bluuebunny/crossref_metadata_2025_split huggingface dataset:
What do women want to see in a personalized breast cancer risk report? A qualitative study of Asian women of two countries
Authors: Aldila Fatma , Fiona Ng FJ , Audrienna Jessica , Lynn Lim SJ , Tang Shannon , Tanu Sabrina Gabriel , Fernandez Eric Aria , Agatha Faustina Audrey , Wijaya Marco , Sormin Stevany Tiurma Br , Sani Levana , Irwanto Astrid , Haryono Samuel J. , Li Jingmei , Chan Alexandre , Hartman Mikael 
Published: September 2023

AbstractIntroductionA breast cancer risk assessment tool using Polygenic Risk Score (PRS) of 313 single nucleotide polymorphisms and a risk prediction algorithm from the Gail Model had been established and validated for Asian populations. However, effective ways for delivering personalized risk information have not been fully explored yet. Through facilitated focus group discussions, we assessed the preferences of women from two Asian countries regarding the presentation of risk results, the level of detail provided for explanations, and recommendations for follow-up actions.MethodsWe conducted ten focus group discussions between July and October 2022 with thirty-two Asian women above the age of 25. The discussions aimed to evaluate the views and perceptions of women in Indonesia and Singapore in relation to personalized breast cancer risk assessment. All participants received either a detailed high-risk or low-risk mock report and were assigned to either high-risk result or low-risk result focus group based on the report they had randomly received. All focus group discussion content was then thematically analyzed.ResultsParticipants indicated a preference for a comprehensive report that included follow-up steps and information for managing their breast cancer risk. Additionally, they highlighted the need for visuals without colors that project intimidation as well as a summary on the first page of the report to support interpretations. In the context of the report’s content, participants preferred personalized recommendations for risk reduction, and communication styles could be enhanced through the use of simplified language. Furthermore, we found out that Singaporeans receiving low-risk results were less likely to seek additional physician follow-ups compared to Indonesians, due to their greater breast cancer prevention awareness. Finally, participants found the report useful and would like to see similar reports on other diseases in the future.ConclusionOverall, most patients prefer a test report to strike a balance between content and complexity. The study also highlighted the importance of the psychological impact of patients receiving their test reports, which is greatly influenced by the patients’ degree of understanding and interpretation of the reports. Lastly, as most patients would likely increase their engagement with their physicians upon receiving their test results, future studies could be extended to physicians who are directly involved in the patient care delivery of breast cancer prevention.
Gene protein sequence evolution can predict the rapid divergence of ovariole numbers inDrosophila
Authors: Whittle Carrie A. , Extavour Cassandra G. 
Published: September 2023

AbstractOvaries play key roles in fitness and evolution: they are essential female reproductive structures that develop and house the eggs in sexually reproducing animals. InDrosophila, the mature ovary contains multiple tubular egg-producing structures known as ovarioles. Ovarioles arise from somatic cellular structures in the larval ovary called terminal filaments, formed by terminal filament cells and subsequently enclosed by sheath cells. As in many other insects, ovariole number per female varies extensively inDrosophila. At present however, there is a striking gap of information on genetic mechanisms and evolutionary forces that shape the well-documented rapid interspecies divergence of ovariole numbers. To address this gap, here we studied genes associated withD. melanogasterovariole number or functions based on recent experimental and transcriptional datasets from larval ovaries, including terminal filaments and sheath cells, and assessed their rates and patterns of molecular evolution in five closely related species of themelanogastersubgroup that exhibit species-specific differences in ovariole numbers. From comprehensive analyses of protein sequence evolution (dN/dS), branch-site positive selection, expression specificity (tau) and phylogenetic regressions (PGLS), we report evidence of 42 genes that showed signs of playing roles in the genetic basis of interspecies evolutionary change ofDrosophilaovariole number. These included the signalling genesupd2andIlp5and extracellular matrix genesvkgandCol4a1, whose dN/dS predicted ovariole numbers among species. Together, we propose a model whereby a set of ovariole-involved gene proteins have an enhanced evolvability, including adaptive evolution, facilitating rapid shifts in ovariole number amongDrosophilaspecies.Significance StatementOvaries inDrosophila, like in other insects, contain egg producing structures, known as ovarioles. The number of ovarioles per female varies amongDrosophilaspecies, but little is known about the genes and evolutionary dynamics that may shape interspecies changes in ovariole numbers. Here, useda prioriexperimental and transcriptome data fromD. melanogasterto identify genes involved in ovariole formation and functions, and studied their molecular evolution among its closely related species within themelanogastersubgroup. Using a multi-layered analysis consisting of protein sequence divergence (dN/dS), adaptive evolution, expression breadth, and phylogenetic regressions, we identified 42 genes whose molecular evolution patterns were well linked to ovariole numbers divergence. Further, gene protein sequence divergence was often predictive of species ovariole numbers.
Performance comparison of Accucopy, Sequenza, and ControlFreeC
Authors: Fan Xinping , Huang Yu S. 
Published: September 2023

