bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymerase acidic subunit of H9N2 polymerase complex induces cell apoptosis by binding to PDCD 7 in A549 cells
Authors: Wang Shaohua , Li Na , Jin Shugang , Zhang Ruihua , Xu Tong 
Published: April 2021

Abstract
Background
H9N2 influenza virus, a subtype of influenza A virus, can spread across different species and induce the respiratory infectious disease in humans, leading to a severe public health risk and a huge economic loss to poultry production. Increasing studies have shown that polymerase acidic (PA) subunit of RNA polymerase in ribonucleoproteins complex of H9N2 virus involves in crossing the host species barriers, the replication and airborne transmission of H9N2 virus.

Methods
Here, to further investigate the role of PA subunit during the infection of H9N2 influenza virus, we employed mass spectrometry (MS) to search the potential binding proteins of PA subunit of H9N2 virus. Our MS results showed that programmed cell death protein 7 (PDCD7) is a binding target of PA subunit. Co-immunoprecipitation and pull-down assays further confirmed the interaction between PDCD7 and PA subunit. Overexpression of PA subunit in A549 lung cells greatly increased the levels of PDCD7 in the nuclear and induced cell death assayed by MTT assay.

Results
Flow cytometry analysis and Western blot results showed that PA subunit overexpression significantly increased the expression of pro-apoptotic protein, bax and caspase 3, and induced cell apoptosis. However, knockout of PDCD7 effectively attenuated the effects of PA overexpression in cell apoptosis.

Conclusions
In conclusion, the PA subunit of H9N2 virus bind with PDCD7 and regulated cell apoptosis, which provide new insights in the role of PA subunit during H9N2 influenza virus infection.
Randomized clinical trial of the effect of the onset time of skin-to-skin contact at birth, immediate compared to early, on the duration of breastfeeding in full term newborns
Authors: Agudelo Sergio I , Gamboa Oscar A , Acuña Eduardo , Aguirre Lina , Bastidas Sarah , Guijarro Jennifer , Jaller María , Valderrama María , Padrón María Lucia , Gualdrón Nathalie , Obando Evelyn , Rodríguez Fabio , Buitrago Lina 
Published: April 2021

Abstract
Background
Skin-to-skin contact (SSC) compared to separation at birth has a positive effect on breastfeeding. However, separation at birth is common with negative impact on breastfeeding. The aim was to determine the effect of immediate SSC compared to early SSC on the duration of exclusive breastfeeding.

Methods
A randomized multicentre parallel clinical trial was conducted in two hospitals in Cundinamarca (Colombia) between November 2018 and January 2020. Low-risk full term newborns at birth were included. Neonates were assigned to immediate (in the first minute after birth) or early onset (start exactly at 60 min of life) skin to skin contact. Monthly follow-up was performed until 6 months of age. The primary outcome was the percentage of exclusively breastfed infants at 6 months (time in months with human milk as the only source of food). Secondary outcomes were the percentage of infants with exclusive breastfeeding at 3 months, duration in months of exclusive breastfeeding, neonate’s breastfeeding ability, percentage of weight change between birth and the first week of life and hospitalization in the neonatal unit in the first week. A bivariate analysis was performed to determine the variables associated with exclusive breastfeeding at 6 months. A survival analysis was performed to evaluate the effect of the onset of SSC on exclusive breastfeeding duration.

Results
A total of 297 newborns were included: 49.8% (n = 148) in the immediate SSC group, and 50.2% (n = 149) in the early SSC group. The mean duration of exclusive breastfeeding in both groups was 5 months. There were no differences between the groups in the percentage of exclusive breastfeeding at 6 months (relative risk [RR] 1.06, 95% CI 0.72, 1.58) or in the duration of exclusive breastfeeding (hazard ratio [HR] 0.98, 95% CI 0.74, 1.28).

Conclusions
The percentage of infants and the duration of exclusive breastfeeding in the first 6 months of age were the same between the two groups of SSC interventions. Given the current barriers to its implementation, the results of this study could positively impact the use of SSC at birth and standardize the intervention and improve breastfeeding indicators.

