bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombus Degradation by Fibrinolytic Enzyme ofStenotrophomonassp. Originated from Indonesian Soybean-Based Fermented Food on Wistar Rats
Authors: Nailufar Florensia , Tjandrawinata Raymond R. , Suhartono Maggy T.
Published: August 2016

Objective.To evaluate thrombus degrading effect of a fibrinolytic enzyme from food originStenotrophomonassp. of Indonesia.Methods. Prior to animal study, the enzyme safety was tested using cell culture. The effect on expression of tissue plasminogen activator was also analysed in the cell culture. Forin vivostudies, 25 Wistar rats were used: normal control, negative control, treatment groups with crude and semipurified enzyme given orally at 25 mg/kg, and positive control group which received Lumbrokinase at 25 mg/kg. Blood clot in the tail was induced by kappa carrageenan injection at 1 mg/kg BW.Results. Experiment with cell culture confirmed the enzyme safety at the concentration used and increased expression of tPA. Decreasing of thrombus was observed in the positive group down to 70.35 ± 23.11% of the negative control animals (100%). The thrombus observed in the crude enzyme treatment was down to 56.99 ± 15.95% and 71.5 ± 15.7% for semipurified enzyme. Scanning electron microscopy showed clearly that bood clots were found in the animals injected with kappa carrageenan; however, in the treatment and positive groups, the clot was much reduced.Conclusions. Oral treatment of enzyme fromStenotrophomonassp. of Indonesian fermented food was capable of degrading thrombus induced in Wistar rats.
An Enhanced Collaborative Optimization Approach with Design Structure Matrix Algorithms to Group and Decouple Multidisciplines
Authors: Yao Xifan , Zhou Jifeng , Li Yongxiang , Liu Erhui
Published: August 2016

To improve the solution efficiency and reliability of multidisciplinary design optimization (MDO), an enhanced MDO approach, called sequenced collaborative optimization (SCO), is proposed. The proposed approach introduces the design structure matrix (DSM) to describe the coupling effects among disciplines and aggregates those mutually coupling disciplines into the strong tie groups among similar ones and the weak tie among heterogeneous ones through clustering algorithms. Further, those in the same group are sequenced by the DSM division algorithm. Moreover, by adding constraints, the groups are made independent, resulting in a tree structure without loops, thus decoupling the original multidisciplinary problem into several independent collaborative optimization modules. In the end, an example is employed to verify the efficiency and reliability of the approach.
Endoscopic versus Percutaneous Biliary Drainage in Palliation of Advanced Malignant Hilar Obstruction: A Meta-Analysis and Systematic Review
Authors: Moole Harsha , Dharmapuri Sirish , Duvvuri Abhiram , Dharmapuri Sowmya , Boddireddy Raghuveer , Moole Vishnu , Yedama Prathyusha , Bondalapati Naveen , Uppu Achuta , Yerasi Charan
Published: August 2016

Background. Palliation in advanced unresectable hilar malignancies can be achieved by endoscopic (EBD) or percutaneous transhepatic biliary drainage (PTBD). It is unclear if one approach is superior to the other in this group of patients.Aims. Compare clinical outcomes of EBD versus PTBD.Methods.(i) Study Selection Criterion. Studies using PTBD and EBD for palliation of advanced unresectable hilar malignancies.(ii) Data Collection and Extraction. Articles were searched in Medline, PubMed, and Ovid journals.(iii) Statistical Method. Fixed and random effects models were used to calculate the pooled proportions.Results. Initial search identified 786 reference articles, in which 62 articles were selected and reviewed. Data was extracted from nine studies (N=546) that met the inclusion criterion. The pooled odds ratio for successful biliary drainage in PTBD versus EBD was 2.53 (95% CI = 1.57 to 4.08). Odds ratio for overall adverse effects in PTBD versus EBD groups was 0.81 (95% CI = 0.52 to 1.26). Odds ratio for 30-day mortality rate in PTBD group versus EBD group was 0.84 (95% CI = 0.37 to 1.91).Conclusions. In patients with advanced unresectable hilar malignancies, palliation with PTBD seems to be superior to EBD. PTBD is comparable to EBD in regard to overall adverse effects and 30-day mortality.
Crowdsource Based Indoor Localization by Uncalibrated Heterogeneous Wi-Fi Devices
Authors: Kim Wooseong , Yang Sungwon , Gerla Mario , Lee Eun-Kyu
Published: August 2016

Many indoor localization techniques that rely on received signals from Wi-Fi access points have been explored in the last decade. Recently, crowdsourced Wi-Fi fingerprint attracts much attention, which leads to a self-organized localization system avoiding painful survey efforts. However, this participatory approach introduces new challenges with no previously proposed techniques such as heterogeneous devices, short measurement time, and multiple values for a single position. This paper proposes an efficient localization method combating the three major technical issues in the crowdsourcing based systems. We evaluate our indoor positioning method using 5 places with different radio environment and 8 different mobile phones. The experimental results show that the proposed approach provides consistent localization accuracy and outperforms existing localization algorithms.
Modelling a Coupled Thermoelectromechanical Behaviour of Contact Elements via Fractal Surfaces
Authors: Mazzucco G. , Moro F. , Guarnieri M.
Published: August 2016

