bluuebunny/crossref_metadata_2025 huggingface dataset:
Fermion masses and mixings in a 3-3-1 model withQ4symmetry
Authors: Vien V. V. , Khoi D. P.
Published: June 2019

We construct a renormalizable [Formula: see text] model with [Formula: see text] symmetry accommodating the observed pattern of fermion masses and mixings with Dirac CP violation phase. The smallness of the active neutrino masses arises from a combination of type I and type II seesaw mechanisms. Both normal and inverted neutrino mass ordering are viable in our model in which the obtained physical observables of the lepton sector are well consistent with the global fit of neutrino oscillation data [P. F. de Salas et al., Phys. Lett. B 782, 633 (2018)] while the CKM matrix is unity at tree level and the quark masses are in good agreement with the experimental data [Particle Data Group (M. Tanabashi et al.), Phys. Rev. D 98, 030001 (2018)]. Furthermore, the model also predicts an effective Majorana neutrino mass parameter of [Formula: see text] eV for normal hierarchy and [Formula: see text] for inverted hierarchy which are consistent with the constraints given in [P. F. de Salas et al., Phys. Lett. B 782, 633 (2018)].
Tubular groups, 1-relator groups and nonpositive curvature
Authors: Button J. O.
Published: June 2019

We show (using results of Wise and of Woodhouse) that a tubular group is always virtually special (meaning that it has a finite index subgroup embedding in a RAAG) if the underlying graph is a tree. We also adapt Gardam and Woodhouse’s argument on tubular groups which double cover 1-relator groups to show there exist 1-relator groups which are CAT(0) but not residually finite.
Can fermionic dark matter mimic supermassive black holes?
Authors: Argüelles C. R. , Krut A. , Rueda J. A. , Ruffini R.
Published: June 2019

We analyze the intriguing possibility of explaining both dark mass components in a galaxy: the dark matter (DM) halo and the supermassive dark compact object lying at the center, by a unified approach in terms of a quasi-relaxed system of massive, neutral fermions in general relativity. The solutions to the mass distribution of such a model that fulfill realistic halo boundary conditions inferred from observations, develop a high-density core supported by the fermion degeneracy pressure able to mimic massive black holes at the center of galaxies. Remarkably, these dense core-diluted halo configurations can explain the dynamics of the closest stars around Milky Way’s center (SgrA*) all the way to the halo rotation curve, without spoiling the baryonic bulge-disk components, for a narrow particle mass range [Formula: see text]–[Formula: see text][Formula: see text]keV.
An interview with Lana Yarosh
Authors: Anjum Bushra
Published: June 2019

In this series of interviews with innovation leaders, Ubiquity Associate Editor and software engineer, Dr. Bushra Anjum, sits down with Prof. Lana Yarosh of the University of Minnesota to discuss geophysical and emotional distances as they relate to social disconnection and our evergrowing dependence on technology.
Sirtuin 3 silencing impairs mitochondrial biogenesis and metabolism in colon cancer cells
Authors: Torrens-Mas Margalida , Hernández-López Reyniel , Pons Daniel-Gabriel , Roca Pilar , Oliver Jordi , Sastre-Serra Jorge
Published: June 2019

Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase and targets several crucial enzymes against oxidative stress. Recent reports suggest that SIRT3 could also participate in the quality and quantity control of mitochondria. The aim of this study was to analyze whether SIRT3 silencing in colon cancer cells could affect mitochondrial biogenesis and impair mitochondrial function. For this purpose, metastatic colon cancer cell line SW620 was transfected with a specific shRNA against SIRT3 to obtain a stable knockdown. Gene expression and protein levels of several proteins related to mitochondrial biogenesis and function were determined by RT-qPCR and Western blotting. Mitochondrial function was studied by analyzing COX, ATPase, and LDH enzymatic activities, oxygen consumption, superoxide levels, and mitochondrial membrane potential. Confocal images were also taken to study mitochondrial morphology, and cell motility and clonogenicity were also studied. SIRT3 silencing resulted in a reduced mitochondrial biogenesis and function, as evidenced by the decrease in proteins such as PGC-1α and mitochondrial transcription factor A and lower levels of OXPHOS complexes. Furthermore, COX activity and oxygen consumption were also diminished after SIRT3 knockdown. Finally, SIRT3-silenced cells showed mitochondrial aggregation compared with control cells as well as reduced motility and colony formation ability. In conclusion, SIRT3 silencing in SW620 cancer cells leads to decreased mitochondrial biogenesis and mitochondrial dysfunction, ultimately affecting cell viability and could be a therapeutic strategy to render cells more sensitive to treatment.
In vivo validation of a miniaturized electrochemical oxygen sensor for measuring intestinal oxygen tension
Authors: Gray Mark E. , Marland Jamie R. K. , Dunare Camelia , Blair Ewen O. , Meehan James , Tsiamis Andreas , Kunkler Ian H. , Murray Alan F. , Argyle David , Dyson Alex , Singer Mervyn , Potter Mark A.
Published: June 2019

Recent advances in the fields of electronics and microfabrication techniques have led to the development of implantable medical devices for use within the field of precision medicine. Monitoring visceral surface tissue O2 tension ([Formula: see text]) by means of an implantable sensor is potentially useful in many clinical situations, including the perioperative management of patients undergoing intestinal resection and anastomosis. This concept could provide a means by which treatment could be tailored to individual patients. This study describes the in vivo validation of a novel, miniaturized electrochemical O2 sensor to provide real-time data on intestinal [Formula: see text]. A single O2 sensor was placed onto the serosal surface of the small intestine of anesthetized rats that were exposed to ischemic (superior mesenteric artery occlusion) and hypoxemic (alterations in inspired fractional O2 concentrations) insults. Control experiments demonstrated that the sensors can function and remain stable in an in vivo environment. Intestinal [Formula: see text] decreased following superior mesenteric artery occlusion and with reductions in inspired O2 concentrations. These results were reversible after reinstating blood flow or by increasing inspired O2 concentrations. We have successfully developed an anesthetized rat intestinal ischemic and hypoxic model for validation of a miniaturized O2 sensor to provide real-time measurement of intestinal [Formula: see text]. Our results support further validation of the sensors in physiological conditions using a large animal model to provide evidence of their use in clinical applications where monitoring visceral surface tissue O2 tension is important.

