bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parenting in Plastic Surgery Residency
Authors: Wallace Chelsea C. , Edmunds R. Wesley , Bourne Debra , Wong Lesley 
Published: April 2022

Background:
In 1994, Mackinnon advocated that plastic surgery residents should have accessible child care to promote a productive return to work. Decades later, lack of adequate child care remains a dilemma for trainees. The authors’ survey aims to evaluate childrearing during plastic surgery training.

Methods:
An anonymous, voluntary survey was sent to plastic surgery residents. It evaluated demographics, childcare accommodations, and attitudes/issues surrounding childrearing during residency.

Results:
There were 32 respondents: 66 percent women and 34 percent men. Seventy-five percent were married, and 38 percent were parents. Seventy-five percent of male parents compared to 12 percent of female parents reported that their spouse was the primary childcare source. One hundred percent of respondents with children reported that child care creates a financial burden. Three percent of respondents felt their institution provided services to arrange adequate child care. Sixty-three percent of residents felt their program did not allow flexibility to accommodate childcare needs. Female residents missed work twice as often and were twice as likely to require a co-resident to cover clinical duties because of childcare difficulties when compared to male residents (p = 0.296 and p = 0.145). Sixty-seven percent of women agreed with the statement, “If you had to pick a residency program today, the availability of on-site child care would influence your decision,” compared to only 9 percent of men (p = 0.002).

Conclusions:
Training institutions are not meeting the childcare needs of plastic surgery trainees. If the specialty wishes to recruit and retain the top applicants, it must improve the childcare accommodations for residents. All institutions with plastic surgery residency programs should provide affordable, accessible child care that accommodates the 24-hour natures of both patient care and parenthood.
The background and legacy of Lewontin's apportionment of human genetic diversity
Authors: Novembre John 
Published: April 2022

Lewontin's 1972 article ‘The apportionment of human diversity’ described a key feature of human genetic diversity that would have profound impacts on conversations regarding genetics and race: the typical genetic locus varies much less between classical human race groupings than one might infer from inspecting the features historically used to define those races, like skin pigmentation. From this, Lewontin concluded: ‘Human racial classification … is now seen to be of virtually no genetic or taxonomic significance’ (p. 397). Here, 50 years after the paper's publication, the goal is to understand the origins and legacy of the paper. Aided by insights from published papers and interviews with several of Lewontin's contemporaries, I review the 1972 paper, asking about the intellectual background that led to the publication of the paper, the development of its impact, the critiques of the work and the work's application and limitations today. The hope is that by gaining a clearer understanding of the origin and reasoning of the paper, we might dispel various confusions about the result and sharpen an understanding of the enduring value and insight the result provides.This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.
Human genetic admixture through the lens of population genomics
Authors: Gopalan Shyamalika , Smith Samuel Pattillo , Korunes Katharine , Hamid Iman , Ramachandran Sohini , Goldberg Amy 
Published: April 2022

Over the past 50 years, geneticists have made great strides in understanding how our species' evolutionary history gave rise to current patterns of human genetic diversity classically summarized by Lewontin in his 1972 paper, ‘The Apportionment of Human Diversity’. One evolutionary process that requires special attention in both population genetics and statistical genetics is admixture: gene flow between two or more previously separated source populations to form a new admixed population. The admixture process introduces ancestry-based structure into patterns of genetic variation within and between populations, which in turn influences the inference of demographic histories, identification of genetic targets of selection and prediction of complex traits. In this review, we outline some challenges for admixture population genetics, including limitations of applying methods designed for populations without recent admixture to the study of admixed populations. We highlight recent studies and methodological advances that aim to overcome such challenges, leveraging genomic signatures of admixture that occurred in the past tens of generations to gain insights into human history, natural selection and complex trait architecture.
This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.
Mathematical constraints onFST: multiallelic markers in arbitrarily many populations
Authors: Alcala Nicolas , Rosenberg Noah A. 
Published: April 2022

