bluuebunny/crossref_metadata_2025_split huggingface dataset:
The complete diploid reference genome of RPE-1 identifies human phased epigenetic landscapes
Authors: Volpe Emilia , Corda Luca , Di Tommaso Elena , Pelliccia Franca , Ottalevi Riccardo , Licastro Danilo , Guarracino Andrea , Capulli Mattia , Formenti Giulio , Tassone Evelyne , Giunta Simona 
Published: November 2023

SUMMARYComparative analysis of recent human genome assemblies highlights profound sequence divergence that peaks within polymorphic loci such as centromeres. This raises the question about the adequacy of relying on human reference genomes to accurately analyze sequencing data derived from experimental cell lines. Here, we generated the complete diploid genome assembly for the human retinal epithelial cells (RPE-1), a widely used non-cancer laboratory cell line with a stable karyotype, to use as matched reference for multi-omics sequencing data analysis. Our RPE1v1.0 assembly presents completely phased haplotypes and chromosome-level scaffolds that span centromeres with ultra-high base accuracy (>QV60). We mapped the haplotype-specific genomic variation specific to this cell line including t(Xq;10q), a stable 73.18 Mb duplication of chromosome 10 translocated onto the microdeleted chromosome X telomere t(Xq;10q). Polymorphisms between haplotypes of the same genome reveals genetic and epigenetic variation for all chromosomes, especially at centromeres. The RPE-1 assembly as matched reference genome improves mapping quality of multi-omics reads originating from RPE-1 cells with drastic reduction in alignments mismatches compared to using the most complete human reference to date (CHM13). Leveraging the accuracy achieved using a matched reference, we were able to identify the kinetochore sites at base pair resolution and show unprecedented variation between haplotypes. This work showcases the use of matched reference genomes for multi-omics analyses and serves as the foundation for a call to comprehensively assemble experimentally relevant cell lines for widespread application.HighlightsWe generated the complete phased genome assembly of one of the most widely used non-cancer cell lines (RPE-1) with a stable diploid karyotypeWe used this genome as a matched reference to analyze sequencing data from RPE-1Mapping to the RPE1v1.0 genome improves alignment quality, faithful assignment of reads to each haplotype, and epigenome peak calling accuracy uncovering inter-haplotype variationUse of the matched reference genome enables epigenetic precision in identifying for the first time the kinetochore site at base pair resolution for each haplotypeThe RPE-1 genome represents a new telomere-to-telomere (T2T) human diploid reference for the scientific community that will advance genetic and epigenetic research across fields using this cell line
Predictability of ecological and evolutionary dynamics in a changing world
Authors: Bozzuto Claudio , Ives Anthony R. 
Published: November 2023

AbstractEcological and evolutionary predictions are being increasingly employed to inform decision-makers confronted with intensifying pressures menacing life on Earth. For these efforts to effectively guide conservation actions, knowing the limit of predictability is pivotal. In this study, we provide realistic expectations about the enterprise of predicting changes in ecological and evolutionary observations through time. We begin with an intuitive explanation of predictability (that is, the extent to which predictions are possible) employing an easy-to-use metric, predictive powerPP(t). To illustrate the challenge of forecasting, we then show that among insects, birds, fishes, and mammals (i) 50% of the populations are predictable at most one year in advance, and (ii) the median one-year-ahead predictive power corresponds to a sobering predictionR2of approximately 20%. Nonetheless, predictability is not an immutable property of ecological systems. For example, different harvesting strategies can impact the predictability of exploited populations to varying degrees. Moreover, considering multivariate time series, incorporating explanatory variables or accounting for time trends (environmental forcing) can enhance predictability. To effectively address the urgent challenge of biodiversity loss, researchers and practitioners must be aware of the predictive information within the available data and explore efficient ways to leverage this information for environmental stewardship.
Going with the flow: evidence for phenotypic variation in cooperative plasticity during predator inspection in Trinidadian guppies (Poecilia reticulata)
Authors: Dimitriadou Sylvia , Padget Rebecca F.B. , Jack Tegen , Darden Safi K. 
Published: November 2023

