bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure‐based drug design and in vitro testing reveal new inhibitors of enoyl‐acyl carrier protein reductases
Authors: Ghattas Mohammad A. , Eissa Nermin A. , Tessaro Francesca , Perozzo Remo , Scapozza Leonardo , Obaid Dana , Atatreh Noor 
Published: May 2019

AbstractThe need for new antibacterial agents is increasingly becoming of great importance as bacterial resistance to current drugs is quickly spreading. Enoyl‐acyl carrier protein reductases (FabI) are important enzymes for fatty acid biosynthesis in bacteria and other micro‐organisms. In this project, we conducted structure‐based virtual screening against the FabI enzyme, and accordingly, 37 compounds were selected for experimental testing. Interestingly, five compounds were able to demonstrate antimicrobial effect with variable inhibition activity against various strains of bacteria and fungi. Minimum inhibitory concentrations of the active compounds were determined and showed to be in low to medium micromolar range. Subsequently, enzyme inhibition assay was carried out for our five antimicrobial hits to confirm their biological target and determine their IC50 values. Three of these tested compounds exhibited inhibition activity for the FabI enzyme where our best hit MN02 had an IC50 value of 7.8 μM. Furthermore, MN02 is a small bisphenolic compound that is predicted to have all required features to firmly bind with the target enzyme. To sum up, hits discovered in this work can act as a good starting point for the future development of new and potent antimicrobial agents.
“It's not an illness, it's just bad luck”: The impact of anaphylaxis on quality of life in adults
Authors: Knibb Rebecca C. , Huissoon Aarnoud P. , Baretto Richard , Ekbote Anjali , Onyango‐Odera Shamim , Screti Cassandra , Newman Kristina L. , Krishna Mamidipudi T. 
Published: May 2019

AbstractBackgroundAn increasing number of adults are being diagnosed with anaphylaxis, but its impact on health‐related quality of life (HRQol) is not known.ObjectiveThe aim of this study was to explore the impact of anaphylaxis on HRQoL of newly diagnosed adults.MethodsInterviews were conducted with 13 adults (aged 40‐71; five males) with anaphylaxis (meeting WAO diagnostic criteria) to drugs, food, venom or spontaneous anaphylaxis, recruited using purposive sampling from allergy clinics in Birmingham, UK. Data were transcribed verbatim and analysed using thematic analysis.ResultsFour themes were generated from the analysis: the journey from fear to frustration; the need to maintain a healthy identity; control over uncertainty; and the supportive role of others. Participants described their first experiences of anaphylaxis as frightening. Managing the condition was associated with frustration and anxiety, in part due to uncertainty regarding when anaphylaxis might occur. Participants did not consider their allergy as an illness and wanted to retain an identity as a healthy person. They felt a strong need to have control over their anaphylaxis so that it did not take over their lives. The support from others was extremely important, but a lack of understanding of anaphylaxis sometimes hindered that support.Conclusions and Clinical RelevanceAnaphylaxis has an adverse impact on the HRQoL of adults irrespective of the cause. More information about anaphylaxis and its management from healthcare professionals may help patients gain a sense of control over their condition and reduce the worry and anxiety associated with it.
A nationwide study on the incidence of mesenteric ischaemia after surgery for rectal cancer demonstrates an association with high arterial ligation
Authors: Sörelius K. , Svensson J. , Matthiessen P. , Rutegård J. , Rutegård M. 
Published: May 2019

AbstractAimThe incidence of mesenteric ischaemia after resection for rectal cancer has not been investigated in a population‐based setting. The use of high ligation of the inferior mesenteric artery might cause such ischaemia, as the bowel left in situ depends on collateral blood supply after a high tie.MethodThe Swedish Colorectal Cancer Registry was used to identify all patients subjected to an abdominal resection for rectal cancer during the years 2007–2017 inclusive. Mesenteric ischaemia within the first 30 postoperative days was recorded, classified as either stoma necrosis or colonic necrosis. Multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for mesenteric ischaemia in relation to high tie, with adjustment for confounding.ResultsSome 14 657 patients were included, of whom 59 (0.40%) had a reoperation for any type of mesenteric ischaemia, divided into 34 and 25 cases of stoma necrosis and colonic necrosis, respectively. Compared with patients who did not require reoperation for mesenteric ischaemia following rectal cancer surgery, the proportion having high tie was greater (54.2% vs 38.5%; P = 0.032). The adjusted OR for reoperation due to any mesenteric ischaemia with high tie was 2.26 (95% CI 1.34–3.79), while the corresponding estimates for stoma and colonic necrosis, respectively, were 1.60 (95% CI 0.81–3.17) and 3.69 (95% CI 1.57–8.66).ConclusionThe incidence of reoperation for mesenteric ischaemia after abdominal resection for rectal cancer is low, but the use of a high tie might increase the risk of colonic necrosis demanding surgery.
T‐cell pseudolymphoma in recurrent herpes simplex virus infection
Authors: Mitteldorf Christina , Geissinger Eva , Pleimes Marc , Schön Michael P. , Kempf Werner 
Published: May 2019

