bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulated Talin1 synergistically boosts β-estradiol-induced proliferation and pro-angiogenesis of eutopic and ectopic endometrial stromal cells in adenomyosis
Authors: Wang Yi-yi , Duan Hua , Wang Sha , Quan Yong-jun , Huang Jun-hua , Guo Zheng-chen 
Published: May 2021

AbstractAdenomyosis (ADS) is an estrogen-dependent gynecological disease with unspecified etiopathogenesis. Local hyperestrogenism may serve a key role in contributing to the origin of ADS. Talin1 is mostly identified to be overexpressed and involved in the progression of numerous human carcinomas through mediating cell proliferation, adhesion and motility. Whether Talin1 exerts an oncogenic role in the pathogenesis of ADS and puts an extra impact on the efficacy of estrogen, no relevant data are available yet. Here we demonstrated that the adenomyotic eutopic and ectopic endometrial stromal cells (ADS_Eu_ESC and ADS_Ec_ESC) treated with β-estradiol (β-E2) presented stronger proliferative and pro-angiogenetic capacities, accompanied by increased expression of PCNA, Ki67, VEGFB and ANGPTL4 proteins. Meanwhile, these promoting effects were partially abrogated by Fulvestrant (ICI 182780, an estrogen-receptor antagonist). Aberrantly upregulation of Talin1 mRNA and protein level was observed in ADS endometrial specimens and stromal cells. Through performing functional experiments in vitro, we further determined that merely overexpression of Talin1 (OV-Talin1) also enhanced ADS stromal cell proliferation and pro-angiogenesis, while the most pronounced facilitating effects were found in the co-intervention group of OV-Talin1 plus β-E2 treatment. Results from the xenograft nude mice model showed that the hypodermic endometrial lesions from co-intervention group had the highest mean weight and volume, compared with that of individual OV-Talin1 or β-E2 treatment. The expression levels of PCNA, Ki67, VEGFB and ANGPTL4 in the lesions were correspondingly elevated the most in the co-intervention group. Our findings unveiled that overexpressed Talin1 might cooperate withβ-E2 in stimulating ADS endometrial stromal cell proliferation and neovascularization, synergistically promoting the growth and survival of ectopic lesions. These results may be beneficial to provide a new insight for clarifying the pathogenesis of ADS.
Neutralization diversity of HIV-1 Indian subtype C envelopes obtained from cross sectional and followed up individuals against broadly neutralizing monoclonal antibodies having distinct gp120 specificities
Authors: Mullick Ranajoy , Sutar Jyoti , Hingankar Nitin , Deshpande Suprit , Thakar Madhuri , Sahay Seema , Ringe Rajesh P. , Mukhopadhyay Sampurna , Patil Ajit , Bichare Shubhangi , Murugavel Kailapuri G. , Srikrishnan Aylur K. , Goyal Rajat , Sok Devin , Bhattacharya Jayanta 
Published: May 2021

AbstractBackgroundThe potential use of the broadly neutralizing monoclonal antibodies (bnAbs) towards prophylaxis and treatment to HIV-1 is currently being explored. While a number of promising bnAbs have been discovered and a few of them have progressed towards clinical development, their extent of neutralization coverage with respect to global HIV-1 variants given the existence of genetically distinct subtypes and recombinants circulating globally is not clearly known. In the present study, we examined the variation in the neutralization susceptibility of pseudoviruses expressing 71 full length primary HIV-1 subtype Cenvsobtained from limited cross-sectional individuals over different time points against four bnAbs that target gp120 with distinct specificities: VRC01, CAP256-VRC26.25, PGDM1400 and PGT121.ResultsWe found significant variations in the susceptibility of Indian clade C to these four bnAbs. These variations were found to be distinct to that observed in African subtype C based on the existing datasets and concordant with their sequence diversity. Trend analysis indicated an increasing neutralization resistance observed over time with CAP25-VRC26.25, PGDM1400 and PGT121 when tested on pseudoviruses expressingenvsobtained from 1999 to 2016. However, inconsistent trend in neutralization susceptibility was observed, when pseudoviruses expressingenvsobtained from three followed up individuals were examined. Finally, through predictive analysis of the 98 Indian subtype C including those assessed in the present study by employing additive model implemented in CombiNAber (http://www.hiv.lanl.gov), we observed two possibilities where combinations of three bnAbs (VRC01/CAP56-VRC26.25/PGT121 and PGDM1400/CAP256-VRC26.25/PGT121) could achieve near 100% neutralization coverage.ConclusionsOur findings not only indicate disparate intra-clade C genetic vis-à-vis neutralization diversities but also warrant the need for more comprehensive study using additional isolates towards comparing inter and intra-clade neutralization diversities which will be necessary for selecting the bnAb combinations suitable for optimal coverage of the region-specific HIV-1 circulating subtypes. Expanding these efforts is imperative for designing efficacious bnAb based intervention strategies for India as well as subtype C in general.
Functional conservation in genes and pathways linking ageing and immunity
Authors: Fabian Daniel K. , Fuentealba Matías , Dönertaş Handan Melike , Partridge Linda , Thornton Janet M. 
Published: May 2021

