bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: BAF-Opathies/SSRIDDs Due to a de novo ACTL6A Variant, Previously Considered to Be Heart-Hand Syndrome
Authors: Yuan Zhuang-Zhuang , Xie Xiao-Hui , Gu Heng , Zhang Wei-Zhi , Hu Yi-Qiao , Yang Yi-Feng , Tan Zhi-Ping 
Published: August 2021

Purpose: This study aims to identify genetic lesions in patients with congenital heart disease (CHD) with or without other phenotypes. In this study, over 400 patients were recruited and several novel variants in known causative genes were identified. A Chinese patient clinically diagnosed with HHS (patent ductus arteriosus, persistent left superior vena cava, and congenital absence of left arm radius) was included in the study cohort.Methods: Targeted, whole exome, and Sanger sequencing were performed to identify genetic lesions. The effects of the variant on ACTL6A RNA and protein were assessed using bioinformatics analysis.Results: At the start of the study, no mutations in known and candidate causative genes associated with CHD were identified. Seven years later, we noticed craniofacial deformities and identified a de novo heterozygous deletion variant in ACTL6A (NM_004301, c.478_478delT; p.F160Lfs*9). Intellectual disability and short stature were identified by a follow-up visit 10 years later. This variant leads to frameshift sequences and a premature termination codon and may affect the features of proteins. According to the nonsense-mediated mRNA decay theory, this variant may induce the decay of ACTL6A mRNA in patients.Conclusion: Our study reported the first ACTL6A variant in a Chinese individual, providing further evidence that ACTL6A is involved in heart and upper limb skeletal and intellectual development, thereby expanding the spectrum of ACTL6A variants. Thus, mutation analysis of the ACTL6A gene should be considered in patients with BAF-opathies or heart-hand syndromes due to potential misdiagnosis. Craniofacial dysmorphisms and intellectual disability are key to distinguishing these two diseases clinically, and attention to developmental delay/intellectual disability and craniofacial deformities will contribute to the diagnosis of BAF-opathies.
Pulmonary Embolism in COVID-19 Patients: Which Diagnostic Algorithm Should We Use?
Authors: Porfidia Angelo , Mosoni Carolina , Talerico Rosa , Porceddu Enrica , Lupascu Andrea , Tondi Paolo , Landi Francesco , Pola Roberto 
Published: August 2021

Introduction: Although pulmonary embolism (PE) is a frequent complication of the clinical course of COVID-19, there is a lack of explicit indications regarding the best algorithm for diagnosing PE in these patients. In particular, it is not clear how to identify subjects who should undergo computed tomography pulmonary angiography (CTPA), rather than simply X-ray and/or high resolution computed tomography (HRCT) of the chest.Methods: We retrospectively analyzed COVID-19 patients who presented to the Emergency Department (ED) of our University hospital with acute respiratory failure, or that developed acute respiratory failure during hospital stay, to determine how many of them had a theoretical indication to undergo CTPA for suspected PE according to current guidelines. Next, we looked for differences between patients who underwent CTPA and those who only underwent X-ray and/or HRCT of the chest. Finally, we determined whether patients with a confirmed diagnosis of PE had specific characteristics that made them different from those with a CTPA negative for PE.Results: Out of 93 subjects with COVID-19 and acute respiratory failure, 73 (78.4%) had an indication to undergo CTPA according to the revised Geneva and Wells scores and the PERC rule-out criteria, and 54 (58%) according to the YEARS algorithm. However, in contrast with these indications, only 28 patients (30.1%) underwent CTPA. Of note, they were not clinically different from those who underwent X-ray and/or HRCT of the chest. Among the 28 subjects who underwent CTPA, there were 10 cases of PE (35.7%). They were not clinically different from those with CTPA negative for PE.Conclusions: COVID-19 patients with acute respiratory failure undergo CTPA, X-ray of the chest, or HRCT without an established criterion. Nonetheless, when CTPA is performed, the diagnosis of PE is anything but rare. Validated tools for identifying COVID-19 patients who require CTPA for suspected PE are urgently needed.
Geological Characteristics and Distribution of Granite Geothermal Reservoir in Southeast Coastal Areas in China
Authors: Zheng Herong , Luo Jun , Zhang Ying , Feng Jianyun , Zeng Yan , Wang Mingchuan 
Published: August 2021

