bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-time TDM-based optimization of continuous-infusion meropenem for improving treatment outcome of febrile neutropenia in oncohaematological patients: results from a prospective, monocentric, interventional study
Authors: Cojutti Pier Giorgio , Lazzarotto Davide , Candoni Anna , Dubbini Maria Vittoria , Zannier Maria Elena , Fanin Renato , Pea Federico 
Published: June 2020

Abstract

Objectives
To assess the role that real-time therapeutic drug monitoring (TDM)-guided optimization of continuous-infusion (CI) meropenem may have in maximizing empirical treatment and in preventing breakthrough infection and/or colonization with carbapenem-resistant Enterobacteriaceae (CRE) among oncohaematological patients with febrile neutropenia (FN).

Methods
A monocentric, interventional, prospective study was conducted. The pharmacodynamic (PD) target was a steady-state meropenem concentration-to-MIC ratio (Css/MIC) of 4–8. The primary endpoint was 14 day all-cause mortality. The secondary endpoint was the prevalence of CRE colonization in rectal swabs of patients rehospitalized within 3 months.

Results
Among the 75 patients enrolled, most (56%) had AML, almost half (37/75, 49.3%) underwent HSCT and one-third (32%) received meropenem as monotherapy. Meropenem dosages were adjusted in 30.1% of TDM reassessments. Gram-negative infections were microbiologically documented in 20.0% of patients. All of the 12 patients having infections caused by in vitro meropenem-susceptible pathogens attained the desired PD target and were cured. Three patients had infections caused by in vitro meropenem-resistant pathogens. Two of these achieved a Css/MIC target of 1 and were cured; the other one achieved a suboptimal PD target (0.59) and died. The 14 day all-cause mortality (10.7%) was significantly associated, at multivariate regression, with HSCT (OR 0.086, 95% CI 0.008–0.936, P = 0.044) and with augmented renal clearance (OR 10.846, 95% CI 1.534–76.672, P = 0.017). None of the patients who had hospital readmissions in the 3 month follow-up (63/75) had CRE colonization in rectal swabs.

Conclusions
Real-time TDM-guided CI meropenem may be a useful approach for attaining adequate exposure and preventing CRE emergence in FN oncohaematological patients.
Genomic prediction using pooled data in a single-step genomic best linear unbiased prediction framework
Authors: Baller Johnna L , Kachman Stephen D , Kuehn Larry A , Spangler Matthew L 
Published: June 2020

AbstractEconomically relevant traits are routinely collected within the commercial segments of the beef industry but are rarely included in genetic evaluations because of unknown pedigrees. Individual relationships could be resurrected with genomics, but this would be costly; therefore, pooling DNA and phenotypic data provide a cost-effective solution. Pedigree, phenotypic, and genomic data were simulated for a beef cattle population consisting of 15 generations. Genotypes mimicked a 50k marker panel (841 quantitative trait loci were located across the genome, approximately once per 3 Mb) and the phenotype was moderately heritable. Individuals from generation 15 were included in pools (observed genotype and phenotype were mean values of a group). Estimated breeding values (EBV) were generated from a single-step genomic best linear unbiased prediction model. The effects of pooling strategy (random and minimizing or uniformly maximizing phenotypic variation within pools), pool size (1, 2, 10, 20, 50, 100, or no data from generation 15), and generational gaps of genotyping on EBV accuracy (correlation of EBV with true breeding values) were quantified. Greatest EBV accuracies of sires and dams were observed when there was no gap between genotyped parents and pooled offspring. The EBV accuracies resulting from pools were usually greater than no data from generation 15 regardless of sire or dam genotyping. Minimizing phenotypic variation increased EBV accuracy by 8% and 9% over random pooling and uniformly maximizing phenotypic variation, respectively. A pool size of 2 was the only scenario that did not significantly decrease EBV accuracy compared with individual data when pools were formed randomly or by uniformly maximizing phenotypic variation (P &gt; 0.05). Pool sizes of 2, 10, 20, or 50 did not generally lead to statistical differences in EBV accuracy than individual data when pools were constructed to minimize phenotypic variation (P &gt; 0.05). Largest numerical increases in EBV accuracy resulting from pooling compared with no data from generation 15 were seen with sires with prior low EBV accuracy (those born in generation 14). Pooling of any size led to larger EBV accuracies of the pools than individual data when minimizing phenotypic variation. Resulting EBV for the pools could be used to inform management decisions of those pools. Pooled genotyping to garner commercial-level phenotypes for genetic evaluations seems plausible although differences exist depending on pool size and pool formation strategy.
Effects of supplemental xylanase on health of the small intestine in nursery pigs fed diets with corn distillers’ dried grains with solubles
Authors: Chen Hongyu , Zhang Shihai , Kim Sung Woo 
Published: June 2020

