bluuebunny/crossref_metadata_2025 huggingface dataset:
A note on the non-inertial similarity solution for von Kármán swirling flow
Authors: Combrinck Madeleine L.
Published: October 2020

This note proposes a non-inertial similarity solution for the classic von Kármán swirling flow as perceived from the rotational frame. The solution is obtained by implementing non-inertial similarity parameters in the non-inertial boundary layer equations. This reduces the partial differential equations to a set of ordinary differential equations that is solved through an integration routine and shooting method.
Sparse Optical Flow Computation Using Wave Equation-Based Energy
Authors: da Silva Maciel Luiz Maurílio , Vieira Marcelo Bernardes
Published: October 2020

Identification of motion in videos is a fundamental task for several computer vision problems. One of the main tools for motion identification is optical flow, which estimates the projection of the 3D velocity of the objects onto the plane of the camera. In this work, we propose a differential optical flow method based on the wave equation. The optical flow is computed by minimizing a functional energy composed by two terms: a data term based on brightness constancy and a regularization term based on energy of the wave. Flow is determined by solving a system of linear equations. The decoupling of the pixels in the solution allows solving the system by a direct or iterative approach and makes the method suitable for parallelization. We present the convergence conditions for our method since it does not converge for all the image points. For comparison purposes, we create a global video descriptor based on histograms of optical flow for the problem of action recognition. Despite its sparsity, results show that our method improves the average motion estimation, compared with classical methods. We also evaluate optical flow error measures in image sequences of a classical dataset for method comparison.
Bridge trisections in rational surfaces
Authors: Lambert-Cole Peter , Meier Jeffrey
Published: October 2020

We study smooth isotopy classes of complex curves in complex surfaces from the perspective of the theory of bridge trisections, with a special focus on curves in [Formula: see text] and [Formula: see text]. We are especially interested in bridge trisections and trisections that are as simple as possible, which we call efficient. We show that any curve in [Formula: see text] or [Formula: see text] admits an efficient bridge trisection. Because bridge trisections and trisections are nicely related via branched covering operations, we are able to give many examples of complex surfaces that admit efficient trisections. Among these are hypersurfaces in [Formula: see text], the elliptic surfaces [Formula: see text], the Horikawa surfaces [Formula: see text], and complete intersections of hypersurfaces in [Formula: see text]. As a corollary, we observe that, in many cases, manifolds that are homeomorphic but not diffeomorphic have the same trisection genus, which is consistent with the conjecture that trisection genus is additive under connected sum. We give many trisection diagrams to illustrate our examples.
Characterization and origin of large Campanian depressions within the Chalk Group of the Danish Central Graben – implications for hydrocarbon exploration and development
Authors: Smit Florian W. H. , Stemmerik Lars , Lüthje Mikael , van Buchem Frans S. P.
Published: October 2020

This study re-examines large and deep U-shaped reflections (2–4 km wide and 100–200 m deep) within the Upper Cretaceous–Danian Chalk Group in the inverted Roar Basin of the Danish North Sea, previously interpreted as a moat associated with a contour-parallel current system and/or erosive channels formed by gravity-driven turbidites. Improved 3D seismic data quality and seismic interpretation techniques helped to identify overlooked reflection terminations, which suggest that rather than a linear depression, the U-shaped reflections outline several bowl-shaped depressions. In addition, vertical high-amplitude columns and vertical discontinuity zones within and below the depressions were recognized and interpreted to indicate the presence of small fluid pipes, suggesting that the formation of the depressions is more complex. Carbon isotope analysis of high acoustic impedance beds within the underlying Lower Cretaceous chalk showed negative δ
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C values down to −20‰, and are interpreted to indicate sediments influenced by methane-derived authigenic carbonates. Permo-Triassic half-grabens seem to have been a major source of gas-bearing fluids, as evidenced by hydrocarbon leakage phenomena within Triassic–Lower Cretaceous strata. In areas where Zechstein salt is present, the leakage root lies at salt welds, causing the formation of focused seismic reflection wipe-out and dim zones. In areas where salt was absent, the leakage root comprises a much more diffuse zone across the fault boundaries of the Permo-Triassic half-graben, and gas chimneys are characterized seismically as broad vertical dim zones up to 10 km wide. Campanian inversion tectonics caused fault reactivation and several hundreds of metres of uplift in the Roar Basin, which created an instability for the trapped gas-bearing fluids. Gentle fluid venting through observed pipes caused sediment suspension and entrainment, which could be carried away by bottom-current activity, causing localized zones of non-deposition and the formation of individual depressions. This model thus does not disregard the role of bottom-current activity in the formation of the depressions, yet it includes a fluid-venting element that fits better with the architecture and overall evidence for fluid-venting features in pre-chalk strata, as well as in the Chalk Group. Importantly, it shows that prior to the thermogenic maturation of the main source rock (i.e. the Bo Member of the Farsund Formation in the Late Miocene), fluid venting had already occurred on the Late Cretaceous seafloor from deeper source rocks that are at present overmature.
Engineering the Composition and Fate of Wild Populations with Gene Drive
Authors: Hay Bruce A. , Oberhofer Georg , Guo Ming
Published: October 2020

