bluuebunny/crossref_metadata_2025 huggingface dataset:
A highly revertible cyc1 mutant of yeast contains a small tandem duplication.
Authors: Das G , Consaul S , Sherman F
Published: January 2021

A mutant, cyc1-96, that reverts spontaneously at an extremely high rate, was uncovered after examining approximately 500 cyc1 mutants which lack or have defective iso-1-cytochrome c in the yeast Saccharomyces cerevisiae. Cloning and DNA sequencing of appropriate fragments revealed that the cyc1-96 mutation contained a 19 bp duplication whereas the spontaneously arising revertants contained the normal wild-type sequence. Because the 19 bp segment in the wild-type sequence is flanked by a 5 bp repeat and because the cyc1-96 mutation arose spontaneously, the 19 bp duplication may have arisen by slippage and misalignment during DNA synthesis. The high reversion rate was not diminished in strains containing the rad52 mutation, which generally reduces mitotic recombination, including recombination associated with the elimination of a segment of a long direct repeat. Thus the loss of segments from short and long duplications occur by different mechanisms. We suggest that the high reversion rates of cyc1-96 and other short duplications are due to misalignment errors during replication.
a/Alpha-specific repression by MAT alpha 2.
Authors: Strathern J , Shafer B , Hicks J , McGill C
Published: January 2021

The product of the MAT alpha 2 gene is a DNA-binding protein that acts as a repressor of two different sets of cell type-specific genes. In alpha cells, the alpha 2 protein represses the transcription of several a-specific genes. In a/alpha cells, the alpha 2 protein acts together with the product of the MATa1 gene, the a1 protein, to repress several genes used by haploids in the mating process. In addition to the mat alpha 2 mutations that result in defects in both types of regulation, other mat alpha 2 alleles have been described that result in defects in the repression of a-specific genes but that do not affect the ability of the alpha 2 and a1 proteins to interact to repress the haploid-specific genes. We report here the isolation of a new class of mat alpha 2 mutations that do not affect the ability of the alpha 2 protein to repress a-specific genes, but that interfere with the ability of the alpha 2 protein to interact with the a1 protein to repress the haploid-specific genes and establish the a/alpha cell type. These mutations may help determine the means by which the a1 protein interacts with alpha 2 to expand the set of genes under its control.
The effects of mutations in the ant promoter of phage P22 depend on context.
Authors: Graña D , Gardella T , Susskind M M
Published: January 2021

Recombination was used to construct 22 two- or three-way combinations of down- and up-mutations in Pant, a strong, near-consensus promoter of phage P22. The relative strengths of these promoters in vivo were assayed by fusing them to an ant/lacZ gene fusion and measuring beta-galactosidase levels produced by lysogens carrying the fusions on single-copy prophages. The results of these assays show that the magnitude of the effect of a promoter mutation can vary considerably when its context is changed by the presence of another mutation. In addition, as Pant approaches conformity with the consensus promoter sequence, the up-mutations decrease promoter strength, even though the same mutations increase promoter strength in the presence of a down-mutation. These context effects imply that individual consensus base pairs cannot be considered to contribute to promoter strength independently.
Different types of recombination events are controlled by the RAD1 and RAD52 genes of Saccharomyces cerevisiae.
Authors: Klein H L
Published: January 2021

Intrachromosomal recombination within heteroallelic duplications located on chromosomes III and XV of Saccharomyces cerevisiae has been examined. Both possible orientations of alleles have been used in each duplication. Three recombinant classes, gene conversions, pop-outs and triplications, were recovered. Some of the recombinant classes were not anticipated from the particular allele orientation of the duplication. Recovery of these unexpected recombinants requires the RAD1 gene. These studies show that RAD1 has a role in recombination between repeated sequences, and that the recombination event is a gene conversion associated with a crossover. These events appear to involve very localized conversion of a heteroduplex region and are distinct from RAD52 mediated gene conversion events. Evidence is also presented to suggest that most recombination events between direct repeats are intrachromatid, not between sister chromatids.
Analysis of a mutator activity necessary for germline transposition and excision of Tc1 transposable elements in Caenorhabditis elegans.
Authors: Mori I , Moerman D G , Waterston R H
Published: January 2021

The Tc1 transposable element family of the nematode Caenorhabditis elegans consists primarily of 1.6-kb size elements. This uniformity of size is in contrast to P in Drosophila and Ac/Ds in maize. Germline transposition and excision of Tc1 are detectable in the Bergerac (BO) strain, but not in the commonly used Bristol (N2) strain. A previous study suggested that multiple genetic components are responsible for the germline Tc1 activity of the BO strain. To analyze further this mutator activity, we derived hybrid strains between the BO strain and the N2 strain. One of the hybrid strains exhibits a single locus of mutator activity, designated mut-4, which maps to LGI. Two additional mutators, mut-5 II and mut-6 IV, arose spontaneously in mut-4 harboring strains. This spontaneous appearance of mutator activity at new sites suggests that the mutator itself transposes. The single mutator-harboring strains with low Tc1 copy number generated in this study should be useful in investigations of the molecular basis of mutator activity. As a first step toward this goal, we examined the Tc1 elements in these low copy number strains for elements consistently co-segregating with mutator activity. Three possible candidates were identified: none was larger than 1.6 kb.
Prepupal differentiation of Drosophila imaginal discs: identification of four genes whose transcripts accumulate in response to a pulse of 20-hydroxyecdysone.
Authors: Fechtel K , Natzle J E , Brown E E , Fristrom J W
Published: January 2021

