bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning of Motion Statistics Reveals the Kinematic Signature of the Identity of a Person in Sign Language
Authors: Bigand Félix , Prigent Elise , Berret Bastien , Braffort Annelies
Published: July 2021

Sign language (SL) motion contains information about the identity of a signer, as does voice for a speaker or gait for a walker. However, how such information is encoded in the movements of a person remains unclear. In the present study, a machine learning model was trained to extract the motion features allowing for the automatic identification of signers. A motion capture (mocap) system recorded six signers during the spontaneous production of French Sign Language (LSF) discourses. A principal component analysis (PCA) was applied to time-averaged statistics of the mocap data. A linear classifier then managed to identify the signers from a reduced set of principal components (PCs). The performance of the model was not affected when information about the size and shape of the signers were normalized. Posture normalization decreased the performance of the model, which nevertheless remained over five times superior to chance level. These findings demonstrate that the identity of a signer can be characterized by specific statistics of kinematic features, beyond information related to size, shape, and posture. This is a first step toward determining the motion descriptors necessary to account for the human ability to identify signers.
Meiotic Crossover Patterning
Authors: Pazhayam Nila M. , Turcotte Carolyn A. , Sekelsky Jeff
Published: July 2021

Proper number and placement of meiotic crossovers is vital to chromosome segregation, with failures in normal crossover distribution often resulting in aneuploidy and infertility. Meiotic crossovers are formed via homologous repair of programmed double-strand breaks (DSBs). Although DSBs occur throughout the genome, crossover placement is intricately patterned, as observed first in early genetic studies by Muller and Sturtevant. Three types of patterning events have been identified. Interference, first described by Sturtevant in 1915, is a phenomenon in which crossovers on the same chromosome do not occur near one another. Assurance, initially identified by Owen in 1949, describes the phenomenon in which a minimum of one crossover is formed per chromosome pair. Suppression, first observed by Beadle in 1932, dictates that crossovers do not occur in regions surrounding the centromere and telomeres. The mechanisms behind crossover patterning remain largely unknown, and key players appear to act at all scales, from the DNA level to inter-chromosome interactions. There is also considerable overlap between the known players that drive each patterning phenomenon. In this review we discuss the history of studies of crossover patterning, developments in methods used in the field, and our current understanding of the interplay between patterning phenomena.
Cardioprotective Role of SIRT5 in Response to Acute Ischemia Through a Novel Liver-Cardiac Crosstalk Mechanism
Authors: Zhou Boda , Xiao Min , Hu Hao , Pei Xiaoxia , Xue Yajun , Miao Guobin , Wang Jifeng , Li Wanqi , Du Yipeng , Zhang Ping , Wei Taotao
Published: July 2021

Protein posttranslational modifications play important roles in cardiovascular diseases. The authors’ previous report showed that the abundance of succinylated and glutarylated proteins was significantly lower in the serum of patients with acute myocardial infarction (AMI) than in that of healthy volunteers, suggesting a potential relationship between protein acylation and AMI. Sirtuin 5 (SIRT5) facilitates the removal of malonyl, succinyl, and glutaryl modification; however, its effects on AMI remain unknown. In this study, the levels of SIRT5 in AMI mouse model was compared. Results showed elevated hepatic SIRT5 after myocardial infarction. Hepatocyte-specific SIRT5 overexpressing mice (liver SIRT5 OE) were generated to address the possible involvement of hepatic SIRT5 in AMI. The areas of myocardial infarction, myocardial fibrosis, and cardiac function in a model of experimental myocardial infarction were compared between liver SIRT5 OE mice and wild-type (WT) mice. The liver SIRT5 OE mice showed a significantly smaller area of myocardial infarction and myocardial fibrosis than the WT mice. The fibroblast growth factor 21 (FGF21) in the blood and myocardium of liver SIRT5 OE mice after AMI was markedly elevated compared with that in WT mice. The results of mass spectrometry showed increased levels of proteins regulating tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid β-oxidation pathways in the liver mitochondria of liver SIRT5 OE mice. These findings showed that SIRT5 may exhibit a cardioprotective effect in response to acute ischemia through a liver-cardiac crosstalk mechanism, probably by increasing the secretion of FGF21 and the improvement of energy metabolism.
Epigenetics of Male Infertility: The Role of DNA Methylation
Authors: Rotondo John Charles , Lanzillotti Carmen , Mazziotta Chiara , Tognon Mauro , Martini Fernanda
Published: July 2021

In recent years, a number of studies focused on the role of epigenetics, including DNA methylation, in spermatogenesis and male infertility. We aimed to provide an overview of the knowledge concerning the gene and genome methylation and its regulation during spermatogenesis, specifically in the context of male infertility etiopathogenesis. Overall, the findings support the hypothesis that sperm DNA methylation is associated with sperm alterations and infertility. Several genes have been found to be differentially methylated in relation to impaired spermatogenesis and/or reproductive dysfunction. Particularly, DNA methylation defects of MEST and H19 within imprinted genes and MTHFR within non-imprinted genes have been repeatedly linked with male infertility. A deep knowledge of sperm DNA methylation status in association with reduced reproductive potential could improve the development of novel diagnostic tools for this disease. Further studies are needed to better elucidate the mechanisms affecting methylation in sperm and their impact on male infertility.
Patchouli Alcohol Improves the Integrity of the Blood-Spinal Cord Barrier by Inhibiting Endoplasmic Reticulum Stress Through the Akt/CHOP/Caspase-3 Pathway Following Spinal Cord Injury
Authors: Huang Chongan , Zhang Weiqi , Chu FeiFan , Qian Hao , Wang Yining , Qi Fangzhou , Ye Mengke , Zhou Jiaying , Lin Zhi , Dong ChenLin , Wang Xiangyang , Wang Qingqing , Jin Haiming
Published: July 2021

