bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unified synthesis and assessment of tumor cell migration inhibitory activity of optically active UTKO1, originally designed moverastin analog
Authors: Ogura Yusuke , Kobayashi Hiroki , Imoto Masaya , Watanabe Hidenori , Takikawa Hirosato 
Published: January 2021

Abstract
UTKO1 is a synthetic analog of a natural tumor cell migration inhibitor, moverastin, isolated from microbial extracts of Aspergillus sp. 7720. UTKO1 was initially developed as a mixture of the stereoisomers. In this study, a concise and unified synthesis of the 4 optically active stereoisomers of UTKO1 was achieved from a known optically pure dihydro-α-ionone through a 5-step sequence. The key transformation in the synthesis was a Nozaki–Hiyama–Kishi (NHK) reaction between an optically active enoltriflate and a known aldehyde to install the chiral allylic hydroxy group at C2′. Simple chromatographic separation of the 2 diastereomers with regard to the allylic hydroxy group was possible by the derivatization into the corresponding acetals with Nemoto's optical resolution reagent, (S)- or (R)-5-allyl-2-oxabicyclo[3.3.0]octene (ALBO). All 4 synthetic stereoisomers of UTKO1 exhibited comparable tumor cell migration inhibitory activity.
Genetic sequence analysis and characterization of bioactive compounds in mushroom-forming fungi
Authors: Suzuki Tomohiro 
Published: January 2021

AbstractMushroom-forming fungi produce unique bioactive compounds that have potential applications as medicines, supplements, and agrochemicals. Thus, it is necessary to clarify the biosynthetic pathways of these compounds using genome and transcriptome analyses. This review introduces some of our research on bioactive compounds isolated from mushrooms, as well as genetic analysis with next-generation sequencing.
Chemical studies on bioactive compounds related to higher fungi
Authors: Kawagishi Hirokazu 
Published: January 2021

Abstract
Hericium erinaceus (Yamabushitake in Japan) is a well-known edible and medicinal mushroom. We discovered antidementia compounds, hericenones C to H, from the fruiting bodies and erinacine A to I from the cultured mycelia of the fungus. Based on the data of the compounds, several clinical experiments were performed using the fungus. “Fairy rings” is a phenomenon that turfgrass grows more prolific or inhibited than the surrounding area as a ring and then occasionally mushrooms develop on the ring. We found fairy-ring causing principles “fairy chemicals” and the biosynthetic routes of the compounds on the purine metabolic pathway in plants and mushrooms.
Fluorescent-dependent comparative Ct method for qPCR gene expression analysis in IVF clinical pre-implantation embryonic testing
Authors: Lal Arnav , Roudebush William E , Mainigi Monica , Chosed Renee J 
Published: January 2021

Abstract
The use of quantitative PCR (qPCR) and other polymerase chain reaction (PCR)-based methods in the field of human in vitro fertilization blastocoel fluid analysis can potentially be utilized for assisting clinicians in embryo selection based on specific gene expression patterns. Since typical Comparative cycle threshold (Ct) analysis utilizes one threshold for runs per gene target and requires an inherent control group, this method is inadequate for analysis of small stochastic systems, such as embryonic-derived fluid. We mathematically demonstrate analytical modifications upon the Comparative Ct qPCR workflow to incorporate a variable fluorescence threshold (utilizing only the parameters defined in the Comparative Ct method), and subsequently demonstrate the typical workflow in which this modified method can successfully quantifiably analyze embryonic blastocoel fluid qPCR analysis.
Mortality after surgery for primary hyperparathyroidism: results from a nationwide cohort
Authors: Nilsson M , Ivarsson K , Thier M , Nordenström E , Bergenfelz A , Almquist M 
Published: January 2021

Abstract

Background
Contemporary patients with primary hyperparathyroidism are often diagnosed with mildly raised serum calcium levels. Previous studies have reported increased mortality in patients with primary hyperparathyroidism. This retrospective cohort study aimed to examine whether contemporary patients operated for primary hyperparathyroidism have higher mortality than the general population, and whether mortality in these patients is associated with serum calcium concentration, adenoma weight or multiglandular disease.