AbstractAt first glance, longevity and immunity appear to be different traits that have not much in common except the fact that the immune system promotes survival upon pathogenic infection. Substantial evidence however points to a molecularly intertwined relationship between the immune system and ageing. Although this link is well-known throughout the animal kingdom, its genetic basis is complex and still poorly understood. To address this question, we here provide a compilation of all genes concomitantly known to be involved in immunity and ageing in humans and three well-studied model organisms, the nematode wormCaenorhabditis elegans, the fruit flyDrosophila melanogaster, and the house mouseMus musculus. By analysing human orthologs among these species, we identified 7 evolutionarily conserved signalling cascades, the insulin/TOR network, three MAPK (ERK, p38, JNK), JAK/STAT, TGF-β, and Nf-κB pathways that act pleiotropically on ageing and immunity. We review current evidence for these pathways linking immunity and lifespan, and their role in the detrimental dysregulation of the immune system with age, known as immunosenescence. We argue that the phenotypic effects of these pathways are often context-dependent and vary, for example, between tissues, sexes, and types of pathogenic infection. Future research therefore needs to explore a higher temporal, spatial and environmental resolution to fully comprehend the connection between ageing and immunity.
Introduction to collection: confronting the challenges of health research in humanitarian crises
Authors: Mistry Amit S. , Kohrt Brandon A. , Beecroft Blythe , Anand Nalini , Nuwayhid Iman 
Published: May 2021

Abstract
Background
Humanitarian crises, such as armed conflict, forced displacement, natural disasters, and major disease outbreaks, take a staggering toll on human health, especially in low-resource settings. Yet there is a dearth of robust evidence to inform the governments, non-governmental organizations (NGOs), and other humanitarian organizations on how to best respond to them. The Fogarty International Center of the U.S. National Institutes of Health commissioned a collection of Research in Practice articles that highlights the experiences of scientists conducting research in the context of humanitarian crises. Unlike traditional research papers, the case analyses in this collection go beyond what research was completed and focus on why the research was important and how it was conducted in these extremely challenging settings.

Discussion
The papers selected for this collection span 27 countries, cover a broad range of humanitarian crises, and discuss a wide variety of disease and health risk factors. Of the 23 papers in the collection, 17 include an author from the affected country and five papers were authored by humanitarian NGOs. Throughout the collection, 43% of the authors were from low- and middle-income countries.
Across the collection, some general themes emerged that are broadly applicable. Importantly, there is a clear need for more, high-quality research to address evidence gaps. Community engagement, already a key element to global health research, was highlighted as especially important for research involving populations dealing with severe trauma and disruption. Partnership with humanitarian actors, including local governments, local and international NGOs, and UN agencies, was found to be a critical strategy as well.

Conclusion
A variety of audiences will find this collection useful. Global health educators can utilize papers to facilitate discussion around public health practice and equitable partnerships, among other topics. Humanitarian response organizations may use the collection to consider how research may inform and improve their work. Global health researchers, funders, and other stakeholders may use the collection to stimulate dialogue around key scientific research questions and better appreciate the importance of conducting research in humanitarian crises in the context of achieving broader global health goals.
SLC6A8-mediated intracellular creatine accumulation enhances hypoxic breast cancer cell survival via ameliorating oxidative stress
Authors: Li Qiao , Liu Manran , Sun Yan , Jin Ting , Zhu Pengpeng , Wan Xueying , Hou Yixuan , Tu Gang 
Published: May 2021

Abstract
Background
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with poor prognosis and limited treatment options. Hypoxia is a key hallmark of TNBC. Metabolic adaptation promotes progression of TNBC cells that are located within the hypoxic tumor regions. However, it is not well understood regarding the precise molecular mechanisms underlying the regulation of metabolic adaptions by hypoxia.