AbstractBackgroundIn cases of herpes virus infection without typical histologic (and clinical) signs it is difficult to achieve the correct diagnosis by histology alone. Some of those cases are prone to be misdiagnosed as cutaneous lymphoma.MethodsThis retrospective study included five patients with herpes simplex virus (HSV)‐associated pseudolymphoma. We investigated clinical, histomorphologic and immunophenotypic features of all patients.ResultsAll biopsy specimens presented a superficial and deep perivascular lymphohistiocytic infiltrate with epidermotropism, atypia and admixed plasma cells to varying degrees. Four of five samples showed lining‐up of lymphocytes in the junctional zone with predominance of CD8+ lymphocytes, in contrast to the dermal part (inverse CD8:CD4 ratio). Papillary edema was found in four of five cases. Clinically, patchy erythema located on the buttocks and adjacent areas was typical, sometimes with erosions and crusts. Medical history of recurrent blisters, pain or itching was additionally helpful.ConclusionWe point out subtle but consistent histomorphologic criteria, which were helpful to diagnose HSV‐associated pseudolymphoma in context with the clinical presentation.
Clustering and ensembling approaches to support surrogate‐based species management
Authors: Sofaer Helen R. , Flather Curtis H. , Skagen Susan K. , Steen Valerie A. , Noon Barry R. 
Published: May 2019

AbstractAimSurrogate species can provide an efficient mechanism for biodiversity conservation if they encompass the needs or indicate the status of a broader set of species. When species that are the focus of ongoing management efforts act as effective surrogates for other species, these incidental surrogacy benefits lead to additional efficiency. Assessing surrogate relationships often relies on grouping species by distributional patterns or by species traits, but there are few approaches for integrating outputs from multiple methods into summaries of surrogate relationships that can inform decision‐making.LocationPrairie Pothole Region of the United States.MethodsWe evaluated how well five upland‐nesting waterfowl species that are a focus of management may act as surrogates for other wetland‐dependent birds. We grouped species by their patterns of relative abundance at multiple scales and by different sets of traits, and evaluated whether empirical validation could effectively select among the resulting species groupings. We used an ensemble approach to integrate the different estimated relationships among species and visualized the ensemble as a network diagram.ResultsEstimated relationships among species were sensitive to methodological decisions, with qualitatively different relationships arising from different approaches. An ensemble provided an effective tool for integrating across different estimates and highlighted the Sora (Porzana carolina), American Avocet (Recurvirostra Americana) and Black Tern (Chlidonias niger) as the non‐waterfowl species expected to show the strongest incidental surrogacy relationships with the waterfowl that are the focus of ongoing management.Main conclusionsAn ensemble approach integrated multiple estimates of surrogate relationship strength among species and allowed for intuitive visualizations within a network. By accounting for methodological uncertainty while providing a simple continuous metric of surrogacy, our approach is amenable to both further validation and integration into decision‐making.
Mediation analysis of the relationship between type 2 diabetes and cardiovascular events and all‐cause mortality: Findings from the SMART cohort
Authors: Sharif Shahnam , Groenwold Rolf H. H. , van der Graaf Yolanda , Berkelmans Gijs F. N. , Cramer Maarten J. , Visseren Frank L. J. , Westerink Jan ,   On behalf of the SMART study group
Published: May 2019

