bluuebunny/crossref_metadata_2025 huggingface dataset:
The carboxy‐terminus of the formin FMNL1ɣ bundles actin to potentiate adenocarcinoma migration
Authors: Miller Eric W. , Blystone Scott D.
Published: April 2019

The formin family of proteins contributes to spatiotemporal control of actin cytoskeletal rearrangements during motile cell activities. The FMNL subfamily exhibits multiple mechanisms of linear actin filament formation and organization. Here we report novel actin‐modifying functions of FMNL1 in breast adenocarcinoma migration models. FMNL1 is required for efficient cell migration and its three isoforms exhibit distinct localization. Suppression of FMNL1 protein expression results in a significant impairment of cell adhesion, migration, and invasion. Overexpression of FMNL1ɣ, but not FMNL1β or FMNL1α, enhances cell adhesion independent of the FH2 domain and FMNL1ɣ rescues migration in cells depleted of all three endogenous isoforms. While FMNL1ɣ inhibits actin assembly in vitro, it facilitates bundling of filamentous actin independent of the FH2 domain. The unique interactions of FMNL1ɣ with filamentous actin provide a new understanding of formin domain functions and its effect on motility of diverse cell types suggest a broader role than previously realized.
Effect of monovalent ion binding on molecular dynamics of the S100‐family calcium‐binding protein calbindin D9k
Authors: Thapa Mahendra , Johnson Eric , Rance Mark
Published: April 2019

Calbindin D9kis a member of the S100 subfamily of EF‐hand calcium binding proteins, and has served as an important model system for biophysical studies. The fast timescale dynamics of the calcium‐free (apo) state is characterized using molecular dynamics simulations. Order parameters for the backbone NH bond vectors are determined from the simulations and compared with experimentally derived values, with a focus on the dynamics of calcium‐binding site I. There is a significant discrepancy between simulated and experimental order parameters for site I residues in the case of no ion bound in site I. However, it was found in the simulations that a Na+ion can bind in site I, and the resulting order parameters determined from the simulations are in excellent agreement with experiment. Comparisons are made to X‐ray structures of other S100 family members in which Na+ions were observed or suggested to be bound in site I. © 2019 Wiley Periodicals, Inc.
Development of a new parameter optimization scheme for a reactive force field based on a machine learning approach
Authors: Nakata Hiroya , Bai Shandan
Published: April 2019

Reactive molecular dynamics (MD) simulation is performed using a reactive force field (ReaxFF). To this end, we developed a new method to optimize the ReaxFF parameters based on a machine learning approach. This approach combines the k‐nearest neighbor and random forest regressor algorithm to efficiently locate several possible ReaxFF parameter sets. As a pilot test of the developed approach, the optimized ReaxFF parameter set was applied to perform chemical vapor deposition (CVD) of an α‐Al2O3 crystal. The crystal structure of α‐Al2O3 was reasonably reproduced even at a relatively high temperature (2000 K). The reactive MD simulation suggests that the (110) surface grows faster than the (0001) surface, indicating that the developed parameter optimization technique could be used for understanding the chemical reaction in the CVD process. © 2019 Wiley Periodicals, Inc.
Behavioral inhibition and posttrauma symptomatology: Moderating effects of safety behaviors and biological sex
Authors: McClure Kenneth E. , Blakey Shannon M. , Kozina Ryan M. , Ripley Adam J. , Kern Shira M. , Clapp Joshua D.
Published: April 2019

Objectives

Behavioral inhibition is a trait‐level factor associated with posttraumatic stress. Safety behaviors may impact this link by interfering with anxiety habituation. The current study examined the unique and interactive effects of behavioral inhibition, safety behaviors, and participant sex on posttrauma symptom clusters.

Method

Participants (N = 131; 75.6% female; M = 19.9 years) completed a trauma history interview and questionnaires assessing behavioral inhibition, safety behavior, and posttrauma symptom severity.

Results

Safety behaviors were associated with intrusion (partial correlations [pr] = 0.319), avoidance (pr = 0.274), cognition‐mood (pr = 0.274), and arousal–reactivity (pr = 0.538) symptoms (all p ≤ 0.001). An interaction of sex and safety behaviors was noted for avoidance (p = 0.047, pr = −0.159) with a significant relation observed only among women (
p < 0.001, pr = 0.442). Safety behaviors also moderated the link between behavioral inhibition and arousal–reactivity (p = 0.002, pr = 0.272) with inhibition predicting symptoms at high levels of safety behavior (p = 0.024, pr = 0.171).

Conclusion

Trauma‐related safety behaviors are associated with greater posttrauma symptoms and evidence differential effects across individual symptom domains.
Drug‐Drug Interaction Studies of Methadone and Antiviral Drugs: Lessons Learned
Authors: Younis Islam R. , Lakota Elizabeth A. , Volpe Donna A. , Patel Vikram , Xu Yun , Sahajwalla Chandra G.
Published: April 2019

