bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors of Hypertension among Diabetic Patients from Yaoundé Central Hospital and Etoug-Ebe Baptist Health Centre, Cameroon
Authors: Kemche Beryl , Saha Foudjo Brice Ulrich , Fokou Elie
Published: June 2020

Uncontrolled blood pressure is a threat to diabetic patients’ life. The aim of this study was to identify risk factors of hypertension among diabetic patients at different stages from Yaoundé Central Hospital and Etoug-Ebe Baptist Health Center of Cameroon. A hospital-based cross-sectional study was conducted for 6 months, and 109 participants (types 1 and 2), aged 24–81 years, were enrolled using simple random sampling. A pretested structured questionnaire was used to collect sociodemographic data, habitual behaviors, clinical history blood pressure, and anthropometric measures. The prevalence of hypertension was 86.2%. Of the total, 13.8% participants were normotensive, 32.1% stage 1 hypertensive, and 54.1% stage 2 hypertensive. Being a male (p=0.046) and not smoking (p=0.036) were negatively associated with stage 1 hypertension whereas eating less than 3 times (p=0.046) and duration of diabetes greater than 9 years among women (p=0.039) were positively associated. Age above 40 years (p=0.002) was negatively associated with stage 2 hypertension. However, age above 40 years had a negative effect among Christian, less educated diabetics, people having diabetes for more than 9 years, and those on medical treatment (5.556≤specific OR≤10.278). Duration of diabetes (age-adjusted OR=1.155; p=0.003) and abnormal waist circumference (crude OR=4.074; p=0.024) were positively associated with stage 2. Abnormal waist-to-hip ratio (crude OR=3.773; p=0.028) and feeding rate greater than 2 times a day (WHR-adjusted OR=3.417; p=0.046) were positively associated with hypertension (stages 1 and 2). This study suggests that hypertension, present at its two stages, is a serious health issue among diabetic patients. Thus, appropriate intervention should be put in place to prevent and control hypertension by managing identified risk factors.
Hepatocellular Expression of SIRT1 and Its Effect on Hepatocellular Carcinoma Progression: A Future Therapeutic Perspective
Authors: Molla Meseret Derbew , Dessie Gashaw , Akalu Yonas , Ayelign Birhanu
Published: June 2020

Hepatocellular carcinoma (HCC) is an aggressive primary hepatic malignancy with a significant morbidity and mortality rate. Although chemotherapy along with surgical incision is believed to be an effective therapeutic approach, to date recurrence is being lifted a major concern. Thus, identifying another best therapeutic approach is becoming the main aim of physicians and scholars. In support of this, recently, several studies reported a significant observation of Sirtuin1 (SIRT1) overexpression in the malignant tumor cells, including HCC. As a result, they believed that overexpression of SIRT1 may have an effect on the progression of HCC by targeting growth and/or apoptotic controlling transcriptional factors/signaling pathways. Similarly, other reports confirmed that SIRT1 inhibition had a direct or indirect role in the control of tumor cell growth and metastasis. Therefore, inhibiting the expression and activity of SIRT1 might have a therapeutic effect to handle HCC. However, there are a limited number of reviews regarding the issue, and here, we summarized hepatocellular expression of SIRT1 and its role on HCC progression.
Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress
Authors: Godoy Paulo R. D. V. , Pour Khavari Ali , Rizzo Marzia , Sakamoto-Hojo Elza T. , Haghdoost Siamak
Published: June 2020

The presence of glioma stem cells (GSCs), which are enriched in neurospheres, may be connected to the radioresistance of glioblastoma (GBM) due to their enhanced antioxidant defense and elevated DNA repair capacity. The aim was to evaluate the responses to different radiation qualities and to reduce radioresistance of U87MG cells, a GBM cell line. U87MG cells were cultured in a 3D model and irradiated with low (24 mGy/h) and high (0.39 Gy/min) dose rates of low LET gamma and high LET carbon ions (1-2 Gy/min). Thereafter, expression of proteins related to oxidative stress response, extracellular 8-oxo-dG, and neurospheres were determined. LD50 for carbon ions was significantly lower compared to LD50 of high and low dose rate gamma radiation. A significantly higher level of 8-oxo-dG was detected in the media of cells exposed to a low dose rate as compared to a high dose rate of gamma or carbon ions. A downregulation of oxidative stress proteins was also observed (NRF2, hMTH1, and SOD1). The NRF2 gene was knocked down by CRISPR/Cas9 in neurosphere cells, resulting in less self-renewal, more differentiated cells, and less proliferation capacity after irradiation with low and high dose rate gamma rays. Overall, U87MG glioma neurospheres presented differential responses to distinct radiation qualities and NRF2 plays an important role in cellular sensitivity to radiation.
Bedside Biliary Drainage without Fluoroscopy for Critically Ill Patients
Authors: Hong Junbo , Zuo Wei , Zhou Xiaodong , Zhou Xiaojiang , Li Guohua , Liu Zhijian , Wang Anjiang , Zhu Yin , Lu Nonghua , Chen Youxiang
Published: June 2020

