bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and effectiveness of non-vitamin K oral anticoagulants versus warfarin in real-world patients with non-valvular atrial fibrillation: a retrospective analysis of contemporary Japanese administrative claims data
Authors: Kohsaka Shun , Katada Jun , Saito Kumiko , Jenkins Aaron , Li Benjamin , Mardekian Jack , Terayama Yasuo
Published: April 2020

Objective

To assess the safety (ie, risk of bleeding) and effectiveness (ie, risk of stroke/systemic embolism (SE)) separately for four non-vitamin K oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban and rivaroxaban) versus warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF), including those at high risk of bleeding and treated with reduced doses of NOACs.

Methods

We conducted a retrospective analysis of electronic health records and claims data from 372 acute care hospitals in Japan for patients with NVAF newly initiated on NOACs or warfarin. Baseline characteristics were balanced using inverse probability of treatment weighting with stabilised weights (s-IPTW). Bleeding risk and stroke/SE risk were expressed as HRs with 95% CIs. Two sensitivity analyses were conducted.

Results

A total of 73 989 patients were eligible for analysis. Notably, 52.8%–81.9% of patients received reduced doses of NOACs. After applying s-IPTW, patient characteristics were well balanced across warfarin/NOAC cohorts. The mean within-cohort age, CHADS2score and CHA2DS2-VASc score were 76 years, 2.2–2.3 and 3.8, respectively. In all age categories, the majority of the HRs for major bleeding, any bleeding and stroke/SE were equal to or below 1 for all NOACs versus warfarin. Apixaban was the only NOAC associated with a significantly lower risk of any bleeding. There was a trend towards increased risk reduction with NOACs versus warfarin in patients with body weight ≥60 kg. In patients with renal disease, the HRs for apixaban versus warfarin were below 1 for major bleeding, any bleeding and stroke/SE, with statistical significance observed for the risk reduction in stroke/SE versus warfarin. In the sensitivity analysis, there were no large differences in HRs between the two observational periods.

Conclusions

In patients with NVAF primarily treated with reduced-dose NOACs, the risks of stroke/SE and major bleeding were significantly lower with NOACs versus warfarin.
Chloroplast genomes of seven species of Coryloideae (Betulaceae): structures and comparative analysis
Authors: Hu Guanglong , Cheng Lili , Huang Wugang , Cao Qingchang , Zhou Lei , Jia Wenshen , Lan Yanping
Published: April 2020

Coryloideae is a subfamily in the family Betulaceae consisting of four extant genera: Carpinus, Corylus, Ostrya, and Ostryopsis. We sequenced the plastomes of six species of Corylus and one species of Ostryopsis for comparative and phylogenetic analyses. The plastomes are 159–160 kb long and possess typical quadripartite cp architecture. The plastomes show moderate divergence and conserved arrangement. Five mutational hotspots were identified by comparing the plastomes of seven species of Coryloideae: trnG-atpA, trnF-ndhJ, accD-psaI, ndhF-ccsA, and ycf1. We assembled the most complete phylogenomic tree for the family Betulaceae using 68 plastomes. Our cp genomic sequence phylogenetic analyses placed Carpinus, Ostrya, and Ostryopsis in a clade together and left Corylus in a separate clade. Within the genus Corylus, these analyses indicate the existence of five subclades reflecting the phylogeographical relationships among the species. The data offer significant genetic information for the identification of species of the Coryloideae, taxonomic and phylogenetic studies, and molecular breeding.
The Impact of Medicare's Alternative Payment Models on the Value of Care
Authors: Liao Joshua M. , Navathe Amol S. , Werner Rachel M.
Published: April 2020

Over the past decade, the Centers for Medicare and Medicaid Services (CMS) have led the nationwide shift toward value-based payment. A major strategy for achieving this goal has been to implement alternative payment models (APMs) that encourage high-value care by holding providers financially accountable for both the quality and the costs of care. In particular, the CMS has implemented and scaled up two types of APMs: population-based models that emphasize accountability for overall quality and costs for defined patient populations, and episode-based payment models that emphasize accountability for quality and costs for discrete care. Both APM types have been associated with modest reductions in Medicare spending without apparent compromises in quality. However, concerns about the unintended consequences of these APMs remain, and more work is needed in several important areas. Nonetheless, both APM types represent steps to build on along the path toward a higher-value national health care system.
Evaluation of Electrochemical Stability and Li-ion Interactions in Ether Functionalized Pyrrolidinium and Phospholanium Ionic Liquids
Authors: Pandian Shanthi , Hariharan Krishnan S. , Adiga Shashishekara P. , Kolake Subramanya Mayya
Published: April 2020

Potential electrolytes for lithium ion batteries (LIB) depicting high electrochemical stability and ionic conductivity still represents a great challenge. Herein, we investigate the reduction stability and Li+cation interactions with substituted cyclic phospholanium (CylP5+) and pyrrolidinium (Pyr+) ionic liquids (ILs) with bis(trifluoromethanesulfonyl)imide (TFSI−) anion. The cations CylP5+and Pyr+are functionalized with varying chain lengths of alkyl and alkoxy substituents and their reduction potentials evaluated with respect to Li+/Li. CylP5+cations, in general have better stability than Pyr+based ILs, while the alkoxy substitution is found to lower the reduction stability compared to alkyl substituents in both ILs. Furthermore, the interaction energies between the substituent modified-cations (C), Li+cation and the anion (A) were evaluated. The ion-pair (C-A) interaction energies on addition of Li+cation is shown to decrease for both Pyr+and CylP5+cations with shorter alkoxy chain lengths, thereby implying faster diffusion of ions due to weaker interactions. Similarly, among the two cations, lowest ΔE were noted between alkoxy substituted [Li(CylP5)]2+cation and TFSI−, signifying faster diffusion of ions in CylP5+based electrolytes than that of Pyr+based ILs. These results govern the synthesis of novel ILs with promising base cation and functionalization for LIB.
Greater lactate accumulation following an acute bout of high-intensity exercise in males suppresses acylated ghrelin and appetite postexercise
Authors: Vanderheyden Luke W. , McKie Greg L. , Howe Greg J. , Hazell Tom J.
Published: April 2020