Different views appear in the literature on the extent of specific cytochrome P450 (CYP) involvement in methadone metabolism. The aim of this work is to leverage knowledge from drug‐drug interaction (DDI) studies in new drug applications between methadone and antiviral medications to better understand methadone disposition and to inform design of future DDI studies with methadone. A database of DDI studies between all FDA‐approved human immunodeficiency virus and hepatitis C virus medications and methadone was constructed. The database contains data from 29 DDI studies. Sixteen of the 29 studies had statistically significant changes in methadone area under the concentration‐time curve. Methadone exposure was either decreased or unchanged when it was coadministered with weak to strong CYP3A inhibitors or a moderate CYP3A4 inducer. Methadone exposure was reduced when it was coadministered with CYP2B6 inducers. The role of other enzymes (CYP2C9, CYP2C19, and CYP2D6) cannot be fully elucidated from these studies. In conclusion, CYP2B6 plays a prominent role in methadone metabolism, although methadone exposure is not sensitive to CYP3A perturbation. In designing methadone DDI studies, (1) measuring R‐ and S‐methadone is more informative than measuring total methadone, and (2) CYP2B6 genotyping of subjects enrolled in methadone DDI studies should be considered. Finally, there is a need for the development of predictive models to determine the influence of medications on methadone disposition.
Characterization of the Effect of Hepatic Impairment on Upadacitinib Pharmacokinetics
Authors: Trueman Sheryl , Mohamed Mohamed‐Eslam F. , Feng Tian , Lacerda Ana Paula , Marbury Thomas , Othman Ahmed A.
Published: April 2019

Upadacitinib is a selective Janus kinase 1 inhibitor being developed for the treatment of several inflammatory autoimmune diseases, including rheumatoid arthritis. Upadacitinib is a nonsensitive substrate for metabolism by cytochrome P450 3A enzymes. This open‐label, single‐dose, multicenter study assessed the pharmacokinetics of upadacitinib following oral administration of a single 15‐mg dose of the upadacitinib extended‐release formulation in subjects with mild (n = 6) and moderate (n = 6) hepatic impairment relative to demographically matched healthy subjects (n = 6). Subjects were assigned to 1 of the 3 groups according to the Child‐Pugh classification. Relative to subjects with normal hepatic function, the ratios (90% confidence intervals) of upadacitinib area under the plasma concentration‐versus‐time profile from time 0 to infinity (AUCinf) for subjects with mild and moderate hepatic impairment were 1.28 (0.91‐1.79) and 1.24 (0.87‐1.76), respectively. The central ratios of upadacitinib maximum observed concentration (Cmax) were 1.04 (0.77‐1.39) and 1.43 (1.05‐1.95) in subjects with mild and moderate hepatic impairment, respectively, compared with subjects with normal hepatic function. No clinically significant changes in vital signs or hematology measurements were observed, and no new safety events were identified in this study. These results indicate that mild and moderate hepatic impairment has no clinically relevant effect on upadacitinib pharmacokinetics.
Histological description of immature Chironomus columbiensis (Diptera: Chironomidae): A potential contribution to environmental monitoring
Authors: Ospina‐Pérez Erika M. , Campeón‐Morales Oscar I. , Richardi Vinicius S. , Rivera‐Páez Fredy A.
Published: April 2019

Chironomids have been widely used in environmental monitoring and toxicity assays. Assessment criteria for chironomids range from the molecular‐biochemical level to the population level. However, the use of markers to evaluate cellular and anatomical changes in organs and systems of individuals under contaminant exposure is still incipient. In this study, we conducted a histological description of the main systems and organs of immature Chironomus columbiensis. We used fourth instar larvae, obtained from a standardized culture, and confirmed this state through morphological and molecular methods. Larvae were fixed in Duboscq solution for insects during 48 hr, dehydrated in increasing dilutions of ethanol, and embedded and mounted in historesin to obtain 3 μm sections. The digestive, nervous, excretory, and integumentary systems and the fat body and testicles were analyzed through longitudinal and transversal sections, stained with hematoxylin–eosin (HE), and further photographed and described through light microscopy. This is the first description of internal morphology performed for C. columbiensis and can help in future histopathological analysis, because through bioaccumulation some of these organs are contaminant targets. It can even be a great taxonomic tool, since the characteristics of the histological pattern of C. columbiensis presented differences compared to other descriptions made in chironomids.
Microwave‐assisted One‐pot, Three‐component Regiospecific and Sterospecific Synthesis of Spiro Indanone Pyrrolidine/Piperidine Fused Nitrochromene Derivatives Through 1,3‐Dipolar Cycloaddition Reactions
Authors: Nayak Sabita , Panda Pravati , Mohapatra Seetaram , Raiguru Bishnuprasad , Baral Nilofar
Published: April 2019

A simple, straightforward, and versatile protocol for the synthesis of spiro indanone pyrrolidine/piperidine fused nitrochromene derivatives is described. The synthesis of a new series of spirocyclic molecules has been expediently accomplished via a one‐pot, three component 1,3‐dipolar cycloaddition reaction. 2‐Phenyl‐nitrochromene dipolarophiles were reacted with azomethine ylides, generated in situ by the condensation of dicarbonyl compound indane‐1,3‐dione and secondary amino acid (L‐proline/pipecolic acid), to produce the corresponding cycloadducts in good yields (85–90%) under classical as well as under microwave irradiation. The cycloaddition reaction was found to be highly regiospecific and diasterospecific. The regiochemical and sterochemical outcome of the cycloaddition reaction is ascertained by 2D NMR (COSY and NOESY) studies.
Evaluation of dried blood spots for hepatitis B and D serology and nucleic acid testing
Authors: Jackson Kathy , Holgate Thomas , Tekoaua Rosemary , Nicholson Suellen , Littlejohn Margaret , Locarnini Stephen
Published: April 2019