Background. Bedside biliary drainage by endoscopic retrograde cholangiopancreatography (ERCP) without fluoroscopy for critically ill patients in the intensive care unit (ICU) remains challenging for endoscopists. The present study was to evaluate the efficacy and safety of radiation‐free ERCP for these patients. Methods. Consecutive ICU patients with severe pancreaticobiliary disorders who underwent bedside radiation‐free ERCP were retrospectively analyzed. Results. Radiation‐free ERCP was performed in 80 patients with acute physiology and chronic health evaluation (APACHE II) score of 24.1 ± 6.2. Cannulation was achieved in 75 (93.75%) patients. Biliary drainage was successfully conducted in 74 (92.5%) patients, including 54 (67.5%) and 20 (25.0%) cases of endoscopic retrograde biliary drainage (ERBD) and endoscopic nasobiliary drainage (ENBD), respectively. Adverse event (mild post‐ERCP pancreatitis (PEP)) occurred only in 1 case. The 30‐day mortality rate of these patients was 36.25% (29/80) and was much more higher in patients with ERBD in contrast to that of patients with ENBD, 40.7% (22/54) vs. 20% (4/20), OR = 2.750, 95%CI = 0.810 − 9.3405, P = 0.110. The APACHE II score in nonsurvivors was significantly higher than survivors, 27.6 ± 4.3 versus 22.2 ± 6.3, P = 0.009. The APACHE II score > 22 was an independent risk factor for mortality, 50% versus 10.7%, 95%CI = 2.148 − 31.569, P = 0.002. Conclusions. Radiation‐free ERCP guided bedside biliary drainage is effective and safe for critically ill patients, and ENBD may be an optimal procedure due to a low mortality in these patients.
Layered Grouting Technology Based on a Comprehensive Water‐to‐Cement Ratio for the Overlying Loess Stratum of Urban Shallow Tunnels
Authors: Yang Teng , Zhang Jiaqi , Zhang Xiao , Zhang Qingsong , Yin Zhanchao
Published: June 2020

Different from sand and clay, loess has special engineering properties; hence, existing soil grouting theories are not suitable for the disaster treatment of shallow loess tunnels. In this study, a fine grouting reinforcement test system was developed, and the Yuhan Road tunnel overlying loess was used as the injection medium. An orthogonal test based on slurry dry density, moisture content, water‐to‐cement ratio, and grouting pressure was conducted. Results revealed that the loess samples have high integrity after grouting, and the cohesion and compressive strength improved significantly. The stress‐strain curve showed that the strengthened samples have greater ultimate and residual strengths than samples before grouting. Through a range analysis, it was determined that water‐to‐cement ratio and moisture content are the main factors affecting loess cohesion and compressive strength. Therefore, a comprehensive test of the water‐to‐cement ratio and moisture content as a single variable was conducted. It was found that their influence on loess cohesion and compressive strength is not a single linear relationship but a combined balance. To characterize the joint effect of water in loess and in slurry on reinforcement, the concept of a comprehensive water‐to‐cement ratio is proposed, and the cohesion and compressive strength curves with respect to this ratio were drawn. An optimal comprehensive water‐to‐cement ratio, which corresponds to the maximum cohesion or compressive strength, was found. Based on this ratio, we further propose a method to calculate the water‐to‐cement ratio of slurry and suitable grouting amount for the Yuhan Road tunnel reinforcement project, in which all solution parameters can be measured via field tests. In the project, a surface layered grouting scheme, based on the optimal comprehensive water‐to‐cement ratio, was designed. After grouting, loess strength was improved significantly, permeability was reduced greatly, and the overall reinforcement effect was suitable; these results provide a reference for similar projects.
Comparative Effects of Isokinetic Training and Virtual Reality Training on Sports Performances in University Football Players with Chronic Low Back Pain‐Randomized Controlled Study
Authors: Nambi Gopal , Abdelbasset Walid Kamal , Elsayed Shereen H. , Alrawaili Saud M. , Abodonya Ahmed M. , Saleh Ayman K. , Elnegamy Tamer E.
Published: June 2020

Objective. The objective of this study is to find and compare the effects of isokinetic training and virtual reality training on sports performances in university football players with chronic low back pain. Design. This is a randomized, double‐blinded controlled study. Methods. The study was conducted on 45LBP participants at university hospital. First group (n = 15) received isokinetic training, second group (n = 15) received virtual reality training, and the control group (n = 15) received conventional training exercises for four weeks. Clinical (pain intensity and player wellness) and sports performance (40 m sprint, 4 × 5 m sprint, submaximal shuttle running, countermovement jump, and squat jump) scores were measured at baseline, after 4 weeks, 8 weeks, and 6 months. Results. Four weeks following training VRT group shows more significant changes in pain intensity and player wellness scores than IKT and control groups (p ≤ 0.001). Sports performance variables (such as 40 m sprint, 4 × 5 m sprint, submaximal shuttle running, countermovement jump, and squat jump) scores also show significant improvement in VRT group than the other two groups (p ≤ 0.001). Conclusion. Overall, our study suggests that strength training through virtual reality training protocol improves pain and sports performances than isokinetic training and other conventional trainings in university football players with chronic low back pain.
Enhancing the Seismic Performance of Precast RC Frames with Cladding Panels through Setting U-Shaped Dampers and Rocking Walls
Authors: Jiang Qing , Wang Hanqin , Feng Yulong , Chong Xun , Huang Junqi , Liu Yibo
Published: June 2020