AbstractCopy number alterations (CNAs) are an important type of genomic aberrations. It plays an important role in tumor pathogenesis and progression of cancer. It is important to detect regions of the cancer genome where copy number changes occur, which may provide clues that drive cancer progression. Deep sequencing technology provides genomic data at single-nucleotide resolution and is considered a better technique for detecting CNAs. There are currently many CNA-detection algorithms developed for whole genome sequencing (WGS) data. However, their detection capabilities have not been systematically investigated. Therefore, we selected three algorithms:Accucopy, Sequenza, andControlFreeC, and applied them to data simulated under different settings. The results indicate that: 1) the correct inference of tumor sample purity is crucial to the inference of CNAs. If the tumor purity is wrongly inferred, the CNA detection will fail. 2) Higher sequencing depth and abundance of CNAs can improve performance. 3) Under the settings tested (sequencing depth at 5X or 30X, purity from 0.1 to 0.9, existence of subclones or not), Accucopy is the best-performing algorithm overall. For coverage=5X samples, ControlFreeC requires tumor purity to be above 50% to perform well. Sequenza can only perform well in high-coverage and more-CNA samples.
Genetic basis and evolution of structural color polymorphism in an Australian songbird
Authors: Sin Simon Yung Wa , Ke Fushi , Chen Guoling , Huang Pei-Yu , Enbody Erik , Karubian Jordan , Webster Michael S. , Edwards Scott V. 
Published: September 2023

AbstractIsland organisms often evolve phenotypes divergent from their mainland counterparts, providing a useful system for studying adaption under differential selection. Some island birds have melanic plumage differing from the color of mainland conspecifics, a trait proposed as an insular adaptation. In the white-winged fairywren (Malurus leucopterus), subspecies on two islands have a black nuptial plumage whereas the subspecies on the Australian mainland has a blue nuptial plumage. The black subspecies have a feather nanostructure that could produce a blue structural color, suggesting a blue ancestor. An earlier study proposed independent evolution of melanism on the islands based on the history of subspecies divergence. However, the genetic basis of melanism and the origin of color differentiation in this group are still unknown. Here, we used whole-genomes to investigate the genetic basis of melanism by comparing the blue and blackM. leucopterussubspecies to identify highly divergent genomic regions. We identified a well-known pigmentation geneASIPand four candidate genes that may contribute to feather nanostructure development. We also detected signatures of a selective sweep in genomic regions containingASIPandSCUBE2not in the black subspecies, as predicted by earlier work, but in the blue subspecies, which possesses many derived SNPs in these regions, suggesting that the mainland subspecies has re-evolved a blue plumage from a black ancestor. This re-evolution was likely driven by a pre-existing female preference. Our findings provide new insight into the evolution of plumage coloration in island versus continental populations, and, importantly, we identify candidate genes that likely play roles in the development and evolution of feather structural coloration.
Whole mitogenome analysis highlights demographic history and shared connections among distal Indigenous groups of Mexico Complete mitogenome sequencing from 60 Mexican Native American groups
Authors: Flores-Huacuja Marlen , Snow Meradeth , Ramos-Madrigal Jazmín , Contreras-Cubas Cecilia , Barajas-Olmos Francisco , González-Oliver Angélica , Mendoza-Caamal Elvia , Cicerón-Arellano Isabel , Centeno-Cruz Federico , Córdova Emilio J. , Baca Paulina , Flores-Martínez Silvia Esperanza , Ortiz-López Rocío , Reynolds Austin W. , Kostic Aleksandar David , Villafan-Bernal José Rafael , Galaviz-Hernández Carlos , García-Zapién Alejandra Guadalupe , Miranda-Ortíz Haydee , Lazalde-Ramos Blanca Patricia , Loeza-Becerra Francisco , Carnevale Alessandra , Rangel-Villalobos Héctor , Sosa-Macías Martha , Rojas-Martinez Augusto , Martínez-Hernández Angélica , García-Ortiz Humberto , Orozco Lorena 
Published: September 2023