Spinal cord injury (SCI) is a destructive and complex disorder of the central nervous system (CNS) for which there is no clinical treatment. Blood-spinal cord barrier (BSCB) rupture is a critical event in SCI that aggravates nerve injury. Therefore, maintaining the integrity of the BSCB may be a potential method to treat SCI. Here, we showed that patchouli alcohol (PA) exerts protective effects against SCI. We discovered that PA significantly prevented hyperpermeability of the BSCB by reducing the loss of tight junctions (TJs) and endothelial cells. PA also suppressed endoplasmic reticulum stress and apoptosis in vitro. Furthermore, in a rat model of SCI, PA effectively improved neurological deficits. Overall, these results prove that PA exerts neuroprotective effects by maintaining BSCB integrity and thus be a promising candidate for SCI treatment.
Lysine Fatty Acylation: Regulatory Enzymes, Research Tools, and Biological Function
Authors: Komaniecki Garrison , Lin Hening
Published: July 2021

Post-translational acylation of lysine side chains is a common mechanism of protein regulation. Modification by long-chain fatty acyl groups is an understudied form of lysine acylation that has gained increasing attention recently due to the characterization of enzymes that catalyze the addition and removal this modification. In this review we summarize what has been learned about lysine fatty acylation in the approximately 30 years since its initial discovery. We report on what is known about the enzymes that regulate lysine fatty acylation and their physiological functions, including tumorigenesis and bacterial pathogenesis. We also cover the effect of lysine fatty acylation on reported substrates. Generally, lysine fatty acylation increases the affinity of proteins for specific cellular membranes, but the physiological outcome depends greatly on the molecular context. Finally, we will go over the experimental tools that have been used to study lysine fatty acylation. While much has been learned about lysine fatty acylation since its initial discovery, the full scope of its biological function has yet to be realized.
Surface Mechanism of Fe3+ Ions on the Improvement of Fine Monazite Flotation With Octyl Hydroxamate as the Collector
Authors: Zheng Qingzhu , Qian Yunlou , Zou Dan , Wang Zhen , Bai Yang , Dai Haidong
Published: July 2021

Froth flotation of fine minerals has always been an important research direction in terms of theory and practice. In this paper, the effect and mechanism of Fe3+ on improving surface hydrophobicity and flotation of fine monazite using sodium octyl hydroxamate (SOH) as a collector were investigated through a series of laboratory tests and detection measurements including microflotation, fluorescence spectrum, zeta potential, and X-ray photoelectron spectroscopy (XPS). Flotation tests have shown that fine monazite particles (−26 + 15 μm) cannot be floated well with the SOH collector compared to the coarse fraction (−74 + 38 μm). However, adding a small amount of Fe3+ to the pulp before SOH can significantly improve the flotation of fine monazite. This is because the addition of Fe3+ promotes the adsorption of SOH and greatly improves the hydrophobicity of the monazite surface. This can result in the formation of a more uniform and dense hydrophobic adsorption layer, as shown by the fluorescence spectrum and zeta potential results. From the XPS results, Fe3+ reacts with surface O atoms on the surface of monazite to form a monazite–Osurf–Fe group that acts as a new additional active site for SOH adsorption. A schematic model was also proposed to explain the mechanism of Fe3+ for improving surface hydrophobicity and flotation of fine monazite using octyl hydroxamate as a collector. The innovative point of this study is using a simple reagent scheme to float fine mineral particles rather than traditional complex processes.
DNA Condensation Triggered by the Synergistic Self-Assembly of Tetraphenylethylene-Viologen Aggregates and CT-DNA
Authors: Saraswathi Sajena Kanangat , Karunakaran Varsha , Maiti Kaustabh Kumar , Joseph Joshy
Published: July 2021