Areas with the highest burden of hepatitis B virus (HBV) infection are often low‐middle‐income countries with limited access to diagnosis due to isolation, affordability, and/or feasibility. Dried blood spots (DBSs) provide an alternative for remote areas where collection and transportation of serum is impractical. In this study, the application of DBS for serological and molecular detection of HBV and hepatitis D virus (HDV) was evaluated. Hepatitis B surface antigen was detected in 87 of 91 (95.6%) DBS. Seventeen of 21 (81%) had detectable HBeAg and 52 of 71 (73.2%) were anti‐HBe positive. Anti‐HD was detectable in 11 of 12 (91.6%) spiked control DBS after an initial failure to detect in patient DBS. HBV DNA was detected from 50 of 70 (71.4%) DBS with serum loads greater than 200 IU/mL in an in‐house assay and 18 of 24 (75%) DBS with loads exceeding 389 IU/mL in a commercial assay. Using linear regression, HBV DNA loads from DBS were able to predict serum loads in 46 of 50 (92%) samples to within 1 log of actual serum load. HDV RNA was detected in 42 of 47 (89%) DBS with serum levels greater than 7200 IU/mL. DBSs are recommended for diagnosis of HBV, monitoring, and detection of high loads in pregnant women where peripheral blood testing remains unfeasible. Detection of HDV RNA from DBS may prove useful in endemic areas.
Climate variations over the southern Altai Mountains and Dzungarian Basin region, central Asia, since 1580 CE
Authors: Oyunmunkh Byambaa , Weijers Stef , Loeffler Joerg , Byambagerel Suran , Soninkhishig Nergui , Buerkert Andreas , Goenster‐Jordan Sven , Simmer Clemens
Published: April 2019

An improved knowledge of long‐term climatic variations over the Altai‐Dzungarian region will increase our understanding of the current climate and help to predict the effects of global warming on future water availability in this region. We sampled 77 Larix sibirica Ledeb. trees at upper and lower treelines in the southern Mongolian Altai mountains and reconstructed temperature and precipitation for longer periods than previous studies from this area. We reconstructed mean June–July air temperatures for the period 1402–2012 and June–December precipitation for the period 1569–2012 based on tree ring width chronologies. The temperature and precipitation reconstructions explain 39.7 and 41.3% of the respective station observation variance during the common periods. The precipitation reconstruction shows alternating wet and dry conditions during the Little Ice Age (1580–1874) followed by more stable conditions until a late 20th century wetting. The temperature reconstruction attributes the warmest period to the 20th century, which follows cooler periods related to volcanic and low solar activities during the Little Ice Age. Long‐term climatic variation and change over the Altai‐Dzungarian region is inferred from the analysis of the combined temperature and precipitation reconstructions for the common period 1580–2012. Accordingly, this region has become warmer since 1875 as the number of warm/moist and warm/dry years increased by 2 and 14%, respectively, while the number of cool/moist and cool/dry years both decreased by 8% compared to the Little Ice Age. Our findings also reveal a late 20th century cool and wet period, which has also been observed across other mountainous areas of China and Nepal. This period was most probably caused by volcanic‐induced cooling and coincided positive phases of the Arctic Oscillation and North Atlantic Oscillation promoting an intensified subtropical westerly jet and a positive summer rainfall anomaly over the Altai‐Dzungarian region.
Large‐scale climatic factors driving glacier recession in the Greater Caucasus, 20th–21st century
Authors: Toropov Pavel A. , Aleshina Maria A. , Grachev Alexei M.
Published: April 2019

Over the past 30 years, there has been a catastrophic reduction of the glacierized area in the mountains of the Greater Caucasus, with the values reaching 0.69% per year. Physical mechanisms accountable for such intense melting are investigated in this study. The main trends in the temperature‐moisture regime of the Caucasus and adjacent areas for the period 1982–2015 were recovered based on instrumental data and the ERA‐Interim data reanalysis. It is demonstrated that there is statistically significant warming for the summer season in the region as a whole. No statistically significant changes were detected in the precipitation regime, despite the increase in the integral moisture content of the atmosphere and in the potential convective energy. The integral moisture content growth is compensated by the increase in the moisture divergence. This happens due to the intensification of large‐scale descending atmospheric motions. As a result, the seasonal and annual precipitation amounts do not change significantly. Such effects are possibly the consequence of the global process of “widening of the tropics.” This process is most clearly manifested in the expansion of the Hadley cell and the northward shift of its descending branch. This process can lead to an increased frequency of anticyclones over the southern regions of Europe during the warm part of the year. This, in turn, leads to a negative cloud cover trend as well as an increase in the closely related radiation balance. Apparently, this process is the cause of the intensive reduction of the glaciation area in the North Caucasus.
Nomograms Predict Cancer‐Specific and Overall Survival of Patients With Primary Limb Leiomyosarcoma
Authors: Wang Wei , Hong Jianqiao , Meng Jiahong , Wu Haobo , Shi Mingmin , Yan Shigui , Huang Yiting
Published: April 2019

