bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of trimodal and bimodal therapy in a selective-surgery paradigm for locally advanced oesophageal squamous cell carcinoma
Authors: Zhou N , Mitchell K G , Corsini E M , Truong V T T , Antonoff M B , Mehran R J , Rajaram R , Rice D C , Roth J A , Sepesi B , Swisher S G , Vaporciyan A A , Walsh G L , Ajani J A , Hofstetter W L 
Published: April 2021

Abstract

Background
Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated.

Methods
Patients with stage II–III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response.

Results
Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P &lt; 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper–mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P &lt; 0.001).

Conclusion
In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival outcomes may be due to patient selection; therefore, a selective-surgery strategy in oesophageal squamous cell carcinoma is a reasonable approach.
Modelling the Impact of Vector Control on Lymphatic Filariasis Programs: Current Approaches and Limitations
Authors: Davis E L , Prada J , Reimer L J , Hollingsworth T D 
Published: April 2021

Abstract
Vector control is widely considered an important tool for lymphatic filariasis (LF) elimination but is not usually included in program budgets and has often been secondary to other policy questions in modelling studies. Evidence from the field demonstrates that vector control can have a large impact on program outcomes and even halt transmission entirely, but implementation is expensive. Models of LF have the potential to inform where and when resources should be focused, but often simplify vector dynamics and focus on capturing human prevalence trends, making them comparatively ill-designed for direct analysis of vector control measures. We review the recent modelling literature and present additional results using a well-established model, highlighting areas of agreement between model predictions and field evidence, and discussing the possible determinants of existing disagreements. We conclude that there are likely to be long-term benefits of vector control, both on accelerating programs and preventing resurgence.
Graft reduction surgery is associated with poorer outcome after lung transplantation: a single-centre propensity score-matched analysis
Authors: Montoya Pilar , Bello Irene , Ascanio Fernando , Romero Laura , Pérez Javier , Rosado Joel , Sánchez Leire , Sacanell Judith , Ribas Montserrat , Berastegui Cristina , Deu Maria , Jáuregui Alberto 
Published: April 2021

Abstract

OBJECTIVES
Implanted lung volume-reduction surgery due to donor/recipient size mismatch could affect both lung function and survival. We examined the outcomes of lung volume-reduction procedures post-lung transplant.

METHODS
We retrospectively reviewed 366 consecutive adult lung transplants carried out between January 2014 and December 2018 at one single centre. Patients were divided into either a non-reduced-size lung transplant or a reduced-size lung transplant (RT) group. To adjust for covariates, a propensity score analysis was performed. Survival was estimated using the Kaplan–Meier method. Differences were considered significant with P-values &lt;0.05.

RESULTS
In the RT group, 45 patients (12.3%) had some type of graft reduction surgery: 31 (68.9%) patients had pulmonary lobectomies and 14 (31.1%) wedge resections. Of the total cohort, 30 patients (8.2%) were prioritized, 23% of whom required graft reduction surgery. The propensity score analysis matched 41 patients in each group. In the RT group, there was an increased need for cardiopulmonary bypass (P = 0.017) during surgery and extracorporeal membrane oxygenation (P = 0.025) after lung transplant. Furthermore, the median length of mechanical ventilation was higher (P = 0.008), and lung function at discharge, 3 and 6 months post-lung transplant was significantly lower in the RT group (P &lt; 0.05). Survival analysis demonstrated a significantly poorer overall outcome at 1, 3 and 5 years post-lung transplantation in patients with a reduced graft (P = 0.007), while the 1-year conditional survival was also worse in this group (P = 0.025).

CONCLUSIONS
Graft reduction surgery in lung transplant recipients is associated with lower pulmonary function and poorer overall survival. However, it does allow transplantation in prioritized recipients for whom it might otherwise be impossible to find an organ of suitable size.
Atrial fibrillation and kidney function: a bidirectional Mendelian randomization study
Authors: Park Sehoon , Lee Soojin , Kim Yaerim , Lee Yeonhee , Kang Min Woo , Kim Kwangsoo , Kim Yong Chul , Han Seung Seok , Lee Hajeong , Lee Jung Pyo , Joo Kwon Wook , Lim Chun Soo , Kim Yon Su , Kim Dong Ki 
Published: April 2021

Abstract

Aims
The aim of this study was to investigate the causal effects between atrial fibrillation (AF) and kidney function.