We have isolated and initially characterized a novel set of four genes expressed during the prepupal differentiation of imaginal discs of Drosophila melanogaster. These four ecdysone-dependent genes are named EDG-42A, EDG-64CD, EDG-78E and EDG-84A-1 based on their respective chromosomal locations. Their expression is like that expected for genes encoding proteins that participate in the formation of the pupal cuticle. Transcripts complementary to these genes accumulate in imaginal discs during an 18-hr in vitro culture period that begins with a 6-hr pulse of 20-hydroxyecdysone (20-HE). Transcripts for three of these genes were not detected in imaginal discs following culture in the absence or the continuous presence of 20-HE (1 microgram/ml). Transcripts corresponding to EDG-64CD exhibit delayed accumulation in the continuous presence of 20-HE. Transcripts corresponding to three of the genes are only detected in the prepupal stage of development. Only EDG-64CD is complementary to transcripts present at other stages of development. One of the genes, EDG-78E, encodes a pupal cuticle protein. This is the first reported isolation of a set of steroid hormone-responsive genes that require first the presence, then removal of hormone for transcript accumulation.
Use of isogenic lines and simultaneous probing to identify DNA markers tightly linked to the tm-2a gene in tomato.
Authors: Young N D , Zamir D , Ganal M W , Tanksley S D
Published: January 2021

The Tm-2a gene of tomato confers resistance to the viral pathogen, tobacco mosaic virus. Like many economically important plant genes, Tm-2a has been characterized phenotypically and by classical linkage analysis, yet nothing is known about its gene product. We report here the isolation of two DNA clones which are very tightly linked to the Tm-2a gene. These clones were identified by testing 122 genomic clones as hybridization probes against Southern blots consisting of DNA from pairs of nearly isogenic lines with or without the Tm-2a gene. Screening such a large number of clones in a short period of time was facilitated by co-labeling and simultaneous probing of sets of up to 10 random genomic clones. Tightly linked clones were distinguished by the fact that they exhibited one or more restriction fragment length polymorphisms between the nearly isogenic lines. Tight linkage of the clones with Tm-2a was verified in a segregating F(2) population. Both mapped to the same locus 0.4 +/- 0.4 centimorgans away from Tm-2a and may provide starting points for a genomic ;;walk'' to this gene. Due to the availability of isogenic lines in many plant species, the strategy outlined in this paper should be widely applicable for selecting DNA clones tightly linked to genes of interest.
Aging modulated by theDrosophilainsulin receptor through distinct structure-defined mechanisms
Authors: Yamamoto Rochele , Palmer Michael , Koski Helen , Curtis-Joseph Noelle , Tatar Marc
Published: January 2021

Mutations of the Drosophila melanogaster insulin/IGF signaling system slow aging, while also affecting growth and reproduction. To understand this pleiotropy, we produced an allelic series of single codon substitutions in the Drosophila insulin receptor, InR. We generated InR substitutions using homologous recombination and related each to emerging models of receptor tyrosine kinase structure and function. Three mutations when combined as trans-heterozygotes extended lifespan while retarding growth and fecundity. These genotypes reduced insulin-stimulated Akt phosphorylation, suggesting they impede kinase catalytic domain function. Among these genotypes, longevity was negatively correlated with egg production, consistent with life-history trade-off theory. In contrast, one mutation (InR353) was located in the kinase insert domain, a poorly characterized element found in all receptor tyrosine kinases. Remarkably, wild-type heterozygotes with InR353 robustly extended lifespan without affecting growth or reproduction and retained capacity to fully phosphorylate Akt. The Drosophila insulin receptor kinase insert domain contains a previously unrecognized SH2 binding motif. We propose the kinase insert domain interacts with SH2-associated adapter proteins to affect aging through mechanisms that retain insulin sensitivity and are independent of reproduction.
Duration of diabetes-related complications and mortality in type 1 diabetes: a national cohort study
Authors: Bjerg Lasse , Gudbjörnsdottir Soffia , Franzén Stefan , Carstensen Bendix , Witte Daniel R , Jørgensen Marit E , Svensson Ann-Marie
Published: January 2021

Background

People with type 1 diabetes often live for many years with different combinations of diabetes-related complications. We aimed to quantify how complication duration and total complication burden affect mortality, using data from national registers.

Methods

This study included 33 396 individuals with type 1 diabetes, registered in the Swedish National Diabetes Register at any time between 2001 and 2012. Each individual was followed and classified according to their time-updated diabetes-related complication status. The main outcomes were all-cause mortality, cardiovascular (CV) mortality and non-CV mortality. Poisson models were used to estimate the rate of these outcomes as a function of the time-updated complication duration.

Results

Overall, 1748 of the 33 396 individuals died during 198 872 person-years of follow-up. Overall, the time-updated all-cause mortality rate ratio (MRR) was 2.25 [95% confidence interval (CI): 1.99–2.54] for patients with diabetic kidney disease, 0.98 (0.82–1.18) for patients with retinopathy and 4.00 (3.56–4.50) for patients with cardiovascular disease relative to individuals without complications. The excess rate was highest in the first period after a diagnosis of CVD, with an 8-fold higher mortality rate, and stabilized after some 5 years. After diagnosis of diabetic kidney disease, we observed an increase in all-cause mortality with an MRR of around 2 compared with individuals without diabetic kidney disease, which stabilized after few years.