Methods
Patients from a Swedish national cohort consisting of patients registered in the Scandinavian Quality Register for Thyroid, Parathyroid, and Adrenal Surgery 2003–2013, were matched with population controls. The National Patient Register, the Swedish Cause of Death Register, and socioeconomic data were cross-linked. End of follow-up was 10 years after surgery, 31 December 2015, or emigration. Mortality was analysed by standardized mortality ratio, Kaplan–Meier survival estimates, and univariable and multivariable Cox regression. Multiple imputation by chained equations was performed on missing data.

Results
After exclusions, there were 5009 patients with primary hyperparathyroidism and 14 983 controls. Multivariable Cox regression analysis adjusted for age, sex, Charlson Co-morbidity Index, marital status, level of education, disposable income, and period of surgery showed lower mortality in patients than controls (hazard ratio (HR) 0.83, 95 per cent c.i. 0.75 to 0.92). In univariable Cox regression of mortality in patients, serum calcium concentration (mmoles per litre) was associated with mortality (HR 2.20, 1.53 to 3.16). This association remained in multivariable Cox regression after multiple imputation (HR 1.79, 1.19 to 2.70).

Conclusion
Mortality was not increased in patients operated for primary hyperparathyroidism compared with controls in a contemporary setting. Preoperative serum calcium concentration might, however, influence survival.
Speckle-tracking echocardiography in comparison with ejection fraction for prediction of cardiovascular mortality in patients with end-stage renal disease
Authors: Terhuerne Janna , van Diepen Merel , Kramann Rafael , Erpenbeck Johanna , Dekker Friedo , Marx Nikolaus , Floege Jürgen , Becker Michael , Schlieper Georg 
Published: January 2021

Abstract

Background
Cardiovascular disease is the major cause of death in end-stage renal disease (ESRD). To develop better means to assess cardiovascular risk in these patients, we compared conventional echocardiography-derived left ventricular ejection fraction (EF) with the novel method of 2D speckle-tracking echocardiography to determine cardiac strain.

Methods
Predictive performances of conventional EF and speckle-tracking echocardiography-derived global longitudinal strain (GLS) were compared using receiver-operator curve (ROC) analyses and calibration by calibration plots. We also took into account other known cardiovascular risk factors through multivariable logistic regression analysis.

Results
The study comprised 171 ESRD patients (mean age 64 years, 64% male) on maintenance dialysis therapy (93% haemodialysis, 7% peritoneal dialysis) for an average period of 39 months. During 2.1 years of follow-up, 42 patients (25%) died from cardiovascular disease. ROC analysis of GLS resulted in an area under the curve of 0.700 [95% confidence interval (CI) 0.603–0.797] compared with an area under the curve of EF of 0.615 (95% CI 0.514–0.716) (P = 0.059 for difference). The total absolute deviation between predicted and observed outcome frequencies obtained by calibration plots were 13.8% for EF compared with only 6.4% for GLS. Best results of ROC analysis (area under the curve = 0.759; P = 0.06), calibration and goodness-of-fit (χ2 = 28.34, P ≤ 0.0001, R2 = 0.25) were achieved for GLS added to a baseline model consisting of known cardiovascular risk factors in a multivariate regression analysis.