Methods and results
We performed a bidirectional summary-level Mendelian randomization (MR) analysis implementing the results from a large-scale genome-wide association study for estimated glomerular filtration rate (eGFR) by the CKDGen (N = 765 348) and AF (N = 588 190) to identify genetic instruments. The inverse variance weighted method was the main MR method used. For replication, an allele score-based MR was performed by individual-level data within a UK Biobank cohort of white British ancestry individuals (N = 337 138). A genetic predisposition to AF was significantly associated with decreased eGFR [for log-eGFR, beta −0.003 (standard error, 0.0005), P &lt; 0.001] and increased risk of chronic kidney disease [beta 0.059 (0.0126), P &lt; 0.001]. The significance remained in MR sensitivity analyses and the causal estimates were consistent when we limited the analysis to individuals of European ancestry. Genetically predicted eGFR did not show a significant association with the risk of AF [beta −0.366 (0.275), P = 0.183]. The results were similar in allele score-based MR, as allele score for AF was significantly associated with reduced eGFR [for continuous eGFR, beta −0.079 (0.021), P &lt; 0.001], but allele score for eGFR did not show a significant association with risk of AF [beta −0.005 (0.008), P = 0.530].

Conclusions
Our study supports that AF is a causal risk factor for kidney function impairment. However, an effect of kidney function on AF was not identified in this study.
A capture-based assay for detection and characterization of transposon polymorphisms in maize
Authors: Li Minqi , Noshay Jaclyn M , Dong Xiaoxiao , Springer Nathan M , Li Qing 
Published: April 2021

Abstract
Transposons can create allelic diversity that affects gene expression and phenotypic diversity. The detection of transposon polymorphisms at a genome-wide scale across a large population is difficult. Here, we developed a targeted sequencing approach to monitor transposon polymorphisms of interest. This approach can interrogate the presence or absence of transposons reliably across various genotypes. Using this approach, we genotyped a set of 965 transposon-related presence/absence polymorphisms in a diverse panel of 16 maize (Zea mays L.) inbred lines that are representative of the major maize breeding groups. About 70% of the selected regions can be effectively assayed in each genotype. The consistency between the capture-based assay and PCR-based assay are 98.6% based on analysis of 24 randomly selected transposon polymorphisms. By integrating the transposon polymorphisms data with gene expression data, ∼18% of the assayed transposon polymorphisms were found to be associated with variable gene expression levels. A detailed analysis of 18 polymorphisms in a larger association panel confirmed the effects of 10 polymorphisms, with one of them having a stronger association with expression than nearby SNP markers. The effects of seven polymorphisms were tested using a luciferase-based expression assay, and one was confirmed. Together, this study demonstrates that the targeted sequencing assay is an effective way to explore transposon function in a high-throughput manner.
Tales From the Front Lines: The Creative Essay as a Tool for Teaching Genetics
Authors: Koehler Kara E , Hawley R Scott 
Published: April 2021

Abstract
In contrast to the more typical mock grant proposals or literature reviews, we describe the use of the creative essay as a novel tool for teaching human genetics at the college level. This method has worked well for both nonmajor and advanced courses for biology majors. The 10- to 15-page essay is written in storylike form and represents a student's response to the choice of 6–8 scenarios describing human beings coping with various genetic dilemmas. We have found this tool to be invaluable both in developing students' ability to express genetic concepts in lay terms and in promoting student awareness of genetic issues outside of the classroom. Examples from student essays are presented to illustrate these points, and guidelines are suggested regarding instructor expectations of student creativity and scientific accuracy. Methods of grading this assignment are also discussed.
Reconstructing the Prior Probabilities of Allelic Phylogenies
Authors: Golding G Brian 
Published: April 2021

Abstract
In general when a phylogeny is reconstructed from DNA or protein sequence data, it makes use only of the probabilities of obtaining some phylogeny given a collection of data. It is also possible to determine the prior probabilities of different phylogenies. This information can be of use in analyzing the biological causes for the observed divergence of sampled taxa. Unusually “rare” topologies for a given data set may be indicative of different biological forces acting. A recursive algorithm is presented that calculates the prior probabilities of a phylogeny for different allelic samples and for different phylogenies. This method is a straightforward extension of Ewens' sample distribution. The probability of obtaining each possible sample according to Ewens' distribution is further subdivided into each of the possible phylogenetic topologies. These probabilities depend not only on the identity of the alleles and on 4Nμ (four times the effective population size times the neutral mutation rate) but also on the phylogenetic relationships among the alleles. Illustrations of the algorithm are given to demonstrate how different phylogenies are favored under different conditions.
Genetic Analysis of Early Flowering Mutants in Arabidopsis Defines a Class of Pleiotropic Developmental Regulator Required for Expression of the Flowering-Time Switch Flowering Locus C
Authors: Zhang Hua , Ransom Callista , Ludwig Philip , van Nocker Steven 
Published: April 2021