A three-dimensional coupled thermoelectromechanical model for electrical connectors is here proposed to evaluate local stress and temperature distributions around the contact area of electric connectors under different applied loads. A micromechanical numerical model has been developed by merging together the contact theory approach, which makes use of the so-called roughness parameters obtained from experimental measurements on real contact surfaces, with the topology description of the rough surface via the theory of fractal geometry. Particularly, the variation of asperities has been evaluated via the Weierstrass-Mandelbrot function. In this way the micromechanical model allowed for an upgraded contact algorithm in terms of effective contact area and thermal and electrical contact conductivities. Such an algorithm is subsequently implemented to construct a global model for performing transient thermoelectromechanical analyses without the need of simulating roughness asperities of contact surfaces, so reducing the computational cost. A comparison between numerical and analytical results shows that the adopted procedure is suitable to simulate the transient thermoelectromechanical response of electric connectors.
Statistical Approaches for the Construction and Interpretation of Human Protein-Protein Interaction Network
Authors: Hu Yang , Zhang Ying , Ren Jun , Wang Yadong , Wang Zhenzhen , Zhang Jun
Published: August 2016

The overall goal is to establish a reliable human protein-protein interaction network and develop computational tools to characterize a protein-protein interaction (PPI) network and the role of individual proteins in the context of the network topology and their expression status. A novel and unique feature of our approach is that we assigned confidence measure to each derived interacting pair and account for the confidence in our network analysis. We integrated experimental data to infer human PPI network. Our model treated the true interacting status (yes versus no) for any given pair of human proteins as a latent variable whose value was not observed. The experimental data were the manifestation of interacting status, which provided evidence as to the likelihood of the interaction. The confidence of interactions would depend on the strength and consistency of the evidence.
Malrotated Subhepatic Caecum with Subhepatic Appendicitis: Diagnosis and Management
Authors: Chong Hock Chin , Chai Feng Yih , Balakrishnan Dhayal , Asilah Siti Mohd Desa , Adila Irene Nur Ibrahim , Syibrah Khuzaimah Zahid
Published: August 2016

Subhepatically located caecum and appendix is a very rare entity. It occurs due to the anomaly in fetal gut rotation that results in an incomplete rotation and fixation of the intestine. Appendicitis, which is a common surgical emergency, in combination with the abnormal subhepatic location, presents a great challenge in its diagnosis and management. Here, we describe a 42-year-old male with chronic dyspepsia who presented with sepsis and severe pain at his right hypochondriac and epigastric region. The final diagnosis was acute appendicitis of the subhepatic appendix. Our discussion focuses on the diagnostic approach and clinical and surgical management. We hope that our report will increase the awareness among the clinicians and hasten the management of such rare condition to avoid complications.
A New Impact Time and Angle Control Guidance Law for Stationary and Nonmaneuvering Targets
Authors: Yang Zhe , Wang Hui , Lin Defu , Zang Luyao
Published: August 2016

A guidance problem for impact time and angle control applicable to cooperative attack is considered based on the sliding mode control. In order to satisfy the impact angle constraint, a line-of-sight rate polynomial function is introduced with four tuning parameters. And the time-to-go derivative with respect to a downrange orientation is derived to minimize the impact time error. Then the sliding mode control surface with impact time and angle constraints is constructed using nonlinear engagement dynamics to provide an accurate solution. The proposed guidance law is easily extended to a nonmaneuvering target using the predicted interception point. Numerical simulations are performed to verify the effectiveness of the proposed guidance law for different engagement scenarios.
Supine Frequent Ventricular Extrasystoles in a Pregnant Woman without Structural Heart Disease
Authors: Ferreira Natália Stela Sandes , Barros Tatiana La Croix , Gismondi Ronaldo Altenburg
Published: August 2016

Arrhythmias are the most common cardiac complication during gestational period and may occur in women with or without known structural heart disease. Premature extra beats and sustained tachyarrhythmias are the most common arrhythmias in pregnancy. Symptomatic episodes occur in 20–44% of pregnant women, usually as palpitations, dizziness, or syncope. We searched on Pubmed for ventricular premature complexes (VPC) in pregnant women and found no case reporting increased incidence of this arrhythmia while supine. The aim of this study is to report a case of a pregnant woman without previous structural heart disease that presented a great number of VPC when supine. The arrhythmogenesis increase during pregnancy is multifactorial. In the reported case, we believe that augmented venous return was the most important pathophysiologic process. When the patient changes to left lateral decubitus, there could be a sudden release of the inferior vena cava, causing an abrupt augmentation of venous return to the right heart chambers and increasing the risk of arrhythmias. Obstetricians and primary care physicians should be aware of palpitations and related patient complains while they are asleep or supine.
The Effects of Different Extraction Methods on Antioxidant Properties, Chemical Composition, and Thermal Behavior of Black Seed (Nigella sativa L.) Oil
Authors: Mohammed Nameer Khairullah , Abd Manap Mohd Yazid , Tan Chin Ping , Muhialdin Belal J. , Alhelli Amaal M. , Meor Hussin Anis Shobirin
Published: August 2016