Conclusions

In this cohort we show that duration of diabetes-related complications is an important determinant of mortality in type 1 diabetes, for example the MRR associated with CVD is highest in the first period after diagnosis of CVD. A stronger focus on time-updated information and thorough consideration of complication duration may improve risk stratification in routine clinical practice.
Empirical risk minimization for dynamical systems and stationary processes
Authors: McGoff Kevin , Nobel Andrew B
Published: January 2021

We introduce and analyze a general framework for empirical risk minimization in which the observations and models of interest may be stationary systems or processes. Within the framework, which is presented in terms of dynamical systems, empirical risk minimization can be studied as a two-step procedure in which (i) the trajectory of an observed (but unknown) system is fit by a trajectory of a known reference system via minimization of cumulative per-state loss, and (ii) an invariant parameter estimate is obtained from the initial state of the best fit trajectory. We show that the weak limits of the empirical measures of best-matched trajectories are dynamically invariant couplings (joinings) of the observed and reference systems with minimal risk. Moreover, we establish that the family of risk-minimizing joinings is convex and compact and that it fully characterizes the asymptotic behavior of the estimated parameters, directly addressing identifiability. Our analysis of empirical risk minimization applies to well-studied problems such as maximum likelihood estimation and non-linear regression, as well as more complex problems in which the models of interest are stationary processes. To illustrate the latter, we undertake an extended analysis of system identification from quantized trajectories subject to noise, a problem at the intersection of dynamics and statistics.
A comprehensive assessment of carbapenem use across 90 Veterans Health Administration hospitals with defined stewardship strategies for carbapenems
Authors: Suzuki Hiroyuki , Perencevich Eli , Goto Michihiko , Alexander Bruce , Nair Rajeshwari , Puig-Asensio Mireia , Ernst Erika , Livorsi Daniel J
Published: January 2021

Objectives

Carbapenems are an important target for antimicrobial stewardship (AS) efforts. In this study, we sought to compare different hospital-based strategies for improving carbapenem use.

Methods

We analysed a cohort of all patients hospitalized at Veterans Health Administration (VHA) acute care hospitals during 2016 and a mandatory survey that characterized each hospital’s carbapenem-specific AS strategy into one of three types: no strategy (NS), prospective audit and feedback (PAF) or restrictive policies (RP). Carbapenem use was compared using risk-adjusted generalized estimating equations that accounted for clustering within hospitals. Two infectious disease (ID) physicians independently performed manual chart reviews in 425 randomly selected cases. Auditors assessed carbapenem appropriateness with an assessment score on Day 4 of therapy.

Results

There were 429 062 admissions in 90 sites (24 NS, 8 PAF, 58 RP). Carbapenem use was lower at PAF than NS sites [rate ratio (RR) 0.6 (95% CI 0.4–0.9); P = 0.01] but similar between RP and NS sites. Carbapenem prescribing was considered appropriate/acceptable in 215 (50.6%) of the reviewed cases. Assessment scores were lower (i.e. better) at RP than NS sites (mean 2.3 versus 2.7; P < 0.01) but did not differ significantly between NS and PAF sites. ID consultations were more common at PAF/RP than NS sites (51% versus 29%; P < 0.01). ID consultations were associated with lower (i.e. better) assessment scores (mean 2.3 versus 2.6; P < 0.01).

Conclusions

In this VHA cohort, PAF strategies were associated with lower carbapenem use and ID consultation and RP strategies were associated with more appropriate carbapenem prescribing. AS and ID consultations may work complementarily and hospitals could leverage both to optimize carbapenem use.
Mortality attributable to third-generation cephalosporin resistance in Gram-negative bloodstream infections in African hospitals: a multi-site retrospective study
Authors: Dramowski Angela , Ong’ayo Gerald , Rehman Andrea M , Whitelaw Andrew , Labi Appiah-Korang , Obeng-Nkrumah Noah , Ndir Awa , Magwenzi Marcelyn T , Onyedibe Kenneth , Wolkewitz Martin , de Kraker Marlieke E A , Scott J Anthony G , Aiken Alexander M ,   MBIRA study collaborators, Mujuru Hilda , Odipo Emily , Mwarumba Salim , Mturi Neema , Gordon N Claire , Diop Amadou , Ndiaye Aissatou Thilor , Shwe David , Diala Udochukwu M , Okolo Mark , Grundmann Hajo
Published: January 2021

Background

Bloodstream infections (BSI) caused by Enterobacteriaceae show increasing frequency of resistance to third-generation cephalosporin (3GC) antibiotics on the African continent but the mortality impact has not been quantified.

Methods

We used historic data from six African hospitals to assess the impact of 3GC resistance on clinical outcomes in Escherichia coli and Klebsiella pneumoniae BSI. We matched each bacteraemic patient to two uninfected patients. We compared outcomes between 3GC-susceptible and 3GC-resistant BSI and their respective uninfected controls using Cox regression models.

Results

For 1431 E. coli BSI patients, we matched 1152 (81%) 3GC-susceptible and 279 (19%) 3GC-resistant cases to 2263 and 546 uninfected inpatient controls. For 1368 K. pneumoniae BSI patients, we matched 502 (37%) 3GC-susceptible and 866 (63%) 3GC-resistant cases to 982 and 1656 uninfected inpatient controls. We found that 3GC-resistant E. coli had similar hazard ratios (HRs) for in-hospital mortality over their matched controls as compared to susceptible infections over their controls (ratio of HRs 1.03, 95% CI 0.73–1.46). Similarly, 3GC-resistance in K. pneumoniae BSI was not associated with mortality (ratio of HR 1.10, 95% CI 0.80–1.52). Estimates of mortality impact varied by site without a consistent pattern.

