bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete Circular Genome Sequence of a Multidrug-Resistant Escherichia coli Strain from Cuba Obtained with Nanopore and Illumina Hybrid Assembly
Authors: Hernández-Fillor Rosa Elena , Brilhante Michael , Espinosa Ivette , Perreten Vincent
Published: November 2019

The complete genome sequence of a multidrug-resistant
Escherichia coli
strain isolated from a healthy pig in Cuba was determined using short and long reads. This strain carried four plasmids, including a 42,683-kb IncX1 plasmid, which contains the third-generation cephalosporin resistance gene
bla
CTX-M-32
together with other disinfectant and antibiotic resistance genes.
A history of pore water oxygen isotope evolution in the Cretaceous Travis Peak Formation in East Texas
Authors: Denny Adam C. , Fall András , Orland Ian J. , Valley John W. , Eichhubl Peter , Laubach Stephen E.
Published: November 2019

Oxygen isotope analyses of diagenetic cements can provide detailed evidence of sedimentary burial processes and conditions, as the δ18O values of precipitating minerals reflect contemporaneous local δ18Owater and temperature conditions. Uncertainties in the timing and rates of pore water δ18O evolution in sedimentary basins can complicate interpretation of these records. Fracture-bridging (0.5–1 mm) quartz cements observed in sandstones of the Cretaceous Travis Peak Formation in the East Texas basin show clear growth-zoning by cathodoluminescence and contain detailed fluid inclusion records of temperature that make them excellent candidates for interrogating prolonged histories of basin temperature and the evolution of δ18O in basin pore water. New secondary ion mass spectrometer (SIMS) δ18Oquartz isotopic data from fluid inclusion-rich quartz bridges in Travis Peak sandstones record a steady increase of pore water δ18O values from ∼5 to 7‰ (VSMOW; Vienna Standard Mean Ocean Water) as the sandstone warms from ∼130 to 150 °C. To help evaluate whether this trend could be generated solely from local water-rock interactions in response to burial compaction, a one-dimensional closed system isotopic burial model was created to simulate how δ18Owater values change in a quartz-dominated sandstone during diagenesis. Using both directly measured and inferred rates of Travis Peak compaction, the magnitude of change in δ18Owater that we calculate from quartz bridge geochemistry cannot be reasonably modeled solely by local quartz mechanical compaction, pressure solution, and cementation processes, necessitating significant fluxes of silica and high-δ18O water from outside of the sandstones prior to maximum burial. This indicates that even units which appear surrounded by significant barriers to fluid flow (i.e., mudrock-bounded channel sandstones) may have been infiltrated and diagenetically modified by large fluxes of fluid on geologic time scales.
Association between disease-modifying therapies for multiple sclerosis and healthcare utilisation on a population level: a retrospective cohort study
Authors: Al-Sakran Lina , Marrie Ruth Ann , Blackburn David , Knox Katherine , Evans Charity
Published: November 2019

Objective

Disease-modifying therapy (DMT) use in multiple sclerosis (MS) has increased significantly. However, the impact of DMTs on healthcare use is limited and conflicting, and rarely examined at a population level. This study examined the association between DMTs and healthcare utilisation at the population level.

Design

Retrospective cohort.

Setting

Health administrative data from Saskatchewan, Canada (1997–2016).

Participants

To test for associations at the population level, we identified two cohorts. The general population cohort included all Saskatchewan residents ≥18 years who were drug plan beneficiaries. The MS cohort included individuals ≥18 years, identified using a validated definition (≥3 hospital, physician or drug claims for MS).

Main outcome measures and methods

To test for an association between the total number of DMT dispensations per year and the total number of hospitalisations we used negative binomial regression fitted with generalised estimating equations (GEE); only hospitalisations that occurred after the date of MS diagnosis (date of first claim for MS or demyelinating disease) were extracted. To test for an association between the number of DMT dispensations and physician claims, negative binomial distributions with GEE were fit as above. Results were reported as rate ratios (RR), with 95% CIs, and calculated for every 1000 DMT dispensations.

Results

The number of DMT dispensations was associated with a decreased risk for all-cause (RR=0.994; 95% CI 0.992 to 0.996) and MS-specific (RR=0.909; 95% CI 0.880 to 0.938) hospitalisations. The number of DMT dispensations was not associated with the number of all-cause (RR=1.006; 95% CI 0.990 to 1.022) or MS-specific (RR=0.962; 95% CI 0.910 to 1.016) physician claims.

Conclusion

Increased DMT use in Saskatchewan was associated with a reduction in hospitalisations, but did not impact the number of physician services used. Additional research on cost-benefit and differing treatment strategies would provide further insight into the true impact of DMTs on healthcare utilisation at a population level.
Patients' spirituality perspectives at the end of life: a qualitative evidence synthesis
Authors: Clyne Barbara , O’Neill Sinead M , Nuzum Daniel , O'Neill Michelle , Larkin James , Ryan Máirín , Smith Susan M
Published: November 2019

Background

Understanding patient perceptions of their spiritual needs when approaching the end of life is essential to support the delivery of patient-centred care.

Aim

To conduct a qualitative evidence synthesis on spirituality and spiritual care needs at the end of life in all healthcare settings from the patients’ perspective.

Design

Studies were included where they were primary qualitative studies exploring spirituality in patients with a life expectancy of 12 months or less in any setting. Two reviewers independently screened titles, extracted data and conducted methodological quality appraisal. A thematic synthesis was conducted. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) - Confidence in the Evidence from Reviews of Qualitative research (CERQual) was used to summarise the certainty of the evidence.

