bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Transapical Transcatheter Mitral Valve Implantation
Authors: Hsiung Ming-Chon , Yin Wei-Hsian , Lee Yung-Tsai , Tsao Tien-Ping , Lee Kuo-Chen , Huang Kuan-Chih , Chen Pei-En , Chiang Wei-Hsuan , Tung Tao-Hsin , Wei Jeng 
Published: June 2021

Purpose: In this study, transapical transcatheter mitral valve-in-valve implantation (TAMVI) was compared with surgical redo mitral valve replacement (SRMVR) in terms of clinical outcomes.Methods: We retrospectively identified patients with degenerated mitral bioprosthesis or failed annuloplasty rings who underwent redo SRMVR or TAMVI at our medical center. Clinical outcomes were based on echocardiography results.Results: We retrospectively identified patients with symptomatic mitral bioprosthetic valve dysfunction (n = 58) and failed annuloplasty rings (n = 14) who underwent redo SRMVR (n = 36) or TAMVI (n = 36). The Society of Thoracic Surgeons Predicted Risk of Mortality scores were higher in the TAMVI group (median: 9.52) than in the SRMVR group (median: 5.59) (p-value = 0.02). TAMVI patients were more severe in New York Heart Association (p-value = 0.04). The total procedure time (skin to skin) and length of stay after procedures were significantly shorter in the TAMVI group, and no significant difference in mortality was noted after adjustment for confounding factors (p-value = 0.11). The overall mean mitral valve pressure gradient was lower in the TAMVI group than in the SRMVR group at 24 months (p &lt; 0.01). Both groups presented a decrease in the severity of mitral and tricuspid regurgitation at 3–24 months.Conclusions: In conclusion, the statistical analysis is still not robust enough to make a claim that TAMVI is an appropriate alternative. The outcome of the patient appears only to be related to the patient's pre-operative STS score. Additional multi-center, longitudinal studies are warranted to adequately assess the effect of TAMVI.
Geologic and Structural Evolution of the NE Lau Basin, Tonga: Morphotectonic Analysis and Classification of Structures Using Shallow Seismicity
Authors: Anderson Melissa O. , Norris-Julseth Chantal , Rubin Kenneth H. , Haase Karsten , Hannington Mark D. , Baxter Alan T. , Stewart Margaret S. 
Published: June 2021

The transition from subduction to transform motion along horizontal terminations of trenches is associated with tearing of the subducting slab and strike-slip tectonics in the overriding plate. One prominent example is the northern Tonga subduction zone, where abundant strike-slip faulting in the NE Lau back-arc basin is associated with transform motion along the northern plate boundary and asymmetric slab rollback. Here, we address the fundamental question: how does this subduction-transform motion influence the structural and magmatic evolution of the back-arc region? To answer this, we undertake the first comprehensive study of the geology and geodynamics of this region through analyses of morphotectonics (remote-predictive geologic mapping) and fault kinematics interpreted from ship-based multibeam bathymetry and Centroid-Moment Tensor data. Our results highlight two notable features of the NE Lau Basin: 1) the occurrence of widely distributed off-axis volcanism, in contrast to typical ridge-centered back-arc volcanism, and 2) fault kinematics dominated by shallow-crustal strike slip-faulting (rather than normal faulting) extending over ∼120 km from the transform boundary. The orientations of these strike-slip faults are consistent with reactivation of earlier-formed normal faults in a sinistral megashear zone. Notably, two distinct sets of Riedel megashears are identified, indicating a recent counter-clockwise rotation of part of the stress field in the back-arc region closest to the arc. Importantly, the Riedel structures identified in this study directly control the development of complex volcanic-compositional provinces, which are characterized by variably-oriented spreading centers, off-axis volcanic ridges, extensive lava flows, and point-source rear-arc volcanoes. This study adds to our understanding of the geologic and structural evolution of modern backarc systems, including the association between subduction-transform motions and the siting and style of seafloor volcanism.
The Influences of TSH Stimulation Level, Stimulated Tg Level and Tg/TSH Ratio on the Therapeutic Effect of 131I Treatment in DTC Patients
Authors: Zheng Wei , Rui Zhongying , Wang Xuan , Li Ning , Tan Jian , Liu Wei 
Published: June 2021

