bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of left atrial appendage occlusion in high-risk patients
Authors: Masoud Ahmed , Bartoletti Stefano , Fairbairn Timothy , Khurana Ayush , Velavan Periaswamy , Morrison William Lindsay , Khalatbari Afshin , Aggarwal Suneil , Sharma Nikhill , Kirchhof Paulus , Gupta Dhiraj
Published: November 2017

Objective

Percutaneous left atrial appendage (LAA) occlusion can be an interventional alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation.

Methods

We delivered LAA occlusion therapy using a standardised approach to patient referral, multidisciplinary team assessment, implant criteria, imaging and follow-up. We analysed patient characteristics, efficacy and safety of the implant procedure, and 12-month outcomes.

Results

Of 143 referrals from October 2014 to December 2016, 83 patients (age 76±8years, 32.5% female, mean CHAD2S2-VASc score 4 ±1) were offered LAA occlusion. Eighty (95.3%) had previous major bleeding (intracranial in 59%). LAA occluder implantation with an Amulet device was successful in 82 (98.8%), with periprocedural major adverse events occurring in 5 (6.0%) patients (2 device embolisations including 1 death, 2 major bleeds). Cardiac imaging in 75 (94%) patients 2months following implant showed device-related thrombus in 1 case (1.3%) and minor (<5mm) device leaks in 13 (17.1%). Over a median 12-month follow-up, 3 (3.8%) ischaemic strokes, 2 (2.5%) haemorrhagic strokes and 5 (6.3%) major extracranial bleeds occurred. All-cause mortality was 10%, with most deaths (7, 87.5%) due to non-cardiovascular causes.

Conclusions

LAA occlusion may be a reasonable option for stroke prevention inhigh-risk patients with atrial fibrillation ineligible for anticoagulation. However, procedural complication rates are not insignificant, and patients remain at risk of serious adverse events and death even after successful implant.
Pain assessment in companion animals: an update
Authors: Reid Jacky , Scott Marian , Nolan Andrea
Published: November 2017

An article ‘Pain assessment in animals’ was previously published in In Practice (Reid and others 2013). This short article aims to bring the reader up to date with what we consider to be significant advances in the field of pain assessment in companion animals.
Common dental frustrations and how to overcome them
Authors: Perry Rachel
Published: November 2017

Prevalence of periodontal disease remains high in companion animals and, if neglected, can seriously affect an animal's health and welfare. Often owners do not appreciate the risks that come alongside poor dental health and encouraging them to invest in preventive measures for their pet can be challenging. Here, Rachel Perry discusses techniques for communicating with owners about their pet's dental health, and how to tackle a client's reluctance to treat early‐stage periodontal disease.
Defect in phosphoinositide signalling through a homozygous variant inPLCB3causes a new form of spondylometaphyseal dysplasia with corneal dystrophy
Authors: Ben-Salem Salma , Robbins Sarah M , LM Sobreira Nara , Lyon Angeline , Al-Shamsi Aisha M , Islam Barira K , Akawi Nadia A , John Anne , Thachillath Pramathan , Al Hamed Sania , Valle David , Ali Bassam R , Al-Gazali Lihadh
Published: November 2017

Background

Bone dysplasias are a large group of disorders affecting the growth and structure of the skeletal system.

Methods

In the present study, we report the clinical and molecular delineation of a new form of syndromic autosomal recessive spondylometaphyseal dysplasia (SMD) in two Emirati first cousins. They displayed postnatal growth deficiency causing profound limb shortening with proximal and distal segments involvement, narrow chest, radiological abnormalities involving the spine, pelvis and metaphyses, corneal clouding and intellectual disability. Whole genome homozygosity mapping localised the genetic cause to 11q12.1–q13.1, a region spanning 19.32 Mb with ~490 genes. Using whole exome sequencing, we identified four novel homozygous variants within the shared block of homozygosity. Pathogenic variants in genes involved in phospholipid metabolism, such asPLCB4andPCYT1A,are known to cause bone dysplasia with or without eye anomalies, which led us to selectPLCB3as a strong candidate. This gene encodes phospholipase C β 3, an enzyme that converts phosphatidylinositol 4,5 bisphosphate (PIP2) to inositol 1,4,5 triphosphate (IP3) and diacylglycerol.

Results

The identified variant (c.2632G>T) substitutes a serine for a highly conserved alanine within the Ha2’ element of the proximal C-terminal domain. This disrupts binding of the Ha2’ element to the catalytic core and destabilises PLCB3. Here we show that this hypomorphic variant leads to elevated levels of PIP2in patient fibroblasts, causing disorganisation of the F-actin cytoskeleton.

