bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transposable element-derived sequences in vertebrate development
Authors: Etchegaray Ema , Naville Magali , Volff Jean-Nicolas , Haftek-Terreau Zofia 
Published: January 2021

AbstractTransposable elements (TEs) are major components of all vertebrate genomes that can cause deleterious insertions and genomic instability. However, depending on the specific genomic context of their insertion site, TE sequences can sometimes get positively selected, leading to what are called “exaptation” events. TE sequence exaptation constitutes an important source of novelties for gene, genome and organism evolution, giving rise to new regulatory sequences, protein-coding exons/genes and non-coding RNAs, which can play various roles beneficial to the host. In this review, we focus on the development of vertebrates, which present many derived traits such as bones, adaptive immunity and a complex brain. We illustrate how TE-derived sequences have given rise to developmental innovations in vertebrates and how they thereby contributed to the evolutionary success of this lineage.
Composition of the metabolomic bio-coronas isolated from Ocimum sanctum and Rubia tinctorum
Authors: Kurepa Jasmina , Smalle Jan A. 
Published: January 2021

Abstract
Objective
Nanoharvesting from intact plants, organs, and cultured cells is a method in which nanoparticles are co-incubated with the target tissue, which leads to the internalization of nanoparticles. Internalized nanoparticles are coated in situ with specific metabolites that form a dynamic surface layer called a bio-corona. Our previous study showed that metabolites that form the bio-corona around anatase TiO2 nanoparticles incubated with leaves of the model plant Arabidopsis thaliana are enriched for flavonoids and lipids. The present study focused on the identification of metabolites isolated by nanoharvesting from two medicinal plants, Ocimum sanctum (Tulsi) and Rubia tinctorum (common madder).

Results
To identify metabolites that form the bio-corona, Tulsi leaves and madder roots were incubated with ultra-small anatase TiO2 nanoparticles, the coated nanoparticles were collected, and the adsorbed molecules were released from the nanoparticle surface and analyzed using an untargeted metabolomics approach. Similar to the results in which Arabidopsis tissue was used as a source of metabolites, TiO2 nanoparticle bio-coronas from Tulsi and madder were enriched for flavonoids and lipids, suggesting that nanoharvesting has a wide-range application potential. The third group of metabolites enriched in bio-coronas isolated from both plants were small peptides with C-terminal arginine and lysine residues.
Pre-adolescence DNA methylation is associated with lung function trajectories from pre-adolescence to adulthood
Authors: Sunny Shadia Khan , Zhang Hongmei , Mzayek Fawaz , Relton Caroline L. , Ring Susan , Henderson A. John , Ewart Susan , Holloway John W. , Arshad S. Hasan 
Published: January 2021

Abstract
Background
The pattern of lung function development from pre-adolescence to adulthood plays a significant role in the pathogenesis of respiratory diseases. Inconsistent findings in genetic studies on lung function trajectories, the importance of DNA methylation (DNA-M), and the critical role of adolescence in lung function development motivated the present study of pre-adolescent DNA-M with lung function trajectories. This study investigated epigenome-wide associations of DNA-M at cytosine-phosphate-guanine dinucleotide sites (CpGs) at childhood with lung function trajectories from childhood to young adulthood.

Methods
DNA-M was measured in peripheral blood at age 10 years in the Isle of Wight (IOW) birth cohort. Spirometry was conducted at ages 10, 18, and 26 years. A training/testing-based method was used to screen CpGs. Multivariable logistic regressions were applied to assess the association of DNA-M with lung function trajectories from pre-adolescence to adulthood. To detect differentially methylated regions (DMRs) among CpGs, DMR enrichment analysis was conducted. Findings were further tested in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Pathway analyses were performed on the mapped genes of the identified CpGs and DMRs. Biological relevance of the identified CpGs was assessed with gene expression. All analyses were stratified by sex.

Results
High and low trajectories of FVC, FEV1, and FEV1/FVC in each sex were identified. At PBonferroni < 0.05, DNA-M at 96 distinct CpGs (41 in males) showed associations with FVC, FEV1, and FEV1/FVC trajectories in IOW cohort. These 95 CpGs (cg24000797 was disqualified) were further tested in ALSPAC; 44 CpGs (19 in males) of these 95 showed the same directions of association as in the IOW cohort; and three CpGs (two in males) were replicated. DNA-M at two and four CpGs showed significant associations with the corresponding gene expression in males and females, respectively. At PFDR < 0.05, 23 and 10 DMRs were identified in males and females, respectively. Pathways were identified; some of those were linked to lung function and chronic obstructive lung diseases.