AbstractAssortative interactions can be key for the evolution and maintenance of cooperation. The propensity for cooperative behaviour to be met with equal cooperativeness can arise from partner conditional responses or fixed cooperative traits, but also a combination of both; something that has yet to be investigated outside of humans. We explored whether individuals differing in trait cooperativeness also differed in plasticity of their conditional response to partner cooperativeness. To identify when selection may favour high or low plasticity as a function of cooperativeness, we also developed an evolutionary simulation model, where individuals’ probability of cooperating was modelled alongside their plasticity. Our empirical results suggest that guppies (Poecilia reticulata) bred to make high cooperative investments in the context of predator inspection exhibit greater conditional response plasticity than guppies bred to make lower investments. Our agent-based model found that more cooperative individuals will show greater plasticity in their propensity to cooperate, compared to less cooperative individuals, except when there are no consequences of nobody cooperating. Combined, our findings show that more cooperative individuals might benefit from a greater capacity to adjust behaviour than less cooperative individuals – this could have implications for assortment by cooperative behaviour.
Benchmarking and integrating human B-cell receptor genomic and antibody proteomic profiling
Authors: Lê Quý Khang , Chernigovskaya Maria , Stensland Maria , Singh Sachin , Leem Jinwoo , Revale Santiago , Galson Jacob D. , Nyman Tuula A. , Snapkow Igor , Greiff Victor 
Published: November 2023

AbstractImmunoglobulins (Ig), which exist either as B-cell receptors (BCR) on the surface of B cells or as antibodies when secreted, play a key role in the recognition and response to antigenic threats. The capability to jointly characterize the BCR and antibody repertoire is crucial in understanding human adaptive immunity. From peripheral blood, bulk BCR sequencing (bulkBCR-seq) currently provides the highest sampling depth, single-cell BCR sequencing (scBCR-seq) allows for paired chain characterization, and antibody peptide sequencing by tandem mass spectrometry (Ab-seq) provides information on the composition of secreted antibodies in the serum. Although still rare, studies combining these three technologies would comprehensively capture the humoral immune response. Yet, it has not been benchmarked to what extent the datasets generated by these three technologies overlap and complement each other. To address this question, we isolated peripheral blood B cells from healthy donors and sequenced BCRs at bulk and single-cell level, in addition to utilizing publicly available sequencing data. Integrated analysis was performed on these datasets, resolved by replicates and across individuals. Simultaneously, serum antibodies were isolated, digested with multiple proteases, and analyzed with Ab-seq. Systems immunology analysis showed high concordance in repertoire features between bulk and scBCR-seq within individuals, especially when replicates were utilized. In addition, Ab-seq identified clonotype-specific peptides using both bulk and scBCR-seq library references, demonstrating the feasibility of combining scBCR-seq and Ab-seq for reconstructing paired-chain Ig sequences from the serum antibody repertoire. Collectively, our work serves as a proof-of-principle for combining bulk sequencing, single-cell sequencing, and mass spectrometry as complementary methods towards capturing humoral immunity in its entirety.
Inspiring Diverse Researchers in Virginia: Cultivating Research Excellence Through a Career Building Program
Authors: Mata-McMurry Lina V. , Phillips Jennifer V. , Burks Sandra G. , Greene Adam , Syed Sana , Johnston Karen C. 
Published: November 2023

AbstractHistorically underrepresented groups in biomedical research have continued to experience low representation despite shifting demographics. Diversity fosters inclusive, higher quality, and innovative team science. One avenue for diversifying research teams is integrating diversity-focused initiatives into Clinical and Translational Science Award (CTSA) Programs, such as the integrated Translational Health Research Institute of Virginia (iTHRIV). In 2020, iTHRIV participated in Building Up, developed by the University of Pittsburgh CTSA, intended to increase representation and improve career support for underrepresented groups in the biomedical workforce. Drawing lessons from this study, iTHRIV implemented the “inspiring Diverse Researchers in Virginia” (iDRIV) program. This year-long program provided education, coaching, mentoring, and sponsorship for underrepresented early-career investigators in the biomedical workforce. To date, 24 participants have participated in the program across three cohorts. Participants have been predominantly female (92%), with 33% identifying as Hispanic/Latinx, 29% as Black, and 13% Asian. Notably, 38% of scholars have subsequently achieved at least one accomplishment, such as receiving a local research honor or award and an extramural funding award from a foundation or federal agency. The iTHRIV iDRIV program serves as a model for providing career support to developing investigators from underrepresented backgrounds, with the overall goal of improving patient health.
Naturalistic drug cue reactivity in heroin use disorder: orbitofrontal synchronization as a marker of craving and recovery
Authors: Kronberg Greg , Ceceli Ahmet O. , Huang Yuefeng , Gaudreault Pierre-Olivier , King Sarah G. , McClain Natalie , Alia-Klein Nelly , Goldstein Rita Z. 
Published: November 2023