Conclusions

Our results connect a homozygous loss of function variant inPLCB3with a new SMD associated with corneal dystrophy and developmental delay (SMDCD).
Erythropoietin reduces collagen deposition after myocardial infarction but does not improve cardiac function
Authors: Pessoa Fernanda Gallinaro , Mady Charles , Fonseca Keila Cardoso Barbosa , de Oliveira-Fonoff Adriana Morgan , Salemi Vera Maria Cury , Jordão Maurício Rodrigues , Fernandes Fabio , Ramires Felix José Alvarez
Published: November 2017

Myocardial remodeling includes inappropriate collagen deposition in the interstitium. Erythropoietin (EPO) may have cardioprotective effects. We aimed to assess the role of EPO on myocardial remodeling during the chronic phase. We studied 60 Wistar rats divided into the following groups: control (CT), control + EPO (CT + EPO), myocardial infarction + EPO (MI + EPO), and myocardial infarction (MI). The interstitial collagen volume fraction (ICVF) was quantified and echocardiography was performed. We quantified asymmetric dimethylarginine and glutathione by ELISA, and used real-time PCR to assess apoptosis and inflammation. Western blotting was used to evaluate inflammatory proteins and tissue inhibitors of metalloproteinases (TIMPs), and TUNEL staining was used to detect apoptosis. For matrix metalloproteinases (MMPs), we performed zymography. Parametric and nonparametric analyses were performed according to normality testing. ICVF was greater in MI groups (p < 0.001) and was attenuated by EPO (p = 0.05). The MMP-2 did not show any difference between groups. The TIMP-1 and TIMP-2 did not have difference between groups. The MI groups had worse fraction shortening (p < 0.001), without EPO protection (p = 0.666). The MI groups had increased left ventricle diastolic dimension (p < 0.001) without EPO attenuation (p = 0.79). EPO did not act on oxidative stress. Apoptosis and inflammation were not modulated by EPO. We concluded that EPO attenuated interstitial collagen accumulation, but did not protect from heart dilation or dysfunction.
Glutamine protection in an experimental model of acetaminophen nephrotoxicity
Authors: Brovedan Marco A. , Molinas Sara M. , Pisani Gerardo B. , Monasterolo Liliana A. , Trumper Laura
Published: November 2017

Acetaminophen (APAP) is a widely prescribed analgesic and antipyretic drug. In the present work, we studied the effects of glutamine (Gln) in an in vivo model of APAP-induced nephrotoxicity in male Wistar rats. Renal function, histological characteristics, and Na+,K+-ATPase cortical abundance and distribution were analyzed. The appearance of HSP70 and actin in urine was also evaluated. Myeloperoxidase (MPO) activity in cortical tissue was measured as an index of the inflammatory response. Gln administration 30 min before APAP protected from the renal functional and histological damage promoted by APAP. Rats that received the dual treatment Gln and APAP (Gln/APAP) showed the same level of Na+,K+-ATPase cortical induction as APAP-treated animals, but the enzyme maintained its normal basolateral localization. HSP70 abundance was increased up to the same level in the Gln, APAP, and Gln/APAP groups. Urinary HSP70 and actin were detected only in the APAP-treated animals, reinforcing the protection of renal tubular integrity afforded by the Gln pretreatment. Gln pretreatment also protected from the increment in MPO activity promoted by APAP. Our results support the idea that Gln pretreatment could be a therapeutic option to prevent APAP-induced renal injury.
MODELING HOUSEHOLD PARTICIPATION DECISIONS BETWEEN DOMESTIC AND INTERNATIONAL TRIPS BY SEMI-NONPARAMETRIC REGRESSIONS
Authors: YEH CHIA-YU , LIU KANG ERNEST
Published: November 2017

Globalization has caused many countries to experience significant slowdown, thus, tourism development becomes the primary policy to stimulate the economy. Investigating the demand of leisure activities is necessary for the development of a tourism industry with sound policies. This research adopts demographic data to allocate the factors affecting participation decisions and utilizes semi-nonparametric (SNP) regressions to analyze household decision regarding domestic and international trips. By combining a parametric component with a nonparametric component, the SNP method increases the flexibility of participation decision models from relaxing distributional assumptions. The results of this study reveal that decision-making for both domestic and international trips is jointly determined. Various factors, including income, capital gain ratio, age and education, are decisive to trip types, indicating the market segmentation of tourism businesses. Moreover, SNP regression performs superior to the traditional bivariate probit model, suggesting that the model developed in this research can provide comprehensive results for policy implications.
Optimal Design Methodology for Frequency Compensation Circuits in Logging Cable Transmission Channel
Authors: Cui Qian , Shuang Kai
Published: November 2017

Bandwidth limitation is a vital problem for high-speed data transmission in logging cable telemetry systems (LCTSs). This paper proposes a frequency compensation method with an analog circuit design, possessing high flexibility and robustness. Analytical expressions are derived for the relationship between pole-zero and gain, deviations caused by high temperature; and are then verified via simulation. To address the efficacy of the circuit design, a real case with low computation complexity and high accuracy is proposed and employed. The case of a 7[Formula: see text]km LCTS shows frequency compensation with a 200% bandwidth expansion — from 160[Formula: see text]kHz at [Formula: see text]55[Formula: see text]dB of the original cable to 300[Formula: see text]kHz at [Formula: see text]3[Formula: see text]dB — and a 60[Formula: see text]dB improvement in high frequency gain. After comparing the signals with and without compensation, the improvements in transmission performance by the proposed pre-emphasis circuit and equalizer are confirmed.
Patient-Reported Outcome Following Ulnotriquetral Ligament Split Tear Repair
Authors: Tang Camelia Qian Ying , Lai Sean Wei Hong , Leow Geraldine , Tay Shian Chao
Published: November 2017

Background: While the clinical presentation and mechanism of injury of ulnotriquetral (UT) ligament split tear had been well described, there has been no other studies that has reported on the outcome of a UT ligament repair. This study aims to look at the patient-reported outcomes following UT ligament split tear repair.