Data sources

Six databases (Medline, Embase, Cochrane, CINAHL, PsycINFO, Applied Social Science Index and Abstracts) were searched from inception up to January 2019.

Results

Fifty papers (42 unique datasets), incorporating data from 710 patients were included. Studies recruited from a mix of inpatient, outpatient, hospice and community settings across 12 different countries. Three overarching themes were generated: the concept of spirituality, spiritual needs and distress, and spiritual care resources. Relationships were an intrinsic component of spirituality.

Conclusion

Meeting patients’ spiritual needs is an integral part of end-of-life care. This work emphasises that supporting relationships should be a central focus of spiritual care for patients at the end of life.

PROSPERO registration number

CRD42019122062
Concurrent mutations in other epigenetic modulators portend better prognosis in BCOR-mutated myelodysplastic syndrome
Authors: Badaat Ibraahim , Mirza Sabbir , Padron Eric , Sallman David , Komrokji Rami , Song Jinming , Hussaini Mohammad O
Published: November 2019

Introduction

The role of single mutations has been extensively studied myelodysplastic syndromes (MDS), but the impact of genetic aberrations in the context of other mutations is less well understood.BCORis an epigenetic transcriptional corepressor. In MDS,BCORmutations are rare and certain mutations are associated with poor prognosis. Our aim was to investigate the role of concurrent mutations in epigenetic MDS-driver genes inBCOR-mutated MDS. We hypothesised that these would be redundant and would not contribute to worse prognosis.

Methods

Internal Next Generation Sequencing (NGS) database with targeted genetic profiling of >4000 tumor cases was queried to locate cases of MDS with BCL6 Corepressor protein (BCOR) mutations only (pBCOR) and cBCOR (comutated epigenetic modulators:TET2,ASXL1,DNMT3A,EZH2,IDH2,IDH1,BCORL1,ATRX). Overall survival was determined by chart review. Fischer’s exact test and unpaired t-test was performed for statistical analysis.

Results

25 patients with cBCOR were detected. Only five MDS patients with pBCOR were found. The number of patients with comutations (cBCOR) in epigenetic modulators comprisedTET2(n=5),ASXL1(n=9),DNMT3A(n=11),EZH2(n=2),IDH2(n=4), IDH1 (n=1),BCORL1(n=3),ATRX(n=1). cBCOR overall survival was 23.8 months versus 11.8 months for pBCOR group.

Conclusions

In this study, we confirm the rarity ofBCORmutations. Our results show that there is a trend towards poorer prognosis in patient with pBCOR versus cBCOR although statistical significance was not reached. This may be due to enrichment of poor cytogenetics in pBCOR or increased responsiveness to hypomethylating agents in cBCOR. Larger studies are needed to validate our data.
Deep phenotyping, including quantitative ciliary beating parameters, and extensive genotyping in primary ciliary dyskinesia
Authors: Blanchon Sylvain , Legendre Marie , Bottier Mathieu , Tamalet Aline , Montantin Guy , Collot Nathalie , Faucon Catherine , Dastot Florence , Copin Bruno , Clement Annick , Filoche Marcel , Coste André , Amselem Serge , Escudier Estelle , Papon Jean-Francois , Louis Bruno
Published: November 2019

Background

Primary ciliary dyskinesia (PCD) is a rare genetic disorder resulting in abnormal ciliary motility/structure, extremely heterogeneous at genetic and ultrastructural levels. We aimed, in light of extensive genotyping, to identify specific and quantitative ciliary beating anomalies, according to the ultrastructural phenotype.

Methods

We prospectively included 75 patients with PCD exhibiting the main five ultrastructural phenotypes (n=15/group), screened all corresponding PCD genes and measured quantitative beating parameters by high-speed video-microscopy (HSV).

Results

Sixty-eight (91%) patients carried biallelic mutations. Combined outer/inner dynein arms (ODA/IDA) defect induces total ciliary immotility, regardless of the gene involved. ODA defect induces a residual beating with dramatically low ciliary beat frequency (CBF) related to increased recovery stroke and pause durations, especially in case of DNAI1 mutations. IDA defect with microtubular disorganisation induces a low percentage of beating cilia with decreased beating angle and, in case of CCDC39 mutations, a relatively conserved mean CBF with a high maximal CBF. Central complex defect induces nearly normal beating parameters, regardless of the gene involved, and a gyrating motion in a minority of ciliated edges, especially in case of RSPH1 mutations. PCD with normal ultrastructure exhibits heterogeneous HSV values, but mostly an increased CBF with an extremely high maximal CBF.

Conclusion

Quantitative HSV analysis in PCD objectives beating anomalies associated with specific ciliary ultrastructures and genotypes. It represents a promising approach to guide the molecular analyses towards the best candidate gene(s) to be analysed or to assess the pathogenicity of the numerous sequence variants identified by next-generation-sequencing.
Cardiac valve involvement in ADAR-related type I interferonopathy
Authors: Crow Yanick , Keshavan Nandaki , Barbet Jacques Patrick , Bercu Geanina , Bondet Vincent , Boussard Charlotte , Dedieu Nathalie , Duffy Darragh , Hully Marie , Giardini Alessandro , Gitiaux Cyril , Rice Gillian Inara , Seabra Luis , Bader-Meunier Brigitte , Rahman Shamima
Published: November 2019

Background

Adenosine deaminases acting on RNA (ADAR) mutations cause a spectrum of neurological phenotypes ranging from severe encephalopathy (Aicardi-Goutières syndrome) to isolated spastic paraplegia and are associated with enhanced type I interferon signalling. In children, non-neurological involvement in the type I interferonopathies includes autoimmune and rheumatological phenomena, with calcifying cardiac valve disease only previously reported in the context of MDA5 gain-of-function.