AbstractMovies captivate groups of individuals (the audience), especially if they contain themes of common motivational interest to the group. In drug addiction, a key mechanism is maladaptive motivational salience attribution whereby drug cues outcompete other reinforcers within the same environment or context. We predicted that while watching a drug-themed movie, where cues for drugs and other stimuli share a continuous narrative context, fMRI responses in individuals with heroin use disorder (iHUD) will preferentially synchronize during drug scenes. Results revealed such drug-biased synchronization in the orbitofrontal cortex (OFC), ventromedial and ventrolateral prefrontal cortex, and insula. After 15 weeks of inpatient treatment, there was a significant reduction in this drug-biased shared response in the OFC, which correlated with a concomitant reduction in dynamically-measured craving, suggesting synchronized OFC responses to a drug-themed movie as a neural marker of craving and recovery in iHUD.
Adenine base editing corrects point mutation in mitochondrial single-stranded binding protein (SSBP1) to improve mitochondrial function
Authors: Cha Ju Hyuen , Lee Seok-Hoon , Yun Yejin , Choi Won Hoon , Koo Hansol , Jung Sung Ho , Chae Ho Byung , Lee Dae Hee , Lee Seok Jae , Jo Dong Hyun , Kim Jeong Hun , Song Jae-Jin , Chae Jong-Hee , Lee Jun Ho , Oh Seung Ha , Park Jiho , Kang Jin Young , Bae Sangsu , Lee Sang-Yeon 
Published: November 2023

AbstractMutations in nuclear genes that regulate the mitochondrial DNA (mtDNA) replication machinery have been linked to mtDNA depletion syndromes. Through whole-genome sequencing, we identified a heterozygous missense mutation (c.272G>A:p.Arg91Gln) in single-stranded binding protein 1 (SSBP1), a crucial protein involved in mtDNA replication. The proband manifested symptoms including sensorineural deafness, congenital cataract, optic atrophy, macular dystrophy, and myopathy, all of which are compatible with mtDNA depletion disease. We found that thisSSBP1mutation impeded multimer formation and DNA-binding affinity, which led to reduced efficiency of mtDNA replication and altered mitochondria dynamics. To correct this mutation, we tested two adenine base editor (ABE) variants using patient-derived fibroblasts. One variant, NG-Cas9-based ABE8e (NG-ABE8e), exhibited higher editing efficacy (up to 30% editing), and edited cells showed signs of improved mitochondrial replication and function, including increased mtDNA and ATP production. However, these cells also had higher frequencies of off-target editing of nearby nucleotides, but the risks from bystander editing were limited due to mostly silent mutations and off-target sites in non-translated regions. The other variant, NG-Cas9-based ABE8eWQ (NG-ABE8eWQ), had a safer therapeutic profile with very few off-target effects, but this came at the cost of lower editing efficacy (up to 10% editing). Despite this, NG-ABE8eWQ-edited cells still restored replication and improved mtDNA copy number, which in turn recovery of compromised mitochondrial function. As these therapeutic strategies make their way into the clinic, our research suggests that base editing-based gene therapies may be a promising treatment for mitochondrial diseases, including those associated withSSBP1mutations.
The qMini assay identifies an overlooked class of splice variants
Authors: Guan Bin , Bender Chelsea , Pantrangi Madhulatha , Moore Nia , Reeves Melissa , Naik Amelia , Li Huirong , Goetz Kerry , Blain Delphine , Agather Aime , Cukras Catherine , Zein Wadih M. , Huryn Laryssa A. , Brooks Brian P. , Hufnagel Robert B. 
Published: November 2023

