bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of p-Type NiO Pocket and Ultra-Thin Graphene Layer on the RF Performance of β-Ga2O3 MOSFET
Authors: Yadava Narendra , Mani Shivangi , Chauhan R. K.
Published: April 2020

In this work, the RF performance of proposed p-type NiO pocket based β-Ga2O3/graphene heterostructure MOSFET has been investigated. The figure of merits (FOMs) for its performance investigation includes transconductance (gm), output conductance (gd), intrinsic capacitances (gate to drain capacitance Cgd and gate to source capacitance Cgs) and cut-off frequency (fT). The large signal CW RF performance is also investigated which includes output power (POUT), power-added efficiency (PAE) and power gain (Gp) as a key FOMs. The key idea behind this work is to demonstrate a device with improved RF performance and low leakages. The RF characteristics of the proposed device have been studied to show its utility in the wireless applications. The introduction of ultra-thin graphene layer beneath the channel region results in 0.85 times lower Cgs, 1.04 times improvement in fT and 1.5 dB superior GP in comparison to the p-type NiO pocket based β-Ga2O3 (NiO-GO) MOSFET. The proposed structure shows superior RF performance with low leakages.
Pharmacological activation of TGR5 promotes intestinal growth via a GLP-2-dependent pathway in mice
Authors: Hunt Jenna Elizabeth , Billeschou Anna , Windeløv Johanne Agerlin , Hartmann Bolette , Ullmer Christoph , Holst Jens Juul , Kissow Hannelouise
Published: April 2020

Using the specific Takeda G protein-receptor-5 (TGR5) agonist RO5527239 and GLP-2 receptor knockout mice, we show that activation of TGR5 led to the increase in colonic GLP-1 and GLP-2 concomitant with a GLP-2 dependent growth response in the proximal portion of the small intestine.
Gut leakage enhances sepsis susceptibility in iron-overloaded β-thalassemia mice through macrophage hyperinflammatory responses
Authors: Visitchanakun Peerapat , Saisorn Wilasinee , Wongphoom Jutamas , Chatthanathon Piraya , Somboonna Naraporn , Svasti Saovaros , Fucharoen Suthat , Leelahavanichkul Asada
Published: April 2020

Although the impact of iron accumulation in several organs of patients with thalassemia is well known, the adverse effect of iron accumulation in gut is not frequently mentioned. Here, we demonstrated iron-induced gut-permeability defect, impact of organismal molecules from gut translocation of, and macrophage functional defect upon the increased sepsis susceptibility in thalassemia mice.
Apohemoglobin-haptoglobin complex attenuates the pathobiology of circulating acellular hemoglobin and heme
Authors: Munoz Carlos J. , Pires Ivan S. , Baek Jin Hyen , Buehler Paul W. , Palmer Andre F. , Cabrales Pedro
Published: April 2020

This study highlights the apoHb-Hp complex as a novel therapeutic strategy to attenuate the adverse systemic and microvascular responses to intravascular Hb and heme exposure. In vitro and in vivo Hb exchange and heme transfer experiments demonstrated proof-of-concept Hb/heme ligand transfer to apoHb-Hp. The apoHb-Hp complex reverses Hb- and heme-induced systemic hypertension and microvascular vasoconstriction, preserves microvascular blood flow, and functional capillary density. In summary, the unique properties of the apoHb-Hp complex prevent adverse systemic and microvascular responses to Hb and heme-albumin exposure and introduce a novel therapeutic approach to facilitate simultaneous removal of extracellular Hb and heme.
Alpha Power Transformed Log-Logistic Distribution with Application to Breaking Stress Data
Authors: Aldahlan Maha A.
Published: April 2020

In this paper, a new three-parameter lifetime distribution is introduced; the new model is a generalization of the log-logistic (LL) model, and it is called the alpha power transformed log-logistic (APTLL) distribution. The APTLL distribution is more flexible than some generalizations of log-logistic distribution. We derived some mathematical properties including moments, moment-generating function, quantile function, Rényi entropy, and order statistics of the new model. The model parameters are estimated using maximum likelihood method of estimation. The simulation study is performed to investigate the effectiveness of the estimates. Finally, we used one real-life dataset to show the flexibility of the APTLL distribution.
Dynamic Characteristics of Encased Differential Gear Train with Journal Bearing
Authors: Yang Jie , Yue Yanjiong , Zhu Rupeng , Chen Weifang , Li Miaomiao
Published: April 2020

Taking the marine encased differential gear train as an example, the relationship between the journal bearing parameters and the meshing force of the transmission system is analyzed. In this paper, the dynamic model of the encased differential gear train with journal bearing is established considering the factors of time-varying meshing stiffness and comprehensive transmission error. In this dynamic model, four stiffnesses and four damping coefficients are applied to characterize the asymmetry and interaction of the oil film stiffness and damping of planet bearing. The system responses are calculated by the Fourier series numerical algorithm. The results show that the introduction of journal bearing in encased differential gear train can contribute to gearbox vibration reduction. Moreover, the planet bearing parameters (e.g., clearance-to-radius ratio and eccentricity ratio) of the differential stage affect the meshing forces of both the differential and encased stages. In addition, the influence of the planet bearing parameters of the encased stage on the meshing force of the encased stage is more obvious than that of the differential stage. This work may develop a theoretical analysis framework for the design and manufacture of marine transmission systems in the future.
Bound State Solutions of Three-Dimensional Klein-Gordon Equation for Two Model Potentials by NU Method
Authors: Tazimi N. , Ghasempour A.
Published: April 2020