Development of small organic chromophores as DNA condensing agents, which explore supramolecular interactions and absorbance or fluorescence-based tracking of condensation and gene delivery processes, is in the initial stages. Herein, we report the synthesis and electrostatic/groove binding interaction–directed synergistic self-assembly of the aggregates of two viologen-functionalized tetraphenylethylene (TPE-V) molecules with CT-DNA and subsequent concentration-dependent DNA condensation process. TPE-V molecules differ in their chemical structure according to the number of viologen units. Photophysical and morphological studies have revealed the interaction of the aggregates of TPE-V in Tris buffer with CT-DNA, which transforms the fibrous network structure of CT-DNA to partially condensed beads-on-a-string-like arrangement with TPE-V aggregates as beads via electrostatic and groove binding interactions. Upon further increasing the concentration of TPE-V, the “beads-on-a-string”-type assembly of TPE-V/CT-DNA complex changes to completely condensed compact structures with 40–50 nm in diameter through the effective charge neutralization process. Enhancement in the melting temperature of CT-DNA, quenching of the fluorescence emission of ethidium bromide/CT-DNA complex, and the formation of induced CD signal in the presence of TPE-V molecules support the observed morphological changes and thereby verify the DNA condensation abilities of TPE-V molecules. Decrease in the hydrodynamic size, increase in the zeta potential value with the addition of TPE-V molecules to CT-DNA, failure of TPE-V/cucurbit(8)uril complex to condense CT-DNA, and the enhanced DNA condensation ability of TPE-V2 with two viologen units compared to TPE-V1 with a single viologen unit confirm the importance of positively charged viologen units in the DNA condensation process. Initial cytotoxicity analysis on A549 cancer and WI-38 normal cells revealed that these DNA condensing agents are non-toxic in nature and hence could be utilized in further cellular delivery studies.
A Deliberative Orientation to Governing Carbon Dioxide Removal: Actionable Recommendations for National-Level Action
Authors: Borth Amanda C. , Nicholson Simon
Published: July 2021

Effective and legitimate governance of carbon dioxide removal (CDR) requires that the needs, interests, and perspectives of those liable to bear the burdens of CDR's effects be present in decision-making and oversight processes. This ideal has been widely recognized in prior academic work. How, though, in a practical sense, is this deliberative aspect of CDR governance to be understood? In this policy brief, we look at the future incorporation of carbon removal pledges into the nationally determined contributions (NDCs) of countries under the Paris Agreement, and we argue for and explore adeliberative orientationwhen it comes to the inclusion of CDR into country-level climate change response goals. The aim is to provide practical guidance on deliberation as a toolkit and set of practices.
On the Determination of Coordination Numbers of Coupled DEM-DFN Model for Modeling Fractured Rocks
Authors: Xu Xiaoyi , Fu Li-Yun , Liu Ning , Han Tongcheng
Published: July 2021

Natural fractured rocks usually contain background granular media and multi-scale fractures. The coordination number is a crucial factor to characterize the connection of microstructural elements. The determination of coordination numbers for modeling fractured rocks is essential to interpret the distribution of cracks related to micromechanical properties. We have built a consistent workflow of discrete element models (DEMs) coupled with discrete fracture networks (DFNs). This DEM-DFN model could provide a simple formulation for high calculation efficiency to model a more realistic and detailed description of fracture system. A series of numerical experiments are set up, aiming to correlate window radius, particle size, and crack length, which will benefit the window selection for measuring coordination numbers based on the crack characteristics. The coordination number determined in the DEM-DFN modeling can be used to identify crack patterns in the spatial distribution.
Margin-to-Margin Seafloor Spreading in the Eastern Gulf of Aden: A 16 Ma-Long History of Deformation and Magmatism from Seismic Reflection, Gravity and Magnetic Data
Authors: Gillard Morgane , Leroy Sylvie , Cannat Mathilde , Sloan Heather
Published: July 2021

In this paper we present and analyze spreading-parallel seismic transects that image the oceanic crust in the eastern Gulf of Aden, from the Oman to the Socotra margins, across the active Sheba mid-oceanic ridge and between the Socotra-Hadbeen and Eastern Gulf of Aden Fracture Zones. The correlation of potential field data sets and gravity modelling allow us to document the spreading history of this oceanic basin from the onset of seafloor spreading ∼16 Ma-ago to the present. Two main oceanic sub-domains display distinct structural characteristics associated with different magmatic budgets at this mid-ocean ridge. In addition, we document the occurrence of a magmatic pulse at the Sheba Ridge around 11 Ma leading to the construction of a magmatic plateau in the western part of the studied area. This event led to substantial deformation and additional magmatism in previously formed oceanic crust. It could be related to an off-axis magmatic event previously identified in the adjacent Sheba segment, itself possibly related to the Afar plume.
Are Markers of Systemic Inflammatory Response Useful in the Management of Patients With Neuroendocrine Neoplasms?
Authors: Giannetta Elisa , La Salvia Anna , Rizza Laura , Muscogiuri Giovanna , Campione Severo , Pozza Carlotta , Colao Annamaria Anita LIvia , Faggiano Antongiulio
Published: July 2021