To date, there have been no data to predict the survival of patients with leiomyosarcoma from soft limb tissue because of the rarity of this disease. Nomograms have been widely applied in clinical oncology to precisely predict the survival of individual patients. This was a retrospective study to construct and validate nomograms to predict the cancer‐specific survival (CSS) and overall survival (OS) of patients with primary limb leiomyosarcoma (PL‐LMS). A total of 1,208 patients with LMS from limb soft tissue were collected from the Surveillance, Epidemiology, and End Results database from 1975 to 2015. We identified independent prognostic factors using univariate and multivariate Cox analyses. These prognostic factors were then included in the nomograms to predict 3‐ and 5‐year CSS and OS rates. Finally, we validated the nomograms internally and externally. A total of 1208 patients were collected and divided into validation (N = 604) and training (N = 604) groups. Age, race, grade, tumor size, stage, and surgical types were demonstrated as independent prognostic factors for CSS and OS (all p < 0.05) and further used to construct the nomograms. The concordance index (C‐index) for CSS was 0.857 for internal validation and 0.727 for external validation. The C‐index for OS and CSS both demonstrated that the nomogram prediction agreed perfectly with actual survival. We developed nomograms to predict CSS and OS in PL‐LMS patients and can benefit from using them to identify patients’ mortality risk and make more precise assessments regarding survival. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1649–1657, 2019.
New Design Process for Anatomically Enhanced Osteosynthesis Plates
Authors: Tkany Luisa , Hofstätter Bernhard , Petersik Andreas , Miehling Jörg , Wartzack Sandro , Sesselmann Stefan
Published: April 2019

This study evaluated the implementation and effectiveness of an iterative process aimed to quantify and enhance the anatomical fit of an osteosynthesis plate design for the fifth metacarpal bone regarding a defined shape‐based acceptance criterion (SAC) while complying with basic clinical requirements and engineering limitations. The process was based on employing virtual tools (a database of individual three‐dimensional bone models, statistical analysis of the bone geometry, and proprietary software tools) to evaluate conformity between plate designs and bone shape. The conformity was quantified by the mean distance between plate and bone (MBP). The enhancement was completed when the median MBP of the population was below the SAC threshold. This was fulfilled by the third plate design (two enhancement iterations). The intentionally abstract enhancement process may serve as a guideline for development of plate designs for other indications. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1508–1517, 2019.
Comparative Evaluation of the Book‐Type Acellular Bone Scaffold and Fibrocartilage Scaffold for Bone‐Tendon Healing
Authors: Lu Hongbin , Tang Yifu , Liu Fei , Xie Shanshan , Qu Jin , Chen Can
Published: April 2019

Bone‐tendon (B‐T) healing is a clinical challenge due to its limited regeneration capability. Fibrocartilage regeneration and bone formation at the healing site are two critical factors for B‐T healing. Promoting fibrocartilage regeneration and bone formation by tissue‐engineering may be a promising treatment strategy. In this study, we innovatively fabricated two kinds of acellular scaffolds from bone or fibrocartilage tissues, namely the book‐type the acellular bone scaffold (BABS) and the book‐type acellular fibrocartilage scaffold (BAFS). Histologically, the two scaffolds well preserved the native extracellular matrix (ECM) structure without cellular components. In vitro studies showed BABS is superior in osteogenic inducibility, while BAFS has good chondrogenic inducibility. To comparatively investigate the efficacy on B‐T healing, the BABS or BAFS were, respectively, implanted into a rabbit partial patellectomy model. Macroscopically, a regenerated bone‐tendon insertion (BTI) was bridging the residual patella and patellar‐tendon with no signs of infection and osteoarthritis. Radiologically, more new bone was formed at the healing interface in the BABS group as compared with the BAFS or control (CTL) groups (p < 0.05). Histologically, at postoperative week 16, histological scores were significantly better for regenerated fibrocartilage in the BAFS group or BABS group compared with the CTL group, but the BAFS group showed a significantly larger score than the BABS groups (p < 0.05). Biomechanical evaluation indicated a higher failure load and stiffness were shown in the BAFS group than those in the BABS or CTL groups at week 16 (p < 0.05). This study indicated that the BAFS is a more promising scaffold for B‐T healing in comparison with the BABS. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1709–1722, 2019
Bone Microarchitecture and Distal Radius Fracture Pattern Complexity
Authors: Daniels Anne M. , Theelen Luuk M. A. , Wyers Caroline E. , Janzing Heinrich M. J. , van Rietbergen Bert , Vranken Lisanne , van der Velde Robert Y. , Geusens Piet P. M. M. , Kaarsemaker Sjoerd , Poeze Martijn , van den Bergh Joop P.
Published: April 2019

Distal radius fractures (DRFs) occur in various complexity patterns among patients differing in age, gender, and bone mineral density (BMD). Our aim was to investigate the association of patient characteristics, BMD, bone microarchitecture, and bone strength with the pattern complexity of DRFs. In this study, 251 patients aged 50–90 years with a radiologically confirmed DRF who attended the Fracture Liaison Service of VieCuri Medical Centre, the Netherlands, between November 2013 and June 2016 were included. In all patients fracture risk factors and underling metabolic disorders were evaluated and BMD measurement with vertebral fractures assessment by dual‐energy X‐ray absorptiometry was performed. Radiographs of all DRFs were reviewed by two independent investigators to assess fracture pattern complexity according to the AO/OTA classification in extra‐articular (A), partially articular (B), and complete articular (C) fractures. For this study, patients with A and C fractures were compared. Seventy‐one patients were additionally assessed by high‐resolution peripheral quantitative computed tomography. Compared to group A, mean age, the proportion of males, and current smokers were higher in group C, but BMD and prevalent vertebral fractures were not different. In univariate analyses, age, male gender, trabecular area, volumetric BMD (vBMD), and stiffness were associated with type C fractures. In multivariate analyses, only male gender (odds ratio (OR) 8.48 95% confidence interval (CI) 1.75–41.18, p = 0.008]) and age (OR 1.11 [95% CI 1.03–1.19, p = 0.007]) were significantly associated with DRF pattern complexity. In conclusion, our data demonstrate that age and gender, but not body mass index, BMD, bone microarchitecture, or strength were associated with pattern complexity of DRFs.© 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. J Orthop Res 37:1690–1697, 2019
Effect of Femoral Head Size, Subject Weight, and Activity Level on Acetabular Cement Mantle Stress Following Total Hip Arthroplasty
Authors: Del‐Valle‐Mojica Jose‐Francisco , Alonso‐Rasgado Teresa , Jimenez‐Cruz David , Bailey Colin G , Board Tim N
Published: April 2019