Methods: 18 wrists (13 right and 5 left) in 17 patients (12 males and 5 females, mean age 25.0 ± 8.4 years, range 16–50 years) who had UT ligament split tear and undergone surgical repair between November 2007 and December 2013 were retrospectively analysed. Patient-reported outcome of resolution of pain, and objective measurements such as improvement in grip strength and range of movement of the wrist were recorded. Patients were followed up until the pain was completely resolved or the last documented consultation. The mean follow-up duration was 16.2 months.

Results: 94% reported improvements post-surgery, of which 63% reported complete resolution of pain. 6% reported no improvement in pain post-operatively. No patient reported worsening of pain after the surgery. There was significant improvement in grip strength from a mean of 23.5 kg to 27.1 kg. There was no significant change in range of motion of the wrist.

Conclusions: The majority of patients reported resolution or improvement of pain after surgical repair. In addition, there was statistically significant improvement in grip strength recorded.
Management of the Pediatric Patient Following Upper Extremity Replantation or Revascularization: A Suggested Protocol
Authors: Sundet Alec , Ipaktchi Kyros , Kunrath Claudia , Banegas Rodrigo N.
Published: November 2017

Background: Traumatic pediatric amputations of the hand and upper extremity can have long-term financial, psychological, developmental, and functional consequences that readily extend beyond the realm of that which is normally encountered in comparatively injured adults. These factors, along with a paucity of medical comorbidities, have guided a more liberal and aggressive approach to treating pediatric amputations in hopes of optimizing psychosocial, aesthetic, and developmental outcomes. Furthermore, advances in pharmacology and microsurgical replantation techniques have allowed what were otherwise exceedingly rare surgeries to become commonplace in hospitals all over the world. Despite these gains, vascular thrombosis remains the leading cause of failure in microvascular surgeries. A recent survey showed that 96% of reconstructive surgeons use some form of anticoagulation therapy in their treatment, but no consensus regarding pharmacologic agents, dosing, or efficacy exists. The risk of thrombosis is further complicated by the dynamic nature of vasculature in response to stressors such as sympathetic tone, decreased intravascular volume, and response to external temperature. Given the lack of a higher-level evidence to guide the replantation surgeon in postoperative orders, we created an inclusive protocol, outlining complete and proper management of the pediatric patient following revascularization or replantation surgery.

Methods: We reviewed the methods employed by our microvascular surgeons and consulted with board-certified pediatricians to produce a final document that was adopted ubiquitously among our providers.

Results: We do not have head-to-head data demonstrating improved outcomes with use of the protocol. Nonetheless, the original document has been modified and reproduced here for your consideration and use.

Conclusions: Since initiating the protocol, we feel it has helped standardize our practice, avoid instances of incomplete or missed order sets, and facilitate interdisciplinary management through decreased gaps in communication, especially in those surgeries terminating in the middle of the night.
Spontaneous Rupture of the Extensor Pollicis Longus with the Extensor Pollicis Brevis Deformity
Authors: Ikeda Kazuo , Osamura Naoki , Tada Kaoru
Published: November 2017

This paper examines three cases of spontaneous ruptures of the extensor pollicis longus (EPL) with the extensor pollicis brevis (EPB) deformity. The patients ranged from 39 to 71 years old. Non-dominant hands were involved in all three cases. There were no trauma nor pathological cause of EPL ruptures. A tendon transfer using the extensor indicis proprius was performed in each case. Intraoperative findings showed hypoplastic EPB in one case and EPB defects in two cases. A weak or defective EPB puts an excessive load on the EPL, which might be one of the causes of spontaneous EPL rupture.
GIS Enabled SPH-Soil Modeling for the Post-Failure Flow of Landslides Under Seismic Loadings
Authors: Hu Man , Liu Qiuqiang , Wu Fei , Yu Mengting , Jiang Shenghua
Published: November 2017

Landslide can usually be induced by a strong earthquake, and it causes very serious property damage and human casualties. Modeling of post-failure flow of landslides is one of the important approaches that can be used to simulate landslide flow developments and predict the landslide hazard zone. In this paper, a Smoothed Particle Hydrodynamics (SPH) model based on the constitution of elastic-plastic constitutive mechanics for soil has been developed for simulating the behavior of a class of geo-materials under the seismic loadings. Our SPH-Soil model considers the plastic behavior of the materials, and hence it is very important for more accurate and realistic simulations of geo-materials of soil type. The implemented materials laws in the SPH-Soil code include classical elastic-plasticity with a linear elastic part, and different applicable yield surfaces with nonassociated flow rules. In order to apply this model to actual landslide modeling the Geographic Information System (GIS) is utilized to generate site-specific models. We have thus developed a C# code to generate the particles of a given landslide site, which produces realistic particle mass and actual complicated boundaries for the SPH-Soil model. With GIS enabled, complex topography and irregular boundary can be accurately and easily built up. Then the SPH-Soil code has been applied to the well-known Daguangbao landslide, which was triggered by Wenchuan earthquake in 2008. The topographies after failure were compared with that obtained from field collected data and good agreement was found.
Not merely a protective packing organ? A review of fascia and its force transmission capacity
Authors: Wilke Jan , Schleip Robert , Yucesoy Can A. , Banzer Winfried
Published: November 2017