Conclusion
The identified CpGs at pre-adolescence have the potential to serve as candidate markers for lung function trajectory prediction and chronic lung diseases.
Performance of the QPLEX™ Alz plus assay, a novel multiplex kit for screening cerebral amyloid deposition
Authors: Park Jong-Chan , Jung Keum Sim , Kim Jiyeong , Jang Ji Sung , Kwon Sunghoon , Byun Min Soo , Yi Dahyun , Byeon Gihwan , Jung Gijung , Kim Yu Kyeong , Lee Dong Young , Han Sun-Ho , Mook-Jung Inhee 
Published: January 2021

Abstract
Background
Alzheimer’s disease (AD) is an irreversible neurodegenerative disease characterized by the hallmark finding of cerebral amyloid deposition. Many researchers have tried to predict the existence of cerebral amyloid deposition by using easily accessible blood plasma samples, but the effectiveness of such strategies remains controversial.

Methods
We developed a new multiplex kit, the QPLEX™ Alz plus assay kit, which uses proteomics-based blood biomarkers to prescreen for cerebral amyloid deposition. A total of 300 participants who underwent Pittsburgh compound B (PiB)-positron emission tomography (PET) which allows imaging of cerebral amyloid deposition were included in this study. We compared the levels of QPLEX™ biomarkers between patients who were classified as PiB-negative or PiB-positive, regardless of their cognitive function. Logistic regression analysis followed by receiver operating characteristic (ROC) curve analysis was performed. The kit accuracy was tested using a randomized sample selection method.

Results
The results obtained using our assay kit reached 89.1% area under curve (AUC) with 80.0% sensitivity and 83.0% specificity. Further validation of the QPLEX™ Alz plus assay kit using a randomized sample selection method showed an average accuracy of 81.5%.

Conclusions
Our QPLEX™ Alz plus assay kit provides preliminary evidence that it can be used as blood marker to predict cerebral amyloid deposition but independent validation is needed.
Distinct network topology in Alzheimer’s disease and behavioral variant frontotemporal dementia
Authors: Ng Adeline Su Lyn , Wang Juan , Ng Kwun Kei , Chong Joanna Su Xian , Qian Xing , Lim Joseph Kai Wei , Tan Yi Jayne , Yong Alisa Cui Wen , Chander Russell Jude , Hameed Shahul , Ting Simon Kang Seng , Kandiah Nagaendran , Zhou Juan Helen 
Published: January 2021

Abstract
Background
Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively. It remains unclear if inter-network relationships and whole-brain network topology are also altered and underpin cognitive and social–emotional functional deficits.

Methods
In total, 111 participants (50 AD, 14 bvFTD, and 47 age- and gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Functional connectivity was derived among 144 brain regions of interest. Graph theoretical analysis was applied to characterize network integration, segregation, and module distinctiveness (degree centrality, nodal efficiency, within-module degree, and participation coefficient) in AD, bvFTD, and healthy participants. Group differences in graph theoretical measures and empirically derived network community structures, as well as the associations between these indices and cognitive performance and neuropsychiatric symptoms, were subject to general linear models, with age, gender, education, motion, and scanner type controlled.

Results
Our results suggested that AD had lower integration in the default and control networks, while bvFTD exhibited disrupted integration in the salience network. Interestingly, AD and bvFTD had the highest and lowest degree of integration in the thalamus, respectively. Such divergence in topological aberration was recapitulated in network segregation and module distinctiveness loss, with AD showing poorer modular structure between the default and control networks, and bvFTD having more fragmented modules in the salience network and subcortical regions. Importantly, aberrations in network topology were related to worse attention deficits and greater severity in neuropsychiatric symptoms across syndromes.