Interpretations of values of theFSTmeasure of genetic differentiation rely on an understanding of its mathematical constraints. Previously, it has been shown thatFSTvalues computed from a biallelic locus in a set of multiple populations andFSTvalues computed from a multiallelic locus in a pair of populations are mathematically constrained as a function of the frequency of the allele that is most frequent across populations. We generalize from these cases to report here the mathematical constraint onFSTgiven the frequencyMof the most frequent allele at amultialleliclocus in a set ofmultiplepopulations. Using coalescent simulations of an island model of migration with an infinitely-many-alleles mutation model, we argue that the joint distribution ofFSTandMhelps in disentangling the separate influences of mutation and migration onFST. Finally, we show that our results explain a puzzling pattern of microsatellite differentiation: the lowerFSTin an interspecific comparison between humans and chimpanzees than in the comparison of chimpanzee populations. We discuss the implications of our results for the use ofFST.This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.
Forensic genetics through the lens of Lewontin: population structure, ancestry and race
Authors: Jobling Mark A. 
Published: April 2022

In his famous 1972 paper, Richard Lewontin used ‘classical’ protein-based markers to show that greater than 85% of human genetic diversity was contained within, rather than between, populations. At that time, these same markers also formed the basis of forensic technology aiming to identify individuals. This review describes the evolution of forensic genetic methods into DNA profiling, and how the field has accounted for the apportionment of genetic diversity in considering the weight of forensic evidence. When investigative databases fail to provide a match to a crime-scene profile, specific markers can be used to seek intelligence about a suspect: these include inferences on population of origin (biogeographic ancestry) and externally visible characteristics, chiefly pigmentation of skin, hair and eyes. In this endeavour, ancestry and phenotypic variation are closely entangled. The markers used show patterns of inter- and intrapopulation diversity that are very atypical compared to the genome as a whole, and reinforce an apparent link between ancestry and racial divergence that is not systematically present otherwise. Despite the legacy of Lewontin's result, therefore, in a major area in which genetics coincides with issues of public interest, methods tend to exaggerate human differences and could thereby contribute to the reification of biological race.
This article is part of the theme issue ‘Celebrating 50 years since Lewontin's apportionment of human diversity’.
Tumor necrosis factor α modulates excitatory and inhibitory neurotransmission in a concentration-dependent manner
Authors: Kleidonas Dimitrios , Kirsch Matthias , Andrieux Geoffroy , Pfeifer Dietmar , Boerries Melanie , Vlachos Andreas 
Published: April 2022

ABSTRACTMicroglia, the brain’s resident immune cells, have been implicated in important brain functions, such as synaptic transmission and plasticity. The pro-inflammatory cytokine tumor necrosis factor α (TNFα), which is produced and secreted by microglia, has been linked to the expression of synaptic plasticity in neurons. However, the role of TNFα-mediated activation of microglia has not been addressed in this context. Here, we assessed concentration-dependent effects of TNFα on the balance of synaptic excitation/inhibition and the activation of microglia using mouse organotypic entorhino-hippocampal tissue cultures. We found that low concentrations of TNFα enhanced excitatory synaptic strength while not affecting inhibitory neurotransmission. At higher concentrations, TNFα increased inhibitory neurotransmission without affecting excitatory synaptic strength. Both low and high concentrations of TNFα induced the synaptic accumulation of GluA1-containing AMPA receptors, suggesting that a high concentration of TNFα exerts a homeostatic effect on excitatory neurotransmission that prevents synaptic strengthening. Consistent with this, high, but not low, concentrations of TNFα activated microglia. Moreover, high concentrations of TNFα enhanced excitatory neurotransmission in microglia-depleted tissue cultures. These findings extend our knowledge on the role of TNFα on synaptic plasticity by demonstrating concentration-dependent effects on excitatory and inhibitory neurotransmission. They reveal a TNFα-mediated negative feedback mechanism on excitatory neurotransmission that is dependent on the activation of microglia, thereby emphasizing their role as gatekeepers of TNFα-mediated plasticity and homeostasis.
BANKSY: A Spatial Omics Algorithm that Unifies Cell Type Clustering and Tissue Domain Segmentation
Authors: Singhal Vipul , Chou Nigel , Lee Joseph , Liu Jinyue , Chock Wan Kee , Lin Li , Chang Yun-Ching , Teo Erica , Lee Hwee Kuan , Chen Kok Hao , Prabhakar Shyam 
Published: April 2022