We used sodium bicarbonate to increase lactate accumulation or sodium chloride as a placebo. Our findings further implicate lactate as a mediator of exercise-induced appetite suppression given exercise-induced increases in lactate during the sodium bicarbonate session altered peripheral concentrations of appetite-regulating hormones, culminating in a reduction of appetite. This supports a lactate-dependent mechanism of appetite suppression following high-intensity exercise and highlights the potential of using lactate as a means of inducing a caloric deficit.
Elevated exercise blood pressure in middle-aged women is associated with altered left ventricular and vascular stiffness
Authors: Sarma Satyam , Howden Erin , Carrick-Ranson Graeme , Lawley Justin , Hearon Christopher , Samels Mitchel , Everding Braden , Livingston Sheryl , Adams-Huet Beverley , Palmer M. Dean , Levine Benjamin D.
Published: April 2020

Women are at increased risk for heart failure with preserved ejection fraction (HFpEF) largely due to higher prevalence of arterial and cardiac stiffening. We were able to identify several subclinical markers of early (stages A and B) HFpEF pathophysiology largely on the basis of exercise blood pressure (BP) response in otherwise healthy middle-aged women. Exercise BP response may be an inexpensive screening tool to identify women at highest risk for developing future HFpEF.
Cardiomyocyte slowly activating delayed rectifier potassium channel: regulation by exercise and β-adrenergic signaling
Authors: Wang Xinrui , Fitts Robert H.
Published: April 2020

Results demonstrate that exercise training (TRN) downregulates ventricular IKs channel current and the channel’s responsiveness to β-agonist factors mediated by TRN-induced decline in channel subunits KCNQ1 and KCNE1 and the A-kinase anchoring protein yotiao. The reduced IKs current helps explain the TRN-induced prolongation of the action potential in basal conditions and, coupled with previously reported upregulation of the KATP channel, results in a more efficient heart that is better able to respond to beat-by-beat changes in metabolism.
Tea Polysaccharide (TPS) Reduces Astrocytes Apoptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation by Regulating the miR-375/SRXN1 Axis
Authors: Jiang Ying , Sun Hongmei , Yin Zhiqi , Yan Jun
Published: April 2020

Objective. To investigate the effect of tea polysaccharides (TPS) mediated by miR-375/SRXN1 axis on mice with cerebral ischemia-reperfusion injury and proliferation and apoptosis of astrocytes (AS) conducted with oxygen-glucose deprivation/reoxygenation (OGD/R). Methods. Mouse model of middle cerebral artery occlusion (MCAO) and OGD/R-induced AS injury model were established; brain obstruction volume was measured by TTC staining; dry/wet weight ratio was used for measuring brain water content; hydrogen peroxide (H2O2) content in brain tissue was measured by H2O2 assay kit; cell viability and apoptosis rate were detected by MTT assay and flow cytometry, respectively; the expression level of miR-375 in OGD/R-AS was detected using qPCR; dual-luciferase reporter assay was used to verify the targeting relationship between miR-375 and SRXN1; mRNA levels of miR-375, SRXN1, Bcl-2, Bax, and caspase-3 were measured by qPCR; the protein levels of SRXN1, Bcl-2, Bax, and caspase-3 were measured by Western blotting. Results. The volume of cerebral obstruction, brain water content and H2O2 content in mice decreased gradually with the increase of TPS concentration. TPS treatment in vitro could effectively improve OGD/R-AS viability and reduce the apoptotic rate; overexpression of miR-375 inhibited AS viability but increased the apoptotic rate; TPS treatment resulted in a decrease in the expression of miR-375 in OGD/R-AS; MiR-375 targeted SRXN1 in AS; inhibition of miR-375 expression significantly upregulated SRXN1 levels; TPS treatment with simultaneous overexpression of SRXN1 significantly increased OGD/R-AS activity and reduced apoptosis; however, TPS treatment with simultaneous overexpression of SRXN1 and miR-375 resulted in no significant difference in cell viability and apoptosis rate compared with the control group. Conclusion. TPS reduces astrocyte injury induced by cerebral ischemia-reperfusion in mice by regulating the miR-375/SRXN1 molecular axis.
Protection of Sensitive Data in Industrial Internet Based on Three-Layer Local/Fog/Cloud Storage
Authors: Liu Jing , Yuan Changbo , Lai Yingxu , Qin Hua
Published: April 2020

