bluuebunny/crossref_metadata_2025 huggingface dataset:
Document Language Models, Query Models, and Risk Minimization for Information Retrieval
Authors: Lafferty John , Zhai Chengxiang
Published: August 2017

We present a framework for information retrieval that combines document models and query models using a probabilistic ranking function based on Bayesian decision theory. The framework suggests an operational retrieval model that extends recent developments in the language modeling approach to information retrieval. A language model for each document is estimated, as well as a language model for each query, and the retrieval problem is cast in terms of risk minimization. The query language model can be exploited to model user preferences, the context of a query, synonomy and word senses. While recent work has incorporated word translation models for this purpose, we introduce a new method using Markov chains defined on a set of documents to estimate the query models. The Markov chain method has connections to algorithms from link analysis and social networks. The new approach is evaluated on TREC collections and compared to the basic language modeling approach and vector space models together with query expansion using Rocchio. Significant improvements are obtained over standard query expansion methods for strong baseline TF-IDF systems, with the greatest improvements attained for short queries on Web data.
On Cybersecurity Loafing and Cybercomplacency
Authors: Stafford Tom
Published: August 2017

As we begin to publish more articles in the area of cybersecurity, a case in point being the fine set of security papers presented in this particular issue as well as the upcoming special issue on Advances in Behavioral Cybersecurity Research which is currently in the review phase, it comes to mind that there is an emerging rubric of interest to the research community involved in security. That rubric concerns itself with the increasingly odd and inexplicable degree of comfort that computer users appear to have while operating in an increasingly threat-rich online environment. In my own work, I have noticed over time that users are blissfully unconcerned about malware threats (Poston et al., 2005; Stafford, 2005; Stafford and Poston, 2010; Stafford and Urbaczewski, 2004). This often takes the avenue of "it can't happen to me," or, "that's just not likely," but the fact is, since I first started noticing this odd nonchalance it seems like it is only getting worse, generally speaking. Mind you, a computer user who has been exploited and suffered harm from it will be vigilant to the end of his or her days, but for those who have scraped by, "no worries," is the order of the day, it seems to me.

This is problematic because the exploits that are abroad in the online world these days are a whole order of magnitude more harmful than those that were around when I first started studying the matter a decade ago. I would not have commented on the matter, having long since chalked it up to the oddities of civilian computing, so to speak, but an odd pattern I encountered when engaging in a research study with trained corporate users brought the matter back to the fore recently. I have been collecting neurocogntive data on user response to security threats, and while my primary interest was to see if skin conductance or pupillary dilation varied during exposure to computer threat scenarios, I noticed an odd pattern that commanded my attention and actually derailed my study for a while as I dug in to examine it.
Public Sector Shared Services Move Out of the "Back-Office"
Authors: Tomasino Arthur P. , Fedorowicz Jane , Williams Christine B.
Published: August 2017

Shared service providers typically host routine and administrative business processes as a way to standardize company practices and increase efficiency. In the public sector, however, its application to functions critical to an organization"s central mission is moving shared services out of the "back-office." This research employs and extends Bergeron"s (2003) framework to case analysis of two public safety networks within the United States, and prompts the addition of two new characteristics for public sector shared services, Public Policy and Type of Service. In this sector, we find that legislative controls, i.e. policy, manage information and communications technology (ICT) investment to meet efficiency and especially effectiveness goals, while mission criticality serves to trump cost considerations. Recommendations resulting from this research should lead to improvements in the cost and performance of public-sector shared services and their role in ICT-supported, mission-critical, shared services.
Awakening the Dormant Dream
Authors: Mourmant Gaëtan , Voutsina Katerina
Published: August 2017

This paper addresses an under-investigated thematic area of Information Technology (IT) personnel turnover literature: IT Entrepreneurial Turnover. It introduces the concept of entrepreneurial mind-shift in order to shed light on the conditions that influence turnover behavior for nascent IT entrepreneurs. The study follows a grounded theory methodological approach and utilizes two different sets of data. The first data set comes from interviews with 62 IT entrepreneurs, and the second comes from the quotes of over 200 famous authors/entrepreneurs. The analysis of data revealed the types of perceptual shifts IT professionals experience when they realize that they are ready to quit their salaried job and start a new business. The results of the study show that after certain types of 'disrupting events' or the gradual completion of a phase, nascent entrepreneurs start perceiving things through a new lens. In their eyes, the creation of a new venture seemed more feasible than ever before. The introduction of the entrepreneurial mind-shift construct has implications for both research and practice. First, it enriches the stream of literature that brings the concepts of IT personnel turnover and entrepreneurship together. Second, it is a practical tool for all stakeholders involved in the IT Entrepreneurial Turnover process.
“Calories in, calories out” and macronutrient intake: the hope, hype, and science of calories
Authors: Howell Scott , Kones Richard
Published: August 2017

One of the central tenets in obesity prevention and management is caloric restriction. This perspective presents salient features of how calories and energy balance matter, also called the “calories in, calories out” paradigm. Determinants of energy balance and relationships to dietary macronutrient content are reviewed. The rationale and features of the carbohydrate-insulin hypothesis postulate that carbohydrate restriction confers a metabolic advantage. According to this model, a large amount of fat intake is enabled without weight gain. Evidence concerning this possibility is detailed. The relationship and application of the laws of thermodynamics are then clarified with current primary research. Strong data indicate that energy balance is not materially changed during isocaloric substitution of dietary fats for carbohydrates. Results from a number of sources refute both the theory and effectiveness of the carbohydrate-insulin hypothesis. Instead, risk for obesity is primarily determined by total calorie intake.
All-trans-retinoic acid-mediated cytoprotection in LLC-PK1 renal epithelial cells is coupled to p-ERK activation in a ROS-independent manner
Authors: Sapiro Jessica M. , Monks Terrence J. , Lau Serrine S.
Published: August 2017

