bluuebunny/crossref_metadata_2025 huggingface dataset:
Functionally Related Genes Cluster into Genomic Regions That Coordinate Transcription at a Distance in Saccharomyces cerevisiae
Authors: Cera Alanna , Holganza Maria K. , Hardan Ahmad Abu , Gamarra Irvin , Eldabagh Reem S. , Deschaine Megan , Elkamhawy Sarah , Sisso Exequiel M. , Foley Jonathan J. , Arnone James T.
Published: March 2019

The two-dimensional, physical positioning of genes along a chromosome can impact proper transcriptional regulation throughout a genomic region. The transcription of neighboring genes is correlated in a genome-wide manner, which is a characteristic of eukaryotes. Many coregulated gene families can be found clustered with another member of the same set—which can result in adjacent gene coregulation of the pair. Due to the myriad gene families that exhibit a nonrandom genomic distribution, there are likely multiple mechanisms working in concert to properly regulate transcriptional coordination of functionally clustered genes. In this study, we utilized budding yeast in an attempt to elucidate mechanisms that underlie this coregulation: testing and empirically validating the enhancer-promoter hypothesis in this species and reporting that functionally related genes cluster to genomic regions that are more conducive to transcriptional regulation at a distance. These clusters rely, in part, on chromatin maintenance and remodelers to maintain proper transcriptional coordination. Our work provides insight into the mechanisms underlying adjacent gene coregulation.
Emergence of New Delhi Metallo-β-Lactamase (NDM-5) in
Klebsiella quasipneumoniae
from Neonates in a Nigerian Hospital
Authors: Brinkac Lauren M. , White Richard , D’Souza Roshan , Nguyen Kevin , Obaro Stephen K. , Fouts Derrick E.
Published: March 2019

Carbapenem-resistant
Klebsiella pneumoniae
is of global health importance, yet there is a paucity of genome-based studies in Africa. Here we report fatal blood-borne NDM-5-producing
K. quasipneumoniae
subsp.
similipneumoniae
infections from Nigeria, Africa. New Delhi metallo-β-lactamase (NDM)-producing
Klebsiella
spp. are responsible for high mortality and morbidity, with the NDM-5 variant showing elevated carbapenem resistance. The prevalence of NDM-5 in
Klebsiella
has been limited primarily to
K. pneumoniae
, with only one isolate being collected from Africa. During an outbreak of sepsis in a teaching hospital in Nigeria, five NDM-5-producing
K. quasipneumoniae
subsp.
similipneumoniae
sequence type 476 isolates were identified. Given the increased resistance profile of these strains, this study highlights the emerging threat of
bla
NDM-5
dissemination in hospital environments. The observation of these NDM-5-producing isolates in Africa stresses the urgency to improve monitoring and clinical practices to reduce or prevent the further spread of resistance.
Infected chronic sinus secondary to a retained fragment of radial artery introducer sheath following percutaneous coronary intervention (PCI)
Authors: Ghazala Christopher George , Marrow Benjamin Alexander , Kearney Dermot , Harrison John William Kenneth
Published: March 2019

Coronary angiography and percutaneous coronary intervention (PCI) are frequently performed procedures in the UK and the developed world, with the radial artery becoming the preferred route of access. A chronically retained macroscopic fragment of radial artery introducer sheath is a very rare complication that has not, to our knowledge, been reported. We report the case of a 62-year-old woman who underwent PCI and developed a persisting infected sinus and abscess at the cannulation site despite multiple courses of antibiotics. Surgical exploration of the forearm recovered a foreign body that was found in the brachioradialis muscle and resembled a fragment of hydrophilic sheath. In conclusion, this case highlights that it is possible to leave macroscopic fragments of hydrophilic sheaths in situ. This is likely to be encountered during difficult access, especially during arterial spasm, and it is advised that the sheath and any other vascular access device is thoroughly inspected following removal.
Prone ventilation in a patient with severe ARDS having a floating sternum
Authors: Sahoo Alok Kumar , Tripathy Swagata , Singh Santosh Kumar
Published: March 2019

Prone ventilation is used to manage patients with refractory hypoxia in the critical care unit. Complex chest trauma and chest drains have been a considered relative contraindication to prone ventilation. To the best of our knowledge, it is hitherto unreported in patients having traumatic floating sternum and acute respiratory distress. We present a brief case report of a patient with floating sternum (complete disruption of sternum) managed successfully by prone position ventilation.
Association of venous varix and developmental venous anomaly: report of a case and review of literature
Authors: Naik Suprava , Bhoi Sanjeev K
Published: March 2019

Cerebral developmental venous anomalies (DVAs) are the most frequently encountered cerebral vascular malformation. Most are asymptomatic and incidentally detected. Here we present a case of DVA associated with venous varix presented with chronic headache. A 50-year-old woman presented with right hemicranial headache since 6 months. There was no neurological deficit. MRI showed a well-defined oval T2 hyperintense, T1 isointense extra-axial lesion in the right parietal region showing intense homogeneous enhancement. Prominent vascular flow void was extending from the lesion up to the deep parietal white matter. Subtle thin linear areas of blooming noted in the parietal white matter converging towards the vascular flow void. The venous sac is in communication with the cortical vein draining to the superior sagittal sinus. These MRI findings favoured a diagnosis of DVA in the right parietal lobe with prominent draining vein forming a cortical venous varix. The patient was managed conservatively with symptomatic treatment for headache.
Associations of nicotine dependence and fat distribution in Chinese male adults: a cross-sectional study in Lanxi, China
Authors: Wei Chen , Ye Sunyue , Sheng Jessica Ruolin , Ma Xiaoguang , Ru Yuan , Zhang Liang , Guo Huilan , Zhu Shankuan
Published: March 2019

Introduction

Previous studies have showed association between smoking and central fat distribution. However, the impact of smoking on whole body fat distribution, particularly peripheral fat distribution remains unclear.