Conclusions
In summary, in chronic dialysis patients, GLS is a more precise predictor of cardiovascular mortality than conventional echocardiography-derived EF.
Roxadustat and thyroid-stimulating hormone suppression
Authors: Tokuyama Atsuyuki , Kadoya Hiroyuki , Obata Atsushi , Obata Takahiro , Sasaki Tamaki , Kashihara Naoki 
Published: January 2021

Abstract
Hypoxia-inducible factor prolyl-hydroxylase inhibitors belong to a new class of orally administered drugs for treating anemia in patients with chronic kidney disease (CKD). The prevalence of hypothyroidism is disproportionately high in patients with CKD on hemodialysis. We report a rapid suppression of thyroid-stimulating hormone (TSH) and decrease in free triiodothyronine (T3) and free tetraiodothyronine levels after switching from darbepoetin alfa to roxadustat in a hemodialysis patient with hypothyroidism on levothyroxine therapy. This was reversed after stopping roxadustat. Roxadustat has structural similarity with T3 and is a selective activating ligand for thyroid hormone receptor-β possibly suppressing TSH release.
Suboptimal personal protective equipment and SARS-CoV-2 infection in Nephrologists: a Spanish national survey
Authors: Quiroga Borja , Sánchez-Álvarez Emilio , Ortiz Alberto , de Sequera Patricia ,   the Spanish Society of Nephrology
Published: January 2021

Abstract

Background
Healthcare workers have been overexposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the current pandemic, but there is little information on the impact of SARS-CoV-2 on nephrologists. The aim of this study was to assess SARS-CoV-2 infections in nephrologists in the first and second pandemic waves, describing risk factors and clinical features.

Methods
This national survey was sent to Spanish nephrologists. Epidemiological data, comorbidities and medications were collected and compared between infected and non-infected nephrologists. Symptoms, prescribed treatments and outcomes are described for infected nephrologists.

Results
Three hundred and twenty-seven nephrologists (66% female, age 46 ± 11 years) completed the survey. Of them, 62 (19%) were infected by SARS-CoV-2. Infection was detected by real-time reverse transcription-polymerase chain reaction in the 37 symptomatic patients (62%) and by serological tests in 25 (38%) asymptomatic individuals. Five (8%) of the infected nephrologists were hospitalized. Contrary to the general population, most infections occurred during the first pandemic wave and, specifically, during the first month, when personal protective equipment (PPE) shortages were more severe. Factors associated with infection in univariate analysis were younger age (P = 0.004), work in non-nephrology departments (P = 0.045), higher exposure to coronavirus disease 2019 patients (P &lt; 0.001), lack of appropriate PPE (P &lt; 0.001) and non-O ABO blood group. In an adjusted multivariate model, only lack of appropriate PPE remained predictive of infection [hazard ratio 3.5 (95% confidence interval 1.9–6.8), P &lt; 0.0001].

Conclusions
SARS-CoV-2 infection was frequent among nephrologists, was frequently diagnosed late and was associated with working conditions.
Evaluation of Thyroid Function in Pregnant Women Using Automated Immunoassays
Authors: Geno K Aaron , Reed Matthew S , Cervinski Mark A , Nerenz Robert D 
Published: January 2021

Abstract

Introduction
Automated free thyroxine (FT4) immunoassays are widely available, but professional guidelines discourage their use in pregnant women due to theoretical under-recoveries attributed to increased thyroid hormone binding capacity and instead advocate the use of total T4 (TT4) or free thyroxine index (FTI). The impact of this recommendation on the classification of thyroid status in apparently euthyroid pregnant patients was evaluated.

Methods
After excluding specimens with thyroid autoantibody concentrations above reference limits, thyroid-stimulating hormone (TSH), FT4, TT4, and T-uptake were measured on the Roche Cobas® platform in remnant clinical specimens from at least 147 nonpregnant women of childbearing age and pregnant women at each trimester. Split-sample comparisons of FT4 as measured by the Cobas and equilibrium dialysis were performed.

Results
FT4 decreased with advancing gestational age by both immunoassay and equilibrium dialysis. TSH declined during the first trimester, remained constant in the second, and increased throughout the third, peaking just before delivery. Interpretation of TT4 concentrations using 1.5-times the nonpregnant reference interval classified 13.6% of first trimester specimens below the lower reference limit despite TSH concentrations within trimester-specific reference intervals. Five FTI results from 480 pregnant individuals (about 1.0%) fell outside the manufacturer’s reference interval.