In this study, we investigate the relativistic Klein-Gordon equation analytically for the Deng-Fan potential and Hulthen plus Eckart potential under the equal vector and scalar potential conditions. Accordingly, we obtain the energy eigenvalues of the molecular systems in different states as well as the normalized wave function in terms of the generalized Laguerre polynomials function through the NU method, which is an effective method for the exact solution of second-order linear differential equations.
Utilisation Efficiency of Construction Land in China’s Coastal Cities Based on Debt Level
Authors: Wang Hui , Qiao Lu , Tian Chuang , Lin Qiaoqiao
Published: April 2020

Optimising the allocation of population, land, and capital production resources is crucial for promoting an efficient urbanisation and solving the urban land financial problem. This study uses a panel threshold model to identify the response boundary of urban construction land use efficiency to government debt level for 51 postfinancial crisis Chinese coastal cities. The results indicate that the threshold of economic development level and provincial gross domestic product (per capita gross domestic product: pgdp) are 2.67 and 5.17, respectively. In cities with relatively backward economic development, an expansion of the government debt scale hinders the improvement of the utilisation efficiency of construction land. Also, the threshold value of the government’s accumulated debt level threshold (sd) is 15.83%. When cities fall below the government accumulated debt level threshold (sd < 15.83%), the new debt level has a positive effect on the utilisation efficiency of construction land. When sd > 15.83%, the new debt level impedes the improvement of the utilisation efficiency of construction land. Local governments should reduce their dependence on land finance in cities with high cumulative debt ratios, especially those with negative responses to both thresholds (pgdp and sd thresholds). This study’s findings can provide a reference for a sustainable promotion of new urbanisation in both China and in other countries to avoid the risk of land urbanisation.
Improvement of Flavonoids in Lemon Seeds on Oxidative Damage of Human Embryonic Kidney 293T Cells Induced by H2O2
Authors: Yang Dingyi , Jiang Yong , Wang Yuqing , Lei Qianqian , Zhao Xin , Yi Ruokun , Zhang Xin
Published: April 2020

In this study, flavonoids in lemon seeds (FLS) were used to assess its improvement on the oxidative damage of human embryonic kidney 293T cells (HEK 293T cells) induced by H2O2. In vitro experiments showed that the survival rates of HEK 293T cells treated with different flavonoid concentrations (50 μg/mL, 100 μg/mL, and 150 μg/mL) exceeded 95%, indicating no significant toxic effect. Compared with the normal group, H2O2 (0.3 mmol/L) resulted significantly in oxidative stress injury of HEK 293T cells. The survival rate of the damaged cells increased after treatment with flavonoids, and the survival rate of cells treated with a high concentration (150 μg/mL) of flavonoids was 76.2%. Flavonoids also effectively inhibited H2O2-induced apoptosis. At the same time, flavonoid treatment significantly reduced the malondialdehyde content in cells and increased the levels of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px). Quantitative polymerase chain reaction (qPCR) and Western blot analysis also suggested that FLS upregulated mRNA and protein expressions of CAT, SOD (SOD1, SOD2), GSH (GSH1), and GSH-Px in H2O2-induced oxidative damage of HEK 293T cells. The high-performance liquid chromatography analysis demonstrated that FLS contained six compounds, including gallocatechin, caffeic acid, epicatechin, vitexin, quercetin, and hesperidin. FLS were proven to have a good antioxidant capacity in vitro and improve significantly the oxidative damage of HEK 293T cells induced by H2O2. The biological activity value warrants investigation in additional studies.
Severe Generalized Epidermolysis Bullosa Simplex in Two Hong Kong Children due to De Novo Variants in KRT14 and KRT5
Authors: Chong Shuk Ching , Hon Kam Lun , Scaglia Fernando , Chow Chung Mo , Fu Yu Ming , Chiu Tor Wo , Leung Alexander K. C.
Published: April 2020

We report two Hong Kong children with severe generalized epidermolysis bullosa simplex (EBS), the most severe form of EBS, without a family history of EBS. EBS is a rare genodermatosis usually inherited in an autosomal dominant fashion although rare autosomal recessive cases have been reported. Genetic studies in these patients showed that the first case was due to a novel de novo heterozygous variant, c.377T>G (NM_000526.5 (c.377T>G, p.Leu126Arg)) in the KRT14 gene and the second case was due to a rare de novo heterozygous variant c.527A>G (NM_000424.4, c.527A>G, p.Asn176Ser) in the KRT5 gene. To our knowledge, the c.377T>G variant in the KRT14 gene has not been previously reported, and the c.527A>G variant in the KRT5 gene is a rare cause of severe generalized EBS. In severe generalized EBS, infants exhibit severe symptoms at the onset; however, they tend to improve with time. A precise genetic diagnosis in these two cases aided in counseling the families concerning the prognosis in their affected children and the recurrence risk for future pregnancies.
Enhanced Optical Output of Near-Ultraviolet Light-Emitting Diodes by a Monolayer of Nanospheres
Authors: Wan Wei , Chen Zhanxu , Chen Yongzhu , Chen Gengyan
Published: April 2020

The optical output of near-ultraviolet (NUV) light-emitting diodes (LEDs) was improved by including a monolayer of hexagonal close-packed polystyrene (PS) nanospheres. PS nanospheres with different sizes were deposited on the indium tin oxide layer of the NUV LEDs. The electroluminescence results showed that the light extraction efficiency of the NUV LEDs was increased by the inclusion of PS nanospheres, and the maximum optical output enhancement was obtained when the size of the nanospheres was close to the light wavelength. The largest enhancement of the optical output of 1.27-fold was obtained at an injection current of 100 mA. The enhanced optical output was attributed to part of the incident light beyond the critical angle being extracted when the exit surface of the NUV LEDs had a PS nanosphere monolayer. This method may serve as a low-cost and effective approach to raise the efficiency of NUV LEDs.
Real-World Experience with AGA Guidelines in the Management of Crohn’s Disease following Ileocolonic Resection: A Retrospective Cohort Study
Authors: Tang Shasha , Liu Wei , Qi Weilin , Yu Tunan , Cao Qian , Ge Xiaolong , Zhou Wei
Published: April 2020