The Nigella sativa L. popularly referred to as black seeds are widely used as a form of traditional nutrition and medicine. N. sativa seeds were used for the extraction of their oil by way of supercritical fluid extraction (SFE) and cold press (CP) to determine the physicochemical properties, antioxidant activity, and thermal behavior. The GC‐MS results showed the primary constituents in the Nigella sativa oil (NSO) were Caryophyllene (17.47%) followed by thymoquinone (TQ) (11.80%), 1,4‐Cyclohexadiene (7.17%), longifolene (3.5%), and carvacrol (1.82%). The concentration of TQ was found to be 6.63 mg/mL for oil extracted using SFE and 1.56 mg/mL for oil extracted by CP method. The antioxidant activity measured by DPPH and the IC50 was 1.58 mg/mL and 2.30 mg/mL for SFE oil and cold pressed oil, respectively. The ferric reducing/antioxidant power (FRAP) activity for SFE oil and CP oil was 538.67 mmol/100 mL and 329.00 mmol/100 mL, respectively. The total phenolic content (TPC) of SFE oil was 160.51 mg/100 mL and 94.40 mg/100 mL for CP oil presented as gallic acid equivalents (GAE). This research showed that a high level of natural antioxidants could be derived from NSO extracted by SFE.
Enhanced Recovery after Surgery in a Single High-Volume Surgical Oncology Unit: Details Matter
Authors: Fitzgerald Timothy L. , Mosquera Catalina , Koutlas Nicholas J. , Vohra Nasreen A. , Edwards Kimberly V. , Zervos Emmanuel E.
Published: August 2016

Benefits of ERAS protocol have been well documented; however, it is unclear whether the improvement stems from the protocol or shifts in expectations. Interdisciplinary educational seminars were conducted for all health professionals. However, one test surgeon adopted the protocol. 394 patients undergoing elective abdominal surgery from June 2013 to April 2015 with a median age of 63 years were included. The implementation of ERAS protocol resulted in a decrease in the length of stay (LOS) and mortality, whereas the difference in cost was found to be insignificant. For the test surgeon, ERAS was associated with decreased LOS, cost, and mortality. For the control providers, the LOS, cost, mortality, readmission rates, and complications remained similar both before and after the implementation of ERAS. An ERAS protocol on the single high-volume surgical unit decreased the cost, LOS, and mortality.
Gait Analysis of Conventional Total Knee Arthroplasty and Bicruciate Stabilized Total Knee Arthroplasty Using a Triaxial Accelerometer
Authors: Tomite Takenori , Saito Hidetomo , Aizawa Toshiaki , Kijima Hiroaki , Miyakoshi Naohisa , Shimada Yoichi
Published: August 2016

One component of conventional total knee arthroplasty is removal of the anterior cruciate ligament, and the knee after total knee arthroplasty has been said to be a knee with anterior cruciate ligament dysfunction. Bicruciate stabilized total knee arthroplasty is believed to reproduce anterior cruciate ligament function in the implant and provide anterior stability. Conventional total knee arthroplasty was performed on the right knee and bicruciate stabilized total knee arthroplasty was performed on the left knee in the same patient, and a triaxial accelerometer was fitted to both knees after surgery. Gait analysis was then performed and is reported here. The subject was a 78-year-old woman who underwent conventional total knee arthroplasty on her right knee and bicruciate stabilized total knee arthroplasty on her left knee. On the femoral side with bicruciate stabilized total knee arthroplasty, compared to conventional total knee arthroplasty, there was little acceleration in thex-axis direction (anteroposterior direction) in the early swing phase. Bicruciate stabilized total knee arthroplasty may be able to replace anterior cruciate ligament function due to the structure of the implant and proper anteroposterior positioning.
Oxidation‐Reduction Potential as a Biomarker for Severity and Acute Outcome in Traumatic Brain Injury
Authors: Bjugstad Kimberly B. , Rael Leonard T. , Levy Stewart , Carrick Matthew , Mains Charles W. , Slone Denetta S. , Bar-Or David
Published: August 2016

There are few reliable markers for assessing traumatic brain injury (TBI). Elevated levels of oxidative stress have been observed in TBI patients. We hypothesized that oxidation‐reduction potential (ORP) could be a potent biomarker in TBI. Two types of ORP were measured in patient plasma samples: the static state of oxidative stress (sORP) and capacity for induced oxidative stress (icORP). Differences in ORP values as a function of time after injury, severity, and hospital discharge were compared using ANOVAs with significance at p ≤ 0.05. Logit regression analyses were used to predict acute outcome comparing ORP, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS), and Glasgow Coma Scale (GCS). Antioxidant capacity (icORP) on day 4 was prognostic for acute outcomes (p < 0.05). An odds ratio of 4.08 was associated with poor acute outcome when icORP > 7.25 μC. IcORP was a better predictor than ISS, AIS, or GCS scores. sORP increased in those with the highest ISS values (p < 0.05). Based on these findings ORP is useful biomarker for severity and acute outcome in TBI patients. Changes in ORP values on day 4 after injury were the most prognostic, suggesting that patients’ response to brain injury over time is a factor that determines outcome.
Analyses of the Calendaring Process for Performance Optimization of Li-Ion Battery Cathode
Authors: Oladimeji Charles F. , Moss Pedro L. , Weatherspoon Mark H.
Published: August 2016