AbstractForty pigs [10.7 ± 1.2 kg initial body weight (BW) at 6 wk of age] were used in a 21-d study to evaluate the effects of supplemental xylanase (Hostazym X 100, Huvepharma, Inc., Peachtree City, GA) in nursery diets on digesta viscosity, nutrient digestibility, health of the small intestine, and growth performance when supplemented with corn distillers’ dried grains with solubles (DDGS). Pigs were individually housed and randomly allotted to four treatments in a 2 × 2 factorial arrangement (n = 20/factor, 0% or 30% DDGS and 0 or 1,500 endo-pentosanase unit/kg xylanase as two factors) based on sex and initial BW. Feed intake and BW were recorded weekly. On day 15 of the study, TiO2 in diets (0.3%) was used as an indigestible marker to calculate apparent ileal digestibility (AID). Plasma samples were collected on day 19 to measure tumor necrosis factor-alpha (TNF-α), malondialdehyde, and peptide YY. On day 21, all pigs were euthanized to collect tissues from duodenum, jejunum, and colon to measure morphology, TNF-α, and malondialdehyde concentrations. Distal jejunal digesta were collected to measure viscosity. Ileum digesta were collected to measure AID of nutrients. During the entire period, supplemental xylanase increased (P &lt; 0.05) average daily gain (ADG; 616 to 660 g/d) of nursery pigs, whereas DDGS (0 or 30%) did not affect ADG. On week 3, average daily feed intake (ADFI) was increased (P &lt; 0.05) when fed DDGS (1,141 to 1,267 g/d) and there was an interaction (P &lt; 0.05) between two factors indicating that supplemental xylanase decreased ADFI when DDGS was used in a diet. Use of DDGS increased (P &lt; 0.05) viscosity [1.86 to 2.38 centipoise (cP)], whereas supplemental xylanase reduced (P &lt; 0.05) viscosity (2.27 to 1.96 cP) of jejunal digesta. The AID of dry matter (DM) and gross energy (GE) were improved (P &lt; 0.05) by supplemental xylanase. Plasma TNF-α was decreased (P &lt; 0.05, 108.5 to 69.9 pg/mL) by supplemental xylanase. Use of DDGS reduced (P &lt; 0.05) villus height:crypt depth ratio (1.46 to 1.27), whereas supplemental xylanase increased (P &lt; 0.05) the crypt depth (360 to 404 µm) in duodenum. In conclusion, feeding a diet with 30% DDGS to nursery pigs for 3 wk had no negative effect on growth performance, whereas reduced AID of DM and GE, increased TNF-α level in colon tissue, and reduced the ratio of villus height to crypt depth. Dietary supplementation of xylanase reduced digesta viscosity improving AID of nutrients, reduced inflammatory response, and altered intestinal morphology, collectively improving ADG of nursery pigs regardless of the use of DDGS in a diet.
The Novel Psychoactive Substance Cumyl-CH-MEGACLONE: Human Phase-I Metabolism, Basic Pharmacological Characterization and Comparison to Other Synthetic Cannabinoid Receptor Agonists with a γ-Carboline-1-One Core
Authors: Haschimi Belal , Giorgetti Arianna , Mogler Lukas , Nagy Tibor Zsigmond , Kramer Selina , Halter Sebastian , Boros Sándor , Dobos Adrienn , Hidvégi Előd , Auwärter Volker 
Published: June 2020