Industrial Internet technology has developed rapidly, and the security of industrial data has received much attention. At present, industrial enterprises lack a safe and professional data security system. Thus, industries urgently need a complete and effective data protection scheme. This study develops a three-layer framework with local/fog/cloud storage for protecting sensitive industrial data and defines a threat model. For real-time sensitive industrial data, we use the improved local differential privacy algorithm M-RAPPOR to perturb sensitive information. We encode the desensitized data using Reed–Solomon (RS) encoding and then store them in local equipment to realize low cost, high efficiency, and intelligent data protection. For non-real-time sensitive industrial data, we adopt a cloud-fog collaborative storage scheme based on AES-RS encoding to invisibly provide multilayer protection. We adopt the optimal solution of distributed storage in local equipment and the cloud-fog collaborative storage scheme in fog nodes and cloud nodes to alleviate the storage pressure on local equipment and to improve security and recoverability. According to the defined threat model, we conduct a security analysis and prove that the proposed scheme can provide stronger data protection for sensitive data. Compared with traditional methods, this approach strengthens the protection of sensitive information and ensures real-time continuity of open data sharing. Finally, the feasibility of our scheme is validated through experimental evaluation.
Correlation of Patient-Reported Outcome (PRO-2) with Endoscopic and Histological Features in Ulcerative Colitis and Crohn’s Disease Patients
Authors: Dragasevic Sanja , Sokic-Milutinovic Aleksandra , Stojkovic Lalosevic Milica , Milovanovic Tamara , Djuranovic Srdjan , Jovanovic Ivan , Rajic Sanja , Stojkovic Mirjana , Milicic Biljana , Kmezic Stefan , Oluic Branislav , Aleksic Marko , Pavlovic Markovic Aleksandra , Popovic Dragan
Published: April 2020

Background and Objectives. Determination of inflammatory bowel disease activity determines further therapeutic approach and follow-up. The aim of our study was to investigate correlation between patients’ reported symptoms and endoscopic and histological disease activity. Methods. A cross-sectional study was conducted in consecutive newly diagnosed patients with inflammatory bowel disease in a tertiary care referral center. The initial evaluation included patient-reported outcome for stool frequency subscore and rectal bleeding. Endoscopic activity was determined using the Mayo scoring system for ulcerative colitis and the Simple Endoscopic Score for Crohn’s disease. Histopathological activity was assessed using a validated numeric scoring system. Results. We included 159 patients (63 Crohn’s disease with colonic involvement and 96 with ulcerative colitis). We found significant correlation between the Mayo endoscopic subscoring system and histology activity in ulcerative colitis, while no correlation was found in patients with Crohn’s disease. Patient-reported outcome showed inverse correlation with endoscopic and histological activity in Crohn’s disease (rs=−0.67; rs=−0.72), while positive correlation was found in ulcerative colitis (rs=0.84; rs=0.75). Interpretation and Conclusions. Patient-reported outcome is a practical and noninvasive tool for assessment of disease activity in ulcerative colitis patients but not in Crohn’s disease.
Efficacy and Safety of Integrated Traditional Chinese Medicine and Western Medicine on the Treatment of Rheumatoid Arthritis: A Meta‐Analysis
Authors: Xing Qi , Fu Ling , Yu Zhichao , Zhou Xueping
Published: April 2020

Objective. Integrated therapy of traditional Chinese medicine (TCM) and Western medicine (WM) has gradually been applied to the treatment of rheumatoid arthritis (RA). Recently published studies have provided a wealth of data and information about the effectiveness of combination treatments, but high‐quality evidence‐based meta‐analysis on this issue is not available yet. This study was conducted to compare and evaluate the efficacy and safety of the integrated therapy for RA. Methods. PubMed, EMBASE, and the Cochrane Library were searched up to January 2020. Randomized controlled trials (RCTs) that compared the efficacy and safety of integrative TCM‐WM with WM alone for RA were included. The outcome measures contained therapeutic effects (TEs), tender joint count (TJC), swollen joint count (SJC), duration of morning stiffness (DMS), grip strength (GS), disease activity score in 28 joints (DAS28), rheumatoid factor (RF), anti‐cyclic peptide containing citrulline (anti‐CCP), erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), and adverse events (AEs) to assess the efficacy and safety of different treatments. Results. A total of 20 RCTs with 2269 patients met the inclusion criteria. TCM used in these studies included Chinese herbal decoctions and tablets or capsules made from herbs and their extracts, while WM included disease‐modifying antirheumatic drugs (DMARDs), nonsteroidal anti‐inflammatory drugs (NSAIDs), and glucocorticoids (GC). Compared with patients receiving WM treatment alone, patients with integrative TCM‐WM treatment showed better TEs (OR = 3.03, 95% CI [2.36, 3.88]). The integrative treatment group showed reductions in TJC (MD = −1.17, 95% CI [−2.12, −0.21]), SJC (MD = −0.87, 95% CI [−1.85, 0.10]), DMS (SMD = −0.69, 95% CI [−0.98, −0.41]), DAS28 (MD = −0.43, 95% CI [−0.57, −0.29]), RF (SMD = −0.59, 95% CI [−0.91, −0.27]), anti‐CCP (SMD = −0.21, 95% CI [−0.36, −0.06]), ESR (MD = −8.36, 95% CI [−12.60, −4.12]), and CRP (MD = −6.73, 95% CI [−9.38, −4.08]), and increment in GS (SMD = 0.12, 95% CI [−0.63, 0.87]). AEs, especially gastrointestinal disorders, abnormal liver function, leukopenia, skin allergies and rashes, headaches and dizziness, and alopecia, significantly decreased (OR = 0.37, 95% CI [0.29, 0.47]) in the integrative treatment group. Conclusions. The findings of this meta‐analysis indicate that integrative TCM‐WM could obtain effective and safe results in the treatment of RA. Using TCM as an adjunctive therapy in RA has great prospects for further development.
Research on the Combination Method of Temporal Conflict Evidence Based on Transition Matrix
Authors: Wu Bin , Yi Xiao
Published: April 2020