Olivine structure LiFePO4(LFP) was synthesized via solid state processes, using Li2CO3, NH4H2PO4, and FeC2O4·H2O and C12H22O11as precursor materials. The effects of calendaring are analyzed in terms of electrochemical performance, cycle life, surface morphology, and ac impedance analysis. The resulting LFP electrode was divided into calendared and uncalendared samples. Under electrochemical impedance testing, the calendared and uncalendared electrodes exhibited a charge transfer resistance of 157.8 Ω and 182.4 Ω, respectively. The calendared electrode also exhibited a higher discharge capacity of about 130 mAh/g at0.1Ccompared to a discharge capacity of 120 mAh/g at0.1Cfor the uncalendared electrode.
Applying a Locally Linear Embedding Algorithm for Feature Extraction and Visualization of MI-EEG
Authors: Li Mingai , Luo Xinyong , Yang Jinfu , Sun Yanjun
Published: August 2016

Robotic-assisted rehabilitation system based on Brain-Computer Interface (BCI) is an applicable solution for stroke survivors with a poorly functioning hemiparetic arm. The key technique for rehabilitation system is the feature extraction of Motor Imagery Electroencephalography (MI-EEG), which is a nonlinear time-varying and nonstationary signal with remarkable time-frequency characteristic. Though a few people have made efforts to explore the nonlinear nature from the perspective of manifold learning, they hardly take into full account both time-frequency feature and nonlinear nature. In this paper, a novel feature extraction method is proposed based on the Locally Linear Embedding (LLE) algorithm and DWT. The multiscale multiresolution analysis is implemented for MI-EEG by DWT. LLE is applied to the approximation components to extract the nonlinear features, and the statistics of the detail components are calculated to obtain the time-frequency features. Then, the two features are combined serially. A backpropagation neural network is optimized by genetic algorithm and employed as a classifier to evaluate the effectiveness of the proposed method. The experiment results of 10-fold cross validation on a public BCI Competition dataset show that the nonlinear features visually display obvious clustering distribution and the fused features improve the classification accuracy and stability. This paper successfully achieves application of manifold learning in BCI.
Computationally Efficient Angle and Polarization Estimation in the Presence of Multipath Propagation Using Dual-Polarization Vector Sensor Array
Authors: Si Weijian , Zhao Pinjiao , Qu Zhiyu , Wang Liwei
Published: August 2016

This paper presents a computationally efficient angle and polarization estimation method for a mixture of uncorrelated and coherent sources using a dual-polarization vector sensor array. The uncorrelated sources are separated from the coherent sources on the basis of the modulus property of eigenvalues. The angles of the uncorrelated sources are estimated by employing rotational invariance and the associated polarization is obtained from the estimate of the uncorrelated array response matrix through elementwise division. For the distinguished coherent sources, two Hankel matrices are constructed from the elements of the estimated coherent array response matrix of each coherent group, from which two rotational-invariant submatrix pairs are extracted for estimating the coherent angles with a high precision. The least-square solution to the coherent polarization equation is derived for estimating the coherent polarization parameters. For each uncorrelated source and coherent group, the proposed method estimates the associated angle and polarization parameters separately, which avoids the need of 3D spectral search. In comparison with the existing methods, the simulation results show that the proposed method yields favorable performance in terms of computational efficiency and estimation accuracy.
Repeat Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Patients with Suspected Pancreatic Cancer: Diagnostic Yield and Associated Change in Access to Appropriate Care
Authors: Mitchell Robert A. , Stanger Dylan , Shuster Constantin , Telford Jennifer , Lam Eric , Enns Robert
Published: August 2016

Background.There is a high incidence of inconclusive cytopathology at initial EUS-FNA (endoscopic ultrasound-guided fine-needle aspiration) for suspected malignant pancreatic lesions. To obtain appropriate preoperative or palliative chemotherapy for pancreatic cancer, definitive cytopathology is often required. The utility of repeat EUS-FNA is not well established.Methods. A retrospective cohort study was conducted evaluating the yield of repeat EUS-FNA in determining a cytological diagnosis in patients who had undergone a prior EUS-FNA for diagnosis of suspected malignant pancreatic lesions with inconclusive cytopathology. The wait times to the second procedure and to decisions regarding therapy were calculated.Results.Overall, 45 repeat EUS-FNA procedures were performed over seven years for suspected malignant pancreatic lesions. Cytopathological class (I to IV) changed between first and second EUS-FNA in 32 patients (71%). Of 34 patients with an initially nonconclusive diagnosis, 20 had a conclusive diagnosis (59%) on repeat EUS-FNA. The cumulative yield after repeat EUS-FNA for definite pancreatic adenocarcinoma was 7 (16%). The median time interval between first and second EUS-FNA was 31 (7–175) days.Conclusions. A substantial number of patients had a definitive diagnosis of adenocarcinoma on repeat FNA and were, therefore, subsequently able to access appropriate care.
Idiopathic Sclerosing Encapsulating Peritonitis: A Rare Cause of Subacute Intestinal Obstruction
Authors: Lim Mei Chin , Chotai Niketa Chandrakant , Giron Danilo Medina
Published: August 2016