Given the increasing incidence of neuroendocrine neoplasms (NENs) over the past few decades, a more comprehensive knowledge of their pathophysiological bases and the identification of innovative NEN biomarkers represents an urgent unmet need. There is still little advance in the early diagnosis and management of these tumors, due to the lack of sensible and specific markers with prognostic value and ability to early detect the response to treatment. Chronic systemic inflammation is a predisposing factor for multiple cancer hallmarks, as cancer proliferation, progression and immune-evading. Therefore, the relevance of inflammatory biomarkers has been identified as critical in several types of tumours, including NENs. A bidirectional relationship between chronic inflammation and development of NENs has been reported. Neuroendocrine cells can be over-stimulated by chronic inflammation, leading to hyperplasia and neoplastic transformation. As the modulation of inflammatory response represents a therapeutic target, inflammatory markers could represent a promising new key tool to be applied in the diagnosis, the prediction of response to treatment and also as prognostic biomarkers in NENs field. The present review provides an overview of the pre-clinical and clinical data relating the potentially usefulness of circulating inflammatory markers: neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), cytokines and tissue inflammatory markers (PD-1/PD-L1), in the management of NENs. (1) NLR and PLR have both demonstrated to be promising and simple to acquire biomarkers in patients with advanced cancer, including NEN. To date, in the context of NENs, the prognostic role of NLR and PLR has been confirmed in 15 and 4 studies, respectively. However, the threshold value, both for NLR and PLR, still remains not defined. (2) Cytokines seem to play a central role in NENs tumorigenesis. In particular, IL-8 levels seems to be a good predictive marker of response to anti-angiogenic treatments. (3) PD-1 and PD-L1 expression on tumour cells and on TILs, have demonstrated to be promising predictive and prognostic biomarkers in NENs. Unfortunately, these two markers have not been validated so far and further studies are needed to establish their indications and utility.
Newer Insights Into Fetal Growth and Body Composition
Authors: Ikenoue Satoru , Kasuga Yoshifumi , Endo Toyohide , Tanaka Mamoru , Ochiai Daigo
Published: July 2021

Based on epidemiological and experimental evidence, the origins of childhood obesity and early onset metabolic syndrome can be extended back to developmental processes during intrauterine life. It is necessary to actively investigate antecedent conditions that affect fetal growth by developing reliable measures to identify variations in fetal fat deposition and body composition. Recently, the resolution of ultrasonography has remarkably improved, which enables better tissue characterization and quantification of fetal fat accumulation. In addition, fetal fractional limb volume has been introduced as a novel measure to quantify fetal soft tissue volume, including fat mass and lean mass. Detecting extreme variations in fetal fat deposition may provide further insights into the origins of altered fetal body composition in pathophysiological conditions (i.e., fetal growth restriction or fetal macrosomia), which are predisposed to the metabolic syndrome in later life. Further studies are warranted to determine the maternal or placental factors that affect fetal fat deposition and body composition. Elucidating these factors may help develop clinical interventions for altered fetal growth and body composition, which could potentially lead to primary prevention of the future risk of metabolic dysfunction.
Preoperatively Predicting the Central Lymph Node Metastasis for Papillary Thyroid Cancer Patients With Hashimoto’s Thyroiditis
Authors: Min Yu , Huang Yizhou , Wei Minjie , Wei Xiaoyuan , Chen Hang , Wang Xing , Chen Jialin , Xiang Ke , Feng Yang , Yin Guobing
Published: July 2021

Background

The preoperative distinguishment of lymph nodes with reactive hyperplasia or tumor metastasis plays a pivotal role in guiding the surgical extension for papillary thyroid carcinoma (PTC) with Hashimoto’s thyroiditis (HT), especially in terms of the central lymph node (CLN) dissection. We aim to identify the preparative risk factors for CLN metastasis in PTC patients concurrent with HT.

Materials and Methods

We retrospectively reviewed and analyzed the data including the basic information, preoperative sonographic characteristics, and thyroid function of consecutive PTC patients with HT in our medical center between Jan 2019 and Apr 2021. The Chi-square and Fisher’s exact tests were used for comparison of qualitative variables among patients with or without CLN metastasis. Univariate and multivariate logistic regression analyses were used to determine the risk factors for CLN metastasis. The nomogram was constructed and further evaluated by two cohorts produced by 1,000 resampling bootstrap analysis.

Results

A total of 98 in 214 (45.8%) PTC patients were identified with CLN metastasis. In multivariate analysis, four variables including high serum thyroglobulin antibody (TgAb) level (>1,150 IU/ml), lower tumor location, irregular margin of CLN, and micro-calcification in the CLN were determined to be significantly associated with the CLN metastasis in PTC patients with HT. An individualized nomogram was consequently established with a favorable C-index of 0.815 and verified via two internal validation cohorts.

Conclusions

Our results indicated that preoperatively sonographic characteristics of the tumor and lymph node condition combined with serum TgAb level can significantly predict the CLN in PTC patients with HT and the novel nomogram may further help surgeons to manage the CLN in this subpopulation.
The Role of Urban Green Space in Promoting Inclusion: Experiences From the Netherlands
Authors: De Haas Wim , Hassink Jan , Stuiver Marian
Published: July 2021

Urban Green Space (UGS) is considered to be beneficial for health and wellbeing of urban residents. But there is growing evidence that benefits are not equally distributed. In this article we aim to understand the role that UGS plays in the process of social exclusion and the role urban greening strategies can play in enhancing social equity for specific groups that are excluded: elderly people with dementia, people with mental issues and people from an underprivileged neighborhood. The concepts of inclusion and exclusion and their relation to UGS are discussed. Four exclusion mechanisms are distinguished based on the role of the physical and societal environment and on the role of actors involved (public or private). Further, we identify four discourses behind possible strategies and measures to promote inclusion. These mechanisms and discourses are confronted with an analysis of three cases promoting inclusion of elderly with dementia, people with mental health issues and people from an underprivileged neighborhood. Succesful inclusion strategies in these cases are based on alignment between private actors initiatives and public actions. The cases indicate that public and private actors need to cooperate better in order to make UGS part of inclusion strategies.
Estimating Benefits of Nature-based Solutions: Diverging Values From Choice Experiments With Time or Money Payments
Authors: Hagedoorn Liselotte C. , Koetse Mark J. , van Beukering Pieter J. H.
Published: July 2021

