bluuebunny/crossref_metadata_2025 huggingface dataset:
Population Pharmacokinetics and Safety of Solithromycin following Intravenous and Oral Administration in Infants, Children, and Adolescents
Authors: Gonzalez Daniel , James Laura P. , Al-Uzri Amira , Bosheva Miroslava , Adler-Shohet Felice C. , Mendley Susan R. , Bradley John S. , Espinosa Claudia , Tsonkova Eva , Moffett Kathryn , Marquez Lucila , Simonsen Kari A. , Stoilov Stefan , Boakye-Agyeman Felix , Jasion Theresa , Hornik Christoph P. , Hernandez Robert , Benjamin Daniel K. , Cohen-Wolkowiez Michael
Published: June 2018

Solithromycin is a novel fluoroketolide antibiotic which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children.
Revisiting the Lyme Disease Serodiagnostic Algorithm: the Momentum Gathers
Authors: Marques Adriana R.
Published: June 2018

Lyme disease is a tick-borne illness caused by
Borreliella
(
Borrelia
)
burgdorferi
, and it is the most common vector-borne disease in the United States, with an estimated incidence of 300,000 cases per year. The currently recommended approach for laboratory support of the diagnosis of Lyme disease is a standard two-tiered (STT) algorithm comprised of an enzyme-linked immunoassay (EIA) or immunofluorescence assay (IFA), followed by Western blotting (WB).
Genomic Insight into Symbiosis-Induced Insect Color Change by a Facultative Bacterial Endosymbiont, “
Candidatus
Rickettsiella viridis”
Authors: Nikoh Naruo , Tsuchida Tsutomu , Maeda Taro , Yamaguchi Katsushi , Shigenobu Shuji , Koga Ryuichi , Fukatsu Takema
Published: June 2018

Members of the genus
Rickettsiella
are bacterial pathogens of insects and other arthropods. Recently, a novel facultative endosymbiont, “
Candidatus
Rickettsiella viridis,” was described in the pea aphid
Acyrthosiphon pisum
, whose infection causes a striking host phenotype: red and green genetic color morphs exist in aphid populations, and upon infection with the symbiont, red aphids become green due to increased production of green polycyclic quinone pigments. Here we determined the complete genome sequence of the symbiont. The 1.6-Mb circular genome, harboring some 1,400 protein-coding genes, was similar to the genome of entomopathogenic
Rickettsiella grylli
(1.6 Mb) but was smaller than the genomes of phylogenetically allied human pathogens
Coxiella burnetii
(2.0 Mb) and
Legionella pneumophila
(3.4 Mb). The symbiont’s metabolic pathways exhibited little complementarity to those of the coexisting primary symbiont
Buchnera aphidicola
, reflecting the facultative nature of the symbiont. The symbiont genome harbored neither polyketide synthase genes nor the evolutionarily allied fatty acid synthase genes that are suspected to catalyze the polycyclic quinone synthesis, indicating that the green pigments are produced not by the symbiont but by the host aphid. The symbiont genome retained many type IV secretion system genes and presumable effector protein genes, whose homologues in
L. pneumophila
were reported to modulate a variety of the host's cellular processes for facilitating infection and virulence. These results suggest the possibility that the symbiont is involved in the green pigment production by affecting the host’s metabolism using the secretion machineries for delivering the effector molecules into the host cells.

IMPORTANCE
Insect body color is relevant to a variety of biological aspects such as species recognition, sexual selection, mimicry, aposematism, and crypsis. Hence, the bacterial endosymbiont “
Candidatus
Rickettsiella viridis,” which alters aphid body color from red to green, is of ecological interest, given that different predators preferentially exploit either red- or green-colored aphids. Here we determined the complete 1.6-Mb genome of the symbiont and uncovered that, although the red-green color transition was ascribed to upregulated production of green polycyclic quinone pigments, the symbiont genome harbored few genes involved in the polycyclic quinone biosynthesis. Meanwhile, the symbiont genome contained type IV secretion system genes and presumable effector protein genes, whose homologues modulate eukaryotic cellular processes for facilitating infection and virulence in the pathogen
Legionella pneumophila
. We propose the hypothesis that the symbiont may upregulate the host’s production of polycyclic quinone pigments via cooption of secretion machineries and effector molecules for pathogenicity.
Online Parallel-Machine Scheduling in KRT Environment to Minimize Total Weighted Completion Time
Authors: Li Wenjie , Liu Hailing , Li Shisheng
Published: June 2018

This paper studies online scheduling on [Formula: see text] identical parallel machines under the KRT environment, where jobs arrive over time and “KRT” means that in the online setting no jobs can be released when all of the machines are busy. The goal is to determine a feasible schedule to minimize the total of weighted completion times. When [Formula: see text], we prove that WSPT is an optimal online algorithm. When [Formula: see text], we first present a lower bound [Formula: see text], and then show that WSPT is a 2-competitive online algorithm for the case [Formula: see text]. For the case in which [Formula: see text] and all jobs have equal processing times, we provide a best possible online algorithm with a competitive ratio of [Formula: see text].
Finiteness of the set of virtual knots with a given state number
Authors: Nakamura Takuji , Nakanishi Yasutaka , Satoh Shin
Published: June 2018