We present a case of a previously healthy 50-year-old gentleman who had recurrent vomiting and abdominal pain of two-month duration. The patient was subsequently diagnosed with abdominal cocoon on computed tomography. Idiopathic sclerosing encapsulating peritonitis, also known as abdominal cocoon, is a rare cause of small bowel obstruction. Visualization of variable encasement of the small bowel loops by a characteristic membranous sac, either preoperatively with cross-sectional imaging or intraoperatively, is the key to diagnosis. This is a highly treatable condition; surgical excision of the sac with adhesiolysis facilitates a full recovery in affected patients.
Reversible Oxygenation of 2,4-Diaminobutanoic Acid-Co(II) Complexes
Authors: Cheng Xiang , Huang Yan , Li Hui , Yue Fan , Wen Hongmei , Wang Jide
Published: August 2016

This paper introduces the structural characterization and studies on reversible oxygenation behavior of a new oxygen carrier Co(II)-2,4-diaminobutanoic acid (DABA) complex in aqueous solution. The composition of the oxygenated complex was determined by gas volumetric method, molar ratio method, and mass spectrometry, and the formula of the oxygenated complex was determined to be [Co(DABA)2O2]. In aqueous solution, the complex can continuously uptake and release dioxygen and exhibit excellent reversibility of oxygenation and deoxygenation ability. This complex can maintain 50% of its original oxygenation capacity after 30 cycles in 24 h and retain 5% of the original oxygenation capacity after more than 260 cycles after 72 h. When a ligand analogue was linked to histidine (His), the new complex exhibited as excellent reversible oxygenation property as His-Co(II) complex. Insight into the relationship between structural detail and oxygenation properties will provide valuable suggestion for a new family of oxygen carriers.
A Scheme for Verification on Data Integrity in Mobile Multicloud Computing Environment
Authors: Cao Laicheng , He Wenwen , Guo Xian , Feng Tao
Published: August 2016

In order to verify the data integrity in mobile multicloud computing environment, a MMCDIV (mobile multicloud data integrity verification) scheme is proposed. First, the computability and nondegeneracy of verification can be obtained by adopting BLS (Boneh-Lynn-Shacham) short signature scheme. Second, communication overhead is reduced based on HVR (Homomorphic Verifiable Response) with random masking and sMHT (sequence-enforced Merkle hash tree) construction. Finally, considering the resource constraints of mobile devices, data integrity is verified by lightweight computing and low data transmission. The scheme improves shortage that mobile device communication and computing power are limited, it supports dynamic data operation in mobile multicloud environment, and data integrity can be verified without using direct source file block. Experimental results also demonstrate that this scheme can achieve a lower cost of computing and communications.
Ethnomedicinal Uses of Honeybee Products in Lithuania: The First Analysis of Archival Sources
Authors: Pranskuniene Zivile , Bernatoniene Jurga , Simaitiene Zenona , Pranskunas Andrius , Mekas Tauras
Published: August 2016

Lithuania has old ethnomedicine traditions, consisting of many recipes with herbal, animal, and mineral original ingredients. All these findings were mostly collected in Lithuanian language, often in local community’s dialects, and stored only in archives. We analyzed archival sources about honeybee and its products used for medicinal purposes dated from 1886 till 1992 in different parts of Lithuania. We systematized and presented the most important information about bees and their products: indication for usage, ingredients used in the recipe, their preparation techniques, and application for therapeutic purposes. Researchers in Lithuania are now looking for new evidence based indications and preparation and standardization methods of bee products. Archival sources are a foundation for studies in Lithuania. The results can be integrated into scientifically approved folk medicine practices into today’s healthcare.
Atmospheric Effect on Cosmic Ray Muons at High Cut-Off Rigidity Station
Authors: Maghrabi Abdullrahman , Almutayri Mohammed
Published: August 2016

Cosmic ray data and radiosonde measurements from Riyadh, Saudi Arabia (Rc = 14.4 GV), for the period 2002–2012, were used to study the effect of atmospheric pressure, level of pion production, and temperature at that level, on cosmic ray muons. We found that, even if corrections were made to the detected muons using these three parameters, seasonal variations of the cosmic rays still exist. This suggests that other terrestrial and/or extraterrestrial causes may be considered. The levels of pion production and atmospheric pressure are inversely correlated with the muon rate. On the other hand, the temperature at the pion production level is correlated with muons in spring and winter and inversely correlated in fall and summer. There is no clear explanation for this behavior.
Maxillary Osteomyelitis: A Rare Entity
Authors: Habib Ayaaz , Sivaji Nagaraj , Ashraf Tauseef
Published: August 2016

Osteomyelitis of the maxilla is now a rare event with the advent of antibiotics. The two predominant causes are odontogenic infections and sinusitis. Immunocompromised states such as diabetes, HIV, and malnutrition increase the risk of osteomyelitis. It is important to recognize this early as it is a difficult entity to treat with potentially serious consequences. We report an unusual case of right sided maxillary osteomyelitis in a lady with poorly controlled diabetes in rural Lincolnshire. Biopsy of the right maxillary bone showed features of acute osteomyelitis. This responded well to a prolonged course of oral antibiotics.
A Case‐Control Study on the Oxidative Balance of 50% Autologous Serum Eye Drops
Authors: Gus Patrícia Ioschpe , Marinho Diane , Zelanis Samira , Belló-Klein Adriane , Locatelli Claudete , Nicola Felipe , Kunzler Ana Laura , Fernandes Tania Regina Gatelli , Carraro Cristina Campos , Barbosa Luciene
Published: August 2016