Conflict evidence combination is an important research topic in evidence theory. In this paper, two kinds of transition matrices are constructed based on the Markov model; one is the unordered transition matrix, which satisfies the commutative law, and the other is the temporal transition matrix, which does not satisfy the commutative law, but it can handle the combination of temporal evidence well. Then, a temporal conflict evidence combination model is proposed based on these two transition matrices. First, the transition probability at the first n time is calculated through the model of unordered transition probability, and then, the transition matrix from the N + 1 time is used to solve the combination problem of temporal conflict evidence. The effectiveness of the transition matrix in the research of conflict evidence combination method is proved by the example analysis.
Separable Nonlinear Least-Squares Parameter Estimation for Complex Dynamic Systems
Authors: Dattner Itai , Ship Harold , Voit Eberhard O.
Published: April 2020

Nonlinear dynamic models are widely used for characterizing processes that govern complex biological pathway systems. Over the past decade, validation and further development of these models became possible due to data collected via high-throughput experiments using methods from molecular biology. While these data are very beneficial, they are typically incomplete and noisy, which renders the inference of parameter values for complex dynamic models challenging. Fortunately, many biological systems have embedded linear mathematical features, which may be exploited, thereby improving fits and leading to better convergence of optimization algorithms. In this paper, we explore options of inference for dynamic models using a novel method of separable nonlinear least-squares optimization and compare its performance to the traditional nonlinear least-squares method. The numerical results from extensive simulations suggest that the proposed approach is at least as accurate as the traditional nonlinear least-squares, but usually superior, while also enjoying a substantial reduction in computational time.
Development and Validation of a Bordetella pertussis Whole-Genome Screening Strategy
Authors: da Silva Antunes Ricardo , Quiambao Lorenzo G. , Sutherland Aaron , Soldevila Ferran , Dhanda Sandeep Kumar , Armstrong Sandra K. , Brickman Timothy J. , Merkel Tod , Peters Bjoern , Sette Alessandro
Published: April 2020

The immune response elicited by the protective whole-cell pertussis (wP) versus the less-protective acellular pertussis (aP) vaccine has been well characterized; however, important clinical problems remain unsolved, as the inability of the currently administered aP vaccine is resulting in the reemergence of clinical disease (i.e., whooping cough). Strong evidence has shown that original, childhood aP and wP priming vaccines provide a long-lasting imprint on the CD4+ T cells that impacts protective immunity. However, aP vaccination might prevent disease but not infection, which might also affect the breadth of responses to Bordetella pertussis (BP) antigens. Thus, characterizing and defining novel targets associated with T cell reactivity are of considerable interest. Here, we compare the T cell reactivity of original aP and wP priming for different antigens contained or not contained in the aP vaccine and define the basis of a full-scale genomic map of memory T cell reactivity to BP antigens in humans. Our data show that the original priming after birth with aP vaccines has higher T cell reactivity than originally expected against a variety of BP antigens and that the genome-wide mapping of BP using an ex vivo screening methodology is feasible, unbiased, and reproducible. This could provide invaluable knowledge towards the direction of a new and improved pertussis vaccine design.
Analysis of Occupational Stress and Its Relationship with Secretory Immunoglobulin A in the Xinjiang Plateau Young Military Recruits
Authors: Tao Ning , An Hengqing , Zhang Jianjiang , Zhang Yuanyue , Jin Lu , Xu Lei , Liu Jiwen , Xu Xinjuan
Published: April 2020

Background. With the continuous improvement of the modernization of the Chinese military and the major adjustments made by the state to the recruitment policy, the newly recruited military undergone multiple pressures such as targeted high‐intensity military training and environmental changes. The mental health of military has become a crucial factor of improving the fighting capacity effectiveness of the troops. Objectives. To explore occupational stress of young recruits in the Xinjiang plateau environment during their basic military training period and analyze the relationship between occupational stress and secretory immunoglobulin A (sIgA) levels. Methods. Using multistage stratified cluster random sampling, 625 recruits stationed at Xinjiang plateau command in 2014 were enrolled as subjects. Occupational stress was assessed by the Occupational Stress Inventory Revised Edition (OSI‐R). sIgA in saliva was quantified by enzyme‐linked immunosorbent assay. The resulting data were analyzed using descriptive statistics, nonparametric tests, and correlation analysis. Results. Based on demographic characteristics, occupational stress was higher in the urban group than the rural group, coping ability for stress was greater in individuals who were students before joining the army than nonstudents, occupational stress was higher in smokers than nonsmokers, and coping ability for stress was higher in nonsmokers than in smokers (all P < 0.05). Being an only child, educational level and age were not significantly related to occupational stress scores (P > 0.05). Salivary sIgA level was higher in the high occupational stress group than in the low stress group (P < 0.01). Salivary sIgA was positively correlated with scores on the occupational role and personal strain questionnaires (rs = 0.229, rs = 0.268, P < 0.01). Conclusion. Demographic characteristics influenced occupational stress among young recruits in cold and high‐altitude area. Further, there were some relationships between occupational stress and salivary sIgA in young military recruits.
Identification of DeleteriousNOTCHMutation as Novel Predictor to Efficacious Immunotherapy in NSCLC
Authors: Zhang Kai , Hong Xiaohua , Song Zhengbo , Xu Yu , Li Chengcheng , Wang Guoqiang , Zhang Yuzi , Zhao Xiaochen , Zhao Zhengyi , Zhao Jing , Huang Mengli , Huang Depei , Qi Chuang , Gao Chan , Cai Shangli , Gu Feifei , Hu Yue , Xu Chunwei , Wang Wenxian , Lou Zhenkun , Zhang Yong , Liu Li
Published: April 2020

Purpose:

NOTCH signaling is associated with tumorigenesis, mutagenesis, and immune tolerance in non–small cell lung cancer (NSCLC), indicating its association with the clinical benefit of immune checkpoint inhibitors (ICI). We hypothesized that NOTCH mutation in NSCLC might be a robust predictor of immunotherapeutic efficacy.