NEW & NOTEWORTHY This is the first report of real-time continuous measurements of intestinal oxygen tension made using a microfabricated O2 sensor. Using a developed rodent model, we have validated this sensor's ability to accurately measure dynamic and reversible changes in intestinal oxygenation that occur through ischemic and hypoxemic insults. Continuous monitoring of local intestinal oxygenation could have value in the postoperative monitoring of patients having undergone intestinal surgery.
Celiac disease: should we care about microbes?
Authors: Caminero Alberto , Verdu Elena F.
Published: June 2019

The prevalence of celiac disease (CeD) has increased in the last decades, suggesting a role for environmental factors in addition to gluten. Several cohort studies have shown that different gastrointestinal infections increase CeD risk. However, the mechanisms by which microbes participate in CeD have remained elusive. Recently, with the use of animal models, both viral and bacterial opportunistic pathogens were shown to induce immune activation relevant for CeD. The hypothesis that viral and/or bacterial infections can contribute to immune activation and breakdown of tolerance toward gluten in genetically susceptible individuals is therefore reinforced. Here, we discuss the evidence regarding the role of microbes in promoting CeD and the specific pathways triggered by microbes that could participate in CeD pathogenesis. Understanding these pathways will allow us to develop optimal microbiota-modulating strategies to help prevent CeD.
NTPDase1 and -2 are expressed by distinct cellular compartments in the mouse colon and differentially impact colonic physiology and function after DSS colitis
Authors: Grubišić Vladimir , Perez-Medina Alberto L. , Fried David E. , Sévigny Jean , Robson Simon C. , Galligan James J. , Gulbransen Brian D.
Published: June 2019

ATP is both an important mediator of physiological gut functions such as motility and epithelial function, and a key danger signal that mediates cell death and tissue damage. The actions of extracellular ATP are regulated through the catalytic functions extracellular nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), -2, -3, and -8, which ultimately generate nucleosides. Ectonucleotidases have distinct cellular associations, but the specific locations and functional roles of individual NTPDases in the intestine are still poorly understood. Here, we tested the hypothesis that differential and cell-selective regulation of purine hydrolysis by NTPDase1 and -2 plays important roles in gut physiology and disease. We studied Entpd1 and Entpd2 null mice in health and following colitis driven by 2% dextran sulfate sodium (DSS) administration using functional readouts of gut motility, epithelial barrier function, and neuromuscular communication. NTPDase1 is expressed by immune cells, and the ablation of Entpd1 altered glial numbers in the myenteric plexus. NTPDase2 is expressed by enteric glia, and the ablation of Entpd2 altered myenteric neuron numbers. Mice lacking either NTPDase1 or -2 exhibited decreased inhibitory neuromuscular transmission and altered components of inhibitory junction potentials. Ablation of Entpd2 increased gut permeability following inflammation. In conclusion, the location- and context-dependent extracellular nucleotide phosphohydrolysis by NTPDase1 and -2 substantially impacts gut function in health and disease.

NEW & NOTEWORTHY Purines are important mediators of gastrointestinal physiology and pathophysiology. Nucleoside triphosphate diphosphohydrolases (NTPDases) regulate extracellular purines, but the roles of specific NTPDases in gut functions are poorly understood. Here, we used Entpd1- and Entpd2-deficient mice to show that the differential and cell-selective regulation of purine hydrolysis by NTPDase1 and -2 plays important roles in barrier function, gut motility, and neuromuscular communication in health and disease.
Combination of CCl4 with alcoholic and metabolic injuries mimics human liver fibrosis
Authors: Brol Maximilian Joseph , Rösch Felicitas , Schierwagen Robert , Magdaleno Fernando , Uschner Frank Erhard , Manekeller Steffen , Queck Alexander , Schwarzkopf Katharina , Odenthal Margarete , Drebber Uta , Thiele Maja , Lingohr Philipp , Plamper Andreas , Kristiansen Glen , Lotersztajn Sophie , Krag Aleksander , Klein Sabine , Rheinwalt Karl P. , Trebicka Jonel
Published: June 2019

Metabolic and alcoholic liver injuries result in nonalcoholic (NAFLD) or alcoholic (ALD) fatty liver disease, respectively. In particular, presence of fibrosis in NAFLD and ALD requires treatment, but development of drugs is hampered by the lack of suitable models with significant fibrosis. The carbon tetrachloride (CCl4) liver fibrosis model does not reflect human NAFLD or ALD, but CCl4 may serve as a fibrosis accelerator in addition to another injury. Ethanol in drinking water (16%) or Western diet (WD) were administered for 7 wk in mice either alone or in combination with CCl4 intoxications. Extent of fibrosis, steatosis, and inflammation was assessed by histology, transcription, and biochemistry. Furthermore, transcription of fibrosis, proliferation, and inflammation-related genes was studied on human liver samples with fibrosis resulting from hepatitis C virus infection ( n = 7), NAFLD ( n = 8), or ALD ( n = 7). WD or ethanol alone induced only mild steatosis and inflammation. Combination of CCl4 and WD induced the most severe steatosis together with significant liver fibrosis and moderate inflammation. Combination of CCl4 and ethanol induced the strongest inflammation, with significant liver fibrosis and moderate steatosis. The relationship pattern between fibrosis, proliferation, and inflammation of human ALD was mostly similar in mice treated with CCl4 and ethanol. The combination of CCl4 intoxication with WD validates previous data suggesting it as an appropriate model for human nonalcoholic steatohepatitis. Especially, CCl4 plus ethanol for 7 wk induces ALD in mice, providing a model suitable for further basic research and drug testing.