AbstractEach cell type in a solid tissue has a characteristic transcriptome and spatial arrangement, both of which are observable using modern spatial omics assays. However, the common practice is still to ignore spatial information when clustering cells to identify cell types. In fact, spatial location is typically considered only when solving the related, but distinct, problem of demarcating tissue domains (which could include multiple cell types). We present BANKSY, an algorithm that unifies cell type clustering and domain segmentation by constructing a product space of cell and neighbourhood transcriptomes, representing cell state and microenvironment, respectively. BANKSY’s spatial kernel-based feature augmentation strategy improves per-formance and scalability on both tasks when tested on FISH-based and sequencing-based spatial omics data. Uniquely, BANKSY identified hitherto undetected niche-dependent cell states in two mouse brain regions. Lastly, we show that quality control of spatial omics data can be formulated as a domain identification problem and solved using BANKSY. BANKSY represents a biologically motivated, scalable, and versatile framework for analyzing spatial omics data.
Dcifer: an IBD-based method to calculate genetic distance between polyclonal infections
Authors: Gerlovina Inna , Gerlovin Boris , Rodríguez-Barraquer Isabel , Greenhouse Bryan 
Published: April 2022

AbstractAn essential step toward reconstructing pathogen transmission and answering epidemiologically relevant questions from genomic data is obtaining pairwise genetic distance between infections. For recombining organisms such as malaria parasites, relatedness measures quantifying recent shared ancestry would provide a meaningful distance, suggesting methods based on identity by descent (IBD). While the concept of relatedness and consequently an IBD approach is fairly straightforward for individual parasites, the distance between polyclonal infections, which are prevalent in malaria, presents specific challenges and awaits a general solution that could be applied to infections of any clonality and accommodate multiallelic (e.g. microsatellite or microhaplotype) and biallelic (SNP) data. Filling this methodological gap, we present Dcifer (Distance for complex infections: fast estimation of relatedness), a method for calculating genetic distance between polyclonal infections, which is designed for unphased data, explicitly accounts for population allele frequencies and complexity of infection, and provides reliable inference. Dcifer’s IBD-based framework allows us to define model parameters that represent interhost relatedness and to propose corresponding estimators with attractive statistical properties. By using combinatorics to account for unobserved phased haplotypes, Dcifer is able to quickly process large datasets and estimate pairwise relatedness along with measures of uncertainty. We show that Dcifer delivers accurate and interpretable results and detects related infections with statistical power that is 2-4 times greater than that of approaches based on identity by state. Applications to real data indicate that relatedness structure aligns with geographic locations. Dcifer is implemented in a comprehensive publicly available software package.
The shape of aroma: measuring and modeling citrus oil gland distribution
Authors: Amézquita Erik J. , Quigley Michelle Y. , Ophelders Tim , Seymour Danelle , Munch Elizabeth , Chitwood Daniel H. 
Published: April 2022

