bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bereaved Parents’ Health Outcomes Following the Death of Their Child
Authors: Dias Nancy , Friebert Sarah , Donelan Jennifer , Schoemann Alexander M. , Morris Ashley , Guard Kaitlin , Grossoehme Daniel H. 
Published: October 2021

Objective: The death of one’s child may negatively affect parental health. Existing models exploring parental bereavement do not provide sufficient frameworks to understand the complexities of health outcomes. The purpose of this study was to examine the health status of bereaved parents. Method: Cross-sectional retrospective study of bereaved parents whose children died at this hospital between 2002 and 2019. A study-specific demographic questionnaire, the National Institutes of Health Roadmap Patient-Reported Outcomes Measurement Information System (PROMIS) initiative. Depressive symptoms were assessed using the PROMIS v1.0 Emotional Distress–Depression—Short Form 8a ( Pilkonis et al., 2011 ). PROMIS measures (depressive symptoms, anxiety, applied cognitive functioning, physical functioning, sleep disturbance), and a measure of posttraumatic growth were mailed and included a link to self-enter data via Research Electronic Data Capture (REDCap, n.d. ) or return paper copies. Results: One hundred fifty surveys were returned (22% response rate). Mean participant age was 41.6 years ( SD = 10.3 years; 83% female). Participants’ health history responses show greater prevalence of depressive symptoms, anxiety, and sleep disorders after their child’s death. The largest difference on PROMIS measures was poorer physical function in the bereaved cohort than in the general population. There were no differences in PROMIS scores based on participant gender or on the presence of surviving siblings. Among those reporting smoking or alcohol consumption, qualitative data suggest that although some might increase use, such use might decrease over time. Conclusions: Bereaved parents manifest poorer psychological and cognitive functioning, and their physical functioning was substantially poorer than the general population mean. Bereaved parents may benefit from proactive guidance normalizing potential challenges to health status and behavior, including appropriate psychoeducational resources. Implications for Impact Statement Bereaved parents have poorer physical and mental health when compared with the general population. Clinicians that care for these parents must offer health promotion and disease prevention measures early to improve their long-term health outcomes.
Loss of TRIM31 promotes breast cancer progression through regulating K48- and K63-linked ubiquitination of p53
Authors: Guo Yafei , Li Qin , Zhao Gang , Zhang Jie , Yuan Hang , Feng Tianyu , Ou Deqiong , Gu Rui , Li Siqi , Li Kai , Lin Ping 
Published: October 2021

AbstractBreast cancer is the most common cancer in the world. Relapse and metastasis are important factors endangering the life of breast cancer patients, but the mechanism is still unclear. The stabilization of p53 is essential for preventing carcinogenesis, and ubiquitination is one of the main ways to regulate the stability of p53. Tripartite motif-containing 31 (TRIM31) is a new member of the TRIM family and functions as an E3 ubiquitin ligase. It acts as a cancer promoter or suppressor in the malignant processes of multiple cancers. However, the function of TRIM31 in breast cancer progression remains unknown. In this study, we showed that TRIM31 is downregulated in breast cancer tissues and negatively correlated with breast cancer progression. Both gain- and loss-of-function assays indicated that TRIM31 inhibits the proliferation, colony formation, migration, and invasion of breast cancer cells. Further investigation demonstrated that TRIM31 directly interacts with p53, and inducing the K63-linked ubiquitination of p53 via its RING domain, Meanwhile, TRIM31 suppresses the MDM2-mediated K48-linked ubiquitination of p53 through competitive inhibiting the interaction of MDM2 and p53, leading to the p53 stabilization and activation. Knockdown of p53 reversed the inhibitory effects of TRIM31 on the growth and metastasis of breast cancer cells. Moreover, we found that the RING and coiled-coil (C–C) domains of TRIM31 were essential for its tumor suppressor function. Taken together, our findings reveal a novel mechanism by which TRIM31 suppresses breast cancer development through the stabilization and activation of p53 and define a promising therapeutic strategy for restoring TRIM31 to treat breast cancer.
CircNPHP4 in monocyte-derived small extracellular vesicles controls heterogeneous adhesion in coronary heart atherosclerotic disease
Authors: Xiong Feng , Mao Rui , Zhang Lijuan , Zhao Ruohan , Tan Kunyue , Liu Chunxia , Xu JunBo , Du Guanghong , Zhang Tongtong 
Published: October 2021