Methods
RNA sequencing was performed to analyze the gene expression profiles in MDA-MB-231 cell line (20% O2 and 1% O2). Expressions of Slc6a8, which encodes the creatine transporter protein, were detected in breast cancer cells and tissues by quantitative real-time PCR. Immunohistochemistry was performed to detect SLC6A8 protein abundances in tumor tissues. Clinicopathologic correlation and overall survival were evaluated by chi-square test and Kaplan-Meier analysis, respectively. Cell viability assay and flow cytometry analysis with Annexin V/PI double staining were performed to investigate the impact of SLC6A8-mediated uptake of creatine on viability of hypoxic TNBC cells. TNBC orthotopic mouse model was used to evaluate the effects of creatine in vivo.

Results
SLC6A8 was aberrantly upregulated in TNBC cells in hypoxia. SLC6A8 was drastically overexpressed in TNBC tissues and its level was tightly associated with advanced TNM stage, higher histological grade and worse overall survival of TNBC patients. We found that SLC6A8 was transcriptionally upregulated by p65/NF-κB and mediated accumulation of intracellular creatine in hypoxia. SLC6A8-mediated accumulation of creatine promoted survival and suppressed apoptosis via maintaining redox homeostasis in hypoxic TNBC cells. Furthermore, creatine was required to facilitate tumor growth in xenograft mouse models. Mechanistically, intracellular creatine bolstered cell antioxidant defense by reducing mitochondrial activity and oxygen consumption rates to reduce accumulation of intracellular reactive oxygen species, ultimately activating AKT-ERK signaling, the activation of which protected the viability of hypoxic TNBC cells via mediating the upregulation of Ki-67 and Bcl-2, and the downregulation of Bax and cleaved Caspase-3.

Conclusions
Our study indicates that SLC6A8-mediated creatine accumulation plays an important role in promoting TNBC progression, and may provide a potential therapeutic strategy option for treatment of SLC6A8 high expressed TNBC.
Inhibition of DEC2 is necessary for exiting cell dormancy in salivary adenoid cystic carcinoma
Authors: Yang Xiao , Wu Jia-shun , Li Mao , Zhang Wei-long , Gao Xiao-lei , Wang Hao-fan , Yu Xiang-hua , Pang Xin , Zhang Mei , Liang Xin-hua , Tang Ya-ling 
Published: May 2021

Abstract
Background
Patients were prone to have poor prognosis once dormant tumor cells being reactivated. However, the molecular mechanism of tumor cell dormancy remains poorly understood. This study aimed to investigate the function of DEC2 in the dormancy of salivary adenoid cystic carcinoma (SACC) in vitro and vivo.

Methods
The function of DEC2 in tumor dormancy of SACC was investigated in nude mice by establishing primary and lung metastasis model. Meanwhile, the interaction between hypoxia and SACC dormancy and the role of DEC2 were demonstrated through CoCl2 induced hypoxia–mimicking microenvironments. Furthermore, the expression of DEC2 was detected by immunohistochemical staining in primary SACC samples with and without recurrence.

Results
In the primary SACC, DEC2 overexpression inhibited cell proliferation, increased cell population arrested in G0/G1 phase, and participated in dormancy regulation, which limited tumor growth. Intriguingly, in the model of lung metastasis, the level of DEC2 was reduced significantly and resulted in dormancy exit and growth resumption of SACC cells. Then, we found that DEC2 may associate with hypoxia in contributing to tumor dormancy, which might provide a possible cue to explain the different roles of DEC2 in primary and metastasis lesions. And overexpression of DEC2 induced dormancy and promoted migration and invasion through activating EMT program. Finally, DEC2 positive expression was shown to be significantly correlated with recurrence and dormancy of SACC patients.