Results

We describe three patients with biallelic ADAR mutations who developed calcifying cardiac valvular disease in late childhood (9.5–14 years). Echocardiography revealed progressive calcification of the valvular leaflets resulting in valvular stenosis and incompetence. Two patients became symptomatic with biventricular failure after 5–6.5 years. In one case, disease progressed to severe cardiac failure despite maximal medical management, with death occurring at 17 years. Another child received mechanical mitral and aortic valve replacement at 16 years with good postoperative outcome. Histological examination of the affected valves showed fibrosis and calcification.

Conclusions

Type I interferonopathies of differing genetic aetiology demonstrate an overlapping phenotypic spectrum which includes calcifying cardiac valvular disease. Individuals with ADAR-related type I interferonopathy may develop childhood-onset multivalvular stenosis and incompetence which can progress insidiously to symptomatic, and ultimately fatal, cardiac failure. Regular surveillance echocardiograms are recommended to detect valvular disease early.
FGFR3 autoantibodies in sensory neuronopathy
Authors: Latov Norman
Published: November 2019

FGFR3 antibodies have been associated with sensory neuropathy, but many questions remain regarding their use in clinical practice.
Catatonia with GABAAreceptor antibodies
Authors: Samra Kiran , Rogers Jonathan , Mahdi-Rogers Mohamed , Stanton Biba
Published: November 2019

A 22-year-old African woman developed acute behavioural change, against a background of sickle cell disease with strokes requiring a ventriculoperitoneal shunt. She alternated between mutism with prolonged staring and posturing, and a state of agitation with elation and echolalia. Cerebrospinal fluid (CSF) protein was elevated and electroencephalogram showed mild slowing with bitemporal slow and sharp waves. We suspected catatonia secondary to possible autoimmune encephalitis but her condition persisted despite intravenous methylprednisolone. After identifying a positive serum anti-gamma-aminobutyric acid-A (GABAA) antibody, treatment with intravenous immunoglobulin, oral corticosteroids and rituximab led to gradual improvement. Patients with catatonia may show reduced GABAAreceptor density and there are two other reports of catatonia with anti-GABAAantibodies. This patient’s treatment response supports the antibody’s causative role.
Hirayama disease causing hand tremor on neck flexion
Authors: Lui Tun Hing
Published: November 2019

A 21-year-old man presented with right-hand intrinsic muscle wasting and right-hand tremor on neck flexion. MR scan of cervical spine was normal in the neutral position, but on neck flexion showed anterior shift and flattening of the cervical cord, with prominent posterior epidural space and engorged epidural venous plexus. We diagnosed Hirayama disease and his condition stabilised with a neck collar and physiotherapy.
Enhancement of salt-stressed cucumber tolerance by application of glucose for regulating antioxidant capacity and nitrogen metabolism
Authors: Ma Siguang , Guo Shirong , Chen Jie , Sun Jin , Wang Yu , Shu Sheng
Published: November 2019

The current study was carried out to assess the potential functions of exogenous glucose (Glu) on plant growth, nitrogen metabolism, and antioxidant defense system in cucumber seedings under salt stress. Our results revealed that the cucumber seedlings exposed to salinity for 7 d exhibited a significant reduction of plant height, and fresh and dry weight. The salt-induced growth inhibition was effectively alleviated by foliar application of 100 mmol L−1 Glu. Exogenous Glu supplementation strikingly reduced the malondialdehyde content and controlled overaccumulation of superoxide anion ([Formula: see text]) generation rate in the salt-stressed cucumber leaves. In addition, Glu significantly increased the antioxidant enzymes activities such as super oxidase dismutase, peroxidase, catalase and ascorbate peroxidase, and regulated gene expressions of encoding these enzymes, which decreased oxidative damage induced by salt stress. The [Formula: see text] content significantly decreased, but the [Formula: see text] level significantly increased due to salt treatment. However, Glu significantly increased the activities of nitrate reductase and nitrite reductase in salt-stressed cucumber leaves, which coincided with modulating the gene expressions of key enzymes of nitrogen metabolism, and thus, promoted the conversion of ammonium nitrogen to amino acids and proteins. These results suggest that exogenous Glu could alleviate salt-induced growth inhibition through regulating antioxidant capacity and nitrogen metabolism, which is associated with an improvement of cucumber growth and salt tolerance.
A novel understanding of global DNA methylation in bobcat (Lynx rufus)
Authors: Cantrell Bonnie , Friedman Sydney , Lachance Hannah , Bernier Chris , Murdoch Brenda , Frattini Stefano , Talenti Andrea , Crepaldi Paola , McKay Stephanie
Published: November 2019

Epigenetic mechanisms may provide a novel prospective of bobcat (Lynx rufus) adaptation to habitat loss/fragmentation. Previous research has focused on bobcat behavior and genetics, but epigenetics has not been studied in bobcat. The aim of this study was to determine the quantity of global DNA methylation in the liver of 30 bobcats. DNA was extracted from liver samples obtained from the Vermont Fish and Wildlife Department. The percent of global DNA methylation was quantified and calculated using the MethylFlashTM Methylated DNA 5-mC Quantification Kit from Epigentek (Farmingdale, NY, USA). Age, sex, and carcass weight data were collected at sampling and analyzed with percent of global DNA methylation. Global DNA methylation was found to range from 0.46% to 2.76%. Age ranged from <1 to 12 years old and weight ranged from 3.18 to 13.61 kg. Further analysis of differential methylation may provide insight into novel means of bobcat conservation within different regions of Vermont. These results reinforce the need for genome-wide epigenetic studies in conservation biology.
Single-muon rate reduction for beam dump operation of the K12 beam line at CERN
Authors: Rosenthal M. , Banerjee D. , Bernhard J. , Brugger M. , Charitonidis N. , van Dijk M. , Döbrich B. , Gatignon L. , Gerbershagen A. , Montbarbon E. , Rae B. , Spadaro T.
Published: November 2019