AbstractSplice variants are known to cause diseases by utilizing alternative splice sites, potentially resulting in protein truncation or mRNA degradation by nonsense-mediated decay. Splice variants are verified when altered mature mRNA sequences are identified in RNA analyses or minigene assays. Using a quantitative minigene assay, qMini, we uncovered a previously overlooked class of disease-associated splice variants that did not alter mRNA sequence but decreased mature mRNA level, suggesting a potentially new pathogenic mechanism.
The provision of information on time-lapse imaging: A systematic analysis of UK fertility clinics websites
Authors: Perrotta Manuela , Zampino Letizia , Geampana Alina , Bhide Priya 
Published: November 2023

Structured AbstractResearch QuestionThis study aims to systematically analyse the provision of information on Time-lapse Imaging (TLI) by UK fertility clinic websites.DesignWe conducted an analysis of 106 clinic websites that offer fertility treatment to self-funded patients. The analysis aimed to examine whether these clinics offer TLI, the associated cost for patients, and the clarity and quality of the provided information.ResultsOut of the 106 websites analysed, 71 (67%) claimed to offer TLI, with 17 being NHS clinics and 54 being private clinics. Among these websites, 25 (35.2%) mentioned charging patients between £300 and £850, 25 (35.8%) claimed not to charge patients, and 21 (29.6%) did not provide any cost information for TLI. Although TLI is generally considered safe for patients and embryos, only 21 (29.6%) websites provided information on the associated risks. Furthermore, 64 (90.1%) websites made claims or implied that TLI leads to improved clinical outcomes by enhancing embryo selection. Notably, 34 (47.9%) websites did not mention or provide any links to the HFEA traffic light system. Additionally, 30 (42.2%) websites made claims regarding the effectiveness of TLI that contradicted the assessment of the HFEA, referring to early, mostly unspecified, studies.ConclusionsIt is crucial to provide patients with clear and accurate information to enable them to make fully informed decisions about TLI, particularly when they are responsible for the associated costs. The findings of this study raise concerns about the reliability and accuracy of the information available on fertility clinic websites, which are typically the primary source of information for patients.
Implementation of One Health surveillance systems: opportunities and challenges - Lessons learned from the OH-EpiCap application
Authors: Tegegne Henok Ayalew , Freeth Frederick T. A. , Bogaardt Carlijn , Taylor Emma , Reinhardt Johana , Collineau Lucie , Prada Joaquin M , Hénaux Viviane 
Published: November 2023

ABSTRACTAs the complexity of health systems has increased over time, there is an urgent need for developing multi-sectoral and multi-disciplinary collaboration within the domain of One Health (OH). Despite the efforts to promote collaboration in health surveillance and overcome professional silos, implementing OH surveillance systems in practice remains challenging for multiple reasons. In this study, we describe the lessons learned from the evaluation of OH surveillance using OH-EpiCap (an online evaluation tool for One Health epidemiological surveillance capacities and capabilities), the challenges identified with the implementation of OH surveillance, and the main barriers that contribute to its sub-optimal functioning, as well as possible solutions to address them. We conducted eleven case studies targeting the multi-sectoral surveillance systems for antimicrobial resistance in Portugal and France,Salmonellain France, Germany, and the Netherlands,Listeriain The Netherlands, Finland and Norway,Campylobacterin Norway and Sweden, and psittacosis in Denmark. These evaluations facilitated the identification of common strengths and weaknesses, focusing on the organization and functioning of existing collaborations and their impacts on the surveillance system. Lack of operational and shared leadership, adherence to FAIR data principles, sharing of techniques, and harmonized indicators led to poor organization and sub-optimal functioning of OH surveillance systems. In most cases, the effectiveness of OH surveillance over traditional surveillance, operational costs, behavioural changes, and population health outcomes brought by the OH surveillance have not been evaluated. To this end, the establishment of a formal governance body with representatives from each sector could assist in overcoming long-standing barriers. Moreover, demonstrating the impacts of OH-ness of surveillance may facilitate the implementation of OH surveillance systems.
A retrospective analysis of the diagnostic performance of an FDA approved software for the detection of intracranial hemorrhage
Authors: Pourmussa Bianca , Gorovoy David 
Published: November 2023