Conclusions
These findings provide a novel insight into the role of DEC2 gene in tumor dormancy and metastasis.
Serial Lipocalin 2 and Oncostatin M levels reflect inflammation status and treatment response in axial spondyloarthritis
Authors: Tsui Florence W. L. , Lin Aifeng , Sari Ismail , Zhang Zhenbo , Tsui Hing Wo , Inman Robert D. 
Published: May 2021

Abstract
Background
Informative serum biomarkers for monitoring inflammatory activity and treatment responses in axial spondyloarthritis (axSpA) are lacking. We assessed whether Lipocalin 2 (LCN2) and Oncostatin M (OSM), both having roles in inflammation and bone remodeling, may accurately reflect chronic joint inflammation and treatment response in axSpA. Previous reports in animal models showed involvement of LCN2 and OSM in joint/gut inflammation. We asked whether they also play a role in human axSpA.

Methods
We analyzed a longitudinal observational axSpA cohort (286 patients) with yearly clinical assessments and concurrent measurements of serum LCN2 and OSM (1204 serum samples) for a mean of 4 years. Biomarker levels were correlated with MRI scoring and treatment response.

Results
Persistent and transient elevation of LCN2 and OSM were observed in axSpA patients. Persistent elevation of LCN2 or OSM, but not CRP, correlated with sacroiliac joint (SIJ) MRI SPARCC scores (Pearson’s correlation p = 0.0005 and 0.005 for LCN2 and OSM respectively), suggesting that LCN2/OSM outperforms CRP as reflective of SIJ inflammation. We observed both concordant and discordant patterns of LCN2 and OSM in relationship to back pain, the cardinal clinical symptom in axSpA. Twenty-six percent (73/286) of the patients remained both clinically and serologically active (CASA). Sixty percent (173/286) of the patients became clinically quiescent, with back pain resolved, but 53% (92/173) of them were serologically active (CQSA), indicating that pain control may not indicate control of joint inflammation, as reflected by positive MRI imaging of SIJ. With respect to treatment responses, transient elevation of LCN2 or OSM over time was predictive of better response to all treatments.

Conclusion
In axSpA, persistent LCN2 and/or OSM elevation reflects chronic SIJ inflammation and suboptimal treatment response. In our cohort, half of the currently deemed clinically quiescent patients with back pain resolved continued to demonstrate chronic joint inflammation. LCN2 and OSM profiling outperforms CRP as a predictive measure and provides an objective assessment of chronic local inflammation in axSpA patients.
Mendelian randomization: estimation of inpatient hospital costs attributable to obesity
Authors: Dick Katherine , Schneider John E. , Briggs Andrew , Lecomte Pascal , Regnier Stephane A. , Lean Michael 
Published: May 2021

Abstract
Background
Mendelian Randomization is a type of instrumental variable (IV) analysis that uses inherited genetic variants as instruments to estimate causal effects attributable to genetic factors. This study aims to estimate the impact of obesity on annual inpatient healthcare costs in the UK using linked data from the UK Biobank and Hospital Episode Statistics (HES).

Methods
UK Biobank data for 482,127 subjects was linked with HES inpatient admission records, and costs were assigned to episodes of care. A two-stage least squares (TSLS) IV model and a TSLS two-part cost model were compared to a naïve regression of inpatient healthcare costs on body mass index (BMI).

Results
The naïve analysis of annual cost on continuous BMI predicted an annual cost of £21.61 [95% CI £20.33 – £22.89] greater cost per unit increase in BMI. The TSLS IV model predicted an annual cost of £14.36 [95% CI £0.31 – £28.42] greater cost per unit increase in BMI. Modelled with a binary obesity variable, the naïve analysis predicted that obese subjects incurred £205.53 [95% CI £191.45 – £219.60] greater costs than non-obese subjects. The TSLS model predicted a cost £201.58 [95% CI £4.32 – £398.84] greater for obese subjects compared to non-obese subjects.

Conclusions
The IV models provide evidence for a causal relationship between obesity and higher inpatient healthcare costs. Compared to the naïve models, the binary IV model found a slightly smaller marginal effect of obesity, and the continuous IV model found a slightly smaller marginal effect of a single unit increase in BMI.
On a fractional-order p-Laplacian boundary value problem at resonance on the half-line with two dimensional kernel
Authors: Imaga O. F. , Iyase S. A. 
Published: May 2021

AbstractIn this work, we consider the solvability of a fractional-order p-Laplacian boundary value problem on the half-line where the fractional differential operator is nonlinear and has a kernel dimension equal to two. Due to the nonlinearity of the fractional differential operator, the Ge and Ren extension of Mawhin’s coincidence degree theory is applied to obtain existence results for the boundary value problem at resonance. Two examples are used to validate the established results.
Metagenomic analysis reveals the shared and distinct features of the soil resistome across tundra, temperate prairie, and tropical ecosystems
Authors: Qian Xun , Gunturu Santosh , Guo Jiarong , Chai Benli , Cole James R. , Gu Jie , Tiedje James M. 
Published: May 2021