A state of a virtual knot diagram [Formula: see text] is a collection of circles obtained from [Formula: see text] by splicing all the real crossings. For each integer [Formula: see text], we denote by [Formula: see text] the number of states of [Formula: see text] with [Formula: see text] circles. The [Formula: see text]-state number [Formula: see text] of a virtual knot [Formula: see text] is the minimum number of [Formula: see text] for [Formula: see text] of [Formula: see text]. Let [Formula: see text] be the set of virtual knots [Formula: see text] with [Formula: see text] for an integer [Formula: see text]. In this paper, we study the finiteness of [Formula: see text]. We determine the finiteness of [Formula: see text] for any [Formula: see text] and [Formula: see text] for any [Formula: see text].
Half-exact coherent functors over Dedekind domains
Authors: Banda Adson
Published: June 2018

Let [Formula: see text] be a principal ideal domain (PID) or more generally a Dedekind domain and let [Formula: see text] be a coherent functor from the category of finitely generated [Formula: see text]-modules to itself. We classify the half-exact coherent functors [Formula: see text]. In particular, we show that if [Formula: see text] is a half-exact coherent functor over a Dedekind domain [Formula: see text], then [Formula: see text] is a direct sum of functors of the form [Formula: see text], [Formula: see text] and [Formula: see text], where [Formula: see text] is a finitely generated projective [Formula: see text]-module, [Formula: see text] a nonzero prime ideal in [Formula: see text] and [Formula: see text].
Interactive Visualization for Group Decision Analysis
Authors: Bajracharya S. , Carenini G. , Chamberlain B. , Chen K. , Klein D. , Poole D. , Taheri H. , Öberg G.
Published: June 2018

Identifying the best solutions to large infrastructure decisions is a context-dependent multi-dimensional multi-stakeholder challenge in which competing objectives must be identified and trade-offs made. Our aim is to identify and explore features in an interactive visualization tool to help make group decision analysis more participatory, transparent, and comprehensible. We extended the interactive visualization tool ValueCharts to create Group ValueCharts. The new tool was introduced in two real-world scenarios in which stakeholders were in the midst of wrestling with decisions about infrastructure investment. We modeled the alternatives under consideration, for both scenarios, using prescribed criteria identified by domain experts. Participants in both groups were given instructions on how to use the tool to represent their preferences. Preferences for all participants were then displayed and discussed. The discussions were audio-recorded and the participants were surveyed to evaluate usability. The results indicate that participants felt the tool improved group interaction and information exchange and made the discussion more participatory. They expressed that visualizing individual preferences improved the ability to analyze decision outcomes based on everyone’s preferences. Additionally, the participants strongly concurred that the tool revealed disagreements and agreements and helped identify sticking points. These results suggest that a group decision tool that allows group members to input their individual preferences and then collectively probe into any differences makes the process of decision-making more participatory, transparent, and comprehensible and increases the quality and quantity of information exchange.
Robotic control for cognitive UWB radar
Authors: Brüggenwirth Stefan , Rial Fernando
Published: June 2018

In the paper, we describe a trajectory planning problem for a six-DoF robotic manipulator arm that carries an ultra-wideband (UWB) radar sensor with synthetic aperture (SAR). The resolution depends on the trajectory and velocity profile of the sensor head. The constraints can be modeled as an optimization problem to obtain a feasible, collision-free target trajectory of the end-effector of the manipulator arm in Cartesian coordinates that minimizes observation time. For 3D reconstruction, the target is observed in multiple height slices. For through-the-wall radar the sensor can be operated in sliding mode for scanning larger areas. For IED inspection the spotlight mode is preferred, constantly pointing the antennas towards the target to obtain maximum azimuth resolution. UWB sensors typically use a wide spectrum shared by other RF communication systems. This may become a limiting factor on system sensitivity and severely degrade the image quality. Cognitive radars can adapt dynamically their bandwidth, frequency and other transmit parameters to the radio frequency environment to avoid interference with primary users.
Law and History: Mirror of Government in China
Authors: Wang Gungwu
Published: June 2018

This text is the revised version of the transcript of my lecture “Chinese Historiography, on History as a Mirror of Government” that was given at the Nanyang Technological University on 23rd March 2018 as part of the 3rd UBIAS Intercontinental Academia (ICA) on Laws: Rigidity and Dynamics.
NUMA-Caffe
Authors: Roy Probir , Song Shuaiwen Leon , Krishnamoorthy Sriram , Vishnu Abhinav , Sengupta Dipanjan , Liu Xu
Published: June 2018

Convolution Neural Networks (CNNs), a special subcategory of Deep Learning Neural Networks (DNNs), have become increasingly popular in industry and academia for their powerful capability in pattern classification, image processing, and speech recognition. Recently, they have been widely adopted in High Performance Computing (HPC) environments for solving complex problems related to modeling, runtime prediction, and big data analysis. Current state-of-the-art designs for DNNs on modern multi- and many-core CPU architectures, such as variants of Caffe, have reported promising performance in speedup and scalability, comparable with the GPU implementations. However, modern CPU architectures employ
Non-Uniform Memory Access
(NUMA) technique to integrate multiple sockets, which incurs unique challenges for designing highly efficient CNN frameworks. Without a careful design, DNN frameworks can easily suffer from long memory latency due to a large number of memory accesses to remote NUMA domains, resulting in poor scalability. To address this challenge, we propose NUMA-aware multi-solver-based CNN design, named
NUMA-Caffe
, for accelerating deep learning neural networks on multi- and many-core CPU architectures. NUMA-Caffe is independent of DNN topology, does not impact network convergence rates, and provides superior scalability to the existing Caffe variants. Through a thorough empirical study on four contemporary NUMA-based multi- and many-core architectures, our experimental results demonstrate that NUMA-Caffe significantly outperforms the state-of-the-art Caffe designs in terms of both throughput and scalability.
DDRNoC
Authors: Ejaz Ahsen , Papaefstathiou Vassilios , Sourdis Ioannis
Published: June 2018