AbstractThe study of mitochondrial DNA is a valuable tool to delve into the demographic history of human populations. Particularly in the Americas, five widespread Native American specific mitochondrial lineages have been identified. Here we included the complete mitogenome sequencing of 572 Indigenous individuals belonging to 60 populations spanning the Mexican territory. Our results show a great diversity of matrilineages widespread across the country, revealing shared mtDNA haplogroups in populations from distant regions. We identified all the five main Native American haplogroups clades, including 83 different subhaplogroups, from which nine are novel. The most frequent of the novel haplogroups was A2+64. A phylogenetic inference suggests that A2+64 comes from an ancestral maternal lineage that spread into the Caribbean islands. Additionally, a demographic reconstruction from whole mitogenomes showed an exponential increase in female Ne around 10 Ka ago in all the tested regions. All these findings suggest a genetic persistence through Mexico and possibly the Americas, in agreement with the model of the Mesoamerican-related expansion into the Caribbean and South America.
A dynamic Boolean model of molecular and cellular interactions represents psoriasis development and predicts drug candidates
Authors: Tsirvouli Eirini , Noël Vincent , Flobak Åsmund , Calzone Laurence , Kuiper Martin 
Published: September 2023

AbstractPsoriasis is a chronic skin disease affecting 2-3% of the global population. Psoriasis arises from complex interactions between keratinocytes and immune cells, leading to uncontrolled inflammation, immune hyperactivation and perturbed keratinocyte life cycle. Although the latest generation of drugs have greatly improved psoriasis management, the disease remains incurable, and the substantial variability in treatment response calls for novel approaches to comprehend the intricate mechanisms underlying disease development and to discover potential drug targets. In this study, we present a multiscale population model that captures the dynamics of cell-specific phenotypes in psoriasis, integrating discrete logical formalism and population dynamics simulations. Through simulations and network metrics, we identify potential pairwise interventions as alternative treatment options. Specifically, The model predictions suggest that targeting neutrophil activation in conjunction with either PGE2 production or STAT3 signaling shows promise comparable to IL-17 inhibition, which is currently the most used treatment option for moderate and severe cases of psoriasis. Our findings underscore the significance of considering complex intercellular interactions and intracellular signaling cascades in psoriasis, and highlight the importance of computational approaches in unraveling complex biological systems for drug target identification.Author summaryIn our study, we aimed to uncover the complex mechanisms underlying psoriasis and identify potential treatment options. By utilizing a computational model, we simulated the dynamic interactions between different cell types involved in psoriasis, such as immune cells and keratinocytes. Our model predicts that targeting neutrophil activation, combined with either PGE2 production or STAT3 signaling, may yield comparable effectiveness to the current standard treatment for moderate or severe psoriasis, namely IL-17 inhibition. Our study underscores the importance of computational modeling in unraveling the complexities of disease systems and provides a foundation for identifying new candidate treatment options in psoriasis that should be tested in the lab.
Ghost W chromosomes and unique genome architecture in ghost moths of the family Hepialidae
Authors: Chung Voleníková Anna , Sahara Ken , Štundlová Jana , Dalíková Martina , Koutecký Petr , Grof-Tisza Patrick , Simonsen Thomas J. , Žurovec Michal , Provazníková Irena , Walters James R. , Marec František , Nguyen Petr 
Published: September 2023