SummaryCitrus come in diverse sizes and shapes, and play a key role in world culture and economy. Citrus oil glands in particular contain essential oils which include plant secondary metabolites associated with flavor and aroma. Capturing and analyzing nuanced information behind the citrus fruit shape and its oil gland distribution provides a morphology-driven path to further our insight into phenotype-genotype interactions.We investigated the shape of citrus fruit of 51 accessions based on 3D X-ray CT scan reconstructions. Accessions include all three ancestral citrus species, accessions from related genera, and several interspecific hybrids. We digitally separate and compare the size of fruit endocarp, mesocarp, exocarp, and oil gland tissue. Based on the centers of the oil glands, overall fruit shape is approximated with an ellipsoid. Possible oil gland distributions on this ellipsoid surface are explored using directional statistics.There is a strong allometry along fruit tissues; that is, we observe a strong linear relationship between the volume of any pair of major tissues. This suggests that the relative growth of fruit tissues with respect to each other follows a power law. We also observe that on average, glands distance themselves from their nearest neighbor following a square root relationship, which suggests normal diffusion dynamics at play.The observed allometry and square root models point to the existence of biophysical developmental constraints that govern novel relationships between fruit dimensions from both evolutionary and breeding perspectives. Understanding these biophysical interactions prompt an exciting research path on fruit development and breeding.Societal Impact StatementCitrus are intrinsically connected to human health and culture, including preventing human diseases like scurvy, and inspiring sacred rituals. Citrus fruits come in a stunning number of different sizes and shapes, ranging from small clementines to oversized pummelos, and fruits display a vast diversity of flavors and aromas. These qualities are key in both traditional and modern medicine and the production of cleaning and perfume products. By quantifying and modeling overall fruit shape and oil gland distribution, we can gain further insight into citrus development and the impacts of domestication and improvement on multiple characteristics of the fruit.
First clinical validation of whole genome screening on standard trophectoderm biopsies of preimplantation embryos
Authors: Xia Yuntao , Chertman Willy , Chandramohan Dhruva , Katz Maria , Bechor Elan , Podgursky Ben , Hoxie Michael , Zhang Qinnan , Kang Jessica , Blue Edwina , Chen Justin , Schleede Justin , Slotnick Nathan , Du Xiaoli , Kort Jonathan , Boostanfar Robert , Urcia Eric , Behr Barry , Siddiqui Noor 
Published: April 2022

AbstractWhole Genome Sequencing (WGS) is used in healthcare and in the clinic, with the notable exception of preimplantation genetic testing (PGT). In PGT, only a few cells are available for sequencing, requiring DNA amplification which reduces data quality, sequence fidelity and sharply limits subsequent clinical impact. Here we demonstrate the first clinical validation of WGS on embryo biopsies using our lab development protocol, opening the door to broad use of WGS in fertility. We find that amplified DNA with comparable sensitivity and specificity to genomic DNA when performing whole genome sequencing assays. DNA amplification on cell lines and donated human embryos had an amplification success rate of >99.9% and 98.2% respectively and accuracy on both was >99.9% on aneuploidy status. GIAB samples (Genome in the Bottle reference NA12878) showed that our amplified DNA was broadly comparable to genomic DNA (99.99% accuracy, 99.99% specificity, 98.0% sensitivity and 98.1% precision). Using our assay, we were able to call variants, detect mitochondrial heteroplasmy, perform high precision screening without access to parental genomes, detect compound heterozygous variants, and score microdups/dels and uniparental disomies (to reduce risk of diseases such as DiGeorge syndrome and Prader-Willi syndrome). Our clinical study suggests that the full spectrum of traditional clinical genome bioinformatics, so far reserved to large samples, can now be performed on embryos before implantation.
Scan-Centric, Frequency-Based Method for Characterizing Peaks from Direct Injection Fourier transform Mass Spectrometry Experiments
Authors: Flight Robert M , Mitchell Joshua M , Moseley Hunter NB 
Published: April 2022

AbstractWe introduce a novel, scan-centric method for characterizing peaks from direct injection multi-scan Fourier transform mass spectra of complex samples that utilizes frequency values derived directly from the spacing of raw m/z points in spectral scans. Our peak characterization method utilizes intensity independent noise removal and normalization of scan-level data to provide a much better fit of relative intensity to natural abundance probabilities for low abundance isotopologues that are not present in all of the acquired scans. Moreover, our method calculates both peak- and scan-specific statistics incorporated within a series of quality control steps that are designed to robustly derive peak centers, intensities and intensity ratios with their scan-level variances. These cross-scan characterized peaks are suitable for use in our previously published peak assignment methodology, Small Molecule Isotope Resolved Formula Enumeration (SMIRFE).
Compendium-wide analysis of P. aeruginosa core and accessory genes reveal more nuanced transcriptional patterns
Authors: Lee Alexandra J. , Doing Georgia , Neff Samuel L. , Reiter Taylor , Hogan Deborah A. , Greene Casey S. 
Published: April 2022