AbstractSmall extracellular vesicles (sEVs)-derived circular RNAs (circRNAs) could regulate gene expression in recipient cells, and dysregulation of sEVs-derived circRNAs has been implicated in several diseases. However, the expression and function of sEVs-derived circRNAs in coronary heart atherosclerotic disease (CAD) remain unknown. In this study, we investigated global changes in the expression patterns of circRNAs in sEVs from CAD-related monocytes and identified circNPHP4 as a significantly upregulated circRNA. Knockdown of circNPHP4 inhibited heterogeneous adhesion between monocytes and coronary artery endothelial cells and reduced ICAM-1 and VCAM-1 expression. Investigations of the underlying mechanisms revealed that circNPHP4 contains a functional miR-1231-binding site. Mutation of the circNPHP4-binding sites in miR-1231 abolished the interaction, as indicated by a luciferase reporter assay. Furthermore, circNPHP4 affected the expression of miR-1231 and its target gene EGFR. Overexpression of miR-1231 blocked the inhibitory effect of circNPHP4 on heterogeneous adhesion. Moreover, downregulation of miR-1231 restored heterogeneous adhesion upon inhibition by circNPHP4 silencing. Additionally, circNPHP4 overexpression was correlated with aggressive clinicopathological characteristics in CAD patients. A multivariate logistic regression model and bootstrapping validation showed that circNPHP4 overexpression had a good risk prediction capability for CAD. The decision curve analysis revealed that using the CAD nomogram that included circNPHP4 overexpression to predict the risk of CAD was beneficial. Our results suggest that sEVs-derived circNPHP4 can serve as a potential target for CAD treatments or as a potential diagnostic marker for CAD patients.
The FOXM1/RNF26/p57 axis regulates the cell cycle to promote the aggressiveness of bladder cancer
Authors: Yi Lu , Wang Haohui , Li Wei , Ye Kun , Xiong Wei , Yu Haixin , Jin Xin 
Published: October 2021

AbstractBladder cancer is one of the most lethal cancers in the world. Despite the continuous development of medical technologies and therapeutic strategies, the overall survival rate of bladder cancer has not changed significantly. Targeted therapy is a new promising method for bladder cancer treatment. Thus, an in-depth study of the molecular mechanism of the occurrence and development of bladder cancer is urgently needed to identify novel therapeutic candidates for bladder cancer. Here, bioinformatics analysis demonstrated that RNF26 was one of the risk factors for bladder cancer. Then, we showed that RNF26 is abnormally upregulated in bladder cancer cells and tissues and that higher RNF26 expression is an unfavorable prognostic factor for bladder cancer. Moreover, we found that RNF26 promotes bladder cancer progression. In addition, we showed that RNF26 expression is promoted by FOXM1 at the transcriptional level through MuvB complex. The upregulated RNF26 in turn degrades p57 (CDKN1C) to regulate the cell cycle process. Collectively, we uncovered a novel FOXM1/RNF26/p57 axis that modulates the cell cycle process and enhances the progression of bladder cancer. Thus, the FOXM1/RNF26/p57 signaling axis could be a candidate target for the treatment of bladder cancer.
Upregulation of CPNE7 in mesenchymal stromal cells promotes oral squamous cell carcinoma metastasis through the NF-κB pathway
Authors: Ji Xiaoli , Sun Tianyong , Xie Shang , Qian Hua , Song lixiang , Wang lihua , Liu Hongwei , Feng Qiang 
Published: October 2021