Experimental Design:

Multiple-dimensional data including genomic, transcriptomic, and clinical data from cohorts of NSCLC internal and public cohorts involving immunotherapeutic patients were analyzed. Polymorphism Phenotyping v2 (PolyPhen-2) system was performed to determine deleterious NOTCH mutation (del-NOTCHmut). Further investigation on molecular mechanism was performed in The Cancer Genome Atlas (TCGA) data via CIBERSORT and gene set enrichment analysis.

Results:

Our 3DMed cohort (n = 58) and other four cohorts (Rizvi, POPLAR/OAK, Van Allen, and MSKCC; n = 1,499) uncovered marked correlation between NOTCH1/2/3 mutation and better ICI outcomes in EGFR/ALKWT population, including objective response rate (2.20-fold, P = 0.001), progression-free survival [HR, 0.61; 95% confidence interval (CI), 0.46–0.81; P = 0.001], and overall survival (HR, 0.56; 95% CI, 0.32–0.96; P = 0.035). Del-NOTCHmut exhibited better predictive function than non-deleterious NOTCH mutation, potentially via greater transcription of genes related to DNA damage response and immune activation. Del-NOTCHmut was not linked with prognosis in TCGA cohorts and chemotherapeutic response, but was independently associated with immunotherapeutic benefit, delineating the predictive, but not prognostic, utility of del-NOTCHmut.

Conclusions:

This work distinguishes del-NOTCHmut as a potential predictor to favorable ICI response in NSCLC, highlighting the importance of genomic profiling in immunotherapy. More importantly, our results unravel a possibility of personalized combination immunotherapy as adding NOTCH inhibitor to ICI regimen in NSCLC, for the optimization of ICI treatment in clinical practice.
The Clinical Significance of Seminoma Component in Testicular Mixed Germ Cell Tumour
Authors: Akan Serkan , Ediz Caner , Tavukcu Hasan Hüseyin , Ozgun Alpaslan , Yilmaz Omer
Published: April 2020

Background: The aim of this study was to examine clinical/pathological characteristics, prognosis and tendency to metastasis of mixed germ cell tumours (MGCTs) that contain a seminoma component. Methods: A total of 111 MGCT cases between 2008 and 2018 were retrospectively enrolled. The patients were divided into 2 groups according to the absence (group 1) or presence (group 2) of seminoma component in MGCTs. Patients’ age, complaints at admission to our clinic, primary tumour localization, primary tumour size, preoperative testicular tumour markers, MGCT histopathological components and percentages, lymphovascular invasion, pathological tumour stage, postoperative testicular tumour markers, presence of lymph node involvement in abdominal tomography, lung metastasis based on thorax tomography, clinical tumour stage, adjunctive therapies performed, state of recurrence and survival were compared in 2 groups. Results: The mean age of the patients was 24.51 ± 4.79 years. The mean age, initial complaint rates, primary tumour size, postoperative testicular tumour markers, presence of lymphovascular invasion, presence of lymph node involvement and lung metastasis were found to be higher in group 2 than in group 1, although these differences were not statistically significant. Especially, it was found that a seminoma component rate of 30% and higher had a higher tendency for a poor prognosis. Conclusion: Although the word “seminoma” may be initially interpreted as an indication of good prognosis, a seminoma component in MGCTs is actually not a good prognostic factor. MGCTs that contain a seminoma component (especially 30% and higher) can have a higher tendency for occult metastatic disease.
Novel Insights and New Developments Regarding Coagulation Revealed by Studies of the Anti-Factor IXa (Activated Factor IX)/Factor X Bispecific Antibody, Emicizumab
Authors: Yada Koji , Nogami Keiji
Published: April 2020

Emicizumab is a humanized anti-FIXa/FX (factor IXa/X) bispecific monoclonal antibody that mimics FVIIIa (activated factor VIII) cofactor function. The hemostatic efficacy of emicizumab has been confirmed in clinical studies of patients with hemophilia A, irrespective of the presence of FVIII inhibitors. Emicizumab differs in some properties from FVIIIa molecule. Emicizumab requires no activation by thrombin and is not inactivated by activated protein C, but emicizumab-mediated coagulation is regulatable and maintains hemostasis. A small amount of FIXa (activated factor IX) is required to initiate emicizumab-mediated hemostasis, whereas tissue factor/FVIIa (activated factor VII)-mediated FXa (activated factor X) and thrombin activation initiates FVIIIa-mediated hemostasis. Fibrin formation, followed by fibrinolysis, appears to be similar between emicizumab- and FVIIIa-mediated hemostasis. These results suggest possible future uses of emicizumab for treating hemorrhagic diseases other than hemophilia A and reveal previously unobservable behaviors of procoagulation and anticoagulation factors in conventional hemostasis. Here, we have reviewed novel insights and new developments regarding coagulation highlighted by emicizumab.
Arterial Stiffness
Authors: Chen Yabing , Zhao Xinyang , Wu Hui
Published: April 2020