Although all- trans-retinoic acid (ATRA) provides protection against a variety of conditions in vivo, particularly ischemia, the molecular mechanisms underpinning these effects remain unclear. The present studies were designed to assess potential mechanisms by which ATRA affords cytoprotection against renal toxicants in LLC-PK1 cells. Pretreatment of LLC-PK1 cells with ATRA (25 μM) for 24 h afforded cytoprotection against oncotic cell death induced by p-aminophenol (PAP), 2-(glutathion- S-yl)hydroquinone (MGHQ), and iodoacetamide but not against apoptotic cell death induced by cisplatin. Inhibition of protein synthesis with cycloheximide blunted ATRA protection, indicating essential cell survival pathways must be engaged before toxicant exposure to provide cytoprotection. Interestingly, ATRA did not prevent the PAP-induced generation of reactive oxygen species (ROS) nor did it alter glutathione levels. Moreover, ATRA had no significant effect on Nrf2 protein expression, and the Nrf2 inducers sulforaphane and MG132 did not influence ATRA cytoprotection, suggesting cytoprotective pathways beyond those that influence ROS levels contribute to ATRA protection. In contrast, ATRA rapidly (15 min) induced levels of the cellular stress kinases p-ERK and p-AKT at concentrations of ATRA (10 and 25 μM) required for cytoprotection. Consistent with a role for p-ERK in ATRA-mediated cytoprotection, inhibition of p-ERK with PD98059 reduced the ability of ATRA to afford protection against PAP toxicity. Collectively, these data suggest that p-ERK and its downstream targets, independent of ROS and antioxidant signaling, are important contributors to the cytoprotective effects of ATRA against oncotic cell death.
OAB without an overactive bladder in the acute prostaglandin E2 rat model
Authors: Hokanson James A. , Langdale Christopher L. , Sridhar Arun , Grill Warren M.
Published: August 2017

Intravesical prostaglandin E2 (PGE2) was previously used to induce overactive bladder (OAB) symptoms, as it reduces bladder capacity in rats and causes a “strong urgency sensation” in healthy women. However, the mechanism by which this occurs is unclear. To clarify how PGE2 reduces bladder capacity, 100 µM PGE2 was administered intravesically during open, single-fill cystometry with simultaneous measurement of sphincter EMG in the urethane-anesthetized female Wistar rat. PGE2 was also applied to the urethra or bladder selectively by use of a ligature at the bladder neck before (urethra) or during (bladder) closed-outlet, single-fill cystometry. Additional tests of urethral perfusion with PGE2 were made. PGE2 decreased bladder capacity, increased voiding efficiency, and increased sphincter EMG during open cystometry compared with saline controls. The number of nonvoiding contractions did not change with PGE2; however, bladder compliance decreased. During closed-outlet cystometry, PGE2 applied only to the bladder or the urethra did not decrease bladder capacity. Urethral infusion of PGE2 decreased urethral perfusion pressure. Taken together, these results suggest that intravesical PGE2 may decrease bladder capacity by targeting afferents in the proximal urethra. This may occur through urethral relaxation and decreased bladder compliance, both of which may increase activation of proximal urethra afferents from distension of the proximal urethra. This hypothesis stands in contrast to many hypotheses of urgency that focus on bladder dysfunction as the primary cause of OAB symptoms. Targeting the urethra, particularly urethral smooth muscle, may be a promising avenue for the design of drugs and devices to treat OAB.
Intercepting virtual balls approaching under different gravity conditions: evidence for spatial prediction
Authors: Russo Marta , Cesqui Benedetta , La Scaleia Barbara , Ceccarelli Francesca , Maselli Antonella , Moscatelli Alessandro , Zago Myrka , Lacquaniti Francesco , d’Avella Andrea
Published: August 2017

To accurately time motor responses when intercepting falling balls we rely on an internal model of gravity. However, whether and how such a model is also used to estimate the spatial location of interception is still an open question. Here we addressed this issue by asking 25 participants to intercept balls projected from a fixed location 6 m in front of them and approaching along trajectories with different arrival locations, flight durations, and gravity accelerations (0 g and 1 g). The trajectories were displayed in an immersive virtual reality system with a wide field of view. Participants intercepted approaching balls with a racket, and they were free to choose the time and place of interception. We found that participants often achieved a better performance with 1 g than 0 g balls. Moreover, the interception points were distributed along the direction of a 1 g path for both 1 g and 0 g balls. In the latter case, interceptions tended to cluster on the upper half of the racket, indicating that participants aimed at a lower position than the actual 0 g path. These results suggest that an internal model of gravity was probably used in predicting the interception locations. However, we found that the difference in performance between 1 g and 0 g balls was modulated by flight duration, the difference being larger for faster balls. In addition, the number of peaks in the hand speed profiles increased with flight duration, suggesting that visual information was used to adjust the motor response, correcting the prediction to some extent.