AbstractA remarkable shift in Mesenchymal stromal cells (MSCs) plays an important role in cancer metastasis, but the molecular mechanism is still unclear. CPNE7, a calcium-dependent phospholipid-binding protein, mediates signal transduction and metastasis in many tumours. Here, we demonstrated that MSCs derived from OSCC (OSCC-MSCs) promoted the metastasis of OSCC cells by transwell assay and animal models through epithelial to mesenchymal transition (EMT) (p < 0.05). RNA-sequencing, ELISA, neutralizing antibody and CXCR2 inhibitor assay confirmed that CXCL8 secreted by OSCC-MSCs was associated with the upregulated expression of CPNE7 by immunohistochemical and western blotting (p < 0.05). This is mechanistically linked to the activation of CPNE7 to NF-κB pathway-induced metastasis, including phosphorylated p65 and IκBa. CPNE7 silencing inhibited metastatic abilities and the expression of CXCL8, phosphorylated p65, IκBa, and p65 nuclear translocation by western blotting and immunofluorescence, while CPNE7 overexpression markedly promoted these events (p < 0.05). We also identified that Nucleolin could be bind CPNE7 and IκBa by co-immunoprecipitation. Together, our results suggest that upregulation of CPNE7 in MSCs interacted with surface receptor -Nucleolin and then combined with IκBa to promoted phosphorylated IκBa and p65 nuclear translocation to active NF-κB pathway, and then regulates CXCL8 secretion to promote the metastasis of OSCC cells. Therefore, CPNE7 in MSCs could be promising therapeutic targets in OSCC.
The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends
Authors: Schneider Matthias M. , Gautam Saurabh , Herling Therese W. , Andrzejewska Ewa , Krainer Georg , Miller Alyssa M. , Trinkaus Victoria A. , Peter Quentin A. E. , Ruggeri Francesco Simone , Vendruscolo Michele , Bracher Andreas , Dobson Christopher M. , Hartl F. Ulrich , Knowles Tuomas P. J. 
Published: October 2021

AbstractMolecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disaggregate otherwise irreversible aggregate species such as α-synuclein fibrils, which accumulate in Parkinson’s disease. However, the mechanisms and kinetics of this key functionality are only partially understood. Here, we combine microfluidic measurements with chemical kinetics to study α-synuclein disaggregation. We show that Hsc70 together with its co-chaperones DnaJB1 and Apg2 can completely reverse α-synuclein aggregation back to its soluble monomeric state. This reaction proceeds through first-order kinetics where monomer units are removed directly from the fibril ends with little contribution from intermediate fibril fragmentation steps. These findings extend our mechanistic understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and inform on possibilities and limitations of this strategy in the development of therapeutics against synucleinopathies.
Rapid incidence estimation from SARS-CoV-2 genomes reveals decreased case detection in Europe during summer 2020
Authors: Smith Maureen Rebecca , Trofimova Maria , Weber Ariane , Duport Yannick , Kühnert Denise , von Kleist Max 
Published: October 2021

AbstractBy October 2021, 230 million SARS-CoV-2 diagnoses have been reported. Yet, a considerable proportion of cases remains undetected. Here, we propose GInPipe, a method that rapidly reconstructs SARS-CoV-2 incidence profiles solely from publicly available, time-stamped viral genomes. We validate GInPipe against simulated outbreaks and elaborate phylodynamic analyses. Using available sequence data, we reconstruct incidence histories for Denmark, Scotland, Switzerland, and Victoria (Australia) and demonstrate, how to use the method to investigate the effects of changing testing policies on case ascertainment. Specifically, we find that under-reporting was highest during summer 2020 in Europe, coinciding with more liberal testing policies at times of low testing capacities. Due to the increased use of real-time sequencing, it is envisaged that GInPipe can complement established surveillance tools to monitor the SARS-CoV-2 pandemic. In post-pandemic times, when diagnostic efforts are decreasing, GInPipe may facilitate the detection of hidden infection dynamics.
Spatial deconvolution of HER2-positive breast cancer delineates tumor-associated cell type interactions
Authors: Andersson Alma , Larsson Ludvig , Stenbeck Linnea , Salmén Fredrik , Ehinger Anna , Wu Sunny Z. , Al-Eryani Ghamdan , Roden Daniel , Swarbrick Alex , Borg Åke , Frisén Jonas , Engblom Camilla , Lundeberg Joakim 
Published: October 2021