This article introduces DDRNoC, an on-chip interconnection network capable of routing packets at Dual Data Rate. The cycle time of current 2D-mesh Network-on-Chip routers is limited by their control as opposed to the datapath (switch and link traversal), which exhibits significant slack. DDRNoC capitalizes on this observation, allowing two flits per cycle to share the same datapath. Thereby, DDRNoC achieves higher throughput than a Single Data Rate (SDR) network. Alternatively, using lower voltage circuits, the above slack can be exploited to reduce power consumption while matching the SDR network throughput. In addition, DDRNoC exhibits reduced clock distribution power, improving energy efficiency, as it needs a slower clock than a SDR network that routes packets at the same rate. Post place and route results in 28nm technology show that, compared to an iso-voltage (1.1V) SDR network, DDRNoC improves throughput proportionally to the SDR datapath slack. Moreover, a low-voltage (0.95V) DDRNoC implementation converts that slack to power reduction offering the 1.1V SDR throughput at a substantially lower energy cost.
Real-Time Inland CCTV Ship Tracking
Authors: Xiao Lei , Xu Minghai , Hu Zhongyi
Published: June 2018

The predator algorithm is a representative pioneering work that achieves state-of-the-art performance on several popular visual tracking benchmarks and with great success when commercially applied to real-time face tracking in long-term unconstrained videos. However, there are two major drawbacks of predator algorithm when applied to inland CCTV (closed-circuit television) ship tracking. First, the LK short-term tracker within predator algorithm easily tends to drift if the target ship suffers partial or even full occlusion, mainly because the corner-points-like features employed by LK tracker are very sensitive to occlusion appearance change. Second, the cascaded detector within the predator algorithm searches for candidate objects in a predefined scale set, usually including 3-5 elements, which hampers the tracker to adapt to the potential diverse scale variations of the target ship. In this paper, we design a random projection based short-term tracker which can dramatically ease the tracking drift when the ship is under occlusion. Furthermore, a forward-backward feedback mechanism is proposed to estimate the scale variation between two consecutive frames. We prove that these two strategies gain significant improvements over the predator algorithm and also show that the proposed method outperforms several other state-of-the-art trackers.
The Regulation of Inflammation by Innate and Adaptive Lymphocytes
Authors: Cronkite David Alex , Strutt Tara M.
Published: June 2018

Inflammation plays an essential role in the control of pathogens and in shaping the ensuing adaptive immune responses. Traditionally, innate immunity has been described as a rapid response triggered through generic and nonspecific means that by definition lacks the ability to remember. Recently, it has become clear that some innate immune cells are epigenetically reprogrammed or “imprinted” by past experiences. These “trained” innate immune cells display altered inflammatory responses upon subsequent pathogen encounter. Remembrance of past pathogen encounters has classically been attributed to cohorts of antigen-specific memory T and B cells following the resolution of infection. During recall responses, memory T and B cells quickly respond by proliferating, producing effector cytokines, and performing various effector functions. An often-overlooked effector function of memory CD4 and CD8 T cells is the promotion of an inflammatory milieu at the initial site of infection that mirrors the primary encounter. This memory-conditioned inflammatory response, in conjunction with other secondary effector T cell functions, results in better control and more rapid resolution of both infection and the associated tissue pathology. Recent advancements in our understanding of inflammatory triggers, imprinting of the innate immune responses, and the role of T cell memory in regulating inflammation are discussed.
Protective Effect of Ginkgo biloba and Magnetized Water on Nephropathy in Induced Type 2 Diabetes in Rat
Authors: Zayed Ahmed E. , Saleh Ahmed , Gomaa Asmaa M. S. , Abd-Elkareem Mahmoud , Anwar Mamdouh M. , Hassanein Khaled M. A. , Elsherbiny Mohsen M. , Kotb Ahmed M.
Published: June 2018

We aimed in our current study to explore the protective effect of Ginkgo biloba (GB) and magnetized water (MW) against nephrotoxicity associating induced type 2 diabetes mellitus in rat. Here, we induced diabetes by feeding our lab rats on a high fat‐containing diet (4 weeks) and after that injecting them with streptozotocin (STZ). We randomly divided forty rats into four different groups: nontreated control (Ctrl), nontreated diabetic (Diabetic), Diabetic+GB (4‐week treatment), and Diabetic+MW (4‐week treatment). After the experiment was finished, serum and kidney tissue samples were gathered. Blood levels of glucose, triglycerides, cholesterol, creatinine, and urea were markedly elevated in the diabetic group than in the control group. In all animals treated with GB and MW, the levels of urea, creatinine, and glucose were significantly reduced (all P < 0.01). GB and MW attenuated glomerular and tubular injury as well as the histological score. Furthermore, they normalized the contents of glutathione reductase and SOD2. In summary, our data showed that GB and MW treatment protected type 2 diabetic rat kidneys from nephrotoxic damages by reducing the hyperlipidemia, uremia, oxidative stress, and renal dysfunction.
Evaluation of the Wound Healing Activity of the Crude Extract of Leaves of Acanthus polystachyus Delile (Acanthaceae)
Authors: Demilew Wubante , Adinew Getnet Mequanint , Asrade Seyfe
Published: June 2018

