bluuebunny/crossref_metadata_2025_split huggingface dataset:
G protein coupled estrogen receptor attenuates mechanical stress-mediated apoptosis of chondrocyte in osteoarthritis via suppression of Piezo1
Authors: Sun Yi , Leng Ping , Guo Pengcheng , Gao Huanshen , Liu Yikai , Li Chenkai , Li Zhenghui , Zhang Haining 
Published: August 2021

Abstract
Background
Apoptosis of chondrocyte is involved in osteoarthritis (OA) pathogenesis, and mechanical stress plays a key role in this process by activation of Piezo1. However, the negative regulation of signal conduction mediated by mechanical stress is still unclear. Here, we elucidate that the critical role of G protein coupled estrogen receptor (GPER) in the regulation of mechanical stress-mediated signal transduction and chondrocyte apoptosis.

Methods
The gene expression profile was detected by gene chip upon silencing Piezo1. The expression of GPER in cartilage tissue taken from the clinical patients was detected by RT-PCR and Western blot as well as immunohistochemistry, and the correlation between GPER expression and OA was also investigated. The chondrocytes exposed to mechanical stress were treated with estrogen, G-1, G15, GPER-siRNA and YAP (Yes-associated protein)-siRNA. The cell viability of chondrocytes was measured. The expression of polymerized actin and Piezo1 as well as the subcellular localization of YAP was observed under laser confocal microscope. Western blot confirmed the changes of YAP/ Rho GTPase activating protein 29 (ARHGAP29) /RhoA/LIMK /Cofilin pathway. The knee specimens of osteoarthritis model were stained with safranin and green. OARSI score was used to evaluate the joint lesions. The expressions of GPER and YAP were detected by immunochemistry.

Results
Expression profiles of Piezo1- silenced chondrocytes showed that GPER expression was significantly upregulated. Moreover, GPER was negatively correlated with cartilage degeneration during OA pathogenesis. In addition, we uncovered that GPER directly targeted YAP and broadly restrained mechanical stress-triggered actin polymerization. Mechanism studies revealed that GPER inhibited mechanical stress-mediated RhoA/LIMK/cofilin pathway, as well as the actin polymerization, by promoting expression of YAP and ARHGAP29, and the YAP nuclear localization, eventually causing the inhibition of Piezo1. YAP was obviously decreased in degenerated cartilage. Silencing YAP caused significantly increased actin polymerization and activation of Piezo1, and an increase of chondrocyte apoptosis. In addition, intra-articular injection of G-1 to OA rat effectively attenuated cartilage degeneration.

Conclusion
We propose a novel regulatory mechanism underlying mechanical stress-mediated apoptosis of chondrocyte and elucidate the potential application value of GPER as therapy targets for OA.
HAZ Characterization and Mechanical Properties of QP980-DP980 Laser Welded Joints
Authors: Xue Junliang , Peng Peng , Guo Wei , Xia Mingsheng , Tan Caiwang , Wan Zhandong , Zhang Hongqiang , Li Yongqiang 
Published: August 2021

AbstractThe QP980-DP980 dissimilar steel joints were fabricated by fiber laser welding. The weld zone (WZ) was fully martensitic structure, and heat-affected zone (HAZ) contained newly-formed martensite and partially tempered martensite (TM) in both steels. The super-critical HAZ of the QP980 side had higher microhardness (~ 549.5 Hv) than that of the WZ due to the finer martensite. A softened zone was present in HAZ of QP980 and DP980, the dropped microhardness of softened zone of the QP980 and DP980 was Δ 21.8 Hv and Δ 40.9 Hv, respectively. Dislocation walls and slip bands were likely formed at the grain boundaries with the increase of strain, leading to the formation of low angle grain boundaries (LAGBs). Dislocation accumulation more easily occurred in the LAGBs than that of the HAGBs, which led to significant dislocation interaction and formation of cracks. The electron back-scattered diffraction (EBSD) results showed the fraction of LAGBs in sub-critical HAZ of DP980 side was the highest under different deformation conditions during tensile testing, resulting in the failure of joints located at the sub-critical HAZ of DP980 side. The QP980-DP980 dissimilar steel joints presented higher elongation (~ 11.21%) and ultimate tensile strength (~ 1011.53 MPa) than that of DP980-DP980 similar steel joints, because during the tensile process of the QP980-DP980 dissimilar steel joint (~ 8.2% and 991.38 MPa), the strain concentration firstly occurred on the excellent QP980 BM. Moreover, Erichsen cupping tests showed that the dissimilar welded joints had the lowest Erichsen value (~ 5.92 mm) and the peak punch force (~ 28.4 kN) due to the presence of large amount of brittle martensite in WZ and inhomogeneous deformation.
Disconnectome of the migraine brain: a “connectopathy” model
Authors: Silvestro Marcello , Tessitore Alessandro , Caiazzo Giuseppina , Scotto di Clemente Fabrizio , Trojsi Francesca , Cirillo Mario , Esposito Fabrizio , Tedeschi Gioacchino , Russo Antonio 
Published: August 2021