Recent research indicates that fascia is capable of changing its biomechanical properties. Moreover, as it links the skeletal muscles, forming a body-wide network of multidirectional myofascial continuity, the classical conception of muscles as independent actuators has been challenged. Hence, the present synthesis review aims to characterize the mechanical relevance of the connective tissue for the locomotor system. Results of cadaveric and animal studies suggest a clinically relevant myofascial force transmission to neighboring structures within one limb (e.g., between synergists) and in the course of muscle-fascia chains (e.g., between leg and trunk). Initial in vivo trials appear to underpin these findings, demonstrating the existence of nonlocal exercise effects. However, the factors influencing the amount of transmitted force (e.g., age and physical activity) remain controversial, as well as the role of the central nervous system within the context of the observed remote exercise effects.
Oxidative Stress‐Related Parthanatos of Circulating Mononuclear Leukocytes in Heart Failure
Authors: Bárány Tamás , Simon Andrea , Szabó Gergő , Benkő Rita , Mezei Zsuzsanna , Molnár Levente , Becker Dávid , Merkely Béla , Zima Endre , Horváth Eszter M.
Published: November 2017

Background. The present study aims to examine the oxidative stress‐related activation of poly(ADP‐ribose) polymerase (PARP), a cause of parthanatos in circulating mononuclear leukocytes of patients with chronic heart failure (CHF), that was rarely investigated in the human setting yet. Methods. Patients with CHF (n = 20) and age‐ and body mass index‐matched volunteers (n = 15) with a normal heart function were enrolled. C‐reactive protein, N‐terminal probrain‐type natriuretic peptide (pro‐BNP), plasma total peroxide level (PRX), plasma total antioxidant capacity (TAC), oxidative stress index (OSI), leukocyte lipid peroxidation (4‐hydroxynonenal; HNE), protein tyrosine nitration (NT), poly(ADP‐ribosyl)ation (PARylation), and apoptosis‐inducing factor (AIF) translocation were measured in blood samples of fasting subjects. Results. Plasma PRX, leukocyte HNE, NT, PARylation, and AIF translocation were significantly higher in the heart failure group. Pro‐BNP levels in all study subjects showed a significant positive correlation to PRX, OSI, leukocyte HNE, NT, PARylation, and AIF translocation. Ejection fraction negatively correlated with the same parameters. Among HF patients, a positive correlation of pro‐BNP with PRX, OSI, and PARylation was still present. Conclusions. Markers of oxidative‐nitrative stress, PARP activation, and AIF translocation in blood components showed correlation to reduced cardiac function and the clinical appearance of CHF. These results may reinforce the consideration of PARP inhibition as a potential therapeutic target in CHF.
HPV16 E6 Promotes Breast Cancer Proliferation via Upregulation of COX-2 Expression
Authors: Wang Y. X. , Li Y. Z. , Zhang Z. Y. , Wang J. Q. , Cui J. , Qian X. L.
Published: November 2017

Background.Breast cancer remains the leading cause of cancer-related mortality worldwide. It has been indicated that human papillomaviruses 16 (HPV16) might participate in the pathogenesis and development of breast cancer. However, the detected rate of HPV16 varies with region. We will investigate HPV16 E6 expression in North China and explore the effects and mechanism of HPV16 E6 on breast cancer proliferation in this study.Methods.The expressions of HPV16 E6 and COX-2 in paraffin-embedded tissues of the invasive ductal breast cancer were detected by qPCR and IHC. The effects of HPV16 E6 on breast cancer proliferation were determined by function studies. The mechanism of HPV16 E6 in promoting breast cancer proliferation was explored by Western blot and Dual-Luciferase Reporter Assay.Results.HPV16 E6 was positive in 28% invasive ductal breast carcinoma in North China; HPV16 E6 promoted breast cancer proliferation. Inhibition of COX-2 by siCOX-2 or Celecoxib attenuated the proliferation of breast cancer cells with HPV16 E6 expression; and the upregulation of COX-2 could be suppressed by the inhibition of NF-κB activity.Conclusion.HPV16 E6 promotes breast cancer proliferation by activation of NF-κB signaling pathway and increase of COX-2 expression. COX-2 will be a potential target for HPV16 E6-associated breast cancer.
Short-Term Postoperative Cognitive Dysfunction and Inflammatory Response in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Pilot Study
Authors: Yu Hui , Dong Rui , Lu Yayuan , Yang Xi , Chen Chang , Zhang Zongze , Peng Mian
Published: November 2017

Objectives. To assess the association between short-term postoperative cognitive dysfuction (POCD) and inflammtory response in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Design. A prospective cohort study. Setting. University medical centre. Participants. Fifty-one adult patients who had undergone CRS-HIPEC and twenty control participants. Measurements. The inflammatory marker levels in plasma and cognitive function were measured. Results. Twenty (39.2%, 20/51) patients developed POCD at 1 w after CRS-HIPEC. The patients with POCD had higher serum interleukin 1β (IL-1β), serum amyloid A (SAA), S100 calcium-binding protein β (S-100β), and high mobility group box-1 protein (HMGB-1) levels at 1 and 24 h postoperatively than patients without POCD. There was an association between POCD and the maximum IL-1β and S-100β concentrations in serum, which remained following adjustment for age and FBS. Conclusion. In this pilot study, perioperative inflammatory marker levels increase significantly after CRS-HIPEC in adult patients, and such elevations are associated with the development of short-term cognitive dysfunction after this complex surgery. These results suggested the need for a larger RCT to replicate and confirm these findings.
Preparation of AuNPs/GQDs/SiO2 Composite and Its Catalytic Performance in Oxidation of Veratryl Alcohol
Authors: Yang Yaoyao , Zhang Jiali , Zhang Fangwei , Guo Shouwu
Published: November 2017