Trial registration
ClinicalTrials.gov NCT02687685.
Feasibility, acceptability, and potential efficacy of an innovative postnatal home-based breastfeeding peer support programme in Hong Kong: a feasibility and pilot randomised controlled trial
Authors: Lok Kris Yuet-Wan , Chow Charlotte L. Y. , Shing Jeffery Sheung Yu , Smith Robert , Lam Christine Chi Oi , Bick Debra , Chang Yan-Shing 
Published: April 2021

AbstractBackgroundAs suggested by the World Health Organization, breastfeeding peer support is being introduced worldwide to support women’s breastfeeding needs. Evidence has shown that when such support is offered to women, the duration and exclusivity of breastfeeding is increased. We developed an innovative home-based intervention to sustain exclusive breastfeeding in Hong Kong. However, potential barriers must be addressed before a full randomised controlled trial (RCT) is conducted. The aim of this study was to determine the feasibility of a breastfeeding support programme with home-based visits from peer supporters over a six month period among postpartum Chinese women in Hong Kong.MethodsWe conducted a feasibility and pilot randomised controlled trial. Twenty primiparous women intending to breastfeed their healthy term singleton infant were recruited from a hospital in Kowloon, Hong Kong between February and March 2019. Participants were randomly allocated to the intervention or control group. Participants in the intervention group received five home-based visits with a peer supporter over a six month period, as well as standard care, whereas participants in the control group received standard care only. We assessed feasibility, compliance, and acceptability of the breastfeeding peer support programme. Other outcomes assessed were breastfeeding self-efficacy, duration, and exclusivity.ResultsIt was feasible to recruit and train existing peer supporters, and peer supporters were able to deliver the intervention, which was acceptable to women, but rates of stopping the intervention and loss to follow-up were high. There was higher retention seen within the first month. Women interviewed at the end of the study reported that the intervention was positive. The cessation risk of any, and exclusive breastfeeding were not statistically different between the intervention and control groups.ConclusionsThis study provided valuable information on feasibility of the trial design and intervention. Modifications to the intervention, such as targeting women with lower breastfeeding self-efficacy, or combining home visits with technology and telephone follow-up may be more appropriate in a larger trial. Implementing the programme early during the antenatal phase and tailoring peer support to most appropriately sustain exclusive breastfeeding and other feeding modes should be incorporated in a future home-based peer support arm.Trial registrationNCT03705494on 15 Oct 2018.
Circ_0116061 regulated the proliferation, apoptosis, and inflammation of osteoarthritis chondrocytes through regulating the miR-200b-3p/SMURF2 axis
Authors: Zheng Wei , Hou Guanhua , Li Yong 
Published: April 2021

Abstract
Background
Circular RNA (circRNA) has been shown to be associated with osteoarthritis (OA) progression. Circ_0116061 has been found to be highly expressed in OA cartilage tissues, but its role and mechanism in OA progression remain unclear.

Methods
Expression levels of circ_0116061, microRNA (miR)-200b-5p, and Smad ubiquitin regulatory factor 2 (SMURF2) were detected using quantitative real-time PCR. The proliferation and apoptosis of cells were measured using cell counting kit 8 (CCK8) assay, colony formation assay, and flow cytometry. Furthermore, the protein levels of proliferation-related marker, apoptosis-related markers, inflammatory factors, and SMURF2 were tested using western blot (WB) analysis. In addition, the interaction between miR-200b-3p and circ_0116061 or SMURF2 was examined using dual-luciferase reporter assay and biotin-labeled RNA pull-down assay.

Results
Circ_0116061 and SMURF2 were highly expressed, and miR-200b-3p was lowly expressed in OA cartilage tissues. Knockdown of circ_0116061 could promote the proliferation and inhibit the apoptosis and inflammation of OA chondrocytes. MiR-200b-3p could be sponged by circ_0116061, and its inhibitor could reverse the regulation of circ_0116061 silencing on the biological functions of OA chondrocytes. SMURF2 was a target of miR-200b-3p, and its expression was positively regulated by circ_0116061. Silencing of SMURF2 also could enhance the proliferation and suppress the apoptosis and inflammation of OA chondrocytes. Furthermore, the regulation of circ_0116061 silencing on the biological functions of OA chondrocytes also could be reversed by SMURF2 overexpression.

Conclusion
Our data showed that circ_0116061 might regulate the miR-200b-3p/SMURF2 axis to promote the progression of OA.
The influence of TCM constitutions and neurocognitive function in elderly Macau individuals
Authors: Zhang Zhuo , Chuang Yaochen , Ke Xinyu , Wang Ji , Xu Youhua , Zhao Yonghua , Bian Ying 
Published: April 2021

