were adopted to evaluate prognosis-related factors. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) gene enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were performed to identify the key biological process related to KDF1. Then the expression of KDF1 in ovarian cancer tissues was validated by streptavidin–peroxidase (SP) immunohistochemistry. The proliferation and invasion ability of KDF1 were determined by EdU and Transwell assay, respectively, with KDF1 gene silencing and overexpression. The mRNA expression of KDF1 was determined by qPCR. The protein expression of KDF1 was determined using the Western blot.

Methods: By performing differential expression analysis on the ovarian cancer data of the TCGA database, it was found that KDF1 is highly expressed in ovarian cancer patients and associated with poorer overall survival (OS) and progression-free survival (PFS) of ovarian cancer patients. The highly expressed KDF1 may reduce cell adhesion according to GO, KEGG, and GSEA results. After analysis combining the relevant clinical features, we found that the high expression of KDF1 is an independent prognostic factor of ovarian cancer and associated with platinum resistance and tumor metastasis in ovarian cancer. At the same time, the BioGRID database showed that there might be protein–protein interaction between KDF1 and E-cadherin. Then we further validated that the high expression of KDF1 had a close correlation with the stage and grade of ovarian cancer in ovarian cancer tissue chips. Silencing KDF1 inhibited the proliferation and invasion ability of SKOV3 cells. By contrast, ectopic expression of KDF1 promoted the proliferation and invasion ability of A2780 cells. We also found that KDF1 can interact with E-cadherin and regulate the expression of Wnt5A and β-catenin, hence activating Wnt/β-catenin pathway via in vitro and vivo experiments.

Conclusions: Based on the bioinformatics analysis, in vitro experiments, and an in vivo study, it is indicated that KDF1 played an important role in ovarian cancer progression and might be a therapeutic target for patients with ovarian cancer.
Epigenetic Modifier Supplementation Improves Mitochondrial Respiration and Growth Rates and Alters DNA Methylation of Bovine Embryonic Fibroblast Cells Cultured in Divergent Energy Supply
Authors: Crouse Matthew S. , Caton Joel S. , Claycombe-Larson Kate J. , Diniz Wellison J. S. , Lindholm-Perry Amanda K. , Reynolds Lawrence P. , Dahlen Carl R. , Borowicz Pawel P. , Ward Alison K.
Published: February 2022

Epigenetic modifiers (EM; methionine, choline, folate, and vitamin B12) are important for early embryonic development due to their roles as methyl donors or cofactors in methylation reactions. Additionally, they are essential for the synthesis of nucleotides, polyamines, redox equivalents, and energy metabolites. Despite their importance, investigation into the supplementation of EM in ruminants has been limited to one or two epigenetic modifiers. Like all biochemical pathways, one-carbon metabolism needs to be stoichiometrically balanced. Thus, we investigated the effects of supplementing four EM encompassing the methionine–folate cycle on bovine embryonic fibroblast growth, mitochondrial function, and DNA methylation. We hypothesized that EM supplemented to embryonic fibroblasts cultured in divergent glucose media would increase mitochondrial respiration and cell growth rate and alter DNA methylation as reflected by changes in the gene expression of enzymes involved in methylation reactions, thereby improving the growth parameters beyond Control treated cells. Bovine embryonic fibroblast cells were cultured in Eagle’s minimum essential medium with 1 g/L glucose (Low) or 4.5 g/L glucose (High). The control medium contained no additional OCM, whereas the treated media contained supplemented EM at 2.5, 5, and 10 times (×2.5, ×5, and ×10, respectively) the control media, except for methionine (limited to ×2). Therefore, the experimental design was a 2 (levels of glucose) × 4 (levels of EM) factorial arrangement of treatments. Cells were passaged three times in their respective treatment media before analysis for growth rate, cell proliferation, mitochondrial respiration, transcript abundance of methionine–folate cycle enzymes, and DNA methylation by reduced-representation bisulfite sequencing. Total cell growth was greatest in High ×10 and mitochondrial maximal respiration, and reserve capacity was greatest (p < 0.01) for High ×2.5 and ×10 compared with all other treatments. In Low cells, the total growth rate, mitochondrial maximal respiration, and reserve capacity increased quadratically to 2.5 and ×5 and decreased to control levels at ×10. The biological processes identified due to differential methylation included the positive regulation of GTPase activity, molecular function, protein modification processes, phosphorylation, and metabolic processes. These data are interpreted to imply that EM increased the growth rate and mitochondrial function beyond Control treated cells in both Low and High cells, which may be due to changes in the methylation of genes involved with growth and energy metabolism.
Monogenic Versus Multifactorial Inheritance in the Development of Isolated Cleft Palate: A Whole Genome Sequencing Study
Authors: Lace Baiba , Pajusalu Sander , Livcane Diana , Grinfelde Ieva , Akota Ilze , Mauliņa Ieva , Barkāne Biruta , Stavusis Janis , Inashkina Inna
Published: February 2022