Conclusions
Our findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.
Targeting the IL-5 pathway in eosinophilic asthma: a comparison of mepolizumab to benralizumab in the reduction of peripheral eosinophil counts
Authors: Ghassemian Arian , Park Jane Jiyoon , Tsoulis Michael W. , Kim Harold 
Published: January 2021

Abstract
Background
Mepolizumab and benralizumab are biologics approved for severe eosinophilic asthma. Mepolizumab is an anti-interlukin-5 (IL-5) antibody while benralizumab is an anti-interleukin-5 receptor alpha (IL-5Rα) antibody targeting the IL-5 receptor on eosinophils. Both therapies reduce oral corticosteroid requirements and asthma exacerbations. However, no head-to-head studies have been published. The aim of the present study was to compare the efficacy of peripheral eosinophil reduction of mepolizumab and benralizumab.

Methods
A retrospective chart review was conducted on patients with severe eosinophilic asthma who were approved for either IL-5 agent. Patients with noted non-adherence or those who were on fluctuating doses of corticosteroids for non-asthma related illnesses were excluded. The last detectable eosinophil count for each patient prior to start of therapy was compared to the highest eosinophil count noted after therapy start with at least 30 days of adherence.

Results
Thirty-six patients taking mepolizumab and 19 patients taking benralizumab met the inclusion criteria and had both pre-treatment and post-treatment eosinophil counts. Baseline characteristics were not statistically different between those on mepolizumab and benralizumab therapy. The mean pre-therapy serum eosinophil count did not statistically differ between patients on mepolizumab (597.2 cells/µL) compared to benralizumab (521.6 cells/µL), p = 0.3769. While both therapies resulted in a significant decrease in eosinophil count (p < 0.0001); the mean decrease did not statistically differ between patients taking mepolizumab compared to those on benralizumab, p = 0.9079. Nonetheless, 100% of patients receiving benralizumab had undetectable eosinophil counts post-therapy compared to 31% of patients receiving mepolizumab (p < 0.0001).

Conclusion
Both mepolizumab and benralizumab are potent targets of the IL-5 pathway with the ability to significantly reduce peripheral eosinophil counts. While there is there is no statistical difference in the magnitude of eosinophil reduction offered by each agent, benralizumab is able to decrease peripheral eosinophil counts to 0 cells/µL in more patients than mepolizumab.
Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice
Authors: Dong Liyang , Wang Ying , Zheng Tingting , Pu Yanan , Ma Yongbin , Qi Xin , Zhang Wenzhe , Xue Fei , Shan Zirui , Liu Jiameng , Wang Xuefeng , Mao Chaoming 
Published: January 2021

AbstractBackgroundAs one of the main functional forms of mesenchymal stem cells (MSCs), MSC-derived extracellular vesicles (MSC-EVs) have shown an alternative therapeutic option in experimental models of allergic asthma. Oxygen concentration plays an important role in the self-renewal, proliferation, and EV release of MSCs and a recent study found that the anti-asthma effect of MSCs was enhanced by culture in hypoxic conditions. However, the potential of hypoxic MSC-derived EVs (Hypo-EVs) in asthma is still unknown.MethodsBALB/c female mice were sensitized and challenged with ovalbumin (OVA), and each group received PBS, normoxic human umbilical cord MSC-EVs (Nor-EVs), or Hypo-EVs weekly. After treatment, the animals were euthanized, and their lungs and bronchoalveolar lavage fluid (BALF) were collected. With the use of hematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Masson’s trichrome staining, enzyme-linked immune sorbent assay (ELISA), Western blot analysis, and real-time PCR, the inflammation and collagen fiber content of airways and lung parenchyma were investigated.ResultsHypoxic environment can promote human umbilical cord MSCs (hUCMSCs) to release more EVs. In OVA animals, the administration of Nor-EVs or Hypo-EVs significantly ameliorated the BALF total cells, eosinophils, and pro-inflammatory mediators (IL-4 and IL-13) in asthmatic mice. Moreover, Hypo-EVs were generally more potent than Nor-EVs in suppressing airway inflammation in asthmatic mice. Compared with Nor-EVs, Hypo-EVs further prevented mouse chronic allergic airway remodeling, concomitant with the decreased expression of pro-fibrogenic markers α-smooth muscle actin (α-SMA), collagen-1, and TGF-β1-p-smad2/3 signaling pathway. In vitro, Hypo-EVs decreased the expression of p-smad2/3, α-SMA, and collagen-1 in HLF-1 cells (human lung fibroblasts) stimulated by TGF-β1. In addition, we showed that miR-146a-5p was enriched in Hypo-EVs compared with that in Nor-EVs, and Hypo-EV administration unregulated the miR-146a-5p expression both in asthma mice lung tissues and in TGF-β1-treated HLF-1. More importantly, decreased miR-146a-5p expression in Hypo-EVs impaired Hypo-EV-mediated lung protection in OVA mice.ConclusionOur findings provided the first evidence that hypoxic hUCMSC-derived EVs attenuated allergic airway inflammation and airway remodeling in chronic asthma mice, potentially creating new avenues for the treatment of asthma.
Fetal sex and maternal postpartum depressive symptoms: findings from two prospective pregnancy cohorts
Authors: Cowell Whitney , Colicino Elena , Askowitz Talia , Nentin Farida , Wright Rosalind J. 
Published: January 2021