ABSTRACTThe classical model of sex chromosome evolution has been recently challenged in moths and butterflies (Lepidoptera). According to the current hypothesis, the adoption of a supernumerary chromosome may have driven the transition from the Z0 to the WZ sex chromosome system in females. However, the evolutionary history of the W chromosome remains enigmatic, especially in the early-diverging lepidopteran lineages. In ghost moths of the family Hepialidae, one of the most basal lepidopteran clades, there is conflicting evidence regarding their sex chromosomes. In this study, we aimed to clarify the status of the hepialid W chromosome. Using cytogenetics and genomics, we investigated the karyotype, sex chromosomes, genome size and repeatome of multiple ghost moth species and reconstructed basic phylogenetic relationships in the group. Our data show that Hepialidae have unusually large genomes (reaching up to 1C = 3 Gb) and are the oldest known lepidopteran clade with a W chromosome. However, the W does not form a typical heterochromatin body in polyploid nuclei, known as sex chromatin, previously employed to detect the presence of W chromosomes across Lepidoptera. Moreover, in some species, the W does not exhibit distinct repeat content and can escape detection via methods that rely on W-specific sequences. Analysis of the Z chromosome confirmed highly conserved gene content, arguing for a possible origin of the hepialid W chromosome from a B chromosome. We hypothesize that the mechanism underlying the formation of sex chromatin could be used in future research to study the origin of the W chromosome.
The mediating role of trust in physicians on the association between multidimensional health literacy and medication adherence in hemodialysis: A cross-sectional study
Authors: Inanaga Ryohei , Toida Tatsunori , Aita Tetsuro , Kanakubo Yusuke , Ukai Mamiko , Toishi Takumi , Kawaji Atsuro , Matsunami Masatoshi , Okada Tadao , Munakata Yu , Suzuki Tomo , Kurita Noriaki 
Published: September 2023

AbstractRationale & ObjectiveBasic health literacy (HL) and trust in physicians can influence medication adherence (MA) in dialysis patients. However, how high-order HL is associated with MA, and how trust in physicians mediates this association remain unclear. We assessed the interrelationships between HL, trust in physicians, and MA, and investigated the mediating role of trust in physicians in the relationship between HL and MA.Study DesignMulticenter cross-sectional study.Setting & ParticipantsJapanese adults receiving outpatient hemodialysis at six dialysis centers.ExposuresMultidimensional HL was measured using the 14-item Functional, Communicative, and Critical Health Literacy Scale. Trust in physicians was measured using the five-item Wake Forest Physician Trust Scale.OutcomeMA was measured using the 12-item Adherence Starts Knowledge (ASK-12) scale.Analytical ApproachA series of general linear models was created to analyze the associations between HL and ASK-12 scores with and without trust in physicians. Mediation analysis was performed to determine whether trust in physicians mediated this association.ResultsIn total, 455 patients were analyzed. Higher functional and communicative HL were associated with lower barriers to MA (per 1-point increase: -1.90 (95% confidence interval (CI): -2.67, -1.13) and -2.11 (95% CI: -3.35, -0.87), respectively), whereas higher critical HL was associated with higher barriers (per 1-point increase: 1.67 (95% CI: 0.43, 2.90)). After controlling for trust in physicians, the magnitude of the association between HLs and MA decreased. Trust in physicians partially mediated the association between functional or communicative HL and MA (especially “beliefs”) and completely mediated the association between critical HL and MA (especially “behaviors”).LimitationPossible reverse causation.ConclusionsIn addition to functional HL, communicative and critical HL were associated with MA, and their associations were mediated by trust in physicians. To effectively improve MA, individualized strategies for each HL and favorable physician–patient interactions are important.
Chronotype is Associated with Sleep Quality in Older Adults
Authors: Sauers Scott C. , Toedebusch Cristina D. , Richardson Rachel , Spira Adam P. , Morris John C. , Holtzman David M. , Lucey Brendan P. 
Published: September 2023