This review focuses on the association between vascular calcification and arterial stiffness, highlighting the important genetic factors, systemic and local microenvironmental signals, and underlying signaling pathways and molecular regulators of vascular calcification. Elevated oxidative stress appears to be a common procalcification factor that induces osteogenic differentiation and calcification of vascular cells in a variety of disease conditions such as atherosclerosis, diabetes mellitus, and chronic kidney disease. Thus, the role of oxidative stress and oxidative stress–regulated signals in vascular smooth muscle cells and their contributions to vascular calcification are highlighted. In relation to diabetes mellitus, the regulation of both hyperglycemia and increased protein glycosylation, by AGEs (advanced glycation end products) and
O
-linked β-N-acetylglucosamine modification, and its role in enhancing intracellular pathophysiological signaling that promotes osteogenic differentiation and calcification of vascular smooth muscle cells are discussed. In the context of chronic kidney disease, this review details the role of calcium and phosphate homeostasis, parathyroid hormone, and specific calcification inhibitors in regulating vascular calcification. In addition, the impact of the systemic and microenvironmental factors on respective intrinsic signaling pathways that promote osteogenic differentiation and calcification of vascular smooth muscle cells and osteoblasts are compared and contrasted, aiming to dissect the commonalities and distinctions that underlie the paradoxical vascular-bone mineralization disorders in aging and diseases.
Coronary Disease Surveillance in the Community: Angiography and Revascularization
Authors: Gerber Yariv , Gibbons Raymond J. , Weston Susan A. , Fabbri Matteo , Herrmann Joerg , Manemann Sheila M. , Frye Robert L. , Asleh Rabea , Greason Kevin , Killian Jill M. , Roger Véronique L.
Published: April 2020

Background

Temporal declines in cardiac stress tests results, coronary revascularization, and cardiovascular mortality have suggested a decline in the population burden of coronary disease until the 2000s. However, recent data indicate these favorable trends could be ending. We aimed to assess the evolution of the population burden of coronary disease in the community by examining trends in angiography and revascularization.

Methods and Results

We analyzed age‐ and sex‐adjusted trends from all coronary angiographic diagnostic procedures and revascularizations performed in Olmsted County, MN from 2000 to 2018. A total of 12 981 invasive angiograms were performed among 9049 individuals (64% men; 55% aged ≥65 years). Adjusted angiography rates decreased by 30% (95%
CI
, 25%–34%) between 2000 and 2009 and leveled off thereafter. Including
computed tomography,
angiography uncovered an increase in angiography use in recent years (risk ratio=1.15 [95%
CI
, 1.07–1.23] for 2018 versus 2014) and a decline in the prevalence of anatomic
CAD
from 2000 to 2018.
CAD
severity declined substantially from 2000 to 2009, followed by a plateau. Among 6570 revascularizations (72% men; 57% aged ≥65 years), 77% were percutaneous coronary interventions and 23% coronary artery bypass graft surgeries. The adjusted revascularization rates declined by 34% (95%
CI
, 27%–39%) from 2000 to 2009, followed by a plateau (risk ratio=1.10 [95%
CI
, 1.00–1.22]).

Conclusions

Between 2000 and 2018 in the community, coronary angiography use declined initially, leveled off, and then increased. Trends in
CAD
severity and revascularization use decreased then plateaued. The most recent trends are concerning as they suggest the burden of coronary disease is no longer declining. This warrants reinvigorated primary prevention and population surveillance.
Forensic identification of CITES Appendix I Cupressaceae using anatomy and mass spectrometry
Authors: Carmona Rene J. , Wiemann Michael C. , Baas Pieter , Barros Cristobal , Chavarria Gabriela D. , McClure Pamela J. , Espinoza Edgard O.
Published: April 2020

Alerce (Fitzroya cupressoides (Mol.) Johnst.) and Guaitecas cypress (Pilgerodendron uviferum (Don) Florin) are two of the three closely-related species of conifers in the Cupressaceae that are endemic to southern Chile and Argentina. Both are listed in Appendix I of the Convention on International Trade in Endangered Species of Fauna and Flora (CITES). The presence or absence of nodular (conspicuously pitted) end walls in the parenchyma cells provide good diagnostic characters to separate the two species wood anatomically, but the latter is sometimes difficult to distinguish. Therefore, a collaborative project was designed to study the chemical-molecular expression of these species by analyzing the heartwood using DART TOFMS (Direct Analysis in Real-Time (DART) Time-of-Flight Mass Spectrometry (TOFMS). This study compares the anatomical features of heartwood for both species and demonstrates that anatomy in conjunction with chemistry can separate them. DART TOFMS analysis combined with PCA was able to unequivocally determine taxonomic source with a statistical certainty of 99%. The mass spectra results obtained from heartwood demonstrated that identification is feasible after a few seconds, using a very small sample. DART TOFMS is a robust tool for reliable species identification and is useful to identify the taxonomic source of finished products or timber that are suspected of being illegally harvested.
Taxonomic revision of the genus Stenocephalum (Vernonieae, Asteraceae)

Authors: DEMATTEIS MASSIMILIANO , ANGULO MARÍA BETIANA
Published: April 2020

The genus Stenocephalum Sch.Bip. (Vernonieae, Asteraceae) can be distinguished from the remaining South American members of the tribe by 4–11 florets per capitula, cylindrical involucres and cymose inflorescences. It can also be separated from other American genera of the tribe by the pollen grains, which are tricolporate and echinolophate, with a total of 29 lacunae arranged in a regular pattern, with a lacuna at each pole and without equatorial lacunae (type “C” pollen). At present, the genus comprises 7 species distributed from Mexico to Argentina. In this paper, all the entities recognized up to now are described and illustrated and one species is added to the group. The possible phylogenetic relationships of the genus are also discussed and the geographic distribution of most species is revised to include larger areas.
Lectotype of Solidago ×niederederi (Asteraceae) selected from a recently rediscovered original material