Abstract
The Arabidopsis flowering-repressor gene FLOWERING LOCUS C (FLC) is a developmental switch used to trigger floral induction after extended growth in the cold, a process termed vernalization. In vernalized plants, FLC becomes transcriptionally silenced through a process that involves an epigenetic mechanism. We identified recessive mutations designated vernalization independence (vip) that confer cold-independent flowering and suppression of FLC. These mutations also lead to developmental pleiotropy, including specific defects in floral morphology, indicating that the associated genes also have functions unrelated to flowering time. We identified the VIP3 gene by positional cloning and found that it encodes a protein consisting almost exclusively of repeated Trp-Asp (WD) motifs, suggesting that VIP3 could act as a platform to assemble a protein complex. Constitutive transgenic expression of VIP3 in vernalized plants is insufficient to activate FLC, and thus VIP3 probably participates in the regulation of FLC as one component of a more extensive mechanism. Consistent with this, genetic analyses revealed that the VIP loci define a functional gene class including at least six additional members. We suggest that VIP3 and other members of this gene class could represent a previously unrecognized flowering mechanism.
DNA Polymorphism in the β-EsteraseGene Cluster ofDrosophila melanogaster
Authors: Balakirev Evgeniy S , Chechetkin V R , Lobzin V V , Ayala Francisco J 
Published: April 2021

AbstractWe have analyzed nucleotide polymorphism within a 5.3-kb region encompassing the functional Est-6 gene and the ψEst-6 putative pseudogene in 28 strains of Drosophila melanogaster and one of D. simulans. Two divergent sequence types were detected, which are not perfectly associated with Est-6 allozyme variation. The level of variation (π) is very close in the 5′-flanking region (0.0059) and Est-6 gene (0.0057), but significantly higher in the intergenic region (0.0141) and putative pseudogene (0.0122). The variation in the 3′-flanking region is intermediate (0.0083). These observations may reflect different levels of purifying selection in the different regions. Strong linkage disequilibrium occurs within the region studied, with the largest values revealed in the putative pseudogene and 3′-flanking region. Moreover, recombination is restricted within ψEst-6. Gene conversion is detected both within and (to a lesser extent) between Est-6 and ψEst-6. The data indicate that ψEst-6 exhibits some characteristics that are typical of nonfunctional genes, while other characteristics are typically attributed to functional genes; the same situation has been observed in other pseudogenes (including Drosophila). The results of structural entropy analysis demonstrate higher structural ordering in Est-6 than in ψEst-6, in accordance with expectations if ψEst-6 is indeed a pseudogene. Taking into account that the function of ψEst-6 is not known (but could exist) and following the terminology of J. Brosius and S. J. Gould, we suggest that the term “potogene” may be appropriate for ψEst-6, indicating that it is a potential gene that may have acquired some distinctive but unknown function.
PrBn, a Major Gene Controlling Homeologous Pairing in Oilseed Rape (Brassica napus) Haploids
Authors: Jenczewski Eric , Eber Frédérique , Grimaud Agnès , Huet Sylvie , Lucas Marie Odile , Monod Hervé , Chèvre Anne Marie 
Published: April 2021

AbstractPrecise control of chromosome pairing is vital for conferring meiotic, and hence reproductive, stability in sexually reproducing polyploids. Apart from the Ph1 locus of wheat that suppresses homeologous pairing, little is known about the activity of genes that contribute to the cytological diploidization of allopolyploids. In oilseed rape (Brassica napus) haploids, the amount of chromosome pairing at metaphase I (MI) of meiosis varies depending on the varieties the haploids originate from. In this study, we combined a segregation analysis with a maximum-likelihood approach to demonstrate that this variation is genetically based and controlled mainly by a gene with a major effect. A total of 244 haploids were produced from F1 hybrids between a high- and a low-pairing variety (at the haploid stage) and their meiotic behavior at MI was characterized. Likelihood-ratio statistics were used to demonstrate that the distribution of the number of univalents among these haploids was consistent with the segregation of a diallelic major gene, presumably in a background of polygenic variation. Our observations suggest that this gene, named PrBn, is different from Ph1 and could thus provide complementary information on the meiotic stabilization of chromosome pairing in allopolyploid species.
Characterization of High-Copy-Number Retrotransposons From the Large Genomes of the Louisiana Iris Species and Their Use as Molecular Markers
Authors: Kentner Edward K , Arnold Michael L , Wessler Susan R 
Published: April 2021