NEW & NOTEWORTHY Alcoholic fatty liver disease with significant fibrosis is generated within 7 wk using carbon tetrachloride as a fibrosis accelerator and administering gradually ethanol (up to 16%) in mice. The similarity in the pattern of steatosis, inflammation, and fibrosis involved in alcoholic fatty liver disease to those of the human condition renders this mouse model suitable as a preclinical model for drug development.
Regulation of renal NaDC1 expression and citrate excretion by NBCe1-A
Authors: Osis Gunars , Webster Kierstin L. , Harris Autumn N. , Lee Hyun-Wook , Chen Chao , Fang Lijuan , Romero Michael F. , Khattri Ram B. , Merritt Matthew E. , Verlander Jill W. , Weiner I. David
Published: June 2019

Citrate is critical for acid-base homeostasis and to prevent calcium nephrolithiasis. Both metabolic acidosis and hypokalemia decrease citrate excretion and increase expression of Na+-dicarboxylate cotransporter 1 (NaDC1; SLC13A2), the primary protein involved in citrate reabsorption. However, the mechanisms transducing extracellular signals and mediating these responses are incompletely understood. The purpose of the present study was to determine the role of the Na+-coupled electrogenic bicarbonate cotransporter (NBCe1) A variant (NBCe1-A) in citrate metabolism under basal conditions and in response to acid loading and hypokalemia. NBCe1-A deletion increased citrate excretion and decreased NaDC1 expression in the proximal convoluted tubules (PCT) and proximal straight tubules (PST) in the medullary ray (PST-MR) but not in the PST in the outer medulla (PST-OM). Acid loading wild-type (WT) mice decreased citrate excretion. NaDC1 expression increased only in the PCT and PST-MR and not in the PST-MR. In NBCe1-A knockout (KO) mice, the acid loading change in citrate excretion was unaffected, changes in PCT NaDC1 expression were blocked, and there was an adaptive increase in PST-MR. Hypokalemia in WT mice decreased citrate excretion; NaDC1 expression increased only in the PCT and PST-MR. NBCe1-A KO blocked both the citrate and NaDC1 changes. We conclude that 1) adaptive changes in NaDC1 expression in response to metabolic acidosis and hypokalemia occur specifically in the PCT and PST-MR, i.e., in cortical proximal tubule segments; 2) NBCe1-A is necessary for normal basal, metabolic acidosis and hypokalemia-stimulated citrate metabolism and does so by regulating NaDC1 expression in cortical proximal tubule segments; and 3) adaptive increases in PST-OM NaDC1 expression occur in NBCe1-A KO mice in response to acid loading that do not occur in WT mice.
Transcriptional profiling of the zebrafish proximal tubule
Authors: Sander Veronika , Salleh Liam , Naylor Richard W. , Schierding William , Sontam Dharani , O’Sullivan Justin M. , Davidson Alan J.
Published: June 2019

The hepatocyte nuclear factor-1β (Hnf1b) transcription factor is a key regulator of kidney tubule formation and is associated with a syndrome of renal cysts and early onset diabetes. To further our understanding of Hnf1b in the developing zebrafish kidney, we performed RNA sequencing analysis of proximal tubules from hnf1b-deficient larvae. This analysis revealed an enrichment of gene transcripts encoding transporters of the solute carrier (SLC) superfamily, including multiple members of slc2 and slc5 glucose transporters. An investigation of expression of slc2a1a, slc2a2, and slc5a2 as well as a poorly studied glucose/mannose transporter encoded by slc5a9 revealed that these genes undergo dynamic spatiotemporal changes during tubule formation and maturation. A comparative analysis of zebrafish SLC genes with those expressed in mouse proximal tubules showed a substantial overlap at the level of gene families, indicating a high degree of functional conservation between zebrafish and mammalian proximal tubules. Taken together, our findings are consistent with a role for Hnf1b as a critical determinant of proximal tubule transport function by acting upstream of a large number of SLC genes and validate the zebrafish as a physiologically relevant model of the mammalian proximal tubule.
Cyclophilin D knockout protects the mouse kidney against cyclosporin A-induced oxidative stress
Authors: Klawitter Jelena , Klawitter Jost , Pennington Alexander , Kirkpatrick Bruce , Roda Galen , Kotecha Nidhi C. , Thurman Joshua M. , Christians Uwe
Published: June 2019