Composites of gold nanoparticles and graphene quantum dots (AuNPs/GQDs) exhibit excellent dispersibility in aqueous solutions. Thus, it is difficult to separate them from wet reaction systems when they are used as catalysts. To resolve this issue, in this study, an AuNPs/GQDs composite was immobilized on silicon dioxide through the hydrothermal method, which involved the formation of an amide bond between the surface GQDs of the AuNPs/GQDs composite and the amino group of the silane. The as-synthesized AuNPs/GQDs/SiO2 composite was found to be suitable for use as a heterogeneous catalyst for the oxidation of veratryl alcohol in water and exhibited catalytic activity comparable to that of bare AuNPs/GQDs as well as better recyclability.
Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation
Authors: Lee Yun Bin , Choi Jong Ho , Kim Eun Nam , Seok Jin , Lee Hyun-Jung , Yoon Jung-Hwan , Kim Gi Jin
Published: November 2017

In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial β-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33—a posttranscriptional regulator of CPT1A—in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production—an indicator of mitochondrial function—was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism.
Effects of FTY720 on Lung Injury Induced by Hindlimb Ischemia Reperfusion in Rats
Authors: Wang Liangrong , Chen Feifei , Pan Yafei , Lin Lina , Xiong Xiangqing
Published: November 2017

Background. Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid mediator involved in modulating inflammatory process. We investigated the effects of FTY720, a structural analogue of S1P after phosphorylation, on lung injury induced by hindlimb ischemia reperfusion (IR) in rats.Methods. Fifty Sprague-Dawley rats were divided into groups SM, IR, F3, F5, and F10. Group SM received sham operation, and bilateral hindlimb IR was established in group IR. The rats in groups F3, F5, and F10 were pretreated with 3, 5, and 10 mg/kg/d FTY720 for 7 days before IR. S1P lyase (S1PL), sphingosine kinase (SphK) 1, and SphK2 mRNA expressions, wet/dry weight (W/D), and polymorphonuclear/alveolus (P/A) in lung tissues were detected, and the lung injury score was evaluated.Results. W/D, P/A, and mRNA expressions of S1PL, SphK1, and SphK2 were higher in group IR than in group SM, while these were decreased in both groups F5 and F10 as compared to IR (p<0.05). The lung tissue presented severe lesions in group IR, which were attenuated in groups F5 and F10 with lower lung injury scores than in group IR (p<0.05).Conclusions. FTY720 pretreatment could attenuate lung injury induced by hindlimb IR by modulating S1P metabolism and decreasing pulmonary neutrophil infiltration.
Efficient Expression of Maltohexaose-Forming α-Amylase from Bacillus stearothermophilus in Brevibacillus choshinensis SP3 and Its Use in Maltose Production
Authors: Li Zhu , Su Lingqia , Duan Xuguo , Wu Dan , Wu Jing
Published: November 2017

The maltohexaose-forming, Ca2+-independent α-amylase gene from Bacillus stearothermophilus (AmyMH) was efficiently expressed in Brevibacillus choshinensis SP3. To improve the production of AmyMH in B. choshinensis SP3, the temperature and initial pH of culture medium were optimized. In addition, single-factor and response surface methodologies were pursued to optimize culture medium. Addition of proline to the culture medium significantly improved the production of recombinant α-amylase in B. choshinensis SP3. This improvement may result from improved cellular integrity of recombinant B. choshinensis SP3 in existence of proline. Culture medium optimization resulted in an 8-fold improvement in α-amylase yield, which reached 1.72 × 104 U·mL−1. The recombinant α-amylase was applied to the production of maltose on a laboratory scale. A maltose content of 90.72%, which could be classified as an extremely high maltose syrup, could be achieved using 15% (m/v) corn starch as the substrate. This study demonstrated that the B. choshinensis SP3 expression system was able to produce substantial quantities of recombinant α-amylase that has potential application in the starch industry.
Global Dynamics of a Periodic SEIRS Model with General Incidence Rate
Authors: Ávila-Vales Eric , Rivero-Esquivel Erika , García-Almeida Gerardo Emilio
Published: November 2017

We consider a family of periodic SEIRS epidemic models with a fairly general incidence rate of the form Sf(I), and it is shown that the basic reproduction number determines the global dynamics of the models and it is a threshold parameter for persistence of disease. Numerical simulations are performed using a nonlinear incidence rate to estimate the basic reproduction number and illustrate our analytical findings.
Multilevel Thresholding Method Based on Electromagnetism for Accurate Brain MRI Segmentation to Detect White Matter, Gray Matter, and CSF
Authors: Sandhya G. , Babu Kande Giri , Savithri T. Satya
Published: November 2017