In cases where cemented components are used in total hip arthroplasty, damage, or disruption of the cement mantle can lead to aseptic loosening and joint failure. Currently, the relationship between subject activity level, obesity, and prosthetic femoral head size and the risk of aseptic loosening of the acetabular component in cemented total hip arthroplasty is not well understood. This study aims to provide an insight into this. Finite element models, validated with experimental data, were developed to investigate stresses in the acetabular cement mantle and pelvic bone resulting from the use of three prosthetic femoral head sizes, during a variety of daily activities and one high impact activity (stumbling) for a range of subject body weights. We found that stresses in the superior quadrants of the cortical bone‐cement interface increased with prosthetic head size, patient weight, and activity level. In stumbling, average von Mises stresses (22.4 MPa) exceeded the bone cement yield strength for an obese subject (143 kg) indicating that the cement mantle would fail. Our results support the view that obesity and activity level are potential risk factors for aseptic loosening of the acetabular component and provide insight into the increased risk of joint failure associated with larger prosthetic femoral heads. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1771–1783, 2019
Furan formation from ingredient interactions and furan mitigation by sugar alcohols and antioxidants of bamboo leaves in milk beverage model systems
Authors: Guo Jun , Zhao Runmin , Li Jiaqi , Wu Dongyan , Yang Qiyue , Zhang Yan , Wang Shuo
Published: April 2019

BACKGROUND

Furan is a potential carcinogen that can be formed in various heat‐treated foods, including milk beverages. Studies on the formation and mitigation of furan in milk beverages are rare. In the present study, the effects of ingredients on furan formation and the reduction of furan by sugar alcohols and antioxidants of bamboo leaves (AOB) were investigated in a milk beverage model system.

RESULTS

The results obtained demonstrated that the Maillard reaction is the major pathway for furan formation in a milk beverage model system, and the type of sugar has a great influence on furan formation. High fructose corn syrup (HFCS 55) was more favorable for furan formation than sucrose. Thermal oxidation of ascorbic acid and lipids significantly enhanced furan generation. Xylitol, sorbitol and mannitol inhibited furan formation in model systems by replacing sucrose or HFCS. The maximum inhibition percentage of furan formation was observed when sucrose/HFCS was substituted completely by xylitol and the inhibition rate was 78.28% and 88.64% separately for the sucrose/HFCS‐containing system. AOB significantly inhibited furan formation and the inhibition rate reached 32.13% and 28.52% separately for the sucrose/HFCS‐containing system.

CONCLUSION

The present study demonstrates that the use of sugar alcohols and AOB could be a feasible way of reducing furan formation in thermally processed milk beverages. © 2019 Society of Chemical Industry
Percutaneous management of malignant biliary disease
Authors: Riaz Ahsun , Pinkard John P. , Salem Riad , Lewandowski Robert J.
Published: April 2019

Percutaneous biliary interventions have established their role in the management of benign and malignant biliary disease. There are limited data comparing procedures performed by gastroenterologists and interventional radiologists in managing malignant biliary obstruction. Endoscopic procedures performed by gastroenterologists are not completely benign with reported complications ranging from 2% to 15%. It is important that gastroenterologists and interventional radiologists collaborate to form algorithms for management of malignant biliary obstruction which provide safe and efficacious care to these patients.
Organized cryogel composites with 3D hierarchical porosity as an extraction adsorbent for nucleosides
Authors: Zhao Shuling , Zou Yulin , Wang Yaya , Zhang Haixia , Liu Xiaoyan
Published: April 2019

Macroscopic monoliths are highly desirable in many fields of application. Herein, well organized organic–inorganic cryogel composite with a three‐dimensional hierarchical meso‐ and macroporous structure are presented, which were produced by in situ copolymerization of mesoporous multifunctional silica (size: 1–20 μm; pore: 2–20 nm mostly) and monomers (hydroxyethyl methacrylate and diallyldimethylammonium chloride) in water below the freezing point. This copolymerization method effectively adjusted the macropores of the basic cryogel, and the nanosilica was more homogeneously dispersed in the basic cryogel. The specific surface area of the cryogel composite was increased 17 times versus than that of the basic cryogel. The abundant meso‐ and macroporous pores on the cryogel composite provided sufficient reactive sites favorable for the efficient mass transport of target compounds. When the cryogel composite, as solid phase extraction adsorbent, was coupled with high‐performance liquid chromatography, an analytical tool, the nucleosides were quantified with good selectivity, lower detection limits (0.9–1.3 ng/mL) and satisfactory recoveries of greater than 80% from spiked human serum.
Analysis of two‐dimensional models for liquid chromatographic reactors of cylindrical geometry
Authors: Uche Ugochukwu David , Qamar Shamsul , Seidel‐Morgenstern Andreas
Published: April 2019