Methods

Nicotine dependence was assessed in a total of 1264 male adults aged 18–80 years using the Fagerström Test for Nicotine Dependence (FTND). Smoking status was categorised as non-smokers, former and current smokers with very low, low/moderate, or high FTND scores. Body fat distribution was determined using the dual energy X-ray absorptiometry and anthropometric measurements. Multivariable linear regression models were applied to examine the adjusted associations between body fat distribution and smoking in all participants, and its association with FTND scores in the current smokers.

Results

Greater waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), trunk fat percentage (%TF), android fat percentage (%AF) and android-to-gynoid fat mass ratio (AOI); but lower legs fat percentage (%LegF), limb fat percentage (%LimbF) and gynoid fat percentage (%GF) were found in current smokers with high FTND scores compared with non-smokers. In current smokers aged 60 years or older, FTND scores had positive associations with WC, WHR, WHtR, %TF, %AF and AOI, and negative associations with %LegF, %LimbF and %GF.

Conclusions

Nicotine dependence was positively associated with central fat distribution and negatively associated with peripheral fat distribution in Chinese male adults, particularly in those older or heavy smokers, and these associations were independent from body mass index, which might be due to long exposure to smoking.
Relationship between serum osteocalcin/undercarboxylated osteocalcin and type 2 diabetes: a systematic review/meta-analysis study protocol
Authors: Liu Yihui , Liu Xiaoying , R Lewis Joshua , Brock Kaye , C Brennan-Speranza Tara , Teixeira-Pinto Armando
Published: March 2019

Introduction

The global burden of type 2 diabetes (T2DM) is steadily increasing. Experimental studies have demonstrated that a novel hormone secreted by bone cells, osteocalcin (OC), can stimulate beta-cell proliferation and improve insulin sensitivity in mice. Observational studies in humans have investigated the relationship between OC and metabolic parameters, and T2DM. Importantly, few studies have reported on the undercarboxylated form of OC (ucOC), which is the putative active form of OC suggested to affect glucose metabolism.

Objectives

We will conduct a systematic review and meta-analysis to: (1) compare the levels of serum OC and ucOC between T2DM and normal glucose-tolerant controls (NGC); (2) investigate the risk ratios between serum OC and ucOC, and T2DM; (3) determine the correlation coefficient between OC and ucOC and fasting insulin levels, homeostatic model assessment-insulin resistance, haemoglobin A1c and fasting glucose levels and (4) explore potential sources of between-study heterogeneity. The secondary objective is to compare the serum OC and ucOC between pre-diabetes (PD) and NGC and between T2DM and PD.

hods and analysis

This study will report items in line with the guidelines outlined in preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology. We will include observational studies (cohort, case-control and cross-sectional studies) and intervention studies with baseline data. Three databases (MEDLINE, EMBASE and SCOPUS) will be searched from inception until July 2018 without language restrictions. Two reviewers will independently screen the titles and abstracts and conduct a full-text assessment to identify eligible studies. Discrepancies will be resolved by consensus with a third reviewer. The risk of bias assessment will be conducted by two reviewers independently based on the Newcastle-Ottawa Scale. Potential sources of between-study heterogeneity will be tested using meta-regression/subgroup analyses. Contour-enhanced funnel plots and Egger’s test will be used to identify potential publication bias.

Ethics and dissemination

Formal ethical approval is not required. We will disseminate the results to a peer-reviewed publication and conference presentation.

PROSPERO registration number

CRD42017073127.
Capturing the experience of the hospital-stay journey from admission to discharge using diaries completed by patients in their own words: a qualitative study
Authors: Webster Craig S , Jowsey Tanisha , Lu Lucy M , Henning Marcus A , Verstappen Antonia , Wearn Andy , Reid Papaarangi M , Merry Alan F , Weller Jennifer M
Published: March 2019

Objective

To capture and better understand patients’ experience during their healthcare journey from hospital admission to discharge, and to identify patient suggestions for improvement.

Design

Prospective, exploratory, qualitative study. Patients were asked to complete an unstructured written diary expressed in their own words, recording negative and positive experiences or anything else they considered noteworthy.

Participants and setting

Patients undergoing vascular surgery in a metropolitan hospital.

Primary outcome measures

Complete diary transcripts underwent a general inductive thematic analysis, and opportunities to improve the experience of care were identified and collated.