Insects play important roles as predators, prey, pollinators, recyclers, hosts, parasitoids, and sources of economically important products. They can also destroy crops; wound animals; and serve as vectors for plant, animal, and human diseases. Gene drive—a process by which genes, gene complexes, or chromosomes encoding specific traits are made to spread through wild populations, even if these traits result in a fitness cost to carriers—provides new opportunities for altering populations to benefit humanity and the environment in ways that are species specific and sustainable. Gene drive can be used to alter the genetic composition of an existing population, referred to as population modification or replacement, or to bring about population suppression or elimination. We describe technologies under consideration, progress that has been made, and remaining technological hurdles, particularly with respect to evolutionary stability and our ability to control the spread and ultimate fate of genes introduced into populations.
Antisense Drugs Make Sense for Neurological Diseases
Authors: Bennett C. Frank , Kordasiewicz Holly B. , Cleveland Don W.
Published: October 2020

The genetic basis for most inherited neurodegenerative diseases has been identified, yet there are limited disease-modifying therapies for these patients. A new class of drugs—antisense oligonucleotides (ASOs)—show promise as a therapeutic platform for treating neurological diseases. ASOs are designed to bind to the RNAs either by promoting degradation of the targeted RNA or by elevating expression by RNA splicing. Intrathecal injection into the cerebral spinal fluid results in broad distribution of antisense drugs and long-term effects. Approval of nusinersen in 2016 demonstrated that effective treatments for neurodegenerative diseases can be identified and that treatments not only slow disease progression but also improve some symptoms. Antisense drugs are currently in development for amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, and Angelman syndrome, and several drugs are in late-stage research for additional neurological diseases. This review highlights the advances in antisense technology as potential treatments for neurological diseases.
Hedgehog Signaling in Intestinal Development and Homeostasis
Authors: Walton Katherine D. , Gumucio Deborah L.
Published: October 2020

The hedgehog (Hh) signaling pathway plays several diverse regulatory and patterning roles during organogenesis of the intestine and in the regulation of adult intestinal homeostasis. In the embryo, fetus, and adult, intestinal Hh signaling is paracrine: Hh ligands are expressed in the endodermally derived epithelium, while signal transduction is confined to the mesenchymal compartment, where at least a dozen distinct cell types are capable of responding to Hh signals. Epithelial Hh ligands not only regulate a variety of mesenchymal cell behaviors, but they also direct these mesenchymal cells to secrete additional soluble factors (e.g., Wnts, Bmps, inflammatory mediators) that feed back to regulate the epithelial cells themselves. Evolutionary conservation of the core Hh signaling pathway, as well as conservation of epithelial/mesenchymal cross talk in the intestine, has meant that work in many diverse model systems has contributed to our current understanding of the role of this pathway in intestinal organogenesis, which is reviewed here.
Early return of reflected waves increases right ventricular wall stress in chronic thromboembolic pulmonary hypertension
Authors: Fukumitsu Masafumi , Westerhof Berend E. , Ruigrok Dieuwertje , Braams Natalia J. , Groeneveldt Joanne A. , Bayoumy Ahmed A. , Marcus J. Tim , Meijboom Lilian J. , de Man Frances S. , Westerhof Nico , Bogaard Harm-Jan , Vonk Noordegraaf Anton
Published: October 2020

In chronic thromboembolic pulmonary hypertension (CTEPH), proximal localization of vessel obstructions is associated with poor right ventricular (RV) function compared with distal localization, though pulmonary vascular resistance, vascular compliance, characteristic impedance, and the magnitude of wave reflection are similar. In proximal CTEPH, the RV is exposed to an earlier return of the reflected wave. Early wave reflection may increase RV wall stress and compromise RV function.
Sympathetic neural modulation of arterial stiffness in humans
Authors: Nardone Massimo , Floras John S. , Millar Philip J.
Published: October 2020

Elevated large-artery stiffness is recognized as an independent predictor of cardiovascular and all-cause mortality. The mechanisms responsible for such stiffening are incompletely understood. Several recent cross-sectional and acute experimental studies have examined whether sympathetic outflow, quantified by microneurographic measures of muscle sympathetic nerve activity (MSNA), can modulate large-artery stiffness in humans. A major methodological challenge of this research has been the capacity to evaluate the independent neural contribution without influencing the dynamic blood pressure dependence of arterial stiffness. The focus of this review is to summarize the evidence examining 1) the relationship between resting MSNA and large-artery stiffness, as determined by carotid-femoral pulse wave velocity or pulse wave reflection characteristics (i.e., augmentation index) in men and women; 2) the effects of acute sympathoexcitatory or sympathoinhibitory maneuvers on carotid-femoral pulse wave velocity and augmentation index; and 3) the influence of sustained increases or decreases in sympathetic neurotransmitter release or circulating catecholamines on large-artery stiffness. The present results highlight the growing evidence that the sympathetic nervous system is capable of modulating arterial stiffness independent of prevailing hemodynamics and vasomotor tone.
Docking Studies on Potential Mechanisms for Decreasing Insulin Resistance by the Tangzhiqing Herbal Formula
Authors: Hao Jia , Han Lifeng , Zhang Yi , Wang Tao
Published: October 2020