Importance. Autologous serum (AS) eye drops are recommended for severe dry eye in patients with ocular surface disease. No description of the antioxidant balance of AS eye drops has been reported in the literature. Objective. This study sought to evaluate the total reactive antioxidant potential (TRAP) and concentration of reactive oxygen species (ROS) in samples of 50% AS eye drops and their correlations with the demographic characteristics and lifestyle habits of patients with ocular surface disease and healthy controls. Design. This was a case‐control study with a 3‐month follow‐up period. Participants. 16 patients with severe dry eye disease of different etiologies and 17 healthy controls matched by age, gender, and race were included. Results. TRAP and ROS were detected at all evaluated times. There were no differences in the mean ROS (p = 0.429) or TRAP (p = 0.475) levels between cases and controls. No statistically significant differences in the concentrations of ROS or TRAPs were found at 0, 15, or 30 days (p for ROS = 0.087 and p for TRAP = 0.93). Neither the demographic characteristics nor the lifestyle habits were correlated with the oxidative balance of the 50% AS eye drops. Conclusions and Relevance. Both fresh and frozen 50% AS eye drops present antioxidant capacities and ROS in an apparently stable balance. Moreover, patients with ocular surface disease and normal controls produce equivalent AS eye drops in terms of oxidative properties.
Drug-Driven Synthetic Lethality: Bypassing Tumor Cell Genetics with a Combination of AsiDNA and PARP Inhibitors
Authors: Jdey Wael , Thierry Sylvain , Russo Christophe , Devun Flavien , Al Abo Muthana , Noguiez-Hellin Patricia , Sun Jian-Sheng , Barillot Emmanuel , Zinovyev Andrei , Kuperstein Inna , Pommier Yves , Dutreix Marie
Published: August 2016

Purpose: Cancer treatments using tumor defects in DNA repair pathways have shown promising results but are restricted to small subpopulations of patients. The most advanced drugs in this field are PARP inhibitors (PARPi), which trigger synthetic lethality in tumors with homologous recombination (HR) deficiency. Using AsiDNA, an inhibitor of HR and nonhomologous end joining, together with PARPi should allow bypassing the genetic restriction for PARPi efficacy.

Experimental Design: We characterized the DNA repair inhibition activity of PARPi (olaparib) and AsiDNA by monitoring repair foci formation and DNA damage. We analyzed the cell survival to standalone and combined treatments of 21 tumor cells and three nontumor cells. In 12 breast cancer (BC) cell lines, correlation with sensitivity to each drug and transcriptome were statistically analyzed to identify resistance pathways.

Results: Molecular analyses demonstrate that olaparib and AsiDNA respectively prevent recruitment of XRCC1 and RAD51/53BP1 repair enzymes to damage sites. Combination of both drugs increases the accumulation of unrepaired damage resulting in an increase of cell death in all tumor cells. In contrast, nontumor cells do not show an increase of DNA damage nor lethality. Analysis of multilevel omics data from BC cells highlighted different DNA repair and cell-cycle molecular profiles associated with resistance to AsiDNA or olaparib, rationalizing combined treatment. Treatment synergy was also confirmed with six other PARPi in development.

Conclusions: Our results highlight the therapeutic interest of combining AsiDNA and PARPi to recapitulate synthetic lethality in all tumors independently of their HR status. Clin Cancer Res; 23(4); 1001–11. ©2016 AACR.
A Window of MHM Demethylation Correlates with Key Events in Gonadal Differentiation in the Chicken
Authors: Yang Xiurong , Deng Jixian , Zheng Jiangxia , Xia Li , Yang Zhuliang , Qu Lujiang , Chen Sirui , Xu Guiyun , Jiang Hesheng , Clinton Michael , Yang Ning
Published: August 2016

The MHM (male hypermethylated) region on the chicken Z chromosome is of interest in terms of sex determination both because hypermethylation of the promoter in males results in female-specific expression, and in females the non-coding transcripts accumulate in the region of a locus that encodes a key candidate gene for testis differentiation in birds - DMRT1. However, it has yet to be established whether MHM plays a role in either sex determination or gonadal development in chicken. Here, we sought to establish the MHM methylation pattern during chicken gonadal development and determine how this pattern correlates with the expression profiles of genes involved in sex determination and gonadal differentiation. As expected, we found that MHM methylation levels were higher in male than in female gonads at most stages of development. We also showed that there was no significant difference in the methylation patterns between the right and left gonad and that the pattern of methylation in female gonads was not affected by sex reversal. However, we did find an unexpected window where MHM promoter methylation levels were very low in both males and females. This developmental window coincided with a stage of gonad development where there is a dramatic increase in expression of key testis genes in males and of key ovary genes in females. The current study raises the possibility that the non-coding RNA transcripts of MHM may affect testis and ovary differentiation by influencing sex-specific gene expression.
MicroRNA-199a Targets the Fatty Acid Transport Protein 1 Gene and Inhibits the Adipogenic Trans-Differentiation of C2C12 Myoblasts
Authors: Qi Renli , Long Dingbiao , Wang Jing , Wang Qi , Huang Xiaofeng , Cao Chunting , Gao Guangliang , Huang Jinxiu
Published: August 2016