Results

We recruited 113 patients in order to collect 80 completed diaries from 78 participants (a participant response rate of 69%), recording patients’ experiences of their hospital-stay journey. Participating patients were a median (range) age of 69 (21–99) years and diaries contained a median (range) of 197 (26–1672) words each. Study participants with a tertiary education wrote more in their diaries than those without—a median (range) of 353.5 (48–1672) vs 163 (26–1599) words, respectively (Mann-Whitney U test, p=0.001). Three primary and eight secondary themes emerged from analysis of diary transcripts—primary themes being: (1) communication as central to care; (2) importance of feeling cared for and (3) environmental factors shaping experiences. In the great majority, participants reported positive experiences on the hospital ward. However, a set of 12 patient suggestions for improvement were identified, the majority of which could be addressed with little cost but result in substantial improvements in patient experience. Half of the 12 suggestions for improvement fell into primary theme 1, concerning opportunities to improve communication between healthcare providers and patients.

Conclusions

Unstructured diaries completed in a patient’s own words appear to be an effective and simple approach to capture the hospital-stay experience from the patient’s own perspective, and to identify opportunities for improvement.
Sealing the hole: endoscopic management of acute gastrointestinal perforations
Authors: Gabr Ahmed
Published: March 2019

Acute perforations are one of the recognised complications of both diagnostic and therapeutic gastrointestinal (GI) endoscopy. The incidence rate varies according to the type of procedure and the anatomical location within the GI tract. For decades, surgical treatment has been the standard of care, but endoscopic closure has become a more popular approach, due to feasibility and the reduction of the burden of surgery. Various devices are available now such as through-the-scope clips, over-the-scope clips, endoscopic suturing devices, stents, bands and omental patch. All have been tested in studies done on humans or animal models, with a reasonable overall technical and clinical success rate, proving efficiency and feasibility of endoscopic closure. The choice of which device to use depends on the site and the size of the perforation. It also depends on availability of thee device and the endoscopist’s experience. A number of factors that could predict success of endoscopic closure or favour surgical treatment have been suggested in different studies. After successful endoscopic closure, patients are usually kept nil by mouth and receive antibiotics for a duration that varied between different studies.
Canadian neurosurgeons’ views on medical assistance in dying (MAID): a cross-sectional survey of Canadian Neurosurgical Society (CNSS) members
Authors: Althagafi Alwalaa , Ekong Chris , Wheelock Brian W , Moulton Richard , Gorman Peter , Reddy Kesh , Christie Sean , Fleetwood Ian , Barry Sean
Published: March 2019

Background

The Supreme Court of Canada removed the prohibition on physicians assisting in patients dying on 6 February 2015. Bill C-14, legalising medical assistance in dying (MAID) in Canada, was subsequently passed by the House of Commons and the Senate on 17 June 2016. As this remains a divisive issue for physicians, the Canadian Neurosurgical Society (CNSS) has recently published a position statement on MAID.

Methods

We conducted a cross-sectional survey to understand the views and perceptions among CNSS members regarding MAID to inform its position statement on the issue. Data was collected from May to June 2016.

Results

Of the 300 active membes of the CNSS who recevied the survey, 89 respondents completed the survey, 71% of whom were attending neurosurgeons and 29% were neurosurgery residents. Most respondents,74.2%, supported the right of physicians to participate in MAID with 7.8% opposing. 37% had current patients in their practice fitting the criteria for MAID. 23.6% had been asked by patients to assist with MAID, but only 11% would consider personally providing it. 84% of neurosurgeons surveyed supported the physicians’ right to conscientious objection to MAID while 21% thought attending surgeons should be removed from the inquiry and decision-making process. 43.8% agreed that the requirment to refer a patient to a MAID service should be mandatory. Glioblastoma multiforme (65%), quadriplegia/quadriparesis secondary to spinal tumour/trauma (54%) and Parkinson’s disease (24%) were the most common suggested potential indications for MAID among the neurosurgical population.

Conclusions

Our results demonstrate that most neurosurgeons in Canada are generally supportive of MAID in select patients. However, they also strongly support the physicians’ right to conscientious objection.
Does Spinal Anesthesia Affect Cerebral Oxygenation During Transurethral Prostatectomy?
Authors: Atallah Mohamed M. , Hoeft Andreas , El-Ghorouri Mohamed A. , Hammouda Golinar E. , Saied Mostafa MA
Published: March 2019

Background and Objectives

Transurethral resection of the prostate (TURP) is associated with the unique complication of transurethral resection of prostate syndrome (TURS), which is attributed to the absorption of irrigating fluid. This study was initiated to investigate the effects of spinal anesthesia and TURP on cerebral oxygen balance.

Methods

Thirty patients scheduled for TURP were included. Jugular bulb oxygen saturation (SjbO2) was measured via retrograde cannulation of jugular venous bulb. Spinal anesthesia was initiated by 3 mL hyperbaric 0.5% bupivacaine injected at L3-L4 in the sitting position, producing a block to the T10 dermatome. Hemodynamic measurements and arterial and jugular bulb blood gasometry were performed before and after spinal anesthesia, throughout surgery, and during the postoperative period.

Results

A significant decrease of cerebral perfusion pressure after spinal anesthesia was accompanied by a significant decrease of SjbO2 below a preoperative value of 61% ± 1. Eight patients developed yawning, irritability, restlessness, and nausea toward the end of surgery, and these were considered to be early signs of TURS. These patients demonstrated SjbO2 below 55% and 50% in 63% and 42% of respective data set points.