An approach combining U-shaped dampers (USDs) and rocking walls is proposed in this paper to improve the seismic performance of traditional precast reinforced concrete (RC) frames with cladding panels (PRCFCPs): (1) the steel bar and USD connection methods are adopted at the top and bottom of the cladding panels to use the relative deformation between the cladding panels and the main structure and then dissipate the seismic energy and (2) rocking walls are added to the structure to control the structural deformation profiles. The USD numerical model is calibrated using the test data, and a series of nonlinear pushover analyses, dynamic time-history analyses, and incremental dynamic analyses are successively performed to compare the seismic performance and collapse capacity of the PRCFCP, PRCFCP with USDs (PRCFCP-USD), and PRCFCP with USDs and rocking walls (PRCFCP-USD-RW).The results show that the USDs in the PRCFCP-USD-RW undergo more uniform deformation along the structural height and higher energy dissipation efficiency and the PRCFCP-USD-RW exhibits enhanced seismic performance and collapse capacity, which verify the superiority of the proposed combined approach.
Concomitant Use of Herbal and Conventional Medicines among Patients with Diabetes Mellitus in Public Hospitals of Addis Ababa, Ethiopia: A Cross‐Sectional Study
Authors: Meshesha Solomon Getnet , Yeshak Mariamawit Yonathan , Gebretekle Gebremedhin Beedemariam , Tilahun Zelalem , Fenta Teferi Gedif
Published: June 2020

Introduction. The majority of the population in developing countries including Ethiopia still relies on traditional medicines (TMs). Patients with chronic illness like diabetes mellitus (DM) are dissatisfied with conventional medicines and thus are more likely to simultaneously use herbal medicines (HMs). However, such practice could result in potential herb‐drug interaction. This study aimed to identify the commonly used HMs among patients with DM and determine the magnitude of concomitant use of herbal and conventional antidiabetic medicines. Method. A health facility‐based cross‐sectional study design was employed using both quantitative and qualitative data collection methods to determine the magnitude of concomitant use. Patients with DM and prescribers from four public hospitals were the study population for the quantitative and qualitative study, respectively. Simple descriptive statistics were used to describe variables for the quantitative data, and content analysis had been conducted manually for qualitative data. Result. Out of 791 respondents, 409 (51.7%) used traditional medicine at least once in their life time, and 357 (45.1%) used traditional medicine in the last six months prior to data collection. A majority (288 (80.7%)) of the respondents used HMs after starting the conventional antidiabetic medicines within the last six months. Moringa stenopetala, Thymus vulgaris, Trigonella foenum-graecum, Nigella sativa, and Allium sativum were among the frequently mentioned HMs. Prescribers were requesting patients’ HM use when they saw sign of liver toxicity and skin disease, and they were not documenting their history in the patient’s chart. Conclusion. Concomitant use of herbal and conventional antidiabetic medicines was a common practice. Cognizant of its potentially serious herb‐drug interactions, efforts should be made to improve awareness and knowledge of healthcare providers about HM potential effects. Further studies on dose, frequency, duration, and modes of interaction are recommended.
Inhibition of JNK Alleviates Chronic Hypoperfusion-Related Ischemia Induces Oxidative Stress and Brain Degeneration via Nrf2/HO-1 and NF-κB Signaling
Authors: Khan Muhammad Sohail , Khan Amjad , Ahmad Sareer , Ahmad Riaz , Rehman Inayat U. R. , Ikram Muhammad , Kim Myeong Ok
Published: June 2020

Cerebral ischemia is one of the leading causes of neurological disorders. The exact molecular mechanism related to chronic unilateral cerebral ischemia-induced neurodegeneration and memory deficit has not been precisely elucidated. In this study, we examined the effect of chronic ischemia on the induction of oxidative stress and c-Jun N-terminal kinase-associated detrimental effects and unveiled the inhibitory effect of specific JNK inhibitor (SP600125) on JNK-mediated brain degeneration in adult mice. Our behavioral, biochemical, and immunofluorescence studies revealed that chronic ischemic injuries sustained increased levels of oxidative stress-induced active JNK for a long time, whereas SP600125 significantly reduced the elevated level of active JNK and further regulated Nrf2/HO-1 and NF-κB signaling, which have been confirmed in vivo. Neuroinflammatory mediators and loss of neuronal cells was significantly reduced with the administration of SP600125. Ischemic brain injury caused synaptic dysfunction and memory impairment in mice. However, these were significantly improved with SP600125. On the whole, these findings suggest that elevated ROS-mediated JNK is a key mediator in chronic ischemic conditions and has a crucial role in neuroinflammation, neurodegeneration, and memory dysfunction. Our findings suggest that chronic oxidative stress associated JNK would be a potential target in time-dependent studies of chronic ischemic conditions induced brain degeneration.
Antimicrobial Activity of Cultivable Endophytic and Rhizosphere Fungi Associated with “Mile‐a‐Minute,” Mikania cordata (Asteraceae)
Authors: Jayatilake Pavithra L. , Munasinghe Helani
Published: June 2020

Endophytic and rhizosphere fungi are understood to be aiding the host plant to overcome a range of biotic and abiotic stresses (nutrition depletion, droughts, etc.) hence, they remain to be reservoirs of plethora of natural products with immense use. Consequently, this investigation of endophytic and rhizosphere fungi isolated from Mikania cordata (a perennial vine that is well established in Sri Lanka) for their antimicrobial properties was performed with the aim of future derivation of potential beneficial pharmaceutical products. Leaves, twigs, and roots of M. cordata were utilized to isolate a total of 9 endophytic fungi out of which the highest amount (44%) accounted was from the twigs. A sample of the immediate layer of soil adhering to the root of M. cordata was utilized to isolate 15 rhizosphere fungi. Fusarium equiseti and Phoma medicaginis were endophytes that were identified based on colony and molecular characteristics. The broad spectrum of antimicrobial activity depicted by F. equiseti (MK517551) was found to be significantly greater (p ≤ 0.05, inhibitory against Bacillus cereus ATCC 11778, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 25853) than P. medicaginis (MK517550) (inhibitory against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 25853) as assessed using the Kirby‐Bauer disk diffusion method. Trichoderma virens and Trichoderma asperellum were rhizospere fungi that exhibited remarkable antimicrobial properties against the test pathogens chosen for the study. T. asperellum indicated significantly greater bioactivity against all four bacterial pathogens and Candida albicans ATCC 10231 under study. The ranges of minimum inhibitory concentrations (MICs) of the fungi depicting antimicrobial properties were determined. The results obtained suggest that F. equiseti, P. medicaginis, T. asperellum, and T. virens of M. cordata harness bioprospective values as natural drug candidates. This is the first report on isolation and evaluation of the antimicrobial properties of endophytic and rhizosphere fungi of Mikania cordata.
Synthesis, Characterization, and In Vitro Cytotoxicity of Platinum(II) Complexes Bearing Chiral Tetradentate Salicylaldimine Ligands
Authors: Nguyen Quang Trung , Pham Thi Phuong Nam , Nguyen Van Tuyen
Published: June 2020