Nature-based solutions (NBS) provide a promising means to a climate resilient future. To guide investments in NBS, stated preference studies have become a common tool to evaluate the benefits of NBS in developing countries. Due to subsistence lifestyles and generally lower incomes, SP studies in developing countries increasingly use time payments as an alternative to the traditionally implemented money payments. It remains unclear, however, how time values should be converted into money values, how the payment affects willingness to pay (WTP) estimates, and how this influence varies across settings with different levels of market integration. We compare the results of choice experiments that use either time or money payments and that are implemented in urban and rural Ghana. The choice experiments target to value different NBS aimed at erosion prevention and other ecosystem service benefits along the highly erosion prone Ghanaian coastline. Time payments are converted into monetary units using two generic wage-based conversion rates and one novel individual-specific non-wage-based conversion rate. We find higher WTP estimates for the time payments. Moreover, we find that the underlying implicit assumptions related to the currently commonly applied generic wage-based conversion rates do not hold. Finally, we find higher levels of market integration and smaller WTP disparities in the urban site, providing evidence that market integration allows for convergence of WTP estimates. These results provide guidance on the accurate estimation of NBS benefits through the implementation of stated preference studies with time payments.
Ligand Binding Domain of Estrogen Receptor Alpha Preserve a Conserved Structural Architecture Similar to Bacterial Taxis Receptors
Authors: Lakshmanan Mangalath Divya , Hassan Mohammed Shabeer Ali
Published: July 2021

It remains a mystery why estrogen hormone receptors (ERs), which are highly specific toward its endogenous hormones, are responsive to chemically distinct exogenous agents. Does it indicate that ERs are environmentally regulated? Here, we speculate that ERs would have some common structural features with prokaryotic taxis receptor responsive toward environmental signals. This study addresses the low specificity and high responsiveness of ERs toward chemically distinct exogenous substances, from an evolutionary point of view. Here, we compared the ligand binding domain (LBD) of ER alpha (α) with the LBDs of prokaryotic taxis receptors to check if LBDs share any structural similarity. Interestingly, a high degree of similarity in the domain structural fold architecture of ERα and bacterial taxis receptors was observed. The pharmacophore modeling focused on ligand molecules of both receptors suggest that these ligands share common pharmacophore features. The molecular docking studies suggest that the natural ligands of bacterial chemotaxis receptors exhibit strong interaction with human ER as well. Although phylogenetic analysis proved that these proteins are unrelated, they would have evolved independently, suggesting a possibility of convergent molecular evolution. Nevertheless, a remarkable sequence divergence was seen between these proteins even when they shared common domain structural folds and common ligand-based pharmacophore features, suggesting that the protein architecture remains conserved within the structure for a specific function irrespective of sequence identity.
The Added Value of Whole-Exome Sequencing for Anomalous Fetuses With Detailed Prenatal Ultrasound and Postnatal Phenotype
Authors: He Miao , Du Liu , Xie Hongning , Zhang Lihe , Gu Yujun , Lei Ting , Zheng Ju , Chen Dan
Published: July 2021

Objectives

The objective of the study was to explore the added value of whole-exome sequencing (WES) in abnormal fetuses with detailed prenatal ultrasound and postnatal phenotype with normal karyotype and chromosomal microarray analysis (CMA).

Methods

Parents of fetuses with structural abnormalities by prenatal ultrasound who consented to provide fetal samples were prospectively recruited from January 2017 to December 2019. With aneuploidies or cases with copy number variations (CNVs) excluded, WES was performed for cases with normal karyotype and CMA results. Detailed prenatal ultrasound and postnatal imaging or pathology features were recommended for further interpretation of genetic variants.

Results

WES was performed for 94 eligible fetuses, DNA samples of which were extracted from 53 parent–fetus trios and 41 proband-only fetal tissues. A diagnostic genetic variant was identified in 37 (39.4%) of 94 fetuses, and 34 (64.2%) were detected in 53 trios, which was significantly greater than 3 (7.3%) in 41 proband-only cases (p < 0.001). In 34 trios with diagnostic genetic variants, 23 (67.6%) were de novo and 11 (32.4%) were inherited with two homozygous and nine heterozygous variants. Fourteen (14.9%) of 94 fetuses had a variant of uncertain significance (VUS). Among 94 cases, six affected pregnancies continued and 88 terminated, and 57 of 88 terminated cases underwent postmortem examinations. With accurate phenotypes demonstrated by prenatal ultrasound and postnatal autopsies, the clinical phenotypes were correlated in 33 (89.2%) of 37 cases with specific genotypes, with the highest matching ratio in skeletal diseases (20/33, 60.6%).