Background. Medicinal plants play indispensable roles to treat various ailments. Acanthus polystachyus is one of the medicinal plants used traditionally for treatment of wounds. However, there were no scientific reports documented so far on the wound healing activities of this plant. Thus, the present study provides a scientific evaluation for the wound healing potential of the crude extract of A. polystachyus leaves. Methods. The crude extraction was carried out using 80% methanol. The crude extract was prepared in 5% (w/w) and 10% (w/w) ointment and evaluated for wound healing activity using excision, infected, and incision wound models in Swiss albino mice. Results. Both 5%  and 10% (w/w) ointments significantly reduced period of epithelialization and increased wound contraction rate and tensile strength compared to the negative control group (P < 0.05). The wound healing activity of 10% (w/w) ointment treated group was greater than 5% (w/w) and nitrofurazone ointment treated groups in S. aureus infected wound model. Conclusion. These results demonstrate that the crude extract of A. polystachyus leaves possesses wound healing activities. This justifies the traditional claimed use of the plant for treating uninfected and infected wounds caused by S. aureus.
Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats
Authors: Seo Mi Kyoung , Kim Young Hoon , McIntyre Roger S. , Mansur Rodrigo B. , Lee Yena , Carmona Nicole E. , Choi Ah Jeong , Kim Gyung-Mee , Lee Jung Goo , Park Sung Woo
Published: June 2018

Recent studies have shown that antipsychotic drugs have epigenetic effects. However, the effects of antipsychotic drugs on histone modification remain unclear. Therefore, we investigated the effects of antipsychotic drugs on the epigenetic modification of the BDNF gene in the rat hippocampus. Rats were subjected to chronic restraint stress (6 h/d for 21 d) and then were administered with either olanzapine (2 mg/kg) or haloperidol (1 mg/kg). The levels of histone H3 acetylation and MeCP2 binding at BDNF promoter IV were assessed with chromatin immunoprecipitation assays. The mRNA levels of total BDNF with exon IV, HDAC5, DNMT1, and DNMT3a were assessed with a quantitative RT-PCR procedure. Chronic restraint stress resulted in the downregulation of total and exon IV BDNF mRNA levels and a decrease in histone H3 acetylation and an increase in MeCP2 binding at BDNF promoter IV. Furthermore, there were robust increases in the expression of HDAC5 and DNMTs. Olanzapine administration largely prevented these changes. The administration of haloperidol had no effect. These findings suggest that the antipsychotic drug olanzapine induced histone modification of BDNF gene expression in the hippocampus and that these epigenetic alterations may represent one of the mechanisms underlying the actions of antipsychotic drugs.
Severe Postpartum Hemorrhage Complicated with Liver Infarction Resulting in Hepatic Failure Necessitating Liver Transplantation
Authors: Peng I-Ting , Chung Ming-Ting , Lin Ching-Chung
Published: June 2018

Postpartum hemorrhage remains a major threat to maternal health. Intervention after critical blood loss or development of disseminated intravascular coagulation may lead to disastrous organ failure and poor outcomes. A 30-year-old woman was transferred to our emergency department due to massive postpartum hemorrhage. Shock and disseminated intravascular coagulation ensued, and the patient’s condition quickly deteriorated. We performed an emergency hysterectomy, but blood loss had been massive. Moreover, there was another episode of internal bleeding that led to further blood loss. Ischemic injury to the liver was tremendous, with resulting progressive jaundice and hepatic encephalopathy. The patient required liver transplantation. Imaging studies and operative findings showed a large area of hepatic infarction. Unfortunately, the patient died of intractable sepsis shortly after liver transplantation. Disseminated intravascular coagulation and resultant hepatic infarction combined with ischemic hepatitis were the direct cause of death in our case.
Individual, Group, and Organizational Factors Affecting Group Bidding Decisions for Construction Projects
Authors: Yan Peng , Liu Junying , Skitmore Martin
Published: June 2018

Deciding whether bid for the construction project is classic risk‐based decision‐making that is crucial to the survival and prosperousness of construction companies. More contractors are adopting group bidding decision‐making to reduce the number of incorrect decisions. However, previous related studies mainly focus on project factors that overlook the members of bidding groups and the interaction between bidding group members. The aim of this paper, therefore, is to investigate the potential factors that influence group bidding decision‐making for construction projects. Twenty factors relating to individual, group, and organizational levels are identified through a literature review and interviews with experienced practitioners. A questionnaire survey of 203 Chinese international contractors is conducted to obtain the importance of the factors involved. The results of the ranking analysis indicate 14 critical factors, among which “risk perception” and “team decision preference” are regarded as the two most significant. Moreover, 20 factors can be classified into five groupings: (1) values and strategic goals, (2) collaboration and learning orientation, (3) consensus reaching, (4) risk awareness, and (5) empowerment and development, with risk awareness having an especially strong influence. This research deepens the understanding of factors belonging to different organizational levels that need to be highlighted during the group bidding decision‐making process and provides strategies for bidding groups and their companies to improve their decision performance.
Genetic Algorithm Based QoS Perception Routing Protocol for VANETs
Authors: Zhang Guoan , Wu Min , Duan Wei , Huang Xinming
Published: June 2018

A genetic algorithm (GA) based QoS perception routing protocol (GABR) is proposed to guarantee the quality of service (QoS) influenced by broken links between vehicles and the failure of packets transmission in a vehicular ad hoc network (VANET). With the observation that all improvable paths are probed by the intersection based routing protocol, the genetic GA is utilized to optimize the global available paths which satisfies the QoS requirement. Moreover, by means of the numerical results, it is shown that the proposed scheme is significantly improved compared with protocols of the intersection based routing (IBR) and connectivity aware routing (CAR) in terms of transmission delay and packet loss rate.
Oxidative and Antioxidative Stress Status in Children with Inflammatory Bowel Disease as a Result of a Chronic Inflammatory Process
Authors: Grzybowska-Chlebowczyk Urszula , Wysocka-Wojakiewicz Paulina , Jasielska Martyna , Cukrowska Bożena , Więcek Sabina , Kniażewska Maria , Chudek Jerzy
Published: June 2018