Insulin resistance (IR) is considered as one of the principal pathways of type 2 diabetes mellitus pathogenesis and is associated with a series of abnormal signaling pathways. Tangzhiqing (TZQ) herbal formula is a well‐known antidiabetic traditional Chinese medicine and has been used to treat type 2 diabetes mellitus and prediabetes for many years in China. We selected 13 natural products as representative compounds of the main active components in TZQ to investigate the interaction of these natural products with key signal proteins associated with IR using two different docking calculations. Salvianolic acids A and C (phenolic acids from Salvia miltiorrhiza), rutin (a flavonoid from Morus alba), paeoniflorin (a saponin from Paeonia lactiflora), and quercitrin (a flavonoid from Crataegus pinnatifida) showed great docking abilities towards multiple target proteins. These results have contributed to a clearer understanding regarding the regulation mechanism of TZQ on IR and have provided direction for further pharmacological studies.
Altered Functional Integration in the Salience and Default Mode Networks in Euthymic Pediatric Bipolar Disorder
Authors: Cao Weifang , Chen Haoran , Jiao Qing , Cui Dong , Guo Yongxin , Gao Weijia , Qiu Jianfeng , Su Linyan , Lu Guangming
Published: October 2020

Accumulating studies demonstrate emotional and cognitive dysregulation in the euthymic period of pediatric bipolar disorder (PBD). However, the relative contribution of functional integration in human brain to disturbed emotion and cognitive function in the euthymic PBD patients remains unclear. In this study, 16 euthymic PBD patients and 16 healthy controls underwent resting-state functional magnetic resonance imaging. A data-driven functional connectivity analysis was used to investigate functional connectivity changes of the euthymic PBD. Compared with healthy controls, the euthymic PBD exhibited greater global functional connectivity density in the left anterior insula and lower global functional connectivity density in the right temporoparietal junction, the left angular gyrus, and the bilateral occipital lobule. A distant functional connectivity analysis demonstrated altered integration within the salience and default mode networks in euthymic PBD. Correlation analysis found that altered functional connectivity of the salience network was related to the reduced performance in the backward digit span test, and altered functional connectivity of the default mode network was related to the Young Mania Rating Scale in euthymic PBD patients. Our findings indicated that disturbed functional integration in salience and default mode networks might shed light on the physiopathology associated with emotional and cognitive dysregulation in PBD.
lncRNA DLGAP1‐AS2 Knockdown Inhibits Hepatocellular Carcinoma Cell Migration and Invasion by Regulating miR‐154‐5p Methylation
Authors: Chen Kai , Zhang Zhuqing , Yu Aijun , Li Jian , Liu Jinlong , Zhang Xuejun
Published: October 2020

Objective. DLGAP1‐AS2 has been characterized as an oncogenic lncRNA in glioma. Our preliminary microarray analysis revealed the altered expression of DLGAP1‐AS2 in hepatocellular carcinoma (HCC), but the role of DLGAP1‐AS2 in HCC remains unknown. Method. Expression of DLGAP1‐AS2 and miR‐154‐5p in paired HCC and nontumor tissues from 62 HCC patients was determined by RT‐qPCR. The 62 HCC patients were followed up for 5 years to analyze the prognostic value of DLGAP1‐AS2 for HCC. DLGAP1‐AS2 knockdown and miR‐154‐5p overexpression was achieved in HCC cells to study the relationship between them. Methylation of miR‐154‐5p was analyzed by methylation‐specific PCR. Cell proliferation was analyzed by CCK‐8 assay. Results. DLGAP1‐AS2 was upregulated in HCC and predicted poor survival. miR‐154‐5p was downregulated in HCC and inversely correlated with DLGAP1‐AS2. In HCC cells, DLGAP1‐AS2 knockdown resulted in the upregulation of miR‐154‐5p expression and decreased methylation of miR‐154‐5p gene. Transwell assay showed that DLGAP1‐AS2 knockdown and miR‐154‐5p overexpression inhibited cell invasion and migration, and the combination of LGAP1‐AS2 knockdown and miR‐154‐5p overexpression showed stronger effects. Conclusion. DLGAP1‐AS2 knockdown may inhibit HCC cell migration and invasion by regulating miR‐154‐5p methylation.
Diffusively-Coupled Rock-Paper-Scissors Game with Mutation in Scale-Free Hierarchical Networks
Authors: Nagatani Takashi , Ichinose Genki
Published: October 2020

We present a metapopulation dynamic model for the diffusively-coupled rock-paper-scissors (RPS) game with mutation in scale-free hierarchical networks. We investigate how the RPS game changes by mutation in scale-free networks. Only the mutation from rock to scissors (R-to-S) occurs with rate μ. In the network, a node represents a patch where the RPS game is performed. RPS individuals migrate among nodes by diffusion. The dynamics are represented by the reaction-diffusion equations with the recursion formula. We study where and how species coexist or go extinct in the scale-free network. We numerically obtained the solutions for the metapopulation dynamics and derived the transition points. The results show that, with increasing mutation rate μ, the extinction of P species occurs and then the extinction of R species occurs, and finally only S species survives. Thus, the first and second dynamical phase transitions occur in the scale-free hierarchical network. We also show that the scaling law holds for the population dynamics which suggests that the transition points approach zero in the limit of infinite size.
Limited-Budget Formation Control for High-Order Linear Swarm Systems with Fix Topologies
Authors: Dang Hongtao , Wang Le , Zhang Yan , Yang Jianye
Published: October 2020

This paper discusses limited-budget time-varying formation design and analysis problems for a high-order linear swarm system with a fixed communication topology. Firstly, the communication topology among agents is modeled as an undirected and connected graph, and a new formation control protocol with an energy integral term is proposed to realize formation control and to guarantee the practical energy assumption is less than the limited energy budget. Then, by the matrix inequality tool, sufficient conditions for limited-budget formation design and analysis are proposed, respectively, which are scalable and checkable since they are independent of the number of agents of a swarm system and can be transformed into linear matrix inequality constraints. Moreover, an explicit expression of the formation center function is given, which contains the formation function part and the cooperative state part and is not associated with the derivatives of the formation functions. Finally, a numerical simulation is shown to demonstrate the effectiveness of theoretical results.
Study on the Coupling Frequency of Double-Sided Submerged Ring-Stiffened Cylindrical Shells
Authors: Yu Anbin , Zhao Yinglong , Wang Youqian , Zhang Ben
Published: October 2020