Conclusion

The neurologic symptoms in patients undergoing TURP during spinal anesthesia might not only be caused by absorption of irrigating fluid but also by impairment of cerebral oxygenation.
High-Dose Ropivacaine Wound Infiltration for Pain Relief After Inguinal Hernia Repair
Authors: Pettersson Nils , Emanuelsson B-M , Reventlid Håkan , Hahn Robert G.
Published: March 2019

Background and Objectives

Early data on ropivacaine, a recently introduced local anesthetic, indicate a longer duration of skin analgesia than with bupivacaine, along with lower toxicity. The objective of this study was to evaluate ropivacaine 7.5 mg/mL for wound infiltration pain relief after hernia surgery, in higher doses than used before, in an open, nonrandomized design.

Methods

Twenty otherwise healthy men underwent elective unilateral open hernia repair by the same surgeon. General anesthesia was used during surgery, and infiltration of the operating field with 300 mg (n = 10) or 375 mg (n = 10) ropivacaine, 7.5 mg/mL, was employed for postoperative pain relief. Any sign of an adverse event was recorded. Plasma concentrations of ropivacaine were monitored. Pain at rest and on mobilization was regularly assessed over 24 hours by a visual analog scale. Patients' ability to walk and void and the need for supplementary analgesics were recorded.

Results

No serious adverse effects occurred. Plasma concentrations showed large variations but no toxic levels. No significant differences between the two groups were detected in pain scores which were low in both groups, at rest or on mobilization, or in the consumption of supplementary analgesics. At 4 hours, 19 patients were able to walk. Within 8 hours of surgery, all patients had passed urine without any problem. Wound healing was normal.

Conclusions

Infiltration of ropivacaine 7.5 mg/mL during hernia surgery can be employed safely in doses of 300 mg and 375 mg to control pain after hernia surgery. The lower dose is recommended, since the higher one did not give any clinically relevant advantages.
Close-range photogrammetry with spherical panoramas for mapping spatial location and measuring diameters of trees under forest canopies
Authors: Lu Mei-Kuei , Lam Tzeng Yih , Perng Bo-Hao , Lin Ho-Tung
Published: March 2019

Measurement of tree attributes is important to collect information for forest management. Close-range photogrammetry with spherical panoramas has seen very little development and applications compared with aerial photography. This study develops methods to extract azimuth, horizontal distance, diameter at breast height, and upper stem diameters of individual trees from spherical panoramas based on (i) the trigonometry principle (TRIGO), (ii) the TRIGO corrected for terrain slope (TRIGOSLP), and (iii) the pinhole camera model (PINHOLE). Twenty-three horizontal point sample plots were randomly established in plantations in Taiwan, for a sample size of 486 trees. Results showed that tree azimuth was accurately and precisely estimated. TRIGO performed the worst in accuracy and precision for all other tree attributes. TRIGOSLP improved the results of TRIGO but had large estimation errors. PINHOLE achieved the best overall precision for all other tree attributes but was slightly inaccurate for estimating upper stem diameters. PINHOLE requires approaching a tree to attach a target of known size but has the ability to extract an almost continuous set of upper stem diameters from the tree, which could improve estimation of tree volume. Thus, PINHOLE could potentially be an alternative measurement system for hard-to-measure tree attributes.
Robustness of quantum correlation for accelerating two atoms coupled with electromagnetic field
Authors: Huang Zhiming , Situ Haozhen
Published: March 2019

In this paper, we investigate the behaviors of quantum correlation quantified by trace norm measurement-induced nonlocality (TMIN) for two uniformly accelerated atoms coupled with electromagnetic vacuum fluctuation in the Minkowski vacuum. We firstly discuss the solving process of master equation that governs the system evolution based on the Pauli matrix presentation for two-qubit state. Similar to [Y. Q. Yang et al., Phys. Rev. A 94, 032337 (2016)], we analyze the degradation, creation, revival and enhancement of quantum correlation for different initial states and polarizations of two atoms, and the influence of interatomic separation and acceleration on quantum correlation. Compared with the entanglement dynamics discussed in [Y. Q. Yang et al., Phys. Rev. A 94, 032337 (2016)], it is found that quantum correlation exhibits better robustness than entanglement. This may be helpful for quantum information processing.
Hamiltonian formalism of topologically massive electrodynamics
Authors: Kim Taegyu , Kouwn Seyen , Oh Phillial
Published: March 2019

We consider the four-dimensional topologically massive electrodynamics in which a gauge field interacts with rank two antisymmetric tensor field through a topological interaction. The photon becomes massive by eating the rank two tensor field, which is dual to the Higgs mechanism. We explicitly demonstrate the nature of the mechanism by performing a canonical analysis of the theory and discuss various aspects of it.
Factorization method for exact solution of the non-central modified Killingbeck potential plus a ring-shaped-like potential
Authors: Mbadjoun B. Tchana , Ema’a J. M. Ema’a , Yomi Jean , Abiama P. Ele , Ben-Bolie G. H. , Ateba P. Owono
Published: March 2019

In this paper, we study the Schrödinger equation with non-central modified Killingbeck potential plus a ring-shaped-like potential problem, which is not spherically symmetric. The factorization method is used to solve the hypergeometric equation types which lead to solutions with the associate Laguerre function for the radial part and Jacobi polynomial for the polar part. We introduce the raising and lowering operators to calculate the energies eigenvalues, which show that the lack of spherical symmetry removes the degeneracy of second quantum number m which is completely expected. These obtained energies are better to explain the superposition of the energy levels of the atoms in the crystalline structure of molecules.
Infrared evidence for pressure-induced phase transition of α-Si3N4
Authors: Lei Jin-Qiao , Luo Yan , Chen Hong-Jie , Wang Shan-Min , Liu Ke , Zhou Xiao-Lin
Published: March 2019