The southeast coastal areas in China have distributed lots of granite outcrops of different periods. Previous research has shown that granite geothermal reservoirs are also distributed under sedimentary basins in these areas, such as in Zhangzhou basin. Therefore, granites with fractures buried in deep can be used as a potential deep geothermal reservoir in these areas. In order to study geological conditions of the deep granite reservoir and discuss the genesis of the deep granite geothermal system, rock geochemistry and zircon U-Pb chronology from outcrop and parts of the drilling cores of granitic rocks have been analyzed, combined with the anatomy of the deep seismic data and electromagnetic detection data in selected area. Based on the results of geochemistry and zircon U-Pb chronology, most granites in this area are of Yanshanian periods. Based on the seismic data, the thickness of the overlying strata on granite in Huangshadong area of Huizhou City is up to 1.5 km. According to the regional geological survey, multi-stage joints are developed in the granite, and most of hot springs rise from intersection of fracture with different directions to the surface. The heat source in the study area mainly comes from the mantle carried up by the deep NNE-trending faults. There are a large number of thermal springs at the intersection of the surface and the NW-trending fault, and the NW-trending fault provides the drainage conditions for the upwelling of underground thermal springs. There is a huge amount of deep granite geothermal resources in the southeast coastal area. The analysis of deep granite geological conditions and genetic models can provide guidance for the evaluation of deep granite geothermal resources and the further optimization of favorable zones in these areas.
Cost-Effectiveness of Dipeptidylpeptidase-4 Inhibitors Added to Metformin in Patients With Type 2 Diabetes in China
Authors: Lin Wen-Qiang , Cai Zhong-jie , Chen Tingting , Liu Mao-Bai , Li Na , Zheng Bin 
Published: August 2021

PurposeDipeptidylpeptidase-4 (DPP-4) inhibitors, including linagliptin, alogliptin, saxagliptin, sitagliptin, and vildagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM) patients in China. This study assessed the economic outcomes of different DPP-4 inhibitors in patients with T2DM inadequately controlled with metformin in the Chinese context.Materials and MethodsIn this study, the validated Chinese Outcomes Model for T2DM (COMT) was conducted to project economic outcomes from the perspective of Chinese healthcare service providers. Efficacy and safety, medical expenditure, and utility data were derived from the literature, which were assigned to model variables. The primary outputs of the model included the lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analysis was conducted to assess the potential uncertainties of parameters.ResultsOf the five competing strategies, alogliptin 25 mg strategy yielded the most significant health outcome, which associated with improvements in discounted QALY of 0.007, 0.014, 0.011, and 0.022 versus linagliptin 5 mg, saxagliptin 5 mg, sitagliptin 100 mg and vildagliptin50 mg, respectively. The sitagliptin 100 mg strategy was the cheapest option. The ICER of alogliptin 25 mg against sitagliptin 100 mg strategy was $6,952 per additional QALY gained, and the rest of the strategies were dominated or extended dominated. The most influential parameters were the cost of DPP-4 inhibitors and their treatment efficacy.ConclusionsThese results suggested that alogliptin was a preferred treatment option compared with other DPP-4 inhibitors for Chinese patients whose T2DM are inadequately controlled on metformin monotherapy.
An Explorative Study on Monocyte Reprogramming in the Context of Periodontitis In Vitro and In Vivo
Authors: Noz Marlies P. , Plachokova Adelina S. , Smeets Esther M.M. , Aarntzen Erik H. J. G. , Bekkering Siroon , Vart Prya , Joosten Leo A. B. , Netea Mihai G. , Riksen Niels P. 
Published: August 2021