Abstract
Synthetic cannabinoids (SC) remain one of the largest groups of new psychoactive substances on the European drug market. In December 2018, Cumyl-CH-MEGACLONE, a novel SC based on a γ-carboline-1-one core structure, was firstly identified in Hungary and later also other European countries. This work aims to reveal the pharmacological characteristics and phase-I metabolism of Cumyl-CH-MEGACLONE and compare the data to its analogs Cumyl-PEGACLONE and 5F-Cumyl-PEGACLONE. The purified substance was characterized by means of gas chromatography–mass spectrometry (GC–MS), liquid chromatography–quadrupole time-of-flight mass spectrometry (LC–QToF-MS), attenuated total reflection infrared spectroscopy (ATR-FTIR) and nuclear magnetic resonance spectroscopy. Phase-I metabolites were identified by LC–QToF-MS analysis combined with a scheduled precursor ion list of authentic urine samples and confirmed by comparison with metabolites built in vitro by pooled human liver microsome assays. Pharmacological data were obtained in a competitive ligand binding assay and a receptor activation assay at the human cannabinoid receptor 1 (hCB1). The structure of 5-cyclohexylmethyl-2-(2-phenylpropan-2-yl)-2,5-dihydro-1H-pyrido[4,3-b]indol-1-one (semisystematic name: Cumyl-CH-MEGACLONE) was identified in a herbal blend as the main active ingredient. Investigation of phase-I biotransformation of Cumyl-CH-MEGACLONE led to three monohydroxylated metabolites (M08, M10 and M13) as reliable urinary markers for proof of consumption. At the hCB1, Cumyl-CH-MEGACLONE shows high binding affinity with Ki = 1.01 nM (2.5-fold higher than JWH-018), an EC50 of 1.22 nM and high efficacy with EMAX = 143.4% above constitutive activity of the receptor (1.13-fold higher than JWH-018). Comparison to the analogs 5F-Cumyl-PEGACLONE and Cumyl-PEGACLONE (both are hCB1 full agonists carrying a 5-fluoropentyl or pentyl chain instead of the cyclohexylmethyl moiety) suggests that Cumyl-CH-MEGACLONE is more likely to resemble the pharmacologic profile of the latter one.
Report on a New Opioid NPS: Chemical and In Vitro Functional Characterization of a Structural Isomer of the MT-45 Derivative Diphenpipenol
Authors: Cannaert Annelies , Hulpia Fabian , Risseeuw Martijn , Van Uytfanghe Katleen , Deconinck Eric , Van Calenbergh Serge , Blanckaert Peter , Stove Christophe 
Published: June 2020

Abstract
In this paper, the identification and full characterization of a novel non-fentanyl opioid sourced online, which is a member of the 1-substituted-4-(1,2-diphenylethyl)piperazine derivatives related to MT-45, is reported. The sample was sold under the name “diphenpipenol,” (3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylethyl]phenol), although extensive NMR analysis showed that the product obtained was actually a diphenpipenol structural isomer, (2-[4-(2-methoxyphenyl)piperazin-1-yl]-1,2-diphenylethanol). Liquid chromatography time-of-flight mass spectrometry identified an exact mass for the protonated molecule of m/z 389.2264, with two prominent fragment ions (m/z 91.0567 and 150.0937), which were not reported in earlier literature describing MT-45 derivatives. The chemical characterization was finalized by gas chromatography–mass spectrometry, high-performance liquid chromatography diode array detector and Fourier-transform infrared spectroscopy analyses. This product is a clear example of the trend that new non-fentanyl opioids are reappearing on the recreational drug market to escape the recent changes in (inter)national legislation concerning fentanyl analogues. Although in this particular case, the product’s potency and efficacy were relatively low, other new non-fentanyl opioids might possess stronger potencies and therefore pose greater health risks for ignorant users. The fact that the product was sold under the wrong name further demonstrates the well-known problematic issue of a mismatch between the adverted and true identity, confirming the irregularities of the online new psychoactive substances market.
Cannabis sativa as a Host of Rice Root Aphid (Hemiptera: Aphididae) in North America
Authors: Cranshaw Whitney , Wainwright-Evans Suzanne 
Published: June 2020