AbstractThe Louisiana iris species Iris brevicaulis and I. fulva are morphologically and karyotypically distinct yet frequently hybridize in nature. A group of high-copy-number TY3/gypsy-like retrotransposons was characterized from these species and used to develop molecular markers that take advantage of the abundance and distribution of these elements in the large iris genome. The copy number of these IRRE elements (for iris retroelement), is ∼1 × 105, accounting for ∼6–10% of the ∼10,000-Mb haploid Louisiana iris genome. IRRE elements are transcriptionally active in I. brevicaulis and I. fulva and their F1 and backcross hybrids. The LTRs of the elements are more variable than the coding domains and can be used to define several distinct IRRE subfamilies. Transposon display or S-SAP markers specific to two of these subfamilies have been developed and are highly polymorphic among wild-collected individuals of each species. As IRRE elements are present in each of 11 iris species tested, the marker system has the potential to provide valuable comparative data on the dynamics of retrotransposition in large plant genomes.
Estimating Mutation Rate: How to Count Mutations?
Authors: Fu Yun-Xin , Huai Haying 
Published: April 2021

Abstract
Mutation rate is an essential parameter in genetic research. Counting the number of mutant individuals provides information for a direct estimate of mutation rate. However, mutant individuals in the same family can share the same mutations due to premeiotic mutation events, so that the number of mutant individuals can be significantly larger than the number of mutation events observed. Since mutation rate is more closely related to the number of mutation events, whether one should count only independent mutation events or the number of mutants remains controversial. We show in this article that counting mutant individuals is a correct approach for estimating mutation rate, while counting only mutation events will result in underestimation. We also derived the variance of the mutation-rate estimate, which allows us to examine a number of important issues about the design of such experiments. The general strategy of such an experiment should be to sample as many families as possible and not to sample much more offspring per family than the reciprocal of the pairwise correlation coefficient within each family. To obtain a reasonably accurate estimate of mutation rate, the number of sampled families needs to be in the same or higher order of magnitude as the reciprocal of the mutation rate.
An Argonaute-Like Protein Is Required for Meiotic Silencing
Authors: Lee Dong W , Pratt Robert J , McLaughlin Malcolm , Aramayo Rodolfo 
Published: April 2021

Abstract
We demonstrate the involvement of suppressor of meiotic silencing-2 (sms-2+), a Neurospora gene coding for an Argonaute-like protein, in meiotic silencing and normal sexual development.
False Discovery Rate in Linkage and Association Genome Screens for Complex Disorders
Authors: Sabatti Chiara , Service Susan , Freimer Nelson 
Published: April 2021

AbstractWe explore the implications of the false discovery rate (FDR) controlling procedure in disease gene mapping. With the aid of simulations, we show how, under models commonly used, the simple step-down procedure introduced by Benjamini and Hochberg controls the FDR for the dependent tests on which linkage and association genome screens are based. This adaptive multiple comparison procedure may offer an important tool for mapping susceptibility genes for complex diseases.
Molecular Characterization of a Family of Tandemly Repeated DNA Sequences, TR-1, in Heterochromatic Knobs of Maize and Its Relatives
Authors: Hsu F C , Wang C J , Chen C M , Hu H Y , Chen C C 
Published: April 2021

Abstract
Two families of tandem repeats, 180-bp and TR-1, have been found in the knobs of maize. In this study, we isolated 59 clones belonging to the TR-1 family from maize and teosinte. Southern hybridization and sequence analysis revealed that members of this family are composed of three basic sequences, A (67 bp); B (184 bp) or its variants B′ (184 bp), 2/3B (115 bp), 2/3B′ (115 bp); and C (108 bp), which are arranged in various combinations to produce repeat units that are multiples of ∼180 bp. The molecular structure of TR-1 elements suggests that: (1) the B component may evolve from the 180-bp knob repeat as a result of mutations during evolution; (2) B′ may originate from B through lateral amplification accompanied by base-pair changes; (3) C plus A may be a single sequence that is added to B and B′, probably via nonhomologous recombination; and (4) 69 bp at the 3′ end of B or B′, and the entire sequence of C can be removed from the elements by an unknown mechanism. Sequence comparisons showed partial homologies between TR-1 elements and two centromeric sequences (B repeats) of the supernumerary B chromosome. This result, together with the finding of other investigators that the B repeat is also fragmentarily homologous to the 180-bp repeat, suggests that the B repeat is derived from knob repeats in A chromosomes, which subsequently become structurally modified. Fluorescence in situ hybridization localized the B repeat to the B centromere and the 180-bp and TR-1 repeats to the proximal heterochromatin knob on the B chromosome.