bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mate-Pair Sequencing Enables Identification and Delineation of Balanced and Unbalanced Structural Variants in Prenatal Cytogenomic Diagnostics
Authors: Qian Jicheng , Wang Huilin , Liang Hailei , Zheng Yuting , Yu Mingyang , Tse Wing Ting , Kwan Angel Hoi Wan , Wong Lo , Wong Natalie Kwun Long , Wah Isabella Yi Man , Lau So Ling , Hui Shuk Yi Annie , Chau Matthew Hoi Kin , Chen Xiaoyan , Zhang Rui , Poon Liona C , Leung Tak Yeung , Liu Pengfei , Choy Kwong Wai , Dong Zirui 
Published: January 2025

Abstract

Background
Mate-pair sequencing detects both balanced and unbalanced structural variants (SVs) and simultaneously informs in relation to both genomic location and orientation of SVs for enhanced variant classification and clinical interpretation, while chromosomal microarray analysis (CMA) only reports deletion/duplication. Herein, we evaluated its diagnostic utility in a prospective back-to-back prenatal comparative study with CMA.

Methods
From October 2021 to September 2023, 426 fetuses with ultrasound anomalies were prospectively recruited for mate-pair sequencing and CMA in parallel for prenatal genetic diagnosis. Balanced/unbalanced SVs and regions with absence of heterozygosity (AOH) were detected and classified independently, and comparisons were made between mate-pair sequencing and CMA to assess concordance. In addition, novel SVs were investigated for potential RNA perturbations using cultured cells, whenever available.

Results
Mate-pair sequencing and CMA successfully yielded results for all 426 fetuses without the need for cell culturing. In addition, mate-pair sequencing identified 19 cases with aneuploidies, 16 cases with pathogenic simple deletions/duplications, and 5 cases with pathogenic translocations/insertions, providing a 25% incremental diagnostic yield compared to CMA (9.4%, 40/426 vs 7.6%, 32/426). Furthermore, by identifying the location and orientation of SVs, mate-pair sequencing improved the variant interpretation and/or follow-up approach for 40.0% (12) of the 30 cases with likely clinically significant deletions/duplications reported by CMA. Lastly, both platforms reported 3 cases (3/426) with multiple regions of AOH likely attributable to parental consanguinity.

Conclusions
Mate-pair sequencing detects additional balanced/unbalanced SVs and improves variant interpretation in comparison to CMA, indicating its potential to serve as a comprehensive prenatal cytogenomic diagnostic method.
Innovations in Short-Read Sequencing Technologies and Their Applications to Clinical Genomics
Authors: Polonis Katarzyna , Blommel Joseph H , Hughes Andrew E O , Spencer David , Thompson Joseph A , Schroeder Molly C 
Published: January 2025

Abstract

Background
Massively parallel sequencing (MPS) of nucleic acids has been a transformative technology for basic and applied genomic science, increasing efficiencies and decreasing costs to enable studies of unprecedented scope and impact. In clinical settings, these technological and scientific advances have led to the development of tests that are increasingly fast, comprehensive, and more frequently employed. Practitioners of genomic medicine have applied these tools across clinical settings, including diagnosis of inherited disorders and cancers and infectious disease detection and surveillance. In recent years, the commercial marketplace for MPS sequencers and reagents has been dominated by a few companies. The growing demand for sequencing has led to the recent emergence of several new sequencing platforms with techniques that may provide alternatives or improvements to existing workflows or allow the adoption of sequencing workflows in new settings. Clinical genomics laboratories will evaluate these platforms from a unique perspective, focusing on how technological advancements can improve patient care.

Content
This review describes short-read sequencing platforms provided by Illumina, Element Biosciences, MGI, PacBio, Singular Genomics, Thermo Fisher Scientific, and Ultima Genomics. This review discusses their innovative approaches, principles, workflows, and applications.