Abstract
Rice root aphid, Rhopalosiphum rufiabdominale (Sasaki), is a cosmopolitan species widespread in North America. Most records of this insect are of its association with roots of grasses and sedges, but known hosts also include numerous broadleaved plants both grown outdoors and in greenhouses. Indoor grown Cannabis sativa L., particularly when intensively grown for marijuana production, has also emerged as a common host for this insect in the United States and Canada. On this crop, it has an anholocyclic life cycle where it is almost entirely found in association with plant roots. Colonization of new plants is largely by alate forms that may emerge from soil in large numbers as plants near maturity.
Collection and Rearing of Container Mosquitoes and a 24-h Addition to the CDC Bottle Bioassay
Authors: Parker Casey 
Published: June 2020

Abstract
Container mosquitoes (Diptera: Culicidae) oviposit their eggs in both natural and artificial containers. Many container mosquito species also serve as important vectors of disease-causing pathogens including Aedes aegypti, Ae. albopictus, and Ae. triseriatus. Control of these species can be done through the use of adulticide sprays. The efficacy of these treatments is highly dependent on the insecticide susceptibility status of the local mosquito populations. This paper provides protocols on collecting and rearing container mosquitoes for use in the Centers for Disease Control and Prevention (CDC) bottle bioassay. A brief description of the CDC bottle bioassay is provided as well as a standardized protocol for the incorporation of a 24-h mortality to the CDC bottle bioassay. Results from this 24-h holding addition to the CDC bottle bioassay reveal that some forms of resistance may be missed without the incorporation of the additional mortality reading. These protocols provide a foundation for new laboratories to establish rearing protocols and begin conducting resistance monitoring.
Laboratory Assay Evaluation Demystified: A Review of Key Factors Influencing Interpretation of Test Results Using Different Assays for SARS-CoV-2 Infection Diagnosis
Authors: Pham Huy P , Staley Elizabeth M , Raju Dheeraj , Marin Maximo J , Kim Chong H 
Published: June 2020

Abstract
Laboratory tests are an integral part of the diagnosis and management of patients; however, these tests are far from perfect. Their imperfections can be due to patient health condition, specimen collection, and/or technological difficulty with performing the assay and/or interpretation. To be useful clinically, testing requires calculation of positive predictive values (PPVs) and negative predictive values (NPVs). During the current global pandemic of COVID-19 (coronavirus disease 2019), multiple assays with unknown clinical sensitivity and specificity have been rapidly developed to aid in the diagnosis of the disease. Due to a lack of surveillance testing, the prevalence of COVID-19 remains unknown. Hence, using this situation as an clinical example, the goal of this article is to clarify the key factors that influence the PPV and NPV yielded by diagnostic testing, By doing so, we hope to offer health-care providers information that will help them better understand the potential implications of utilizing these test results in clinical patient management.
Peptide–Oleate Complexes Create Novel Membrane-Bound Compartments
Authors: Hansen Jesper S , Tran Tuan Hiep , Cavalera Michele , Paul Sanchari , Chaudhuri Arunima , Lindkvist-Petersson Karin , Ho James C S , Svanborg Catharina 
Published: June 2020

AbstractA challenging question in evolutionary theory is the origin of cell division and plausible molecular mechanisms involved. Here, we made the surprising observation that complexes formed by short alpha-helical peptides and oleic acid can create multiple membrane-enclosed spaces from a single lipid vesicle. The findings suggest that such complexes may contain the molecular information necessary to initiate and sustain this process. Based on these observations, we propose a new molecular model to understand protocell division.
Lateral Gene Transfer Acts As an Evolutionary Shortcut to Efficient C4 Biochemistry
Authors: Phansopa Chatchawal , Dunning Luke T , Reid James D , Christin Pascal-Antoine 
Published: June 2020