This work explains an advanced and accurate brain MRI segmentation method. MR brain image segmentation is to know the anatomical structure, to identify the abnormalities, and to detect various tissues which help in treatment planning prior to radiation therapy. This proposed technique is a Multilevel Thresholding (MT) method based on the phenomenon of Electromagnetism and it segments the image into three tissues such as White Matter (WM), Gray Matter (GM), and CSF. The approach incorporates skull stripping and filtering using anisotropic diffusion filter in the preprocessing stage. This thresholding method uses the force of attraction-repulsion between the charged particles to increase the population. It is the combination of Electromagnetism-Like optimization algorithm with the Otsu and Kapur objective functions. The results obtained by using the proposed method are compared with the ground-truth images and have given best values for the measures sensitivity, specificity, and segmentation accuracy. The results using 10 MR brain images proved that the proposed method has accurately segmented the three brain tissues compared to the existing segmentation methods such as K-means, fuzzy C-means, OTSU MT, Particle Swarm Optimization (PSO), Bacterial Foraging Algorithm (BFA), Genetic Algorithm (GA), and Fuzzy Local Gaussian Mixture Model (FLGMM).
Usability Studies on Mobile User Interface Design Patterns: A Systematic Literature Review
Authors: Punchoojit Lumpapun , Hongwarittorrn Nuttanont
Published: November 2017

Mobile platforms have called for attention from HCI practitioners, and, ever since 2007, touchscreens have completely changed mobile user interface and interaction design. Some notable differences between mobile devices and desktops include the lack of tactile feedback, ubiquity, limited screen size, small virtual keys, and high demand of visual attention. These differences have caused unprecedented challenges to users. Most of the mobile user interface designs are based on desktop paradigm, but the desktop designs do not fully fit the mobile context. Although mobile devices are becoming an indispensable part of daily lives, true standards for mobile UI design patterns do not exist. This article provides a systematic literature review of the existing studies on mobile UI design patterns. The first objective is to give an overview of recent studies on the mobile designs. The second objective is to provide an analysis on what topics or areas have insufficient information and what factors are concentrated upon. This article will benefit the HCI community in seeing an overview of present works, to shape the future research directions.
Optical Coherence Tomography Angiography of Macular Telangiectasia Type 2 with Associated Subretinal Neovascular Membrane
Authors: Villegas Victor M. , Kovach Jaclyn L.
Published: November 2017

Optical coherence tomography angiography (OCTA) is a recently established noninvasive technology for evaluation of the retinal and choroidal vasculature. The literature regarding the findings in macular telangiectasia type 2 (MacTel2) is scarce. We report the OCTA findings associated with a subject with MacTel2 and secondary subretinal neovascularization (SNV). The commercially available Cirrus 5000 with AngioPlex (Zeiss, Jena, Germany) was used, without any subsequent image modification or processing. Subretinal neovascularization was detectable with OCTA at the level of the outer retina and choriocapillaris. Microvascular abnormalities associated with MacTel2 were present mostly in the deep capillary plexus of the retina temporally.
Pulmonary Susceptibility of Neonates to Respiratory Syncytial Virus Infection: A Problem of Innate Immunity?
Authors: Drajac Carole , Laubreton Daphné , Riffault Sabine , Descamps Delphyne
Published: November 2017

Human respiratory syncytial virus (RSV) is a common and highly contagious viral agent responsible for acute lower respiratory infection in infants. This pathology characterized by mucus hypersecretion and a disturbed T cell immune response is one of the major causes of infant hospitalization for severe bronchiolitis. Although different risk factors are associated with acute RSV bronchiolitis, the immunological factors contributing to the susceptibility of RSV infection in infants are not clearly elucidated. Epidemiological studies have established that the age at initial infection plays a central role in the severity of the disease. Thus, neonatal susceptibility is intrinsically linked to the immunological characteristics of the young pulmonary mucosa. Early life is a critical period for the lung development with the first expositions to external environmental stimuli and microbiota colonization. Furthermore, neonates display a lung immune system that profoundly differs to those from adults, with the predominance of type 2 immune cells. In this review, we discuss the latest information about the lung immune environment in the early period of life at a steady state and upon RSV infection and how we can modulate neonatal susceptibility to RSV infection.
Risk Factors of Recurrence and Malignant Transformation of Sinonasal Inverted Papilloma
Authors: Gamrot-Wrzoł Marta , Sowa Paweł , Lisowska Grażyna , Ścierski Wojciech , Misiołek Maciej
Published: November 2017

Sinonasal inverted papilloma is a relatively rare disease; however, it is prevalent enough for every ENT practitioner to encounter it several times throughout medical routines. Despite the developments in experimental and clinical medicine as well as surgical techniques, our knowledge of this disease is still inadequate. With improved imaging and better diagnostic techniques, proper diagnosis and qualification for surgical approaches leave no doubt. Although the endoscopic approach seems to be the gold standard for such condition, some cases may additionally require an external approach. Regardless of the type of surgery, postoperative management is crucial for both healing and long-term follow-up. Unfortunately, the procedures are still lacking in explicit and standardized postoperative management guidelines. Moreover, an important issue is still the need for a biomarker indicative of inverted papilloma and its malignant transformation. Several particles, within the spotlight of the researchers, have been SCCA, Ki-67, Bcl-2, Wnt proteins, and many more. Nevertheless, the topic requires further investigations.
Image Fusion of CT and MR with Sparse Representation in NSST Domain
Authors: Qiu Chenhui , Wang Yuanyuan , Zhang Huan , Xia Shunren
Published: November 2017