Conclusions

In a retrospective analysis, including the use of matched uninfected patients, there did not appear to be an impact of 3GC-resistance on mortality in E. coli or K. pneumoniae BSI in African hospitals, as compared with susceptible BSI with equivalent species. Better information on the actual use of antibiotics in treating infections in African hospitals would improve these impact estimates.
Supervised machine learning to support the diagnosis of bacterial infection in the context of COVID-19
Authors: Rawson Timothy M , Hernandez Bernard , Wilson Richard C , Ming Damien , Herrero Pau , Ranganathan Nisha , Skolimowska Keira , Gilchrist Mark , Satta Giovanni , Georgiou Pantelis , Holmes Alison H
Published: January 2021

Background

Bacterial infection has been challenging to diagnose in patients with COVID-19. We developed and evaluated supervised machine learning algorithms to support the diagnosis of secondary bacterial infection in hospitalized patients during the COVID-19 pandemic.

Methods

Inpatient data at three London hospitals for the first COVD-19 wave in March and April 2020 were extracted. Demographic, blood test and microbiology data for individuals with and without SARS-CoV-2-positive PCR were obtained. A Gaussian Naive Bayes, Support Vector Machine (SVM) and Artificial Neural Network were trained and compared using the area under the receiver operating characteristic curve (AUCROC). The best performing algorithm (SVM with 21 blood test variables) was prospectively piloted in July 2020. AUCROC was calculated for the prediction of a positive microbiological sample within 48 h of admission.

Results

A total of 15 599 daily blood profiles for 1186 individual patients were identified to train the algorithms; 771/1186 (65%) individuals were SARS-CoV-2 PCR positive. Clinically significant microbiology results were present for 166/1186 (14%) patients during admission. An SVM algorithm trained with 21 routine blood test variables and over 8000 individual profiles had the best performance. AUCROC was 0.913, sensitivity 0.801 and specificity 0.890. Prospective testing on 54 patients on admission (28/54, 52% SARS-CoV-2 PCR positive) demonstrated an AUCROC of 0.960 (95% CI: 0.90–1.00).

Conclusions

An SVM using 21 routine blood test variables had excellent performance at inferring the likelihood of positive microbiology. Further prospective evaluation of the algorithms ability to support decision making for the diagnosis of bacterial infection in COVID-19 cohorts is underway.
Evaluation of Sensitivity to Phoxim and Cypermethrin in an Endoparasitoid,Meteorus pulchricornis(Wesmael) (Hymenoptera: Braconidae), and Its Parasitization Efficiency Under Insecticide Stress
Authors: Sheng Sheng , Wang Jiao , Zhang Xiao-rui , Liu Zhi-xiang , Yan Meng-wen , Shao Ying , Zhou Jin-cheng , Wu Fu-an , Wang Jun
Published: January 2021

Insecticides can have consequences for beneficial arthropods. Insect parasitoids can contact insecticides through direct exposure spray droplets or residues on crop foliage. Here, we focus on better understand the response of Meteorus pulchricornis (Wesmael), a parasitoid wasp of lepidopteran pests, and its detoxification mechanisms on stress caused by phoxim and cypermethrin. Hence, we determined the dose–mortality curves and estimating the sublethal concentrations (LC30 and LC50). Then, we applied the sublethal concentrations against adult parasitoids to assess its survival, parasitism efficacy, and also developmental and morphometric parameters of their offspring. Simultaneously, we check the activities of glutathione S-transferase (GST), acetylcholinesterase (AChE), and peroxidase (POD) after sublethal exposure of both insecticides, which has measured until 48 h after treatment. Overall, phoxim and cypermethrin exhibited acute lethal activity toward the parasitoid with LC50 values 4.608 and 8.570 mg/liter, respectively. Also, we detect that LC30 was able to trigger the enzymatic activity of GST, AChE, and POD, suggesting a potential detoxification mechanism. However, even when subjected to sublethal exposure, our results indicate strong negatives effects, in particular for phoxim, which has affected the parasitism efficacy and also the developmental and morphometric parameters of M. pulchricornis offspring. Therefore, it can be concluded that both phoxim and cypermethrin have negative impacts on M. pulchricornis and we suggest cautioning their use and the need for semifield and field assessments to confirm such an impact.
Historic Assessment and Analysis of the Mass Production ofLaricobiusspp. (Coleoptera: Derodontidae), Biological Control Agents for the Hemlock Woolly Adelgid, at Virginia Tech
Authors: Foley Jeremiah R , Jubb Carrie S , Cole D Austin , Mausel David , Galloway Ashley Lamb , Brooks Rachel , Salom Scott M
Published: January 2021