AbstractIn the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra- and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. By integration with single cell data, we spatially map tumor-associated cell types to find tertiary lymphoid-like structures, and a type I interferon response overlapping with regions of T-cell and macrophage subset colocalization. We construct a predictive model to infer presence of tertiary lymphoid-like structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define a high resolution map of cellular interactions in tumors and provide tools generalizing across tissues and diseases.
A microfluidic platform for highly parallel bite by bite profiling of mosquito-borne pathogen transmission
Authors: Kumar Shailabh , Hol Felix J. H. , Pujhari Sujit , Ellington Clayton , Narayanan Haripriya Vaidehi , Li Hongquan , Rasgon Jason L. , Prakash Manu 
Published: October 2021

AbstractMosquito bites transmit a number of pathogens via salivary droplets deposited during blood-feeding, resulting in potentially fatal diseases. Little is known about the genomic content of these nanodroplets, including the transmission dynamics of live pathogens. Here we introduce Vectorchip, a low-cost, scalable microfluidic platform enabling high-throughput molecular interrogation of individual mosquito bites. We introduce an ultra-thin PDMS membrane which acts as a biting interface to arrays of micro-wells. Freely-behaving mosquitoes deposit saliva droplets by biting into these micro-wells. By modulating membrane thickness, we observe species-dependent differences in mosquito biting capacity, utilizable for selective sample collection. We demonstrate RT-PCR and focus-forming assays on-chip to detect mosquito DNA, Zika virus RNA, as well as quantify infectious Mayaro virus particles transmitted from single mosquito bites. The Vectorchip presents a promising approach for single-bite-resolution laboratory and field characterization of vector-pathogen communities, and could serve as a powerful early warning sentinel for mosquito-borne diseases.
Active droploids
Authors: Grauer Jens , Schmidt Falko , Pineda Jesús , Midtvedt Benjamin , Löwen Hartmut , Volpe Giovanni , Liebchen Benno 
Published: October 2021

AbstractActive matter comprises self-driven units, such as bacteria and synthetic microswimmers, that can spontaneously form complex patterns and assemble into functional microdevices. These processes are possible thanks to the out-of-equilibrium nature of active-matter systems, fueled by a one-way free-energy flow from the environment into the system. Here, we take the next step in the evolution of active matter by realizing a two-way coupling between active particles and their environment, where active particles act back on the environment giving rise to the formation of superstructures. In experiments and simulations we observe that, under light-illumination, colloidal particles and their near-critical environment create mutually-coupled co-evolving structures. These structures unify in the form of active superstructures featuring a droplet shape and a colloidal engine inducing self-propulsion. We call them active droploids—a portmanteau of droplet and colloids. Our results provide a pathway to create active superstructures through environmental feedback.
Diet diversity and environment determine the intestinal microbiome and bacterial pathogen load of fire salamanders
Authors: Wang Yu , Smith Hannah K. , Goossens Evy , Hertzog Lionel , Bletz Molly C. , Bonte Dries , Verheyen Kris , Lens Luc , Vences Miguel , Pasmans Frank , Martel An 
Published: October 2021

AbstractDiverse communities of symbiotic microbes inhabit the digestive systems of vertebrates and play a crucial role in animal health, and host diet plays a major role in shaping the composition and diversity of these communities. Here, we characterized diet and gut microbiome of fire salamander populations from three Belgian forests. We carried out DNA metabarcoding on fecal samples, targeting eukaryotic 18S rRNA of potential dietary prey items, and bacterial 16S rRNA of the concomitant gut microbiome. Our results demonstrated an abundance of soft-bodied prey in the diet of fire salamanders, and a significant difference in the diet composition between males and females. This sex-dependent effect on diet was also reflected in the gut microbiome diversity, which is higher in males than female animals. Proximity to human activities was associated with increased intestinal pathogen loads. Collectively, the data supports a relationship between diet, environment and intestinal microbiome in fire salamanders, with potential health implications.
Transcriptomics of chicken cecal tonsils and intestine after infection with low pathogenic avian influenza virus H9N2
Authors: Alqazlan Nadiyah , Emam Mehdi , Nagy Éva , Bridle Byram , Sargolzaei Mehdi , Sharif Shayan 
Published: October 2021