Conclusion

WES has added value in the genetic diagnosis of abnormal fetuses with normal karyotypes and CMA, particularly in skeletal diseases. Using WES in various anomalous fetuses can broaden the understanding of prenatal phenotypes and genetic variants.
KCNMB2-AS1 Promotes Bladder Cancer Progression Through Sponging miR-374a-3p to Upregulate S100A10
Authors: Zhu Jianhua , Huang Yan , Zhang Yong , Huang Rongfu , Huang Chunmei
Published: July 2021

Long non-coding RNAs (lncRNAs) have been reported to play a crucial role in the pathogenesis of numerous cancers. However, the function of lncRNA KCNMB2-AS1 in bladder cancer (BC) remains unclear. In the present study, we aimed to explore the role and underlying mechanisms of KCNMB2-AS1 in bladder cancer progression. We found that lncRNA KCNMB2-AS1 was significantly upregulated both in BC tissues and cell lines, the expression level was highly correlated with pathological TNM stage. Functionally, knockdown of lncRNA KCNMB2-AS1 dramatically inhibited the proliferation, migration, and invasion and of BC cells in vitro, and suppressed tumor growth in vivo. Mechanistically, lncRNA KCNMB2-AS1 could function as a competitive endogenous RNA (ceRNA) through direct sponging miR-374a-3p, which regulated the expression of S100A10. In conclusion, our results demonstrated that lncRNA KCNMB2-AS1 can promote the progression of bladder cancer through regulation of miR-374a-3p/S100A10.
Obesity, Type 2 Diabetes, and the Risk of Carpal Tunnel Syndrome: A Two-Sample Mendelian Randomization Study
Authors: Mi Jiarui , Liu Zhengye
Published: July 2021

Some previous observational studies have reported an increased risk of carpal tunnel syndrome (CTS) in patients with obesity or type 2 diabetes (T2D), which was however, not observed in some other studies. In this study we performed a two-sample Mendelian randomization to assess the causal effect of obesity, T2D on the risk of CTS. Single nucleotide polymorphisms associated with the body mass index (BMI) and T2D were extracted from genome-wide association studies. Summary-level results of CTS were available through FinnGen repository. Univariable Mendelian randomization (MR) with inverse-variance-weighted method indicated a positive correlation of BMI with CTS risk [odds ratio (OR) 1.66, 95% confidence interval (CI), 1.39–1.97]. Genetically proxied T2D also significantly increased the risk of CTS [OR 1.17, 95% CI (1.07–1.29)]. The causal effect of BMI and T2D on CTS remained consistent after adjusting for each other with multivariable MR. Our mediation analysis indicated that 34.4% of BMI’s effect of CTS was mediated by T2D. We also assessed the effects of several BMI and glycemic related traits on CTS. Waist circumference and arm fat-free mass were also causally associated with CTS. However, the associations disappeared after adjusting for the effect of BMI. Our findings indicate that obesity and T2D are independent risk factors of CTS.
Population Genetic Structure and Contribution of Philippine Chickens to the Pacific Chicken Diversity Inferred From Mitochondrial DNA
Authors: Godinez Cyrill John P. , Dadios Peter June D. , Espina Dinah M. , Matsunaga Megumi , Nishibori Masahide
Published: July 2021

The Philippines is considered one of the biodiversity hotspots for animal genetic resources. In spite of this, population genetic structure, genetic diversity, and past population history of Philippine chickens are not well studied. In this study, phylogeny reconstruction and estimation of population genetic structure were based on 107 newly generated mitochondrial DNA (mtDNA) complete D-loop sequences and 37 previously published sequences of Philippine chickens, consisting of 34 haplotypes. Philippine chickens showed high haplotypic diversity (Hd= 0.915 ± 0.011) across Southeast Asia and Oceania. The phylogenetic analysis and median-joining (MJ) network revealed predominant maternal lineage haplogroup D classified throughout the population, while support for Philippine–Pacific subclade was evident, suggesting a Philippine origin of Pacific chickens. Here, we observed Philippine red junglefowls (RJFs) at the basal position of the tree within haplogroup D indicating an earlier introduction into the Philippines potentially via mainland Southeast Asia (MSEA). Another observation was the significantly low genetic differentiation and high rate of gene flow of Philippine chickens into Pacific chicken population. The negative Tajima’sDand Fu’sFsneutrality tests revealed that Philippine chickens exhibited an expansion signal. The analyses of mismatch distribution and neutrality tests were consistent with the presence of weak phylogeographic structuring and evident population growth of Philippine chickens (haplogroup D) in the islands of Southeast Asia (ISEA). Furthermore, the Bayesian skyline plot (BSP) analysis showed an increase in the effective population size of Philippine chickens, relating with human settlement, and expansion events. The high level of genetic variability of Philippine chickens demonstrates conservation significance, thus, must be explored in the future.
Credibility Assessment in Asylum Claims Based on Sexual Orientation by the Greek Asylum Service: A Deep-Rooted Culture of Disbelief
Authors: Zisakou Sophia
Published: July 2021