Abstract
Background
In the past decades a plethora of studies has been conducted to explore resting-state functional connectivity (RS-FC) of the brain networks in migraine with conflicting results probably due to the variability and susceptibility of signal fluctuations across the course of RS-FC scan. On the other hand, the structural substrates enabling the functional communications among the brain connectome, characterized by higher stability and reproducibility, have not been widely investigated in migraine by means of graph analysis approach. We hypothesize a rearrangement of the brain connectome with an increase of both strength and density of connections between cortical areas specifically involved in pain perception, processing and modulation in migraine patients. Moreover, such connectome rearrangement, inducing an imbalance between the competing parameters of network efficiency and segregation, may underpin a mismatch between energy resources and demand representing the neuronal correlate of the energetically dysfunctional migraine brain.

Methods
We investigated, using diffusion-weighted MRI imaging tractography-based graph analysis, the graph-topological indices of the brain “connectome”, a set of grey matter regions (nodes) structurally connected by white matter paths (edges) in 94 patients with migraine without aura compared to 91 healthy controls.

Results
We observed in migraine patients compared to healthy controls: i) higher local and global network efficiency (p < 0.001) and ii) higher local and global clustering coefficient (p < 0.001). Moreover, we found changes in the hubs topology in migraine patients with: i) posterior cingulate cortex and inferior parietal lobule (encompassing the so-called neurolimbic-pain network) assuming the hub role and ii) fronto-orbital cortex, involved in emotional aspects, and visual areas, involved in migraine pathophysiology, losing the hub role. Finally, we found higher connection (edges) probability between cortical nodes involved in pain perception and modulation as well as in cognitive and affective attribution of pain experiences, in migraine patients when compared to healthy controls (p < 0.001). No correlations were found between imaging and clinical parameters of disease severity.

Conclusion
The imbalance between the need of investing resources to promote network efficiency and the need of minimizing the metabolic cost of wiring probably represents the mechanism underlying migraine patients’ susceptibility to triggers. Such changes in connectome topography suggest an intriguing pathophysiological model of migraine as brain “connectopathy”.
Expression of the circular RNAs in astaxanthin promotes cholesterol efflux from THP-1 cells based on RNA-seq
Authors: Liu Jie , Wei Yue , Lin Yong , Zhang Peiwen , Zhang Zhexiao , Huang Hairong , Wu Hongfu , Zou Tangbin 
Published: August 2021

Abstract
Background
It is reported that circular RNAs (circRNAs) play a key role in atherosclerosis (AS). Foam cell formation, which is the main feature of AS, can be significantly inhibited by cholesterol efflux.

Methods
We established a model of astaxanthin (AST) promoting cholesterol efflux from macrophages through oil red O staining, real-time quantitative PCR (qRT-PCR), and western blot and used RNA sequencing to detect the expression of circRNAs in AST-treated and untreated THP-1 cells. Finally, siRNA transfection screened out circRNAs that were significantly differentially expressed. The data analysis was performed by Student’s t test and P < 0.05 was considered statistically significant.