AbstractBackgroundTraditional Chinese medicine (TCM) constitution contributes to predicating disease occurrence and pathological progress. In this study, we investigate the correlation between TCM constitution and neurocognitive function in elderly Macau individuals.MethodsA total of 313 older adults from elderly healthcare centers were recruited at random. The data of gender, age, education, sleeping hours, physical activities were collected, and the Geriatric Depression Scale, Hong Kong version of the Montreal Cognitive Assessment (MoCA) and categories of TCM constitution were administered.ResultsOf the 313 elderly individuals enrolled in this study, 86 (27.48%) were of balanced constitution. Among the other categories of TCM constitution, the most was Yin-deficiency (23.32%), followed by 53 (16.93%) with Phlegm-dampness. The average neurocognitive score of all elderly individuals was 18.01 ± 6.25. After adjusting for all possible confounds, multiple linear regression analysis showed that Qi-depressed constitution and neurocognitive scores were negatively correlated (β = − 2.66, 95%CI − 4.99 ~ − 0.33), Meanwhile, Yin-deficient constitution and neurocognitive scores were negatively correlated (β = − 2.10, 95%CI − 3.73 ~ − 0.47). Compared with balanced constitution, Qi-depressed constitution mainly affected visual–spatial ability dimension (β = − 0.91, 95%CI − 1.54 ~ − 0.28) and naming dimension (β = − 0.64, 95%CI − 1.04 ~ − 0.25), Yin-deficient constitution mainly affected visual space dimension (β = − 0.53, 95%CI − 0.97 ~ − 0.08).ConclusionQi-depressed and Yin-deficient constitutions are associated with and contributed to the decline of neurocognitive function in senior adults, especially visual–spatial ability and naming dimensions. Further investigations into how TCM constitutions interact with neurocognitive function are needed.
Adiponectin-mimetic novel nonapeptide rescues aberrant neuronal metabolic-associated memory deficits in Alzheimer’s disease
Authors: Ali Tahir , Rehman Shafiq Ur , Khan Amjad , Badshah Haroon , Abid Noman Bin , Kim Min Woo , Jo Myeung Hoon , Chung Seung Soo , Lee Hyoung-gon , Rutten Bart P. F. , Kim Myeong Ok 
Published: April 2021

Abstract
Background
Recently, we and other researchers reported that brain metabolic disorders are implicated in Alzheimer’s disease (AD), a progressive, devastating and incurable neurodegenerative disease. Hence, novel therapeutic approaches are urgently needed to explore potential and novel therapeutic targets/agents for the treatment of AD. The neuronal adiponectin receptor 1 (AdipoR1) is an emerging potential target for intervention in metabolic-associated AD. We aimed to validate this hypothesis and explore in-depth the therapeutic effects of an osmotin-derived adiponectin-mimetic novel nonapeptide (Os-pep) on metabolic-associated AD.

Methods
We used an Os-pep dosage regimen (5 μg/g, i.p., on alternating days for 45 days) for APP/PS1 in amyloid β oligomer-injected, transgenic adiponectin knockout (Adipo−/−) and AdipoR1 knockdown mice. After behavioral studies, brain tissues were subjected to biochemical and immunohistochemical analyses. In separate cohorts of mice, electrophysiolocal and Golgi staining experiments were performed. To validate the in vivo studies, we used human APP Swedish (swe)/Indiana (ind)-overexpressing neuroblastoma SH-SY5Y cells, which were subjected to knockdown of AdipoR1 and APMK with siRNAs, treated with Os-pep and other conditions as per the mechanistic approach, and we proceeded to perform further biochemical analyses.

Results
Our in vitro and in vivo results show that Os-pep has good safety and neuroprotection profiles and crosses the blood-brain barrier. We found reduced levels of neuronal AdipoR1 in human AD brain tissue. Os-pep stimulates AdipoR1 and its downstream target, AMP-activated protein kinase (AMPK) signaling, in AD and Adipo−/− mice. Mechanistically, in all of the in vivo and in vitro studies, Os-pep rescued aberrant neuronal metabolism by reducing neuronal insulin resistance and activated downstream insulin signaling through regulation of AdipoR1/AMPK signaling to consequently improve the memory functions of the AD and Adipo−/− mice, which was associated with improved synaptic function and long-term potentiation via an AdipoR1-dependent mechanism.