Laricobius nigrinus (Coleoptera: Derodontidae) Fender and Laricobius osakensis (Coleoptera: Derodontidae) Montgomery and Shiyake have been mass produced by Virginia Tech as biological control agents for the hemlock woolly adelgid (HWA), Adelges tsugae (Hemiptera: Adelgidae) Annand, for the past 15 and 9 yr, respectively. Herein, we describe modifications of our rearing procedures, trends and analyses in the overall production of these agents, and the redistribution of these agents for release to local and federal land managers. Based on these data, we have highlighted three major challenges to the rearing program: 1) high mortality during the subterranean portion of its life cycle (averaging 63% annually) reducing beetle production, 2) asynchrony in estivation emergence relative to the availability of their host HWA minimizing food availability, and 3) unintended field collections of Laricobius spp. larvae on HWA provided to lab-reared larvae complicating rearing procedures. We further highlight corresponding avenues of research aimed at addressing each of these challenges to further improve Laricobius spp. production.
Fine Particulate Matter Air Pollution and Mortality Risk Among US Cancer Patients and Survivors
Authors: Coleman Nathan C , Ezzati Majid , Marshall Julian D , Robinson Allen L , Burnett Richard T , Pope C Arden
Published: January 2021

Background

Exposure to fine particulate matter (PM2.5) air pollution has been linked to increased risk of mortality, especially cardiopulmonary and lung cancer mortality. It is unknown if cancer patients and survivors are especially vulnerable to PM2.5 air pollution exposure. This study evaluates PM2.5 exposure and risk for cancer and cardiopulmonary mortality in cohorts of US cancer patients and survivors.

Methods

A primary cohort of 5 591 168 of cancer patients and a 5-year survivor cohort of 2 318 068 was constructed using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, linked with county-level estimates of long-term average concentrations of PM2.5. Cox proportional hazards models were used to estimate PM2.5-mortality hazard ratios controlling for age-sex-race combinations and individual and county-level covariables.

Results

Of those who died, 26% died of noncancer causes, mostly from cardiopulmonary disease. Minimal PM2.5-mortality associations were observed for all-cause mortality (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00 to 1.03) per 10 µg/m3 increase in PM2.5. Substantial adverse PM2.5-mortality associations were observed for cardiovascular (HR = 1.32, 95% CI = 1.26 to 1.39), chronic obstructive pulmonary disease (HR = 1.10, 95% CI = 1.01 to 1.20), influenza and pneumonia (HR = 1.55, 95% CI = 1.33 to 1.80), and cardiopulmonary mortality combined (HR = 1.25, 95% CI = 1.21 to 1.30). PM2.5-cardiopulmonary mortality hazard ratio was higher for cancer patients who received chemotherapy or radiation treatments.

Conclusions

Air pollution is adversely associated with cardiopulmonary mortality for cancer patients and survivors, especially those who received chemotherapy or radiation treatment. Given ubiquitous and involuntary air pollution exposures and large numbers of cancer patients and survivors, these results are of substantial clinical and public health importance.
Cecal volvulus complicated by evisceration case report
Authors: Johnson Kylie , Williams Ben , Steen Eric
Published: January 2021

This case of bowel obstruction with multiple postoperative complications provides unique insight into the challenges faced by providers caring for intellectually disabled patients with acute surgical abdominal pathology and poor compliance. In this case, the component separation was utilized as a method of facilitated wound closure and compliance in a postoperative course highlighted by both dehiscence and wound infection. The patient, only able to communicate the presence of abdominal pain due to his disability, was surgically managed for a bowel obstruction secondary to a cecal volvulus. The difficulty in initial communication and patient noncompliance help illustrate the individualized care these patients require. This report will demonstrate both the challenges present in the management of intellectually disabled patients with abdominal wounds, as well as the use of component separation in providing both initial wound closure and continued wound integrity with the goal of reducing postoperative complications in patients with decreased compliance.
Usage of Plasma Presepsin, C-Reactive Protein, Procalcitonin and Proadrenomedullin to Predict Bacteremia in Febril Neutropenia of Pediatric Hematological Malignancy Patients
Authors: Arıkan Kamile , Karadag-Oncel Eda , Aytac Selin , Cetin Mualla , Cengiz Ali Bülent , Gümrük Fatma , Kara Ates , Ceyhan Mehmet
Published: January 2021

Objective

To investigate the value of presepsin and proadrenomedullin (proADM) as new markers for febrile neutropenia, by comparing them with conventional markers.

Methods

Plasma specimens for presepsin, proADM, C-reactive protein (CRP), and procalcitonin (PCT) were collected every 3 days during each episode of febrile neutropenia.

Results

A total of 39 patients experiencing a collective 47 episodes of febrile neutropenia with hematological malignant neoplasms, as well as 40 healthy control patients without infectious disease, were enrolled in this study. Levels of the studied analytes in the presepsin 1 group (with baseline values taken at admission), presepsin 2 group (values recorded on the 3rd day of febrile neutropenia), and presepsin 3 group (values recorded on the 6th day of hospitalization) were all higher in the subgroups with bacteremia. C-reactive protein 1 (baseline value taken at admission), procalcitonin 1 (as recorded at admission), and procalcitonin 2 (recorded on the 3rd day of febrile neutropenia) were higher in the subroups with bacteremia (P =.03, P = .04, and P = .04, respectively). In multivariate logistic regression analysis, presepsin 1 and/or PCT 1/CRP 1 combined analysis was superior in predicting bacteremia.