AbstractBackgroundFetal sex is known to modify the course and complications of pregnancy, with recent evidence of sex-differential fetal influences on the maternal immune and endocrine systems. In turn, heightened inflammation and surges in reproductive hormone levels associated with pregnancy and parturition have been linked with the development of perinatal depression. Here, we examined whether there is an association between fetal sex and maternal depression assessed during the prenatal and postnatal periods.MethodsThe study included two multi-ethnic, prospective pregnancy cohorts that enrolled women from prenatal clinics in the Northeastern United States between 2001 and 2018. Maternal depressive symptoms were measured during the prenatal and postnatal periods using the Edinburgh Postpartum Depression Scale (EPDS), and newborn sex was reported by the mother following delivery. We used logistic regression to examine associations between fetal sex and maternal depressive symptoms (EPDS > 10) during the prenatal period only, postnatal period only, or both periods versus no depressive symptoms during either period. We considered both unadjusted models and models adjusted for a core set of sociodemographic and lifestyle variables.ResultsIn adjusted models using PRISM data (N= 528), women pregnant with a male versus female fetus had significantly greater odds of depressive symptoms during the postnatal period compared to women without depressive symptoms during either period (odds ratio [OR] = 5.24, 95% confidence interval [CI] = 1.93, 14.21). The direction of results was consistent in the ACCESS cohort, although the findings did not reach statistical significance (OR = 2.05, 95% CI = 0.86, 4.93). Significant associations were not observed in either cohort among women with prenatal symptoms only or women with prenatal and postnatal symptoms.ConclusionsMale fetal sex was associated with the onset of depressive symptoms during the postnatal period.
ANCA-negative microscopic polyangiitis with diffuse alveolar hemorrhage masquerading as congestive heart failure
Authors: Mollaeian Arash , Chan Nina , Aloor Rohit , Iding Jeffery S. , Arend Lois J. , Saeidabadi Seyed Hootan Forghani , Haas Christopher J. 
Published: January 2021

Abstract
Background
Microscopic polyangiitis (MPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), involving small and medium sized vessels, often affecting the kidneys and lungs. Anti-neutrophil cytoplasmic antibody (ANCA) is detected in up to 90% of cases of MPA and its detection helps guide diagnosis, however cases of ANCA-negative MPA have been reported, hence definitive diagnosis relies on tissue biopsy.

Case report
A 23-year-old man was evaluated for dyspnea and pleuritic chest pain, and found to have bilateral intra-alveolar opacities and hilar adenopathy. Diagnostic work up revealed positive anti-nuclear antibodies (ANA) and negative ANCA, which in the setting of a non-classical presentation, delayed diagnosis and appropriate treatment. Due to persistent symptoms and a high suspicion for autoimmune disease with pulmonary-renal syndrome, he underwent lung biopsy which revealed intra-alveolar hemorrhage and capillaritis indicative of microscopic polyangiitis (MPA). Surprisingly, kidney biopsy was not typical of classic MPA, but revealed less common features. Due to therapeutic noncompliance he was readmitted multiple times thereafter with rare complications of MPA such as acute pancreatitis and hemorrhagic pericardial effusion with tamponade.