PurposeTo study the influences of pre-ablation TSH stimulation level, sTg and sTg/TSH ratio on the therapeutic effect of the first 131I treatment in DTCs.MethodsAccording to the thyroid stimulating hormone (TSH) levels (mU/l), all the 479 differentiated thyroid cancer (DTC) patients were divided into two groups: TSH &lt; 30 and TSH ≥ 30. The TSH ≥ 30 group was divided into three subgroups: 30 ≤ TSH &lt; 60, 60 ≤ TSH &lt; 90 and TSH ≥ 90. The clinical features and the therapeutic effects of the first 131I treatment were analyzed. The cutoffs of stimulated thyroglobulin (sTg) and sTg/TSH ratio were calculated to predict the therapeutic effect of 131I treatment.ResultsAmong the three subgroups, the TSH ≥ 90 subgroup was younger and less likely to be associated with cervical lymph node metastasis (LNM). The postoperative levothyroxine (L-T4) dose in the 60 ≤ TSH &lt; 90 subgroup was the lowest. Between the two groups, patients in the TSH &lt; 30 group had higher postoperative L-T4 dose and longer thyroid hormone withdrawal (THW) time. The excellent response rates six months after the first 131I treatment among the three subgroups and between the two groups were not of statistical significance. The distribution of different TSH stimulation levels among each response group was similar. The cutoffs for the better therapeutic effect of the first 131I treatment in sTg and sTg/TSH were &lt; 9.51 ng/ml and &lt; 0.11, respectively. Both univariate and multivariate logistic regressions showed that cervical LNM, distant metastasis, higher sTg and higher sTg/TSH ratio predicted poorer therapeutic effect.ConclusionsThere was no significant influence of TSH stimulation levels before the first 131I treatment on the therapeutic effect of DTC. The sTg/TSH ratio can be considered as another predictor of 131I therapeutic effect.
CRISPR/Cas9 ADCY7 Knockout Stimulates the Insulin Secretion Pathway Leading to Excessive Insulin Secretion
Authors: Alhaidan Yazeid , Christesen Henrik Thybo , Lundberg Elena , Balwi Mohammed A. Al , Brusgaard Klaus 
Published: June 2021

AimDespite the enormous efforts to understand Congenital hyperinsulinism (CHI), up to 50% of the patients are genetically unexplained. We aimed to functionally characterize a novel candidate gene in CHI.PatientA 4-month-old boy presented severe hyperinsulinemic hypoglycemia. A routine CHI genetic panel was negative.MethodsA trio-based whole-exome sequencing (WES) was performed. Gene knockout in the RIN-m cell line was established by CRISPR/Cas9. Gene expression was performed using real-time PCR.ResultsHyperinsulinemic hypoglycemia with diffuse beta-cell involvement was demonstrated in the patient, who was diazoxide-responsive. By WES, compound heterozygous variants were identified in the adenylyl cyclase 7, ADCY7 gene p.(Asp439Glu) and p.(Gly1045Arg). ADCY7 is calcium-sensitive, expressed in beta-cells and converts ATP to cAMP. The variants located in the cytoplasmic domains C1 and C2 in a highly conserved and functional amino acid region. RIN-m(-/-Adcy7) cells showed a significant increase in insulin secretion reaching 54% at low, and 49% at high glucose concentrations, compared to wild-type. In genetic expression analysis Adcy7 loss of function led to a 34.1-fold to 362.8-fold increase in mRNA levels of the insulin regulator genes Ins1 and Ins2 (p ≤ 0.0002), as well as increased glucose uptake and sensing indicated by higher mRNA levels of Scl2a2 and Gck via upregulation of Pdx1, and Foxa2 leading to the activation of the glucose stimulated-insulin secretion (GSIS) pathway.ConclusionThis study identified a novel candidate gene, ADCY7, to cause CHI via activation of the GSIS pathway.
Effectiveness of a Yoga-Based Lifestyle Protocol (YLP) in Preventing Diabetes in a High-Risk Indian Cohort: A Multicenter Cluster-Randomized Controlled Trial (NMB-Trial)
Authors: Raghuram Nagarathna , Ram Venkat , Majumdar Vijaya , SK Rajesh , Singh Amit , Patil Suchitra , Anand Akshay , Judu Ilavarasu , Bhaskara Srikanta , Basa Jagannadha Rao , Nagendra Hongasandra Ramarao 
Published: June 2021