Conclusion

Presepsin could be used in combination with other biomarkers to detect bacteremia.
Estimation of the size and structure of the broad line region using Bayesian approach
Authors: Mandal Amit Kumar , Rakshit Suvendu , Stalin C S , Petrov R G , Mathew Blesson , Sagar Ram
Published: January 2021

Understanding the geometry and kinematics of the broad line region (BLR) of active galactic nuclei (AGN) is important to estimate black hole masses in AGN and study the accretion process. The technique of reverberation mapping (RM) has provided estimates of BLR size for more than 100 AGN now; however, the structure of the BLR has been studied for only a handful number of objects. Towards this, we investigated the geometry of the BLR for a large sample of 57 AGN using archival RM data. We performed systematic modelling of the continuum and emission line light curves using a Markov chain Monte Carlo method based on Bayesian statistics implemented in PBMAP (Parallel Bayesian code for reverberation−MAPping data) code to constrain BLR geometrical parameters and recover velocity integrated transfer function. We found that the recovered transfer functions have various shapes such as single-peaked, double-peaked, and top-hat suggesting that AGN have very different BLR geometries. Our model lags are in general consistent with that estimated using the conventional cross-correlation methods. The BLR sizes obtained from our modelling approach is related to the luminosity with a slope of 0.583 ± 0.026 and 0.471 ± 0.084 based on H β and H α lines, respectively. We found a non-linear response of emission line fluxes to the ionizing optical continuum for 93 ${{\ \rm per\ cent}}$ objects. The estimated virial factors for the AGN studied in this work range from 0.79 to 4.94 having a mean at 1.78 ± 1.77 consistent with the values found in the literature.
Vibrio cholerae FruR facilitates binding of RNA polymerase to the fru promoter in the presence of fructose 1-phosphate
Authors: Yoon Chang-Kyu , Kang Deborah , Kim Min-Kyu , Seok Yeong-Jae
Published: January 2021

In most bacteria, efficient use of carbohydrates is primarily mediated by the phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS), which concomitantly phosphorylates the substrates during import. Therefore, transcription of the PTS-encoding genes is precisely regulated by transcriptional regulators, depending on the availability of the substrate. Fructose is transported mainly through the fructose-specific PTS (PTSFru) and simultaneously converted into fructose 1-phosphate (F1P). In Gammaproteobacteria such as Escherichia coli and Pseudomonas putida, transcription of the fru operon encoding two PTSFru components, FruA and FruB, and the 1-phosphofructokinase FruK is repressed by FruR in the absence of the inducer F1P. Here, we show that, contrary to the case in other Gammaproteobacteria, FruR acts as a transcriptional activator of the fru operon and is indispensable for the growth of Vibrio cholerae on fructose. Several lines of evidence suggest that binding of the FruR-F1P complex to an operator which is located between the –35 and –10 promoter elements changes the DNA structure to facilitate RNA polymerase binding to the promoter. We discuss the mechanism by which the highly conserved FruR regulates the expression of its target operon encoding the highly conserved PTSFru and FruK in a completely opposite direction among closely related families of bacteria.
The metabolite methylglyoxal-mediated gene expression is associated with histone methylglyoxalation
Authors: Fu Zheng-Wei , Li Jian-Hui , Feng Yu-Rui , Yuan Xiao , Lu Ying-Tang
Published: January 2021

Methylglyoxal (MG) is a byproduct of glycolysis that functions in diverse mammalian developmental processes and diseases and in plant responses to various stresses, including salt stress. However, it is unknown whether MG-regulated gene expression is associated with an epigenetic modification. Here we report that MG methylglyoxalates H3 including H3K4 and increases chromatin accessibility, consistent with the result that H3 methylglyoxalation positively correlates with gene expression. Salt stress also increases H3 methylglyoxalation at salt stress responsive genes correlated to their higher expression. Following exposure to salt stress, salt stress responsive genes were expressed at higher levels in the Arabidopsis glyI2 mutant than in wild-type plants, but at lower levels in 35S::GLYI2 35S::GLYII4 plants, consistent with the higher and lower MG accumulation and H3 methylglyoxalation of target genes in glyI2 and 35S::GLYI2 35S::GLYII4, respectively. Further, ABI3 and MYC2, regulators of salt stress responsive genes, affect the distribution of H3 methylglyoxalation at salt stress responsive genes. Thus, MG functions as a histone-modifying group associated with gene expression that links glucose metabolism and epigenetic regulation.
Product-market integration with endogenous firm heterogeneity
Authors: Ledezma Ivan
Published: January 2021

This paper proposes a general equilibrium oligopoly model in which firm heterogeneity is endogenously reproduced through technology adoption decisions. The model can explain persistent oligopolistic market structures and prices in spite of free entry and market enlargement. Moreover, strong selection might deteriorate average cost efficiency due to strategic interactions. Integrating identical countries can be welfare-improving. But distributional issues and tensions between welfare and scale economies may arise. The theory can be motivated by recent evidence on oligopolistic market structures resisting globalization forces.
Algorithm for calculating high disease activity in SLE
Authors: Hoi Alberta , Nim Hieu T , Koelmeyer Rachel , Sun Ying , Kao Amy , Gunther Oliver , Morand Eric
Published: January 2021

Background

The ability to identify lupus patients in high disease activity status (HDAS) without knowledge of the SLEDAI could have application in selection of patients for treatment escalation or enrolment in trials. We sought to generate an algorithm that could calculate via model fitting the presence of HDAS using simple demographic and laboratory values.

Methods

We examined the association of high disease activity (HDA) with demographic and laboratory parameters using prospectively collected data. An HDA visit is recorded when SLEDAI-2K ≥10. We utilized the use of combinatorial search to find algorithms to build a mathematical model predictive of HDA. Performance of each algorithm was evaluated using multi-class area under the receiver operating characteristic curve and the final model was compared with the naïve Bayes classifier, and analysed using the confusion matrix for accuracy and misclassification rate.