AbstractAimTo quantify the magnitude and specific contributions of known cardiovascular risk factors leading to higher cardiovascular risk and all‐cause mortality caused by type 2 diabetes (T2D).MethodsMediation analysis was performed to assess the relative contributions of known classical risk factors for vascular disease in T2D (insulin resistance, systolic blood pressure, renal function, LDL‐cholesterol, triglycerides and micro‐albuminuria), and what proportion of the effect of T2D on cardiovascular events and all‐cause mortality these factors mediate in the Second Manifestations of ARTerial disease (SMART) cohort consisting of 1910 T2D patients.ResultsOnly 35% (95% CI 15‐71%) of the excess cardiovascular risk caused by T2D is mediated by the classical cardiovascular risk factors. The largest mediated effect was through insulin resistance [proportion of mediated effect (PME) 18%, 95% CI 3‐37%], followed by elevated triglycerides (PME 8%, 95% CI 4‐14%) and micro‐albuminuria (PME 7%, 95% CI 3‐17%). Only 42% (95% CI 18‐73%) of the excess mortality risk was mediated by the classical risk factors considered. The largest mediated effect was by micro‐albuminuria (PME 18%, 95% CI 10‐29%) followed by insulin resistance (PME 15%, 95% CI 1‐33%).ConclusionA substantial amount of the increased cardiovascular risk and all‐cause mortality caused by T2D cannot be explained by traditional vascular risk factors. Future research should focus on identifying non‐classical pathways that might further explain the increased cardiovascular and mortality risk caused by T2D.
On nonlinear dependencies in African stock markets
Authors: Okorie Idika E. , Nadarajah Saralees 
Published: May 2019

AbstractFerreira, Dionisio, and Correia (2018. Physica A: Statistical Mechanics and Its Applications. 505, 680–687) showed that African stock markets at different time frames (before the Lehman Brothers financial crisis, during the crisis, and after the crisis) do not satisfy the efficient market hypothesis. Here, we provide evidence by means of six different nonparametric tests, and the fit of GARCH(1, 1), TGARCH(1, 1) and EGARCH(1, 1) models accounting for day of the week and month of the year effects that the majority of African stock markets do comply with the efficient market hypothesis.
Identifying mortality risk factors amongst acute coronary syndrome patients admitted to Arabian Gulf hospitals using machine‐learning methods
Authors: Raza Syed Asif , Thalib Lukman , Al Suwaidi Jassim , Sulaiman Kadhim , Almahmeed Wael , Amin Haitham , AlHabib Khalid F. 
Published: May 2019

AbstractAcute coronary syndrome (ACS) is a leading cause of mortality and morbidity in the Arabian Gulf. In this study, the in‐hospital mortality amongst patients admitted with ACS to Arabian Gulf hospitals is predicted using a comprehensive modelling framework that combines powerful machine‐learning methods such as support‐vector machine (SVM), Naïve Bayes (NB), artificial neural networks (NN), and decision trees (DT). The performance of the machine‐learning methods is compared with that of the performance of a commonly used statistical method, namely, logistic regression (LR). The study follows the current practise of computing mortality risk using risk scores such as the Global Registry of Acute Coronary Events (GRACE) score, which has not been validated for Arabian Gulf patients. Cardiac registry data of 7,000 patients from 65 hospitals located in Arabian Gulf countries are used for the study. This study is unique as it uses a contemporary data analytics framework. A k‐fold (k = 10) cross‐validation is utilized to generate training and validation samples from the GRACE dataset. The machine‐learning‐based predictive models often incur prejudgments for imbalanced training data patterns. To mitigate the data imbalance due to scarce observations for in‐hospital mortalities, we have utilized specialized methods such as random undersampling (RUS) and synthetic minority over sampling technique (SMOTE). A detailed simulation experimentation is carried out to build models with each of the five predictive methods (LR, NN, NB, SVM, and DT) for the each of the three datasets k‐fold subsamples generated. The predictive models are developed under three schemes of the k‐fold samples that include no data imbalance, RUS, and SMOTE. We have implemented an information fusion method rooted in computing weighted impact scores obtain for an individual medical history attributes from each of the predictive models simulated for a collective recommendation based on an impact score specific to a predictor. Finally, we grouped the predictors using fuzzy c‐mean clustering method into three categories, high‐, medium‐, and low‐risk factors for in‐hospital mortality due to ACS. Our study revealed that patients with medical history related to the presences of peripheral artery disease, congestive heart failure, cardiovascular transient ischemic attack valvular disease, and coronary artery bypass grafting amongst others have the most risk for in‐hospital mortality.
An Instrument for the Determination of a Hydropneumograph in a Bubbling Spring
Authors: Agnew Robert J. , Halihan Todd , Holtzhower Lantz , Norton Brian 
Published: May 2019