Background/Aims: Muscle cells are able to trans-differentiate into adipocytes with adipogenesis induction. MicroRNAs (miRNAs), a class of small non-coding RNAs, widely participate in the regulation of growth and development of cells. However, the expression and regulatory role of miRNAs in the trans-differentiation of muscle cell are largely unknown. Methods: C2C12 myoblasts were inducted to adipogenesis trans-differentiation and microarrays were used to assay the changes of expression profile of miRNAs. MiR-199a, a miRNA showed significant change in the trans-differentiation, was selected for the subsequent function study via over- expression and knock down. Results: Dozens of miRNAs showed different changes followed the adipogenesis trans-differentiation of C2C12 cells. In which, miR-199a was decreased in the adipogenic cells and miR-199a over-expression inhibited the trans-differentiation and decreased lipid accumulation in the cells. Moreover, Fatty acid transport protein 1 (Fatp1), a major regulator of trans-membrane transportation and the oxidative metabolism of free fatty acids, was showed to be a target of miR-199a by computational and luciferase reporter assays. Additionally, Fatp1 knock-down by small interfering RNA had similar inhibitory effects on the trans-differentiation in C2C12 cells. Conclusion: Our study reveals an important role for miR-199a in the regulation of adipogenic trans-differentiation in muscle cells via suppression of Fatp1 gene.
Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP)
Authors: Li Chanjuan , Ding Hongjuan , Tian Jing , Wu Lili , Wang Yun , Xing Yuan , Chen Min
Published: August 2016

Background/Aims: Forkhead Box Protein C2 (FOXC2) has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT) in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50) of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP) and its parental cell line (SKOV3). Small hairpin RNA (shRNA) was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26μM) (P<0.01) and acquired EMT phenotype and invasive characteristics. Gain- and loss-of-function assays indicated that shRNA-mediated FOXC2 knockdown could reverse EMT and reduce the capacity of migration, invasion, attachment and detachment in SKOV3/CDDP cell line and upregulation of FOXC2 could induce the reverse effects in parental SKOV3 cell line. Furthermore, it was found that activation of ERK or AKT/GSK-3β signaling pathways was involved in FOXC2-promoting EMT in CDDP-resistant ovarian cancer cells. Conclusions: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer.
The New -474(C→T) Substitution Discovered in the HBG2 Promoter of a Sardinian δβ-Thalassemia Carrier
Authors: Trova Sandro , Mereu Paolo , Cocco Elena , Masala Bruno , Manca Laura , Pirastru Monica
Published: August 2016

During a screening for hemoglobinopathies, we found a carrier of the Sardinian δβ-thalassemia condition. The proband's hematology and hemoglobin (Hb) profile agreed with those of the other carriers previously identified during our diagnostic program except for the fetal Hb (HbF) composition, which consisted of both α2Aγ2 and α2Gγ2 instead of nearly 100% α2Aγ2. In order to explain the unusual γ-chain ratio, sequencing of the Gγ promoter was carried out and revealed two nucleotide substitutions in cis: C→T at position -474 and A→G at position -309 from the Cap site. The latter had previously been observed in subjects with raised HbF levels, although it has not yet been evaluated at functional level. We used the luciferase assay to determine whether the two mutations modify the transcriptional activity of the Gγ promoter. Results indicated that the observed in vivo Gγ-globin production cannot be translated into increased in vitro promoter function, suggesting that the assessed mutations cannot be considered as functional single nucleotide polymorphisms per se; instead, a more complex regulatory mechanism might be involved.
Patient Selection and Timing of Continuous Renal Replacement Therapy
Authors: Ostermann Marlies , Joannidis Michael , Pani Antonello , Floris Matteo , De Rosa Silvia , Kellum John A. , Ronco Claudio ,   on behalf of the 17th Acute Disease Quality Initiative (ADQI) Consensus Group
Published: August 2016

When and in whom to initiate continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) remains a highly controversial topic with large practice variation around the world. Even within countries, practice variation exists and recommendations for clinical practice are not specific. In this article, we report the consensus recommendations for timing and patient selection for CRRT - the results of the 2016 Acute Disease Quality Initiative XVII conference on ‘precision CRRT'. We suggest that these recommendations could serve to develop the best clinical practice and standards of care for use of CRRT in patients with AKI. Finally, we identify and highlight the areas of ongoing uncertainty and propose an agenda for future research.
Precision Fluid Management in Continuous Renal Replacement Therapy
Authors: Murugan Raghavan , Hoste Eric , Mehta Ravindra L. , Samoni Sara , Ding Xiaoqiang , Rosner Mitchell H. , Kellum John A. , Ronco Claudio ,   on behalf of the Acute Disease Quality Initiative (ADQI) Consensus Group
Published: August 2016

Fluid management during continuous renal replacement therapy (CRRT) in critically ill patients is a dynamic process that encompasses 3 inter-related goals: maintenance of the patency of the CRRT circuit, maintenance of plasma electrolyte and acid-base homeostasis and regulation of patient fluid balance. In this article, we report the consensus recommendations of the 2016 Acute Disease Quality Initiative XVII conference on ‘Precision Fluid Management in CRRT'. We discuss the principles of fluid management, describe various prescription methods to achieve circuit integrity and introduce the concept of integrated fluid balance for tailoring fluid balance to the needs of the individual patient. We suggest that these recommendations could serve to develop the best clinical practice and standards of care for fluid management in patients undergoing CRRT. Finally, we identify and highlight areas of uncertainty in fluid management and set an agenda for future research.
Amyotrophic Lateral Sclerosis Incidence and Previous Prescriptions of Drugs for the Nervous System
Authors: D'Ovidio Fabrizio , d'Errico Angelo , Farina Elena , Calvo Andrea , Costa Giuseppe , Chiò Adriano
Published: August 2016