Background. Postoperative endoscopic recurrence (PER) is common in patients with Crohn’s disease (CD) after surgery. The impact of the American Gastroenterological Association (AGA) guideline adherence on PER in real life remains unclear. Methods. The postoperative management of CD patients undergoing ileocolonic resection with anastomosis from 2017 to 2018 was conducted based on the AGA guidelines. Colonoscopies were performed within one year after surgery. Clinical data and risk factors for endoscopic recurrence were analyzed focusing on postoperative pharmacological prophylaxis. Results. All patients were at a high risk of postoperative recurrence according to the AGA guidelines. PER occurred in 29 (28.7%) of these patients. The overall PER rate was 39.2% at one year. The PER rate in patients treated with nitroimidazole, thiopurines, infliximab, or a combination of thiopurines and infliximab for postoperative prophylaxis was 88.1%, 34.1%, 20.5%, and 0%, respectively. Cox regression showed that smoking at the time of surgery and AGA guideline adherence were independent factors associated with PER (HR: 3.75, 95% CI: 1.36-10.33, P=0.01; HR: 0.36, 95% CI: 0.15-0.86, P=0.02). In addition, further investigation revealed that educational background was the main factor related to patients’ nonadherence to AGA guidelines. Conclusions. The majority of CD patients who undergo surgery in clinical practice may be at a high risk of disease recurrence. Thiopurines and infliximab are effective in preventing endoscopic recurrence. Guideline nonadherence is associated with PER at one year, thus indicating that there is room for improvement in adherence to the AGA guidelines.
Spatiotemporal Regulation of ΔNp63 by TGFβ-Regulated miRNAs Is Essential for Cancer Metastasis
Authors: Bui Ngoc H.B. , Napoli Marco , Davis Andrew John , Abbas Hussein A. , Rajapakshe Kimal , Coarfa Cristian , Flores Elsa R.
Published: April 2020

ΔNp63 is a transcription factor of the p53 family and has crucial functions in normal development and disease. The expression pattern of ΔNp63 in human cancer suggests dynamic regulation of this isoform during cancer progression and metastasis. Many primary and metastatic tumors express high levels of ΔNp63, while ΔNp63 loss is crucial for tumor dissemination, indicating an oscillatory expression of ΔNp63 during cancer progression. Here, we use genetically engineered orthotopic mouse models of breast cancer to show that while depletion of ΔNp63 inhibits primary mammary adenocarcinoma development, oscillatory expression of ΔNp63 in established tumors is crucial for metastatic dissemination in breast cancer. A TGFβ-regulated miRNA network acted as upstream regulators of this oscillatory expression of ΔNp63 during cancer progression. This work sheds light on the pleiotropic roles of ΔNp63 in cancer and unveils critical functions of TGFβ in the metastatic process.

Significance:

This study unveils TGFβ signaling and a network of four miRNAs as upstream regulators of ΔNp63, providing key information for the development of therapeutic strategies to treat cancers that commonly overexpress ΔNp63.
Blocking Angiopoietin-2 Promotes Vascular Damage and Growth Inhibition in Mouse Tumors Treated with Small Doses of Radiation
Authors: Kallio Pauliina , Jokinen Elina , Högström Jenny , Das Suvendu , Heino Sarika , Lähde Marianne , Brodkin Jefim , Korhonen Emilia A. , Alitalo Kari
Published: April 2020

Abnormal vasculature in tumors leads to poor tissue perfusion and cytostatic drug delivery. Although drugs inducing vascular normalization, for example, angiopoietin-2 (Ang2)-blocking antibodies, have shown promising results in preclinical tumor models, clinical studies have so far shown only little efficacy. Because Ang2 is known to play a protective role in stressed endothelial cells, we tested here whether Ang2 blocking could enhance radiation-induced tumor vascular damage. Tumor-bearing mice were treated with anti-Ang2 antibodies every 3 or 4 days starting 3 days before 3 × 2 Gy or 4 × 0.5 Gy whole-body or tumor-focused radiation. Combination treatment with anti-Ang2 and radiation improved tumor growth inhibition and extended the survival of mice with melanoma or colorectal tumors. Single-cell RNA-sequencing revealed that Ang2 blocking rescued radiation-induced decreases in T cells and cells of the monocyte/macrophage lineage. In addition, anti-Ang2 enhanced radiation-induced apoptosis in cultured endothelial cells. In vivo, combination treatment decreased tumor vasculature and increased tumor necrosis in comparison with tumors treated with monotherapies. These results suggest that a combination of Ang2-blocking antibodies with radiation increases tumor growth inhibition and extends the survival of tumor-bearing mice.

Significance:

These findings offer a preclinical rationale for further testing of the use of radiation in combination with Ang2-blocking antibodies to improve the overall outcome of cancer treatment.
High Expression of Interleukin-12A and Its Association with the Clinicopathology and Prognosis of Differentiated Thyroid Cancer
Authors: Zhang Guo-Qiang , Shen Chen-Tian , Song Hong-Jun , Qiu Zhong-Ling , Luo Quan-Yong
Published: April 2020