AbstractObjectiveTo determine the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of Rapid ICH, a commercially available AI model, in detecting intracranial hemorrhage (ICH) on non-contrast computed tomography (NCCT) examinations of the head at a single regional medical center.MethodsRapidAI’s Rapid ICH is incorporated into real time hospital workflow to assist radiologists in the identification of ICH on NCCT examinations of the head. 412 examinations from August 2022 to January 2023 were pulled for analysis. Scans in which it was unclear if ICH was present or not, as well as scans significantly affected by motion artifact were excluded from the study. The sensitivity, specificity, accuracy, PPV, and NPV of the software were then assessed retrospectively for the remaining 406 NCCT examinations using prior radiologist report as the ground-truth. A two tailedztest with α = 0.05 was preformed to determine if the sensitivity and specificity of the software in this study were significantly different from Rapid ICH’s reported sensitivity and specificity. Additionally, the software’s performance was analyzed separately for the male and female populations and a chi-square test of independence was used to determine if model correctness significantly depended on sex.ResultsOf the 406 scans assessed, Rapid ICH flagged 82 ICH positive cases and 324 ICH negative cases. There were 80 examinations (19.7%) truly positive for ICH and 326 examinations (80.3%) negative for ICH. This resulted in a sensitivity of 71.3%, 95% CI [61.3%-81.2%], a specificity of 92.3%, 95% CI [89.4%-95.2%], an accuracy of 88.2%, 95% CI [85.0%-91.3%], a PPV of 69.5%, 95% CI [59.5%-79.5%], and an NPV of 92.9%, 95% CI [90.1%-95.7%]. Two examinations were excluded due to no existing information on patient sex in the electronic medical record. The resulting sensitivity was significantly different from the sensitivity reported by Rapid ICH (95%),z= 2.60,p= .009 although the resulting specificity was not significantly different from the specificity reported by Rapid ICH (94%),z= 0.65,p= .517. The model performance did not depend on sex per the chi-square test of independence:X2(1 degree of freedom,N= 404) = 1.95,p= .162 (p> 0.05).ConclusionRapid ICH demonstrates exceptional capability in the identification of ICH, but its performance when used at this site differs from the values advertised by the company, and from assessments of the model’s performance by other research groups. Specifically, the sensitivity of the software at this site is significantly different from the sensitivity reported by the company. These results underscore the necessity for independent evaluation of the software at institutions where it is implemented.
An exploration into the impact of the COVID-19 pandemic on maternal mental health in high-and middle-income countries with a case study in East Sussex
Authors: Sabesan Abbeishna , Ackley Caroline , Stone Sophia 
Published: November 2023

AbstractBackgroundThe physical isolation that the Coronavirus pandemic enforced resulted in a decline in mental health that disproportionally affected higher risk individuals, including women in the perinatal period. The wellbeing of perinatal women was, at times, neglected due to hospital and governmental isolation regulations. The aim of this study was to conduct a scoping review and Key Informant Interviews (KII) to identify gaps and opportunities for further research, and to distinguish discrepancies and correlations between the two sources of information.MethodsTwo methods were utilised: a scoping review and KIIs. The scoping review identified relevant articles through a database search on Google Scholar, PubMed and EBSCO. The KIIs were conducted virtually with counsellors working in a maternal mental health charity in South-East England. Both methods collected qualitative data and were thematically analysed.Results95 articles were eligible for the review and 5 participants were recruited for the KIIs. Thematic analysis revealed 6 themes in both sources (1) demographics; (2) support; (3) policy; (4) insecurity; (5) anxiety; and (6) milestones. Between the two datasets there were no disparities in the impacts of changing policies, fear of the virus, and the grief caused by missing perinatal milestones on mental health. Significant discrepancies were identified in the influence of demographic characteristics, which was a risk factor for adverse mental health outcomes.ConclusionThe most prominent theme in the review is the reduced support available, whilst the KIIs indicate that changing hospital policies are the main cause of harm to perinatal mental health. Birth trauma is deemed to be of significance in the interviews but not in the literature. Further research should focus on the impact of the pandemic on recovery following birth trauma to identify long-term implications and facilitate policy changes to reduce the risk of birth trauma/ post-traumatic stress disorder.