NEW & NOTEWORTHY Here we show that an internal model of gravity plays a key role in predicting where to intercept a fast-moving target. Participants also assumed an accelerated motion when intercepting balls approaching in a virtual environment at constant velocity. We also show that the role of visual information in guiding interceptive movement increases when more time is available.
A Language and Preprocessor for User-Controlled Generation of Synthetic Programs
Authors: Chiu Alton , Garvey Joseph , Abdelrahman Tarek S.
Published: August 2017

We describe Genesis, a language for the generation of synthetic programs. The language allows users to annotate a template program to customize its code using statistical distributions and to generate program instances based on those distributions. This effectively allows users to generate programs whose characteristics vary in a statistically controlled fashion, thus improving upon existing program generators and alleviating the difficulties associated with ad hoc methods of program generation. We describe the language constructs, a prototype preprocessor for the language, and five case studies that show the ability of Genesis to express a range of programs. We evaluate the preprocessor’s performance and the statistical quality of the samples it generates. We thereby show that Genesis is a useful tool that eases the expression and creation of large and diverse program sets.
New Pharmacophore from the Stem Bark Fractions of Acacia decurrens (Willd), an Invasive South Africa Tree
Authors: Okoli Bamidele Joseph , Modise Johannes Sekomeng
Published: August 2017

The tolerance of Acacia decurrens, an invasive species, was exploited pharmacologically in this study. Phytochemical screening revealed important secondary metabolites. Importantly, the assay shows that ethyl acetate and methanol fractions are sources of phytochemicals compared to the hexane and chloroform fractions. A bioassay-guided in vitro assay of the extracts led to the eventual isolation of four bioactive compounds by column chromatography, identification, and characterisation with the aid of GCMS, UV-Vis, FTIR, and NMR. The antimicrobial screening by disc diffusion assay revealed 22.2%, 44.4%, 66.7%, and 77.8% microbial inhibition by 2-methyl-octahydro-indene-4-carboxylic acid (AD1), 6-methyldecahydro-1H-phenanthren-9-one (AD2), 8-hydroxytetradecahydro-chrysene-1-carb aldehyde (AD3), and 8,9-dihydroxy-7-(2-hydroxy-ethyl)-9,9a-hexahydro-1H,3H-2-thia-5a-aza cyclopenta[b]anthracen-6-one (AD4), respectively. Compounds AD3 and AD4 are the most potent antibacterial compounds against Gram-positive bacteria with MIC 12.5–6.25 μg/ml. Antioxidant study of the compounds assayed with DPPH and ABTS•+ revealed that compound (AD4) is the most efficient DPPH radical scavenger with IC50 30.07 ± 0.31 and ABTS•+ scavenging activity of 4363.2 ± 452.4 μmol of TE/gDW. This provides scientific information on four pharmacophores with phyto-antioxidants and antimicrobial potential, despite the classification of A. decurrens as a Category 2 invasive plant by the National Water Act.
Intrathecal Resiniferatoxin Modulates TRPV1 in DRG Neurons and Reduces TNF-Induced Pain-Related Behavior
Authors: Leo M. , Schulte M. , Schmitt L.-I. , Schäfers M. , Kleinschnitz C. , Hagenacker T.
Published: August 2017

Transient receptor potential vanilloid-1 (TRPV1) is a nonselective cation channel, predominantly expressed in sensory neurons. TRPV1 is known to play an important role in the pathogenesis of inflammatory and neuropathic pain states. Previous studies suggest interactions between tumor necrosis factor- (TNF-) alpha and TRPV1, resulting in a modulation of ion channel function and protein expression in sensory neurons. We examined the effect of intrathecal administration of the ultrapotent TRPV1 agonist resiniferatoxin (RTX) on TNF-induced pain-associated behavior of rats using von Frey and hot plate behavioral testing. Intrathecal injection of TNF induces mechanical allodynia (2 and 20 ng/kg) and thermal hyperalgesia (200 ng) 24 h after administration. The additional intrathecal administration of RTX (1.9 μg/kg) alleviates TNF-induced mechanical allodynia and thermal hyperalgesia 24 h after injection. In addition, TNF increases the TRPV1 protein level and number of TRPV1-expressing neurons. Both effects could be abolished by the administration of RTX. These results suggest that the involvement of TRPV1 in TNF-induced pain offers new TRPV1-based experimental therapeutic approaches and demonstrates the analgesic potential of RTX in inflammatory pain diseases.
Shock Mechanism Analysis and Simulation of High-Power Hydraulic Shock Wave Simulator
Authors: Xu Xiaoqiu , Tao Han , Han Junwei
Published: August 2017

The simulation of regular shock wave (e.g., half-sine) can be achieved by the traditional rubber shock simulator, but the practical high-power shock wave characterized by steep prepeak and gentle postpeak is hard to be realized by the same. To tackle this disadvantage, a novel high-power hydraulic shock wave simulator based on the live firing muzzle shock principle was proposed in the current work. The influence of the typical shock characteristic parameters on the shock force wave was investigated via both theoretical deduction and software simulation. According to the obtained data compared with the results, in fact, it can be concluded that the developed hydraulic shock wave simulator can be applied to simulate the real condition of the shocking system. Further, the similarity evaluation of shock wave simulation was achieved based on the curvature distance, and the results stated that the simulation method was reasonable and the structural optimization based on software simulation is also beneficial to the increase of efficiency. Finally, the combination of theoretical analysis and simulation for the development of artillery recoil tester is a comprehensive approach in the design and structure optimization of the recoil system.
Modeling and Analysis of a Multi-Degree-of-Freedom Micro-Vibration Simulator
Authors: Wang Xiaoming , Xu Zhenbang , He Shuai , Wu Qingwen , Li Hang , Zhao Yaping , He Lei
Published: August 2017