Background: The inflammatory microenvironment is closely related to the occurrence and development of cancer. Members of the interleukin-12 (IL-12) cytokine family play synergistic or antagonistic roles in the tumor microenvironment, in the form of classic heterodimers or newly discovered monomers or homodimers. Objective: The purpose of this study was to investigate the association between IL-12A and the clinicopathology and prognosis of differentiated thyroid cancer (DTC). Methods: A total of 101 pathologically confirmed DTC patients were included in this study. Immunohistochemistry was performed to assess IL-12A expression in DTC and corresponding paracancerous tissues. The associations of IL-12A with clinicopathology and prognosis were evaluated. Results: IL-12A was expressed in both normal thyroid tissues and DTC, but its expression level was significantly higher in DTC than in normal thyroid tissues (p < 0.001). IL-12A was positively correlated with tumor size (p = 0.027), risk stratification (p = 0.020), and TNM (Tumor-Node-Metastasis) stage (p = 0.024), but not with age, sex, pathological type, multifocality, extrathyroid extension, lymph node metastasis, and distant metastasis (all p > 0.05). Lymphocytic thyroiditis was found in 26/101 patients (25.7%), which was negatively associated with IL-12A expression (p = 0.018). Multivariate logistic regression analysis showed that risk stratification was the significant independent predictor of IL-12A expression. The rate of disease persistence or recurrence (P&R) was 13/101 (12.9%), and a positive relationship was found between IL-12A expression and P&R (p = 0.020). Disease-free survival was affected by factors such as tumor size, extrathyroid extension, tumor stage (T stage), and IL-12A expression, with p values of 0.006, 0.048, 0.002, and 0.012, respectively. Multivariate Cox proportional-hazards analysis showed that tumor size ≥2 cm (hazard ratio [HR] = 4.041 [95% CI: 1.144–14.274], p = 0.031) and high IL-12A expression (HR = 4.027 [95% CI 1.014–15.994], p = 0.049) were independent predictors of prognosis of DTC patients. Conclusions: IL-12A is highly expressed in DTC and is associated with disease aggressiveness. In addition, IL-12A is an independent predictor of the outcome of DTC.
Coexistence of Autoimmune Hyper- and Hypothyroidism in a Kindred with Reduced Sensitivity to Thyroid Hormone
Authors: Abdellaoui Yasmine , Magkou Dimitra , Bakopoulou Sofia , Zaharia Ramona , Raffin-Sanson Marie-Laure , Cazabat Laure
Published: April 2020

Introduction: Resistance to thyroid hormone beta (RTHβ) is a rare disease with an autosomal dominant transmission. Diagnosis may be challenging especially in patients with hyper- or hypothyroidism. Case Presentation: A 31-year-old male patient with suppressed thyroid-stimulating hormone (TSH), elevated free thyroxine and free triiodothyronine, along with high thyroid receptor antibodies was diagnosed with Graves’ disease. Benzylthiouracil was started. One month later, reduced sensitivity to thyroid hormones was suspected because of persistently high thyroid hormone levels contrasting with high TSH level. Molecular analysis highlighted a 10c.1357C>T p.P453S mutation in the thyroid hormone receptor beta gene (THRB). RTHβ was diagnosed. Several relatives also had RTHβ (the mother, the young son, and 2 out of 3 siblings). Autoimmune hypothyroidism was present in the mother, whereas 2 out of 3 siblings had asymptomatic autoimmunity. Discussion/Conclusion: Both Graves’ disease and autoimmune hypothyroidism were described in patients with RTHβ. We show here for the first time that autoimmune hypo- and hyperthyroidism may coexist in kindred with RTHβ. Seven previously published cases of Graves’ disease and RTHβ were retrieved and analyzed. Treatments and thyroid hormone level targets are discussed as well as the possible link between RTHβ and autoimmune thyroid diseases.
Erfolgreiche Applikation von modifizierten Keystone-Lappen nach Hauttumorablation
Authors: Huang Jiuzuo , Chan Woo Kim , Wang Xiaojun , Yumo Zhao , Nanze Yu , Ru Zhao , Ming Bai , Xiao Long , Park Tae Hwan
Published: April 2020

Die Ablation von Hauttumoren und präkanzerösen Hautläsionen geht mit signifikanten Weichteildefekten einher. Seit einiger Zeit gewinnen Keystone-Lappen als einfaches, vielseitiges und zuverlässiges Verfahren an Beliebtheit. Wir untersuchten die Wirksamkeit der Weichteilrekonstruktion mit modifizierten Keystone-Lappen nach Hauttumorablation in 2 Zentren. Hierzu werteten wir die Akten von Patienten aus, bei denen im Zeitraum von Januar 2017 bis Dezember 2017 eine modifizierte Keystone-Lappenrekonstruktion nach Exzision eines Hauttumors durchgeführt worden war. Diagnose, Lokalisation, Lappengröße und Komplikationen wurden erfasst. 41 modifizierte Keystone-Lappen wurden analysiert; die Größe der abzudeckenden Defekte reichte von 1cm × 1cm bis 18cm × 9,5cm, bei einer durchschnittlichen Größe von 9,8cm × 6,4cm. Gemäß unserer Auswahlstrategie wurde für jeden Weichteildefekt ein modifizierter Keystone-Lappen gestaltet. Die Lappenmaße reichten von 2,2cm × 1cm bis 26cm × 10cm, bei einer durchschnittlichen Größe von 14,3cm × 7,5cm. Bei 2 Patienten (4,9%) trat eine geringgradige Wunddehiszenz auf und bei einem Patienten (2,4%) ein partieller Lappenverlust, aber in allen Fällen heilten die Wunden nach lokaler Wundversorgung ab, ohne dass chirurgische Eingriffe erforderlich wurden. Unsere Auswahlstrategie ist eine durchführbare und zuverlässige Option für die Weichteilrekonstruktion mit modifizierten Keystone-Lappen nach Exzision eines Hauttumors.
Subunguales Melanom: Weniger invasives operatives Verfahren als Standard etablieren
Authors: Schnabl-Scheu Saskia
Published: April 2020