Results

Data on 286 patients, followed for a median of 5.1 years were studied for a total of 5680 visits. Sixteen laboratory parameters were found to be significantly associated with HDA. A total of 216 algorithms were evaluated and the final algorithm chosen was based on seven pathology measures and three demographic variables. It has an accuracy of 88.6% and misclassification rate of 11.4%. When compared with the naïve Bayes classifier [area under the curve (AUC) = 0.663], our algorithm has a better accuracy with AUC = 0.829.

Conclusion

This study shows that building an accurate model to calculate HDA using routinely available clinical parameters is feasible. Future studies to independently validate the algorithm will be needed to confirm its predictive performance.
Draft Genome Resources for Plant-Beneficial Fungi Clonostachys rosea Strains ACM941 and 88-710
Authors: Demissie Zerihun A. , Robinson Kelly A. , Loewen Michele C.
Published: January 2021

Clonostachys rosea strains ACM941 and 88-710 are beneficial microbes recognized for their plant disease control and growth promotion properties, respectively, when applied to economically important crops. In addition to their geographical and functional overlap, the two strains also share a high degree of genetic similarity. In an effort to identify the subtleties that underlie their strain-specific applications, their genomic sequence is reported here. The genome size of ACM941 was estimated to be 56.9 Mb, encoding 17,585 putative genes, while strain 88-710 was estimated to have a 55.5 Mb genome size, containing 17,188 predicted genes. Overall, ACM941 and 88-710 share >96% of their encoded genomes, such that their strain-specific characteristics are likely encoded in either the remaining variable 4% or differentially regulated shared genes or both. These genomic sequences form a foundation for future studies aimed at identifying the genomic and metabolic machinery driving their respective beneficial properties.
Antifungal Activity and Biological Characteristics of the Novel Fungicide Quinofumelin AgainstSclerotinia sclerotiorum
Authors: Tao Xian , Zhao Huahua , Xu Haorong , Li Zhongke , Wang Jianxin , Song Xiushi , Zhou Mingguo , Duan Yabing
Published: January 2021

Sclerotinia sclerotiorum is a devastating plant pathogen with a broad host range and worldwide distribution. The application of chemical fungicides is a primary strategy for controlling this pathogen. However, under the high selective pressure of chemical fungicides, fungicide resistance has emerged and gradually increased, resulting in the failure to control S. sclerotiorum in the field. Quinofumelin is a novel quinoline fungicide, but its antifungal activities against plant pathogens have been rarely reported. Here, we determined the antifungal activity of quinofumelin against S. sclerotiorum in vitro and in planta. The median effect concentration (EC50) values ranged from 0.0004 to 0.0059 µg ml−1with a mean EC50of 0.0017 ± 0.0009 µg ml−1and were normally distributed (P = 0.402). In addition, no cross resistance was observed between quinofumelin and other fungicides, dimethachlone, boscalid, or carbendazim, which are commonly used to manage S. sclerotiorum. Quinofumelin did not affect glycerol and oxalic acid production of either carbendazim-sensitive or -resistant isolates. Moreover, quinofumelin exhibited excellent protective, curative, and translaminar activity against S. sclerotiorum on oilseed rape leaves. Protective activity was higher than curative activity. Interestingly, quinofumelin inhibited the formation of the infection cushion in S. sclerotiorum, which may contribute to the control efficacy of quinofumelin against S. sclerotiorum in the field. Our findings indicate that quinofumelin has excellent control efficacy against S. sclerotiorum in vitro and in planta as compared with extensively used fungicides and could be used to manage carbendazim- and dimethachlone-resistance in S. sclerotiorum in the field.
Current prevalence of self-monitoring of blood pressure during pregnancy: the BUMP Survey
Authors: Tucker Katherine L. , Hodgkinson James , Wilson Hannah M. , Crawford Carole , Stevens Richard , Lay-Flurrie Sarah , Dale Madeleine , Astbury Nerys , Chappell Lucy C. , McManus Richard J.
Published: January 2021

Objective:

To understand the current prevalence of, and attitudes to, self-monitoring of blood pressure (BP) during pregnancy.

Methods:

Five thousand, five hundred and fifty-five pregnant women from antenatal clinics in 16 hospitals in England were invited to complete a survey.

Main outcome measures:

The primary outcome was the proportion of women currently BP self-monitoring. Secondary outcomes included self-monitoring schedules and women's interactions with clinicians regarding self-monitoring. Population characteristics including risk factors for preeclampsia, ethnicity and deprivation level were considered.

Results:

Completed surveys were received and analysed from 5181 pregnant women (93% response rate). Comparison to hospital demographic data suggests that respondents were representative of the UK population. Nine hundred and eighty-three of 5181 (19%) women were currently self-monitoring their BP, constituting 189 of 389 (49%) hypertensive women and 794 of 4792 (17%) normotensive women. However, only 482 of 983 (49%) reported ever sharing this information with antenatal care teams. Of those who self-monitored, 68% (668/983) were able to provide a previous BP reading, compared with 1% (67/5181) of those who did not self-monitor.