IntroductionThough several lines of evidence support the utility of yoga-based interventions in diabetes prevention, most of these studies have been limited by methodological issues, primarily sample size inadequacy. Hence, we tested the effectiveness of yoga-based lifestyle intervention against diabetes risk reduction in multicentre, large community settings of India, through a single-blind cluster-randomized controlled trial, Niyantrita Madhumeha Bharat Abhiyan (NMB). Research Design and MethodsNMB-trial is a multicentre cluster-randomized trial conducted in 80 clusters [composed of rural units (villages) and urban units (Census Enumeration Blocks)] randomly assigned in a 1:1 ratio to intervention and control groups. Participants were individuals (age, 20–70 years) with prediabetes (blood HbA1c values in the range of 5.7–6.4%) and IDRS ≥ 60. The intervention included the practice of yoga-based lifestyle modification protocol (YLP) for 9 consecutive days, followed by daily home and weekly supervised practices for 3 months. The control cluster received standard of care advice for diabetes prevention. Statistical analyses were performed on an intention-to-treat basis, using available and imputed datasets. The primary outcome was the conversion from prediabetes to diabetes after the YLP intervention of 3 months (diagnosed based upon HbA1c cutoff &gt;6.5%). Secondary outcome included regression to normoglycemia with HbA1c &lt;5.7%.ResultsA total of 3380 (75.96%) participants were followed up at 3 months. At 3 months post-intervention, overall, diabetes developed in 726 (21.44%) participants. YLP was found to be significantly effective in halting progression to diabetes as compared to standard of care; adjusted RRR was 63.81(95% CI = 56.55–69.85). The YLP also accelerated regression to normoglycemia [adjusted Odds Ratio (adjOR) = 1.20 (95% CI, 1.02–1.43)]. Importantly, younger participants (≤40 years) were found to regress to normoglycemia more effectively than the older participants Pinteraction&lt;0.001. ConclusionBased on the significant risk reduction derived from the large sample size, and the carefully designed randomized yoga-based intervention on high-risk populations, the study is a preliminary but strong proof-of-concept for yoga as a potential lifestyle-based treatment to curb the epidemic of diabetes. The observed findings also indicate a potential of YLP for diabetes prevention in low/moderate risk profile individuals that needs large-scale validation.Trial RegistrationClinical Trial Registration Number: CTRI/2018/03/012804.
Low Moisture Anhydrous Ammonia Pretreatment of Four Lignocellulosic Materials—Distillers Dried Grains With Solubles, Corn Gluten Feed, Corn Fiber, and Oil Palm Frond
Authors: Mahmud Nazira , Rosentrater Kurt A. 
Published: June 2021

Lignin and hemicellulose structures in cellulosic materials serve as a barrier for enzyme reactions. A pretreatment step is often needed to break these components to allow the biomass to be utilized as a source of value-added products. Various available pretreatment methods possess common drawbacks of the high amount of liquid and chemical requirements, harsh process conditions, and the high amount of waste produced, which driving up the production costs of bioproducts. Low moisture anhydrous ammonia (LMAA) pretreatment capable of eliminating those drawbacks. In this study, Distillers Dried Grains with Solubles (DDGS), corn gluten feed (CGF), corn fiber (CF), and oil palm frond (OPF) with different moisture contents were subjected to LMAA pretreatment at the specific ammonia loading rate, 1 h ammoniation, and 75°C incubation temperature. This pretreatment successfully decreased the lignin content of the materials, increased their percentage of α-cellulose, and improved enzymatic digestibility for most of the materials tested. The effect of moisture content (30 and 50% db) was found to be more significant than that of incubation time (24 and 72 h).
How Children Are Protected From COVID-19? A Historical, Clinical, and Pathophysiological Approach to Address COVID-19 Susceptibility
Authors: Massalska Magdalena Anna , Gober Hans-Jürgen 
Published: June 2021