Background: An increased frequency of psychotic disorders in amyotrophic lateral sclerosis (ALS) families compared to controls has been reported. Aim of our study was to assess the relationship between nervous system drugs prescriptions and subsequent onset of ALS in a large Italian population. Methods: The study population consisted of all subjects over 15 years at the 2001 Italian census, resident in Turin since 1996 (n = 687,324), followed up for ALS occurrence from 2002 to 2014. Exposure to nervous system drugs was measured until 2012, or until 1 year before ALS onset. The association was estimated for ever and cumulative exposure, through Cox proportional Hazards models adjusted for sex, age, education, marital status and drug co-exposure. Results: In the analysis for ever exposure, opioids were significantly inversely associated with ALS risk (hazard ratio (HR) 0.59; 95% CI 0.35-0.97), while antiepileptics (HR 1.35; 95% CI 0.92-2.00) showed a marginally significantly positive association. Examining cumulative exposure, the protective role of opioids associated with more than 4 prescriptions and the risk effect of antiepileptics for over 6 prescriptions was confirmed. Conclusions: The present study revealed associations of ALS onset with previous exposure to opioids, maybe through the activation of δ receptor and σ receptors and antiepileptics, which are novel findings to our knowledge.
Cell-Free Placental DNA in Maternal Plasma in Relation to Placental Health and Function
Authors: Manokhina Irina , Singh Tanjot K. , Robinson Wendy P.
Published: August 2016

Background: While cell-free placental DNA (cfp-DNA) increases in response to certain pathological conditions, confounding variables, such as placental size, may also contribute to its release. Furthermore, the relationship between cfp-DNA and maternal serum proteins has not been well investigated. Objective: To analyze plasma cfp-DNA levels and correlate with measurable placental parameters, maternal serum proteins, or pathologic conditions reflecting placental dysfunction. Method: Methylated fraction of RASSF1A was quantified in maternal plasma as a measure of cfp-DNA in a cohort of 86 pregnant women. Results: Placental dimensions or weight had no impact on cfp-DNA levels in noncomplicated pregnancies (n = 63). However, an association between β-hCG and cfp-DNA levels (p = 0.0012) was detected. Complications occurred in 23 pregnancies including chromosomal abnormalities, gestational hypertension, intrauterine growth restriction, and preterm birth. There was overall a skewed distribution (<-1 SD or >1 SD from mean) for cfp-DNA in the abnormal group, although due to the small number of samples for each pathology, we provide only descriptive data to assess possible trends in cfp-DNA variation. Conclusion: While cfp-DNA levels outside of the normal range may reflect placental distress, this relationship may be masked by a number of physiological confounders. The independence of cfp-DNA from β-hCG levels commonly assessed in pregnancy need to be further addressed.
Sex Differences in Mental Stress‐Induced Myocardial Ischemia in Patients With Coronary Heart Disease
Authors: Vaccarino Viola , Wilmot Kobina , Mheid Ibhar Al , Ramadan Ronnie , Pimple Pratik , Shah Amit J. , Garcia Ernest V. , Nye Jonathon , Ward Laura , Hammadah Muhammad , Kutner Michael , Long Qi , Bremner J. Douglas , Esteves Fabio , Raggi Paolo , Quyyumi Arshed A.
Published: August 2016

Background

Emerging data suggest that young women with coronary heart disease (
CHD
) are disproportionally vulnerable to the adverse cardiovascular effects of psychological stress. We hypothesized that younger, but not older, women with stable
CHD
are more likely than their male peers to develop mental stress‐induced myocardial ischemia (
MSIMI
).

Methods and Results

We studied 686 patients (191 women) with stable coronary heart disease (
CHD
). Patients underwent
99m
Tc‐sestamibi myocardial perfusion imaging at rest and with both mental (speech task) and conventional (exercise/pharmacological) stress testing. We compared quantitative (by automated software) and visual parameters of inducible ischemia between women and men and assessed age as an effect modifier. Women had a more‐adverse psychosocial profile than men whereas there were few differences in medical history and
CHD
risk factors. Both quantitative and visual indicators of ischemia with mental stress were disproportionally larger in younger women. For each 10 years of decreasing age, the total reversibility severity score with mental stress was 9.6 incremental points higher (interaction,
P
<0.001) and the incidence of
MSIMI
was 82.6% higher (interaction,
P
=0.004) in women than in men. Incidence of
MSIMI
in women ≤50 years was almost 4‐fold higher than in men of similar age and older patients. These results persisted when adjusting for sociodemographic and medical risk factors, psychosocial factors, and medications. There were no significant sex differences in inducible ischemia with conventional stress.

Conclusions

Young women with stable
CHD
are susceptible to
MSIMI
, which could play a role in the prognosis of this group.