Authors: SKOKANOVÁ KATARÍNA , MEREĎA Jr. PAVOL , ŠINGLIAROVÁ BARBORA , ŠPANIEL STANISLAV
Published: April 2020

Solidago ×niederederi Khek (1905: 22) is a hybrid between North-American S. canadensis Linnaeus (1753: 878) and European native S. virgaurea Linnaeus (1753: 880). Solidago canadensis was introduced to Europe in the 17th century (Kowarik 2003). It has spread invasively throughout Europe since the second half of the 19th century (Weber 1998), reaching, besides sites disturbed by human activity, also (semi)natural biotopes, as forest edges, abandoned meadows and field margins which are often inhabited by native S. virgaurea. Their hybrid was discovered for the first time in nature by a local schoolmaster Franz Niedereder in the area of Vorderstoder village (Austria). Niedereder sent a plant material of the assumed hybrid to Eugen Johan Khek (born in 1861, Neuhaus/Jindřichov Hradec; died in 1927, Vienna), the pharmacist and botanist who lived in Vienna since 1889 (Anonymous 1916). Khek described the hybrid species under the name S. ×niederederi in honour of his discoverer (Khek 1905). The protologue indicates that the relevant communication between Niedereder and Khek was going on between July 1900 (when they met for the first time) and February 1905 (when the hybrid’s description was published). Before its description, Khek studied the hybrid for four years and he saw a herbarium material from Niedereder as well as a living material. In the protologue, no particular herbarium specimens or illustrations had been indicated or associated with S. ×niederederi (Khek 1905).
An annotated checklist of the Iranian Brentidae (Coleoptera: Curculionoidea)
Authors: GHAHARI HASSAN , COLONNELLI ENZO
Published: April 2020

An annotated synopsis of Iranian Brentidae (Coleoptera: Curculionoidea) is provided as a basis for future studies, with notes on distribution and plant associations. In total, 123 species from 41 genera and 3 subfamilies, Apioninae (109 species within 32 genera), Brentinae (3 species within 3 genera) and Nanophyinae (11 species within 6 genera) are listed. Six species, Allomalia setulosa (Tournier, 1869), Corimalia fausti fausti (Reitter, 1890), Melanapion (Rhodapion) hauseri (Wagner, 1906), Protapion assimile assimile (Kirby, 1808), Pseudoperapion brevirostre (Herbst, 1797) and Titanomalia komaroffi (Faust, 1877) are new records for the fauna of Iran.
Konradus leehermani—a new genus and species of Philonthina from the Neotropical region and its phylogenetic relationships (Coleoptera: Staphylinidae: Staphylininae)
Authors: CHANI-POSSE MARIANA RAQUEL , RAMÍREZ-SALAMANCA JOSÉ MANUEL
Published: April 2020

Konradus leehermani Chani-Posse & Ramírez-Salamanca, a new genus and species of the subtribe Philonthina (tribe Staphylinini) from the Tropical Andes of Ecuador, is described and illustrated. A dataset of 57 morphological characters scored for 23 taxa representing main clades of Philonthina and its putative sister groups was prepared and analysed by maximum parsimony and Bayesian inference. Both analytical methods unambiguously placed Konradus within the Neotropical (NT) lineage of Philonthina. Phylogenetic relationships of Konradus with other Neotropical representatives are proposed and discussed.
Forecasting Severe Weather with Random Forests
Authors: Hill Aaron J. , Herman Gregory R. , Schumacher Russ S.
Published: April 2020

Using nine years of historical forecasts spanning April 2003–April 2012 from NOAA’s Second Generation Global Ensemble Forecast System Reforecast (GEFS/R) ensemble, random forest (RF) models are trained to make probabilistic predictions of severe weather across the contiguous United States (CONUS) at Days 1–3, with separate models for tornado, hail, and severe wind prediction at Day 1 in an analogous fashion to the Storm Prediction Center’s (SPC’s) convective outlooks. Separate models are also trained for the western, central, and eastern CONUS. Input predictors include fields associated with severe weather prediction, including CAPE, CIN, wind shear, and numerous other variables. Predictor inputs incorporate the simulated spatiotemporal evolution of these atmospheric fields throughout the forecast period in the vicinity of the forecast point. These trained RF models are applied to unseen inputs from April 2012 to December 2016, and their forecasts are evaluated alongside the equivalent SPC outlooks. The RFs objectively make statistical deductions about the relationships between various simulated atmospheric fields and observations of different severe weather phenomena that accord with the community’s physical understandings about severe weather forecasting. Using these quantified flow-dependent relationships, the RF outlooks are found to produce calibrated probabilistic forecasts that slightly underperform SPC outlooks at Day 1, but significantly outperform their outlooks at Days 2 and 3. In all cases, a blend of the SPC and RF outlooks significantly outperforms the SPC outlooks alone, suggesting that use of RFs can improve operational severe weather forecasting throughout the Day 1–3 period.
Walking Into the Sunset: How Criminal Achivement Shapes the Desistance Process: Criminal Achievement and the Desistance Process
Authors: Vidal Sabrina , Ouellet Frédéric , Dubois Marie-Ève
Published: April 2020

According to the criminal career paradigm, the link between past and future criminal activities is important and the desistance process may vary for individuals whose criminal trajectories were punctuated by failure compared with those who achieved a certain level of success. This study, based on the life narratives of 27 individuals who maintained a state of nonoffending for more than a year, examines how criminal achievement modulates the desistance process. The aim is to understand whether criminal achievement acts as a barrier or a facilitator in the desistance process. A short questionnaire based on the life-history calendar method was used to classify individuals according to the parameters of their criminal careers. Narrative life stories were then used to look at the obstacles and frustrations encountered during desistance. The results show the relation between criminal achievement and desistance is complex: success in criminal activities is not always hindering desistance.
Inter-relationships between left ventricular mass, geometry and arterial stiffness
Authors: Alem Manal M. , Alshehri Abdullah M.
Published: April 2020

Objective

To investigate the inter-relationships between left ventricular mass (LVM), left ventricular (LV) geometry and arterial stiffness parameters (aortic pulse wave velocity [Ao-PWV] and heart rate-corrected augmentation index [c-AIx]) in patients with chronic heart failure (CHF).