Results
In the model of AST promoting cholesterol efflux from THP-1 cells, there were a total of 7276 circRNAs differentially expressed, among which the top 25 upregulated and the top 25 downregulated circRNAs were selected based on the log2 (fold change). GO analysis showed that differential expression of circRNAs in biological process (2066/3098; 66.69%), molecular function (543/3098; 17.53%), and cellular component (489/3098; 15.78%). Based on KEGG analysis, RNA transport was the most enriched pathway. Finally, we obtained 3 significantly upregulated circRNAs by siRNA transfection and qRT-PCR.

Conclusions
The 3 differentially expressed circRNAs may play an important role in the process of AST promoting cholesterol efflux and may be used as biomarkers to prevent AS.
Effects of climate change on marine dumped munitions and possible consequence for inhabiting biota
Authors: Scharsack Jörn Peter , Koske Daniel , Straumer Katharina , Kammann Ulrike 
Published: August 2021

AbstractMarine environments are contaminated with enormous amounts of warfare agents due to military activity and exercise, and the disposal of unused ordnance. Due to corrosion of munition shells, substances are leaking from the warfare materials into the environment. It has to be expected that climate change will influence munition corrosion and distribution of their content. Although there is no doubt about the principle toxicity of many of the munition compounds, including their transformation/degradation products, the impact of munition compounds on marine environments, including their biota are yet only at the beginning to be understood. Recently the intake of munition compounds has been confirmed in mussels and fish collected from contaminated areas. It has become clear that dumped munitions are a continuous source of toxic substances leaking into the environment and that ongoing corrosion will worsen the problem. The present review intends to evaluate the available literature on how climate change might influence the contamination of marine environments and inhabiting biota with munition compounds. Direct testing (or modelling) of climate change scenarios in the context of the marine munition problems has yet not been undertaken. Nevertheless, it can be predicted that climate change effects such as rising temperature and higher frequencies of extreme weather events will accelerate the rates at which disposed ordnance corrodes and consequently accelerate the rate at which munition compounds are leaking out. Climate change will cause elevated stress to biota, ranging from temperature stress and lower availability of oxygen to shifts in salinity and pH. In combination, elevated release of munition related compounds and elevated environmental stress, will put biota under threat, in particular in areas with high munition contamination and limited water exchange, such as the Baltic Sea. On a positive side, biodegradation of organic munition compounds by biota and microorganisms is likely to be accelerated with rising temperature.
The miR-200 family in normal mammary gland development
Authors: Roth Majesta J. , Moorehead Roger A. 
Published: August 2021

AbstractThe miR-200 family of microRNAs plays a significant role in inhibiting mammary tumor growth and progression, and its members are being investigated as therapeutic targets. Additionally, if future studies can prove that miR-200s prevent mammary tumor initiation, the microRNA family could also offer a preventative strategy. Before utilizing miR-200s in a therapeutic setting, understanding how they regulate normal mammary development is necessary. No studies investigating the role of miR-200s in embryonic ductal development could be found, and only two studies examined the impact of miR-200s on pubertal ductal morphogenesis. These studies showed that miR-200s are expressed at low levels in virgin mammary glands, and elevated expression of miR-200s have the potential to impair ductal morphogenesis. In contrast to virgin mammary glands, miR-200s are expressed at high levels in mammary glands during late pregnancy and lactation. miR-200s are also found in the milk of several mammalian species, including humans. However, the relevance of miR-200s in milk remains unclear. The increase in miR-200 expression in late pregnancy and lactation suggests a role for miR-200s in the development of alveoli and/or regulating milk production. Therefore, studies investigating the consequence of miR-200 overexpression or knockdown are needed to identify the function of miR-200s in alveolar development and lactation.
Genomic bases underlying the adaptive radiation of core landbirds
Authors: Wu Yonghua , Yan Yi , Zhao Yuanqin , Gu Li , Wang Songbo , Johnson David H. 
Published: August 2021

Abstract
Background
Core landbirds undergo adaptive radiation with different ecological niches, but the genomic bases that underlie their ecological diversification remain unclear.