Oxidative stress (OS) has been recently implicated in the disease pathogenesis in inflammatory bowel disease (IBD). The aim of the study was to evaluate oxidative and antioxidative stress status and the risk of the atherosclerotic process in children with IBD and functional gastrointestinal disorders (FGID). The prospective study included a group of 71 children during a period of 2 years. In all children, laboratory tests were performed and intima-media complex in the carotid artery was measured (IMC). Low values of OS were more frequent in children with IBD than in the FGID group. The average concentration of oxidized lipoprotein with average density (oxLDL) was lower in patients with IBD. Among patients with IBD, higher concentrations of oxLDL were recorded in patients with longer-duration disease and with higher concentrations of total cholesterol. In the IBD group, more often, higher concentrations of anti-oxLDL were recorded among patients with longer-duration disease. The obtained results did not support the hypothesis of total antioxidant capacity depletion and greater overall OS in patients with IBD. Patients with IBD with a longer duration of the disease have higher concentrations of oxLDL and anti-oxLDL.
Giant Adrenal Myelolipoma in a Patient without Endocrine Disorder: A Case Report and a Review of the Literature
Authors: Nakayama Yoshifumi , Matayoshi Nobutaka , Akiyama Masaki , Sawatsubashi Yusuke , Nagata Jun , Hisaoka Masanori , Hirata Keiji
Published: June 2018

We herein present a surgically treated case of huge adrenal myelolipoma. A 62-year-old woman presented to our surgical outpatient clinic with a retroperitoneal tumor. A clinical examination revealed an elastic soft, smooth-surfaced, painless, child-head-sized tumor with poor mobility, which was located in the left upper abdomen. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen revealed an uneven tumor surrounding the stomach, spleen, pancreas, and left kidney, which was 20 × 18 × 10 cm in size. The retroperitoneal tumor was resected. The tumor was attached to the surrounding organs, including the pancreas, spleen, and left kidney, but had not directly invaded these organs. The tumor was yellow and elastic soft and covered with a thin film. The origin of the tumor was suggested to be the left adrenal gland. The weight of the excised tumor was 1500 g. The histopathological diagnosis was adrenal myelolipoma. The patient had an uneventful recovery and was discharged from the hospital on the thirteenth day after the operation. She has been followed up in our outpatient clinic.
Pancreas as an Occult Source of Recurrent Salmonella enteritidis Bacteremia in an Immunocompromised Patient
Authors: Tai Don Bambino Geno , Upadhyay Laxmi , Jain Ruchika , Goldstein Robert
Published: June 2018

Salmonella infection usually presents as gastroenteritis and enteric fever. Some cases of bacteremia can lead to invasion of different organ systems and become occult sources for recurrence. Almost all organs of the body can be affected and have been reported in the literature. We report a rare case of repeated Salmonella enteritidis infection in a patient with systemic lupus erythematosus. She was treated with intravenous and oral antibiotics but still had recurrence of fevers and bacteremia. After a thorough workup, pancreatic abscesses were identified and drained with abscess culture revealing Salmonella enteritidis. She was then treated with a prolonged course of antibiotics and finally cleared the infection. This case demonstrates that nontyphoid Salmonella can be invasive and cause persistent infection. This is particularly pertinent in immunocompromised patients who are at an increased risk of infection. An aggressive workup and prolonged antibiotic course might be beneficial for this subset of patients.
Diagnostic Markers for Nonspecific Inflammatory Bowel Diseases
Authors: Derkacz Alicja , Olczyk Pawel , Komosinska-Vassev Katarzyna
Published: June 2018

The nonspecific inflammatory bowel diseases (IBD) represent a heterogeneous group of chronic inflammatory disorders of the gastrointestinal tract, and Leśniowski-Crohn’s disease (CD) and ulcerative colitis (UC) are among the two major clinical forms. Despite the great progress in understanding the pathogenesis of these diseases, their etiology remains unclear. Genetic, immune, and environmental factors are thought to play a key role. The correct diagnosis of nonspecific inflammatory bowel diseases as well as the determination of disease activity, risk stratification, and prediction of response to therapy still relies on a multidisciplinary approach based on clinical, laboratory, endoscopic, and histologic examination. However, considerable effort has been devoted to the development of an accurate panel of noninvasive biomarkers that have increased diagnostic sensitivity and specificity. Laboratory biomarkers useful in differentiating IBD with functional disorders and in evaluating disease activity, prognosis, and treatment selection for IBD are presented in this study.
Robustness of Time Reversal versus All‐Rake Transceivers in Multiple Access Channels
Authors: De Nardis Luca , Fiorina Jocelyn , Ferrante Guido Carlo , Di Benedetto Maria-Gabriella
Published: June 2018