Conclusions
Indirect FT4 immunoassay results interpreted in the context of trimester-specific reference intervals provide a practical and viable alternative to TT4 or FTI. Declining FT4 and increasing TSH concentrations near term suggest that declining FT4 is not an analytical artifact but represents a true physiological change in preparation for labor and delivery.
Predicting Damage to Hop Cones by Tetranychus urticae (Acari: Tetranychidae)
Authors: Woods Joanna L , Iskra Anne E , Gent David H 
Published: January 2021

Abstract
Twospotted spider mite (Tetranychus urticae Koch) is a cosmopolitan pest of numerous plants, including hop (Humulus lupulus L.). The most costly damage from the pest on hop results from infestation of cones, which are the harvested product, which can render crops unsalable if cones become discolored. We analyzed 14 yr of historical data from 312 individual experimental plots in western Oregon to identify risk factors associated with visual damage to hop cones from T. urticae. Logistic regression models were fit to estimate the probability of cone damage. The most predictive model was based on T. urticae-days during mid-July to harvest, which correctly predicted occurrence and nonoccurrence of cone damage in 91 and 93% of data sets, respectively, based on Youden’s index. A second model based on the ratio of T. urticae to predatory arthropods late in the season correctly predicted cone damage in 92% of data sets and nonoccurrence of damage in 77% of data sets. The model based on T. urticae abundance performed similarly when validated in 23 commercial hop yards, whereas the model based on the predator:prey ratio was relatively conservative and yielded false-positive predictions in 11 of the 23 yards. Antecedents of these risk factors were explored and quantified by structural equation modeling. A simple path diagram was constructed that conceptualizes T. urticae invasion of hop cones as dependent on prior density of the pest on leaves in early spring and summer, which in turn influences the development of predatory arthropods that mediate late-season density of the pest. In summary, the biological insights and models developed here provide guidance to pest managers on the likelihood of visual cone damage from T. urticae that can inform late-season management based on both abundance of the pest and its important predators. This is critically important because a formal economic threshold for T. urticae on hop does not exist and current management efforts may be mistimed to influence the pest when crop damage is most probable. More broadly, this research suggests that current management practices that target T. urticae early in the season may in fact predispose yards to later outbreaks of the pest.
Prevalence of diabetes and impact on cardiovascular events and mortality in patients with chronic coronary syndromes, across multiple geographical regions and ethnicities
Authors: Mak Koon-Hou , Vidal-Petiot Emmanuelle , Young Robin , Sorbets Emmanuel , Greenlaw Nicola , Ford Ian , Tendera Michal , Ferrari Roberto , Tardif Jean-Claude , Udell Jacob A , Escobedo Jorge , Fox Kim M , Steg Philippe Gabriel ,   the CLARIFY Investigators
Published: January 2021

AbstractBackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis &gt;50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564
Female sterile mutations on the second chromosome of Drosophila melanogaster. I. Maternal effect mutations.
Authors: Schüpbach T , Wieschaus E 
Published: January 2021

Abstract
In mutagenesis screens for recessive female sterile mutations on the second chromosome of Drosophila melanogaster 529 chromosomes were isolated which allow the homozygous females to survive, but cause them to be sterile. In 136 of these lines, mutant females produce morphologically normal eggs which cannot support normal embryonic development. These "maternal-effect" mutations fall into 67 complementation groups which define 23 multiply hit and 44 singly hit loci. In eggs from 14 complementation groups development is blocked before the formation of a syncytial blastoderm. In eggs from 12 complementation groups development is abnormal before cellularization, 17 complementation groups cause abnormal cellularization, 12 complementation groups cause changes in cellular morphology in early gastrulation stages, and 12 complementation groups seem to affect later embryonic development.
A cytogenetic analysis of the Punch-tudor region of chromosome 2R in Drosophila melanogaster.
Authors: O'Donnell J , Boswell R , Reynolds T , Mackay W 
Published: January 2021