AbstractThe adaptation of proteins for novel functions often requires changes in their kinetics via amino acid replacement. This process can require multiple mutations, and therefore extended periods of selection. The transfer of genes among distinct species might speed up the process, by providing proteins already adapted for the novel function. However, this hypothesis remains untested in multicellular eukaryotes. The grass Alloteropsis is an ideal system to test this hypothesis due to its diversity of genes encoding phosphoenolpyruvate carboxylase, an enzyme that catalyzes one of the key reactions in the C4 pathway. Different accessions of Alloteropsis either use native isoforms relatively recently co-opted from other functions or isoforms that were laterally acquired from distantly related species that evolved the C4 trait much earlier. By comparing the enzyme kinetics, we show that native isoforms with few amino acid replacements have substrate KM values similar to the non-C4 ancestral form, but exhibit marked increases in catalytic efficiency. The co-option of native isoforms was therefore followed by rapid catalytic improvements, which appear to rely on standing genetic variation observed within one species. Native C4 isoforms with more amino acid replacements exhibit additional changes in affinities, suggesting that the initial catalytic improvements are followed by gradual modifications. Finally, laterally acquired genes show both strong increases in catalytic efficiency and important changes in substrate handling. We conclude that the transfer of genes among distant species sharing the same physiological novelty creates an evolutionary shortcut toward more efficient enzymes, effectively accelerating evolution.
Flow cytometry assay for the detection of single-copy DNA in human lymphocytes
Authors: Uno Naoki , Kaku Norihito , Morinaga Yoshitomo , Hasegawa Hiroo , Yanagihara Katsunori 
Published: June 2020

Abstract
Specific nucleic acid sequences can be detected in individual cells by in situ hybridization. However, when very few copies of a target sequence are present per cell, its signal is undetectable by flow cytometry. Although various approaches have been developed to increase fluorescence signals for in situ hybridization, flow cytometric detection of specific genomic DNA sequences has not been established. Here, we present a flow cytometry assay for detection of single-copy genomic sequences in human lymphocytes using in situ PCR with universal energy transfer-labelled primers.
Against the Public Goods Conception of Public Health
Authors: Bernstein Justin , Randall Pierce 
Published: June 2020

AbstractPublic health ethicists face two difficult questions. First, what makes something a matter of public health? While protecting citizens from outbreaks of communicable diseases is clearly a matter of public health, is the same true of policies that aim to reduce obesity, gun violence or political corruption? Second, what should the scope of the government’s authority be in promoting public health? May government enact public health policies some citizens reasonably object to or policies that are paternalistic? Recently, some theorists have attempted to address these questions by arguing that something is a matter of public health if and only if it involves a health-related public good, such as clean water or herd immunity. Relatedly, they have argued that appeals to the promotion of public health should only be used to justify the provision of health-related public goods. This public goods conception of public health (PGC) is meant to enjoy advantages over its rivals in three respects: it provides a better definition of public health than rival views, it respects moral disagreement, and it avoids licensing objectionably paternalistic public health policies. We argue, however, that the PGC does just as poorly, or worse, than its rivals in all three respects.
Emerging public health challenge in UK: perception and belief on increased COVID19 death among BAME healthcare workers
Authors: Moorthy Arumugam , Sankar Thangasamy K 
Published: June 2020

Abstract

Background
Coronavirus infection Disease 19 impacted every part of the world and routine life. Recent report from the Office of national statistics in UK reported disproportionate death among Black Asian and minority ethnic (BAME) population. NHS is heavily relied on the BAME work force both in front line and in the community. We attempted to explore the beliefs and perception about reported worrying issue among BAME health work force in a Diverse city of Leicester.

Methods
This is a cross-sectional survey using 20 questions in an electronic format. The target population was identified through Leicester Asian Doctors Society and Leicester Asian Nurses Society. The questionnaire was then distributed electronically to the members. Survey questionnaire was accessed by 372, incomplete response (172) were excluded and 200 completed responses were analysed.

Results
Majority of BAME workforce are routinely involved in front line duties. More than 70% were anxious about their role during this pandemic. The Personal Protective Equipment (PPE) supply was adequate, and the support received from the local healthcare providers was more than satisfactory. The work force perceived co-morbidity, lack of PPE and testing were one of the few reasons for increased death in BAME. BAME group felt adequate provision of PPE, increased testing and improving mental health well-being is required to alleviate concerns and improve BAME working life in NHS.

Conclusion
BAME workforce are routinely involved in front line work and current anxiety level is very high. Adequate provision of mental health support with clear risk stratification for return to work is required urgently.