X-ray diffraction (XRD) method and structural refinement were used to characterize the sample of [Formula: see text]-Si3N4. Rietveld analyses of XRD data confirmed that the sample belongs to hexagonal crystal (space group of P31c, No:159). The refined structural parameters are in agreement with the available theoretical and synchrotron radiation experimental results. Then, the infrared (IR) spectra of [Formula: see text]-Si3N4under 22 GPa were investigated with the diamond anvil cell (DAC). According to the IR absorption spectra at 296.3 K and 2 hPa (Observation range from 400 cm[Formula: see text] to 12,500 cm[Formula: see text]), we observed 23 IR active peaks. Normalized Fourier transform infrared (FTIR) absorption spectra under high pressure and room-temperature (296.3 K) show that [Formula: see text]-Si3N4undergoes a phase transition at 16.3 GPa and changes from hexagonal to cubic phase, namely, [Formula: see text]-Si3N4, which is very close to the result of our theoretical calculations, i.e., the phase transition pressure is 16.3 GPa.
Constraining values of bag constant for strange star candidates
Authors: Aziz Abdul , Ray Saibal , Rahaman Farook , Khlopov M. , Guha B. K.
Published: March 2019

We provide a strange star model under the framework of general relativity by using a general linear equation of state (EOS). The solution set thus obtained is employed on altogether 20 compact star candidates to constraint values of MIT bag model. No specific value of the bag constant ([Formula: see text]) a priori is assumed, rather possible range of values for bag constant is determined from observational data of the said set of compact stars. To do so, the Tolman–Oppenheimer–Volkoff (TOV) equation is solved by homotopy perturbation method (HPM) and hence we get a mass function for the stellar system. The solution to the Einstein field equations represents a nonsingular, causal and stable stellar structure which can be related to strange stars. Eventually, we get an interesting result on the range of the bag constant as [Formula: see text]. We have found the maximum surface redshift [Formula: see text] and shown that the central redshift ([Formula: see text]) cannot have value larger than [Formula: see text], where [Formula: see text]. Also, we provide a possible value of bag constant for neutron star with quark core using hadronic as well as quark EOS.
Texture classification using the rotational-invariant local symmetric tetra pattern
Authors: Suruliandi A. , Sinduja A. , Raja S. P.
Published: March 2019

Feature extraction plays a key role in pattern recognition problems. The texture feature is an important feature which helps to describe an image with textural information. A new texture descriptor, the Local Symmetric Tetra Pattern (LSTP), is proposed in this work. This descriptor is developed for the local description of an image. It considers not only the surrounding eight neighbors, but also the eight pixels at the next level to describe the texture efficiently. For every pixel, the maximum edge value, the number of negative sign bits and the number of positive sign bits for each degree of symmetry are computed. Image classification is experimented using the Original Brodatz, Outex and Kylberg Texture Dataset v.1.0 databases. The investigation results are compared with existing method which shows promising achievement of the proposed techniques in terms of their evaluation measures. It is also found that the proposed texture descriptor is rotationally invariant.
Blockholders on Boards and CEO Compensation, Turnover and Firm Valuation
Authors: Agrawal Anup , Nasser Tareque
Published: March 2019

We find that the presence of independent directors who are blockholders (IDBs) in firms promotes better CEO contracting and monitoring, and higher firm valuation. Using a panel of about 11,500 firm-years with a unique, hand-collected dataset on IDB-identity and a novel instrument, we find that firms with IDBs have lower excess CEO pay, lower flow and stock of CEO equity incentives, and higher valuations. These effects are substantial and robust. Our findings imply that by making it easier for blockholders to obtain a board seat, proxy access rules or bylaws can benefit shareholders.
Trade Intensity and Liquidity
Authors: Brigida Matt , Pratt William
Published: March 2019

This analysis investigates how liquidity is affected by periods of high trade intensity. Using an orderbook constructed directly from CME FIX/FAST messages and timestamped to the millisecond, we test whether the number of changes in the orderbook, the size of the bid–ask spread, and the number of trades in the few seconds before a trade have an effect on the book’s liquidity in the milliseconds after the trade. Since we calculate liquidity over a period of 100[Formula: see text]ms after a trade, we focus on liquidity provided by high-frequency traders (HFTs). We find evidence consistent with larger bid–ask spreads leading to greater amounts of liquidity being provided by HFT post-trade, and HFT providing liquidity when there is more activity in the orderbook. We further find that more trades lead to reduced liquidity, consistent with trades incorporating private information, and market makers’ fear of being adversely selected when providing liquidity.
Programming Stimuli-Responsive Behavior into Biomaterials
Authors: Badeau Barry A. , DeForest Cole A.
Published: March 2019