A series of platinum(II) complexes with chiral Schiff base ligands derived from various salicylaldehydes with (R,R′)- and (S,S′)-cyclohexanediamine were synthesized and characterized by ESI-MS, IR, and NMR. Obtained spectra with typical signals were in agreement with suggested molecular formulae of the complexes. Their photophysical properties were studied by UV-visible and emission spectroscopies. The UV-Vis showed the typical band with low energy at visible range 400–500 nm for MLCT, and this band can emit the luminescent band with emission maximum wavelengths at 529–595 nm. The in vitro cytotoxicity of obtained platinum(II) complexes was screened for KB and MCF-7 human cancer cell lines. The results showed that (S)-enantiomers were more active than (R)-enantiomers and the different positions of methoxy group in salicyl ring gave different cytotoxicities.
Immortalizing Mesenchymal Stromal Cells from Aged Donors While Keeping Their Essential Features
Authors: Piñeiro-Ramil María , Castro-Viñuelas Rocío , Sanjurjo-Rodríguez Clara , Rodríguez-Fernández Silvia , Hermida-Gómez Tamara , Blanco-García Francisco J. , Fuentes-Boquete Isaac , Díaz-Prado Silvia
Published: June 2020

Human bone marrow-derived mesenchymal stromal cells (MSCs) obtained from aged patients are prone to senesce and diminish their differentiation potential, therefore limiting their usefulness for osteochondral regenerative medicine approaches or to study age-related diseases, such as osteoarthiritis (OA). MSCs can be transduced with immortalizing genes to overcome this limitation, but transduction of primary slow-dividing cells has proven to be challenging. Methods for enhancing transduction efficiency (such as spinoculation, chemical adjuvants, or transgene expression inductors) can be used, but several parameters must be adapted for each transduction system. In order to develop a transduction method suitable for the immortalization of MSCs from aged donors, we used a spinoculation method. Incubation parameters of packaging cells, speed and time of centrifugation, and valproic acid concentration to induce transgene expression have been adjusted. In this way, four immortalized MSC lines (iMSC#6, iMSC#8, iMSC#9, and iMSC#10) were generated. These immortalized MSCs (iMSCs) were capable of bypassing senescence and proliferating at a higher rate than primary MSCs. Characterization of iMSCs showed that these cells kept the expression of mesenchymal surface markers and were able to differentiate towards osteoblasts, adipocytes, and chondrocytes. Nevertheless, alterations in the CD105 expression and a switch of cell fate-commitment towards the osteogenic lineage have been noticed. In conclusion, the developed transduction method is suitable for the immortalization of MSCs derived from aged donors. The generated iMSC lines maintain essential mesenchymal features and are expected to be useful tools for the bone and cartilage regenerative medicine research.
Evaluation of a Novel Missense Mutation inABCB4Gene Causing Progressive Familial Intrahepatic Cholestasis Type 3
Authors: Saleem Komal , Cui Qingbo , Zaib Tahir , Zhu Siqi , Qin Qian , Wang Yusi , Dam Jinxi , Ji Wei , Liu Peng , Jia Xueyuan , Wu Jie , Bai Jing , Fu Songbin , Sun Wenjing
Published: June 2020

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a hepatic disorder occurring predominantly in childhood and is difficult to diagnose. PFIC3, being a rare autosomal recessive disease, is caused by genetic mutations in both alleles ofABCB4, resulting in the disruption of the bile secretory pathway. The identification of pathogenic effects resulting from different mutations in ABCB4 is the key to revealing the internal cause of disease. These mutations cause truncation, instability, misfolding, and impaired trafficking of the MDR3 protein. Here, we reported a girl, with a history of intrahepatic cholestasis and progressive liver cirrhosis, with an elevated gamma-glutamyltransferase level. Genetic screeningviawhole exome sequencing found a novel homozygous missense mutationABCB4:c.1195G>C:p.V399L, and the patient was diagnosed with PFIC3. Various computational tools predicted the variant to be deleterious and evolutionary conserved. For functional characterization studies, plasmids, encodingABCB4wild-type and selected established mutant constructs, were expressed in human embryonic kidney (HEK-293T) and hepatocellular carcinoma (HepG2) cells.In vitroexpression analysis observed a reduced expression of mutant protein compared to wild-type protein. We found thatABCB4wild type was localized at the apical canalicular membrane, while mutant p.V399L showed intracellular retention. Intracellular mistrafficking proteins usually undergo proteasomal or lysosomal degradation. We found that after treatment with proteasomal inhibitor MG132 and lysosomal inhibitor bafilomycin A1, MDR3 expression of V399L was significantly increased. A decrease in MDR3 expression of mutant V399L protein may be a result of proteasomal or lysosomal degradation. Pharmacological modulator cyclosporin A and intracellular low temperature (30°C) treatment significantly rescued both the folding defect and the active maturation of the mutant protein. Our study identified a novel pathogenic mutation which expanded the mutational spectrum of theABCB4gene and may contribute to understanding the molecular basis of PFIC3. Therefore, genetic screening plays a conclusive role in the diagnosis of rare heterogenic disorders like PFIC3.
Image Demosaicing Based on Generative Adversarial Network
Authors: Luo Jingrui , Wang Jie
Published: June 2020