Multimodal image fusion techniques can integrate the information from different medical images to get an informative image that is more suitable for joint diagnosis, preoperative planning, intraoperative guidance, and interventional treatment. Fusing images of CT and different MR modalities are studied in this paper. Firstly, the CT and MR images are both transformed to nonsubsampled shearlet transform (NSST) domain. So the low-frequency components and high-frequency components are obtained. Then the high-frequency components are merged using the absolute-maximum rule, while the low-frequency components are merged by a sparse representation- (SR-) based approach. And the dynamic group sparsity recovery (DGSR) algorithm is proposed to improve the performance of the SR-based approach. Finally, the fused image is obtained by performing the inverse NSST on the merged components. The proposed fusion method is tested on a number of clinical CT and MR images and compared with several popular image fusion methods. The experimental results demonstrate that the proposed fusion method can provide better fusion results in terms of subjective quality and objective evaluation.
Pulmonary Neuroendocrine Cell Hyperplasia Associated with Surfactant Protein C Gene Mutation
Authors: Jiramethee Norlalak , Erasmus David , Nogee Lawrence , Khoor Andras
Published: November 2017

Familial interstitial lung disease (ILD) is defined as presence of ILD in 2 or more family members. Surfactant protein C (SFTPC) gene mutations are rare, but well-known cause of familial ILD. We reported a 20-year-old male, who was referred for lung transplantation. He was symptomatic at age 3 and underwent surgical lung biopsy at age 6, which revealed a nonspecific interstitial pneumonia (NSIP) pattern. Genetic workup revealed a novel SFTPC mutation in the first intron with a C to A transversion. At age 21, he underwent bilateral lung transplantation. Explanted lung histology suggested NSIP. In addition there was pulmonary neuroendocrine cell (PNEC) hyperplasia and carcinoid tumorlets. His mother had undergone lung transplantation several years earlier, and her explanted lung showed similar pathology. SFTPC mutations are inherited in an autosomal dominant pattern. Various types of ILD have been associated with SFTPC mutation including NSIP, usual interstitial pneumonia (UIP), and desquamative interstitial pneumonia (DIP). PNEC hyperplasia has been described to occur in association with lung inflammation but has not been previously described with familial ILD associated with SFTPC mutation.
Influence of Geometry and Velocity of Rotating Solids on Hydrodynamics of a Confined Volume
Authors: Carvajal-Mariscal Ignacio , Real-Ramírez Cesar A. , Sánchez-Silva Florencio , Cervantes de la Torre Francisco , González-Trejo Jesús
Published: November 2017

Three cylinder‐based geometries were evaluated at five different rotating speeds (ω = 20.94, 62.83, 94.25, 125.66, and 157.08 rad·s−1) to obtain the fluid flow pattern in nonsteady conditions. Two of the models were modified at the lower region, also known as tip section, by means of inverted and right truncated cone geometries, respectively. The experimental technique used a visualization cell and a Particle Imaging Velocimetry installation to obtain the vector field at the central plane of the volume. The Line Integral Convolution Method was used to obtain the fluid motion at the plane. In addition, the scalar kinetic energy and the time series were calculated to perform the normal probability plot. This procedure was used to determine the nonlinear fluid flow pattern. It was also used to identify two different flow regimens in physical and numerical results. As the rotation speed increased, the turbulent regions were placed together and moved. The process makes experimental observation difficult. The biphasic and turbulence constitutive equations were solved with the Computational Fluid Dynamics technique. Numerical results were compared with physical experiments for validation. The model with the inverted truncated cone tip presented better stability in the fluid flow pattern along the rotation speed range.
Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1
Authors: Maher Christina M. , Thomas Jeffrey D. , Haas Derick A. , Longen Charles G. , Oyer Halley M. , Tong Jane Y. , Kim Felix J.
Published: November 2017

Emerging evidence suggests that Sigma1 (SIGMAR1, also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small-molecule modulators of Sigma1 alter endoplasmic reticulum (ER)–associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type I integral membrane glycoprotein that is cotranslationally inserted into the ER and is processed and transported through the secretory pathway. Once at the surface of cancer cells, PD-L1 acts as a T-cell inhibitory checkpoint molecule and suppresses antitumor immunity. Here, we demonstrate that in Sigma1-expressing triple-negative breast and androgen-independent prostate cancer cells, PD-L1 protein levels were suppressed by RNAi knockdown of Sigma1 and by small-molecule inhibition of Sigma1. Sigma1-mediated action was confirmed by pharmacologic competition between Sigma1-selective inhibitor and activator ligands. When administered alone, the Sigma1 inhibitor decreased cell surface PD-L1 expression and suppressed functional interaction of PD-1 and PD-L1 in a coculture of T cells and cancer cells. Conversely, the Sigma1 activator increased PD-L1 cell surface expression, demonstrating the ability to positively and negatively modulate Sigma1 associated PD-L1 processing. We discovered that the Sigma1 inhibitor induced degradation of PD-L1 via autophagy, by a mechanism distinct from bulk macroautophagy or general ER stress–associated autophagy. Finally, the Sigma1 inhibitor suppressed IFNγ-induced PD-L1. Our data demonstrate that small-molecule Sigma1 modulators can be used to regulate PD-L1 in cancer cells and trigger its degradation by selective autophagy.