Background: Amputation is the standard of care even for early-stage subungual melanomas (SUMs), known as nail apparatus melanoma, because the nail bed and nail matrix are close to the distal phalanx. However, a recent study demonstrated that not all patients with SUMs had histologic invasion of the underlying distal phalanx. As most SUMs occur in the thumb or big toe, amputation of either the thumb or big toe substantially interferes with activities of daily living, including poor cosmesis, loss of function, and phantom pain. Non-amputative digit preservation surgery can thus be applied in such cases without compromising patient prognosis. Methods: We are conducting a multi-institutional single-arm trial to confirm the safety and efficacy of non-amputative digit preservation surgery. We will compare our results with those reported in the Japanese Melanoma Study, in which patients underwent amputation for SUMs as a traditional standard of care. Patients aged between 20 and 80 years with stage I, II, or III without evidence of tumor invasion to the underlying distal phalanx on preoperative radiograph are included in the study. The primary endpoint is major relapse-free survival (major RFS), which does not include local recurrence as an event; secondary endpoints include overall survival, digit-preservation survival, relapse-free survival, local relapse-free survival, partial relapse-free survival, and incidence of adverse events. A total of 85 patients from 21 Japanese institutions will be recruited within 5.5 years, and the follow-up period will last at least 5 years. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in August 2017, and patient enrollment began in November 2017. Ethical approval was obtained from each institutionʼs Institutional Review Board prior to patient enrollment. Discussion: This is the first prospective trial to confirm the safety and efficacy of non-amputative digit preservation surgery for SUM without distant metastasis or bony invasion. The results of this trial could provide evidence to support this less-invasive surgery as a new standard of care to preserve adequately functioning digits. Trial Registration: Registry number: UMIN000029997 . Date of Registration: 16/Nov/2017. Date of First Participant Enrollment: 12/Dec/2017.
Chromoblastomykose: Mit der Kombination aus PDT und Antimykotika zum Erfolg
Authors: Lehmann Percy
Published: April 2020

Background: Chromoblastomycosis is a chronic skin and subcutaneous fungal infection caused by dematiaceous fungi and is associated with low cure and high relapse rates. In southern China, Fonsecaea monophora and Fonsecaea pedrosoi are the main causative agents. Principal findings: We treated 5 refractory and complex cases of chromoblastomycosis with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with oral antifungal drugs. The lesions improved after 4 to 9 sessions of ALA-PDT treatment at an interval of one or two weeks, and in some cases, mycological testing results became negative. The isolates were assayed for susceptibility to antifungal drugs and ALA-PDT in vitro, revealing sensitivity to terbinafine, itraconazole and voriconazole, with ALA-PDT altering the cell wall and increasing reactive oxygen species production. Conclusions: These results provide the basis for the development of a new therapeutic approach, and ALA-PDT combined with oral antifungal drugs constitutes a promising alternative method for the treatment of refractory and complex cases of chromoblastomycosis.
Hautalterung: Über die Rolle von Fibroblasten-Wachstumsfaktoren
Authors: Schulz Andrea
Published: April 2020

Cutaneous aging is a complex and continuous biological process characterized by cellular and molecular alterations, with progressive reduction of the bodyʼs capacity to maintain the homeostasis, senescence, and/or apoptosis of the dermal cells. Fibroblast growth factors (FGF) have elicited studies to evaluate their role of repair and remodeling of the dermis during the skin anti-aging process, since they are regulatory proteins that mediate important signaling pathways and act on cell regeneration and repair processes. FGF acts primarily through binding to tyrosine kinase receptors through the autophosphorylation of their residues, promoting the phosphorylation of serine, threonine, and tyrosine residues of specific target proteins such as Raf-1, MAPK/Erk kinase, and extracellular signal-regulated kinase-1, which are part of the cascade of MAP kinases (mitogen-activated protein kinase). Then, FGF initiate signaling cascades inside the cell, where each kinase activates the following by phosphorylation, resulting in alterations of cellular functions. In addition, the FGF has a relevant role in anti-aging therapy because it is related to collagen and elastin synthesis activation responsible for skin resistance and elasticity, characteristics that are diminished with skin aging. Thus, the present article aims to review several scientific studies that demonstrated the cell signaling involved with the action of FGF on skin aging.
Do multi ao bilateralismo
Authors: Donadelli Laura Meneghim , Pereira Matheus De Oliveira
Published: April 2020

O presente artigo analisa o engajamento dos Estados Unidos da América (EUA) na América Latina, enquadrando como foco da análise o campo da segurança hemisférica. A partir de uma perspectiva que combina história e conjuntura, identificamos duas lógicas principais de projeção dos interesses de segurança estadunidenses sobre a região: o multi e o bilateralismo. Associamos tais lógicas à conjuntura e à permeabilidade dos países da região às agendas estadunidenses em diferentes momentos, tomando como referência fontes documentais e a literatura corrente. Assim sendo, organizamos o trabalho em quatro seções: Na primeira delas, destacamos o lugar da segurança na construção da hegemonia dos EUA sobre o continente; em seguida apresentamos de modo sucinto os principais conceitos empregados na análise, como as Seguranças Coletiva, Cooperativa e Multidimensional. A terceira seção sumariza a evolução histórica da cooperação regional em segurança e, por fim, são apresentadas algumas considerações finais sobre a temática.
Deformações da interioridade
Authors: Alonso Mariangela
Published: April 2020

A arte expressionista realiza-se por meio da tendência à deformação dos aspectos naturais da realidade como forma de traduzir de modo subjetivo o indivíduo e o cenário que o cerca, reivindicando, assim, a presença dos sentimentos em oposição à representação objetiva. As questões suscitadas pela estética expressionista não deixaram de se fazer sentir na escrita de O lustre (1946), segundo romance de Clarice Lispector, cujas confluências remetem a traços do grotesco. O plano discursivo desta narrativa revela-se cruzado, demorado e interrompido a todo o momento por reflexões e miragens da personagem Virgínia. Nesse contexto, o objetivo deste artigo é focalizar marcas da estética expressionista como força dissonante da ficção de Clarice Lispector.
O discurso homoerótico feminino na canção e a ditadura militar brasileira
Authors: Gonçalves Renato
Published: April 2020