Time reversal (TR) is an effective solution in both single user and multiuser communications for moving complexity from the receiver to the transmitter, in comparison to traditional postfiltering based on Rake receivers. Imperfect channel estimation may, however, affect pre‐ versus postfiltering schemes in a different way; this paper analyzes the robustness of time reversal versus All‐Rake (AR) transceivers, in multiple access communications, with respect to channel estimation errors. Two performance indicators are adopted in the analysis: symbol error probability and spectral efficiency. Analytic expressions for both indicators are derived and used as the basis for simulation‐based performance evaluation. Results show that while TR leads to slight performance advantage over AR when channel estimation is accurate, its performance is severely degraded by large channel estimation errors, indicating a clear advantage for AR receivers in this case, in particular when extremely short impulsive waveforms are adopted. Results however also show a stronger non‐Gaussianity of interference in the TR case suggesting that the adoption of a receiver structure adapted to non‐Gaussian interference might tilt the balance towards TR.
Prevalence and Associated Factors of Suicide Ideation and Attempt among Adolescent High School Students in Dangila Town, Northwest Ethiopia
Authors: Amare Tadele , Meseret Woldeyhannes Solomon , Haile Kelemua , Yeneabat Tebikew
Published: June 2018

Background. Suicide is a major public health problem and is common among adolescents worldwide. The true extent of the problem in Ethiopia is difficult to ascertain as suicides and suicidal behavior are significantly underreported and understudied. Objective. We assessed the prevalence and factors associated with suicide ideation and suicide attempt among adolescent high school students in Dangila Town, Ethiopia. Methods. This school-based cross-sectional study was conducted from April to May 2015 in Dangila Town. Data were collected from adolescent high school students using pretested, self-administered Amharic-language questionnaire. We conducted bivariable and multivariable logistic regression to identify the independent factors associated with suicide ideation and attempt. Results. A total of 573 of 603 sampled students participated in the study (95% response rate). The mean (±SD) age of the respondents was 17.52 (±0.97) years. The minimum and maximum ages were 15 and 19 years, respectively. The prevalence of suicide ideation and attempt was 22.5% and 16.2%, respectively. School absenteeism [AOR 4.30, 95% CI (2.03, 9.10)] and poor social support [AOR 5.58, 95% CI (2.25, 13.84)] were positively associated with suicide ideation. Poor social support [AOR 4.55, 95% CI (1.40, 14.77)] and being physically hurt [AOR 4.25, 95% CI (1.77, 10.20)] were positively associated with suicide attempt. Unlike previous studies of adolescents in low-income countries, we find no association between gender or alcohol use and suicidal thoughts or attempts. Conclusion. This study revealed that at least one in five of the adolescents in our sample had experienced suicide ideation and one in six had attempted suicide. School absenteeism, poor social support, and experience of violence were identified as independent contributors to suicide ideation and attempt. These findings suggest a need for education policymakers to implement school-based behavioral therapy programs in collaboration with health institutions and programs to provide social support for vulnerable students.
Reconstruction of Photoreceptor Outer Layers after Steroid Therapy in Solar Retinopathy
Authors: Nakamura Masaki , Komatsu Koji , Katagiri Satoshi , Hayashi Takaaki , Nakano Tadashi
Published: June 2018

Purpose. To report the clinical course of solar retinopathy after steroid therapy. Case Presentation. A 45-year-old male gazed at the sun and noticed bilateral central scotoma and decreased vision after the episode. After 7 weeks from onset, ophthalmic examinations were firstly performed. Decimal best corrected visual acuity (BCVA) was decreased to 0.8 and 0.7 in the right and left eyes. Funduscopy showed a tiny, yellowish spot in the fovea bilaterally. Corresponding to the lesion, optical coherence tomography (OCT) images showed an elevated and blurred ellipsoid zone and loss of the interdigitation zone. A posterior sub-Tenon triamcinolone injection in the right eye and oral prednisolone therapy were performed as a medication. BCVA was improved to 1.2 and 1.0 in the right and left eyes at 9 weeks after medication. OCT images showed ellipsoid zone was gradually improved bilaterally, which became nearly normal at 4 weeks in the right eye and at 21 weeks in the left eye. The loss of the interdigitation zone remained at 12 weeks in the right eye and at 21 weeks at the left eye. Conclusions. We described a case with solar retinopathy who exhibited anatomical recovery of the photoreceptor outer layers by steroid therapy, started after 7 weeks from onset.
Pseudomonas aeruginosa Isolates from Spanish Children: Occurrence in Faecal Samples, Antimicrobial Resistance, Virulence, and Molecular Typing
Authors: Ruiz-Roldán Lidia , Bellés Alba , Bueno Jessica , Azcona-Gutiérrez José Manuel , Rojo-Bezares Beatriz , Torres Carmen , Castillo F. Javier , Sáenz Yolanda , Seral Cristina
Published: June 2018

Pseudomonas aeruginosa is a major opportunistic human pathogen, responsible for nosocomial infections and infections in patients with impaired immune systems. Little data exist about the faecal colonisation by P. aeruginosa isolates in healthy humans. The occurrence, antimicrobial resistance phenotype, virulence genotype, and genetic lineages of P. aeruginosa from faecal samples of children from two different Spanish regions were characterised. Seventy-two P. aeruginosa were isolated from 1,443 faecal samples. Low antimicrobial resistance levels were detected: ceftazidime (8%), cefepime (7%), aztreonam (7%), gentamicin (3%), ciprofloxacin (1%), and imipenem (1%); susceptibility to meropenem, amikacin, tobramycin, levofloxacin, and colistin. Four multidrug-resistant strains were found. Important differences were detected between both geographical regions. Forty-one sequence types were detected among the 48 tested strains. Virulence and quorum sensing genes were analysed and 13 virulotypes were detected, being 26 exoU-positive strains. Alteration in protein OprD showed eight different patterns. The unique imipenem-resistant strain showed a premature stop codon in OprD. Intestinal colonisation by P. aeruginosa, mainly by international clones (as ST244, ST253, and ST274), is an important factor for the systemic infections development and the environmental dissemination. Periodic active surveillance is useful to identify these community human reservoirs and to control the evolution of antibiotic resistance and virulence activity.
Thyroid Storm and Complete Heart Block after Treatment with Radioactive Iodine
Authors: Vennard Kaitlyn , Gilbert Matthew P.
Published: June 2018