The Physics Beyond Colliders study investigates the feasibility of future projects and experiments using CERN facilities. In the scope of this study, a future operation of the NA62 experiment using the existing K12 beam line operated in beam dump mode is discussed. Such a setup allows for a search for dark sector particles, e.g. heavy neutral leptons, dark photons and axions. Production of these hypothetical particles requires the 400GeV/c proton beam extracted from the Super Proton Synchrotron (SPS) to be dumped on a massive dump collimator located in the first part of the K12 beam line. The decay of these dark sector particles, for example, into muons could be detected by the NA62 experimental setup. However, muons created in particle interactions with material and from in-flight decays of secondary hadrons pose a critical background for this kind of experiment. Magnetic sweeping serves as an efficient tool for reducing this background. This paper discusses the simulation studies conducted with the software framework G4beamline to reduce the expected single-muon rate for this experiment. The required beam line modifications, in particular the removal of the beryllium target and repositioning of the dump, have been implemented into this model. A comparison of simulated muon distributions and spectra available experimental data, already taken in test runs, has been made in order to validate the beam line simulation. Finally, additional beam line modifications to further suppress the muon background are elaborated upon. These studies show a potential further reduction of a factor four of the total single-muon rate relative to the nominal setup over the full momentum range, and up to a factor twenty considering only muons with momenta [Formula: see text].
N-soliton and rogue wave solutions of (2+1)-dimensional integrable system with Lax pair
Authors: Issasfa Asma , Lin Ji
Published: November 2019

A new generalized (2[Formula: see text]+[Formula: see text]1)-dimensional model, obtained from the Kadomtsev–Petviashvili (KP) equation considered as a system of nonlinear evolution partial differential equations (PDEs), is introduced. With the usage of the Hirota bilinear method and the KP-hierarchy reduction method, N-soliton solutions of the integrable system are constructed. Considering the case of s[Formula: see text]=[Formula: see text]−1 in the linear differential operators, L1 and L2, and a specific set of parameters, two dark solitons, mixed solutions consisting of soliton-type and periodic waves solution are obtained. Based on the particular definition of the matrix elements, one and two rogue waves solutions expressed in terms of rational functions are derived. It is shown that the fundamental rogue waves are line rogue waves, which is different from the property of the moving line solitons of the soliton equations.
Manipulating Attributes of Natural Scenes via Hallucination
Authors: Karacan Levent , Akata Zeynep , Erdem Aykut , Erdem Erkut
Published: November 2019

In this study, we explore building a two-stage framework for enabling users to directly manipulate high-level attributes of a natural scene. The key to our approach is a deep generative network that can hallucinate images of a scene as if they were taken in a different season (e.g., during winter), weather condition (e.g., on a cloudy day), or at a different time of the day (e.g., at sunset). Once the scene is hallucinated with the given attributes, the corresponding look is then transferred to the input image while preserving the semantic details intact, giving a photo-realistic manipulation result. As the proposed framework hallucinates what the scene will look like, it does not require any reference style image as commonly utilized in most of the appearance or style transfer approaches. Moreover, it allows to simultaneously manipulate a given scene according to a diverse set of transient attributes within a single model, eliminating the need of training multiple networks per each translation task. Our comprehensive set of qualitative and quantitative results demonstrates the effectiveness of our approach against the competing methods.
Energy-aware device drivers for embedded operating systems
Authors: Buschhoff Markus , Falkenberg Robert , Spinczyk Olaf
Published: November 2019

Energy harvesting solutions with rechargeable batteries are a frequent choice to tackle the problems of supplying continuous power to deeply embedded devices like wireless sensor nodes. However, if the utilization of a node is not thoroughly planned, the battery may be drained too early and a continuous operation of such a device may become impossible. Here, an energy-management solution is required to control the flow of energy. As a foundation for energy management in software, we introduce a concept that allows to model energy consumption of hardware and to synthesize energy aware device drivers from these models. Our drivers are able to account the energy consumption of each driver function call at an accuracy of more than 90%. We provide a detailed overhead and accuracy evaluation of a driver implementation and hence prove the feasibility of our concept.
Performance-aware load shedding for monitoring events in container based environments
Authors: Brondolin Rolando , Ferroni Matteo , Santambrogio Marco
Published: November 2019

Runtime monitoring tools have become fundamental to assess the correct operation of complex systems and applications. Unfortunately, the more precise is the monitoring (sampling rate, information granularity, and so on), the higher is the overhead introduced in the system itself. In this paper, we propose a new load shedding framework that enables runtime adaptation of monitoring agents under heavy system load, exploiting an heuristic Load Manager to control the agent status and a runtime support for domain-specific policies. We implemented the proposed methodology on Sysdig, with an average control error improvement of 3.51x (12.25x at most), w.r.t. previous solutions.
Experimental Study on Comprehensive Real‐Time Methods to Determine Geological Condition of Rock Mass along the Boreholes while Drilling in Underground Coal Mines
Authors: Niu Ganggang , Zhang Kai , Yu Bosong , Chen Yanlong , Wu Yu , Liu Jiangfeng
Published: November 2019