No presente artigo, analisamos o discurso homoerótico feminino na canção brasileira em relação à ditadura militar a partir do processo censório do fonograma “O Sorvete” (1974), da cantora, compositora e instrumentista assumidamente lésbica Tuca (1944 - 1978). Após o resgate da questão homoerótica na música brasileira e da trajetória da artista, discutimos as práticas da censura musical e as estratégias de defesa do discurso homoerótico feminino, além de esmiuçarmos o erotismo contido na obra de Tuca. Como resultados, levantamos questionamentos acerca do direcionamento conservador da ditadura militar, a elevação da subjetividade e do homoerotismo à categoria política no cenário pós-1968 e a invisibilidade de Tuca dentro da historiografia oficial da canção popular-comercial brasileira.
Ablation at Right Coronary Cusp as an Alternative and Favorable Approach to Eliminate Premature Ventricular Complexes Originating From the Proximal Left Anterior Fascicle
Authors: Chen Songwen , Lu Xiaofeng , Peng Shi , Xue Yumei , Zhou Genqing , Ling Zhiyu , Wei Yong , Yang Keping , Fu Wenjun , Cai Lidong , Xu Juan , Ouyang Feifan , Liu Shaowen
Published: April 2020

Background:

Premature ventricular complex (PVC) with narrow QRS duration originating from proximal left anterior fascicle (LAF) is challenging for ablation. This study was performed to evaluate the safety and feasibility of ablation from right coronary cusp (RCC) for proximal LAF-PVC and to investigate this PVC’s characteristics.

Methods:

Mapping at RCC and left ventricle and ECG analysis were performed in 20 patients with LAF-PVC.

Results:

The earliest activation site (EAS), with Purkinje potential during both PVC and sinus rhythm, was localized at proximal LAF in 8 patients (proximal group) and at nonproximal LAF in 12 patients (nonproximal group). The Purkinje potential preceding PVC-QRS at the EAS in proximal group (32.6±2.5 ms) was significantly earlier than that in nonproximal group (28.3±4.5 ms,
P
=0.025). Similar difference in the Purkinje potentials preceding sinus rhythm QRS at the EAS was also observed between proximal and nonproximal groups (35.1±4.7 versus 25.2±5.0 ms,
P
<0.001). In proximal group, the distance between the EAS to left His bundle and to RCC was shorter than that of nonproximal group (12.3±2.8 versus 19.7±5.0 mm,
P
=0.002, and 3.9±0.8 versus 15.7±7.8 mm,
P
<0.001, respectively). No difference in the distance from RCC to proximal LAF was identified between the 2 groups. PVCs were successfully eliminated from RCC for all proximal groups but at left ventricular EAS for nonproximal groups. The radiofrequency application times, ablation time, and procedure time of nonproximal group were longer than that of proximal group. Electrocardiographic analysis showed that, when compared with nonproximal group, the PVCs of proximal group had narrower QRS duration; smaller S wave in leads I, V
5
, and V
6
; lower R wave in leads I, aVR, aVL, V
1
, V
2
, and V
4
; and smaller q wave in leads III and aVF. The QRS duration difference (PVC-QRS and sinus rhythm QRS) <15 ms predicted the proximal LAF origin with high sensitivity and specificity.

Conclusions:

PVCs originating from proximal LAF, with unique electrocardiographic characteristics, could be eliminated safely from RCC.
Irrigated Microwave Catheter Ablation Can Create Deep Ventricular Lesions Through Epicardial Fat With Relative Sparing of Adjacent Coronary Arteries
Authors: Qian Pierre C. , Barry Michael A. , Tran Vu T. , Lu Juntang , McEwan Alistair , Thiagalingam Aravinda , Thomas Stuart P.
Published: April 2020

Background:

Radiofrequency ablation depth can be inadequate to reach intramural or epicardial substrate, and energy delivery in the pericardium is limited by penetration through epicardial fat and coronary anatomy. We hypothesized that open irrigated microwave catheter ablation can create deep myocardial lesions endocardially and epicardially though fat while acutely sparing nearby the coronary arteries.

Methods:

In-house designed and constructed irrigated microwave catheters were tested in in vitro phantom models and in 15 sheep. Endocardial ablations were performed at 140 to 180 W for 4 minutes; epicardial ablations via subxiphoid access were performed at 90 to 100 W for 4 minutes at sites near coronary arteries.

Results:

Epicardial ablations at 90 to 100 W produced mean lesion depth of 10±4 mm, width 18±10 mm, and length 29±8 mm through median epicardial fat thickness of 1.2 mm. Endocardial ablations at 180 W reached depths of 10.7±3.3 mm, width of 16.6±5 mm, and length of 20±5 mm. Acute coronary occlusion or spasm was not observed at a median separation distance of 2.7 mm (IQR, 1.2–3.4 mm). Saline electrodes recorded unipolar and bipolar electrograms; microwave ablation caused reductions in voltage and changes in electrogram morphology with loss of pace-capture. In vitro models demonstrated the heat sink effect of coronary flow, as well as preferential microwave coupling to myocardium and blood as opposed to lung and epicardial fat phantoms.