AbstractIn order to enable greater accuracy in the determination of the mass discharge of gas and water‐gas ratios (WGR) in groundwater from springs, we have developed a field‐deployable instrument using commercially available components to independently measure the gas and water mass flow rates in springs with bubbling mixed‐phase flow. Collecting and measuring the free gas phase will allow for further compositional analysis that may be useful in improving gas‐derived parameters such as recharge temperature and age, as well as quantification of methanogenesis and flux of crustal/mantle gasses. By installing a phase separator at the spring discharge, a thermal mass flow sensor is utilized to measure the gas flow rate (ebullition + flux) generated from a spring. The water flow rate is determined by a standard weir. Field performance of the device was tested on a spring discharging from the Arbuckle‐Simpson aquifer near the town of Connerville in south‐central Oklahoma, USA.
Complete genome sequence of Helicobacter pylori B128 7.13 and a single‐step method for the generation of unmarked mutations
Authors: Dawson Emma M. , Dunne Karl A. , Richardson Emily J. , Praszkier Judyta , Alfawaz Dana , Woelfel Simon , De Paoli Amanda , Chaudhry Hassan , Henderson Ian R. , Ferrero Richard L. , Rossiter Amanda E. 
Published: May 2019

AbstractBackgroundHelicobacter pylori represents an interesting model of bacterial pathogenesis given that most infections are asymptomatic, while a minority of infections cause severe gastric disease. H pylori strain B128 7.13 is used extensively to understand H pylori pathophysiology. Due to extensive restriction‐modification systems, the fact that only some H pylori strains are naturally transformable, the inability of common plasmid and transposon vectors to replicate in this bacterium, as well as the limited number of antibiotic cassettes that are functional in H pylori, there are relatively few genetic tools for the mutagenesis of this bacterium.Materials and MethodsHere, we use PacBio and Illumina sequencing to reveal the complete genome sequence of H pylori B128 7.13. Furthermore, we describe a system to generate markerless and scarless mutations on the H pylori chromosome using the counter‐selection marker, galactokinase from Escherichia coli.ResultsWe show that this mutagenesis strategy can be used to generate in‐frame insertions, gene deletions, and multiple independent mutations in B128 7.13. Using the closed genome as a reference, we also report the absence of second site chromosomal mutations and/or rearrangements in our mutagenized strains. We compare the genome sequence of H pylori B128 7.13 with a closely related strain, H pylori B8, and reveal one notable region of difference, which is a 1430 bp insertion encoding a H pylori‐specific DUF874 family protein of unknown function.ConclusionsThis article reports the closed genome of the important H pylori B128 7.13 strain and a mutagenesis method that can be adopted by researchers as an alternative strategy to generate isogenic mutants of H pylori in order to further our understanding of this bacterium.
Confirmation that somatic mutations of beta‐2 microglobulin correlate with a lack of recurrence in a subset of stage II mismatch repair deficient colorectal cancers from the QUASAR trial
Authors: Barrow Paul , Richman Susan D , Wallace Andrew J , Handley Kelly , Hutchins Gordon G A , Kerr David , Magill Laura , Evans D Gareth , Gray Richard , Quirke Phil , Hill James 
Published: May 2019

AimsBeta2‐microglobulin (B2M) forms part of the HLA class I complex and plays a role in metastatic biology. B2M mutations occur frequently in mismatch repair‐deficient colorectal cancer (dMMR CRC), with limited data suggesting they may protect against recurrence. Our experimental study tested this hypothesis by investigating B2M mutation status and B2M protein expression and recurrence in patients in the stage II QUASAR clinical trial.Methods and resultsSanger sequencing was performed for the three coding exons of B2M on 121 dMMR and a subsample of 108 pMMR tumours; 52 with recurrence and 56 without. B2M protein expression was assessed by immunohistochemistry. Mutation status and protein expression were correlated with recurrence and compared to proficient mismatch repair (pMMR) CRCs. Deleterious B2M mutations were detected in 39 of 121 (32%) dMMR tumours. Five contained missense B2M‐variants of unknown significance, so were excluded from further analyses. With median follow‐up of 7.4 years, none of the 39 B2M‐mutant tumours recurred, compared with 14 of 77 (18%) B2M‐wild‐type tumours (P = 0.005); six at local and eight at distant sites. Sensitivity and specificity of IHC in detecting B2M mutations was 87 and 71%, respectively. Significantly (P < 0.0001) fewer (three of 104, 2.9%) of the 108 pMMR CRCs demonstrated deleterious B2M mutations. One pMMR tumour, containing a frameshift mutation, later recurred.ConclusionB2M mutations were detected in nearly one‐third of dMMR cancers, none of which recurred. B2M mutation status has potential clinical utility as a prognostic biomarker in stage II dMMR CRC. The mechanism of protection against recurrence and whether this protection extends to stage III disease remains unclear.
Establishing a reference range for thromboelastograph parameters in the neonatal period
Authors: Liu Qin , Xu Chunfen , Chen Xin , Wang Jia , Ke Zhunhui , Hu Hongbing 
Published: May 2019