Results
Here we used the genome-wide target enrichment sequencing of the genes related to vision, hearing, language, temperature sensation, beak shape, taste transduction, and carbohydrate, protein and fat digestion and absorption to examine the genomic bases underlying their ecological diversification. Our comparative molecular phyloecological analyses show that different core landbirds present adaptive enhancement in different aspects, and two general patterns emerge. First, all three raptorial birds (Accipitriformes, Strigiformes, and Falconiformes) show a convergent adaptive enhancement for fat digestion and absorption, while non-raptorial birds tend to exhibit a promoted capability for protein and carbohydrate digestion and absorption. Using this as a molecular marker, our results show relatively strong support for the raptorial lifestyle of the common ancestor of core landbirds, consequently suggesting a single origin of raptors, followed by two secondary losses of raptorial lifestyle within core landbirds. In addition to the dietary niche, we find at temporal niche that diurnal birds tend to exhibit an adaptive enhancement in bright-light vision, while nocturnal birds show an increased adaption in dim-light vision, in line with previous findings.

Conclusions
Our molecular phyloecological study reveals the genome-wide adaptive differentiations underlying the ecological diversification of core landbirds.
Comparative genomic analysis of a naturally born serpentized pig reveals putative mutations related to limb and bone development
Authors: Jiang Yankai , Cao Xinyue , Wang Haibin 
Published: August 2021

AbstractBackgroundIt is believed that natural selection acts on the phenotypical changes caused by mutations. Phenotypically, from fishes to amphibians to reptiles, the emergence of limbs greatly facilitates the landing of ancient vertebrates, but the causal mutations and evolutionary trajectory of this process remain unclear.ResultsWe serendipitously obtained a pig of limbless phenotype. Mutations specific to this handicapped pig were identified using genome re-sequencing and comparative genomic analysis. We narrowed down the causal mutations to particular chromosomes and even several candidate genes and sites, such like a mutation-containing codon in geneBMP7(bone morphogenetic protein) which was conserved in mammals but variable in lower vertebrates.ConclusionsWe parsed the limbless-related mutations in the light of evolution. The limbless pig shows phenocopy of the clades before legs were evolved. Our findings might help deduce the emergence of limbs during vertebrate evolution and should be appealing to the broad community of human genetics and evolutionary biology.
Mid-term outcomes of off-pump versus on-pump coronary artery bypass graft surgery; statistical challenges in comparison
Authors: Sheikhy Ali , Fallahzadeh Aida , Sadeghian Saeed , Forouzannia Khalil , Bagheri Jamshid , Salehi-Omran Abbas , Tajdini Masih , Jalali Arash , Pashang Mina , Hosseini Kaveh 
Published: August 2021

Abstract
Background
Despite several studies comparing off- and on-pump coronary artery bypass grafting (CABG), the effectiveness and outcomes of off-pump CABG still remain uncertain.

Methods
In this registry-based study, we assessed 8163 patients who underwent isolated CABG between 2014 and 2016. Propensity score matching (PSM), inverse probability of weighting (IPW) and covariate adjustment were performed to correct for and minimize selection bias.

Results
The overall mean age of the patients was 62 years, and 25.7% were women. Patients who underwent off-pump CABG had shorter length of hospitalization (p < 0.001), intubation time (p = 0.003) and length of ICU admission (p < 0.001). Off-pump CABG was associated with higher risk of 30-days mortality (OR: 1.7; 95% CI 1.09–2.65; p = 0.019) in unadjusted analysis. After covariate adjustment and matching (PSM and IPW), this difference was not statistically significant. After an average of 36.1 months follow-up, risk of MACCE and all-cause mortality didn’t have significant differences in both surgical methods by adjusting with IPW (HR: 1.03; 95% CI 0.87–1.24; p = 0.714; HR: 0.91; 95% CI 0.73–1.14; p = 578, respectively).

