bluuebunny/crossref_metadata_2025_split huggingface dataset:
TAVI for Pure Non-calcified Aortic Regurgitation Using a Self-Expandable Transcatheter Heart Valve
Authors: Schneeberger Yvonne , Seiffert Moritz , Schaefer Andreas , Bhadra Oliver D. , Schofer Niklas , Pecha Simon , Westermann Dirk , Blankenberg Stefan , Reichenspurner Hermann , Conradi Lenard 
Published: January 2022

Objectives: Transcatheter aortic valve implantation (TAVI) is routinely performed in patients with severe aortic stenosis (AS). For patients with pure non-calcified aortic regurgitation (AR) who are not suitable for open heart surgery no clear recommendations exist and use of TAVI has been largely off-label. We herein report a series of patients treated with the self-expandable AcurateNeo and Neo2 (Boston Scientific Co., Marlborough, MS, USA) transcatheter heart valve (THV) for pure AR.Methods: Between 05/2017 and 03/2021, 9 patients (88.8% female, 74.4 ± 7.1 years, logEuroSCORE II 5.5 ± 3.6%, STS PROM 6.2 ± 3.0%) received transfemoral (TF) TAVI for pure non-calcified AR following an adjusted valve sizing algorithm. Data were retrospectively analyzed according to updated Valve Academic Research Consortium (VARC-2) definitions.Results: Device success was 100%. Early safety was 77.7% (7/10), due to two (22.2%) cases of acute kidney injury. Thirty-day mortality was 0%, in seven (77.7%) patients no or trace paravalvular leakage (PVL) was seen and mild PVL in two (22.2%) patients at 30-day follow-up. No permanent pacemaker (PPM) was required during 30-day follow-up.Conclusion: In this series of selected patients using the Acurate neo THV for pure non-calcified AR, safety and efficacy were demonstrated. Thirty-day mortality as well as PPM implantation and PVL rates showed excellent results in this high-risk patient cohort. These results will have to be confirmed in larger patient cohorts.
Comparative Quantitative Aortographic Assessment of Regurgitation in Patients Treated With VitaFlow Transcatheter Heart Valve vs. Other Self-Expanding Systems
Authors: Wang Rutao , Kawashima Hideyuki , Gao Chao , Mou Fangjun , Li Ping , Zhang Junjie , Yang Jian , Luo Jianfang , Mylotte Darren , Wijns William , Onuma Yoshinobu , Soliman Osama , Tao Ling , Serruys Patrick W. 
Published: January 2022

ObjectivesTo compare the quantitative angiographic aortic regurgitation (AR) of six self-expanding valves after transcatheter aortic valve replacement (TAVR).BackgroundQuantitative videodensitometric aortography (LVOT-AR) is an accurate and reproducible tool for assessment of AR following TAVR.MethodsThis is a retrospective central core-lab analysis of 1,257 consecutive cine aortograms performed post-TAVR. The study included 107 final aortograms of consecutive patients who underwent TAVR with first-generation VitaFlow in four Chinese centers and 1,150 aortograms with five other transcatheter aortic valves (Evolut Pro, Evolut R, CoreValve, Venus A-Valve, and Acurate Neo). LVOT-AR analyses of these five valves were retrieved from a previously published pooled database.ResultsAmong 172 aortograms of patients treated with VitaFlow, 107 final aortograms (62.2%) were analyzable by LVOT-AR. In this first in man eight cases necessitated a procedural valve in valve due to inappropriate TAVR positioning and severe aortic paravalvular regurgitation. In the VitaFlow group, the mean LVOT-AR of the intermediate aortograms was 7.3 ± 7.8% and the incidence of LVOT-AR &gt;17% was 8.6%. The mean LVOT-AR of the final aortogram was 6.1 ± 6.4% in the VitaFlow group, followed by Evolut Pro (7.3 ± 6.5%), Evolut R (7.9 ± 7.4%), Venus A-valve (8.9 ± 10.0%), Acurate Neo (9.6 ± 9.2%), and lastly CoreValve (13.7 ± 10.7%) (analysis of variance p &lt; 0.001). Post hoc 2-by-2 testing showed that CoreValve had significantly higher LVOT-AR compared with each of the other five THVs. No statistical difference in LVOT-AR was observed between VitaFlow, Evolut Pro, Evolut R, Acurate Neo, and Venus A-valves. The VitaFlow system had the lowest proportion of patients with LVOT-AR &gt;17% (4.7%) (AR after the final aortograms), followed by Evolut Pro (5.3%), Evolut R (8.8%), Acurate Neo (11.3%), Venus A-valve (14.2%), and CoreValve (30.1%) (chi-square p &lt; 0.001).ConclusionCompared to other commercially available self-expanding valves, VitaFlow seems to have a low degree of AR and a low proportion of patients with ≥moderate/severe AR as assessed by quantitative videodensitometric angiography. Once the learning phase is completed, comparisons of AR between different transcatheter heart valves should be attempted in a prospective randomized trial.
Standard Modifiable Cardiovascular Risk Factors Mediate the Association Between Elevated Hair Cortisol Concentrations and Coronary Artery Disease
Authors: Stomby Andreas , Strömberg Susanna , Theodorsson Elvar , Olsen Faresjö Åshild , Jones Mike , Faresjö Tomas 
Published: January 2022