Mitochondrial dysfunction and oxidative stress have been implicated in cyclosporin A (CsA)-induced nephrotoxicity. CsA interacts with cyclophilin D (CypD), an essential component of the mitochondrial permeability transition pore and regulator of cell death processes. Controversial reports have suggested that CypD deletion may or may not protect cells against oxidative stress-induced cell death. In the present study, we treated wild-type (WT) mice and mice lacking CypD [peptidylprolyl isomerase F knockout ( Ppif−/−) mice] with CsA to test the role and contribution of CypD to the widely described CsA-induced renal toxicity and oxidative stress. Our results showed an increase in the levels of several known uremic toxins as well as the oxidative stress markers PGF2α and 8-isoprostane in CsA-treated WT animals but not in Ppif−/− animals. Similarly, a decline in S-adenosylmethionine and the resulting methylation potential indicative of DNA hypomethylation were observed only in CsA-treated WT mice. This confirms previous reports of the protective effects of CypD deletion on the mouse kidney mediated through a stronger resistance of these animals to oxidative stress and DNA methylation damage. However, a negative effect of CsA on the glycolysis and overall energy metabolism in Ppif−/− mice also indicated that additional, CypD-parallel pathways are involved in the toxic effects of CsA on the kidney. In summary, CsA-mediated induction of oxidative stress is associated with CypD, with CypD deletion providing a protective effect, whereas the reduction of energy production observed upon CsA exposure did not depend on the animals’ CypD status.
Alpha-band oscillations track the retrieval of precise spatial representations from long-term memory
Authors: Sutterer David W. , Foster Joshua J. , Serences John T. , Vogel Edward K. , Awh Edward
Published: June 2019

A hallmark of episodic memory is the phenomenon of mentally reexperiencing the details of past events, and a well-established concept is that the neuronal activity that mediates encoding is reinstated at retrieval. Evidence for reinstatement has come from multiple modalities, including functional magnetic resonance imaging and electroencephalography (EEG). These EEG studies have shed light on the time course of reinstatement but have been limited to distinguishing between a few categories. The goal of this work was to use recently developed experimental and technical approaches, namely continuous report tasks and inverted encoding models, to determine which frequencies of oscillatory brain activity support the retrieval of precise spatial memories. In experiment 1, we establish that an inverted encoding model applied to multivariate alpha topography tracks the retrieval of precise spatial memories. In experiment 2, we demonstrate that the frequencies and patterns of multivariate activity at study are similar to the frequencies and patterns observed during retrieval. These findings highlight the broad potential for using encoding models to characterize long-term memory retrieval.

NEW & NOTEWORTHY Previous EEG work has shown that category-level information observed during encoding is recapitulated during memory retrieval, but studies with this time-resolved method have not demonstrated the reinstatement of feature-specific patterns of neural activity during retrieval. Here we show that EEG alpha-band activity tracks the retrieval of spatial representations from long-term memory. Moreover, we find considerable overlap between the frequencies and patterns of activity that track spatial memories during initial study and at retrieval.
Fractal Acoustic Metamaterials with Subwavelength and Broadband Sound Insulation
Authors: Liu Yu , Chen Meng , Xu Wenshuai , Yang Tao , Pei Dongliang , Jiang Heng , Wang Yuren
Published: June 2019

We construct new fractal acoustic metamaterials by coiling up space, which can allow subwavelength‐scale and broadband sound insulation to be achieved. Using the finite element method and the S‐parameter retrieval method, the band structures, the effective parameters, and the transmission losses of these acoustic metamaterials with different fractal orders are researched individually. The results illustrate that it is easy to form low‐frequency bandgaps using these materials and thus achieve subwavelength‐scale sound control. As the number of fractal orders increase, more bandgaps appear. In particular, in the ΓX direction of the acoustic metamaterial lattice, more of these wide bandgaps appear in different frequency ranges, thus providing broadband sound insulation and showing promise for use in engineering applications.
Design and Experimental Validation of a Software-Defined Radio Access Network Testbed with Slicing Support
Authors: Koutlia K. , Ferrús R. , Coronado E. , Riggio R. , Casadevall F. , Umbert A. , Pérez-Romero J.
Published: June 2019

Network slicing is a fundamental feature of 5G systems to partition a single network into a number of segregated logical networks, each optimized for a particular type of service or dedicated to a particular customer or application. The realization of network slicing is particularly challenging in the Radio Access Network (RAN) part, where multiple slices can be multiplexed over the same radio channel and Radio Resource Management (RRM) functions shall be used to split the cell radio resources and achieve the expected behaviour per slice. In this context, this paper describes the key design and implementation aspects of a Software-Defined RAN (SD-RAN) experimental testbed with slicing support. The testbed has been designed consistently with the slicing capabilities and related management framework established by 3GPP in Release 15. The testbed is used to demonstrate the provisioning of RAN slices (e.g., preparation, commissioning, and activation phases) and the operation of the implemented RRM functionality for slice-aware admission control and scheduling.
Orthodontic Treatment Need and the Psychosocial Impact of Malocclusion in 12-Year-Old Hong Kong Children
Authors: Baram Derek , Yang Yanqi , Ren Chong , Wang Ziling , Wong Ricky Wing Kit , Hägg Urban , McGrath Colman , Gu Min
Published: June 2019