Based on the Flügge theory and orthotropic theory, the acoustic vibration coupling model of ring-stiffened cylindrical shell is established by using the wave propagation method and virtual source method. And the effects of water immersion on both sides, free surface, and hydrostatic pressure on the cylindrical shell are considered in the coupling model. Muller three-point iterative method is used to solve the coupling frequency. The calculation results of degradation theory are compared with COMSOL’s calculation results and experimental results, respectively, which verifies the reliability of the theoretical method. Finally, the influence of fluid load, ring rib parameters, boundary conditions, hydrostatic pressure, and free surface on the coupled vibration of ring-stiffened cylindrical shell is analyzed by an example.
Myofunctional Treatment of Anterior Crossbite in a Growing Patient
Authors: Pellegrino Marianna , Cuzzocrea Maria Laura , Rao Walter , Pellegrino Gioacchino , Paduano Sergio
Published: October 2020

The purpose of this case report is to add another means of treatment for the anterior crossbite malocclusion in early mixed dentition. The selected functional device is an eruption guidance appliance (EGA). The analysed patient had a functional anterior crossbite, a mandibular protrusion tendency, and a normodivergent growth pattern. The early treatment was suggested to correct the malocclusion and avoid unfavourable occlusal conditions that could end in a class III malocclusion growth pattern. After 18 months of treatment, with night-time use, the malocclusion was completely resolved. This therapy strategy allowed the correction of the sagittal jaws’ relationship and maximum control of the vertical dimension. After 2 years of follow-up, the results were preserved. The peculiarity of this kind of intraoral orthodontic tools is the use of the erupting forces rather than the active forces. This early treatment of anterior crossbites with EGA may be considered an effective treatment approach for achieving good functional and aesthetic results.
[Retracted] Effects of Arteriovenous Thrombolysis Combined with Mechanical Thrombectomy on Efficacy and Neurological Function of Acute Cerebral Infarct Patients
Authors: Ding Tao , Tang Liwen , Hu Bohong , Yuan Junxin , Li Xiangdong , Wen Jun
Published: October 2020

Objective. To investigate the effects of arteriovenous thrombolysis combined with mechanical thrombectomy on clinical efficacy, neurological function, and the changes of nerve injury markers of acute cerebral infarct (ACI) patients. Methods. A total of 143 cases with ACI admitted to our hospital from June 2017 to June 2019 were elected as research subjects. Among them, 69 cases of patients who received treatment of arteriovenous thrombolysis were considered as group A, and 74 cases of patients who received treatment of arteriovenous thrombolysis combined with mechanical thrombectomy were considered as group B. NIHSS score, clinical efficacy, vascular recanalization, adverse reactions, hemodynamics, neurological injury indexes, duration of coma, length of hospital stay, and prognosis of patients in the two groups were compared. Results. After treatment, the NIHSS score of group A was higher than that of group B (P < 0.05), the clinical efficacy of group B was better than that of group A, and the incidence of adverse reactions was lower than that of group A (P < 0.05). There was no difference in vascular recanalization rate, duration of coma, and prognosis between the two groups (P > 0.05). Length of hospital stay, maximum peak velocity after treatment (Vs), and mean flow rate (Vm) of group A were lower than those of group B, while vascular resistance index (RI), pulsatility index (PI), serum glutamic acid (Glu), neuron‐specific enolase (NES), and S100β protein detected by enzyme‐linked immunosorbent assay (ELISA) of group A were higher than those of group B (P < 0.05). Conclusion. Arteriovenous thrombolysis combined with mechanical thrombectomy has a significant effect on ACI, with high safety and quick effect. In addition, it has a stronger effect on improving and protecting the neurological function of patients, which is worth promoting in clinical practice.
The Intention on Modern Contraceptive Use and Associated Factors among Postpartum Women in Public Health Institutions of Sodo Town, Southern Ethiopia 2019: An Institutional‐Based Cross‐Sectional Study
Authors: Gebeyehu Natnael Atnafu , Lake Eyasu Alem , Gelaw Kelemu Abebe , Azeze Gedion Asnake
Published: October 2020

Background. The postpartum period is an important transitional time for couples to put the decision on family planning utilization. However, women in Ethiopia are usually uncertain about the use of family planning during this period. This cross‐sectional study was, therefore, aimed at determining the intention of modern contraceptive use and associated factors among postpartum women attending the immunization clinic in Sodo town, Ethiopia. Method. This institution‐based cross‐sectional study was conducted among 416 study participants from May 25 to June 20, 2019. The data were collected by using a systematic random sampling technique of interviewer‐administered questionnaires. Descriptive analysis was done, and results were presented in texts and tables. Variables at bivariate analysis with a p value < 0.2 were moved to the multivariate logistic regression model to control potential confounding variables. Statistical tests at p value < 0.05 during multivariate analysis were considered as a cutoff point to determine statistical significance. Results. A total of 416 postpartum women participated in the study yielding a response rate of 98.1%. The prevalence of intention on modern contraceptive use among study participants was 70%. The odds of intention on modern contraceptive use was higher among study participants who had secondary school education (AOR = 2.052, 95% CI: 1.064‐3.958), antenatal care visit (AOR = 1.74; 95% CI: 1.02‐2.95), knowledge on modern contraceptive use (AOR = 2.54; 95% CI: 1.50‐4.28), menses resumption (AOR = 2.05; 95% CI: 1.14‐3.68), and husband approval to use contraceptives (AOR = 2.395, 95% CI: 1.501‐5.458). Conclusion. The intention of modern contraceptive use among postpartum women was low. Family planning providers should emphasize reducing barriers of intention like lack of education, knowledge, male partner approval, antenatal care visit, and advise the impact of menses on fertility.
The Large-Small Group-Based Evolutionary Game on Knowledge Sharing in Uncertain Environment under the Background of Telemedicine Service
Authors: Gao Yuxuan , Sun Bingzhen
Published: October 2020