Digital cameras with a single sensor use a color filter array (CFA) that captures only one color component in each pixel. Therefore, noise and artifacts will be generated when reconstructing the color image, which reduces the resolution of the image. In this paper, we proposed an image demosaicing method based on generative adversarial network (GAN) to obtain high-quality color images. The proposed network does not need any initial interpolation process in the data preparation phase, which can greatly reduce the computational complexity. The generator of the GAN is designed using the U-net to directly generate the demosaicing images. The dense residual network is used for the discriminator to improve the discriminant ability of the network. We compared the proposed method with several interpolation-based algorithms and the DnCNN. Results from the comparative experiments proved that the proposed method can more effectively eliminate the image artifacts and can better recover the color image.
Depression Prevalence in Neuropathic Pain and Its Impact on the Quality of Life
Authors: Cherif Farah , Zouari Hela G. , Cherif Wissal , Hadded Monia , Cheour Majda , Damak Rahma
Published: June 2020

Introduction. The management of neuropathic pain remains complex, generally because of the psychiatric comorbidity that is often underdiagnosed. The objectives of our work were to determine the link between depression and the characteristics of NP on the one hand and quality of life on the other hand, in a sample of subjects consulting for neuropathic pain (NP) regardless of etiology.Methods. We conducted a cross-sectional study involving 61 neuropathic pain consulting patients in whom we assessed five parameters, namely, neuropathic pain based on DN4, pain intensity using EVA, anxiety, and depression according to the HADS and quality of life.Results. The study population mean age was 52.71 ± 14.29 years while the sex ratio (m/f) was 0.52. The neuropathic pain’s most common etiologies were postherpetic pain, carpal tunnel syndrome, and diabetic neuropathy. Depression and anxiety prevailed by 65.6% and 73.7%, respectively. The quality of life was impaired with average SF-12 physical and mental scores of 33.76 ± 8.03 and 37.78 ± 11.52, respectively. The overall mean BPI score was 5.53 ± 1.76. Patients with high DN4 scores were significantly more depressed (p=0.025). A significantly positive association was found between the depression score and the pain intensity (p=0.001,r = 0.41). Depressed subjects had a poor quality of life according to SF-12 and BPI.Conclusion. Given the depressive comorbidity impact on the neuropathic pain components as well as the quality of life, screening for this comorbidity should be part of the baseline ND assessment.
Conjugated Linoleic Acid Grafting Improved Hemocompatibility of the Polycaprolactone Electrospun Membrane
Authors: Tran Nam Minh-phuong , Huynh Toan Le-duc , Phan Binh Ngoc , Dang Nhi Ngoc-thao , Phan Thang Bach , Ha Huong Thi-thanh , Truong Long Phuoc , Huynh Phu Dai , Tran Ngoc Quyen , Vo Van Toi , Ha Phuong Thu , Nguyen Thi-Hiep
Published: June 2020

Polycaprolactone (PCL) is a versatile biomaterial with a wide range of medical applications, but its use in blood-contacting devices is hampered due to insufficient hemocompatibility. In this work, electrospun polycaprolactone (PCL) membranes were chemically grafted with conjugated linoleic acid (CLA) to prevent induced blood coagulation. The density of grafted CLA and its effects on the morphology and wettability of the membranes were examined. The study also investigated how the membrane interacted with human whole blood and platelets to determine its antithrombotic properties. As the results suggested, the grafting caused a negligible effect on the physical properties of the membrane but greatly improved its compatibility with blood, showing that the approach can be investigated further for blood-contacting applications.
Three-Dimensional Digital Surgical Planning and Rapid Prototyped Surgical Guides in Bernese Periacetabular Osteotomy
Authors: Schröder e Souza Bruno Gonçalves , de Souza Bastos Flavia , de Oliveira Valdeci Manoel , Chaoubah Alfredo
Published: June 2020

Bernese periacetabular osteotomy (PAO) developed by Ganz is currently the treatment of choice for skeletally mature symptomatic patients with developmental dysplasia of the hip (DDH) without osteoarthritis. However, the steep learning curve and considerable number of severe complications lead surgeons to seek for alternatives to promote greater reproducibility and safety of this procedure. This is a report of a DDH case surgically treated with the aid of a digital three-dimensional (3D) planning and rapidly prototyped sterile ABS plastic osteotomy guide, developed in Brazil. We present details regarding the planning, guide production, and surgical technique and report the early results of this treatment approach in a single patient. Digital 3D planning and rapidly prototyped surgical guides are applicable and helpful in PAO surgery as shown in this case. We noted no safety issues, good accuracy, and low production costs with this approach.
Shape Effect Analysis of the Mechanical Properties of PVC‐Coated Fabrics under Off‐Axis Tension
Authors: Zhang Lanlan , Zhang Yingying , Zhao Qichong , Xu Junhao , Xue Jigang
Published: June 2020