AimsPeriodontitis is an independent risk factor for cardiovascular disease, but the mechanistic link is not fully understood. In atherosclerotic cardiovascular disease, monocytes can adopt a persistent hyperresponsive phenotype, termed trained immunity. We hypothesized that periodontitis-associated bacteria can induce trained immunity in monocytes, which subsequently accelerate atherosclerosis development.Materials and MethodsWe combined in vitro experiments on human primary monocytes and in vivo techniques in patients with periodontitis to test this hypothesis. Adherent peripheral blood mononuclear cells (PBMCs) were transiently exposed in vitro to Porphyromonas gingivalis for 24 hours, and restimulated with lipopolysaccharide (LPS) or Pam3CysK4 (P3C) six days later, to measure interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) production. In an exploratory observational study, patients with severe periodontitis (63 ± 6 years, n=14) and control subjects with no-to-mild periodontitis (54 ± 10 years, n=14) underwent venipuncture and 2’-deoxy-2’-[18F]fluoro-D-glucose positron-emission-tomography ([18F]FDG PET/CT) scanning.ResultsWhen adherent peripheral blood mononuclear cells (PBMCs) were transiently exposed in vitro to Porphyromonas gingivalis for 24 hours, and restimulated with LPS or P3C six days later, IL-6 and TNFα production was significantly increased (TNFα/P3C, p&lt;0.01). Circulating leukocytes, IL-6 and interleukin-1 receptor antagonist (IL-1Ra) concentrations were generally higher in patients compared to controls (leukocytes: p&lt;0.01; IL-6: p=0.08; IL-1Ra: p=0.10). Cytokine production capacity in PBMCs after 24h stimulation revealed no differences between groups. [18F]FDG PET/CT imaging showed a trend for increased [18F]FDG-uptake in the periodontium [mean standard uptake value (SUVmean), p=0.11] and in femur bone marrow (SUVmean, p=0.06), but no differences were observed for vascular inflammation. Positive correlations between severity of periodontitis, measured by The Dutch Periodontal Screening Index and pocket depth, with circulating inflammatory markers and tissue inflammation were found.ConclusionsP. gingivalis induces long-term activation of human monocytes in vitro (trained immunity). Patients with severe periodontitis did have signs of increased systemic inflammation and hematopoietic tissue activation. However, their circulating monocytes did not show a hyperresponsive phenotype. Together we suggest that trained immunity might contribute to local periodontal inflammation which warrants further investigation.
Long Noncoding RNA RP11-115N4.1 Promotes Inflammatory Responses by Interacting With HNRNPH3 and Enhancing the Transcription of HSP70 in Unexplained Recurrent Spontaneous Abortion
Authors: Liu Meilan , Sun Xiaoyue , Zhu Liqiong , Zhu Menglan , Deng Kewen , Nie Xiaolu , Mo Hanjie , Du Tao , Huang Bingqian , Hu Lihao , Liang Liuhong , Wang Dongyan , Luo Yinger , Yi Jinling , Zhang Jianping , Zhong Xingming , Cao Chunwei , Chen Hui 
Published: August 2021

BackgroundUnexplained recurrent spontaneous abortion (URSA) is a common pregnancy complication and the etiology is unknown. URSA-associated lncRNAs are expected to be potential biomarkers for diagnosis, and might be related to the disease pathogenesis.ObjectiveTo investigate differential lncRNAs in peripheral blood of non-pregnant URSA patients and matched healthy control women and to explore the possible mechanism of differential lncRNAs leading to URSA.MethodsWe profiled lncRNAs expression in peripheral blood from 5 non-pregnant URSA patients and 5 matched healthy control women by lncRNA microarray analysis. Functions of URSA-associated lncRNAs were further investigated in vitro.ResultsRP11-115N4.1 was identified as the most differentially expressed lncRNA which was highly upregulated in peripheral blood of non-pregnant URSA patients (P = 3.63E-07, Fold change = 2.96), and this dysregulation was further validated in approximately 26.67% additional patients (4/15). RP11-115N4.1 expression was detected in both lymphocytes and monocytes of human peripheral blood, and in vitro overexpression of RP11-115N4.1 decreased cell proliferation in K562 cells significantly. Furthermore, heat-shock HSP70 genes (HSPA1A and HSPA1B) were found to be significantly upregulated upon RP11-115N4.1 overexpression by transcriptome analysis (HSPA1A (P = 4.39E-08, Fold change = 4.17), HSPA1B (P = 2.26E-06, Fold change = 2.99)). RNA pull down and RNA immunoprecipitation assay (RIP) analysis demonstrated that RP11-115N4.1 bound to HNRNPH3 protein directly, which in turn activate heat-shock proteins (HSP70) analyzed by protein-protein interaction and HNRNPH3 knockdown assays. Most importantly, the high expression of HSP70 was also verified in the serum of URSA patients and the supernatant of K562 cells with RP11-115N4.1 activation, and HSP70 in supernatant can exacerbate inflammatory responses in monocytes by inducing IL-6, IL-1β, and TNF-α and inhibit the migration of trophoblast cells, which might associate with URSA.ConclusionOur results demonstrated that the activation of RP11-115N4.1 can significantly increase the protein level of HSP70 via binding to HNRNPH3, which may modulate the immune responses and related to URSA. Moreover, RP11-115N4.1 may be a novel etiological biomarker and a new therapeutic target for URSA.
Interleukin 23 Produced by Hepatic Monocyte-Derived Macrophages Is Essential for the Development of Murine Primary Biliary Cholangitis
Authors: Reuveni Debby , Brezis Miriam R. , Brazowski Eli , Vinestock Philip , Leung Patrick S. C. , Thakker Paresh , Gershwin M. Eric , Zigmond Ehud 
Published: August 2021