Thyroid storm is a rare endocrine emergency characterized by dysfunction of multiple organ systems. Thyroid storm is more common in Graves’ disease and can be precipitated by surgery, trauma, infection, metabolic abnormalities, iodine load, and parturition. We present a diagnostically challenging case of thyroid storm precipitated by radioiodine therapy and accompanied by bradycardia, a rare but life-threatening complication related to treatment for hyperthyroidism.
Aberrant FGFR Tyrosine Kinase Signaling Enhances the Warburg Effect by Reprogramming LDH Isoform Expression and Activity in Prostate Cancer
Authors: Liu Junchen , Chen Guo , Liu Zezhen , Liu Shaoyou , Cai Zhiduan , You Pan , Ke Yuepeng , Lai Li , Huang Yun , Gao Hongchang , Zhao Liangcai , Pelicano Helene , Huang Peng , McKeehan Wallace L. , Wu Chin-Lee , Wang Cong , Zhong Weide , Wang Fen
Published: June 2018

The acquisition of ectopic fibroblast growthfactor receptor 1 (FGFR1) expression is well documented in prostate cancer progression. How it contributes to prostate cancer progression is not fully understood, although it is known to confer a growth advantage and promote cell survival. Here, we report that FGFR1 tyrosine kinase reprograms the energy metabolism of prostate cancer cells by regulating the expression of lactate dehydrogenase (LDH) isozymes. FGFR1 increased LDHA stability through tyrosine phosphorylation and reduced LDHB expression by promoting its promoter methylation, thereby shifting cell metabolism from oxidative phosphorylation to aerobic glycolysis. LDHA depletion compromised, whereas LDHB depletion enhanced the tumorigenicity of prostate cancer cells. Furthermore, FGFR1 overexpression and aberrant LDH isozyme expression were associated with short overall survival and biochemical recurrence times in patients with prostate cancer. Our results indicate that ectopic FGFR1 expression reprograms the energy metabolism of prostate cancer cells, representing a hallmark change in prostate cancer progression.

Significance: FGF signaling drives the Warburg effect through differential regulation of LDHA and LDHB, thereby promoting the progression of prostate cancer.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4459/F1.large.jpg. Cancer Res; 78(16); 4459–70. ©2018 AACR.
Licofelone Enhances the Efficacy of Paclitaxel in Ovarian Cancer by Reversing Drug Resistance and Tumor Stem-like Properties
Authors: Hirst Jeff , Pathak Harsh B. , Hyter Stephen , Pessetto Ziyan Y. , Ly Thuc , Graw Stefan , Koestler Devin C. , Krieg Adam J. , Roby Katherine F. , Godwin Andrew K.
Published: June 2018

Drug development for first-line treatment of epithelial ovarian cancer (EOC) has been stagnant for almost three decades. Traditional cell culture methods for primary drug screening do not always accurately reflect clinical disease. To overcome this barrier, we grew a panel of EOC cell lines in three-dimensional (3D) cell cultures to form multicellular tumor spheroids (MCTS). We characterized these MCTS for molecular and cellular features of EOC and performed a comparative screen with cells grown using two-dimensional (2D) cell culture to identify previously unappreciated anticancer drugs. MCTS exhibited greater resistance to chemotherapeutic agents, showed signs of senescence and hypoxia, and expressed a number of stem cell–associated transcripts including ALDH1A and CD133, also known as PROM1. Using a library of clinically repurposed drugs, we identified candidates with preferential activity in MCTS over 2D cultured cells. One of the lead compounds, the dual COX/LOX inhibitor licofelone, reversed the stem-like properties of ovarian MCTS. Licofelone also synergized with paclitaxel in ovarian MCTS models and in a patient-derived tumor xenograft model. Importantly, the combination of licofelone with paclitaxel prolonged the median survival of mice (>141 days) relative to paclitaxel (115 days), licofelone (37 days), or vehicle (30 days). Increased efficacy was confirmed by Mantel–Haenszel HR compared with vehicle (HR = 0.037) and paclitaxel (HR = 0.017). These results identify for the first time an unappreciated, anti-inflammatory drug that can reverse chemotherapeutic resistance in ovarian cancer, highlighting the need to clinically evaluate licofelone in combination with first-line chemotherapy in primary and chemotherapy-refractory EOC.

Significance: This study highlights the use of an in vitro spheroid 3D drug screening model to identify new therapeutic approaches to reverse chemotherapy resistance in ovarian cancer. Cancer Res; 78(15); 4370–85. ©2018 AACR.
A Rare Variant P507L in TPP1 Interrupts TPP1–TIN2 Interaction, Influences Telomere Length, and Confers Colorectal Cancer Risk in Chinese Population
Authors: Li Jiaoyuan , Chang Jiang , Tian Jianbo , Ke Juntao , Zhu Ying , Yang Yang , Gong Yajie , Zou Danyi , Peng Xiating , Yang Nan , Mei Shufang , Wang Xiaoyang , Cheng Liming , Hu Weiguo , Gong Jing , Zhong Rong , Miao Xiaoping
Published: June 2018

Background: Telomere dysfunction triggers cellular senescence and constitutes a driving force for cancer initiation. Genetic variants in genes involved in telomere maintenance may contribute to colorectal cancer susceptibility.