The origin and the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) in early 2020 was accompanied by high rates of mortality in regions belonging to the ancient silk road, such as the south of China, Iran, Turkey and the northern parts of Italy. However, children seem to be spared in the epidemic as very small percentage worldwide being ill. The protection of children and neonates suggests the involvement of a specific component of adaptive immunity present at early development. Native immunoglobulin belonging to the class of IgM is abundantly present in neonates and children and is known for its recognition of self- and altered self-antigens. Native IgM may be able to neutralize virus by the recognition of endogenous “danger signal” encoded in the viral envelope and originally imprinted in the membranes of infected and stressed cells. Noteworthy, thrombosis and vasculitis, two symptoms in severely affected adult and pediatric patients are shared between COVID-19 and patients with Behcet’s disease, an autoimmune disorder exhibiting a region-specific prevalence in countries of the former silk road. Molecular mechanisms and clinical indicators suggest reactive oxygen species as trigger factor for severe progression of COVID-19 and establish a link to the innate immune defense against bacteria. The selective pressure exerted by bacterial pathogens may have shaped the genetics of inhabitants at this ancient trade route in favor of bacterial defense, to the detriment of severe COVID-19 progression in the 21th century.
Unbiased Analysis of Temporal Changes in Immune Serum Markers in Acute COVID-19 Infection With Emphasis on Organ Failure, Anti-Viral Treatment, and Demographic Characteristics
Authors: Laudanski Krzysztof , Jihane Hajj , Antalosky Brook , Ghani Danyal , Phan Uyen , Hernandez Ruth , Okeke Tony , Wu Junnan , Rader Daniel , Susztak Katalin 
Published: June 2021

Identification of novel immune biomarkers to gauge the underlying pathology and severity of COVID-19 has been difficult due to the lack of longitudinal studies. Here, we analyzed serum collected upon COVID-19 admission (t1), 48 hours (t2), and seven days later (t3) using Olink proteomics and correlated to clinical, demographics, and therapeutic data. Older age positively correlated with decorin, pleiotrophin, and TNFRS21 but inversely correlated with chemokine (both C-C and C-X-C type) ligands, monocyte attractant proteins (MCP) and TNFRS14. The burden of pre-existing conditions was positively correlated with MCP-4, CAIX, TWEAK, TNFRS12A, and PD-L2 levels. Individuals with COVID-19 demonstrated increased expression of several chemokines, most notably from the C-C and C-X-C family, as well as MCP-1 and MCP-3 early in the course of the disease. Similarly, deceased individuals had elevated MCP-1 and MCP-3 as well as Gal-9 serum levels. LAMP3, GZMB, and LAG3 at admission correlated with mortality. Only CX3CL13 and MCP-4 correlated positively with APACHE score and length of stay, while decorin, MUC-16 and TNFRSF21 with being admitted to the ICU. We also identified several organ-failure-specific immunological markers, including those for respiratory (IL-18, IL-15, Gal-9) or kidney failure (CD28, VEGF). Treatment with hydroxychloroquine, remdesivir, convalescent plasma, and steroids had a very limited effect on the serum variation of biomarkers. Our study identified several potential targets related to COVID-19 heterogeneity (MCP-1, MCP-3, MCP-4, TNFR superfamily members, and programmed death-ligand), suggesting a potential role of these molecules in the pathology of COVID-19.
Adverse Events Associated With Anti-IL-23 Agents: Clinical Evidence and Possible Mechanisms
Authors: Ru Yi , Ding Xiaojie , Luo Ying , Li Hongjin , Sun Xiaoying , Zhou Mi , Zhou Yaqiong , Kuai Le , Xing Meng , Liu Liu , Luo Yue , Song Jiankun , Chen Jiale , Li Bin , Li Xin 
Published: June 2021