This paper selects polyvinyl chloride‐ (PVC‐) coated fabrics to study its off‐axial tensile behaviors under different off‐axis angles including 0°, 15°, 30°, 45°, 60°, 75°, and 90°. In the experiment, dumbbell‐shaped and strip‐shaped specimens are analyzed for shape effect. The variations in the strain distribution are studied by using digital image correlation (DIC) noncontact full‐field measurement system. The shape and off‐axis angle of specimens are analyzed to predict the influences of shape effect. The results show that the longitudinal strain and shear strain of the coated fabrics are obviously symmetrical to the off‐axis direction. The shear strain distribution of the two kinds is basically the same, but the longitudinal strain fields are different. The off‐axis tensile properties of the material are obviously anisotropic and nonlinear. The tensile testing curve of the specimens mainly consists of three stages: initial linear stage, deformation strengthening stage, and stress strengthening stage. At 0°, the tensile strength is the largest and the elongation at break is the smallest. In contrast, at 45°, the elongation at break is the highest and the tensile strength was the smallest. The properties under the other off‐axis angles were between these two extremes.
Oxygen-Enhanced Optoacoustic Tomography Reveals the Effectiveness of Targeting Heme and Oxidative Phosphorylation at Normalizing Tumor Vascular Oxygenation
Authors: Ghosh Poorva , Guo Yihang , Ashrafi Adnin , Chen Jingyu , Dey Sanchareeka , Zhong Shigen , Liu Jie , Campbell James , Konduri Purna Chaitanya , Gerberich Jeni , Garrossian Massoud , Mason Ralph P. , Zhang Li , Liu Li
Published: June 2020

Multispectral optoacoustic tomography (MSOT) is an emerging noninvasive imaging modality that can detect real-time dynamic information about the tumor microenvironment in humans and animals. Oxygen enhanced (OE)-MSOT can monitor tumor vasculature and oxygenation during disease development or therapy. Here, we used MSOT and OE-MSOT to examine in mice the response of human non–small cell lung cancer (NSCLC) xenografts to a new class of antitumor drugs, heme-targeting agents heme-sequestering peptide 2 (HSP2) and cyclopamine tartrate (CycT). HSP2 inhibits heme uptake, while CycT inhibits heme synthesis in NSCLC cells, where heme is essential for ATP generation via oxidative phosphorylation. HSP2 and CycT can inhibit ATP generation and thereby suppress NSCLC cell tumorigenic functions. MSOT showed that treatment of NSCLC tumors with HSP2 or CycT reduced total hemoglobin, increased oxygen saturation, and enhanced the amplitude of response to oxygen gas breathing challenge. HSP2 and CycT normalized tumor vasculature and improved tumor oxygenation, where levels of several hypoxia markers in NSCLC tumors were reduced by treatment with HSP2 or CycT. Furthermore, treatment with HSP2 or CycT reduced levels of angiogenic factor VEGFA, its receptor VEGFR1, and vascular marker CD34. Together, our data show that heme-targeting drugs HSP2 and CycT elicit multiple tumor-suppressing functions, such as inhibiting angiogenic function, normalizing tumor vasculature, alleviating tumor hypoxia, and inhibiting oxygen consumption and ATP generation.

Significance:

Heme-targeting agents HSP2 and CycT effectively normalize tumor vasculature and alleviate tumor hypoxia, raising the possibility of their combination with chemo-, radio-, and immunotherapies to improve antitumor efficacy.

See related commentary by Tomaszewski, p. 3461
Functional Categorization of BRCA1 Variants of Uncertain Clinical Significance in Homologous Recombination Repair Complementation Assays
Authors: Bouwman Peter , van der Heijden Ingrid , van der Gulden Hanneke , de Bruijn Roebi , Braspenning Merel E. , Moghadasi Setareh , Wessels Lodewyk F.A. ,   the Dutch-Belgian VUS workgroup, Vreeswijk Maaike P.G. , Jonkers Jos
Published: June 2020

Purpose:

Because BRCA1 is a high-risk breast/ovarian cancer susceptibility gene, BRCA1 sequence variants of uncertain clinical significance (VUS) complicate genetic counseling. As most VUS are rare, reliable classification based on clinical and genetic data is often impossible. However, all pathogenic BRCA1 variants analyzed result in defective homologous recombination DNA repair (HRR). Thus, BRCA1 VUS may be categorized based on their functional impact on this pathway.

Experimental Design:

Two hundred thirty-eight BRCA1 VUS—comprising most BRCA1 VUS known in the Netherlands and Belgium—were tested for their ability to complement Brca1-deficient mouse embryonic stem cells in HRR, using cisplatin and olaparib sensitivity assays and a direct repeat GFP (DR-GFP) HRR assay. Assays were validated using 25 known benign and 25 known pathogenic BRCA1 variants. For assessment of pathogenicity by a multifactorial likelihood analysis method, we collected clinical and genetic data for functionally deleterious VUS and VUS occurring in three or more families.

Results:

All three assays showed 100% sensitivity and specificity (95% confidence interval, 83%–100%). Out of 238 VUS, 45 showed functional defects, 26 of which were deleterious in all three assays. For 12 of these 26 variants, we could calculate the probability of pathogenicity using clinical and genetic data, resulting in the identification of 7 (likely) pathogenic variants.