BackgroundIncreased cortisol exposure is a risk factor for coronary artery disease (CAD). It is not clear to what degree this risk is independent from the standard modifiable risk factors (SMuRFs) dyslipidemia, hypertension, and diabetes.AimTo use path analysis to test the direct and indirect association, mediated by SMuRFs, between long-term cortisol levels measured in hair cortisol concentration (HCC) and CAD.MethodsHair was sampled from patients admitted with acute myocardial infarction (n = 203) and a population-based sample without a diagnosis or symptoms of CAD (n = 3,134). The HCC was analyzed using radioimmunoassay and all the participants reported whether they were diagnosed with or treated for diabetes, hypertension, and hyperlipidemia. Path analysis was used to test to what degree the association between logarithmized (ln) HCC and CAD was direct or indirect, mediated by SMuRFs.ResultsParticipants with CAD had elevated HCC compared to those without elevated HCC [median interquartile range (IQR): 75.2 (167.1) vs. 23.6 (35.0) pg/mg, p &lt; 0.0001]. Higher HCC was associated with diabetes, hypertension, and hyperlipidemia, which, in turn, were associated with CAD. In path models, 80% of the association between ln(HCC) and CAD were mediated by SMuRFs, while the direct path between ln(HCC) and CAD was not statistically significant.ConclusionThe SMuRFs diabetes, hyperlipidemia, and hypertension mediate the association between ln(HCC) and CAD. Some association between ln(HCC) and CAD did not operate via the SMuRFs considered and might have a pathway through atherosclerosis or inflammation.
Identification of Shared Genes and Pathways in Periodontitis and Type 2 Diabetes by Bioinformatics Analysis
Authors: Kang Junho , Kwon Eun Jung , Ha Mihyang , Lee Hansong , Yu Yeuni , Kang Ji Wan , Kim Yeongjoo , Lee Eun Young , Joo Ji-Young , Heo Hye Jin , Kim Eun Kyoung , Kim Tae Woo , Kim Yun Hak , Park Hae Ryoun 
Published: January 2022

IntroductionIt is well known that the presence of diabetes significantly affects the progression of periodontitis and that periodontitis has negative effects on diabetes and diabetes-related complications. Although this two-way relationship between type 2 diabetes and periodontitis could be understood through experimental and clinical studies, information on common genetic factors would be more useful for the understanding of both diseases and the development of treatment strategies.Materials and MethodsGene expression data for periodontitis and type 2 diabetes were obtained from the Gene Expression Omnibus database. After preprocessing of data to reduce heterogeneity, differentially expressed genes (DEGs) between disease and normal tissue were identified using a linear regression model package. Gene ontology and Kyoto encyclopedia of genes and genome pathway enrichment analyses were conducted using R package ‘vsn’. A protein-protein interaction network was constructed using the search tool for the retrieval of the interacting genes database. We used molecular complex detection for optimal module selection. CytoHubba was used to identify the highest linkage hub gene in the network.ResultsWe identified 152 commonly DEGs, including 125 upregulated and 27 downregulated genes. Through common DEGs, we constructed a protein-protein interaction and identified highly connected hub genes. The hub genes were up-regulated in both diseases and were most significantly enriched in the Fc gamma R-mediated phagocytosis pathway.DiscussionWe have identified three up-regulated genes involved in Fc gamma receptor-mediated phagocytosis, and these genes could be potential therapeutic targets in patients with periodontitis and type 2 diabetes.
Association of Brachial Ankle Pulse Wave Velocity With New Onset Stroke in Hypertensive Patients Aged Less Than 65 With Normal Fasting Glucose Among Chinese Community-Based Population
Authors: Li Cao , Wang Zhuo , Liu Shuai , Guo Shanshan , Song Yun , Liu Lishun , Zhou Ziyi , Wang Binyan , Huang Meiqing , Wang Ruiqing , Zhai Lijie , Gao Yiming , Qin Xianhui , Wang Xiaobin , Zheng Huaguang , Zhao Zhigang 
Published: January 2022