The geological condition is essential for mining design and disaster control in underground coal mines. The present research focuses on the real‐time assessment method on rock mass condition during drilling boreholes. In situ comprehensive experiments were carried out using three methods, which are measurement while drilling (MWD) system, vibration measurement while drilling (VMWD) system, and borehole camera detecting system. In the MWD system, the operating parameters of the drilling machine were recorded, and a dimensionless index Id based on the collected parameters was adopted to assess the geological condition along the borehole. The results show that the state of rock mass can be well classified using the MWD system for both the cross‐layer and in‐seam boreholes. In the VMWD system, the vibration of the drilling bit was monitored, and the signal was analyzed in both time domain and frequency domain. The results indicate that the rock mass condition can be quantitatively evaluated using the mean square value of the signal and qualitatively estimated using the energy of the spectrum. In the borehole camera system, the photos of the rock mass along the borehole could be well captured, and the identified rock mass condition was used to verify the results of the MWD and VMWD systems. Comprehensive compassion between the results from the three systems shows that all the methods can give valuable information for the geological condition, and the outcomes of the different methods are generally comparable. For practical purposes, the advantages of the involved three detecting systems are discussed.
Generational Difference of Axial Length and Its Risk Factors in Urban and Rural China
Authors: Lin Zhong , Vasudevan Balamurali , Ciuffreda Kenneth J , Gao Tie Ying , Zhou Hong Jia , Liang Yuan Bo
Published: November 2019

Purpose. To compare the axial length difference (ALD) and the estimated generational axial length shift (ALS) from parents to their children and its risk factors in urban and rural China.Methods. Participants were enrolled from two longitudinal cohort studies, the Beijing Myopia Progression Study (BMPS) and the Handan Offspring Myopia Study (HOMS). Ocular biometry was performed in both parents and their children. ALD was defined as the difference between the children’s axial length and the corresponding parental axial length. Generational ALS was estimated according to a binominal prediction model at 18 years of age.Results. 237 and 380 urban and rural Chinese children (6–17 years) and their parents from the BMPS and HOMS, respectively, were enrolled. Children’s axial length was estimated to be closest to the parental axial length at 11 and 9 years of age in the urban and rural areas, respectively; the estimated generational ALS would be 1.53 and 0.57 mm, respectively. Multivariable regression analysis revealed that older children (urbanβ = 0.26,p<0.001; ruralβ = 0.11,p<0.001) and males had larger ALD (urbanβ = 0.55,p<0.001; ruralβ = 0.52,p<0.001) in both areas. Furthermore, urban children with more educated parents (fathers:β = −0.30,p=0.002; mothers:β = −0.29,p=0.004) and more outdoor activity (β = −0.23,p=0.006) had a less ALD.Conclusions. The urban generational axial length shift was estimated to be approximately 1 mm longer than that of the rural area. These results suggest different environmental effects on the ocular development in these two populations of Chinese children.
Impact of SNPs/Haplotypes of IL10 and IFNG on the Development of Diffuse Large B-Cell Lymphoma
Authors: Marangon Amanda Vansan , Colli Cristiane Maria , Cardozo Daniela Maira , Visentainer Jeane Eliete Laguila , Sell Ana Maria , Guimaraes Fernando , Marques Silvia Barbosa Dutra , Lieber Sophia Rocha , Aranha Francisco José Penteado , Zulli Roberto , de Souza Victor Hugo , de Souza Carmino Antonio
Published: November 2019

The purpose of this study was to assess the influence of single-nucleotide polymorphisms (SNPs) on cytokine genes in the development of diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients and 221 controls were investigated. Among them, 97 patients treated with R-CHOP were subdivided into two groups: (i) complete remission of the disease and (ii) patients who progressed to death, relapsed, or had disease progression. The SNPs investigated by PCR-SSP were TNF -308G>A (rs1800629), IFNG +874A>T (rs2430561), IL6 -174G>C (rs1800795), IL10 -1082A>G (rs1800896), IL10 -819C>T (rs1800871), IL10 -592C>A (rs1800872), and TGFB1 codon10T>C (rs1982073) and codon25G>C (rs1800471). In general, the genotypes that have been associated in the literature with lower production or intermediate production of IL-10 and higher production of IFN-γ were associated with the protection of the development of the disease, possibly favoring the Th1 immune response and diminishing the capacity of cell proliferation. However, patients receiving R-CHOP treatment presented unfavorable prognoses in the presence of genotypes related to the intermediate production of IL-10 and high production of TGF-β1, indicating that cytokines may be related to the response to treatment and action mechanisms of Rituximab.
Incidence and Risk Factors for Postoperative Delirium in Patients Undergoing Spine Surgery: A Systematic Review and Meta-Analysis
Authors: Wu Xinjie , Sun Wei , Tan Mingsheng
Published: November 2019