Summary
This review aims to inform laboratory geneticists, clinicians, and researchers about emerging short-read technologies and their applications in clinical genomics. By highlighting their principles and potential contributions, we aim to assist laboratories in selecting suitable solutions for their sequencing needs considering key factors such as applications, throughput, and integration with existing laboratory workflows.
Detection of Clinically Relevant Monogenic Copy-Number Variants by a Comprehensive Genome-Wide Microarray with Exonic Coverage
Authors: Chau Matthew Hoi Kin , Anderson Stephanie A , Song Rodger , Cooper Lance , Ward Patricia A , Yuan Bo , Shaw Chad , Stankiewicz Paweł , Cheung Sau Wai , Vossaert Liesbeth , Wang Yue , Owen Nichole M , Smith Janice , Bacino Carlos A , Schulze Katharina V , Bi Weimin 
Published: January 2025

Abstract

Background
Disease-causing copy-number variants (CNVs) often encompass contiguous genes and can be detected using chromosomal microarray analysis (CMA). Conversely, CNVs affecting single disease-causing genes have historically been challenging to detect due to their small sizes.

Methods
A custom comprehensive CMA (Baylor College of Medicine - BCM v11.2) containing 400k probes and featuring exonic coverage for &gt;4200 known or candidate disease-causing genes was utilized for the detection of CNVs at single-exon resolution. CMA results across a consecutive clinical cohort of more than 13 000 patients referred for genetic investigation at Baylor Genetics were examined. The genomic characteristics of CNVs impacting single protein-coding genes were investigated.

Results
Pathogenic or likely pathogenic (P/LP) CNVs (n = 190) affecting single protein-coding genes were detected in 188 patients, accounting for 9.9% (188/1894) of patients with P/LP CMA findings. The P/LP monogenic CNVs accounted for 9.2% (190/2058) of all P/LP nuclear CNVs detected by CMA. A total of 57.9% (110/190) of P/LP monogenic CNVs were smaller than 50 kb in size. Single exons were affected by 26.3% (50/190) of P/LP monogenic CNVs while 13.2% (25/190) affected 2 exons. CNVs were detected across 107 unique genes associated with predominantly autosomal dominant (AD) and X-linked (XL) conditions but also contributed to autosomal recessive (AR) conditions.

Conclusions
CMA with exon-targeted coverage of disease-associated genes facilitated the detection of small CNVs affecting single protein-coding genes, adding substantial clinical sensitivity to comprehensive CNV investigation. This approach resolved monogenic CNVs associated with autosomal and X-linked monogenic etiologies and yielded multiple significant findings. Monogenic CNVs represent an underrecognized subset of disease-causing alleles for Mendelian disorders.
Integrative Assessment of Total and Intact HIV-1 Reservoir by a 5-Region Multiplexed Rainbow DNA Digital PCR Assay
Authors: Delporte Mareva , Lambrechts Laurens , Blomme Evy E , van Snippenberg Willem , Rutsaert Sofie , Verschoore Maxime , De Smet Evelien , Noppe Ytse , De Langhe Nele , De Scheerder Marie-Angélique , Gerlo Sarah , Vandekerckhove Linos , Trypsteen Wim 
Published: January 2025

Abstract

Background
Persistent latent reservoirs of intact HIV-1 proviruses, capable of rebounding despite suppressive antiretroviral therapy (ART), hinder efforts towards an HIV-1 cure. Hence, assays specifically quantifying intact proviruses are crucial to assess the impact of curative interventions. Two recent assays have been utilized in clinical trials: intact proviral DNA assay (IPDA) and quadruplex quantitative PCR (Q4PCR). While IPDA is more sensitive due to amplifying short fragments, it may overestimate intact fractions by relying only on quantification of 2 proviral regions. Q4PCR samples 4 proviral regions, yet is sequencing-based, favoring amplification of shorter, hence non-intact, proviral sequences.

Methods
Leveraging digital PCR (dPCR) advancements, we developed the “Rainbow” 5-plex proviral HIV-1 DNA assay. This first-in-its-kind assay was evaluated using standard materials and samples from 83 people living with HIV-1, enabling simultaneous quantification of both total and intact HIV-1 DNA levels. HIV proviral unique molecular identifier (UMI)-mediated long-read sequencing (HIV-PULSE) was used to validate the specificity of the Rainbow HIV-1 DNA assay.

Results
The Rainbow assay proved equally sensitive but more specific than IPDA and is not subjected to bias against full-length proviruses, enabling high-throughput quantification of total and intact reservoir size. The near full-length sequences allowed validation of the Rainbow specificity and the design of personalized Rainbow primer/probe sets, which enabled the detection of intact HIV-1 DNA.