BackgroundPrevious studies have shown an association of stroke and brachial ankle pulse wave velocity (baPWV). However, due to limitations on total population size and small numbers of stroke cases, lack of power has prevented further detection among subgroups such as age and laboratory testing.MethodsA total of 19217 participants including 660 incident stroke patients were pooled in the present study. Participants were divided to 2 groups, aged less than 65 years [56.0 (50.0, 61.0)] and aged 65 years or more [70.0 (67.0, 74.0)].ResultsAfter adjustment for demographic, anthropometric, and laboratory parameters, the incident stroke was positively associated to baPWV in the group aged less than 65 years (OR, 1.16; 95% CI, 1.05–1.28), but not in the older group aged 65 or more. When baPWV was assigned as quartiles, a significant, increased risk of new-onset stroke was found in quartiles 3-4 compared with quartile 1. In addition, the predictive value of baPWV for incident stroke was modified by fasting glucose in participants aged less than 65 years (P-interaction = 0.010). An increase in baPWV was strongly, positively associated to new-onset stroke in the subgroup of normal fasting glucose (&lt; 5.6 mmol/L) (OR, 1.34; 95% CI, 1.15 - 1.57), but no effect was seen in the impaired fasting glucose (5.6-7.0 mmol/L) or diabetic fasting glucose (&gt; 7.0 mmol/L) subgroups.ConclusionsIncreased baPWV was significantly associated with new-onset stroke in a hypertensive population aged less than 65 years. Particularly, it is of great importance to monitor baPWV for predicting incident stroke in “relatively healthy” hypertensive patients, i.e. aged less than 65 years with normal fasting glucose.
Quantitative Proteomics Revealed the Pharmacodynamic Network of Bugu Shengsui Decoction Promoting Osteoblast Proliferation
Authors: Wei Xu , Qi Baoyu , Ma Ruyun , Zhang Yili , Liu Ning , Fang Shengjie , Zhu Yanning , Xie Yanming , Dai Jianye , Zhu Liguo 
Published: January 2022

Background and ObjectiveWith high morbidity and disability, osteoporosis is a worldwide bone metabolism disease, regulated by complex pathological processes. Insufficient osteogenesis is greatly essential to osteoporosis. Traditional Chinese Medicine, a complex natural herbal medicine system, has increasingly attracted attention all over the world. Bugu Shengsui Decoction, a compound formula for osteoporosis, has significant clinical effects in the treatment of osteoporosis. Yet the detailed mechanisms are unclear. Thus, we investigated the effects and mechanism of Bugu Shengsui Decoction on osteoporotic rats and osteoblasts in vitro.MethodsIn this study, we evaluated the effect of Bugu Shengsui Decoction in an animal model of orchiectomy. Multi-pharmacology indexes revealed that Bugu Shengsui Decoction obviously improved bone metabolism, bone mineral density, bone morphology, and biomechanics in the castrated rats. Then, serum pharmacology was employed to unveil that Bugu Shengsui Decoction promoted the proliferation and differentiation of osteoblasts. Moreover, quantitative proteomics combined with RNA interference assay was used to analyze and verify the pathway and key targets in pro-proliferation of MC3T3-E1 cells.ResultsBugu Shengsui Decoction obviously improved the worse parameters of bone metabolism, bone mineral density, bone morphology, and biomechanics in a castrated rat model. In vitro, Bugu Shengsui Decoction exerted proliferation- and differentiation-promoting effects of osteoblasts induced by serum starvation. Moreover, quantitative proteomics analysis combined with RNA interfere assay illustrated that Bugu Shengsui Decoction promoted osteogenesis via the PI3K-AKT pathway.ConclusionSummarily, our discoveries certify that Bugu Shengsui Decoction is an effective treatment for osteoporosis via PI3K-AKT. This study is not only a beneficial attempt to explore the detailed mechanism of Traditional Chinese formula but also will provide inspiration for the treatment strategy of osteoporosis.
The First Report of a Missense Variant in RFX2 Causing Non-Syndromic Tooth Agenesis in a Consanguineous Pakistani Family
Authors: Khan Sher Alam , Khan Saadullah , Muhammad Noor , Rehman Zia Ur , Khan Muhammad Adnan , Nasir Abdul , Kalsoom Umm-e- , Khan Anwar Kamal , Khan Hassan , Wasif Naveed 
Published: January 2022

