bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpretable network-guided epistasis detection
Authors: Duroux Diane , Climente-González Héctor , Azencott Chloé-Agathe , Van Steen Kristel 
Published: February 2022

Abstract

Background
Detecting epistatic interactions at the gene level is essential to understanding the biological mechanisms of complex diseases. Unfortunately, genome-wide interaction association studies involve many statistical challenges that make such detection hard. We propose a multi-step protocol for epistasis detection along the edges of a gene-gene co-function network. Such an approach reduces the number of tests performed and provides interpretable interactions while keeping type I error controlled. Yet, mapping gene interactions into testable single-nucleotide polymorphism (SNP)-interaction hypotheses, as well as computing gene pair association scores from SNP pair ones, is not trivial.

Results
Here we compare 3 SNP-gene mappings (positional overlap, expression quantitative trait loci, and proximity in 3D structure) and use the adaptive truncated product method to compute gene pair scores. This method is non-parametric, does not require a known null distribution, and is fast to compute. We apply multiple variants of this protocol to a genome-wide association study dataset on inflammatory bowel disease. Different configurations produced different results, highlighting that various mechanisms are implicated in inflammatory bowel disease, while at the same time, results overlapped with known disease characteristics. Importantly, the proposed pipeline also differs from a conventional approach where no network is used, showing the potential for additional discoveries when prior biological knowledge is incorporated into epistasis detection.
An improved ovine reference genome assembly to facilitate in-depth functional annotation of the sheep genome
Authors: Davenport Kimberly M , Bickhart Derek M , Worley Kim , Murali Shwetha C , Salavati Mazdak , Clark Emily L , Cockett Noelle E , Heaton Michael P , Smith Timothy P L , Murdoch Brenda M , Rosen Benjamin D 
Published: February 2022

Abstract

Background
The domestic sheep (Ovis aries) is an important agricultural species raised for meat, wool, and milk across the world. A high-quality reference genome for this species enhances the ability to discover genetic mechanisms influencing biological traits. Furthermore, a high-quality reference genome allows for precise functional annotation of gene regulatory elements. The rapid advances in genome assembly algorithms and emergence of sequencing technologies with increasingly long reads provide the opportunity for an improved de novo assembly of the sheep reference genome.

Findings
Short-read Illumina (55× coverage), long-read Pacific Biosciences (75× coverage), and Hi-C data from this ewe retrieved from public databases were combined with an additional 50× coverage of Oxford Nanopore data and assembled with canu v1.9. The assembled contigs were scaffolded using Hi-C data with Salsa v2.2, gaps filled with PBsuitev15.8.24, and polished with Nanopolish v0.12.5. After duplicate contig removal with PurgeDups v1.0.1, chromosomes were oriented and polished with 2 rounds of a pipeline that consisted of freebayes v1.3.1 to call variants, Merfin to validate them, and BCFtools to generate the consensus fasta. The ARS-UI_Ramb_v2.0 assembly is 2.63 Gb in length and has improved continuity (contig NG50 of 43.18 Mb), with a 19- and 38-fold decrease in the number of scaffolds compared with Oar_rambouillet_v1.0 and Oar_v4.0. ARS-UI_Ramb_v2.0 has greater per-base accuracy and fewer insertions and deletions identified from mapped RNA sequence than previous assemblies.

Conclusions
The ARS-UI_Ramb_v2.0 assembly is a substantial improvement in contiguity that will optimize the functional annotation of the sheep genome and facilitate improved mapping accuracy of genetic variant and expression data for traits in sheep.
A chromosome-level genome assembly and annotation of the desert horned lizard, Phrynosoma platyrhinos, provides insight into chromosomal rearrangements among reptiles
Authors: Koochekian Nazila , Ascanio Alfredo , Farleigh Keaka , Card Daren C , Schield Drew R , Castoe Todd A , Jezkova Tereza 
Published: February 2022

Abstract

Background
The increasing number of chromosome-level genome assemblies has advanced our knowledge and understanding of macroevolutionary processes. Here, we introduce the genome of the desert horned lizard, Phrynosoma platyrhinos, an iguanid lizard occupying extreme desert conditions of the American southwest. We conduct analysis of the chromosomal structure and composition of this species and compare these features across genomes of 12 other reptiles (5 species of lizards, 3 snakes, 3 turtles, and 1 bird).

Findings
The desert horned lizard genome was sequenced using Illumina paired-end reads and assembled and scaffolded using Dovetail Genomics Hi-C and Chicago long-range contact data. The resulting genome assembly has a total length of 1,901.85 Mb, scaffold N50 length of 273.213 Mb, and includes 5,294 scaffolds. The chromosome-level assembly is composed of 6 macrochromosomes and 11 microchromosomes. A total of 20,764 genes were annotated in the assembly. GC content and gene density are higher for microchromosomes than macrochromosomes, while repeat element distributions show the opposite trend. Pathway analyses provide preliminary evidence that microchromosome and macrochromosome gene content are functionally distinct. Synteny analysis indicates that large microchromosome blocks are conserved among closely related species, whereas macrochromosomes show evidence of frequent fusion and fission events among reptiles, even between closely related species.