Group decision-making is an effective method to deal with complex unstructured problem in uncertain environment, and it has been widely used in many fields such as medical decision-making. This is a novel study that considers the decision-makers as different groups in the group decision-making problems in uncertain environment. This paper aims to present a novel method combined with evolutionary game for decision-making problem of knowledge sharing in uncertain environment between the large and the small groups in Telemedicine service. For this purpose, the evolutionary game model is constructed to solve decision-making problem of large-small group. Through analyzing the evolutionary path and balance, the influencing factors of the selection strategies and objective and subjective factors restricting the establishment of knowledge sharing between the large and small groups cloud be determined. Finally, a numerical simulation experiment is conducted with Matlab to demonstrate the feasibility of the proposed method. In this study, the range of decision groups in the research of group decision-making problem has been expanded, and the complicated factors of knowledge sharing between hospitals in uncertain environment under the background of Telemedicine service have been discussed.
Effectiveness and Safety of Pixantrone for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma in Every-Day Clinical Practice: The Italian Cohort of the PIXA Registry
Authors: Zinzani Pier Luigi , Bregni Marco , Spione Mario , Mitterer Manfred , Musuraca Gerardo , Bugli Annamaria , Piazza Francesco , Pinto Antonello
Published: October 2020

Introduction: Treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) represents a challenge for clinicians due to the lack of therapeutic options. DLBCL is not a rare disease in Italy. Pixantrone is an aza-anthracenedione, which, when compared to anthracyclines and anthracenediones, has a significantly reduced cardiotoxicity while maintaining good anti-tumor activity. However, the evidence on the use of pixantrone in the context of daily clinical practice is scarce. Methods: We focused on the Italian patient subset of a larger European retrospective study (the PIXA Registry) to assess the efficacy and safety of pixantrone in a real-life DLBCL population. The molecular profile of the disease and its impact on drug efficacy were also assessed. Results: Fifteen heavily pretreated DLBCL patients (13 males and 2 females) underwent treatment with pixantrone for a median of 2 cycles (range 1–6). Eight patients were bcl2 positive, 7 bcl6 positive, and 4 myc positive; 4 patients were diagnosed as double-hit, and 2 as triple-hit DLBCL. The overall response rate was 26.7% with a best response rate of 46.7%. Three patients had grade IV adverse events, which caused drug discontinuation. Four patients had 5 cases of grade III toxicities (1 thrombocytopenia, 1 stomatitis, and 3 neutropenia). One mild cardiac toxicity (sinus tachycardia for which no action was required) was possibly related to the study drug. Conclusion: Our data documented drug efficacy that is satisfactory for this high-risk subset of patients with an acceptable toxicity profile. Results indicate that pixantrone could be a significant treatment option in patients with R/R aggressive DLBCL treated in everyday clinical practice.
Causes and Consequences of Metabolic Acidosis in Patients after Kidney Transplantation
Authors: Ritter Alexander , Mohebbi Nilufar
Published: October 2020

Background: Metabolic acidosis (MA) is a common complication in kidney transplantation (KTx). It is more prevalent in KTx than in CKD, and it occurs at higher glomerular filtration rates. The pathophysiologic understanding of MA in KTx and its clinical impact has been highlighted by few recent studies. However, no guidelines exist yet for the treatment of MA after KTx. Summary: MA in KTx seems to share pathophysiologic mechanisms with CKD, such as impaired ammoniagenesis. Additional kidney transplant-specific factors seem to alter not only the prevalence but also the phenotype of MA, which typically shows features of renal tubular acidosis. There is evidence that calcineurin inhibitors, immunological factors, process of donation, donor characteristics, and diet may contribute to MA occurrence. According to several mainly observational studies, MA seems to play a role in disturbed bone metabolism, cardiovascular morbidity, declining graft function, and mortality. A better understanding of the pathophysiology and evidence from randomized controlled trials, in particular, are needed to clarify the role of MA and the potential benefit of alkali treatment in KTx. Alkali therapy might not only be beneficial but also cost effective and safe. Key Messages: MA seems to be associated with several negative outcomes in KTx. A deeper understanding of the pathophysiology and clinical consequences of MA in KTx is crucial. Clinical trials will have to determine the potential benefits of alkali therapy.
Optimizing the Decellularized Porcine Liver Scaffold Protocol
Authors: Alaby Pinheiro Faccioli Lanuza , Suhett Dias  Grazielle , Hoff Victor , Lemos Dias Marlon , Ferreira Pimentel Cibele , Hochman-Mendez Camila , Braz Parente Daniella , Labrunie Ester , Souza Mourão Paulo Antonio , Rogério de Oliveira Salvalaggio Paolo , Goldberg Anna Carla , Campos de Carvalho Antonio Carlos , dos Santos Goldenberg Regina Coeli
Published: October 2020