The aim of this article is to describe and analyze the main practices that the Greek Asylum Service applies to assess credibility in asylum claims based on sexual orientation. The analysis is based on a survey of 60 cases (interviews and first instance decisions). According to the results of the survey, the practices used could be divided into two categories. On the one hand, practices that do not conform with refugee law, the Common European Asylum System, and human rights standards, such as questions around sexual practices of the asylum seekers, stereotyped expectations about applicants’ behavior and knowledge, and arbitrary assessments lacking any legal reasoning. On the other hand, practices that, at first sight, comply with international and European guidelines for credibility assessment but are based on an essentialist understanding of lesbian, gay, and bisexual identity. According to the research, applicants are expected to have passed through a hard process of self-realization which has to be accompanied, by default, by feelings of difference, shame, and suffering. In the article, the author critically reflects on the practices applied, concluding that this notion of sexual orientation as innate and defining one’s identity, fails to take into account the intersections of gender, class, ethnicity, and race, and could lead to unjust judgments.
A Novel Model Based on Serum Biomarkers to Predict Primary Non-Response to Infliximab in Crohn’s Disease
Authors: Li Li , Chen Rirong , Zhang Yingfan , Zhou Gaoshi , Chen Baili , Zeng Zhirong , Chen Minhu , Zhang Shenghong
Published: July 2021

Background

Infliximab is effective in inducing and maintaining remission in patients with Crohn’s disease (CD), but primary non-response (PNR) occurs in 10-30% of cases. We investigated whether serum biomarkers are effective in predicting PNR in patients with CD.

Methods

From January 2016 to April 2020, a total of 260 patients were recruited to this prospective and retrospective cohort study. Serum samples were collected at baseline and week 2 of infliximab treatment. Serum levels of 35 cytokines were assessed in 18 patients from the discovery cohort and were further evaluated in the 60-patient cohort 1. Then, candidate cytokines and other serological biomarkers were used to construct a predictive model by logistic regression in a 182-patient cohort 2. PNR was defined based on the change of CD activity index or clinical symptoms.

Results

Among the 35 cytokines, matrix metalloproteinase 3(MMP3) and C-C motif ligand 2 (CCL2) were two effective serum biomarkers associated with PNR in both the discovery cohort and cohort 1. In cohort 2, serum level of MMP3, CCL2 and C-reactive protein (CRP) at 2 weeks after infliximab injection were independent predictors of PNR, with odds ratios (95% confidence interval) of 1.108(1.059-1.159), 0.940(0.920-0.965) and 1.102(1.031-1.117), respectively. A PNR classifier combining these three indicators had a large area under the curve [0.896(95% CI:0.895-0.897)] and negative predictive value [0.918(95%CI:0.917-0.919)] to predict PNR to infliximab.

Conclusions

MMP3, CCL2, and CRP are promising biomarkers in prediction of PNR to infliximab, and PNR classifier could accurately predict PNR and may be useful in clinical practice for therapy selection.
Fecal Bacteria Implicated in Biofilm Production Are Enriched and Associate to Gastrointestinal Symptoms in Patients With APECED – A Pilot Study
Authors: Hetemäki Iivo , Jian Ching , Laakso Saila , Mäkitie Outi , Pajari Anne-Maria , de Vos Willem M. , Arstila T. Petteri , Salonen Anne
Published: July 2021

Backgrounds and Aims

APECED is a rare autoimmune disease caused by mutations in the Autoimmune Regulator gene. A significant proportion of patients also have gastrointestinal symptoms, including malabsorption, chronic diarrhea, and obstipation. The pathological background of the gastrointestinal symptoms remains incompletely understood and involves multiple factors, with autoimmunity being the most common underlying cause. Patients with APECED have increased immune responses against gut commensals. Our objective was to evaluate whether the intestinal microbiota composition, predicted functions or fungal abundance differ between Finnish patients with APECED and healthy controls, and whether these associate to the patients’ clinical phenotype and gastrointestinal symptoms.

Methods

DNA was isolated from fecal samples from 15 patients with APECED (median age 46.4 years) together with 15 samples from body mass index matched healthy controls. DNA samples were subjected to analysis of the gut microbiota using 16S rRNA gene amplicon sequencing, imputed metagenomics using the PICRUSt2 algorithm, and quantitative PCR for fungi. Extensive correlations of the microbiota with patient characteristics were determined.

Results

Analysis of gut microbiota indicated that both alpha- and beta-diversity were altered in patients with APECED compared to healthy controls. The fraction of Faecalibacterium was reduced in patients with APECED while that of Atopobium spp. and several gram-negative genera previously implicated in biofilm formation, e.g. Veillonella, Prevotella, Megasphaera and Heamophilus, were increased in parallel to lipopolysaccharide (LPS) synthesis in imputed metagenomics. The differences in gut microbiota were linked to patient characteristics, especially the presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and severity of gastrointestinal symptoms.