Objectives. To determine the prevalence of orthodontic treatment need in 12-year-old children in Hong Kong and its relationship with the psychosocial impact of malocclusion and to assess their associations with sociodemographic factors.Materials and Methods. A random sample of 687 12-year-old children was recruited from 45 secondary schools in Hong Kong. Orthodontic treatment need was assessed on study models by five indices: the Dental Health Component of the Index of Orthodontic Treatment Need (IOTN-DHC), the Aesthetic Component of the IOTN (IOTN-AC), the Dental Aesthetic Index (DAI), the Index of Complexity Outcome and Need (ICON), and the Peer Assessment Rating (PAR). The psychosocial impact of malocclusion on participants and sociodemographic factors were obtained from a questionnaire. Logistic regression was used to examine the correlations between treatment need and the psychosocial impact of malocclusion as well as their associations with sociodemographic factors.Results. The final number of participants was 667 (339 boys and 328 girls, participation rate 667/687 = 97.1%). The prevalence of orthodontic treatment need varied depending on the indices used (10.9–47.8%), but significant correlations were found among the five indices (p< 0.01). The uptake of treatment among the cohort was 2.3%. Boys had higher IOTN-DHC (p< 0.05), DAI (p< 0.05), and PAR (p= 0.05) scores than girls. IOTN-AC was significantly associated with the psychosocial impact of malocclusion (p< 0.05). Parents’ level of education and household income were not significantly associated with either treatment need or the psychosocial impact of malocclusion (p> 0.05).Conclusion. The need for orthodontic treatment in 12-year-old children in Hong Kong remained high, and the uptake of treatment was low. Boys had a higher normative treatment need than girls. Among the five indices, IOTN-AC appears to be the best indicator of the psychosocial impact of malocclusion.
Hybrid Flux Method in Monotonicity‐Preserving Scheme for Accurate and Robust Simulation in Supersonic Flow
Authors: Ahn Myeong-Hwan , Lee Duck-Joo
Published: June 2019

The fifth‐order monotonicity‐preserving (MP5) scheme is an accurate and low dissipative numerical method. As a finite‐volume method, MP5 adopts the Roe‐flux scheme for solving the numerical flux in the compressible Euler equation. However, due to the deficiency of the MP limiter and Roe‐flux in maintaining positive density and pressure, the calculation could fail in cases of extreme flow involving small values of density and pressure. In this study, to overcome such a limitation but still to achieve a high‐accuracy of MP5, we propose a hybrid flux method: the Roe‐flux is used in the global computational domain, but the first‐order Lax‐Friedrich (LF)‐flux is adopted only for trouble grids. The numerical results of shock‐tube and complicated interaction problems indicate that the present scheme is more accurate at discontinuities and local extrema compared to the previous scheme, maintaining positive density and pressure values. For two‐dimensional applications, a supersonic jet is explored with different Mach numbers and temperature conditions. As a result, small vortices induced by the shear layer can be clearly captured by the proposed scheme. Furthermore, a simulation was successfully conducted without blow‐up of calculation even in the extreme jet flow condition.
Endovascular Embolization of a Dissected External Carotid Artery Pseudoaneurysm in a Young Female with Neurofibromatosis Complicated by Preeclampsia
Authors: Lalla Sasha , Seecheran Rajeev , Seecheran Valmiki , Persad Sangeeta , Henry Ronald , Seecheran Naveen Anand
Published: June 2019

Carotid artery pseudoaneurysms are infrequently encountered in clinical practice. Major contributory etiologies include blunt trauma, infections, cystic medial necrosis, fibromuscular dysplasia, arteriosclerosis, and congenital abnormalities. The authors report an exceedingly rare case of a dissected external carotid artery pseudoaneurysm in a 26-year-old female patient with neurofibromatosis complicated by preeclampsia at 28-week period of gestation, safely and successfully treated by coil embolization.
Perianal Basal Cell Carcinoma Successfully Managed with Excisional Biopsy
Authors: Aldana Paola C. , Yfantis Harris G. , John Preeti R.
Published: June 2019

Basal cell carcinoma (BCC) is the most common cutaneous malignancy in the United States and is often nonaggressive. Its location in the perianal region is very rare and it is estimated that only 0.08% of all BCCs occur in this region. Herein, we present a case of perianal basal cell carcinoma, nodular type. The diagnosis was made using excisional biopsy of a skin lesion. Immunohistochemical staining confirmed the diagnosis: it showed diffuse and strong positivity for smooth muscle actin (SMA) and monoclonal antibody BER-Ep4 and was negative for carcinoembryonic antigen (CEA), pancytokeratin (AE1/AE3), and epithelial membrane antigen (EMA). The treatment of choice has traditionally been local excision to clear margins but the newest guidelines recommend Mohs Micrographic surgery (MMS) or standard 4mm surgical margins for this high-risk BCC. Our patient was successfully treated using excisional biopsy without recurrence. In select patients with lesions smaller than 1cm, excisional biopsy may be sufficient to treat the disease and may be better tolerated than MMS and wider surgical margins. Literature review suggests a predisposition for perianal BCC in individuals susceptible to cutaneous malignancies. Therefore, any history of cutaneous malignancy should further prompt clinicians to examine nonsun exposed areas on full body skin exams.
A Comparative Analysis of Biosynthetic Gene Clusters in Lean and Obese Humans
Authors: Wang Shengqin , Li Na , Li Nan , Zou Huixi , Wu Mingjiang
Published: June 2019

Obesity is intrinsically linked with the gut microbiome, and studies have identified several obesity-associated microbes. The microbe-microbe interactions can alter the composition of the microbial community and influence host health by producing secondary metabolites (SMs). However, the contribution of these SMs in the prevention and treatment of obesity has been largely ignored. We identified several SM-encoding biosynthetic gene clusters (BGCs) from the metagenomic data of lean and obese individuals and found significant association between some BGCs, including those that produce hitherto unknown SM, and obesity. In addition, the mean abundance of BGCs was positively correlated with obesity, consistent with the lower taxonomic diversity in the gut microbiota of obese individuals. By comparing the BGCs of known SM between obese and nonobese samples, we found that menaquinone produced by Enterobacter cloacae showed the highest correlation with BMI, in agreement with a recent study on human adipose tissue composition. Furthermore, an obesity-related nonribosomal peptide synthetase (NRPS) was negatively associated with Bacteroidetes, indicating that the SMs produced by intestinal microbes in obese individuals can change the microbiome structure. This is the first systemic study of the association between gut microbiome BGCs and obesity and provides new insights into the causes of obesity.
Carbon Nanotube Layer for Reduction of Fiber Print-Through in Carbon Fiber Composites
Authors: Guedes Joana F. , Martins Marta S. S. , Martins Ramiro , Rocha Nuno
Published: June 2019