Stimuli-responsive materials undergo triggered changes when presented with specific environmental cues. These dynamic systems can leverage biological signals found locally within the body as well as exogenous cues administered with spatiotemporal control, providing powerful opportunities in next-generation diagnostics and personalized medicine. Here, we review the synthetic and strategic advances used to impart diverse responsiveness to a wide variety of biomaterials. Categorizing systems on the basis of material type, number of inputs, and response mechanism, we examine past and ongoing efforts toward endowing biomaterials with customizable sensitivity. We draw an analogy to computer science, whereby a stimuli-responsive biomaterial transduces a set of inputs into a functional output as governed by a user-specified logical operator. We discuss Boolean and non-Boolean operations, as well as the various chemical and physical modes of signal transduction. Finally, we examine current limitations and promising directions in the ongoing development of programmable stimuli-responsive biomaterials.
Generalized Born Implicit Solvent Models for Biomolecules
Authors: Onufriev Alexey V. , Case David A.
Published: March 2019

It would often be useful in computer simulations to use an implicit description of solvation effects, instead of explicitly representing the individual solvent molecules. Continuum dielectric models often work well in describing the thermodynamic aspects of aqueous solvation and can be very efficient compared to the explicit treatment of the solvent. Here, we review a particular class of so-called fast implicit solvent models, generalized Born (GB) models, which are widely used for molecular dynamics (MD) simulations of proteins and nucleic acids. These approaches model hydration effects and provide solvent-dependent forces with efficiencies comparable to molecular-mechanics calculations on the solute alone; as such, they can be incorporated into MD or other conformational searching strategies in a straightforward manner. The foundations of the GB model are reviewed, followed by examples of newer, emerging models and examples of important applications. We discuss their strengths and weaknesses, both for fidelity to the underlying continuum model and for the ability to replace explicit consideration of solvent molecules in macromolecular simulations.
Precision Medicine
Authors: Kosorok Michael R. , Laber Eric B.
Published: March 2019

Precision medicine seeks to maximize the quality of health care by individualizing the health-care process to the uniquely evolving health status of each patient. This endeavor spans a broad range of scientific areas including drug discovery, genetics/genomics, health communication, and causal inference, all in support of evidence-based, i.e., data-driven, decision making. Precision medicine is formalized as a treatment regime that comprises a sequence of decision rules, one per decision point, which map up-to-date patient information to a recommended action. The potential actions could be the selection of which drug to use, the selection of dose, the timing of administration, the recommendation of a specific diet or exercise, or other aspects of treatment or care. Statistics research in precision medicine is broadly focused on methodological development for estimation of and inference for treatment regimes that maximize some cumulative clinical outcome. In this review, we provide an overview of this vibrant area of research and present important and emerging challenges.
ELABELA, as a potential diagnostic biomarker of preeclampsia, regulates abnormally shallow placentation via APJ
Authors: Zhou Lu , Sun Hang , Cheng Ran , Fan Xiujun , Lai Shanshan , Deng Cheng
Published: March 2019

Preeclampsia (PE) is a major cause of maternal mortality and morbidity worldwide. Although there has been great progress in the understanding of PE, the exact cause for the disease development is still unclear. Recently, studies showed that genetic deletion of ELABELA (ELA, also known as APELA) could induce PE-like symptoms in mice. However, the role of ELA in the disease development of PE remains elusive. Our objective was to measure the changes of ELA levels in maternal serum, urine, and placenta from preeclamptic pregnant women and healthy pregnant women and evaluate the correlation between ELA levels and the occurrence of PE. Additionally, we investigated the effect of ELA on the migration and proliferation of human trophoblast cells. ELA levels are significantly decreased in late-onset PE pregnancies compared with normal pregnancies. The mRNA and protein expressions of ELA and the apelin receptor (APLNR or APJ) in late-onset PE placental tissues are also decreased. Furthermore, our in vitro study showed that the addition of ELA significantly increased the invasion ability and proliferation of trophoblast cells, which were inhibited by the APJ-specific antagonist ML221. Our study identified ELA as significantly decreased in late-onset PE; therefore, it might play an important role in the pathogenesis of late-onset PE.
Transgenerational impact of maternal obesogenic diet on offspring bile acid homeostasis and nonalcoholic fatty liver disease
Authors: Thompson Michael D. , Derse Alaina , Ferey Jeremie LA , Reid Michaela , Xie Yan , Christ Miranda , Chatterjee Deyali , Nguyen Chau , Harasymowicz Natalia , Guilak Farshid , Moley Kelle H. , Davidson Nicholas Oliver
Published: March 2019

Studies show maternal obesity is a risk factor for metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in offspring. Here we evaluated potential mechanisms underlying these phenotypes. Female C57Bl6 mice were fed chow or an obesogenic high-fat/high-sucrose (HF/HS) diet with subsequent mating of F1 and F2 female offspring to lean males to develop F2 and F3 generations, respectively. Offspring were fed chow or fibrogenic (high transfat, cholesterol, fructose) diets, and histopathological, metabolic changes, and bile acid (BA) homeostasis was evaluated. Chow-fed F1 offspring from maternal HF/HS lineages (HF/HS) developed periportal fibrosis and inflammation with aging, without differences in hepatic steatosis but increased BA pool size and shifts in BA composition. F1, but not F2 or F3, offspring from HF/HS showed increased steatosis on a fibrogenic diet, yet inflammation and fibrosis were paradoxically decreased in F1 offspring, a trend continued in F2 and F3 offspring. HF/HS feeding leads to increased periportal fibrosis and inflammation in chow-fed offspring without increased hepatic steatosis. By contrast, fibrogenic diet-fed F1 offspring from HF/HS dams exhibited worse hepatic steatosis but decreased inflammation and fibrosis. These findings highlight complex adaptations in NAFLD phenotypes with maternal diet.
Antiatherogenic effects of liraglutide in hyperglycemic apolipoprotein E-null mice via AMP-activated protein kinase-independent mechanisms
Authors: Koshibu Masakazu , Mori Yusaku , Saito Tomomi , Kushima Hideki , Hiromura Munenori , Terasaki Michishige , Takada Michiya , Fukui Tomoyasu , Hirano Tsutomu
Published: March 2019