This work presents the analytical solutions of two‐dimensional isothermal reactive general rate models for liquid chromatographic reactors of cylindrical geometry. Both irreversible and reversible reactions are considered. The model equations form a linear system of convection‐diffusion‐reaction partial differential equations coupled with algebraic equations for isotherms. Analytical solutions are derived by integrated implementation of finite Hankel transform, Laplace transform, eigen‐decomposition technique, and conventional ordinary differential equations solution technique. To verify the analytical results, a high‐resolution finite volume scheme is also applied to numerically approximate the model equations. The current results can be very useful to optimize and upgrade the liquid chromatographic reactors.
Water chemistry, solution resistivity, and oxygen reduction reaction in simulated primary coolant of pressurized water reactors
Authors: Zhang Lefu , Arjmand Farzin
Published: April 2019

The effect of temperature (25 °C–300 °C) on the ohmic potential drop (ΔEΩ) and resistivity (Rsol) of a simulated primary coolant of the pressurized water reactors was investigated using electrochemical impedance spectroscopy (EIS) and galvanostatic potentiometry. The variations in the conductivity and pH of the solution showed that by increasing the temperature the magnitude of the Rsol and therefore ΔEΩ of the system first decreases rapidly (until ~150 °C) and then reaches a relatively stable plateau value. Increasing the pressure of the system decreased the magnitude of the Rsol in the oxygenated coolant. Investigation of the oxygen reduction reaction (ORR) on platinum (Pt), 316L stainless steel (SS), Alloy 690, and carbon steel revealed the great effect of water chemistry, in particular pH on the rate of the ORR on these materials. OH− adsorption on Pt reduced the rate of the ORR on this metal at temperatures higher than ~100 °C. Finally, it was found that higher H3O+ concentrations reduce the rate of the ORR on iron‐ and nickel‐based alloys, while increasing the OH− concentration at temperatures higher than ~150 °C accelerates the rate of the ORR on these alloys.
Semi‐Crystalline Polymer Blends for Material Extrusion Additive Manufacturing Printability: A Case Study with Poly(ethylene terephthalate) and Polypropylene
Authors: Chatham Camden A. , Zawaski Callie E. , Bobbitt Daniel C. , Moore Robert B. , Long Timothy E. , Williams Christopher B.
Published: April 2019

Semi‐crystalline polymers are an important class of materials for engineering applications due to their high modulus and barrier properties. Traditional manufacturing methods process semi‐crystalline polymers via rigid molds and well‐controlled temperature and pressure environments to handle the significant change in specific volume occurring during crystallization; however, material extrusion additive manufacturing does not use these features. This often leads to warpage‐induced build failure in fused filament fabrication (FFF). To enable FFF of semi‐crystalline polymers, this work investigates characteristics of immiscible polymer blends (e.g., disparate crystallization behavior and phase separation) to mitigate warping failure during printing. A series of poly(ethylene terephthalate)/polypropylene/polypropylene–graft–maleic anhydride blends are explored and the effect of thermal and morphological characteristics on printability is analyzed. It is shown that these blends can be extruded into filament and printed into a 3D structure. Extrapolations indicate that phase‐separated blends with increased total crystallization half‐time are beneficial for FFF printing.
Glutamate Ionotropic Receptor Kainate Type Subunit 3 (GRIK3) promotes epithelial‐mesenchymal transition in breast cancer cells by regulating SPDEF/CDH1 signaling
Authors: Xiao Bin , Kuang Zhenzhan , Zhang Weiyun , Hang Jianfeng , Chen Lidan , Lei Ting , He Yongyin , Deng Chun , Li Weiwei , Lu Jingrun , Qu Jing , Zhou Quan , Hao Wenbo , Sun Zhaohui , Li Linhai
Published: April 2019

Glutamate Ionotropic Receptor Kainate Type Subunit 3 (GRIK3) is an important excitatory neurotransmitter receptor that plays a significant role in various neurodegenerative diseases. However, the biological functions of GRIK3 in malignancies are largely unknown because of limited related studies. Here, we primarily reported that the expression of GRIK3 was higher in breast cancer tissues than in adjacent noncancerous tissues. GRIK3 expression was also positively correlated with the prognosis of patients with breast cancer. GRIK3 promoted the proliferation and migration abilities of breast cancer cells and enhanced the growth of orthotopically implanted tumors. Mechanically, GRIK3 influenced a range of signaling pathways and key signal transducers, including two epithelial‐mesenchymal transition regulators, SPDEF and CDH1. Heterogenous expression of SPDEF and CDH1 counteracted the migration and invasion abilities, respectively, of breast cancer cells induced by GRIK3. Moreover, overexpression of GRIK3 increased the expression of mesenchymal markers and decreased the expression of epithelial markers, resulting in the translocation of β‐catenin into the nucleus and the increased β‐catenin transcriptional activity. In conclusion, the present study reported a novel oncogenic role of GRIK3. Meanwhile, GRIK3, as a membrane receptor, may also serve as a potential therapeutic target for the treatment of breast cancer.
Retinal dystrophy in an individual carrying a de novo missense variant of SMARCA4
Authors: Cappuccio Gerarda , Brunetti‐Pierri Raffaella , Torella Annalaura , Pinelli Michele , Castello Raffaele , Casari Giorgio , Nigro Vincenzo , Banfi Sandro , Simonelli Francesca ,   TUDP, Brunetti‐Pierri Nicola
Published: April 2019

Background

Coffin–Siris syndrome (CSS) is characterized by intellectual disability, dysmorphic facial features, growth deficiency, microcephaly, and abnormalities of the fifth fingers/toes. CSS is caused by mutations in several genes of the BRG1‐associated factor pathway including SMARCA4.