Methods: In this study, we firstly captured germline mutations in 192 patients with colorectal cancer by sequencing the coding regions of 13 core components implicated in telomere biology. Five potential functional variants were then genotyped and assessed in a case–control set with 3,761 colorectal cancer cases and 3,839 healthy controls. The promising association was replicated in additional 6,765 cases and 6,906 controls. Functional experiments were used to further clarify the potential function of the significant variant and uncover the underlying mechanism in colorectal cancer development.

Results: The two-stage association studies showed that a rare missense variant rs149418249 (c.C1520T and p.P507L) in the 11th exon of TPP1 (also known as ACD, gene ID 65057) was significantly associated with colorectal cancer risk with the ORs being 2.90 [95% confidence interval (CI), 1.04–8.07; P = 0.041], 2.50 (95% CI, 1.04–6.04; P = 0.042), and 2.66 (95% CI, 1.36–5.18; P = 0.004) in discovery, replication, and the combined samples, respectively. Further functional annotation indicated that the TPP1 P507L substitution interrupted TPP1–TIN2 interaction, impaired telomerase processivity, and shortened telomere length, which subsequently facilitated cell proliferation and promoted colorectal cancer development.

Conclusions: A rare variant P507L in TPP1 confers increased risk of colorectal cancer through interrupting TPP1–TIN2 interaction, impairing telomerase processivity, and shrinking telomere length.

Impact: These findings emphasize the important role of telomere dysfunction in colorectal cancer development, and provide new insights about the prevention of this type of cancer. Cancer Epidemiol Biomarkers Prev; 27(9); 1029–35. ©2018 AACR.
МЕТОДОЛОГІЯ ВИКЛАДАННЯ ГАСТРОЕНТЕРОЛОГІЇ СТУДЕНТАМ З АНГЛОМОВНОЮ ФОРМОЮ НАВЧАННЯ НА КАФЕДРІ ВНУТРІШНЬОЇ МЕДИЦИНИ № 2
Authors: Lykhatska H. V.
Published: June 2018

Мета роботи − вивчити методологію викладання гастроентерології англомовним студентам  на кафедрі внутрішньої медицини № 2.Основна частина. На кафедрі внутрішньої медицини № 2 проходять навчання іноземні студенти. Під час проведення практичного заняття викладач використовує індивідуальний підхід до кожного студента. Вивчення нового матеріалу відбувається у формі дискусії. Для цього використовуються  навчальні фільми, мультимедійні презентації тощо. Одним з основних методів контролю знань студентів є тестування. Крім оволодіння теоретичними знаннями, студент аналізує клінічну картину захворювання безпосередньо біля ліжка хворого. На циклі гастроентерології студенти розпізнають основні симптоми і синдроми при захворюваннях органів травлення, ознайомлюються з методами дослідження в гастроентерології, а також самостійно трактують результати проведених досліджень. На лекціях студенти фіксують лекційний матеріал. Ми дійшли висновку, що при поясненні матеріалу потрібно використовувати англійську термінологію, дублюючи її латинською та українською. Основний  лекційний матеріал краще подавати у вигляді логічних схем та таблиць з мінімальним текстовим навантаженням. Викладачі кафедри активно залучають англомовних студентів до участі у всеукраїнських конкурсах студентських наукових робіт. У цьому році наші студенти зайняли два призові місця у галузі “Гастроентерологія” на міжнародних медичних конгресах студентів та молодих учених. Колективом кафедри видано два англомовних підручники з основ внутрішньої медицини, що включають розділ з гастроентерології.Висновки. 1. Динамічне забезпечення педагогічного процесу новітніми інформаційними технологіями, систематичне оновлення навчальних матеріалів, включаючи стендові і тестові завдання, сприяють постійному підвищенню компетенції майбутніх професіоналів. 2. Якісна підготовка англомовних студентів з гастроентерології вимагає заходів з узагальнення здобутого теоретичного та клінічного матеріалу, формування у студента практичних навичок.
РЕАЛІЗАЦІЯ ДИДАКТИЧНИХ ПРИНЦИПІВ У ПРАКТИЦІ НАУКОВОЇ ПІДГОТОВКИ ІНОЗЕМНИХ СТУДЕНТІВ ДО НАВЧАННЯ В МЕДИЧНОМУ УНІВЕРСИТЕТІ
Authors: Lenchuk T. L.
Published: June 2018

Мета роботи – розкрити особливості реалізації основних дидактичних принципів у процесі загальнонаукової підготовки іноземних студентів до навчання у медичному вузі.Основна частина. Проаналізовано останні дослідження і публікації щодо підготовки іноземних студентів у ВНЗ. Реалізація принципу урахування рівня володіння мовою навчання означає, що при навчанні мовою-посередником (російською чи україн­ською) необхідно ураховувати етапи оволодіння нерідною мовою, їх недостатній словниковий запас у процесі підготовки. Так, на різних етапах навчання іноземні студенти-медики володіють по-різному обмеженим, а на початковому етапі вкрай не­достат­нім, лексичним арсеналом, мовними засобами і способами сприйняття й подання інформації.Висновки. Застосування загальних дидактичних принципів при навчанні іноземних студентів-медиків є необхідною, але недостатньою умовою для успішної організації навчального процесу, бо кожний із принципів у певних умовах залежить від контингенту іноземних студентів-медиків, рівня їх базової підготовки, володіння ними мовою-посередником (російською чи українською), їх психоемоційного стану, а також від характеру навчального матеріалу, певного навчального завдання та від інших факторів, що є специфічними саме для навчання нерідною мовою у нерідному середовищі.