AbstractInfluenza viruses cause severe respiratory infections in humans and birds, triggering global health concerns and economic burden. Influenza infection is a dynamic process involving complex biological host responses. The objective of this study was to illustrate global biological processes in ileum and cecal tonsils at early time points after chickens were infected with low pathogenic avian influenza virus (LPAIV) H9N2 through transcriptome analysis. Total RNA isolated from ileum and cecal tonsils of non-infected and infected layers at 12-, 24- and 72-h post-infection (hpi) was used for mRNA sequencing analyses to characterize differentially expressed genes and overrepresented pathways. Statistical analysis highlighted transcriptomic signatures significantly occurring 24 and 72 hpi, but not earlier at 12 hpi. Interferon (IFN)-inducible and IFN-stimulated gene (ISG) expression was increased, followed by continued expression of various heat-shock proteins (HSP), including HSP60, HSP70, HSP90 and HSP110. Some upregulated genes involved in innate antiviral responses included DDX60, MX1, RSAD2 and CMPK2. The ISG15 antiviral mechanism pathway was highly enriched in ileum and cecal tonsils at 24 hpi. Overall, most affected pathways were related to interferon production and the heat-shock response. Research on these candidate genes and pathways is warranted to decipher underlying mechanisms of immunity against LPAIV in chickens.
The movement profile of trunk and neck during habitual vacuuming
Authors: Maurer-Grubinger C. , Haenel J. , Fraeulin L. , Holzgreve F. , Wanke E. M. , Groneberg D. A. , Ohlendorf D. 
Published: October 2021

AbstractMusculoskeletal disorders of the trunk and neck are common among cleaners. Vacuum cleaning is a demanding activity. The aim of this study was to present the movement profile of the trunk and neck during habitual vacuuming. The data were collected from 31 subjects (21f./10 m) using a 3D motion analysis system (Xsens). 10 cycles were analysed in vacuuming PVC and carpet floors with 8 vacuum cleaners. The joint angles and velocities were represented statistically descriptive. When vacuuming, the trunk is held in a forwardly inclined position by a flexion in the hip and rotated from this position. In the joint angles and velocities of the spine, the rotation proved to be dominant. A relatively large amount of movement took place in the cervical spine and also in the lumbar spine. The shown movement profile is rather a comfort area of vacuuming which may serve as a reference for ergonomics in vacuuming.
Serum vitamin D status inversely associates with a prevalence of severe sarcopenia among female patients with rheumatoid arthritis
Authors: Minamino Hiroto , Katsushima Masao , Torii Mie , Yamamoto Wataru , Fujita Yoshihito , Ikeda Kaori , Okamura Emi , Murakami Kosaku , Watanabe Ryu , Murata Koichi , Ito Hiromu , Tanaka Masao , Arai Hidenori , Matsuda Shuichi , Morinobu Akio , Inagaki Nobuya , Hashimoto Motomu 
Published: October 2021

AbstractSarcopenia is an age-related disease with an increased risk of mortality. It is emerging that low serum 25-hydroxyvitamin D [25(OH)D] affects the sarcopenic state in general, but in rheumatoid arthritis (RA), these associations are not understood although the prevalence of vitamin D insufficiency is high in RA. We conducted a cross-sectional study of older female outpatients from our cohort (KURAMA) database. We measured skeletal muscle mass, handgrip strength, and gait-speed to diagnose severe sarcopenia. The serum 25(OH)D concentration was measured using electrochemiluminescence immunoassay. A total of 156 female patients with RA (sarcopenia:44.9%, severe sarcopenia: 29.5%, and without sarcopenia: 25.6%) were enrolled. Classification of vitamin D status at a cutoff point of median 25(OH)D concentration revealed that low 25(OH)D status was associated with a high prevalence of severe sarcopenia and with low measured values of muscle mass, handgrip, and gait speed. Furthermore, multivariable logistic regression analysis identified that low 25(OH)D status was associated with a high prevalence of severe sarcopenia (OR 6.00; 95% CI 1.99–18.08).The same association was observed when the cut-off value was set at 20 ng/ml. In components of sarcopenia, both low physical performance and muscle mass were associated with low 25(OH)D status. In conclusion, vitamin D status was inversely associated with severe sarcopenia, low physical performance, and low skeletal muscle mass. Modification of vitamin D status including vitamin D supplementation should be investigated as a therapeutic strategy for sarcopenic patients with RA.