Methods

Whole‐exome sequencing was performed on a 14‐year‐old female individual who presented with mild intellectual disability and dysmorphic features, tooth abnormalities, and short stature. She had brachydactyly but no aplasia or hypoplasia of the distal phalanx or nail of the fifth digit. She was also found to have retinal dystrophy that has not been previously reported in CSS.

Results

The individual presented herein was found to harbor a previously unreported de novo variant in SMARCA4.

Conclusion

This case expands the phenotypic spectrum of CSS manifestations.
Heinz‐type inequality and bi‐Lipschitz continuity for quasiconformal mappings satisfying inhomogeneous biharmonic equations
Authors: Zhong Deguang , Zhou Yu , Yuan Wenjun
Published: April 2019

Let
be the class of all sense‐preserving homeomorphic self‐mappings of
. The aim of this paper is twofold. First, we obtain Heinz‐type inequality for (K,K′)‐quasiconformal mappings satisfying inhomogeneous biharmonic equation Δ(Δω)  =  g in unit disk
with associated boundary value conditions
and
. Second, we establish biLipschitz continuity for (K,K′)‐quasiconformal mappings satisfying aforementioned inhomogeneous biharmonic equation when
and
are small enough.
Impact of calibration methods for color medical displays on interpreting brain SPECT images
Authors: Shibutani Takayuki , Onoguchi Masahisa , Yoneyama Hiroto , Nakajima Kenichi , Matsuo Shinro , Bamba Yusuke , Saito Shinji
Published: April 2019

Purpose

Color images are visualized on medical monitors that are adjusted by a grayscale standard display function (GSDF) or γ2.2. Although the GSDF is visually displayed as a linear graded grayscale, it does not specify how color medical images should be presented. On the other hand, the usual gamma setting for color images is γ2.2, but it has not been standardized. The color standard display function (CSDF) has recently been proposed as a standardized gamma setting for color medical monitors. However, the influence of various gamma settings on image characteristics should be determined. The present study aimed to identify differences in color‐scale characteristics on nuclear medicine images displayed on medical monitors adjusted by CSDF, GSDF, and γ2.2.

Methods

Transverse normal (n = 1) and abnormal (n = 5) brain perfusion images were generated using a mathematical digital phantom. Transverse phantom and clinical brain images are shown using the clinically applied eight‐color scale. Five nuclear medicine experts visually assessed phantom and clinical images using a defect severity scale that ranged from zero (no defect) to four (defect). Receiver operating characteristic curves were created and areas under the curves (AUCs) were analyzed. Defect scores for the clinical study were evaluated in the nine segments on basal ganglia slice, and defect scores were summed for each patient.

Results

The average defect score for color A significantly differed in multiple comparison tests, but not in post hoc tests. The ranges of AUC for CSDF, GSDF, and γ2.2 were 0.86–0.94, 0.82–0.94, and 0.88–0.97, respectively. The AUCs of CSDF in all color scales did not significantly differ from other gamma settings. The summed defect scores of CSDF were similar to those of other gamma settings.

Conclusion

Nuclear medicine images were equally valid when adjusted by CSDF even at various gamma settings. Nuclear medicine images can be evaluated equally using any gamma setting. Nonetheless, the color gamma setting for medical monitors should be standardized.
Technical Note: Assessing the performance of monthly CBCT image quality QA
Authors: Manger Ryan P. , Pawlicki Todd , Hoisak Jeremy , Kim Gwe‐Ya
Published: April 2019

Purpose

To assess the performance of routine cone‐beam computed tomography (CBCT) quality assurance (QA) at predicting and diagnosing clinically recognizable linac CBCT image quality issues.

Methods

Monthly automated linac CBCT image quality QA data were acquired on eight Varian linacs (Varian Medical Systems, Palo Alto, CA) using the CATPHAN 500 series phantom (The Phantom Laboratory, Inc., Greenwich, NY) and Total QA software (Image Owl, Inc., Greenwich, NY) over 34 months between July 2014 and May 2017. For each linac, the following image quality metrics were acquired: geometric distortion, spatial resolution, Hounsfield Unit (HU) constancy, uniformity, and noise. Quality control (QC) limits were determined by American Association of Physicists in Medicine (AAPM) expert consensus documents Task Group (TG‐142 and TG‐179) and the manufacturer acceptance testing procedure. Clinically recognizable CBCT issues were extracted from the in‐house incident learning system (ILS) and service reports. The sensitivity and specificity of CATPHAN QA at predicting clinically recognizable image quality issues was investigated. Sensitivity was defined as the percentage of clinically recognizable CBCT image quality issues that followed a failing CATPHAN QA. Quality assurance results are categorized as failing if one or more image quality metrics are outside the QC limits. The specificity of CATPHAN QA was defined as one minus the fraction of failing CATPHAN QA results that did not have a clinically recognizable CBCT image quality issue in the subsequent month. Receiver operating characteristic (ROC) curves were generated for each image quality metric by plotting the true positive rate (TPR) against the false‐positive rate (FPR).