Conclusions:

We have functionally categorized 238 BRCA1 VUS using three different HRR-related assays. Classification based on clinical and genetic data alone for a subset of these variants confirmed the high sensitivity and specificity of our functional assays.
Abstract B35: Isolation and characterization of circulating tumor cells (CTCs) from bladder cancer patients using a highly sensitive graphene oxide-based microfluidic device (GO chip)
Authors: Niu Zeqi , Kozminsky Molly A. , Day Kathleen C. , Palmbos Phillip L. , Day Mark L. , Nagrath Sunitha
Published: June 2020

Introduction: A critical research topic in bladder cancer is determining the key regulators in the progression from noninvasive tumor to invasive and ultimately metastatic disease. Although patients with noninvasive bladder cancer can be treated through transurethral resection of bladder tumor and have a high survival rate (~95%), noninvasive bladder tumors recur in 50%-70% of cases. Of these, 10-15% of cases progress to invasive disease. Circulating tumor cells (CTCs) represent the transitional phase of progression between lymphovascular intravasation and distant metastases. Molecular profiling of these CTCs, beyond enumeration, can inform the molecules/pathways important in the invasion process, and potentially help unravel the mechanism of metastasis and provide new targets for therapy. Here we report the application of a highly sensitive graphene oxide-based microfluidic device to isolate and characterize CTCs from bladder cancer patients for the expression of markers implicated in an invasive phenotype.

Methods: An anti-EpCAM and anti-EGFR biotinylated antibody cocktail was immobilized onto the graphene oxide chip (GO chip) to capture CTCs from whole blood. In patient samples, immunofluorescence staining for DAPI (nuclei), cytokeratin (cancer cell marker), EGFR and HER2 (markers of invasive phenotype), and CD45 (white blood cell marker) was used to enumerate CTCs. Cells with a DAPI+CK+CD45- phenotype were counted as CTCs. Blood samples from ten metastatic bladder cancer patients and two healthy controls were processed, stained, and analyzed.

Results: CTCs were found in 10/10 (100%) patients, with an average of 17.70 cells/mL (s = 10.69 cells/mL). 9/10 patients exhibited CTCs that express EGFR, but only one patient had one CTC express HER2.

Conclusion: The antibody-functionalized GO chips were able to successfully capture and enable characterization of CTCs from metastatic bladder cancer patients. EGFR potentially plays an important role in the vascular invasion process.

Citation Format: Zeqi Niu, Molly A. Kozminsky, Kathleen C. Day, Phillip L. Palmbos, Mark L. Day, Sunitha Nagrath. Isolation and characterization of circulating tumor cells (CTCs) from bladder cancer patients using a highly sensitive graphene oxide-based microfluidic device (GO chip) [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B35.
Comprehensive Genomic Analysis of Noonan Syndrome and Acute Myeloid Leukemia in Adults: A Review and Future Directions
Authors: Alhumaid Muhned S. , Dasouki Majed J. , Ahmed Syed O. , AbalKhail Halah , Hagos Samya , Wakil Salma , Hashmi Shahrukh K.
Published: June 2020

Acute myeloid leukemia (AML) in the setting of Noonan syndrome (NS) has been reported before without clear guidelines for treatment or prognosis in these subgroups of patients, most likely due to its rarity and incomplete understanding of the pathogenesis of both diseases. In the current era of next-generation sequencing-based genomic analysis, we can better identify patients with NS with more accurate AML-related prognostic markers. Germline mutations in PTPN11 are the most common cause of NS. Somatic mutations in NPM1 occur frequently in AML. Here, we describe a young adult patient with a novel combined germline PTPN11 and somatic NPM1, IDH1,and BCL6 mutations who presented with fatal AML. In addition, a 50.5-Mb interstitial deletion of 7q21.11-q33 in tumor DNA was detected by chromosomal microarray analysis. While mutations in the transcriptional repressor BCL6 are known to contribute to the pathogenesis of diffuse large B cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), its novel identification in this patient suggests an expanded role in aggressive AML. The identification of key molecular aberrations including the overexpression of SHP2, which drives leukemogenesis and tumorigenesis, has led to the development of novel investigational targeted SHP2 inhibitors.
Pituitary Apoplexy Leading to Cerebral Infarction: A Systematic Review
Authors: Jiang Qiuhong , Xiao Su , Shu Liming , Huang Xinyi , Chen Xiuhui , Hong Hua
Published: June 2020

Background: Cerebral infarction caused by pituitary apoplexy (PA) is rare. To characterize the clinical features of cerebral infarction caused by PA, we performed a systematic review. Summary: The clinical symptoms are mainly sudden headache, hemiplegia, visual impairment, disturbance of consciousness, and ophthalmalgia in patients with cerebral infarction caused by PA. Treatment for this type of infarction is different from treatment for general acute cerebral infarction. Compared to patients who underwent emergency surgery and conservative treatment, patients treated with delayed surgery showed a better prognosis and a lower mortality rate. Compared to patients who underwent craniotomy or conservative treatment, patients who underwent transsphenoidal surgery (TSS) not only improved well but also showed a lower mortality rate. Key Messages: PA rarely causes cerebral infarction, which is a critical condition with a poor prognosis and is more common in men. Delayed surgery and TSS appear to confer a better prognosis in patients with this condition.
Decellularized Porcine Epiphyseal Plate-Derived Extracellular Matrix Powder: Synthesis and Characterization
Authors: Hoang Thi Thai Thanh , Tran Nguyen Diem Huong , Nguyen Dinh Tien Dung  , Nguyen Dai Hai , Truong Minh-Dung
Published: June 2020