Implications: Sigma1 modulators sequester and eliminate PD-L1 by autophagy, thus preventing functional PD-L1 expression at the cell surface. This posits Sigma1 modulators as novel therapeutic agents in PD-L1/PD-1 blockade strategies that regulate the tumor immune microenvironment.

Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/2/243/F1.large.jpg. Mol Cancer Res; 16(2); 243–55. ©2017 AACR.
Loss of Uracil DNA Glycosylase Selectively Resensitizes p53-Mutant and -Deficient Cells to 5-FdU
Authors: Yan Yan , Qing Yulan , Pink John J. , Gerson Stanton L.
Published: November 2017

Thymidylate synthase (TS) inhibitors including fluoropyrimidines [e.g., 5-Fluorouracil (5-FU) and 5-Fluorodeoxyuridine (5-FdU, floxuridine)] and antifolates (e.g., pemetrexed) are widely used against solid tumors. Previously, we reported that shRNA-mediated knockdown (KD) of uracil DNA glycosylase (UDG) sensitized cancer cells to 5-FdU. Because p53 has also been shown as a critical determinant of the sensitivity to TS inhibitors, we further interrogated 5-FdU cytotoxicity after UDG depletion with regard to p53 status. By analyzing a panel of human cancer cells with known p53 status, it was determined that p53-mutated or -deficient cells are highly resistant to 5-FdU. UDG depletion resensitizes 5-FdU in p53-mutant and -deficient cells, whereas p53 wild-type (WT) cells are not affected under similar conditions. Utilizing paired HCT116 p53 WT and p53 knockout (KO) cells, it was shown that loss of p53 improves cell survival after 5-FdU, and UDG depletion only significantly sensitizes p53 KO cells. This sensitization can also be recapitulated by UDG depletion in cells with p53 KD by shRNAs. In addition, sensitization is also observed with pemetrexed in p53 KO cells, but not with 5-FU, most likely due to RNA incorporation. Importantly, in p53 WT cells, the apoptosis pathway induced by 5-FdU is activated independent of UDG status. However, in p53 KO cells, apoptosis is compromised in UDG-expressing cells, but dramatically elevated in UDG-depleted cells. Collectively, these results provide evidence that loss of UDG catalyzes significant cell death signals only in cancer cells mutant or deficient in p53.

Implications: This study reveals that UDG depletion restores sensitivity to TS inhibitors and has chemotherapeutic potential in the context of mutant or deficient p53. Mol Cancer Res; 16(2); 212–21. ©2017 AACR.
Adipocytes Sequester and Metabolize the Chemotherapeutic Daunorubicin
Authors: Sheng Xia , Parmentier Jean-Hugues , Tucci Jonathan , Pei Hua , Cortez-Toledo Omar , Dieli-Conwright Christina M. , Oberley Matthew J. , Neely Michael , Orgel Etan , Louie Stan G. , Mittelman Steven D.
Published: November 2017

Obesity is associated with poorer outcome for many cancers. Previously, we observed that adipocytes protect acute lymphoblastic leukemia (ALL) cells from the anthracycline, daunorubicin. In this study, it is determined whether adipocytes clear daunorubicin from the tumor microenvironment (TME). Intracellular daunorubicin concentrations were evaluated using fluorescence. Daunorubicin and its largely inactive metabolite, daunorubicinol, were analytically measured in media, cells, and tissues using liquid chromatography/mass spectrometry (LC/MS). Expression of daunorubicin-metabolizing enzymes, aldo-keto reductases (AKR1A1, AKR1B1, AKR1C1, AKR1C2, AKR1C3, and AKR7A2) and carbonyl reductases (CBR1, CBR3), in human adipose tissue, were queried using public databases and directly measured by quantitative PCR (qPCR) and immunoblot. Adipose tissue AKR activity was measured by colorimetric assay. Adipocytes absorbed and efficiently metabolized daunorubicin to daunorubicinol, reducing its antileukemia effect in the local microenvironment. Murine studies confirmed adipose tissue conversion of daunorubicin to daunorubicinol in vivo. Adipocytes expressed high levels of AKR and CBR isoenzymes that deactivate anthracyclines. Indeed, adipocyte protein levels of AKR1C1, AKR1C2, and AKR1C3 are higher than all other human noncancerous cell types. To our knowledge, this is the first demonstration that adipocytes metabolize and inactivate a therapeutic drug. Adipocyte-mediated daunorubicin metabolism reduces active drug concentration in the TME. These results could be clinically important for adipocyte-rich cancer microenvironments such as omentum, breast, and marrow. As AKR and CBR enzymes metabolize several drugs, and can be expressed at higher levels in obese individuals, this proof-of-principle finding has important implications across many diseases.

Implications: Adipocyte absorption and metabolism of chemotherapies can reduce cytotoxicity in cancer microenvironments, potentially contributing to poorer survival outcomes. Mol Cancer Res; 15(12); 1704–13. ©2017 AACR.