Abstract
Background
Soil is an important reservoir of antibiotic resistance genes (ARGs), but their potential risk in different ecosystems as well as response to anthropogenic land use change is unknown. We used a metagenomic approach and datasets with well-characterized metadata to investigate ARG types and amounts in soil DNA of three native ecosystems: Alaskan tundra, US Midwestern prairie, and Amazon rainforest, as well as the effect of conversion of the latter two to agriculture and pasture, respectively.

Results
High diversity (242 ARG subtypes) and abundance (0.184–0.242 ARG copies per 16S rRNA gene copy) were observed irrespective of ecosystem, with multidrug resistance and efflux pump the dominant class and mechanism. Ten regulatory genes were identified and they accounted for 13–35% of resistome abundances in soils, among them arlR, cpxR, ompR, vanR, and vanS were dominant and observed in all studied soils. We identified 55 non-regulatory ARGs shared by all 26 soil metagenomes of the three ecosystems, which accounted for more than 81% of non-regulatory resistome abundance. Proteobacteria, Firmicutes, and Actinobacteria were primary ARG hosts, 7 of 10 most abundant ARGs were found in all of them. No significant differences in both ARG diversity and abundance were observed between native prairie soil and adjacent long-term cultivated agriculture soil. We chose 12 clinically important ARGs to evaluate at the sequence level and found them to be distinct from those in human pathogens, and when assembled they were even more dissimilar. Significant correlation was found between bacterial community structure and resistome profile, suggesting that variance in resistome profile was mainly driven by the bacterial community composition.

Conclusions
Our results identify candidate background ARGs (shared in all 26 soils), classify ARG hosts, quantify resistance classes, and provide quantitative and sequence information suggestive of very low risk but also revealing resistance gene variants that might emerge in the future.
First report of three species of Trichoderma isolated from the rhizosphere in Algeria and the high antagonistic effect of Trichoderma brevicompactum to control grey mould disease of tomato
Authors: Hammad Massinissa , Guillemette Thomas , Alem Meriem , Bastide Franck , Louanchi Meriem 
Published: May 2021

Abstract
Background
Grey mould caused by Botrytis cinerea Pers. (teleomorph Botryotinia fuckeliana (de Bary) Whetzel) is one of the most destructive fungal diseases of Mediterranean crops. In Algeria, few studies have been made on the economic impact of this disease. Nevertheless, it is practically present in all tomato and strawberry greenhouses, as well as in prospected vineyards in the north and south of the country. The complexity of chemical control of this disease has led to search for Trichoderma strains that are effective in biological control.

Results
Fifteen isolates of Trichoderma spp. were obtained from vigorous and healthy plants (tomatoes, strawberries, and vines) rhizosphere, and from a commercial bio-compost (Bio-composte®), then identified as T. afroharzianum (four isolates), T. gamsii (four isolates), T. longibrachiatum (three isolates), T. atroviride (one isolate), T. brevicompactum (one isolate), T. breve (one isolate), and T. lixii (one isolate) on the basis of DNA sequence analysis of four genes (ITS, tef1, rpb2, and acl1). In vitro biocontrol tests revealed that four Algerian isolates of Trichoderma spp. (TAtC11, TGS7, TGS10, and TBS1) had a high antagonistic activity against B. cinerea, the mycelial growth has been reduced by 62 to 65% in dual-culture technique, by 62.31 to 64.49% in volatile compounds test, and a high inhibition of germling growth was recorded by TBS1 isolate with 90.68% in Culture filtrates test. Biocontrol tests carried out on tomato plants with T. brevicompactum (TBS1), T. atroviride (TAtC11), and T. lixii (TLiC8) against B. cinerea (BCT04) showed that TBS1 inoculation significantly reduced the incidence of disease by 64.43 and 51.35% in preventive and curative treatment, respectively.

Conclusion
The present study revealed the first report of T. brevicompactum, T. breve, and T. lixii in Algeria, and it also contributes to the promotion of the use of native strains of Trichoderma in biological control leading to a better preservation of soil microbial diversity.