Background and AimsPrimary Biliary Cholangitis (PBC) is an organ-specific autoimmune liver disease. Mononuclear phagocytes (MNPs), comprise of monocyte, dendritic cells and monocyte-derived macrophages, constitute major arm of the innate immune system known to be involved in the pathogenesis of autoimmune disorders. MNPs were shown to accumulate around intra-hepatic bile ducts in livers of PBC patients. Interleukin 23 (IL-23) is a pro-inflammatory cytokine. IL-23-positive cells were detected in livers of patients with advanced stage PBC and IL-23 serum levels found to be in correlation with PBC disease severity. Our overall goal was to assess the importance of IL-23 derived from MNPs in PBC pathogenesis.MethodsWe utilized an inducible murine model of PBC and took advantage of transgenic mice targeting expression of IL-23 by specific MNP populations. Analysis included liver histology assessment, flow cytometry of hepatic immune cells and hepatic cytokine profile evaluation. Specific MNPs sub-populations were sorted and assessed for IL-23 expression levels.ResultsFlow cytometry analysis of non-parenchymal liver cells in autoimmune cholangitis revealed massive infiltration of the liver by MNPs and neutrophils and a decrease in Kupffer cells numbers. In addition, a 4-fold increase in the incidence of hepatic IL-17A producing CD4+ T cells was found to be associated with an increase in hepatic IL23-p19 and IL17A expression levels. Disease severity was significantly ameliorated in both CD11ccreP19flox/flox and CX3CR1creP19 flox/flox mice as assessed by reduced portal inflammation and decreased hepatic expression of various inflammatory cytokines. Amelioration of disease severity was associated with reduction in IL-17A producing CD4+ T cells percentages and decreased hepatic IL23-p19 and IL17A expression levels. qRT-PCR analysis of sorted hepatic MNPs demonstrated high expression levels of IL-23 mRNA specifically by CX3CR1hiCD11c+ monocyte-derived macrophages.ConclusionOur results indicate a major role for IL-23 produced by hepatic monocyte-derived macrophages in the pathogenesis of PBC. These results may pave the road for the development of new immune-based and cell specific therapeutic modalities for PBC patients not responding to current therapies.
Simulating Macular Degeneration to Investigate Activities of Daily Living: A Systematic Review
Authors: Macnamara Anne , Chen Celia , Schinazi Victor R. , Saredakis Dimitrios , Loetscher Tobias 
Published: August 2021