Background. The present study aims to investigate the incidence and risk factors associated with postoperative delirium in patients undergoing spine surgery. Methods. PubMed, EMBASE, Cochrane Library, and Science Citation Index were searched up to August 2019 for studies examining postoperative delirium following spine surgery. Incidence and risk factors associated with delirium were extracted. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for outcomes. The Newcastle–Ottawa Scale (NOS) was used for the study quality evaluation. Results. The final analysis includes a total of 40 studies. The pooled analysis reveals that incidence of delirium is 8%, and there are significant differences for developing delirium in age (OR 1.07; 95% CI 1.04–1.09), age more than 65 (OR 4.77; 95% CI 4.37–5.16), age more than 70 (OR 15.87; 95% CI 6.03–41.73), and age more than 80 (OR 1.91; 95% CI 1.78–2.03) years, male (OR 0.81; 95% CI 0.76–0.86), a history of alcohol abuse (OR 2.11; 95% CI 1.67–2.56), anxiety (OR 1.74; 95% CI 1.04–2.44), congestive heart failure (OR 1.4; 95% CI 1.21–1.6), depression (OR 2.5; 95% CI 1.52–3.49), hypertension (OR 1.12; 95% CI 1.04–1.2), kidney disease (OR 1.41; 95% CI 1.16–1.66), neurological disorder (OR 4.66; 95% CI 4.22–5.11), opioid use (OR 1.86; 95% CI 1.18–2.54), psychoses (OR 2.77; 95% CI 2.29–3.25), pulmonary disease (OR 1.81; 95% CI 1.27–2.35), higher mini-mental state examination (OR 0.7; 95% CI 0.5–0.89), preoperative pain (OR 1.88; 95% CI 1.11–2.64), and postoperative urinary tract infection (OR 5.68; 95% CI 2.41–13.39). Conclusions. A comprehensive understanding of incidence and risk factors of delirium can improve prevention, diagnosis, and management. Risk of postoperative delirium can be reduced based upon identifiable risk factors.
YAP Levels Combined with Plasma CEA Levels Are Prognostic Biomarkers for Early-Clinical-Stage Patients of Colorectal Cancer
Authors: Xu Zihui , Wang Hui , Gao Ling , Zhang Hongfeng , Wang Xiangyang
Published: November 2019

Background. Colorectal cancer (CRC) is one of the most common cancers worldwide. Surgical operation is routinely applied to patients with CRC. An important part of postoperative care for patients is to assess the prognosis of patients, especially those with early-stage cancers. However, effective biomarkers for CRC prognosis remain inadequate. The purpose of this study was to assess the prognostic potential of Yes-associated protein (YAP) and carcinoembryonic antigen (CEA) in early-stage CRC. Methods. A total of 116 matched pairs of CRC tissues and adjacent normal mucosae as well as 73 cases of metastatic lymph nodes were analyzed. Results. The results show that CRC tissues exhibited higher YAP expression compared with the adjacent normal mucosae. Immunohistochemical analysis shows that YAP expression in the CRC or lymphatic metastatic tissues was clearly higher than that in normal mucosae (P<0.01), whereas that in CRC tissues with lymphatic metastasis was higher than that in tissues without lymphatic metastasis (P<0.05). YAP expression is associated with serosal invasion, lymphatic metastasis, lymph node ratio, remote metastasis, Dukes stage, and CEA levels (P<0.05). YAP and CEA are independent predictors of the survival of CRC patients (P<0.05 and P<0.01). YAP predicted CRC prognosis primarily for patients with late-clinical-stage CRC (P=0.002), but not for patients with early-clinical-stage CRC (P=0.083). However, patients with high YAP and high CEA levels exhibited lower overall survival rates than those with low YAP expression in early-clinical-stage CRC (P<0.001). Conclusion. High YAP levels in the cancer tissues combined with high plasma CEA levels are potential biomarkers for predicting CRC prognosis in the early clinical stage.
The Effect of Low Carbohydrate Diet on Polycystic Ovary Syndrome: A Meta-Analysis of Randomized Controlled Trials
Authors: Zhang Xiaoshuai , Zheng Yang , Guo Yanan , Lai Zhiwen
Published: November 2019

Objective. To assess the effect of a low carbohydrate diet (LCD) on women with polycystic ovary syndrome (PCOS). Methods. Data from randomized controlled trials (RCTs) were obtained to perform a meta-analysis of the effects of LCD in PCOS patients. The primary outcomes included the changes in BMI, homeostatic model assessment for insulin resistance (HOMA-IR), and blood lipids, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), follicle-stimulating hormone (FSH), luteotropic hormone (LH), total testosterone (T), and sex hormone-binding globulin (SHBG). Results. Eight RCTs involving 327 patients were included. In comparison with the control group, the LCD decreased BMI (SMD = −1.04, 95% CI (−1.38, −0.70), P<0.00001), HOMA-IR (SMD = −0.66, 95% CI (−1.01, −0.30), P<0.05), TC (SMD = −0.68, 95% CI (−1.35, −0.02), P<0.05), and LDL-C (SMD = −0.66, 95% CI (−1.30, −0.02), P<0.05). Stratified analyses indicated that LCD lasting longer than 4 weeks had a stronger effect on increasing FSH levels (MD = 0.39, 95% CI (0.08, 0.71), P<0.05), increasing SHBG levels (MD = 5.98, 95% CI (3.51, 8.46), P<0.05), and decreasing T levels (SMD = −1.79, 95% CI (−3.22, −0.36), P<0.05), and the low-fat and low-CHO LCD (fat <35% and CHO <45%) had a more significant effect on the levels of FSH (MD = 0.40, 95% CI (0.09, 0.71), P<0.05) and SHBG (MD = 6.20, 95% CI (3.68, 8.72), P<0.05) than the high-fat and low-CHO LCD (fat >35% and CHO <45%). Conclusion. Based on the current evidence, LCD, particularly long-term LCD and low-fat/low-CHO LCD, may be recommended for the reduction of BMI, treatment of PCOS with insulin resistance, prevention of high LDL-C, increasing the levels of FSH and SHBG, and decreasing the level of T level. Together, the analyzed data indicate that proper control of carbohydrate intake provides beneficial effects on some aspects of PCOS and may represent one of the important interventions improving the clinical symptoms of affected patients.
Isolated Testicular Metastasis Diagnosed More than a Decade and a Half Post Primary Treatment for Prostate Cancer
Authors: Abou Heidar Nassib F. , Bustros Gerges , El-Asmar Jose M. , Sabatto Bassel Zein , Degheili Jad A.
Published: November 2019