Fiber print-through effect is a limitation to the use of carbon fiber-reinforced composites in space applications, namely, mirror telescopes. Replica method is used for the production of lightweight telescope mirrors. However, this method requires a polished mandrel, increasing considerably the final cost. In this work, we report a cheaper and simpler alternative production method, which consists in the addition of a carbon nanotube filled epoxy resin layer on the surface of carbon reinforced composites, in order to reduce fiber print-through of the materials. The influence of different carbon nanotube functionalizations, concentrations, and dispersion levels are also assessed. The surface properties are evaluated by interferometry (roughness and waviness) and scanning electron microscopy (morphology). The results show that the waviness, roughness, and consequently fiber print-though are considerably reduced with the addition of a thin layer of nonfunctionalized carbon nanotubes.
Neutrophil Elastase Activity Imaging: Recent Approaches in the Design and Applications of Activity-Based Probes and Substrate-Based Probes
Authors: Jugniot Natacha , Voisin Pierre , Bentaher Abderrazzak , Mellet Philippe
Published: June 2019

The last few decades of protease research has confirmed that a number of important biological processes are strictly dependent on proteolysis. Neutrophil elastase (NE) is a critical protease in immune response and host defense mechanisms in both physiological and disease-associated conditions. Particularly, NE has been identified as a promising biomarker for early diagnosis of lung inflammation. Recent studies have shown an increasing interest in developing methods for NE activity imaging both in vitro and in vivo. Unlike anatomical imaging modalities, functional molecular imaging, including enzymatic activities, enables disease detection at a very early stage and thus constitutes a much more accurate approach. When combined with advanced imaging technologies, opportunities arise for measuring imbalanced proteolytic activities with unprecedented details. Such technologies consist in building the highest resolved and sensitive instruments as well as the most specific probes based either on peptide substrates or on covalent inhibitors. This review outlines strengths and weaknesses of these technologies and discuss their applications to investigate NE activity as biomarker of pulmonary inflammatory diseases by imaging.
Signet Ring Cell Carcinoma of the Lung: A Diagnostic Pitfall in Pregnancy
Authors: Danzinger Sabine , Köstler Wolfgang J. , Funovics Martin , Herac Merima , Müllauer Leonhard , Prosch Helmut , Kölbl Heinz
Published: June 2019

Lung cancer during pregnancy represents a rare disease. In this case report, we present a patient at advanced and metastasized stage of signet ring cell carcinoma who presented in the22ndweek of gestation.
The Application of Induced Pluripotent Stem Cells in Pathogenesis Study and Gene Therapy for Vascular Disorders: Current Progress and Future Challenges
Authors: Peng Guang-Yin , Lin Yang , Li Jing-Jing , Wang Ying , Huang Hao-Yue , Shen Zhen-Ya
Published: June 2019

Vascular disorders are complex diseases with high morbidity and mortality. Among them, the dilated macrovascular diseases (MVD), such as aortic aneurysm and aortic dissection, have presented a huge threat to human health. The pathogenesis of vascular diseases is mostly associated with property alteration of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). Studies have confirmed that induced pluripotent stem cells (iPSCs) can be proliferated and differentiated into other somatic cells, such as VECs and VSMCs. And patient-specific cells could provide detailed human-associated information in regard to pathogenesis or drug responses. In addition, differentiated ECs from iPSC have been widely used in disease modeling as a cell therapy. In this review, we mainly discussed the application of hiPSCs in investigating the pathological mechanism of different inherited vascular diseases and provide a comprehensive understanding of hiPSCs in the field of clinical diagnosis and gene therapy.
High Numbers of Circulating CD57+ NK Cells Associate with Resistance to HER2-Specific Therapeutic Antibodies in HER2+ Primary Breast Cancer
Authors: Muntasell Aura , Servitja Sònia , Cabo Mariona , Bermejo Begoña , Pérez-Buira Sandra , Rojo Federico , Costa-García Marcel , Arpí Oriol , Moraru Manuela , Serrano Laia , Tusquets Ignasi , Martínez María Teresa , Heredia Gemma , Vera Andrea , Martínez-García María , Soria Laura , Comerma Laura , Santana-Hernández Sara , Eroles Pilar , Rovira Ana , Vilches Carlos , Lluch Ana , Albanell Joan , López-Botet Miguel
Published: June 2019