Abstract
Eleven chromosomal deficiencies and several rearrangements in the Pu-tud region of chromosome 2R have been generated and examined cytologically. The Pu locus has been localized to chromosome bands 57C5-6 and tud to 57C7-8. Mutagenesis within the region defined by the deletion intervals has resulted in the isolation of 92 new lethal mutations. Seventy-six of these mutations have been separated into 16 complementation groups that have been ordered and placed cytologically by deletion mapping. All new alleles fully complement tud for both lethal and grandchildless phenotypes. The largest number of new mutations, a total of 25, are Pu alleles.
Spatial autocorrelation analysis of the distribution of genotypes within populations of lodgepole pine.
Authors: Epperson B K , Allard R W 
Published: January 2021

Abstract
Spatial autocorrelation analyses of point samples within two populations of lodgepole pine (Pinus contorta ssp. latifolia) indicate that single-locus mature tree and pollen genotypes are distributed in a nearly random fashion for most of the allozyme loci assayed. This lack of structure in the distributions of most genotypes is consistent with outcrossing rates that are very nearly 1.0 and with estimates indicating that both pollen and seed are dispersed over long distances in lodgepole pine. However, spatial autocorrelation of genotypes for a few loci suggests that genotypes at these loci may be under natural selection.
Ath-2, a second gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice.
Authors: Paigen B , Nesbitt M N , Mitchell D , Albee D , LeBoeuf R C 
Published: January 2021

Abstract
Strain C57BL/6J and A/J differ at two genes determining atherosclerosis susceptibility. The first gene, Ath-1, was described earlier and this report characterizes Ath-2. The alleles at Ath-2 are r for resistance and s for susceptibility to atherosclerosis. The resistant phenotype in female mice is characterized by high plasma high density lipoprotein-cholesterol levels (74 mg/dl +/- SEM 2) and very few lesions/mouse after 14 weeks of consumption of an atherogenic diet (0.1 +/- SEM 0.1 in a predetermined region of the aorta). The susceptible phenotype in female mice is characterized by low levels of high density lipoprotein-cholesterol (35 mg/dl +/- SEM 1) and 1.2 lesions/mouse +/- SEM 0.2 in the same region of the aorta. In Ath-2 heterozygotes, resistance is dominant to susceptibility. Recombinant inbred strains derived from C57BL/6 and A were characterized for Apoa 1, Apoa 2 and susceptibility to atherosclerosis. Ath-1 and Ath-2 interact with each other so that resistant alleles at either locus confer a resistant phenotype to the animal. The map position of Ath-2 is not known, but Ath-2 does not map near genes determining the apolipoproteins for A-I, A-II, or E.
Amino acid sequence similarity between GCN3 and GCD2, positive and negative translational regulators of GCN4: evidence for antagonism by competition.
Authors: Paddon C J , Hannig E M , Hinnebusch A G 
Published: January 2021

Abstract
The GCD2 gene product is required in conditions of amino acid sufficiency to repress the synthesis of GCN4, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. GCD2 is also required unconditionally for cell viability. The constitutive derepression of GCN4 expression and temperature sensitivity for growth associated with GCD2 alleles, known as gcd12 mutations, are completely masked by wild-type GCN3, a positive regulator of GCN4 expression. This observation suggests that GCN3 can promote or at least partially substitute for GCD2 function in normal growth conditions, while acting as an antagonist of GCD2 in amino acid starvation conditions. We report here that the predicted amino acid sequence of GCN3 shows extensive similarity with the carboxyl-terminal portion of GCD2. Based on this finding, it seems likely that gcd12 mutations specifically affect the domain of GCD2 that is similar in sequence to GCN3. We propose that GCN3 can substitute for this domain in a gcd12 mutant grown in normal growth conditions, and that modification of GCN3 in starvation conditions causes it to interfere with, rather than substitute for GCD2 function. A gcd2 deletion and gcd2-1 are each expected to inactivate a second domain for which GCN3 cannot substitute, accounting for the inability of GCN3 to mask the phenotypes associated with these mutations.