Conclusion
This case serves as an important clinical reminder to consider AAV even in those with negative ANCA serologies and a high suspicion for pulmonary-renal syndrome. It also demonstrates the high morbidity in cases of diagnostic delay and inadequate treatment.
The significance of equivocal bone findings in staging PSMA imaging in the preoperative setting: validation of the PSMA-RADS version 1.0
Authors: Kuten Jonathan , Dekalo Snir , Mintz Ishai , Yossepowitch Ofer , Mano Roy , Even-Sapir Einat 
Published: January 2021

Abstract
Background
Assessing the extent of disease in newly diagnosed prostate cancer (PC) patients is crucial for tailoring an appropriate treatment approach. Prostate-specific membrane antigen (PSMA)–targeted positron emission tomography/computed tomography (PET/CT) reportedly has greater accuracy than conventional imaging for staging PC. As with any imaging modality, pitfalls and nonspecific findings do occur. The PSMA reporting and data system (PSMA-RADS) version 1.0 offers structured interpretation of PSMA-targeted studies and classifies lesions by likelihood of clinical significance. The aim of this retrospective study was to evaluate the clinical significance of equivocal bone findings on staging PSMA-targeted imaging, as defined by PSMA-RADS version 1.0, in the preoperative setting. Fifteen of 406 consecutive patients staged by PET/CT prior to radical prostatectomy had equivocal bone lesions. The scans were retrospectively scored with the PSMA-RADS version 1.0 system, blinded to disease course and follow-up data. Postoperative persistence of prostate-specific antigen levels supported by imaging and histological findings was used as the reference standard for the true significance of equivocal imaging findings.

Results
Thirteen of the 15 patients had an overall PSMA-RADS score of 3B, of whom only two had true metastatic disease. The remaining patients had scores of 4 (n = 1) or 5 (n = 1), all confirmed as true positive prostate-related malignant lesions. A per-lesion analysis identified 29 bone lesions, of which 27 were scored PSMA-RADS 3B, and only three of them were true metastases. Thus, debatable lesions proved to have no clinical significance in 84.6% of cases, and only 11% of equivocal PSMA-RADS 3B bone lesions were true positive.

Conclusions
In intermediate and high-risk patients staged prior to radical prostatectomy, the majority of PSMA-RADS 3B lesions are of no clinical relevance. Bone lesions judged as being highly suspicious for metastases (PSMA-RADS 4/5) were all validated as true positives.
Isolation and characterisation of Methylocystis spp. for poly-3-hydroxybutyrate production using waste methane feedstocks
Authors: Rumah Bashir L. , Stead Christopher E. , Claxton Stevens Benedict H. , Minton Nigel P. , Grosse-Honebrink Alexander , Zhang Ying 
Published: January 2021

AbstractWaste plastic and methane emissions are two anthropogenic by-products exacerbating environmental pollution. Methane-oxidizing bacteria (methanotrophs) hold the key to solving these problems simultaneously by utilising otherwise wasted methane gas as carbon source and accumulating the carbon as poly-3-hydroxybutyrate, a biodegradable plastic polymer. Here we present the isolation and characterisation of two novel Methylocystis strains with the ability to produce up to 55.7 ± 1.9% poly-3-hydroxybutyrate of cell dry weight when grown on methane from different waste sources such as landfill and anaerobic digester gas. Methylocystis rosea BRCS1 isolated from a recreational lake and Methylocystis parvus BRCS2 isolated from a bog were whole genome sequenced using PacBio and Illumina genome sequencing technologies. In addition to potassium nitrate, these strains were also shown to grow on ammonium chloride, glutamine and ornithine as nitrogen source. Growth of Methylocystis parvus BRCS2 on Nitrate Mineral Salt (NMS) media with 0.1% methanol vapor as carbon source was demonstrated. The genetic tractability by conjugation was also determined with conjugation efficiencies up to 2.8 × 10–2 and 1.8 × 10–2 for Methylocystis rosea BRCS1 and Methylocystis parvus BRCS2 respectively using a plasmid with ColE1 origin of replication. Finally, we show that Methylocystis species can produce considerable amounts of poly-3-hydroxybutyrate on waste methane sources without impaired growth, a proof of concept which opens doors to their use in integrated bio-facilities like landfills and anaerobic digesters.