Conclusions
Our results demonstrate dynamic karyotypic evolution across Reptilia, with frequent inferred splits, fusions, and rearrangements that have resulted in shuffling of chromosomal blocks between macrochromosomes and microchromosomes. Our analyses also provide new evidence for distinct gene content and chromosomal structure between microchromosomes and macrochromosomes within reptiles.
Use of ‘omics for endometrial timing: the cycle moves on
Authors: Aplin John D , Stevens Adam 
Published: February 2022

ABSTRACT
For some years, the prospect of precise and personalized timing of the endometrial cycle for optimal embryo replacement has been held out as a potential solution to low implantation rates. It is envisaged that a receptive state can be defined and reached at a predictable time, and embryo replacement performed in synchrony. In the last century, morphological changes characteristic of the mid secretory phase were defined in precisely timed cycles in women of proven fertility, but when deviations from this standardized schedule occur, their significance for implantation has remained uncertain. ‘Omics technologies have been widely advocated for staging the endometrial cycle and defining a set of biochemical requirements for implantation, but after two decades of research, improvements to pregnancy rates have not followed, and there is a striking lack of agreement regarding the molecular characterization of the receptive state. Some of the rationale underlying these problems is now emerging with the application of higher-level computational and biological methodology. Here, we consider the challenges of defining an endometrial phenotype that can support implantation and continuing pregnancy. Receptivity may be an emergent trait depending on contributions from multiple proteins that have low pathway connectivity. We recommend that authors choose language which rigorously avoids the implication that protocols for molecular staging of the mid secretory phase inherently identify a state of receptivity to the implanting blastocyst.
Pathological and clinical features of multiple cancers and lung adenocarcinoma: a multicentre study
Authors: Bertoglio Pietro , Ventura Luigi , Aprile Vittorio , Cattoni Maria Angela , Nachira Dania , Lococo Filippo , Rodriguez Perez Maria , Guerrera Francesco , Minervini Fabrizio , Gnetti Letizia , Lenzini Alessandra , Franzi Francesca , Querzoli Giulia , Rindi Guido , Bellafiore Salvatore , Femia Federico , Bogina Giuseppe Salvatore , Bacchin Diana , Kestenholz Peter , Ruffini Enrico , Paci Massimiliano , Margaritora Stefano , Imperatori Andrea Selenito , Lucchi Marco , Ampollini Luca , Terzi Alberto Claudio 
Published: February 2022

Abstract

OBJECTIVES
Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes.

METHODS
We retrospectively reviewed data of patients radically operated on for stage I–II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups.

RESULTS
We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008).

CONCLUSIONS
In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern.
Significance of Lorentz forces on Jeffrey nanofluid flows over a convectively heated flat surface featured by multiple velocity slips and dual stretching constraint: a homotopy analysis approach
Authors: Dawar Abdullah , Wakif Abderrahim , Saeed Anwar , Shah Zahir , Muhammad Taseer , Kumam Poom 
Published: February 2022

Abstract
Motivated by the temporal relaxation feature of the Jeffrey model and its practical uses in the rheological modeling of several vital liquids, this study aimed to present a theoretical analysis of three-dimensional MHD Jeffrey nanofluid flows over a dual stretching surface with velocity slip conditions. By adopting the nonhomogeneous nanofluid model along with the passive control approach of nanoparticles, the current flow problem is solved semi-analytically via the homotopy analysis method for convective heating and multiple slip conditions. Dynamically, the magnetic and viscoelastic parameters have a declining effect on the velocity distributions in both directions in the existence and absence of slip effects, while the Deborah number has generally an escalating influence on the flow distributions. On the other hand, the variations of the velocity profiles in both directions are always greater in the presence of slip effect as compared to the nonslip case. Besides, the velocity stretching factor rises the velocity profiles in both directions. Furthermore, this increasing impact is dominant for the velocity distribution along the $y{\rm{-}}$direction as compared to the velocity field along the $x{\rm{-}}$direction. Thermally, the greater Biot number increases the temperature distribution. However, the bigger Schmidt number reduces the concentration distribution.
The Twin Peaks of the Export Intensity Distribution
Authors: Defever Fabrice , Riaño Alejandro 
Published: February 2022