Conclusion
Our findings show that Os-pep activates AdipoR1/AMPK signaling and regulates neuronal insulin resistance and insulin signaling, which subsequently rescues memory deficits in AD and adiponectin-deficient models. Taken together, the results indicate that Os-pep, as an adiponectin-mimetic novel nonapeptide, is a valuable and promising potential therapeutic candidate to treat aberrant brain metabolism associated with AD and other neurodegenerative diseases.
Out-of-hospital resuscitation of a 3 month old boy presenting with recurrent ventricular fibrillation cardiac arrest: a case report
Authors: Kingsley Peter , Merefield Jonathan , Walker Robert G. , Chapman Fred W. , Faulkner Mark 
Published: April 2021

AbstractA 3 month old boy, with no known health conditions, suffered a sudden collapse at home. On first EMS arrival, ventricular fibrillation (VF) cardiac arrest was identified and resuscitation following UK national guidelines was initiated. He remained in cardiac arrest for over 25 min, during which he received 10 defibrillation shocks, each effective, but with VF reoccurring within a few seconds of each of the first 9. A return of spontaneous circulation (ROSC) was achieved after the 10th shock. The resuscitation was conducted fully in his home, with the early involvement of Advanced Paramedic Practitioners specialising in critical care (APP- CC). Throughout his resuscitation, there remained a strong focus on delivering quality resuscitation in situ, rather than a ‘load and go’ approach that would have resulted in very early conveyance to hospital with on-going CPR.The patient was subsequently discharged home and is making an excellent recovery. The arrest was later determined to have been caused by a primary arrhythmia as a result of a previously unidentified non-obstructive variant hypertrophic cardiomyopathy.We present data downloaded from the defibrillator used during the resuscitation that illustrates clearly the recurrent nature of his fibrillation.
IOERT versus external beam electrons for boost radiotherapy in stage I/II breast cancer: 10-year results of a phase III randomized study
Authors: Ciabattoni Antonella , Gregucci Fabiana , Fastner Gerd , Cavuto Silvio , Spera Antonio , Drago Stefano , Ziegler Ingrid , Mirri Maria Alessandra , Consorti Rita , Sedlmayer Felix 
Published: April 2021

Abstract
Background
Intraoperative radiotherapy with electrons (IOERT) boost could be not inferior to external beam radiotherapy (EBRT) boost in terms of local control and tissue tolerance. The aim of the study is to present the long-term follow-up results on local control, esthetic evaluation, and toxicity of a prospective study on early-stage breast cancer patients treated with breast-conserving surgery with an IOERT boost of 10 Gy (experimental group) versus 5 × 2 Gy EBRT boost (standard arm). Both arms received whole-breast irradiation (WBI) with 50 Gy (2 Gy single dose).

Methods
A single-institution phase III randomized study to compare IOERT versus EBRT boost in early-stage breast cancer was conducted as a non-inferiority trial. Primary endpoints were the evaluation of in-breast true recurrences (IBTR) and out-field local recurrences (LR) as well as toxicity and cosmetic results. Secondary endpoints were overall survival (OS), disease-free survival (DFS), and patient’s grade of satisfaction with cosmetic outcomes.

Results
Between 1999 and 2004, 245 patients were randomized: 133 for IOERT and 112 for EBRT. The median follow-up was 12 years (range 10–16 years). The cumulative risk of IBTR at 5–10 years was 0.8% and 4.3% after IOERT, compared to 4.2% and 5.3% after EBRT boost (p = 0.709). The cumulative risk of out-field LR at 5–10 years was 4.7% and 7.9% for IOERT versus 5.2% and 10.3% for EBRT (p = 0.762). All of the IOERT arm recurrences were observed at > 100 months’ follow-up, whereas the mean time to recurrence in the EBRT group was earlier (55.2 months) (p < 0.05). No late complications associated with IOERT were observed. The overall cosmetic results were scored as good or excellent in physician and patient evaluations for both IOERT and EBRT. There were significantly better scores for IOERT at all time points in physician and patient evaluations with the greatest difference at the end of EBRT (p = 0.006 objective and p = 0.0004 subjective) and most narrow difference at 12 months after the end of EBRT (p = 0.08 objective and p = 0.04 subjective analysis).

Conclusion
A 10-Gy IOERT boost during breast-conserving surgery provides high local control rates without significant morbidity. Although not significantly superior to external beam boosts, the median time to local recurrences after IOERT is prolonged by more than 4 years.
Investigating the sub-regions of the superior parietal cortex using functional magnetic resonance imaging connectivity
Authors: Alahmadi Adnan A. S. 
Published: April 2021