Conclusions

Gut microbiota of patients with APECED is altered and enriched with predominantly gram-negative bacterial taxa that may promote biofilm formation and lead to increased exposure to LPS in the patients. The most pronounced alterations in the microbiota were associated with more severe gastrointestinal symptoms.
The Role of Cytokines in Predicting the Response and Adverse Events Related to Immune Checkpoint Inhibitors
Authors: Wang Min , Zhai Xiaoyang , Li Ji , Guan Jingyuan , Xu Shuhui , Li YuYing , Zhu Hui
Published: July 2021

Recently, the overall survival (OS) and progression-free survival (PFS) of patients with advanced cancer has been significantly improved due to the application of immune checkpoint inhibitors (ICIs). Low response rate and high occurrence of immune-related adverse events (irAEs) make urgently need for ideal predictive biomarkers to identity efficient population and guide treatment strategies. Cytokines are small soluble proteins with a wide range of biological activity that are secreted by activated immune cells or tumor cells and act as a bridge between innate immunity, infection, inflammation and cancer. Cytokines can be detected in peripheral blood and suitable for dynamic detection. During the era of ICIs, many studies investigated the role of cytokines in prediction of the efficiency and toxicity of ICIs. Herein, we review the relevant studies on TNF-α, IFN-γ, IL-6, IL-8, TGF-β and other cytokines as biomarkers for predicting ICI-related reactions and adverse events, and explore the immunomodulatory mechanisms. Finally, the most important purpose of this review is to help identify predictors of ICI to screen patients who are most likely to benefit from immunotherapy.
Involvement of Innate Immune Receptors in the Resolution of Acute Hepatitis B in Woodchucks
Authors: Suresh Manasa , Li Bin , Murreddu Marta G. , Gudima Severin O. , Menne Stephan
Published: July 2021

The antiviral property of small agonist compounds activating pattern recognition receptors (PRRs), including toll-like and RIG-I receptors, have been preclinically evaluated and are currently tested in clinical trials against chronic hepatitis B (CHB). The involvement of other PRRs in modulating hepatitis B virus infection is less known. Thus, woodchucks with resolving acute hepatitis B (AHB) after infection with woodchuck hepatitis virus (WHV) were characterized as animals with normal or delayed resolution based on their kinetics of viremia and antigenemia, and the presence and expression of various PRRs were determined in both outcomes. While PRR expression was unchanged immediately after infection, most receptors were strongly upregulated during resolution in liver but not in blood. Besides well-known PRRs, including TLR7/8/9 and RIG-I, other less-characterized receptors, such as IFI16, ZBP1/DAI, AIM2, and NLRP3, displayed comparable or even higher expression. Compared to normal resolution, a 3–4-week lag in peak receptor expression and WHV-specific B- and T-cell responses were noted during delayed resolution. This suggested that PRR upregulation in woodchuck liver occurs when the mounting WHV replication reaches a certain level, and that multiple receptors are involved in the subsequent induction of antiviral immune responses. Liver enzyme elevations occurred early during normal resolution, indicating a faster induction of cytolytic mechanisms than in delayed resolution, and correlated with an increased expression of NK-cell and CD8 markers and cytolytic effector molecules. The peak liver enzyme level, however, was lower during delayed resolution, but hepatic inflammation was more pronounced and associated with a higher expression of cytolytic markers. Further comparison of PRR expression revealed that most receptors were significantly reduced in woodchucks with established and progressing CHB, and several RNA sensors more so than DNA sensors. This correlated with a lower expression of receptor adaptor and effector molecules, suggesting that persistent, high-level WHV replication interferes with PRR activation and is associated with a diminished antiviral immunity based on the reduced expression of immune cell markers, and absent WHV-specific B- and T-cell responses. Overall, the differential expression of PRRs during resolution and persistence of WHV infection emphasizes their importance in the ultimate viral control during AHB that is impaired during CHB.
Do Gray Whales Count Calories? Comparing Energetic Values of Gray Whale Prey Across Two Different Feeding Grounds in the Eastern North Pacific
Authors: Hildebrand Lisa , Bernard Kim S. , Torres Leigh G.
Published: July 2021

Predators must consume enough prey to support costly events, such as reproduction. Meeting high energetic requirements is particularly challenging for migrating baleen whales as their feeding seasons are typically restricted to a limited temporal window and marine prey are notoriously patchy. We assessed the energetic value of the six most common nearshore zooplankton species collected within the Oregon, United States range of the Pacific Coast Feeding Group (PCFG) gray whale (Eschrichtius robustus) feeding grounds, and compared these results to the energetic value of the predominant amphipod species fed on by Eastern North Pacific (ENP) gray whales in the Arctic. Energetic values of Oregon zooplankton differed significantly between species (Kruskal–Wallis χ2= 123.38, df = 5,p< 0.0001), with Dungeness crab (Cancer magister) megalopae displaying the highest mean caloric content of all tested species (4.21 ± 1.27 kJ g– 1). This value, as well as the mean energetic value of the mysidNeomysis rayii(2.42 ± 1.06 kJ g– 1), are higher than the mean caloric content ofAmpelisca macrocephala, the predominant Arctic amphipod. Extrapolations of these results to daily energetic requirements of gray whales indicate that lactating and pregnant gray whales feeding in the PCFG range would require between 0.7–1.03 and 0.22–0.33 metric tons of prey less per day if they fed on Dungeness crab megalopae orN. rayii, respectively, than a whale feeding onA. macrocephalain the Arctic. Yet, these results do not account for differences in availability of these prey species to foraging gray whales. We therefore suggest that other factors, such as prey density, energetic costs of feeding, or natal philopatry and foraging site fidelity play a role in the differences in population sizes between the PCFG and ENP gray whales. Climate change is implicated in causing reduced body condition and increased mortality of both PCFG and ENP gray whales due to decreased prey availability and abundance. Therefore, improved understanding of prey dynamics in response to environmental variability in both regions is critical.