Background: The syndromic and non-syndromic congenital missing teeth phenotype is termed tooth agenesis. Since tooth agenesis is a heterogeneous disorder hence, the patients show diverse absent teeth phenotypes. Thus identifying novel genes involved in the morphogenesis of ectodermal appendages, including teeth, paves the way for establishing signaling pathways.Methods and Results: We have recruited an autosomal recessive non-syndromic tooth agenesis family with two affected members. The exome sequencing technology identified a novel missense sequence variant c.1421T &gt; C; p.(Ile474Thr) in a regulatory factor X (RFX) family member (RFX2, OMIM: 142,765). During the data analysis eight rare variants on various chromosomal locations were identified, but the co-segregation analysis using Sanger sequencing confirmed the segregation of only two variants RFX2: c.1421T &gt; C; p.(Ile474Thr), DOHH: c.109C &gt; G; p.(Pro37Ala) lying in a common 7.1 MB region of homozygosity on chromosome 19p13.3. Furthermore, the online protein prediction algorithms and protein modeling analysis verified the RFX2 variant as a damaging genetic alteration and ACMG pathogenicity criteria classified it as likely pathogenic. On the other hand, the DOHH variant showed benign outcomes.Conclusion:RFX2 regulates the Hedgehog and fibroblast growth factor signaling pathways, which are involved in the epithelial and mesenchymal interactions during tooth development. Prior animal model studies have confirmed the expression of rfx2 at a developmental stage governing mouth formation. Moreover, its regulatory role and close association with ciliary and non-ciliary genes causing various dental malformations makes it a potential candidate gene for tooth agenesis phenotype. Further studies will contribute to exploring the direct role of RFX2 in human tooth development.
Genomic Analysis Uncovers Immune Microenvironment Characteristics and Drug Sensitivity of Ferroptosis in Breast Cancer Brain Metastasis
Authors: Zhu Lei , Chen Mu , Huang Bingsong , Zhang Tao , Chen Kui , Lian Hao , Liu Min , Zhao Kaijun , Pang Ying , Zhang Jing , Li Qinchuan , Zhong Chunlong 
Published: January 2022

Background: The role of ferroptosis in breast cancer brain metastasis (BCBM) is unclear. This study aimed to explore the ferroptosis-related genes (FRG) relations with the tumor microenvironment, as well as evaluate their values in predicting survival and drug sensitivity in patients with BCBM.Materials and Methods: Genes expression and clinical data were downloaded from Gene Expression Omnibus (GEO). Univariate and multivariate Cox regression analyses were performed to explore the independent prognostic factors. Consensus cluster principal component analysis (PCA) was used to establish the ferroptosis score. Immunological signatures were analyzed by the single-sample gene set enrichment analysis (ssGSEA). Drug sensitivity was evaluated through the estimated half-maximal inhibitory concentration (IC50). Finally, results were validated in external cohorts.Results: Fourteen significantly different FRG were identified between breast cancer (BC) and BCBM tissues. Survival analysis demonstrated HMOX1, PEBP1, KEAP1, and LPCAT3 were significantly associated with overall survival (OS) and relapse-free survival (RFS) (all p &lt; 0.05). High ferroptosis score was correlated with iron ion homeostasis, iron metabolism, higher stromal cells and immune cells scores. Patients with high- and low-ferroptosis scores were characterized by different drug sensitivities. Following external validations, the ferroptosis had distinct expression profiles between the BC and BCBM, and could serve as biomarkers for OS and drug response.Conclusion: Our findings suggested that ferroptosis may be involved in the process of BCBM, and ferroptosis could serve as prognostic biomarkers. Evaluation of ferroptosis may deepen our understanding about the tumor microenvironment, and could help clinicians to make individualized therapy.
Construction and Evaluation of Recombinant Attenuated Edwardsiella piscicida Vaccine (RAEV) Vector System Encoding Ichthyophthirius multifiliis (Ich) Antigen IAG52B
Authors: Swain Banikalyan , Powell Cole T. , Curtiss Roy 
Published: January 2022