To reproduce the disturbance forces and moments generated by the reaction/momentum wheel assembly, a multi-degree-of-freedom micro-vibration simulator is proposed. This can be used in the ground vibration experiments of an optical payload replacing the real action/momentum wheel assembly. First, the detailed structure of the micro-vibration simulator is introduced. Then, the complete system kinematic and dynamic models of the micro-vibration simulator are derived. In addition, the disturbance forces and moments produced by the micro-vibration simulator are calculated. Finally, the normal mode analysis and a cosimulation are adopted to verify the validity of this method. The analysis and simulation results show that the micro-vibration simulator can exactly reproduce the disturbance forces and moments with different amplitudes and different frequency ranges.
Prevalence of Bacterial Vaginosis and Associated Risk Factors among Women Complaining of Genital Tract Infection
Authors: Bitew Adane , Abebaw Yeshiwork , Bekele Delayehu , Mihret Amete
Published: August 2017

Background. Bacterial vaginosis is a global concern due to the increased risk of acquisition of sexually transmitted infections.Objectives. To determine the prevalence of bacterial vaginosis and bacteria causing aerobic vaginitis.Methods. A cross-sectional study was conducted among 210 patients between September 2015 and July 2016 at St. Paul’s Hospital. Gram-stained vaginal swabs were examined microscopically and graded as per Nugent’s procedure. Bacteria causing aerobic vaginitis were characterized, and their antimicrobial susceptibility pattern was determined.Results. The overall prevalence of bacterial vaginosis was 48.6%. Bacterial vaginosis was significantly associated with number of pants used per day (p=0.001) and frequency of vaginal bathing (p=0.045). Of 151 bacterial isolates, 69.5% were Gram-negative and 30.5% were Gram-positive bacteria. The overall drug resistance level of Gram-positive bacteria was high against penicillin, tetracycline, and erythromycin. Cefoxitin and tobramycin were the most active drugs against Gram-positive bacteria. The overall drug resistance level of Gram-negative bacteria was high against tetracycline, ampicillin, and amoxicillin. Amikacin and tobramycin were the most active drugs against Gram-negative bacteria.Conclusions. The prevalence of bacterial vaginosis was high and was affected by individual hygiene. Routine culture of vaginal samples should be performed on patients with vaginitis and the drug susceptibility pattern of each isolate should be determined.
Reducing 30-Day Rehospitalization Rates Using a Transition of Care Clinic Model in a Single Medical Center
Authors: Hudali Tamer , Robinson Robert , Bhattarai Mukul
Published: August 2017

Background. Rehospitalization for medical patients is common. Multiple interventions of varying complexity have been shown to be effective in achieving that goal with variable results in the literature. For medical patients discharged home, no single intervention implemented alone has been shown to have a sustainable effect in preventing rehospitalization. Objective. To study the effect of a transition of care clinic model on the 30-day rehospitalization rate in a single medical center. Methods. Retrospective observational analysis of adult patients discharged home from Memorial Medical Center from September 1, 2014, through December 31, 2014. The primary outcome was to compare hospital readmission rates between patients who followed up with a transition of care (TOC) clinic and those who did not. Results. The study population included 378 patient discharges. A total of 40 patients (10.6%) were readmitted to the hospital within 30 days of discharge. Patients who attended the TOC clinic had a significantly lower 30-day readmission rates (3.8% versus 11.7%). A Cox regression analysis showed that the TOC clinic attendance had a significant negative predication for readmission (HR 0.186, 95% CI 0.038–0.898, P=0.038). Conclusion. Adopting a TOC model after discharging medical patients has reduced the readmission rates in our study.
Intercostal Artery Laceration: Rare Complication of Thoracentesis and Role of Ultrasound in Early Detection
Authors: Mansour Wissam , Samaha Ghassan , El Bitar Sandy , Esper Ziad , Maroun Rabih
Published: August 2017

Hemothorax is a rare but potentially fatal postthoracentesis complication. Early clinical signs may be nonspecific resulting in diagnostic delay. A high index of suspicion is vital for early diagnosis and intervention to avoid further bleeding. Following procedure, early bedside ultrasound findings can be vital for early detection. We report a case of massive hemothorax in a 63-year-old male following therapeutic thoracentesis. Diagnosis was made following highly suggestive sonographic findings prompting thoracotomy and lacerated intercostal artery cauterization.
A Numerical Simulation of Base Shear Forces and Moments Exerted by Waves on Large Diameter Pile
Authors: Cheng You-liang , Xue Zhan-pu , Qu Jiang-man , Jiang Yan
Published: August 2017

To solve the problem of the dynamic variation of wave force diameter of pile foundation for offshore wind turbines, wave force and moment of large diameter pile foundation can be calculated. In this paper, simulation technique is used to calculate the wave force and moment of different large diameter pile foundation, and the base shear force and moment of the interval 20‐degree phase angle are obtained by the base line of the pile. Under the action of a certain load, the complete stress variation of the pile foundation is obtained. According to the basic principle of diffraction theory, the process curve of large diameter pile, and analysis of wave force, diffraction force changes in a certain period of time interval. The results show that the wave after the large diameter pile formed around the vortex, large diameter pile base shear, and moment dynamic change is nonlinear in a complete cycle, the diameter of the pile increases by 0.5 m, and the wave force increases by about 5%, the results show that it provides certain reference value for the offshore pile foundation pile with large diameter primary site. Some significant results for practical application are discussed.
New Frontiers in Genetics, Gut Microbiota, and Immunity: A Rosetta Stone for the Pathogenesis of Inflammatory Bowel Disease
Authors: Zhou Mingxia , He Jing , Shen Yujie , Zhang Cong , Wang Jiazheng , Chen Yingwei
Published: August 2017

Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn’s disease (CD), is a complicated, uncontrolled, and multifactorial disorder characterized by chronic, relapsing, or progressive inflammatory conditions that may involve the entire gastrointestinal tract. The protracted nature has imposed enormous economic burdens on patients with IBD, and the treatment is far from optimal due to the currently limited comprehension of IBD pathogenesis. In spite of the exact etiology still remaining an enigma, four identified components, including personal genetic susceptibility, external environment, internal gut microbiota, and the host immune response, are responsible for IBD pathogenesis, and compelling evidence has suggested that IBD may be triggered by aberrant and continuing immune responses to gut microbiota in genetically susceptibility individuals. The past decade has witnessed the flourishing of research on genetics, gut microbiota, and immunity in patients with IBD. Therefore, in this review, we will comprehensively exhibit a series of novel findings and update the major advances regarding these three fields. Undoubtedly, these novel findings have opened a new horizon and shed bright light on the causality research of IBD.
Natural Transformation of Zinc Oxide Nanoparticles and Their Cytotoxicity and Mutagenicity
Authors: Wang Mei M. , Wang Juan , Cao Rui , Wang Si Y. , Du Hua
Published: August 2017

With rapid development of the nanoindustry, studies focusing on the transformation of nanoparticles (NPs) are required to understand their stability and toxicity after being released into the environment. Here, we characterized the physicochemical properties of ZnO NPs and found that they are naturally alkalized in the presence of air (without the addition of exogenous alkaline substances). Energy dispersive X-ray/X-ray powder diffraction/Fourier transform infrared (EDX/XRD/FTIR)/Raman spectroscopy gave evidence for the formation of hydrozincite (Zn5(CO3)2(OH)6) and zinc hydroxide (Zn(OH)2). Further, we comparatively evaluated the cellular toxicity of pristine and alkalized ZnO NPs. Cell viability testing (colony formation) showed that alkalization time-dependently decreased cytotoxicity. Alkalized NPs exhibited mutagenicity at multiple concentrations, as shown by a CD59 gene loci mutation assay. Variations in toxicity were associated with the chemical transformation of ZnO NPs, and Zn2+ played a key role in the mutagenicity of alkalized NPs. These results indicate that NPs are chemically transformed in the environment. These transformations result in obvious variations in toxicity, suggesting that the NP transformation process should be considered more thoroughly when evaluating toxicity.
Uncertain Associations of Major Bleeding and Concurrent Use of Antiplatelet Agents and Chinese Medications: A Nested Case‐Crossover Study
Authors: Tsai Hsin-Hui , Lin Hsiang-Wen , Tsai Chiu-Lin , Yam Felix K. , Lin Sheng-Shing
Published: August 2017

Despite the evidence that some commonly used Chinese medications (CMs) have antiplatelet/anticoagulant effects, many patients still used antiplatelets combined with CMs. We conducted a nested case‐crossover study to examine the associations between the concomitant use of antiplatelets and CMs and major bleeding using population‐based health database in Taiwan. Among the cohort of 79,463 outpatients prescribed antiplatelets (e.g., aspirin and clopidogrel) continuously, 1,209 patients hospitalized with new occurring bleeding in 2012 and 2013 were included. Those recruited patients served as their own controls to compare different times of exposure to prespecified CMs (e.g., Asian ginseng and dong quai) and antiplatelet agents. The periods of case, control 1, and control 2 were defined as 1–4 weeks, 6–9 weeks, and 13–16 weeks before hospitalization, respectively. Conditional logistic regression analyses found that concurrent use of antiplatelet drugs with any of the prespecified CMs in the case period might not significantly increase the risks of bleeding over that in the control periods (OR = 1.00, 95% CI 0.51 to 1.95 and OR = 1.13, 95% CI 0.65 to 1.97). The study showed no strong relationships between hospitalization for major bleeding events and concurrent use of antiplatelet drugs with the prespecified CMs.
Outcome of Azacitidine Therapy in Acute Myeloid Leukemia Is not Improved by Concurrent Vorinostat Therapy but Is Predicted by a Diagnostic Molecular Signature
Authors: Craddock Charles F. , Houlton Aimee E. , Quek Lynn Swun , Ferguson Paul , Gbandi Emma , Roberts Corran , Metzner Marlen , Garcia-Martin Natalia , Kennedy Alison , Hamblin Angela , Raghavan Manoj , Nagra Sandeep , Dudley Louise , Wheatley Keith , McMullin Mary Frances , Pillai Srinivas P. , Kelly Richard J. , Siddique Shamyla , Dennis Michael , Cavenagh Jamie D. , Vyas Paresh
Published: August 2017

Purpose: Azacitidine (AZA) is a novel therapeutic option in older patients with acute myeloid leukemia (AML), but its rational utilization is compromised by the fact that neither the determinants of clinical response nor its mechanism of action are defined. Co-administration of histone deacetylase inhibitors, such as vorinostat (VOR), is reported to improve the clinical activity of AZA, but this has not been prospectively studied in patients with AML.

Experimental Design: We compared outcomes in 259 adults with AML (n = 217) and MDS (n = 42) randomized to receive either AZA monotherapy (75 mg/m2 × 7 days every 28 days) or AZA combined with VOR 300 mg twice a day on days 3 to 9 orally. Next-generation sequencing was performed in 250 patients on 41 genes commonly mutated in AML. Serial immunophenotyping of progenitor cells was performed in 47 patients.