Methods

This study was a secondary analysis of existing data that were collected from patients with CHF New York Heart Association class I–III with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). Transthoracic echocardiography was performed on all patients, along with measurement of arterial stiffness parameters (Ao-PWV and c-AIx) using sphygmocardiography.

Results

A total of 73 patients (58 males) with a mean ± SD age of 55.9 ± 11.6 years were enrolled in this study. Of these, 20 patients (27.4%) had systemic hypertension, 46 (63.0%) had type 2 diabetes mellitus. Ischaemic heart disease was the main aetiology of CHF (63 of 73 patients; 86.3%). In multiple linear regression, the left ventricular mass index (LVMI) was significantly associated with c-AIx (β = –1.59) and EF (β = –1.51). Comparison of Ao-PWV among the four LV geometric patterns revealed significant differences.

Conclusion

In this cohort of CHF patients, LVMI was predicted by c-AIx and EF. The corresponding values of Ao-PWV were parallel in different LV geometric patterns and confirmed their adverse prognostic values.
Efficacy of combination terazosin and nifedipine therapy in postoperative treatment of distal ureteral stones after transurethral ureteroscopic lithotripsy
Authors: Ju Min , Yu Xiuyue , Wu Weiwei , Qu Jingkun , Zheng Jin
Published: April 2020

Objective

To investigate the efficacy of combination terazosin and nifedipine therapy in postoperative treatment of distal ureteral stones after transurethral ureteroscopic lithotripsy.

Methods

This prospective single-blinded randomized study enrolled 165 patients undergoing transurethral ureteroscopic lithotripsy in our hospital. Patients were randomized into three groups: control, terazosin, and combination treatment (terazosin and nifedipine). Stone discharge rates and times were recorded, along with side effects and complications. Visual Analogue Scale (VAS) score was used to evaluate pain for 7 days postoperatively. International Prostatic Symptoms Score (IPSS) was used to evaluate prostatic function; quality of life (QOL) was evaluated preoperatively and at 7 days postoperatively.

Results

The stone discharge rate was significantly higher in the combination group than in other groups; moreover, mean discharge time was shorter in the combination group. Beginning at 3 days postoperatively, VAS scores were dramatically lower in the combination group than in other groups; IPSS and QOL scores were also lower in the combination group. Edema recurrence was significantly less common in combination and terazosin groups than in the control group. Side effects were similar among groups.

Conclusion

Combination terazosin and nifedipine therapy was safe and effective in postoperative treatment of distal ureteral stones after transurethral ureteroscopic lithotripsy.
Long-segmental ureteral reconstruction using tubularization of ileal seromuscular fold: experimental canine study and preliminary clinical experience
Authors: Chen Qi , Zou Lujia , Liu Rongzong , Mao Shanhua , Hu Yun , Xu Chenyang , Jiang Haowen
Published: April 2020

Objective

This study was performed to investigate the feasibility of tubularization of the ileal seromuscular fold for long-segmental ureteral reconstruction in a canine model and assess the clinical application of this procedure.

Methods

The experimental study was conducted on six beagles. An ileal segment was chosen and folded along its longitudinal axis and thereafter sutured to tubularize the serous surface. The tubularization of the ileal seromuscular fold was designed to be 10 to 12 cm for ureteral substitution. The neo-ureters were pathologically examined. A patient in our hospital also underwent this reconstructive operation. Several blood parameters were assessed and urography was performed for postoperative evaluation.

Results

All animals and the patient tolerated the operation and recovered as planned. No severe postoperative complications occurred. Blood examination revealed that renal function was within the normal range. Urography indicated patency of urine excretion without leakage or stenosis. In the patient, antegrade urography showed rhythmic peristalsis of the neo-ureter. The pathologic examination revealed a healthy condition of the neo-ureter and an open lumen with a serous epithelial lining.

Conclusion

Ureteral reconstruction by tubularization of the ileal seromuscular fold is anatomically possible and was preliminarily validated in a patient in the clinical setting.
Reclaiming the fight against racism in the UK
Authors: Fekete Liz
Published: April 2020

In the light of highly politicised accusations of antisemitism against the Labour Party and its leader during the general election, the author argues for the necessity for activists to reclaim anti-racism. She shows how over a number of years the space for anti-racism has been shrinking. The professionalisation of anti-racism, especially around hate crime, has tended to shift focus from the social to the individual, from the institutional and systemic to personal hatred and bigotry, especially online. With the introduction of the government’s Prevent strategy, a multitude of movements from Right and Left are now considered extremists. Anti-racism has lost its international thrust and its cross-community depths. We should not, she argues, see the new anti-racism as just a change in narrative, but a systematic structural denial which is part and parcel of neoliberalism, witnessed in the chequered histories of those now empowered to promote equality.