Natural killer (NK) cells can orchestrate effective antitumor immunity. The presence of tumor-infiltrating NK cells in diagnostic biopsies predicts pathologic complete response (pCR) to HER2-specific therapeutic antibodies in patients with primary breast cancer. Here, we analyzed whether diversity in circulating NK cells might influence tumor infiltration and HER2-specific therapeutic antibody efficacy. We found that numbers of circulating CD57+ NK cells inversely correlated with pCR to HER2-specific antibody treatment in patients with primary breast cancer independently of age, traditional clinicopathologic factors, and CD16A 158F/V genotype. This association was uncoupled from the expression of other NK-cell receptors, the presence of adaptive NK cells, or changes in major T-cell subsets, reminiscent of cytomegalovirus-induced immunomodulation. NK-cell activation against trastuzumab-coated HER2+ breast cancer cells was comparable in patients with high and low proportions of CD57+ NK cells. However, circulating CD57+ NK cells displayed decreased CXCR3 expression and CD16A-induced IL2-dependent proliferation in vitro. Presence of CD57+ NK cells was reduced in breast tumor–associated infiltrates as compared with paired peripheral blood samples, suggesting deficient homing, proliferation, and/or survival of NK cells in the tumor niche. Indeed, numbers of circulating CD57+ were inversely related to tumor-infiltrating NK-cell numbers. Our data reveal that NK-cell differentiation influences their antitumor potential and that CD57+ NK cells may be a biomarker useful for tailoring HER2 antibody–based therapeutic strategies in breast cancer.
A Case-Control Study of ABCB1, ABCB6, and ABCG1 Polymorphisms and Schizophrenia in a Han Chinese Population
Authors: Ma Gaini , Huang Xiaoye , Bi Yan , Xu Fei , Niu Weibo , Ren Decheng , Sun Qianqian , Guo Zhenming , Yuan Ruixue , Yuan Fan , Wu Xi , Yang Fengping , Wang Lu , Li Weidong , He Lin , Yu Tao , Li Xingwang , Liu Jie , He Guang
Published: June 2019

Background: Schizophrenia (SCZ) is a complex, heritable, and devastating psychiatric disorder. Mutations in the members of ABC transporters have been associated with psychiatric illnesses. Aims: In this study, we investigated whether 9 SNPs in ABCB1 (rs6946119, rs28401781, rs4148739, and rs3747802), ABCB6 (rs1109866, rs1109867, rs3731885, and rs3755047), and ABCG1 (rs182694) contribute to the risk of SCZ in a Han Chinese population. Methods: We conducted a case-control study in a Han Chinese population, involving 1,034 SCZ patients and 1,034 unrelated healthy controls to genotype 9 SNPs. Results: The analysis demonstrated that rs182694 of ABCG1 was significantly different between SCZ patients and controls as to allele (rs182694: p = 0.0070, χ2 = 7.27) and genotype frequencies (rs182694: p = 0.0013, χ2 = 13.35). Conclusions: Our findings support an association between ABCG1 polymorphism and SCZ in a Han Chinese population.
Transcribing and Transforming: Towards Inclusive, Multilingual Child Speech Training for South African Speech-Language Therapy Students
Authors: Pascoe Michelle , Mahura Olebeng , Rossouw Katherine
Published: June 2019

Objective: Phonetic transcription may encourage engagement with language diversity in multilingual settings. We describe how transcription can be used to help South African speech-language therapy (SLT) students engage with the many languages spoken in their country. Objectives were to describe (a) the local context, (b) transcription in the curriculum, and (c) participant observations from staff facilitating the Child Speech course. Method and Materials: A case study approach was used to investigate teaching and learning transcription in a real-life context, the undergraduate second-year Child Speech course in an SLT programme. Document review of curriculum and university documents, national policies, and international best practice guidelines took place, together with participant observations from facilitators. Results: We describe 4 activities that show how transcription skills can be developed while introducing local languages into the curriculum. These activities give students the opportunity to develop transcription skills for a range of local languages, while at the same time encouraging them to learn the languages, construct communal resources, and promote a problem-solving attitude to their practice. Conclusion: Calls to transform higher education in South Africa and “decolonise” curricula are key drivers underpinning this work. Transcription may be a useful tool in preparing students to practise in a multilingual context.
Construct Validity of the Viking Speech Scale
Authors: Pennington Lindsay , Hustad Katherine C.
Published: June 2019

Objective: The Viking Speech Scale (VSS) reliably classifies the speech performance of children with cerebral palsy. This paper aims to establish the construct validity of the VSS by testing the extent to which percentage intelligibility in single word speech and connected speech predicts VSS rating. Patients and Methods: This is a secondary analysis of two sets of anonymised data collected for previous research. The full data set comprised 79 children with cerebral palsy from the US (n = 43) and the UK (n = 36): (43 boys, 36 girls); mean age 7.2 years (SD 3.3). Single word intelligibility was measured using the TOCS+ words for US children and Children’s Speech Intelligibility Measure for the UK children. Connected speech intelligibility was measured from a subset of repeated sentences in TOCS+ for US children and picture description for the UK children. We used ordinal logistic regression to examine prediction of VSS rating by percentage single word and connected speech intelligibility scores in both samples. Results: Percentage single word intelligibility and connected speech intelligibility predicted VSS rating in univariate and multivariate regression models for both the US and UK samples. Conclusion: Intelligibility predicts VSS for both single words and connected speech, establishing the construct validity of VSS.
Leptin, Anxiety Symptoms, and Hypothalamic-Pituitary-Adrenal Axis Activity among Drug-Free, Female Suicide Attempters
Authors: Ambrus Livia , Westling Sofie
Published: June 2019