We have successfully designed and constructed a RAEV vector system with regulated-delayed attenuation in vivo attributes that synthesizes Ichthyophthirius multifiliis (Ich) protective antigen IAG52B to enable vaccination of fish susceptible to edwardsiellosis and white spot disease. The first feature of this vaccine delivery system is an Edwardsiella piscicida strain carrying genomic deletions of asdA. AsdA is an enzyme necessary for the synthesis of diaminopimelic acid (DAP), which is an essential component of the peptidoglycan layer of the cell wall of Gram-negative bacteria. asdA mutant strains have obligate growth requirements for DAP in the medium or a plasmid vector with the wild-type asdA gene enabling synthesis of DAP. This balanced-lethal plasmid vector-host system in E. piscicida enables as a second feature the synthesis of recombinant antigens to induce protective immunity against fish pathogens. Recombinant protective antigen IAG52B from the fish pathogen I. multifiliis was synthesized by RAEV strains harboring the AsdA+ plasmid pG8R8029. The third feature of this vaccine strain is a regulated-delayed attenuation in vivo phenotype that is based on the replacement of an arabinose-regulated araC ParaBAD cassette for the promoters of the fur and crp genes of E. piscicida such that the expression of these genes is dependent on arabinose provided during growth. Thus, following colonization, the Fur and Crp proteins stop being synthesized due to the lack of arabinose and attenuation is progressively achieved in vivo to prevent generation of diseases symptoms. Our vaccine strain χ16022 with the genotype ΔasdA10 ΔPfur170::TT araC ParaBADfur ΔPcrp68::TT araC ParaBADcrp contains the AsdA+ plasmid, pG8R8029, which encodes the IAG52B antigen. Vaccine strain χ16022(pG8R8029) is attenuated and induces systemic and mucosal IgM titer against E. piscicida and Ich in zebrafish. In addition, transcript levels of tnf-α, il-1β, il-6 and il-8 were significantly increased in different tissues of vaccinated zebrafish compared to unimmunized fish. Zebrafish vaccinated with χ16022(pG8R8029) showed 60% survival upon intracoelomic (i.c.) challenge with a lethal dose of virulent E. piscicida strain J118. Our RAEV system could be used as a generalized vaccine-vector system to protect teleost fish against multiple bacterial, viral and parasitic infectious diseases.
Innate Immune Responses of Vaccinees Determine Early Neutralizing Antibody Production After ChAdOx1nCoV-19 Vaccination
Authors: Shen Ching-Fen , Yen Chia-Liang , Fu Yi-Chen , Cheng Chao-Min , Shen Tzu-Chi , Chang Pei-De , Cheng Kuang-Hsiung , Liu Ching-Chuan , Chang Yu-Tzu , Chen Po-Lin , Ko Wen-Chien , Shieh Chi-Chang 
Published: January 2022

BackgroundInnate immunity, armed with pattern recognition receptors including Toll-like receptors (TLR), is critical for immune cell activation and the connection to anti-microbial adaptive immunity. However, information regarding the impact of age on the innate immunity in response to SARS-CoV2 adenovirus vector vaccines and its association with specific immune responses remains scarce.MethodsFifteen subjects between 25-35 years (the young group) and five subjects between 60-70 years (the older adult group) were enrolled before ChAdOx1 nCoV-19 (AZD1222) vaccination. We determined activation markers and cytokine production of monocyte, natural killer (NK) cells and B cells ex vivo stimulated with TLR agonist (poly (I:C) for TLR3; LPS for TLR4; imiquimod for TLR7; CpG for TLR9) before vaccination and 3-5 days after each jab with flow cytometry. Anti-SARS-CoV2 neutralization antibody titers (surrogate virus neutralization tests, sVNTs) were measured using serum collected 2 months after the first jab and one month after full vaccination.ResultsThe older adult vaccinees had weaker vaccine-induced sVNTs than young vaccinees after 1st jab (47.2±19.3% vs. 21.2±22.2%, p value&lt;0.05), but this difference became insignificant after the 2nd jab. Imiquimod, LPS and CpG strongly induced CD86 expression in IgD+CD27- naïve and IgD-CD27+ memory B cells in the young group. In contrast, only the IgD+ CD27- naïve B cells responded to these TLR agonists in the older adult group. Imiquimode strongly induced the CD86 expression in CD14+ monocytes in the young group but not in the older adult group. After vaccination, the young group had significantly higher IFN-γ expression in CD3- CD56dim NK cells after the 1st jab, whilst the older adult group had significantly higher IFN-γ and granzyme B expression in CD56bright NK cells after the 2nd jab (all p value &lt;0.05). The IFN-γ expression in CD56dim and CD56bright NK cells after the first vaccination and CD86 expression in CD14+ monocyte and IgD-CD27-double-negative B cells after LPS and imiquimod stimulation correlated with vaccine-induced antibody responses.ConclusionsThe innate immune responses after the first vaccination correlated with the neutralizing antibody production. Older people may have defective innate immune responses by TLR stimulation and weak or delayed innate immune activation profile after vaccination compared with young people.