Conclusions:

Irrigated microwave catheter ablation may be an effective ablation modality for deep ventricular lesion creation with capacity for fat penetration and sparing of nearby coronary arteries because of cooling endoluminal flow. Clinical translation could improve the treatment of ventricular tachycardia arising from mid myocardial or epicardial substrates.
Validation of Risk Prediction Models to Detect Asymptomatic Carotid Stenosis
Authors: Poorthuis Michiel H. F. , Halliday Alison , Massa M. Sofia , Sherliker Paul , Clack Rachel , Morris Dylan R. , Clarke Robert , de Borst Gert J. , Bulbulia Richard , Lewington Sarah
Published: April 2020

Background

Significant asymptomatic carotid stenosis (
ACS
) is associated with higher risk of strokes. While the prevalence of moderate and severe
ACS
is low in the general population, prediction models may allow identification of individuals at increased risk, thereby enabling targeted screening. We identified established prediction models for
ACS
and externally validated them in a large screening population.

Methods and Results

Prediction models for prevalent cases with ≥50% ACS were identified in a systematic review (975 studies reviewed and 6 prediction models identified [3 for moderate and 3 for severe
ACS
]) and then validated using data from 596 469 individuals who attended commercial vascular screening clinics in the United States and United Kingdom. We assessed discrimination and calibration. In the validation cohort, 11 178 (1.87%) participants had ≥50% ACS and 2033 (0.34%) had ≥70%
ACS
. The best model included age, sex, smoking, hypertension, hypercholesterolemia, diabetes mellitus, vascular and cerebrovascular disease, measured blood pressure, and blood lipids. The area under the receiver operating characteristic curve for this model was 0.75 (95%
CI,
0.74–0.75) for ≥50%
ACS
and 0.78 (95%
CI,
0.77–0.79) for ≥70%
ACS
. The prevalence of ≥50%
ACS
in the highest decile of risk was 6.51%, and 1.42% for ≥70%
ACS
. Targeted screening of the 10% highest risk identified 35% of cases with ≥50%
ACS
and 42% of cases with ≥70%
ACS
.

Conclusions

Individuals at high risk of significant
ACS
can be selected reliably using a prediction model. The best‐performing prediction models identified over one third of all cases by targeted screening of individuals in the highest decile of risk only.
Generating Global Priority for Addressing Rheumatic Heart Disease: A Qualitative Policy Analysis
Authors: Shawar Yusra Ribhi , Shiffman Jeremy
Published: April 2020

Background

Rheumatic heart disease (RHD) poses a high burden in low‐income countries, as well as among indigenous and other socioeconomically disadvantaged populations in high‐income countries. Despite its severity and preventability, RHD receives insufficient global attention and resources. We conducted a qualitative policy analysis to investigate the reasons for recent growth but ongoing inadequacy in global priority for addressing RHD.

Methods and Results

Drawing on social science scholarship, we conducted a thematic analysis, triangulating among peer‐reviewed literature, organizational documents, and 20 semistructured interviews with individuals involved in RHD research, clinical practice, and advocacy. The analysis indicates that RHD proponents face 3 linked challenges, all shaped by the nature of the issue. With respect to
leadership and governance
, the fact that RHD affects mostly poor populations in dispersed regions complicates efforts to coordinate activities among RHD proponents and to engage international organizations and donors. With respect to
solution definition
, the dearth of data on aspects of clinical management in low‐income settings, difficulties preventing and addressing the disease, and the fact that RHD intersects with several disease specialties have fueled proponent disagreements about how best to address the disease. With respect to
positioning
, a perception that RHD is largely a problem for low‐income countries and the ambiguity on its status as a noncommunicable disease have complicated efforts to convince policy makers to act.

Conclusions

To augment RHD global priority, proponents will need to establish more effective governance mechanisms to facilitate collective action, manage differences surrounding solutions, and identify positionings that resonate with policy makers and funders.
Phenome‐Wide Analysis of Short‐ and Long‐Run Disease Incidence Following Recurrent Pregnancy Loss Using Data From a 39‐Year Period
Authors: Westergaard David , Nielsen Anna Pors , Mortensen Laust Hvas , Nielsen Henriette Svarre , Brunak Søren
Published: April 2020

Background

It is unclear how recurrent pregnancy loss (
RPL
) impacts disease risk and whether there is a difference in risk between women with or without a live birth before
RPL
(primary versus secondary
RPL
). We investigated the disease risk following
RPL
, and whether there was a difference between primary and secondary
RPL
.

Methods and Results

Using population‐wide healthcare registries from Denmark, we identified a cohort of 1 370 896 ever‐pregnant women aged 12 to 40 years between 1977 and 2016. Of this cohort, 10 691 (0.77%) fulfilled the criteria for
RPL
(50.0% primary
RPL
). Average follow‐up was 15.8 years. Incidence rate ratios were calculated in a phenome‐wide manner. Diagnoses related to assessment and diagnosis of
RPL
and those appearing later in life were separated using a mixture model. Primary
RPL
increased the risk of subsequent cardiovascular disorders, including atherosclerosis, cerebral infarction, heart failure, and pulmonary embolism, as well as systemic lupus erythematosus, chronic obstructive pulmonary disease, anxiety, and obsessive‐compulsive disorder. Women with secondary
RPL
had no increased risk of cardiovascular disorders. However, we observed an increased risk of gastrointestinal disorders such as irritable bowel syndrome and intestinal malabsorption, as well as mental disorders and obstetric complications.