ABSTRACTIntroductionDisrupted sleep is common in individuals with Alzheimer’s disease (AD) and may be a marker for AD risk. The timing of sleep or chronotype affects sleep-wake activity and is also associated with AD, but little is known about links between sleep and chronotype in older adults. In this study, we tested if different measures of sleep and chronotype are associated among older adults even after adjusting for multiple potentially confounding variables.MethodsParticipants (N=243) with a mean age of 74 underwent standardized cognitive assessments, measurement of CSF AD biomarkers, and sleep monitoring via single-channel EEG, actigraphy, and self-reported sleep logs. Chronotype was defined as the midpoint of sleep measured by actigraphy.ResultsLater mid-point of sleep (i.e., late chronotype) was associated with African American race and greater night-to-night variability in the sleep mid-point. After controlling for age, race, sex, cognitive status, AD biomarkers, and sleep disorders, a later mid-point of sleep was associated with longer rapid eye movement (REM) onset latency, decreased REM sleep time, lower sleep efficiency, increased sleep onset latency, and more awakenings at night. Late chronotype was also associated with increased <2 Hz non-REM slow-wave activity.ConclusionsTo identify individuals at risk for cognitive impairment before symptoms onset, non-invasivein vivomarkers of brain function, such as sleep, are needed to track both future risk of cognitive impairment and response to interventions. Chronotype is a potential modifiable AD risk factor and should also be taken into account when using sleep as a marker for AD risk.
Deep learning classification ofex vivohuman colon tissues using spectroscopic OCT
Authors: Kendall Wesley Y. , Tian Qinyi , Zhao Shi , Mirminachi Seyedbabak , Joseph Abel , Dufault Darin , Shi Chanjuan , Roper Jatin , Wax Adam 
Published: September 2023

AbstractScreening programs for colorectal cancer (CRC) have had a profound impact on the morbidity and mortality of this disease by detecting and removing early cancers and precancerous adenomas with colonoscopy. However, CRC continues to be the third leading cause of cancer-related mortality in both men and woman, partly because of limitations in colonoscopy-based screening. Thus, novel strategies to improve the efficiency and effectiveness of screening colonoscopy are urgently needed. Here, we propose to address this need using an optical biopsy technique based on spectroscopic optical coherence tomography (OCT). The depth resolved images obtained with OCT are analyzed as a function of wavelength to measure optical tissue properties. The optical properties can be used as input to machine learning algorithms as a means to classify adenomatous tissue in the colon. In this study, biopsied tissue samples from the colonic epithelium are analyzedex vivousing spectroscopic OCT and tissue classifications are generated using a novel deep learning architecture, informed by machine learning methods including LSTM and KNN. The overall classification accuracy obtained was 88.9%, 76.0% and 97.9% in discriminating tissue type for these methods. Further, we apply an approach using false coloring ofen faceOCT images based on SOCT parameters and deep learning predictions to enable visual identification of tissue type. This study advances the spectroscopic OCT towards clinical utility for analyzing colonic epithelium for signs of adenoma.
Differentiation and Expansion of Tumor-Infiltrating T Cell Clonotypes Occurs in the Spleen Following Immune Checkpoint Blockade
Authors: Morgan Duncan M. , Horton Brendan L. , Zagorulya Maria , Love J. Christopher , Spranger Stefani 
Published: September 2023

AbstractImmune checkpoint blockade (ICB) enhances tumor-reactive T cell responses against cancer, leading to long-term tumor control and survival in a fraction of patients. Given the increasingly recognized complexity of T cell differentiation that occurs in response to chronic antigen stimulation, it remains unclear precisely which T cell differentiation states are critical for the response to ICB, as well as the anatomic sites at which ICB-mediated reinvigoration of these T cells occurs. We used paired single-cell RNA and T cell receptor (TCR) sequencing to profile endogenous, tumor-reactive CD8+T cells isolated from tumors, tumor-draining lymph nodes, and spleens of mice treated with ICB. We identified an intermediate-exhausted population of T cells in the spleen which underwent the greatest expansion in response to ICB and gave rise to the majority of tumor-infiltrating clonotypes. Increasing concentrations of antigen in the spleen perturbed the differentiation of this phenotype towards a divergent exhausted_KLR state, resulting in reduced numbers of tumor-infiltrating T cells and blunted ICB efficacy. Likewise, an analogous population of exhausted_KLR CD8+T cells in matched human tumor and blood samples and exhibited diminished tumor-trafficking ability. These data demonstrate that the spleen is a critical anatomic site for coordinating the differentiation of tumor-infiltrating clonotypes and their expansion in response to ICB.