Results: Co-administration of VOR did not increase the overall response rate (P = 0.84) or overall survival (OS; P = 0.32). Specifically, no benefit was identified in either de novo or relapsed AML. Mutations in the genes CDKN2A (P = 0.0001), IDH1 (P = 0.004), and TP53 (P = 0.003) were associated with reduced OS. Lymphoid multipotential progenitor populations were greatly expanded at diagnosis and although reduced in size in responding patients remained detectable throughout treatment.

Conclusions: This study demonstrates no benefit of concurrent administration of VOR with AZA but identifies a mutational signature predictive of outcome after AZA-based therapy. The correlation between heterozygous loss of function CDKN2A mutations and decreased OS implicates induction of cell-cycle arrest as a mechanism by which AZA exerts its clinical activity. Clin Cancer Res; 23(21); 6430–40. ©2017 AACR.
Prospective Evaluation of Multimodal Optical Imaging with Automated Image Analysis to Detect Oral Neoplasia In Vivo
Authors: Quang Timothy , Tran Emily Q. , Schwarz Richard A. , Williams Michelle D. , Vigneswaran Nadarajah , Gillenwater Ann M. , Richards-Kortum Rebecca
Published: August 2017

The 5-year survival rate for patients with oral cancer remains low, in part because diagnosis often occurs at a late stage. Early and accurate identification of oral high-grade dysplasia and cancer can help improve patient outcomes. Multimodal optical imaging is an adjunctive diagnostic technique in which autofluorescence imaging is used to identify high-risk regions within the oral cavity, followed by high-resolution microendoscopy to confirm or rule out the presence of neoplasia. Multimodal optical images were obtained from 206 sites in 100 patients. Histologic diagnosis, either from a punch biopsy or an excised surgical specimen, was used as the gold standard for all sites. Histopathologic diagnoses of moderate dysplasia or worse were considered neoplastic. Images from 92 sites in the first 30 patients were used as a training set to develop automated image analysis methods for identification of neoplasia. Diagnostic performance was evaluated prospectively using images from 114 sites in the remaining 70 patients as a test set. In the training set, multimodal optical imaging with automated image analysis correctly classified 95% of nonneoplastic sites and 94% of neoplastic sites. Among the 56 sites in the test set that were biopsied, multimodal optical imaging correctly classified 100% of nonneoplastic sites and 85% of neoplastic sites. Among the 58 sites in the test set that corresponded to a surgical specimen, multimodal imaging correctly classified 100% of nonneoplastic sites and 61% of neoplastic sites. These findings support the potential of multimodal optical imaging to aid in the early detection of oral cancer. Cancer Prev Res; 10(10); 563–70. ©2017 AACR.
Pathological Concordance between Prostate Biopsies and Radical Prostatectomy Using Transperineal Sector Mapping Biopsies: Validation and Comparison with Transrectal Biopsies
Authors: Marra Giancarlo , Eldred-Evans David , Challacombe Ben , Van Hemelrijck Mieke , Polson Alexander , Pomplun Sabine , Foster Christopher S. , Brown Christian , Cahill Declan , Gontero Paolo , Popert Rick , Muir Gordon
Published: August 2017

Background/Aims/Objectives: Our aim was to evaluate the accuracy of systematic transperineal sector mapping biopsy (TPSMB) in predicting Gleason score (GS) at radical prostatectomy (RP), to compare its accuracy with standard transrectal ultrasound-guided biopsies (TRUS) and to establish the clinical impact of discordance between biopsies and RP on subsequent surgical management. Methods: Two hundred fifty-five patients from 2008 to 2013 who underwent RP following TPSMB (n = 204) or TRUS (n = 51), were included in this retrospective multi-institutional study. Concordance between biopsies and RPs GS was assessed both as percentages and with Cohen's Kappa coefficient. All mismatches between biopsies and RP were assessed for significance by 3 urologists using the Delphi method. Results: No differences were present among the groups. Concordance between biopsy and RP GS was 75.49% for TPSMB and 64.70% for TRUS. Kappa coefficient was 0.42 and 0.39 respectively. The Delphi method showed lower clinical impact of GS discordances for TPSMB with 7.8% of patients having significant change, thus being potentially more suitable for other treatment modalities, compared to TRUS (13.7%). Conclusions: TPSMB had a higher accuracy for predicting the GS grade at RP showing superior GS concordance compared with standard TRUS. TPSMB provides an effective technique for systematic prostate biopsy to evaluate overall prostate cancer GS.
Clinical Outcomes of Dietary Replacement of Saturated Fatty Acids with Unsaturated Fat Sources in Adults with Overweight and Obesity: A Systematic Review and Meta-Analysis of Randomized Control Trials
Authors: Hannon Bridget A. , Thompson Sharon V. , An Ruopeng , Teran-Garcia Margarita
Published: August 2017

Background: Obesity and dyslipidemia are frequently treated with dietary interventions before pharmacotherapy is given. Diets high in unsaturated fat have proven advantageous to disease treatment. Aims: The purpose of this systematic review and meta-analysis was to assess the evidence of the effect of saturated fatty acids (SFA) replacement with unsaturated fatty acids (UFA) in metabolically healthy adults with overweight and obesity on markers of dyslipidemia and body composition. Methods: Keyword search was performed in PubMed, CINAHL, and Cochrane Library for randomized controlled trials (RCTs) evaluating the effects of fatty acid substitution in adults with overweight and obesity. Meta-analysis was performed on interventions assessing lipoprotein levels and body composition. Publication bias was assessed by funnel plot inspection, Begg's, and Egger's test. Results: Eight RCTs enrolling 663 participants were included in the review, with intervention durations between 4 and 28 weeks. Although nonsignificant (p = 0.06), meta-analysis found UFA replacement to reduce total cholesterol concentrations by 10.68 mg/dL (95%CI -21.90 to 0.53). Reductions in low-density lipoprotein cholesterol and triglycerides were statistically nonsignificant. Conclusions: Due to null results and a small number of studies included, there is no strong evidence that replacement of SFA with UFA may benefit lipid profiles in this population.
Saline Enemas versus Glycerin Suppositories to Promote Enteral Feeding in Premature Infants: A Pilot Randomized Controlled Trial
Authors: Ibrahim Thowfique , Li Wei Chiang , Bautista Dianne , Sriram Bhavani , Xiangzhen Fay Li , Rajadurai Victor Samuel
Published: August 2017