Conclusions
This innovation offers potential for targeted evaluation and monitoring of potential rebound-competent reservoirs, contributing to HIV-1 management and cure strategies. ClinicalTrials.gov Registration Numbers: NCT04553081, NCT04305665.
Inferring the Demographic History of Aye-Ayes (Daubentonia madagascariensis) from High-Quality, Whole-Genome, Population-Level Data
Authors: Terbot John W , Soni Vivak , Versoza Cyril J , Pfeifer Susanne P , Jensen Jeffrey D 
Published: January 2025

Abstract
The nocturnal aye-aye, Daubentonia madagascariensis, is one of the most elusive lemurs on the island of Madagascar. The timing of its activity and arboreal lifestyle has generally made it difficult to obtain accurate assessments of population size using traditional census methods. Therefore, alternative estimates provided by population genetic inference are essential for yielding much needed information for conservation measures and for enabling ecological and evolutionary studies of this species. Here, we utilize genomic data from 17 individuals—including 5 newly sequenced, high-coverage genomes—to estimate this history. Essential to this estimation are recently published annotations of the aye-aye genome which allow for variation at putatively neutral genomic regions to be included in the estimation procedures, and regions subject to selective constraints, or in linkage to such sites, to be excluded owing to the biasing effects of selection on demographic inference. By comparing a variety of demographic estimation tools to develop a well-supported model of population history, we find strong support for two demes, separating northern Madagascar from the rest of the island. Additionally, we find that the aye-aye has experienced two severe reductions in population size. The first occurred rapidly, ∼3,000 to 5,000 years ago, and likely corresponded with the arrival of humans to Madagascar. The second occurred over the past few decades and is likely related to substantial habitat loss, suggesting that the species is still undergoing population decline and remains at great risk for extinction.
Squirt flow in a tight sandstone: an interlaboratory study
Authors: Ógúnsàmi Abdulwaheed R , Jackson Ian , Pimienta Lucas , Fortin Jérôme 
Published: January 2025

SUMMARY
In the spirit of interlaboratory benchmarking of related techniques, we have re-examined the seismic-frequency mechanical properties of a low-porosity Wilkeson sandstone specimen tested in axial stress oscillation under water-saturated conditions by Pimienta et al. The same specimen has been newly tested at periods of 1–1000 s under dry and argon-, water- and glycerine-saturated conditions by torsional and flexural oscillation methods, allowing direct measurement of the shear modulus G and Young's modulus E and associated strain-energy dissipations. The results show a steady increase of G and E for the dry specimen with increasing pressure, indicative of progressive closure of the compliant intergranular contacts. Under argon- and water-saturated conditions, the measured moduli differ only marginally from those for dry conditions, without any significant stiffening or dispersion, suggesting that such measurements probe the saturated-isobaric regime. In marked contrast, glycerine saturation results in substantially higher and frequency-dependent moduli, along with frequency-dependent dissipation. We attribute this behaviour to the squirt flow transition with decreasing frequency from the saturated-isolated to the saturated-isobaric regime, modelled with a log-normal distribution of relaxation times (broader than the Debye peak of the standard anelastic solid) superimposed upon a monotonically frequency-dependent background. Although there are differences in detail, these findings corroborate those of Pimienta et al. for the same material tested in axial stress oscillation to higher frequencies under water-saturated conditions. Taken together, the two studies thus provide robust support for theoretical models of squirt flow dispersion and dissipation, occurring at frequencies between those of conventional ultrasonic wave-propagation laboratory methods and those of seismic exploration of the shallow crust.
Evaluating the Bouguer layer approximation method in modelling ocean effects on gravity changes induced by earthquakes
Authors: Zhao Xinyu , Zhou Xin 
Published: January 2025