There are few existing methods for shortening the decellularization period for a human-sized whole-liver scaffold. Here, we describe a protocol that enables effective decellularization of the liver obtained from pigs weigh 120 ± 4.2 kg within 72 h. Porcine livers (approx. 1.5 kg) were decellularized for 3 days using a combination of chemical and enzymatic decellularization agents. After trypsin, sodium deoxycholate, and Triton X-100 perfusion, the porcine livers were completely translucent. Our protocol was efficient to promote cell removal, the preservation of extracellular matrix (ECM) components, and vascular tree integrity. In conclusion, our protocol is efficient to promote human-sized whole-liver scaffold decellularization and thus useful to generate bioengineered livers to overcome the shortage of organs.
Fibroblast Growth Factor 23 and α-Klotho Protein Are Associated with Adverse Clinical Outcomes in Non-Dialysis CKD Patients
Authors: Manou Eleni , Thodis Elias , Arsos Georgios , Pasadakis Ploumis , Panagoutsos Stylianos , Papadopoulou Dorothea , Papagianni Aikaterini
Published: October 2020

Background: Fibroblast growth factor 23 (FGF-23) and α-Klotho protein appear to have an important role in the pathogenesis of CKD-mineral and bone disorders. The aim of this study was to investigate the association of FGF-23 and α-Klotho levels with adverse clinical outcomes in patients with non-dialysis CKD. Materials and Methods: We conducted a prospective cohort study, enrolling participants with non-dialysis CKD from a single center in Greece. At enrollment, glomerular filtration rate (GFR) was measured (mGFR) and plasma levels of carboxyl terminal FGF-23 (cFGF-23) and soluble α-Klotho (sKlotho) were determined by enzyme-linked immunoassay. Participants were followed for up to 5 years or until the occurrence of the primary endpoint of initiation of renal replacement therapy or death. Multivariate regression tree analysis was used to identify informative baseline parameters in order to categorize participants. Also, using median values of cFGF-23 and sKlotho, participants were categorized into 4 groups, in whom survival was compared using Kaplan-Meier and Cox regression analysis. Results: 128 participants were enrolled with a median mGFR of 41.5 mL/min/1.73 m2 (IQR = 28.2). Baseline mGFR correlated with cFGF-23 and sKlotho (r = −0.54 and r = 0.49, respectively; p < 0.0001 for both). cFGF-23 and sKlotho levels correlated negatively (r = −0.24, p = 0.006). Multivariate regression tree analysis resulted in 3 groups defined by cutoff values of mGFR (60.9 mL/min/1.73 m2) and phosphate (3.7 mg/dL). These groups correlated with CKD stage, cFGF-23, and sKlotho (p < 0.0001 for all). During a median follow-up of 36 months (IQR = 22), 40 (31.2%) participants reached the primary endpoint (31 initiated renal replacement therapy, 9 died). Survival to primary endpoint differed among the 4 groups formed using median values of both biomarkers, with the low FGF-23/high Klotho and high FGF-23/low Klotho having the longest and shortest survival, respectively. High FGF-23/low Klotho group, compared to the opposite one, had a significantly elevated risk of the primary outcome (HR, 6.8; 95% CI, 2.3–19.6; p = 0.0004). Conclusions: In patients with CKD stages 1–5, the combination of higher cFGF-23 and lower sKlotho levels along with mGFR and serum phosphate was associated with adverse clinical outcomes. The utility of combinations of traditional and novel biomarkers to predict outcomes warrants further study.
Efficacy of Intralesional and Oral Dutasteride in the Treatment of Androgenetic Alopecia: A Systematic Review
Authors: Herz-Ruelas Maira Elizabeth , Álvarez-Villalobos Neri Alejandro , Millán-Alanís Juan Manuel , León-Gutiérrez Humberto de , Ocampo-Garza Sonia Sofía , Gómez-Flores Minerva , Grimalt Ramón
Published: October 2020

Androgenetic alopecia is the most common cause of hair loss [Br J Dermatol. 2011 Jan;164(1):5–15]. Finasteride and minoxidil are the only approved treatments [J Am Acad Dermatol. 2008 Oct;59(4):547–8 and J Eur Acad Dermatology Venereol. 2018 Jan;32(1):11–22]. Dutasteride is more potent than finasteride due to its ability to inhibit both 5-α-reductase type I and II [Our Dermatol Online. 2017 Sep;9(1):75–9] though its adverse effects and long half-life contribute to the reluctance on its oral use. Mesotherapy could be a feasible alternative to avoid systemic exposure and side effects [J Pan-Arab League Dermatologist. 2009 Feb;20(1):137–45]. We aim to perform a systematic review to analyze scientific literature with the purpose of comparing efficacy and adverse effects of both administration routes. Five clinical trials using oral route and 3 intralesional in comparison with placebo met criteria for inclusion. Regarding intralesional dutasteride, only one study [Clin Dermatol. 2001 Mar;19(2):149–54] reported the mean change in hair count. Although both interventions favor over placebo, there are not enough data to reliably compare outcomes obtained between both routes. Mean increase in hair count observed with oral dutasteride was higher (MD: 15.92 hairs [95% CI: 9.87–21.96]; p = <0.00001; I2 = 90%) compared to intralesional dutasteride in Abdallah’s study (MD: 7.90 hairs [95% CI: 7.14–8.66]; p = <0.00001). Future studies are required to assess the therapeutic efficacy of both treatment routes, including head-to-head treatments before well-supported conclusions can be established.
Multiple Sklerose: Neuroinflammation und -degeneration Hand in Hand
Authors: Demitrowitz Nadja , Ziemssen Tjalf
Published: October 2020