AbstractStrains of Pseudomonas aeruginosa, an opportunistic pathogen that causes difficult to treat infections, have significant genomic heterogeneity including the presence of diverse accessory genes that are only present in some strains or clades. Both core genes, which are conserved across strains, and accessory genes have been associated with traits such as biofilm formation and virulence. Much of what we know about core and accessory gene content comes from genome analyses. Here, we use a newly assembled transcriptome compendium to analyze the transcriptional patterns of core and accessory gene expression in PAO1 and PA14 strains across thousands of samples from hundreds of distinct experiments. We found that a subset of core genes were stable, having consistent correlated expression patterns across samples regardless of strain background, with a focus on strains PAO1 and PA14. These stable core genes had fewer co-expressed neighbors that were accessory genes.SignificancePseudomonas aeruginosa is a ubiquitous pathogen. There is a lot of diversity amongst P. aeruginosa strains, some which are clinically relevant. Understanding how these different strain-level traits manifest is important for identifying targets that regulate different traits of interest. With the availability of a PAO1-mapped and PA14-mapped RNA-seq compendium, which contain hundreds of strains, it is now possible to examine the effect of different strains on expression, which can mediate different traits. In this study we developed an approach to compare expression profiles across different P. aeruginosa gene groups – core and accessory genes. This approach revealed a subset of core genes with different transcriptional patterns across strains, which could contribute to trait differences.
A new chemotype of chemically tractable nonsteroidal estrogens based on a thieno[2,3-d]pyrimidine core
Authors: Sammeta Vamshikrishna Reddy , Norris John D. , Artham Sandeep , Torrice Chad D. , Byemerwa Jovita , Joiner Carstyn , Fanning Sean W. , McDonnell Donald P. , Willson Timothy M. 
Published: April 2022

ABSTRACTDespite continued interest in development of nonsteroidal estrogens and antiestrogens, there are only a few chemotypes of estrogen receptor ligands. Using targeted screening in a ligand sensing assay we identified a phenolic thieno[2,3-d]pyrimidine with affinity for estrogen receptor α. An efficient three-step synthesis of the heterocyclic core and structure-guided optimization of the substituents resulted in a series of potent nonsteroidal estrogens. The chemical tractability of the thieno[2,3-d]pyrimidine chemotype will support the design of new estrogen receptor ligands as therapeutic hormones and antihormones.GRAPHICAL ABSTRACT
Habitat preference influences response to changing agricultural landscapes in two long-horned bees
Authors: Hirayama Gaku S. , Ushimaru Atushi 
Published: April 2022

AbstractAgricultural intensification and urban development have drastically influenced pollinators living in semi-natural grasslands. Pollinators are likely to have different responses to these land-use changes; some decline rapidly while others maintain or increase their populations. We predicted differences in interspecific response to land-use changes are partly attributed to differences in habitat preference. We examined the distribution and flower use patterns of two closely relatedEuceraspecies with different habitat preferences. Study sites were meadows surrounding traditional, intensified, and urbanised agricultural lands in the Osaka-Kobe metropolitan area, Japan. Forest-associatedEucera nipponensiswere significantly fewer in consolidated and urbanised meadows than traditional meadows, whereas open land-associatedE. spurcatipesexhibited the opposite. A significant negative relationship between their abundances was also found. Both species foraged on legume flowers most frequently (83.5%), but floral use pattern was significantly different in traditional and consolidated meadows. Bee species preferring stable habitats were vulnerable to land consolidation and urbanisation, while species associated with disturbed habitats maintained or increased population size in meadows with the land-use changes. Thus, recent land uses may have different impacts on species with different habitat preferences.