SUMMARY
Ocean water mass redistributions triggered by earthquakes result in notable changes in the gravity potential field. These oceanic effects can be quantified using two primary methods: solving the sea level equation (SSLE) and the Bouguer layer approximation (BLA). The SSLE accounts for both the direct attraction and the elastic loading response induced by the perturbed ocean water during an earthquake. In contrast, the BLA disregards the elastic loading effect and utilizes the Bouguer correction formula to estimate the impact of direct attraction. In this study, we evaluate the effectiveness of the BLA by comparing it with the SSLE in estimating both coseismic and post-seismic gravity field changes from simulation test and three realistic events, the 2004 Sumatra Mw 9.2, the 2011 Tohoku-Oki Mw 9.0 and the 2014 Iquique Mw 8.1. Our simulations involve a thrust fault and a strike-slip fault beneath a uniform ocean covering, while the Sumatra, the Tohoku-Oki and the Iquique events are under realistic sea-land distribution. Our findings reveal minimal discrepancies between the BLA and SSLE, suggesting that the BLA is effective in correcting oceanic effects for gravity changes of both long and short wavelengths.
The role of CNBP in brain atrophy and its targeting in myotonic dystrophy type 2
Authors: Jennings Katherine , Lindquist Diana , Poonia Ankita , Schoser Benedikt , Schneider-Gold Christiane , Timchenko Nikolai A , Timchenko Lubov 
Published: January 2025

Abstract
Myotonic Dystrophy type 2 (DM2) is a multisystem disease affecting many tissues, including skeletal muscle, heart, and brain. DM2 is caused by unstable expansion of CCTG repeats in an intron 1 of a gene coding for cellular nuclear binding protein (CNBP). The expanded CCTG repeats cause DM2 pathology due to the accumulation of RNA CCUG repeats, which affect RNA processing in patients’ cells. We have previously shown that mutant CCUG repeats reduce CNBP protein in DM2 patients. Reducing Cnbp in Cnbp KO mouse model causes late skeletal muscle atrophy. In this study, we examined if the reduction of Cnbp affects the Central Nervous System (CNS). MRI and DTI analyses showed that total brain volume and grey matter are reduced in Cnbp KO mice, while mean, radial and axonal brain diffusivity is increased. The morphological changes in the brains of Cnbp KO mice are accompanied by reduced stereotypic behavior, anxiety and neuromotor defects. These findings suggest that the reduction of CNBP contributes to CNS pathology in DM2. Since CNBP stability is regulated by pAMPK-dependent phosphorylation, we examined protein levels of pAMPK in DM2 cells and found that the active pAMPK is reduced in DM2. Interaction of CNBP with pAMPK and stability of CNBP protein are also decreased in DM2. Our data show that a small molecule AMPK activator A769662 corrects CNBP stability and normalizes CNBP targets in DM2 fibroblasts. Thus, activators of AMPK could potentially be developed as therapeutics to correct CNBP and reduce muscle and brain atrophies in DM2.
Forging a pathway for connecting skills, knowledge, technology, and participatory decision-making for all through the UN Ocean Decade Challenge 9
Authors: Buchan Pamela M , Mahu Edem , Seeyave Sophie , Arbic Brian K , Sant Gail , Maúre Elígio d R , Mahadeo Sarah , Kostianaia Evgeniia , Hermes Juliet , Sacedon Randa , Sogbanmu Temitope O , Kidwai Samina , Lin Xin , Sun Zhen 
Published: January 2025

Abstract
The UN Ocean Decade Vision 2030 Report identified the role of ocean knowledge in sustainable development and highlighted the need for a clear pathway to achieve its vision. Challenge 9–skills, knowledge, technology, and participatory decision-making for all—is crucial for forging a collaborative and connected pathway for knowledge generation and sharing. This article summarizes the challenges and recommendations in the Challenge 9 White Paper. It then focuses on three aspects that had emergent significance during the White Paper review processes: (1) the language we use around capacity, (2) the need to include multiple and diverse knowledge systems, and (3) the proposition that Challenge 9 is the natural home for access to participation in ocean decision-making.
Capacity sharing to protect and restore ecosystems and biodiversity
Authors: Muller-Karger Frank E , Tan Aileen Shau Hwai , Allcock A Louise , Appeltans Ward , Aguilar Claudia Barón , Blanco Andreu , Bograd Steven J , Costello Mark John , Darnaude Audrey M , Dupuis Britt , Evaux Lucie M , Goodwin Kelly , Jungbluth Sean , Leinen Margaret , Levin Lisa A , Mahapatra Pooja , Martone Rebecca , Nordlund Lina Mtwana , Ndah Anthony B , Pante Eric , Paul Ken , Pearlman Jay , Pelletier Dominique , Relano Veronica , Rogers Alex David , Seeyave Sophie , Soares Joana , Taylor Simon , Pendleton Linwood 
Published: January 2025