BackgroundAnti-interleukin (IL)-23 agents are widely used for autoimmune disease treatment; however, the safety and risks of specific symptoms have not been systematically assessed.ObjectivesThe aim of this study was to summarize the characteristics and mechanisms of occurrence of five immunological and non-immunological adverse events caused by different anti-IL-23 agents.MethodsThe Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched for eligible randomized clinical trials published from inception through May 1, 2020. Randomized clinical trials that reported at least one type of adverse event after treatment were included, regardless of sex, age, ethnicity, and diagnosis. Two investigators independently screened and extracted the characteristics of the studies, participants, drugs, and adverse event types. The Cochrane Handbook was used to assess the methodological quality of the included randomized clinical trials. Heterogeneity was assessed using the I2 statistic. Meta-regression was applied to determine the sources of heterogeneity, and subgroup analysis was used to identify the factors contributing to adverse events.ResultsForty-eight studies were included in the meta-analysis, comprising 25,624 patients treated with anti-IL-23 agents. Serious immunological or non-immunological adverse events were rare. Anti-IL-12/23-p40 agents appeared to cause adverse events more easily than anti-IL-23-p19 agents. The incidence of cancer did not appear to be related to anti-IL-23 agent treatment, and long-term medication could lead to mental diseases. The prevention of complications should be carefully monitored when administered for over approximately 40 weeks to avoid further adverse reactions, and the incidence of infection was the highest among general immunological adverse events.ConclusionsThe application of anti-IL-23 agents induced a series of immunological and non-immunological adverse events, but these agents tend to be well-tolerated with good safety profiles.
Clinical and Microbiological Characteristics of a Community-Acquired Carbapenem-Resistant Escherichia coli ST410 Isolate Harbouring blaNDM-5-Encoding IncX3-Type Plasmid From Blood
Authors: Gu Ji-Na , Chen Lin , Weng Xing-Bei , Yang Xiao-Yan , Pan Dan-Mei 
Published: June 2021

Objectives: The aim of this research was to investigate the clinical and microbiological characteristics of a case of community-acquired carbapenem-resistant Escherichia coli isolated from a patient with a bloodstream infection in China.Methods:Escherichia coli Huamei202001 was recovered from the first blood culture from a patient hospitalised in China. An antimicrobial susceptibility test was performed, and the genome was sequenced on an Illumina HiSeq X 10 platform with a 150-bp paired-end approach. The generated sequence reads were assembled using Unicycler, and the whole genome sequence data were analysed using bioinformatics tools. Moreover, the patient and her main family members obtained a faecal sample screening test for CRE, the positive strain was further isolated and the identification and antimicrobial susceptibility testing was performed.Results:Escherichia coli Huamei202001 belonged to sequence type 410. In addition, a blaNDM-5-encoding IncX3-type plasmid was responsible for the spreading of carbapenem resistance. Only the patient was detected as having a positive faecal sample screening test for CRE. Strain Fec01 was identified as E. coli, and the antibiotic susceptibility profile was the same as that of E. coli Huamei202001.Conclusions:Escherichia coli Huamei202001 is defined as community-acquired carbapenem-resistant Enterobacteriaceae. The clone ST410 that harbours the blaNDM-5-encoding IncX3-type plasmid is causing new high-risk clones globally. Thus, infection control measures should be strengthened to curb the dissemination of IncX3.
Arginine Methyltransferases as Regulators of RNA-Binding Protein Activities in Pathogenic Kinetoplastids
Authors: Campagnaro Gustavo D. , Nay Edward , Plevin Michael J. , Cruz Angela K. , Walrad Pegine B. 
Published: June 2021

A large number of eukaryotic proteins are processed by single or combinatorial post-translational covalent modifications that may alter their activity, interactions and fate. The set of modifications of each protein may be considered a “regulatory code”. Among the PTMs, arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), can affect how a protein interacts with other macromolecules such as nucleic acids or other proteins. In fact, many RNA-binding (RBPs) proteins are targets of PRMTs. The methylation status of RBPs may affect the expression of their bound RNAs and impact a diverse range of physiological and pathological cellular processes. Unlike most eukaryotes, Kinetoplastids have overwhelmingly intronless genes that are arranged within polycistronic units from which mature mRNAs are generated by trans-splicing. Gene expression in these organisms is thus highly dependent on post-transcriptional control, and therefore on the action of RBPs. These genetic features make trypanosomatids excellent models for the study of post-transcriptional regulation of gene expression. The roles of PRMTs in controlling the activity of RBPs in pathogenic kinetoplastids have now been studied for close to 2 decades with important advances achieved in recent years. These include the finding that about 10% of the Trypanosoma brucei proteome carries arginine methylation and that arginine methylation controls Leishmania:host interaction. Herein, we review how trypanosomatid PRMTs regulate the activity of RBPs, including by modulating interactions with RNA and/or protein complex formation, and discuss how this impacts cellular and biological processes. We further highlight unique structural features of trypanosomatid PRMTs and how it contributes to their singular functionality.