Background: Meconium retention is associated with feeding intolerance. Trials using glycerol and Gastrografin to expedite the evacuation of meconium have failed to generate clinically valid results for efficacy and safety. Objective: We assessed the feasibility of aggressive meconium evacuation with saline rectal washout (RW) in very-low-birth-weight infants to reduce the time it took them to reach full enteral feeds. Methods: We conducted an open-label, pilot, randomized controlled trial (RCT) (birth weight stratified, i.e., to 750-999 g and 1,000-1,500 g) of early aggressive meconium evacuation with twice-daily normal saline RW compared to conventional management with glycerin suppositories (GS), until full enteral feeds (110 mL/kg/day) were reached. Primary outcome was time to reach full enteral feeds. Safety, process, and secondary efficacy outcomes were also evaluated. Results: Sixty-one infants were randomized, 28 to RW and 33 to GS. The process and feasibility outcomes were met. RW was found to be safe; none of the RW-randomized infants developed necrotizing enterocolitis (≥ stage II) or complications secondary to RW. Evidence of efficacy was supported: in the 750-999 g stratum (n = 15), the median time to full enteral feeds was shorter with RW (11.0 days, 95% CI: 10.4-11.6) than with GS (15.6 days, 95% CI: 13.0-18.2) by a reduction of 4.6 days (p = 0.027). In the 1,000-1,500 g stratum (n = 46), there was no evidence of benefit: RW 10.2 days (95% CI 8.3-12.1) and GS 10.1 days (95% CI 9.3-10.9, p = 0.304). Conclusion: Our protocol was feasible and an adequately powered RCT is required to confirm the findings of this trial.
Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review
Authors: Watad Abdulla , Bragazzi Nicola Luigi , Adawi Mohammad , Amital Howard , Toubi Elias , Porat Bat-Sheva , Shoenfeld Yehuda
Published: August 2017

Advancements in the field of biomedicine, including the control of infectious diseases through antibiotics and vaccination practices and the prevention of chronic disorders, have led to reduced mortality, increased life expectancy and, as such, growth of the older population. Ageing is accompanied by profound morphological and physiological alterations. In particular, the immune system undergoes a complex series of remodeling/restructuring events, involving almost all compartments - both the innate and the adaptive system. This process is termed immunosenescence or immune dysregulation and, basically, includes 3 events: a reduction in immune response, an increase in the inflammatory and oxidation background (inflammaging and oxi-inflammaging), and a production of autoantibodies. While there is an increase in autoimmunity in the elderly, this does not always translate into an increase in autoimmune diseases, which represent an important cause of morbidity and mortality and affect 5-10% of the world population. Each disease involves a specific age group. Generally speaking, most autoimmune diseases have a decreased peak age of onset, except for very few diseases such as giant cell arteritis and primary biliary cirrhosis, which are more prevalent among the elderly, or inflammatory bowel disease, which has 2 peaks of onset, the first one in young subjects and the other in those older than 60 years. Autoimmune disorders in the elderly have unique clinical presentations, and insidious and atypical symptoms may constitute a challenge for the physician. They are generally milder than in adults and can be controlled by a proper therapeutic treatment. However, despite advancements both in basic and clinical sciences, further studies and investigations are warranted and should be carried out in order to dissect the molecular framework induced by ageing.
Amniotic Fluid Concentrations of Glial Fibrillary Acidic Protein Do Not Correlate with Prenatal Metrics in Fetuses with Myelomeningocele
Authors: Kim Aimee G. , Danzer Enrico , Moldenhauer Julie S. , Khalek Nahla , McClain Lauren E. , Waqar Lindsay N. , Hedrick Holly L. , Johnson Mark P. , Adzick N. Scott , Peranteau William H. , Flake Alan W.
Published: August 2017

Introduction: We investigated the correlation of amniotic fluid (AF) concentrations of glial fibrillary acidic protein (GFAP) with prenatal features of myelomeningocele (MMC) and neurodevelopmental outcome after fetal MMC (fMMC) surgery. Materials and Methods: AF was collected during fMMC surgery between December 2012 and November 2015. AF-GFAP concentration was determined by ELISA. Retrospective chart review identified the characteristics of the defect. Data regarding delivery and 1-year neurodevelopmental outcome was collected from The Children's Hospital of Philadelphia fMMC Registry. Results: Eighty-two AF samples were collected from fMMC surgeries. Perinatal data were obtained from 77 subjects, and 1-year follow-up data from 65 subjects. GFAP concentrations were significantly elevated in MMC compared to myeloschisis (24.1 ± 2.9 and 10.3 ± 1.5 ng/mL; p < 0.0001). A larger percentage of subjects with myeloschisis defects delivered before their scheduled due date (myeloschisis 88.5%; MMC 55.0%; p = 0.003) and delivered at an earlier mean gestational age (34.6 ± 0.4 weeks, n = 26) compared to those with MMC defects (35.2 ± 0.4 weeks, n = 51) (p = 0.04). Discussion: AF-GFAP levels differentiate between MMC and myeloschisis, and raise interesting questions regarding the clinical significance between the 2 types of defects.
Combination Treatment of Low-Frequency Repetitive Transcranial Magnetic Stimulation and Intensive Occupational Therapy for Ataxic Hemiparesis due to Thalamic Hemorrhage
Authors: Urushidani Naoki , Okamoto Takatsugu , Kinoshita Shoji , Yamane Shingo , Tamashiro Hiroaki , Kakuda Wataru , Abo Masahiro
Published: August 2017