Purpose: Investigating difficulties during activities of daily living is a fundamental first step for the development of vision-related intervention and rehabilitation strategies. One way to do this is through visual impairment simulations. The aim of this review is to synthesize and assess the types of simulation methods that have been used to simulate age-related macular degeneration (AMD) in normally sighted participants, during activities of daily living (e.g., reading, cleaning, and cooking).Methods: We conducted a systematic literature search in five databases and a critical analysis of the advantages and disadvantages of various AMD simulation methods (following PRISMA guidelines). The review focuses on the suitability of each method for investigating activities of daily living, an assessment of clinical validation procedures, and an evaluation of the adaptation periods for participants.Results: Nineteen studies met the criteria for inclusion. Contact lenses, computer manipulations, gaze contingent displays, and simulation glasses were the main forms of AMD simulation identified. The use of validation and adaptation procedures were reported in approximately two-thirds and half of studies, respectively.Conclusions: Synthesis of the methodology demonstrated that the choice of simulation has been, and should continue to be, guided by the nature of the study. While simulations may never completely replicate vision loss experienced during AMD, consistency in simulation methodology is critical for generating realistic behavioral responses under vision impairment simulation and limiting the influence of confounding factors. Researchers could also come to a consensus regarding the length and form of adaptation by exploring what is an adequate amount of time and type of training required to acclimatize participants to vision impairment simulations.
Spleen Radiomics Signature: A Potential Biomarker for Prediction of Early and Late Recurrences of Hepatocellular Carcinoma After Resection
Authors: Li Pinxiong , Wu Lei , Li Zhenhui , Li Jiao , Ye Weitao , Shi Zhenwei , Xu Zeyan , Zhu Chao , Ye Huifen , Liu Zaiyi , Liang Changhong 
Published: August 2021

ObjectivesTo explore the usefulness of spleen radiomics features based on contrast-enhanced computed tomography (CECT) in predicting early and late recurrences of hepatocellular carcinoma (HCC) patients after curative resection.MethodsThis retrospective study included 237 HCC patients who underwent CECT and curative resection between January 2006 to January 2016. Radiomic features were extracted from CECT images, and then the spleen radiomics signatures and the tumor radiomics signatures were built. Cox regression analysis was performed to identify the independent risk factors of early and late recurrences. Then, multiple models were built to predict the recurrence-free survival of HCC after resection, and the incremental value of the radiomics signature to the clinicopathologic model was assessed and validated. Kaplan–Meier survival analysis was used to assess the association of the models with RFS.ResultsThe spleen radiomics signature was independent risk factor of early recurrence of HCC. The mixed model that integrated microvascular invasion, tumor radiomics signature and spleen radiomics signature for the prediction of early recurrence achieved the highest C-index of 0.780 (95% CI: 0.728,0.831) in the primary cohort and 0.776 (95% CI: 0.716,0.836) in the validation cohort, and presented better predictive performance than clinicopathological model and combined model. In the analysis of late recurrence, the spleen radiomics signature was the only prognostic factor associated with late recurrence of HCC.ConclusionsThe identified spleen radiomics signatures are prognostic factors of both early and late recurrences of HCC patients after surgery and improve the predictive performance of model for early recurrence.
Maternal-Neonatal Serum Albumin Level and Neonatal Respiratory Distress Syndrome in Late-Preterm Infants
Authors: Ying Qian , You Xue-qin , Luo Fei , Wang Ji-mei 
Published: August 2021

Background: To determine the correlation between maternal-neonatal serum albumin level and respiratory distress syndrome (RDS) in late-preterm infants.Methods: This case-control study included 112 late-preterm newborns admitted to the neonatal intensive care unit of our hospital between January 2018 and July 2019. Those infants were divided into the RDS group (n = 56) and the non-RDS group (n = 56). Levels of maternal-neonatal serum albumin, pregnancy complications, and baseline information of the infants were compared between the two groups.Results: 1. There was no correlation between maternal and neonatal serum albumin measures. The maternal albumin level in the RDS group was lower than that in the control group (33.38 ± 3.31 vs. 33.60 ± 3.31, P &gt; 0.05), but the difference was not statistically significant. The neonatal albumin level in the RDS group was significantly lower than that in the control group (32.70 ± 2.48 vs. 35.66 ± 3.27, P &lt; 0.05). To predict RDS in late-preterm infants, using the albumin cutoff level of 34 g/L provides a sensitivity of 83.9% with a specificity of 62.5%. 2. Gestational age, primipara, placenta previa, antenatal corticosteroid therapy, delivery mode, and neonatal serum albumin level were associated with RDS in the late-preterm infant. 3. After adjustment for gestational age, logistic regression analysis showed that neonatal serum albumin level, placenta previa, and delivery mode were independent risk factors for RDS in late-preterm infants. However, albumin level did not related to the severity of RDS.Conclusion: The decrease in serum albumin within the first day after birth was closely related to the occurrence of RDS in late-preterm infants.