Craniofacial morphogenesis is highly complex, as is the anatomical region involved. Errors during this process, resulting in orofacial clefts, occur in more than 400 genetic syndromes. Some cases of cleft lip and/or palate (CLP) are caused by mutations in single genes; however, complex interactions between genetic and environmental factors are considered to be responsible for the majority of non-syndromic CLP development. The aim of the current study was to identify genetic risk factors in patients with isolated cleft palate (CP) by whole genome sequencing. Patients with isolated CP (n = 30) recruited from the Riga Cleft Lip and Palate Centre, Institute of Stomatology, Riga, were analyzed by whole genome sequencing. Pathogenic or likely pathogenic variants were discovered in genes associated with CP (TBX22, COL2A1, FBN1, PCGF2, and KMT2D) in five patients; hence, rare disease variants were identified in 17% of patients with non-syndromic isolated CP. Our results were relevant to routine genetic counselling practice and genetic testing recommendations. Based on our data, we propose that all newborns with orofacial clefts should be offered genetic testing, at least for a panel of known CLP genes. Only if the results are negative and there is no suggestive family history or additional clinical symptoms (which would support additional exome or genome-wide investigation), should multifactorial empiric recurrence risk prediction tools be applied for families.
A Comprehensive Pan-Cancer Analysis for Pituitary Tumor-Transforming Gene 1
Authors: Gong Siming , Wu Changwu , Duan Yingjuan , Tang Juyu , Wu Panfeng
Published: February 2022

Pituitary tumor-transforming gene 1 (PTTG1) encodes a multifunctional protein that is involved in many cellular processes. However, the potential role of PTTG1 in tumor formation and its prognostic function in human pan-cancer is still unknown. The analysis of gene alteration, PTTG1 expression, prognostic function, and PTTG1-related immune analysis in 33 types of tumors was performed based on various databases such as The Cancer Genome Atlas database, the Genotype-Tissue Expression database, and the Human Protein Atlas database. Additionally, PTTG1-related gene enrichment analysis was performed to investigate the potential relationship and possible molecular mechanisms between PTTG1 and tumors. Overexpression of PTTG1 may lead to tumor formation and poor prognosis in various tumors. Consequently, PTTG1 acts as a potential oncogene in most tumors. Additionally, PTTG1 is related to immune infiltration, immune checkpoints, tumor mutational burden, and microsatellite instability. Thus, PTTG1 could be potential biomarker for both prognosis and outcomes of tumor treatment and it could also be a promising target in tumor therapy.
Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease
Authors: She Shaoping , Ren Liying , Chen Pu , Wang Mingyang , Chen Dongbo , Wang Ying , Chen Hongsong
Published: February 2022

Chemokines are a family of cytokines that orchestrate the migration and positioning of immune cells within tissues and are critical for the function of the immune system. CCR2 participates in liver pathology, including acute liver injury, chronic hepatitis, fibrosis/cirrhosis, and tumor progression, by mediating the recruitment of immune cells to inflammation and tumor sites. Although a variety of chemokines have been well studied in various diseases, there is no comprehensive review presenting the roles of all known chemokine ligands of CCR2 (CCL2, CCL7, CCL8, CCL12, CCL13, CCL16, and PSMP) in liver disease, and this review aims to fill this gap. The introduction of each chemokine includes its discovery, its corresponding chemotactic receptors, physiological functions and roles in inflammation and tumors, and its impact on different immune cell subgroups.
Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity
Authors: Wu Meng , Jia Bei-bei , Li Mo-fei
Published: February 2022

In the complement system, C3 is a central component in complement activation, immune defense and immune regulation. In all pathways of complement activation, the pivotal step is conversion of the component C3 to C3b and C3a, which is responsible to eliminate the pathogen and opsonization. In this study, we examined the immunological properties of C3 and its activated fragment C3a from Japanese flounder (Paralichthys olivaceus) (PoC3 and PoC3a), a teleost species with important economic value. PoC3 is composed of 1655 amino acid residues, contains the six domains and highly conserved GCGEQ sequence of the C3 family. We found thatPoC3expression occurred in nine different tissues and was upregulated by bacterial challenge. In serum, PoC3 was able to bind to a broad-spectrum of bacteria, and purified native PoC3 could directly kill specific pathogen. When PoC3 expression in Japanese flounder was knocked down by siRNA, serum complement activity was significantly decreased, and bacterial replication in fish tissues was significantly increased. Recombinant PoC3a (rPoC3a) exhibited apparent binding capacities to bacteria and Japanese flounder peripheral blood leukocytes (PBL) and induce chemotaxis of PBL. Japanese flounder administered rPoC3a exhibited enhanced resistance against bacterial infection. Taken together, these results indicate that PoC3 is likely a key factor of complement activation, and PoC3 and PoC3a are required for optimal defense against bacterial infection in teleost.