The aim of this study was to develop a porcine epiphyseal plate-derived extracellular matrix powder (PEPEP) for epiphyseal plate regeneration. PEPEP was characterized by chemical assay to determine the contents of DNA and epiphyseal plate complex chemical components (glycosaminoglycan and hydroxyproline). The effects of PEPEP on the viability, proliferation, and differentiation of human bone marrow mesenchymal stem cells (hBMSCs) were also evaluated. hBMSCs cultured in PEPEP exhibited a good distribution with excellent viability after 72 h, demonstrating the ability of PEPEP to support hBMSC proliferation. At week 4 and 6 in vitro, the PEPEP + hBMSCs structure showed chondrogenic ability and an increase in expression of collagen type I, type II, and type X. PEPEP showed a promising ability to enhance cartilage formation and promote chondrocyte differentiation, maturation, and hypertrophy. The results provide insights into the feasibility of PEPEP as a potential material for tissue engineering applications.
NT5C2 Gene Polymorphisms and the Risk of Coronary Heart Disease
Authors: Chen Xianghong , Zhang Zaozhang , Wang Xingfan , Chen Yuewu , Wang Chao
Published: June 2020

Background: Increasing studies have reported that 5′-nucleotidase cytosolic II (NT5C2) has a strong relationship with coronary heart disease (CHD) development. This study was designed to examine the relationship between NT5C2 polymorphisms and CHD in the Chinese Han population. Methods: We studied 501 CHD patients and 496 healthy controls from the Second Affiliated Hospital of Hainan Medical University in Hainan Province, China. Four single nucleotide polymorphisms (SNPs) in NT5C2 were selected and genotyped using Agena MassARRAY technology. Odds ratios and 95% confidence intervals were calculated using logistic regression after adjusting for age and gender. Stratification analysis was performed by age and gender in all individuals; we especially investigated the effects of NT5C2 SNPs on hypertension and diabetes among CHD patients. Results: rs2148198 of NT5C2 was strongly associated with an increased risk of CHD (allele: p = 0.045; codominant: p = 0.007; additive: p = 0.016). Stratified analysis revealed that rs2148198 was associated with increased CHD risk in individuals aged ≤61 years and males. For CHD patients, rs2148198 significantly affected the risk of hypertension and diabetes (p < 0.05). Further, rs79237883 of NT5C2 was associated with decreased susceptibility to hypertension in multiple genetic models for individuals with CHD (allele: p = 0.007; codominant: p = 0.001; dominant: p = 0.001; additive: p = 0.008). Conclusion: This study reports the association of NT5C2 gene variants and CHD susceptibility in the Chinese Han population. Especially, NT5C2 rs2148198 was significantly associated with CHD risk in the subgroups of males, hypertension, and diabetes.
Association of Ultrapure Citicoline, Homotaurine and Vitamin E in the Management of Normotensive Glaucoma: A Case Report
Authors: Verdina Tommaso , Passarelli Nicola , Carlini Alessandra , Chemello Francesca , Mastropasqua Rodolfo , Cavallini Gian Maria
Published: June 2020

Normal tension glaucoma (NTG) remains a therapeutic challenge for the ophthalmologist since there are no effective therapies as the main therapeutic target, i.e., the intraocular pressure (IOP) increase, is missed. We report on the effectiveness of two neuroprotective molecules (ultrapure citicoline plus homotaurine), in combination with a topical hypotensive approach, in the management of NTG in a long-term follow-up (30 months). A 38-year-old Caucasian woman with no significant medical history and a diagnosis of NTG, after an extensive 30-month treatment with oral dietary supplement containing ultrapure citicoline 500 mg, homotaurine 50 mg and vitamin E once per day and topical glaucoma medication (brimonidine + brinzolamide drops twice per day), presented a significantly improved automated 24-2 visual field with a controlled tonometric measurement associated with a stabilization of retinal fiber layer and ganglion cells at OCT examination with patient satisfaction. This finding suggests that ultrapure citicoline together with homotaurine and vitamin E, through a synergistic neuroprotective effect, could be a promising approach in the management of NTG.
Preoperative Bacterobilia Is an Independent Risk Factor of SSIs after Partial PD
Authors: Mintziras Ioannis , Maurer Elisabeth , Kanngiesser Veit , Lohoff Michael , Bartsch Detlef K.
Published: June 2020

Introduction: The impact of bacterobilia on postoperative surgical and infectious complications after partial pancreaticoduodenectomy (PD) is still a matter of debate. Methods: All patients undergoing PD with and without a preoperative biliary drainage (PBD) with complete information regarding microbial bile colonization were included. Logistic regression was applied to assess the influence of bacterobilia on postoperative outcome. Results: One hundred seventy patients were retrospectively analysed. Clinically relevant postoperative complications (Clavien-Dindo ≥ III) occurred in 40 (23.5%) patients, clinically relevant postoperative pancreatic fistulas in 29 (17.1%) patients, and surgical site infections (SSIs) in 16 (9.4%) patients. Thirty-seven of 39 (94.9%) patients with PBD and 33 of 131 (25.2%) patients without PBD had positive bile cultures (p < 0.001). A polymicrobial bile colonization was reported in 9 of 33 (27.3%) patients without PBD and 27 of 37 (73%) patients with PBD (p < 0.001). Resistance to ampicillin-sulbactam was shown in 26 of 37 (70.3%) patients with PBD and 12 of 33 (36.4%) patients without PBD (p = 0.001). PBD (OR 0.015, 95% CI 0.003–0.07, p < 0.001) and male sex (OR 3.286, 95% CI 1.441–7.492, p = 0.005) were independent predictors of bacterobilia in the multivariable analysis. Bacterobilia was the only independent predictor of SSIs in the multivariable analysis (OR 0.143, 95% CI 0.038–0.535, p = 0.004). Conclusions: Patients with a PBD show significantly higher rates of bacterobilia, polymicrobial bile colonization, and resistance to ampicillin-sulbactam. Bacterobilia is an independent predictor of SSI after PD.