Background: Dysregulation of leptin secretion and functioning of the hypothalamic-pituitary-adrenal (HPA) axis may be involved in the pathophysiology of suicide. Preclinical and clinical studies have shown interactions between the HPA axis and leptin. There is also evidence for a negative relationship between leptin and anxiety in humans. However, these possible associations have not been studied in individuals with attempted suicide. Objectives: To examine the relationship between leptin, HPA axis activity, and anxiety in individuals with a recent suicide attempt. Method: Sixty-nine individuals with a recent suicide attempt (n = 37 females; n = 32 males) were recruited and subjected to the Dexamethasone Suppression Test (DST), lumbar puncture, and evaluation with the Comprehensive Psychopathological Rating Scale from which the Brief Scale for Anxiety (BSA) was derived. Leptin was analyzed in cerebrospinal fluid (CSF) and cortisol in serum. Leptin was corrected for body mass index (BMI) by dividing CSF-leptin by BMI (CSF-leptin/BMI). Due to gender-related differences in leptin secretion and HPA axis activity, calculations were made for males and females separately. Results: Significant differences were only found among females; CSF-leptin/BMI levels correlated significantly and negatively with BSA (p < 0.05), pre-DST cortisol, and post-DST serum cortisol at 8 a.m. and 3 p.m. (all p < 0.05). Furthermore, CSF-leptin/BMI was significantly lower in nonsuppressors of dexamethasone as compared to suppressors (p < 0.05). Conclusions: These findings suggest that in females with a recent suicide attempt, low CSF leptin may be related to symptoms of anxiety and a hyperactive HPA axis.
Prognostic Implications of Right Ventricular Remodeling and Function in Patients With Significant Secondary Tricuspid Regurgitation
Authors: Dietz Marlieke F. , Prihadi Edgard A. , van der Bijl Pieter , Goedemans Laurien , Mertens Bart J.A. , Gursoy Erhan , van Genderen Olton S. , Ajmone Marsan Nina , Delgado Victoria , Bax Jeroen J.
Published: June 2019

Background:

In patients with significant (moderate and severe) tricuspid regurgitation (TR), the decision to intervene is influenced by right ventricular (RV) size and function. RV remodeling in significant secondary TR has been underexplored. The aim of this study was to characterize RV remodeling in patients with significant secondary TR and to investigate its prognostic implications.

Methods:

RV remodeling was characterized by transthoracic echocardiography in 1292 patients with significant secondary TR (median age 71 [62–78]; 50% male). Four patterns of RV remodeling were defined according to the presence of RV dilation (tricuspid annulus≥40 mm) and RV systolic dysfunction (tricuspid annulus systolic excursion plane<17 mm): pattern 1, normal RV size and systolic function; pattern 2, dilated RV with preserved systolic function; pattern 3, normal RV size with systolic dysfunction; and pattern 4, dilated RV systolic dysfunction. The primary end point was all-cause mortality and the event rates were compared across the 4 patterns of RV remodeling.

Results:

A total of 183 (14%) patients showed pattern 1 RV remodeling; 256 (20%) showed pattern 2; 304 (24%) presented with pattern 3; and 549 (43%) had pattern 4 RV remodeling. Patients with pattern 4 RV remodeling were more frequently male; more often had coronary artery disease, worse renal function, and impaired left ventricular ejection fraction; and were more often symptomatic. Only 98 (8%) patients underwent tricuspid valve annuloplasty during follow-up. During a median follow-up of 34 (interquartile range, 0–60) months, 510 (40%) patients died. The 5-year survival rate was significantly worse in patients presenting with patterns 3 and 4 RV remodeling in comparison with pattern 1 (52% and 49% versus 70%;
P
=0.002 and
P
<0.001, respectively), and were independently associated with poor outcome on multivariable analysis.

Conclusions:

In patients with significant secondary TR, patients with RV systolic dysfunction have worse clinical outcome regardless of the presence of RV dilation.
Association of Major Adverse Cardiac Events up to 5 Years in Patients With Chest Pain Without Significant Coronary Artery Disease in the Korean Population
Authors: Choi Byoung Geol , Rha Seung‐Woon , Yoon Seong Gyu , Choi Cheol Ung , Lee Min Woo , Kim Suhng Wook
Published: June 2019

Background

Significant coronary artery disease has a well‐known association with long‐term adverse cardiovascular events. In this study, we aimed to evaluate its association with long‐term major adverse clinical events (
MACE
) up to 5 years in patients who presented with chest pain without significant
coronary artery disease
.

Methods and Results

A total of 5890 subjects with chest pain without significant
coronary artery disease
were prospectively enrolled in this study. The mean follow‐up duration was 3.4 years. Multivariable Cox proportional hazards regression analysis was performed for assessing the independent risk factors for
MACE
or sustained angina pectoris.
MACE
was defined as the composite of total death, myocardial infarction, coronary revascularization, stroke, and hospitalization because of heart failure. Ninety‐one (2.2%) patients developed
MACE
, and 309 (8.1%) patients developed sustained
angina pectoris
, both within 5 years. In multivariable Cox proportional hazards regression analysis, the risk of
MACE
was significantly associated with age (per 5 years; hazard ratio [
HR
], 1.44; 95%
CI
, 1.30–1.60) and insignificant coronary stenosis (30%–70%;
HR,
2.03; 95%
CI;
1.28–3.21). The risk of sustained
angina pectoris
was significantly associated with age (per 5 years;
HR,
1.05; 95%
CI,
1.01–1.11), dyslipidemia (
HR,
1.34; 95%
CI
, 1.06–1.70),
insignificant coronary stenosis
(
HR,
2.54; 95%
CI
, 1.94–3.31), coronary artery spasm (HR, 1.42; 95%
CI
, 1.11–1.80), and myocardial bridge (HR, 1.37; 95%
CI
, 1.04–1.81).

Conclusions

In patients without significant
CAD
, aging and
insignificant coronary stenosis
have a strong association with future long‐term
MACE
. Also, aging, dyslipidemia,
insignificant coronary stenosis
,
coronary artery spasm,
and
myocardial bridge
are strongly associated with future
angina pectoris
.