Results

Over the study period, 18 image quality issues were discovered by clinicians while using CBCT to set up the patient and five were reported prior to x‐ray tube repair. The incidents ranged from ring artifacts to uniformity problems. The sensitivity of the TG‐142/179 limits was 17% (four of the prior monthly QC tests detected a clinically recognizable image quality issue). The area under the curve (AUC) calculated for each image quality metric ROC curve was: 0.85 for uniformity, 0.66 for spatial resolution, 0.51 for geometric distortion, 0.56 for noise, 0.73 for HU constancy, and 0.59 for contrast resolution.

Conclusion

Automated monthly QA is not a good predictor of CBCT image quality issues. Of the available metrics, uniformity has the best predictive performance, but still has a high FPR and low sensitivity. The poor performance of CATPHAN QA as a predictor of image quality problems is partially due to its reliance on region‐of‐interest (ROI) based algorithms and a lack of a global algorithm such as correlation. The manner in which image quality issues occur (trending toward failure or random) is still not known and should be studied further. CBCT image quality QA should be adapted based on how CBCT is used clinically.
Full convolutional network based multiple side‐output fusion architecture for the segmentation of rectal tumors in magnetic resonance images: A multi‐vendor study
Authors: Wang Mengmeng , Xie Peiyi , Ran Zhao , Jian Junming , Zhang Rui , Xia Wei , Yu Tao , Ni Caifeng , Gu Jinhui , Gao Xin , Meng Xiaochun
Published: April 2019

Purpose

Accurate segmentation of rectal tumors is a basic and crucial task for diagnosis and treatment of rectal cancer. To avoid tedious manual delineation, an automatic rectal tumor segmentation model is proposed.

Methods

A pretrained Resnet50 model was introduced for feature extraction. To reduce the complexity of the model, all layers after the 13th residual block of ResNet50 were removed, and three side‐output modules were added to the hidden layer of ResNet50 to guide multiscale feature learning. The final boundaries of tumors were determined by fusion of the predictions from side‐output modules. The proposed model was compared with two other models, and the effects of different region of interest (ROI) sizes, loss functions, and side‐output fusion strategy were also evaluated.

Results

The models were trained and evaluated on data from four clinical centers; T2‐weighted magnetic resonance images (T2W‐MRIs) from 461 patients in the first clinical center were used for training, while T2W‐MRIs from 51 patients in the same clinical center and 56 patients in three other clinical centers were used for performance evaluation. The proposed model was superior to the two other models and achieved an average Dice similarity coefficient of 82.39%, sensitivity of 86.32%, specificity of 92.25%, and Hausdorff distance of 12.10 px. In addition, when the ROI contained rectal tumors, the smaller the ROI size, the higher the segmentation accuracy. For a certain ROI size, there were no considerable differences in segmentation results among the loss functions. Compared to the models with single side‐output module, the proposed model performed better.

Conclusions

The results show that the proposed model has potential clinical applications in rectal cancer treatment, particularly with regard to therapeutic response evaluation and preoperative planning.
Characteristic model–based generalized predictive control and its application to the parafoil and payload system
Authors: Tan Panlong , Sun Qinglin , Chen Zengqiang , Jiang Yuxin
Published: April 2019

Generalized predictive control (GPC) has been applied in systems to improve the control performance during the last decades. The designing of predictive model is the essential and vital problem in GPC application. Using characteristic model (CM) as predictive model in GPC can simplify the modeling procedure and improve computing efficiency of GPC. The CM is a kind of simple and easy‐to‐use dynamic model that is equivalent with precise model. Moreover, the creation of CM requires less system information than the practical models. The GPC with CM as predictive model named characteristic model–based generalized predictive control (CMGPC) is proposed in this paper, and it is used in the trajectory tracking control for parafoil and payload system. Simulations and analysis prove that CMGPC is equivalent to traditional GPC and CMGPC is a more efficient way for trajectory tracking of parafoil and payload system compared with conventional proportional integral derivative (PID) method.
Polyglycolic acid copolymers from one‐step cationic polymerization of formaldehyde, carbon monoxide, and epoxides derived from PEG
Authors: Reyhanoglu Yusuf , Gokturk Ersen
Published: April 2019

Biodegradable polyglycolic acid (PGA) is conventionally produced via the ring‐opening polymerization of glycolide, the cyclic dimer form of glycolic acid, in the presence of mostly tin‐based catalyst initiators which are rather known to be cytotoxic materials. Our previous studies revealed an alternative method for the synthesis of PGA from the perfectly alternating copolymerization of formaldehyde (from trioxane) and carbon monoxide (CO) under BrØnsted acidic conditions. The poor physical properties of PGA (insolubility in many organic solvents, brown color, etc.) limit its use in other marketing applications in the industry. To improve on the physical properties of PGA, such as solubility and appearance, copolymerization of trioxane, CO, and a minor amount of epoxides derived from polyethylene glycol (PEG) were performed under the same reaction conditions for PGA synthesis (in DCM, at 800 psi CO pressure, with triflic acid catalyst, reaction duration of 72 hours). The results have shown that the addition of minor quantities of epoxide comonomers vastly improves the appearance of the obtained PGA copolymers and allows for the control of the polymeric properties, such as solubility and melting temperature.