AbstractIntroductionAcquired coagulation disorders are a common cause of neonatal bleeding. The thromboelastograph (TEG) comprehensively assesses haemostatic processes in the body. Unfortunately, the reference range of TEG parameters in the neonatal period has not yet been evaluated, which limits the use of the TEG in neonates. In this study, we aimed to establish the reference range of TEG parameters for the neonatal period.MethodsThis study included 371 full‐term infants (≥37 weeks of gestation), and we divided these infants into three groups according to age as follows: 1, 2‐7 and 8‐28 days. We measured their peripheral blood using TEG, coagulation routine and platelet count tests. We analysed differences among the groups.ResultsThe reference ranges for TEG parameters are presented as medians and reference ranges (2.5th and 97.5th percentiles) as follows: R (clot reaction time, seconds) 4.80 (2.80‐7.17), Angle (fibrin production rate) 69.90 (44.91‐78.89), K (clot kinetics, min) 1.40 (0.80‐4.50), MA (maximum amplitude, mm) 63.50(44.34‐74.66) and LY30 (lysis at 30 minutes, %) 0.10 (0.10‐6.95). There were significant differences in Angle, K, MA and LY30 values between the different neonatal day age groups.ConclusionThis study preliminarily establishes a reference range for TEG parameters during the neonatal period. The age of a newborn had a large influence on TEG parameters. Additionally, we demonstrated a correlation between laboratory tests and TEG parameters for this age period. The reference values provided herein are meaningful for future studies.
Eliciting α7‐nAChR exerts cardioprotective effects on ischemic cardiomyopathy via activation of AMPK signalling
Authors: Lin Zhong‐Hao , Li Yue‐Chun , Wu Shu‐Jie , Zheng Cheng , Lin Yuan‐Zheng , Lian Hao , Lin Wei‐Qian , Lin Jia‐Feng 
Published: May 2019

AbstractOur previous studies have reported that agonist of α7 nicotinic acetylcholine receptors prevented electrophysiological dysfunction of rats with ischaemic cardiomyopathy (ICM) by eliciting the cholinergic anti‐inflammatory pathway (CAP). Adenosine monophosphate‐activated protein kinase (AMPK) signalling is widely recognized exerting cardioprotective effect in various cardiomyopathy. Here, we aimed to investigate whether the protective effects of the CAP are associated with AMPK signalling in ICM. In vivo, coronary artery of rats was ligated for 4 weeks to induce the ICM and then treated with PNU‐282987 (CAP agonist) and BML‐275 dihydrochloride (AMPK antagonist) for 4 weeks. In vitro, primary macrophages harvested from rats were induced inflammation by Lipopolysaccharide (LPS) treatment and then treated with PNU‐282987 and BML‐275 dihydrochloride. In vivo, exciting CAP by PUN‐282987 elicited an activation of AMPK signalling, alleviated ventricular remodeling, modified the cardiac electrophysiological function, reduced the cardiac expression of collagens and inflammatory cytokines and maintained the integrity of ultrastructure in the ischemic heart. However, the benefits of CAP excitation were blunted by AMPK signaling antagonization. In vitro, excitation of the CAP was observed inhibiting the nuclear transfer of NF‐κB p65 of macrophages and promoting the transformation of Ly‐6Chigh macrophages into Ly‐6Clow macrophages. However, inhibiting AMPK signalling by BML‐275 dihydrochloride reversed the CAP effect on LPS‐treated macrophages. Finally, our findings suggest that eliciting the CAP modulates the inflammatory response in ICM through regulating AMPK signalling.