AbstractReceived wisdom suggests that most exporters sell most of their output domestically. We show, however, that the distribution of export intensity varies substantially across countries and is often bimodal, displaying “twin peaks”—that is, large shares of both low- and high-intensity exporters coexisting alongside each other within a country. We reconcile this new stylized fact with an otherwise standard model of trade in which firms face firm-destination-specific revenue shifters that follow a lognormal distribution with sufficiently high dispersion. We structurally estimate the model and show that differences in countries’ size relative to the rest of the world can account for most of the observed cross-country variation in the distribution of export intensity in our data. While policies that incentivize firms to export a high share of their output account for a substantial share of the variation in the dispersion of firm-destination revenue shifters, they cannot fully account for the widespread prevalence of twin peaks around the world.
The predictive value of self-reported allergies for reoperation after index hip arthroscopy
Authors: Srikumar Syian , Feingold Jacob D , Swartwout Erica L , Roberts Sacha A , Ranawat Anil S 
Published: February 2022

ABSTRACT
The purpose of this study is to compare the rate of reoperation after index hip arthroscopy for symptomatic femoroacetabular impingement in patients with, and without, at least one self-reported allergy. Data were collected prospectively in 1468 patients whose records were retrospectively reviewed. After the application of inclusion and exclusion criteria, two cohorts were formed: (i) a study cohort (n = 261) composed of patients with a self-reported allergy and (ii) a control cohort. (n = 666). The allergy cohort had a significantly larger [P &lt; 0.001] reoperation rate (24.1% [63/261]) compared to the control cohort (9.6% [64/66]). Univariate analysis (UVA) and multivariate analysis (MVA) were then performed to better understand the implications of allergy status on the arthroscopic outcome. On UVA the presence of an allergy increased the odds of reoperation after index hip arthroscopy by 2.99 [OR (95% CI): 2.99 (2.04, 4.39); P &lt; 0.001] and for each additional allergy a patient reported, their odds of subsequent surgery increased by 1.27 per allergy [OR (95% CI): 1.27 (1.15, 1.39); P &lt; 0.001]. However, on the MVA, allergy status was not an independent risk factor for reoperation. These findings suggest that allergy status is associated with a higher reoperation rate, however, allergy status alone cannot prognosticate the risk of subsequent surgery. Therefore, allergy status and its association with future surgery after hip arthroscopy should be considered in the context of multiple patient-specific factors that influence the surgical outcome. An understanding of this association enables patient-centered care and will strengthen the physician–patient relationship.
Factors associated with overall survival after recurrence in patients with ER-positive/HER2-negative postmenopausal breast cancer: an ad hoc analysis of the JBCRG-C06 Safari study
Authors: Kawaguchi Hidetoshi , Yamamoto Yutaka , Saji Shigehira , Masuda Norikazu , Nakayama Takahiro , Aogi Kenjiro , Anan Keisei , Ito Yoshinori , Ohtani Shoichiro , Sato Nobuaki , Takano Toshimi , Tokunaga Eriko , Nakamura Seigo , Hasegawa Yoshie , Hattori Masaya , Fujisawa Tomomi , Morita Satoshi , Yamaguchi Miki , Yamashita Hiroko , Yamashita Toshinari , Yotsumoto Daisuke , Toi Masakazu , Ohno Shinji 
Published: February 2022

Abstract

Background
The Safari study (UMIN000015168) was a retrospective, multicenter study in which 1072 consecutive cases of estrogen receptor-positive advanced breast cancer treated using 500 mg fulvestrant were registered. We previously reported the relationship between the patient factors and overall survival after the diagnosis using the same cases and the same factors for the analysis of time to treatment failure in patients with estrogen receptor-positive advanced breast cancer. The current study is an ad hoc analysis that focused on the relationship between the patient factors and overall survival after recurrence by adding factors generally associated with overall survival after recurrence.

Methods
The overall survival after recurrence in patients with estrogen receptor-positive human epidermal growth factor receptor 2 negative recurrent breast cancer was analyzed via univariate and multivariate analyses with a Cox proportional hazards model.

Results
A total of 598 cases were used for the analysis of overall survival after recurrence. Multivariate analysis revealed that favorable overall survival (median, 6.4 years) was significantly correlated with long time from recurrence to fulvestrant use (≥3 years), low nuclear or histological grade (G3 vs. G1), long time to treatment failure of initial palliative endocrine therapy (≥12 months) and long time to initial palliative chemotherapy (≥2 years).