Conclusion:

Many women are now choosing to self-monitor their BP during pregnancy and clinicians should enquire about this proactively and consider providing better information on BP monitoring. Those who self-monitor appear to have better knowledge about their blood pressure. If these findings were replicated nationwide, around 125 000 pregnant women would be currently self-monitoring BP in the UK, yet only half of these women may communicate their readings to their antenatal care teams, suggesting a missed opportunity for enhanced care. Current trials will make the place of self-monitoring in pregnancy clearer.
The Impact of COVID‐19 on Job Prospects and Educational Training for Pediatric Gastroenterology Fellows
Authors: Irastorza Laura E. , Hopson Puanani , Ta Allison , Kemme Sarah , Mallon Daniel , Lee Christine K.
Published: January 2021

Objectives:

The COVID‐19 pandemic has significantly affected graduate medical education with redistribution of trainees, altered clinical care, and decreased research. For graduating trainees, there remains concern that financial stability of health systems will affect the availability of new positions and hiring practices. This survey aims to evaluate the pandemic's impact from pediatric gastroenterology fellows’ perspectives.

Methods:

An anonymous survey was distributed by e‐mail from June 11 to July 1, 2020 to all North American pediatric gastroenterology and advanced training fellows. The survey was tailored for the fellows’ year of training including questions on education, clinical experience, research, and job outlook.

Results:

Of the 434 pediatric gastroenterology fellows, 145 completed the survey. Of all respondents, negative impact was reported in 52% on clinical training, 46% research projects, and 41% procedural confidence. A majority (93%) of third‐year respondents had a job contract signed at the time of the survey; however, 18% of those contracts were subsequently altered with 5 respondents having job contracts rescinded due to hiring freezes. Fifty‐four percent of first‐ and second‐year fellow respondents reported concern regarding finding a job with the majority being second‐year fellows (78%).

Conclusions:

The COVID‐19 pandemic continues to affect the medical system and healthcare professionals. This survey identified significant impact on job acquisition for graduating pediatric gastroenterology fellows and other critical components of training, which are likely applicable to other pediatric trainees. The survey results raise questions about potential strategies to improve medical education and job search success for graduating trainees.
Prevalence and Trends in HIV Infection and Testing Among Adults in the United States: The National Health and Nutrition Examination Surveys, 1999–2018
Authors: McQuillan Geraldine M. , Kruszon-Moran Deanna , Masciotra Silvina , Gu Qiuping , Storandt Renee
Published: January 2021

Background:

HIV antibody testing has been included in the National Health and Nutrition Examination Survey, for ages 18–49 since 1999 and for ages 18–59 years since 2009 enabling estimation of trends in HIV prevalence as part of national surveillance in the U.S. household population. Self-reported HIV testing and antiretroviral use was also included in the survey since 1999.

Setting:

A continuous household-based probability sample of the U.S. population.

Methods:

From 1999 to 2018, 29,020 participants age 18–49 years were tested for HIV antibody and 34,092 participants age 18–59 years were asked about self-report of any previous HIV testing.

Results:

HIV prevalence was 0.41% among those aged 18–59 in 2009–2018 with a nonsignificant trend over time among those aged 18–49 years from 1999–2002 to 2015–2018. However, significant declines in prevalence were seen among those aged 18–39 years (0.37%–0.11%), women (0.22%–0.06%) and non-Hispanic black persons (2.14%–0.80%). Participants aged 18–39 years self-reported a decline in HIV testing, whereas those aged 40–49 and 50–59 years, non-Hispanic black persons and women reported an increase in getting a HIV test. Prevalence of infection and self-reported history of HIV testing varied by demographic and risk groups. HIV testing among HIV-positive persons was 83.9%. Antiretroviral therapy among those HIV-positive was under 50%.

Conclusion:

Although total HIV prevalence and previous self-reported HIV testing remained stable for the last 20 years, there were significant declines in age and demographic subgroups. Prevalence for both outcomes varied by demographic and risk variables.
Entirely Robot-assisted Total Colectomy/Total Proctocolectomy Compared With a Laparoscopic Approach
Authors: Kim Jin Cheon , Lee Jong Lyul , Yoon Yong Sik , Kim Hyung Min , Kim Chan Wook , Park In Ja , Aldilaijan Abdulmohsin Fawzi , Lim Seok-Byung
Published: January 2021

Purpose:

Previous robot-assisted total colectomy/total proctocolectomy (TC/TPC) has been mostly confined to completion proctectomy combined with open or laparoscopic colon dissection. This study describes an integrative method of entirely robot-assisted maintaining anatomical dissection with single docking and one-off arm placement.

Materials and Methods:

Twenty patients who underwent robot-assisted TC/TPC and 36 who underwent laparoscopic procedures at the Asan Medical Center (Seoul, Korea) were enrolled.

Results:

Mean operation time was ∼1 hour longer in the robot-assisted than in the laparoscopic group (P=0.003), due primarily to the extra time required for instrument installation and more frequent transient ileal diversion. Three patients (8%) in the laparoscopic group required conversion to open surgery, compared with none in the robot-assisted group. Rates of postoperative adverse events did not differ in the 2 groups (P=0.063). Short (8 cm) ileal pouches were applied to all patients who underwent robot-assisted TPC/ileal-pouch anal anastomosis, but to one patient who underwent laparoscopic surgery. There were no discrepancies of mean daily bowel movement between patients with short and long ileal pouches 6 months after surgery (P=0.694), showing 5 times per day (range: 1 to 10).

Conclusion:

The advantages of the boom system and motion-sensitive table were successfully utilized to integrate anatomical dissection with the multiquadrant procedures of TC/TPC, with none of these patients requiring conversion to open surgery. Refinement of these techniques may overcome some of the technical and time-related and cost-related concerns of the robotic approach.