Conclusions

RPL
is a risk factor for a spectrum of disorders, which is different for primary and secondary
RPL
. Screening following
RPL
explains some associations, but the remaining findings suggest that
RPL
influences or shares cause with cardiovascular disorders, autoimmune disorders, and mental disorders. Research into the pathophysiology of
RPL
and later diseases merits further investigation.
Long‐Term (10‐Year) Outcomes of Stenting or Bypass Surgery for Left Main Coronary Artery Disease in Patients With and Without Diabetes Mellitus
Authors: Lee Kyusup , Ahn Jung‐Min , Yoon Yong‐Hoon , Kang Do‐Yoon , Park Seo‐Young , Ko Euihong , Park Hanbit , Cho Sang‐Cheol , Park Sangwoo , Kim Tae Oh , Lee Pil Hyung , Lee Seung‐Whan , Park Seong‐Wook , Park Duk‐Woo , Park Seung‐Jung
Published: April 2020

Background

Data are still limited regarding whether there are differential long‐term outcomes after percutaneous coronary intervention versus coronary artery bypass grafting (
CABG
) for left main coronary artery disease with or without diabetes mellitus (
DM
).

Methods and Results

Using the 10‐year data from the
MAIN
‐
COMPARE
(Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty Versus Surgical Revascularization) registry, we sought to examine the effect of
DM
on comparative outcomes after percutaneous coronary intervention or
CABG
in patients with unprotected left main coronary artery disease. The outcomes of interest were all‐cause mortality; a composite of death, Q‐wave myocardial infarction, or stroke; and target‐vessel revascularization. The primary adjusted analyses were performed with the use of propensity scores and inverse‐probability weighting. Of 2240 patients with left main coronary artery revascularization, 722 (32%) had
DM
. In the overall population, the adjusted 10‐year risks of death and composite outcome were similar between percutaneous coronary intervention and
CABG
, irrespective of
DM
status (
P
interaction
: 0.41, mortality; 0.40, composite outcome). However, in the cohort of bare‐metal stents and concurrent
CABG
, we observed differential outcomes after stenting and
CABG
by
DM
status (
P
interaction
: 0.09, mortality; 0.04, composite outcome), favoring
CABG
in patients with DM. In the cohort of drug‐eluting stents and concurrent
CABG
, the better effect of
CABG
over stenting was narrowed in patients with DM without a significant interaction (
P
interaction
: 0.63, mortality; 0.47, composite outcome).

Conclusions

In this cohort of patients with longest follow‐up who underwent left main coronary artery revascularization, the clinical impact of
DM
favoring
CABG
over percutaneous coronary intervention has diminished over time from the bare‐metal stent to the drug‐eluting stent era.

Registration

URL
:
http://www.clini​caltr​ials.gov
. Unique identifier:
NCT
02791412.
Association Between Walking Pace and Stroke Incidence
Authors: Hayes Sara , Forbes John F. , Celis-Morales Carlos , Anderson Jana , Ferguson Lyn , Gill Jason M.R. , Gray Stuart , Hastie Claire , Iliodromoti Stamatina , Lyall Donald , Pellicori Pierpaolo , Sattar Naveed , Welsh Claire E. , Pell Jill
Published: April 2020

Background and Purpose—

Stroke incidence in younger and middle-aged people is growing. Despite this, its associations in this subset of the stroke population are unknown, and prevention strategies are not tailored to meet their needs. This study examined the association between self-reported walking pace and incident stroke.

Methods—

Data from the UK Biobank were used in a prospective population-based study. Three hundred and sixty-three thousand, one hundred and thirty-seven participants aged 37 to 73 years (52% women) were recruited. The associations of self-reported walking pace with stroke incidence over follow-up were investigated using Cox proportional-hazard models.

Results—

Among 363,137 participants, 2705 (0.7%) participants developed a fatal or nonfatal stroke event over the mean follow-up period of 6.1 years (interquartile range, 5.4–6.7). Slow walking pace was associated with a higher hazard for stroke incidence (hazard ratio [HR], 1.45 [95% CI, 1.26–1.66];
P
<0.0001). Stroke incidence was not associated with walking pace among people <65 years of age. However, slow walking pace was associated with a higher risk of stroke among participants aged ≥65 years (HR, 1.42 [95% CI, 1.17–1.72];
P
<0.0001). A higher risk for stroke was observed on those with middle (HR, 1.28 [95% CI, 1.01–1.63];
P
=0.039) and higher (HR, 1.29 [95% CI, 1.05–1.69];
P
=0.012) deprivation levels but not in the least deprived individuals. Similarly, overweight (HR, 1.30 [95% CI, 1.04–1.63];
P
=0.019) and obese (HR, 1.33 [95% CI, 1.09–1.63];
P
=0.004) but not normal-weight individuals had a higher risk of stroke incidence.

Conclusions—

Slow walking pace was associated with a higher risk of stroke among participants over 64 years of age in this population-based cohort study. The addition of the measurement of self-reported walking pace to primary care or public health clinical consultations may be a useful screening tool for stroke risk.
Revision of the genus Reddellomyces (Tuberaceae): a combination of molecular and morphological analysis provides insights into species diversity

Authors: SBISSI IMED , NOUIOUI IMEN , TÜRKOGLU AZIZ , NEFFATI MOHAMED , GTARI MAHER
Published: April 2020

The Australian genus Reddellomyces comprises several closely related symbiotic ascomycetes with chambered gleba (solid ptychothecium), ornamented ascospores and cylindrical paraphyses that are sometimes difficult to identify based on morphological aspects. Several Reddellomyces species are spread with their Australian host plants (Eucalyptus and Acacia) worldwide including Mediterranean areas. Specimens of an unusual truffle were collected from Acacia saligna stands in Tunisian semi-arid lands and eucalypt forest of Antalya (Turkey) dominated by E. camaldulensis Dehnh. and E. grandis W. Hill. Based on morphological features, these fungi are affiliated to Reddellomyces genus, differing from other species of the genus mainly based on ascospore size. Further analysis based on nuclear rDNA LSU and ITS and digital RFLP of the ITS sequenced amplicons with selected restriction endonucleases showed the unique identity of Tunisian specimens within the genus Reddellomyces. Our results showed also that at least six Reddellomyces species are present including two unnamed species restricted to Australia.