Prostate cancer is the most common visceral malignancy among men. It rarely metastasizes to the testicles. We herein present the case of a male patient who underwent a radical prostatectomy for a grade group 3 Gleason score 7 (4+3) prostate adenocarcinoma followed by adjuvant radiation therapy and continuous androgen deprivation therapy after his first biochemical recurrence. Despite optimal management, prostate-specific antigen (PSA) levels rose back up, upon which a PET/CT 68Gallium scan demonstrated an isolated left testicular lesion that turned out to be of prostatic origin following orchiectomy. Testicular metastases from prostate cancer are of unknown prognosis, and the current treatment modality favors an orchiectomy.
Safety Assessment of Methanol Extract ofMelastoma malabathricumL. Leaves following the Subacute and Subchronic Oral Consumptions in Rats and Its Cytotoxic Effect against the HT29 Cancer Cell Line
Authors: Kamsani N. E. , Zakaria Z. A. , Md Nasir N. L. , Mohtarrudin N. , Mohamad Alitheen N. B.
Published: November 2019

Methanol extract ofMelastoma malabathricum(MEMM) has been traditionally used by the Malay to treat various ailments. In an attempt to develop the plant as an herbal product, MEMM was subjected to the subacute and subchronic toxicity and cytotoxicity studies. On the one hand, the subacute study was performed on three groups of male and three groups of female rats (n = 6), which were orally administered with 8% Tween 80 (vehicle control group) or MEMM (500 and 1000 mg/kg) daily for 28 days, respectively. On the other hand, the subchronic study was performed on four groups of rats (n = 6), which were orally administered with 8% Tween 80 (vehicle control group) or MEMM (50, 250, and 500 mg/kg) daily for 90 days, respectively. In thein vitrostudy, the cytotoxic effect of MEMM against the HT29 colon cancer cell line was assessed using the MTT assay. MEMM was also subjected to the UHPLC-ESI-HRMS analysis. The results demonstrated that MEMM administration did not cause any mortality, irregularity of behaviour, modification in body weight, as well as food and water intake following the subacute and subchronic oral treatment. There were no significant differences observed in haematological parameters between treatment and control groups in both studies, respectively. Thein vitrostudy demonstrated that MEMM exerts a cytotoxic effect against the HT29 colon cancer cell line when observed under the inverted and phase-contrast microscope and confirmed by the acridine orange/propidium iodide (AOPI) staining. The UHPLC-ESI-HRMS analysis of MEMM demonstrated the occurrence of several compounds including quercetin,p-coumaric acid, procyanidin A, and epigallocatechin. In conclusion,M. malabathricumleaves are safe for oral consumption either at the subacute or subchronic levels and possess cytotoxic action against the HT29 colon cancer cells possibly due to the synergistic action of several flavonoid-based compounds.
Various Parts of Helianthus annuus Plants as New Sources of Antimalarial Drugs
Authors: Ekasari Wiwied , Widya Pratiwi Dwi , Amanda Zelmira , Suciati  , Widyawaruyanti Aty , Arwati Heny
Published: November 2019

Background. Each part of H. annuus plants is traditionally used as medicinal remedies for several diseases, including malaria. Antimalarial activity of the leaf and the seed has already been observed; however, there is no report about antimalarial activity of the other parts of H. annuus plants. In this study, we assess in vitro and in vivo antimalarial activity of each part of the plants and its mechanism as antimalarial agent against inhibition of heme detoxification. Objective. To investigate the antimalarial activity of various parts of H. annuus. Methods. Various parts of the H. annuus plant were tested for in vitro antimalarial activity against Plasmodium falciparum 3D7 strain (chloroquine-sensitive), in vivo antimalarial activity against P. berghei using Peters’ 4-day suppressive test in BALB/c mice, curative and prophylaxis assay, and inhibition of heme detoxification by evaluating β-hematin level. Results. Ethanol extract of the roots showed the highest antimalarial activity, followed by ethanol extract of leaves, with IC50 values of 2.3 ± 1.4 and 4.3 ± 2.2 μg/mL, respectively and the percentage inhibition of P. berghei of 63.6 ± 8.0 and 59.3 ± 13.2 at a dose of 100 mg/kg, respectively. Ethanol extract of roots produced an ED50 value of 10.6 ± 0.2 mg/kg in the curative test and showed an inhibition of 79.2% at a dose of 400 mg/kg in the prophylactic assay. In inhibition of heme detoxification assay, root and leaf ethanol extracts yielded a lower IC50 value than positive (chloroquine) control with a value of 0.4 ± 0.0 and 0.5 ± 0.0 mg/mL, respectively. Conclusion. There were promising results of the ethanol extracts of root of H. annuus as a new source for the development of a new plant-based antimalarial agent.
Study on the Multitarget Mechanism and Key Active Ingredients of Herba Siegesbeckiae and Volatile Oil against Rheumatoid Arthritis Based on Network Pharmacology
Authors: Yang Xin , Li Yahui , Lv Runlin , Qian Haibing , Chen Xiangyun , Yang Chang Fu
Published: November 2019