Die Multiple Sklerose ist die häufigste chronisch-entzündliche Erkrankung des zentralen Nervensystems, die aufgrund ihrer vielfältigen Symptomatik im Volksmund als die «Erkrankung der 1000 Gesichter» bekannt ist. In den letzten Jahren haben sich die dia­gnostischen und therapeutischen Möglichkeiten gebessert, die eine frühzeitige, an die Krankheitsaktivität angepasste individualisierte Therapie ermöglichen. Im Fokus einer verbesserten Managementstrategie dieser immer noch nicht heilbaren, aber langfristig positiv zu beeinflussenden Erkrankung stehen somit gute interdisziplinäre Früh- und Differentialdiagnose sowie ein gutes Therapiemanagement, das neben der hier weiter ausgeführten immunmodulatorischen Therapie eine ganzheitliche symptomatische Therapie der vielen auftretenden Symptome (z.B. Depression, Spastik, Blasenstörungen, Schmerzen) umfasst.
Vergleichende Analysen des Lungenmikrobioms zwischen Patienten mit ANCA-assoziierten Vaskulitiden und Sarkoidose aus bronchoalveolärer Lavage
Authors: Kahn Nicolas Carlos
Published: October 2020

Microbial involvement in the pathogenesis have been suggested in both antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and sarcoidosis, both of which have lung involvement. However, exhaustive research to assess the bacteria in the lung in AAV and in sarcoidosis have not been performed. We sought to elucidate the distinct dysbiotic lung microbiota between AAV and sarcoidosis. We used 16S rRNA gene high-throughput sequencing to obtain the bacterial community composition of bronchoalveolar lavage fluid (BALF) in patients with AAV (n = 16) compared to patients with sarcoidosis (n = 21). The patients had not undergone therapy with immunosuppressive medication when their BALF was acquired. No difference was observed in α-diversity between patients with AAV and patients with sarcoidosis when using all the detected taxa. We defined the taxa of the oral cavity by using the data of oral microbiota of healthy individuals from the Human Microbiome Project (HMP). The analysis using only oral taxa made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. Besides, the analysis using detected taxa except for oral taxa also made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. A linear negative relationship between the α-diversity and Birmingham vasculitis activity score (BVAS) was detected in the AAV group. The observed p-value for the effect of the disease groups on the ß-diversity was small while the effect of other factors including sex and smoking status did not have small p-values. By excluding oral taxa from all the detected taxa, we found a cluster mainly consisted of sarcoidosis patients which was characterized with microbial community monopolized by Erythrobacteraceae family. Our results suggested the importance of considering the influence of oral microbiota in evaluating lung microbiota.
Efficacy of Low-Carbohydrate Ketogenic Diet in the Treatment of Type 2 Diabetes
Authors: Dashti Hussain M. , Mathew Thazhumpal C. , Al-Zaid Naji S.
Published: October 2020

Low-carbohydrate ketogenic diet (LCKD), originally used as a treatment for childhood epilepsy is currently gaining acceptance as a nutritional therapy for obesity and type 2 diabetes. In addition, this diet has a positive effect on body weight, blood glucose level, glycosylated hemoglobin, plasma lipid profile, and neurological disorders. This review focuses on the therapeutic effectiveness, negative effects, and the rationale of using LCKD for the treatment of type 2 diabetes. It is shown that LCKD contributes to the reduction in the intake of insulin and oral antidiabetic drugs in patients with type 2 diabetes. Furthermore, the data presented in this review reveal the efficacy and cost-effectiveness of LCKD in the management of type 2 diabetes.
Long‐Term Results After Drug‐Eluting Versus Bare‐Metal Stent Implantation in Saphenous Vein Grafts: Randomized Controlled Trial
Authors: Fahrni Gregor , Farah Ahmed , Engstrøm Thomas , Galatius Søren , Eberli Franz , Rickenbacher Peter , Conen David , Mueller Christian , Pfister Otmar , Twerenbold Raphael , Coslovsky Michael , Cattaneo Marco , Kaiser Christoph , Mangner Norman , Schuler Gerhard , Pfisterer Matthias , Möbius‐Winkler Sven , Jeger Raban V. ,   for the BASKET‐SAVAGE‐Investigators*
Published: October 2020

Background

Efficacy data on drug‐eluting stents (DES) versus bare‐metal stents (BMS) in saphenous vein grafts are controversial. We aimed to compare DES with BMS among patients undergoing saphenous vein grafts intervention regarding long‐term outcome.

Methods and Results

In this multinational trial, patients were randomized to paclitaxel‐eluting or BMS. The primary end point was major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and target‐vessel revascularization at 1 year. Secondary end points included major adverse cardiac events and its individual components at 5‐year follow‐up. One hundred seventy‐three patients were included in the trial (89 DES versus 84 BMS). One‐year major adverse cardiac event rates were lower in DES compared with BMS (2.2% versus 16.0%, hazard ratio, 0.14; 95% CI, 0.03–0.64,
P
=0.01), which was mainly driven by a reduction of subsequent myocardial infarctions and need for target‐vessel revascularization. Five‐year major adverse cardiac event rates remained lower in the DES compared with the BMS arm (35.5% versus 56.1%, hazard ratio, 0.40; 95% CI, 0.23–0.68,
P
<0.001). A landmark‐analysis from 1 to 5 years revealed a persistent benefit of DES over BMS (hazard ratio, 0.33; 95% CI, 0.13–0.74,
P
=0.007) in terms of target‐vessel revascularization. More patients in the BMS group underwent multiple target‐vessel revascularization procedures throughout the study period compared with the DES group (DES 1.1% [n=1] versus BMS 9.5% [n=8],
P
=0.013). Enrollment was stopped before the target sample size of 240 patients was reached.