Conclusion
The results of this study indicate that sequential endocrine monotherapy may be a useful treatment option for patients with estrogen receptor-positive/human epidermal growth factor receptor 2 negative recurrent breast cancer who have been successfully treated with initial long-term palliative endocrine therapy.
Novel and Broadly Applicable Microsatellite Markers in Identified Chromosomes of the Philippine Dengue Mosquitoes, Aedes aegypti (Diptera: Culicidae)
Authors: Labiros Dinesse A , Catalig Antonio Mari P , Ymbong Rhoniel Ryan J , Sakuntabhai Anavaj , Lluisma Arturo O , Edillo Frances E 
Published: February 2022

Abstract
Dengue is the leading arboviral infection in the Philippines. Its endemicity in the country is due to the presence of its primary mosquito vector, Aedes aegypti (L.). This species has limited microsatellite markers. This study characterized microsatellite markers screened in silico from intergenic regions of the updated reference genome of Ae. aegypti from Liverpool, U.K. Criteria for good markers are: polymorphic, inherited in a Mendelian codominant manner, no null alleles, selectively neutral, randomly associated, and broadly applicable across different regions. Genotypes were scored using ABI Peak Scanner and were screened for the presence of null alleles. Hardy-Weinberg equilibrium, linkage disequilibrium, and robustness of the markers were determined by GENEPOP using Ae. aegypti samples from selected highland and lowland sites (n = 30 each) in the Philippines and outgroups (Thailand and Vietnam). Mendelian codominant inheritance was examined using F1 offspring of Ae. aegypti family (n = 30 each) derived from samples collected from Cebu city highlands and Maramag, Bukidnon. From the 63 randomly selected markers, nine were polymorphic. Two markers (Aaeg1-3D of chromosome 1 and Aaeg3-4C of chromosome 3) satisfied all criteria, hence, are good broadly useful microsatellite markers. Two other markers (Aaeg2-2E of chromosome 2 and Aaeg3-2A of chromosome 3) met all criteria but deviated from Mendelian codominant inheritance. These new markers of the Philippine Ae. aegypti with their chromosomal locations relative to the other published markers are presented, and will ultimately be useful in a variety of population genetic studies of Ae. aegypti to protect the public health.
Modeling Geographic Uncertainty in Current and Future Habitat for Potential Populations of Ixodes pacificus (Acari: Ixodidae) in Alaska
Authors: Witmer Frank D W , Nawrocki Timm W , Hahn Micah 
Published: February 2022

Abstract
Ixodes pacificus Cooley & Kohls is the primary vector of Lyme disease spirochetes to humans in the western United States. Although not native to Alaska, this tick species has recently been found on domestic animals in the state. Ixodes pacificus has a known native range within the western contiguous United States and southwest Canada; therefore, it is not clear if introduced individuals can successfully survive and reproduce in the high-latitude climate of Alaska. To identify areas of suitable habitat within Alaska for I. pacificus, we used model parameters from two existing sets of ensemble habitat distribution models calibrated in the contiguous United States. To match the model input covariates, we calculated climatic and land cover covariates for the present (1980–2014) and future (2070–2100) climatologies in Alaska. The present-day habitat suitability maps suggest that the climate and land cover in Southeast Alaska and portions of Southcentral Alaska could support the establishment of I. pacificus populations. Future forecasts suggest an increase in suitable habitat with considerable uncertainty for many areas of the state. Repeated introductions of this non-native tick to Alaska increase the likelihood that resident populations could become established.
The Fauna, Diversity, and Bionomics of Culicinae (Diptera: Culicidae) in Hormozgan Province, Southern Iran
Authors: Jaberhashemi Seyed-Aghil , Azari-Hamidian Shahyad , Soltani Aboozar , Azizi Kourosh , Dorzaban Hedayat , Norouzi Mojtaba , Daghighi Elaheh 
Published: February 2022

AbstractHormozgan Province is one of the important foci of malaria in Iran. In addition to malaria pathogens, mosquitoes also transmit the pathogens that cause dirofilariasis and West Nile fever in the province. Also, the threat of emerging aedine-borne viruses that cause infections, such as Chikungunya, dengue, and Zika, is noticeable. There is little information about the fauna and bionomics of Culicinae in the province. The present investigation aimed to study the fauna, diversity, and bionomics of culicines. The study was conducted from September 2016 to April 2017 in four counties of Bandar Abbas, Bandar Khamir, Bashagard, and Jask. In total, 3,236 larvae and 1,901 adults including 16 culicine species were collected. The larvae of Culiseta longiareolata (Macquart) (25.65%), Culex pipiens Linnaeus (16.62%), and Cx. quinquefasciatus Say (16.16%) were most abundant and Cx. hortensis Ficalbi (0.09%) was least abundant. Among adults, Cx. laticinctus Edwards (33.19%), Cx. quinquefasciatus (31.09%), and Cx. pipiens (11.99%) were the most prevalent species and Cs. longiareolata (0.47%), Aedes caballus (Theobald) (0.90%), and Cx. bitaeniorhynchus Giles (0.90%) were the least prevalent species. The pairwise similarities of fauna of the counties and different collecting methods and diversity indices were investigated. More ecological data, especially on host preference, seasonality, and larval habitat characteristics, are needed as a basic knowledge for any intervention measures using integrated vector management.