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) exert potent glucose-lowering effects without increasing risks for hypoglycemia and weight gain. Preclinical studies have demonstrated direct antiatherogenic effects of GLP-1RAs in normoglycemic animal models; however, the underlying mechanisms in hyperglycemic conditions have not been fully clarified. Here we aimed to elucidate the role of AMP-activated protein kinase (AMPK) in antiatherogenic effects of GLP-1RAs in hyperglycemic mice. Streptozotocin-induced hyperglycemic apolipoprotein E-null mice were treated with vehicle, low-dose liraglutide (17 nmol·kg−1·day−1), or high-dose liraglutide (107 nmol·kg−1·day−1) in experiment 1 and the AMPK inhibitor dorsomorphin, dorsomorphin + low-dose liraglutide, or dorsomorphin + high-dose liraglutide in experiment 2. Four weeks after treatment, aortas were collected to assess atherosclerosis. In experiment 1, metabolic parameters were similar among the groups. Assessment of atherosclerosis revealed that high-dose liraglutide treatments reduced lipid deposition on the aortic surface and plaque volume and intraplaque macrophage accumulation at the aortic sinus. In experiment 2, liraglutide-induced AMPK phosphorylation in the aorta was abolished by dorsomorphin; however, the antiatherogenic effects of high-dose liraglutide were preserved. In cultured human umbilical vein endothelial cells, liraglutide suppressed tumor necrosis factor-induced expression of proatherogenic molecules; these effects were maintained under small interfering RNA-mediated knockdown of AMPKα1 and in the presence of dorsomorphin. Conversely, in human monocytic U937 cells, the anti-inflammatory effects of liraglutide were abolished by dorsomorphin. In conclusion, liraglutide exerted AMPK-independent antiatherogenic effects in hyperlipidemic mice with streptozotocin-induced hyperglycemia, with the possible involvement of AMPK-independent suppression of proatherogenic molecules in vascular endothelial cells.
Approaches and Methods to Measure Oxidative Stress in Clinical Samples: Research Applications in the Cancer Field
Authors: Katerji Meghri , Filippova Maria , Duerksen-Hughes Penelope
Published: March 2019

Reactive oxygen species (ROS) are common by-products of normal aerobic cellular metabolism and play important physiological roles in intracellular cell signaling and homeostasis. The human body is equipped with antioxidant systems to regulate the levels of these free radicals and maintain proper physiological function. However, a condition known as oxidative stress (OS) occurs, when ROS overwhelm the body’s ability to readily detoxify them. Excessive amounts of free radicals generated under OS conditions cause oxidative damage to proteins, lipids, and nucleic acids, severely compromising cell health and contributing to disease development, including cancer. Biomarkers of OS can therefore be exploited as important tools in the assessment of disease status in humans. In the present review, we discuss different approaches used for the evaluation of OS in clinical samples. The described methods are limited in their ability to reflect on OS only partially, revealing the need of more integrative approaches examining both pro- and antioxidant reactions with higher sensitivity to physiological/pathological alternations. We also provide an overview of recent findings of OS in patients with different types of cancer. Identification of OS biomarkers in clinical samples of cancer patients and defining their roles in carcinogenesis hold great promise in promoting the development of targeted therapeutic approaches and diagnostic strategies assessing disease status. However, considerable data variability across laboratories makes it difficult to draw general conclusions on the significance of these OS biomarkers. To our knowledge, no adequate comparison has yet been performed between different biomarkers and the methodologies used to measure them, making it difficult to conduct a meta-analysis of findings from different groups. A critical evaluation and adaptation of proposed methodologies available in the literature should therefore be undertaken, to enable the investigators to choose the most suitable procedure for each chosen biomarker.
A Comprehensive Analysis on Abundance, Distribution, and Bionomics of Potential Malaria Vectors in Mannar District of Sri Lanka
Authors: Gunathilaka Nayana , Hapugoda Menaka , Wickremasinghe Rajitha , Abeyewickreme Wimaladharma
Published: March 2019