Conclusions

In this randomized controlled trial with prospective long‐term follow‐up of up to 5 years, DES showed a better efficacy than BMS with sustained benefits over time. DES may be the preferred strategy in this patient population.

Registration

URL:
https://www.clini​caltr​ials.gov
; Unique identifier: NCT00595647.
Molecular assessment of the genus Sargassum (Fucales, Phaeophyceae) from the Mexican coasts of the Gulf of Mexico and Caribbean, with the description of S. xochitlae sp. nov.

Authors: GONZÁLEZ-NIETO DONAJÍ , OLIVEIRA MARIANA C. , NÚÑEZ RESENDIZ MARÍA LUISA , DRECKMANN KURT M. , MATEO-CID LUZ ELENA , SENTÍES ABEL
Published: October 2020

The recognition of many species of Sargassum has been difficult because morphological characters show significant phenotypic variation depending on habitat, season, or even differences at the population level. To resolve some of these systematic issues along the Mexican Atlantic coast, molecular analyses of Sargassum species were carried out using DNA sequences of the COI-5P, ITS-2 and rbcL_S genetic markers. Of the 16 species recorded for the area, five species (S. acinarium, S. mathiesonii, S. pteropleuron, S. pusillum and S. ramifolium) were not found during the collections and their status remains undefined. Phylogenetic analyses of the three molecular markers showed that 10 species with their varieties (S. bermudense, S. buxifolium, S. cymosum, S. filipendula, S. fluitans, S. furcatum, S. hystrix, S. natans, S. polyceratium, and S. vulgare) were grouped into a polytomy, with low genetic diversity. If we consider these markers as suitable for proxy for species delimitation, these species should be synonymized under S. cymosum, the older name. Taxonomic independence was confirmed only for S. platycarpum and our data revealed a new morphologically and molecularly independent species within the genus, described here as Sargassum xochitlae.
Changes in Extreme Precipitation Accumulations during the Warm Season over Continental China
Authors: Chang Meiyu , Liu Bo , Martinez-Villalobos Cristian , Ren Guoyu , Li Shangfeng , Zhou Tianjun
Published: October 2020

Precipitation accumulations, integrated over rainfall events, are investigated using hourly data across continental China during the warm season (May–October) from 1980 to 2015. Physically, the probability of precipitation accumulations drops slowly with event size up to an approximately exponential cutoff scale sL where probability drops much faster. Hence sL can be used as an indicator of high accumulation percentiles (i.e., extreme precipitation accumulations). Overall, the climatology of sL over continental China is about 54 mm. In terms of cutoff changes, the current warming stage (1980–2015) is divided into two periods, 1980–97 and 1998–2015. We find that the cutoff in 1998–2015 increases about 5.6% compared with that of 1980–97, with an average station increase of 4.7%. Regionally, sL increases are observed over East China (10.9% ± 1.5%), Northwest China (9.7% ± 2.5%), South China (9.4% ± 1.4%), southern Southwest China (5.6% ± 1.2%), and Central China (5.3% ± 1.0%), with decreases over North China (−10.3% ± 1.3%), Northeast China (−4.9% ± 1.5%), and northern Southwest China (−3.9% ± 1.8%). The conditional risk ratios for five subregions with increased cutoff sL are all greater than 1.0, indicating an increased risk of large precipitation accumulations in the most recent period. For high precipitation accumulations larger than the 99th percentile of accumulation s99, the risk of extreme precipitation over these regions can increase above 20% except for South China. These increases of extreme accumulations can be largely explained by the extended duration of extreme accumulation events, especially for “extremely extreme” precipitation greater than s99.
The Identification of Multiple Crystalline Zinc Soap Structures Using Infrared Spectroscopy
Authors: Hermans Joen , Helwig Kate
Published: October 2020

The formation of crystalline zinc soaps (zinc salts of fatty acids) in oil paint layers is a common sign of paint degradation. In this study, we have used infrared spectroscopy to systematically identify differences in structure and composition of crystalline zinc soap phases, and report data analysis methods for structure attribution in challenging oil paint samples. Supported by reported crystal structures, it was possible to distinguish two distinct types of zinc soap geometry: a highly symmetrical packing for long-chain saturated soaps (type B) and an alternating packing for zinc soaps with short, unsaturated, or dicarboxylic chains (type A). These two types of packing can be identified by a single or split asymmetric COO stretch vibration band. With this new information, we studied the structure and composition of zinc soaps formed in a zinc white model paint and in a cross-section from the painting Equations in Space by Lawren Harris. Using non-negative matrix factorization, band integration and band position maps, it was possible to clearly identify zinc azelate in the model paint and map its spatial distribution. The same methods showed that the paint cross-section contained both types of zinc soap structure within the same paint layer, with the less symmetrical structure appearing only at the interface with the ground layer. The results give valuable information on the internal chemistry of oil paint layers, and the demonstrated methods can find widespread application for in-depth analysis of infrared microscopy data.