AbstractObjectivesTraditionally, the superior parietal lobule (SPL) is usually investigated as one region of interest, particularly in functional magnetic resonance imaging (fMRI) studies. However, cytoarchitectonic analysis has shown that the SPL has a complex, heterogeneous topology that comprises more than seven sub-regions. Since previous studies have shown how the SPL is significantly involved in different neurological functions—such as visuomotor, cognitive, sensory, higher order, working memory and attention—this study aims to investigate whether these cytoarchitecturally different sub-regions have different functional connectivity to different functional brain networks.MethodsThis study examined 198 healthy subjects using resting-state fMRI and investigated the functional connectivity of seven sub-regions of the SPL to eight regional functional networks.ResultsThe findings showed that most of the seven sub-regions were functionally connected to these targeted networks and that there are differences between these sub-regions and their functional connectivity patterns. The most consistent functional connectivity was observed with the visual and attention networks. There were also clear functional differences between Brodmann area (BA) 5 and BA7. BA5, with its three sub-regions, had strong functional connectivity to both the sensorimotor and salience networks.ConclusionThese findings have enhanced our understanding of the functional organisations of the complexity of the SPL and its varied topology and also provide clear evidence of the functional patterns and involvements of the SPL in major brain functions.
Evaluation of the Spanish population coverage of a prospective HLA haplobank of induced pluripotent stem cells
Authors: Álvarez-Palomo Belén , García-Martinez Iris , Gayoso Jorge , Raya Angel , Veiga Anna , Abad María Luisa , Eiras Adolfo , Guzmán-Fulgencio María , Luis-Hidalgo Mar , Eguizabal Cristina , Santos Silvia , Balas Antonio , Alenda Raquel , Sanchez-Gordo Francisco , Verdugo Laura Ponce , Villa Juliana , Carreras Enric , Vidal Francisco , Madrigal Alejandro , Herrero María José , Rudilla Francesc , Querol Sergi 
Published: April 2021

Abstract
Background
iPSC (induced pluripotent stem cells) banks of iPSC lines with homozygous HLA (human leukocyte antigen) haplotypes (haplobanks) are proposed as an affordable and off-the-shelf approach to allogeneic transplantation of iPSC derived cell therapies. Cord blood banks offer an extensive source of HLA-typed cells suitable for reprogramming to iPSC. Several initiatives worldwide have been undertaken to create national and international iPSC haplobanks that match a significant part of a population.

Methods
To create an iPSC haplobank that serves the Spanish population (IPS-PANIA), we have searched the Spanish Bone Marrow Donor Registry (REDMO) to identify the most frequently estimated haplotypes. From the top ten donors identified, we estimated the population coverage using the criteria of zero mismatches in HLA-A, HLA-B, and HLA-DRB1 with different stringencies: high resolution, low resolution, and beneficial mismatch.

Results
We have calculated that ten cord blood units from homozygous donors stored at the Spanish cord blood banks can provide HLA-A, HLA-B, and HLA-DRB1 matching for 28.23% of the population.

Conclusion
We confirm the feasibility of using banked cord blood units to create an iPSC haplobank that will cover a significant percentage of the Spanish and international population for future advanced therapy replacement strategies.
Bone marrow mesenchymal stem cell exosomes suppress phosphate-induced aortic calcification via SIRT6–HMGB1 deacetylation
Authors: Wei Wenqian , Guo Xiaodong , Gu Lijie , Jia Jieshuang , Yang Man , Yuan Weijie , Rong Shu 
Published: April 2021

Abstract
Background
Vascular calcification associated with chronic kidney disease (CKD) can increase the risk of mortality. Elevated serum levels of high mobility group box 1 (HMGB1) promotes vascular calcification in CKD via the Wnt/β-catenin pathway. Sirtuin 6 (SIRT6) prevents fibrosis in CKD by blocking the expression of β-catenin target genes through deacetylation. This study aimed to investigate whether the inhibition of vascular calcification by bone marrow mesenchymal stem cell (BMSC)-derived exosomes is related to SIRT6 activity and assess the regulatory relationship between HMGB1 and SIRT6.

Methods
CKD characteristics, osteogenic markers, calcium deposition, and the differential expression of HMGB1 and SIRT6 have been measured in a 5/6 nephrectomized mouse CKD model fed a high-phosphate diet to induce aortic calcification. In vitro assays were also performed to validate the in vivo findings.

Results
High phosphate promotes the translocation of HMGB1 from the nucleus to the cytosol and induces the expression of Runx2, osteopontin, and Msx2. However, BMSC-derived exosomes were found to alleviate CKD-related fibrosis and the induction of osteogenic genes although less significantly when SIRT6 expression is suppressed. SIRT6 was found to modulate the cytosol translocation of HMGB1 by deacetylation in vascular smooth muscle cells.

Conclusion
Our results indicate that BMSC-derived exosomes inhibit high phosphate-induced aortic calcification and ameliorate renal function via the SIRT6–HMGB1 deacetylation pathway.