Background. A detailed knowledge of the distribution of the malaria vectors in Mannar district of Sri Lanka has not been studied after 1927. Past records indicated the presence of only seven species of anophelines, namely, An. culicifacies, An. subpictus, An. barbirostris, An. peditaeniatus, An. nigerrimus, An. Jamesii, and An. maculatus. There have been many changes in terms of distribution of Anopheles in the district over time. Methods. Entomological surveillance was conducted on a monthly basis, comprising indoor hand collection, window trap collection, cattle-baited net collection, cattle-baited hut collection, and larval survey from June 2010 to June 2012 in 12 study areas under three entomological sentinel sites. The relationship between seven abiotic variables of the breeding habitats was measured. Pearson’s correlation coefficients were used to determine the associations between climatic variables and anopheline densities. Results. A total of 74,181 mosquitoes belonging to 14 Anopheles species were recorded. An. subpictus was the most predominant species from all techniques representing 92% (n=68,268) of the total anopheline collection. However, Anopheles culicifacies was not recorded from any site during the study period. Larval surveys identified 12 breeding habitat categories including waste water collections, lagoon water collections, and drains which were not recorded as breeding habitats by previous studies. The mean dissolved oxygen level of waste water collections was 3.45±0.15 mg/l. The mean salinity and conductivity of lagoon water collections were 21105±1344 mg/l and 34734±1974 μs/cm, respectively. Conclusion. The present study provides the updated knowledge on anopheline distribution and vector bionomics. Therefore, documentation of the current knowledge would be useful for learners and health authorities to design appropriate vector control measures in the prevention of reintroduction of malaria.
MicroRNA-25 Protects Smooth Muscle Cells against Corticosterone-Induced Apoptosis
Authors: Zhang Bin , Zhang Gaoxing , Wei Tianlu , Yang Zhen , Tan Wenfeng , Mo Ziqing , Liu Jinxue , Li Dong , Wei Yidong , Zhang Lukun , Webster Keith A. , Wei Jianqin
Published: March 2019

Background and Aims. Vascular smooth muscle cells (VSMCs) are central components of atherosclerotic plaque. Loss of VSMCs through apoptotic cell death can cause fibrous cap thinning, necrotic core formation, and calcification that may destabilize plaque. Elevated glucocorticoid levels caused by psychological stress promote VSMC apoptosis and can exacerbate atherosclerosis in mice and humans. Changes in the levels of antiapoptosis microRNA-25 (miR-25) have been linked with heart disease, inflammation, VSMC phenotype, oxidative stress, and apoptosis. Here, we investigated the pathways and mechanisms of glucocorticoid-induced apoptosis of mouse VSMCs and the protective role of miR-25. Methods. Primary mouse VSMCs were cultured +/- corticosterone for 48 h. Apoptosis, ROS, apoptotic protein activities, miR-25, MOAP1, a miR-25 target, and p70S6 kinase were quantified at intervals. The roles of miR-25 were assessed by treating cells with lenti-pre-miR-25 and anti-miR-25. Results. VSMC apoptosis, caspase-3 activity, and Bax were increased by corticosterone, and cell death was paralleled by marked loss of miR-25. Protection was conferred by pre-miR-25 and exacerbated by anti-miR-25. Pre-miR-25 conferred reduced expression of the proapoptotic protein MOAP1, and the protective effects of pre-miR-25 were abrogated by overexpressing MOAP1. The antiapoptotic effects of miR-25 were paralleled by inhibition of the p70S6K pathway, a convergence target for the survival signaling pathways, and protection by pre-miR-25 was abrogated by the p70S6k inhibitor rapamycin. Conclusions. MicroRNA-25 blocks corticosterone-induced VSMC apoptosis by targeting MOAP1 and the p70S6k pathway. Therapeutic manipulation of miR-25 may reduce atherosclerosis and unstable plaque formation associated with chronic stress.
Robust Power System Frequency Estimation Based on a Sliding Window Approach
Authors: Pei Dun , Xia Yili
Published: March 2019

A novel framework for online estimation of the fundamental frequency of power system in both the single‐phase and three‐phase cases is proposed. This is achieved based on the consideration of the relationship among the samples within every four consecutive sliding windows and the use of the Wiener filtering approach and an adaptive filter trained by the least mean square (LMS) algorithm. Compared with the original work proposed in Vizireanu, 2011, which employs the scalar samples, the proposed vector‐valued methods alleviate the drawbacks, such as sensitivity to initial phase value, noise, harmonics, DC offset, and system unbalance. Simulations on both benchmark synthetic cases and for real‐world scenarios support the analysis.
Meta-Analysis of Xihuang Pill Efficacy When Combined with Chemotherapy for Treatment of Breast Cancer
Authors: Mao Dan , Feng Lei , Huang Siqi , Zhang Shaofan , Peng Weijun , Zhang Sifang
Published: March 2019

Objective. To systematically evaluate the efficacy of Xihuang pill (XHP) in breast cancer patients receiving chemotherapy. Methods. Three English and four Chinese databases were searched. Literature was screened using EndNote X7 and data were analyzed by Review Manager. Results. This review included 13 randomized clinical studies of 1272 patients. The results showed that XHP increased the tumor response [risk ratio (RR) = 2.91; 95% confidence interval (CI): 1.98-4.26] and improved Karnofsky performance score (KPS) for breast cancer patients receiving chemotherapy [RR = 4.96; 95% CI = 2.07-11.86]. In addition, XHP treatment significantly reduced chemotherapy-induced adverse events, including nausea and vomiting [RR = 0.50; 95% CI = 0.33-0.74], WBC reduction [RR = 0.71; 95% CI = 0.47-1.06], platelet reduction [RR = 0.53; 95% CI = 0.19-1.44], hemoglobin reduction [RR = 0.31; 95% CI = 0.19-0.52], and hepatic function damage [RR = 0.63; 95% CI = 0.35-1.11]. Conclusion. XHP combined with chemotherapy in comparison with chemotherapy alone could significantly enhance the tumor response, improve KPS, and alleviate toxicity induced by chemotherapy in breast cancer patients.