Conclusion
Off-pump and on-pump techniques have similar 30-day mortality (adjusted, PSM and IPW). Off-pump surgery is probably more cost-effective in short term; however, mid-term survival and MACCE trends in both surgical methods are comparable.
Health status measured by Kansas City Cardiomyopathy Questionnaire-12 in primary prevention implantable cardioverter defibrillator patients with heart failure
Authors: Mattsson Gustav , Wallhagen Marita , Magnusson Peter 
Published: August 2021

Abstract
Background
Self-reported health status as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) in patients with primary prevention implantable cardioverter defibrillators (ICDs) has mainly been reported from randomized trials. However, these studies are often limited to short follow-up and are subject to selection bias. The aim of this study was to assess KCCQ-12 in patients with primary prevention ICD due to either ischemic or nonischemic heart failure.

Methods
This cross-sectional observational study included all patients in Region Gävleborg, Sweden, who because of primary prevention due to heart failure, had an ICD or underwent device replacement between 2007 and 2017. After validation using medical records patients were sent and returned the KCCQ-12 by regular mail.

Results
A total of 118 questionnaires were analyzed (response rate 71.1%). The mean age was 70.9 ± 9.8 years, and a minority was female (n = 20, 16.9%). The mean overall summary score was 71.5 ± 22.4, there was no significant difference between ischemic and nonischemic heart failure (69.5 ± 23.1 vs. 74.4 ± 21.3; p = 0.195). Atrial fibrillation at baseline was associated with lower score for the domains Symptom frequency (70.2 ± 23.2 vs. 82.2 ± 19.2; p = 0.006) and Social limitation (62.1 ± 26.0 vs. 75.6 ± 26.6; p = 0.006) as well as the overall summary score (63.9 ± 21.3 vs. 74.8 ± 22.2; p = 0.004).

Conclusion
In a real-world setting, primary prevention ICD patients with heart failure report an acceptable disease-specific health status at long-term follow-up. Ischemic and nonischemic etiology showed similar health status whereas atrial fibrillation was associated with worse outcome.
Prehospital assessment and management of postpartum haemorrhage- healthcare personnel’s experiences and perspectives
Authors: Leonardsen Ann-Chatrin Linqvist , Helgesen Ann Karin , Ulvøy Linn , Grøndahl Vigdis Abrahamsen 
Published: August 2021

Abstract
Background
Postpartum hemorrhage (PPH) is a serious obstetric emergency, and one of the top five causes of maternal mortality globally. The most common causes of PPH include uterine atony, placental disorders, birth trauma and coagulation defects. Timely diagnosis and early management are critical to reduce morbidity, the need for blood transfusion or even mortality. External, manual aortic compression (AC) has been suggested as an intervention that reduce PPH and extend time for control of bleeding or resuscitation. This procedure is not commonly utilized by healthcare personnel. The incidence of home-births is increasing, and competence in PPH assessment and management is essential in prehospital personnel. The objective was to explore prehospital personnel’s competence in PPH and AC, utilizing different tools.

Methods
The study was conducted in a county in South-eastern Norway, including five ambulance stations. All prehospital personnel (n = 250) were invited to participate in a questionnaire study. The questionnaire included the PPH self-efficacy (PPHSE) and PPH collective efficacy (PPHCE) tools, as well as tool developed utilizing the Delphi technique. Descriptive statistics were used to analyze the quantitative data, while quantitative content analysis was used to analyse free-text responses.

Results
A total of 87 prehospital personnel responded to the questionnaire, 57.5% male, mean age 37.9 years. In total, 80.4% were ambulance workers and/or paramedics, and 96.6 and 97.7% respectively reported to need more education or training in PPH. Moreover, 82.8% reported having managed patient(s) with PPH, but only 2.9% had performed AC. Prehospital personnels’ responses varied extensively regarding knowledge about what PPH is, how to estimate and handle PPH, and how to perform AC. Mean self-efficacy varied from 3.3 to 5.6, while collective efficacy varied from 1.9 to 3.8.

Conclusions
This study indicates that prehospital personnel lack knowledge about PPH and AC, due to various responses to the developed questionnaire. Even though AC is an acknowledged intervention in PPH, few participants reported that this was utilized. Our findings emphasize the need for education and training in PPH and PPH handling generally, and in AC specifically.