Background: Both low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) and intensive occupational therapy (OT) are clinically beneficial for post-stroke patients with upper-limb hemiparesis. However, the usefulness of LF-rTMS and intensive OT for ataxic hemiparesis (AH) is unknown. Methods: The study subjects included 7 patients with AH. All patients had ataxia and mild hemiparesis without a sensory disturbance that was due to thalamic hemorrhage. Each patient was scheduled to receive 20-min rTMS at 1 Hz at the contralesional cerebral hemisphere followed by 120-min intensive OT, daily for 21 sessions. The primary outcome was the motor function of the affected upper limb that was evaluated by using the Fugl-Meyer Assessment (FMA). In addition, the International Cooperative Ataxia Rating Scale (ICARS) score was determined to assess the severity of ataxia. Results: All patients completed the protocol without any adverse effects. The FMA score significantly increased after treatment. Notably, the ICARS score also significantly decreased. Conclusions: Our proposed combination treatment is a safe and feasible neurorehabilitative intervention for patients with AH due to thalamic hemorrhage. Our results demonstrate the possibility that rTMS in combination with intensive OT could improve motor function and alleviated ataxia in patients with AH.
СУЧАСНІ УЯВЛЕННЯ ПРО ПАТОГЕНЕЗ ТА ДІАГНОСТИКУ ГНІЙНО-СЕПТИЧНИХ СТАНІВ У ДІТЕЙ (частина 1)
Authors: Pypa L. V. , Murhina M. M.
Published: August 2017

Мета – узагальнити дані сучасних поглядів на етіологію та патогенез сепсису у різних вікових групах, зокрема у дітей.Проведено аналітичний огляд літератури щодо сучасних поглядів на патогенез, генетичні особливості та діагностичні маркери розвитку гнійно-септичних станів у дітей. Перша частина присвячена сучасним теоріям патогенезу септичних станів у дітей. Описана роль патогенасоційованих молекулекулярних структур Гр+ та Гр- бактерій, механізм їх взаємодії із рецепторами клітин організму, в якому розвивається сепсис. Початок синтезу про- та протизапальних цитокінів запускає патологічний каскад реакцій, які призводять до розвитку синдрому системної запальної відповіді та в подальшому синдрому поліорганної недостатності (СПОН). Описані особливості СПОН при різних етіологічних збудниках септичного процесу та патогенетичні механізми віддалених наслідків перенесеного тяжкого сепсису та септичного шоку. Висновок. Поглиблене розуміння сучасних механізмів розвитку сепсису дозволить більш ефективно проводити діагностику та лікування септичних станів, що своєю чергою зменшить смертність і негативні наслідки після перенесеного сепсису у дітей.
СЕМІОТИКА ІНФЕКЦІЙНИХ ЕКЗАНТЕМ
Authors: Kopcha V. S. , Halnykina S. O. , Vasylieva N. A. , Ishchuk I. S.
Published: August 2017

Представлений огляд даних літератури з проблеми інфекційних висипань. Відзначена їх важлива роль у діагностиці та диференційній діагностиці інфекційних хвороб. Наведена семіотика інфекційних екзантем, що найчастіше трапляються у практиці.
СЛАВНИЙ ЮВІЛЕЙ ПРОФЕСОРА ІВАНА ОЛЕКСАНДРОВИЧА СИТНИКА
Authors: Of authors Collective
Published: August 2017

Дана коротка біографічна інформація про видатного українського вченого-мікробіолога, ветерана Тернопільського державного медичного університету ім. І.Я. Горбачевського, професора, багаторічного керівника кафедри мікробіології зазначеного вишу, наукового керівника чи консультанта когорти добре відомих в Україні та за її межами вчених, блискучого лектора, активного громадського діяча Івана Олександровича Ситника.
ПРОФЕСОР Є.В. НІКІТІН ПОНАД ПІВСТОЛІТТЯ НА СЛУЖБІ ІНФЕКЦІЙНИМ ХВОРИМ
Authors: Of authors Collective
Published: August 2017

Short biographic information is exposed about the known Ukrainian scientist-infectiologist, Professor, Honoured worker of science and technics of Ukraine, laureate of the State Prize of Ukraine, long-term leader of the Department of Infectious Diseases of Odesa National Medical University Yevhen Vasyliovych Nikitin.
ДО ЮВІЛЕЮ МИКОЛИ ДМИТРОВИЧА ЧЕМИЧА
Authors: Of authors Collective
Published: August 2017

Дана коротка біографічна інформація про українського вченого-інфекціоніста, керівника Сумської обласної клініки інфекційних хвороб, завідувача кафедри інфекційних хвороб з епідеміологією Сумського державного університету, члена редакційної колегії Всеукраїнського науково-практичного медичного журналу «Інфекційні хвороби», професора Миколу Дмитровича Чемича.