Background. Herba Siegesbeckiae (HS, Xixiancao in Chinese) is widely used to treat inflammatory joint diseases such as rheumatoid arthritis (RA) and arthritis, and its molecular mechanisms and active ingredients have not been completely elucidated. Methods. In this study, the small molecule ligand library of HS was built based on Traditional Chinese Medicine Systems Pharmacology (TCMSP). The essential oil from HS was extracted through hydrodistillation and analyzed by Gas Chromatography-Mass Spectrometer (GC-MS). The target of RA was screened based on Comparative Toxicogenomics Database (CTD). The key genes were output by the four algorithms’ maximum neighborhood component (MNC), degree, maximal clique centrality (MCC), and stress in cytoHubba in Cytoscape, while biological functions and pathways were also analyzed. The key active ingredients and mechanism of HS and essential oil against RA were verified by molecular docking technology (Sybyl 2.1.1) in treating RA. The interaction between 6 active ingredients (degree ≥ 5) and CSF2, IL1β, TNF, and IL6 was researched based on the software Ligplot. Results. There were 31 small molecule constituents of HS and 16 main chemical components of essential oil (relative content >1%) of HS. There were 47 chemical components in HS. Networks showed that 9 core targets (TNF, IL1β, CSF2, IFNG, CTLA4, IL18, CD26, CXCL8, and IL6) of RA were based on Venn diagrams. In addition, molecular docking simulation indicated that CSF2, IL1β, TNF, and IL6 had good binding activity with the corresponding compounds (degree > 10).The 6 compounds (degree ≥ 5) of HS and essential oil had good interaction with 5 or more targets. Conclusion. This study validated and predicted the mechanism and key active ingredients of HS and volatile oil in treating RA. Additionally, this study provided a good foundation for further experimental studies.
Winner’s Optimal Reimbursement in Contest
Authors: Liu Yong , Dong Shaozeng
Published: November 2019

This paper explores a designer-optimal reimbursement scheme in all-pay auctions with winner’s reimbursement. Assuming the reimbursement is a linear function of the cost of effort, we obtain analytical solutions for the contestants’ symmetrical equilibrium effort and the contest organizer’s expected revenue. We show that if the effort cost function is concave, the optimal reimbursement scheme is to return the full cost to the winner. On the contrary, if the effort cost function is convex, the optimal reimbursement scheme is not to compensate the winner. Moreover, we find that the organizer’s expected revenue may increase or decrease as the number of contestants increases when the winner is fully reimbursed.
Homogeneity Parameter in Contrast-Enhanced Ultrasound Imaging Improves the Classification of Abnormal Cervical Lymph Node after Thyroidectomy in Patients with Papillary Thyroid Carcinoma
Authors: Zhan Jia , Diao Xue-Hong , Chen Yue , Wang Wen-Ping , Ding Hong
Published: November 2019

Objective. To explore the conventional and contrast-enhanced ultrasound (CEUS) features of cervical lymph node metastasis (CLNM) in papillary thyroid carcinoma (PTC) patients postoperatively and analyze its pathological basis. Materials and Methods. Conventional and CEUS were performed in 86 abnormal cervical lymph nodes (ACLNs) from 56 PTC patients who had received thyroidectomy. Then, fine-needle aspiration (FNA) was taken to confirm pathological results, a multivariate analysis was performed to correlate the sonographic features of the CLNM, and then an equation for CLNM was established. Results. Fifty-four lymph nodes were confirmed to be metastasis of PTC by FNA. Intensity at peak time, homogeneity, and color flow patterns, cystic change, or microcalcification and echogenicity were significantly associated with CLNM. Multivariate analysis showed three strongest features (homogeneity, intensity of peak, and cystic change or calcification) to be significantly associated with the evidence of CLNM. Then, the equation was established with the following significant predictive factors: P = 1/1 + exp∑[−3.213 + 2.77 ∗ cystic or calcification + 0.13 ∗ CDFI patterns + 3.65 ∗ homogeneity + 2.43 ∗ intensity at peak time]. Conclusion. Depiction of a heterogeneous hyperenhancement of cervical lymph nodes within CEUS studies and cystic change or microcalcification in conventional ultrasound were identified as predictive for metastatic lymph node invasion, and the equation was more accurate for predicting CLNM compared to single B-mode ultrasound and CEUS feature.
A Calcium-Rich Multimineral Intervention to Modulate Colonic Microbial Communities and Metabolomic Profiles in Humans: Results from a 90-Day Trial
Authors: Aslam Muhammad N. , Bassis Christine M. , Bergin Ingrid L. , Knuver Karsten , Zick Suzanna M. , Sen Ananda , Turgeon D. Kim , Varani James
Published: November 2019

Aquamin is a calcium-, magnesium-, and multiple trace element–rich natural product with colon polyp prevention efficacy based on preclinical studies. The goal of this study was to determine the effects of Aquamin on colonic microbial community and attendant metabolomic profile. Thirty healthy human participants were enrolled in a 90-day trial in which Aquamin (delivering 800 mg of calcium per day) was compared with calcium alone or placebo. Before and after the intervention, colonic biopsies and stool specimens were obtained. All 30 participants completed the study without serious adverse event or change in liver and renal function markers. Compared with pretreatment values, intervention with Aquamin led to a reduction in total bacterial DNA (P = 0.0001) and a shift in the microbial community measured by thetaYC (θYC; P = 0.0087). Treatment with calcium also produced a decline in total bacteria, but smaller than seen with Aquamin, whereas no reduction was observed with placebo in the colon. In parallel with microbial changes, a reduction in total bile acid levels (P = 0.0375) and a slight increase in the level of the short-chain fatty acid (SCFA) acetate in stool specimens (P < 0.0001) from Aquamin-treated participants were noted. No change in bile acids or SCFAs was observed with calcium or placebo. We conclude that Aquamin is safe and tolerable in healthy human participants and may produce beneficial alterations in the colonic microbial community and the attendant metabolomic profile. Because the number of participants was small, the findings should be considered preliminary.