Abstract
Challenge 2 of the UN Ocean Decade focuses on protecting and restoring marine ecosystems and biodiversity as a fundamental requirement to achieve sustainable development. Addressing this challenge requires reliable and timely information on biodiversity and ecosystems. To achieve this, academic, government, and private groups should engage in a process of co-design that aims to facilitate decision-making at the local and national level, and agree on common and interoperable practices for the collection and curation of biology and ecosystem information. Implementing the flow of data to enable the management of human activities and sustainable development will require the sharing of capacity. An all-hands-on-deck effort will help us ensure a better future for ourselves. A positive step would be to identify the minimum essential ocean variables that can serve multiple relevant regional and international frameworks and to link and harmonize the required data and information flow (i.e., for frameworks including the Convention on Biological Diversity Kunming-Montreal Global Biodiversity Framework, the United Nations Framework Convention on Climate Change Paris Agreement, the Biodiversity Beyond National Jurisdiction Agreement, the International Seabed Authority, the Convention on the Conservation of Antarctic Marine Living Resources, the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services, and deep and national ocean fisheries policies). A key strategy is to support and build on existing local and national networks for biodiversity observation. With this information, local communities and nations can better understand and manage how they use marine life and also report on progress toward Sustainable Development Goals.
Unintended and overlooked consequences of exclusionary marine conservation
Authors: Lopes Priscila F M , Constantinescu Ştefan , Silvano Renato A M , Tatui Florin , Teampău Petruța , Vaidianu Natasa 
Published: January 2025

Abstract
Marine conservation efforts, often through top-down marine protected areas (MPAs), have typically prioritized biodiversity over the needs and rights of local communities. This approach can lead to social injustices and unintended consequences, including promoting unsustainable practices and eroding traditional, sound management methods, along with the loss of cultural heritage and identity. This food-for-thought piece explores some of these overlooked ramifications of top-down MPAs, using the Tamoios MPA in Brazil and the Danube Delta Biosphere Reserve in Romania as examples. It highlights how the exclusionary nature of top-down conservation can potentially undermine or delay conservation goals. Integrating local ecological knowledge (LEK) and customary management practices into formal management can be beneficial, regardless of potential limitations and/or disconnection with recommended conservation practices. LEK can serve as a bridge between communities and conservation goals, offering insights into sustainable practices and fostering dialogue. Inclusive approaches that combine LEK with scientific knowledge and involve local communities in decision-making can be beneficial for both new and existing MPAs, especially those that may not have been established in a socially fair way. Prioritizing negotiation and active listening in conservation efforts can help achieve both ecological sustainability and social justice, providing a potentially effective approach to marine conservation.
Tubes and Steklov Eigenvalues in Negatively Curved Manifolds
Authors: Basmajian Ara , Brisson Jade , Hassannezhad Asma , Métras Antoine 
Published: January 2025

Abstract
We consider the Steklov eigenvalue problem on a compact pinched negatively curved manifold $M$ of dimension at least three with totally geodesic boundaries. We obtain a geometric lower bound for the first nonzero Steklov eigenvalue in terms of the total volume of $M$ and the volume of its boundary. We provide examples illustrating the necessity of these geometric quantities in the lower bound. Our result can be seen as a counterpart of the lower bound for the first nonzero Laplace eigenvalue on closed pinched negatively curved manifolds of dimension at least three proved by Schoen in 1982. The proof is composed of certain key elements. We provide a uniform lower bound for the first eigenvalue of the Steklov–Dirichlet problem on a neighborhood of the boundary of $M$ and show that it provides an obstruction to having a small first nonzero Steklov eigenvalue. As another key element of the proof, we give a tubular neighborhood theorem for totally geodesic hypersurfaces in a pinched negatively curved manifold. We give an explicit dependence for the width function in terms of the volume of the boundary and the pinching constant.