bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized comparison of precut papillotomy versus an endoscopic ultrasound-guided rendezvous procedure for difficult biliary access in malignant distal biliary obstruction
Authors: Dhir Vinay , Singh Vivek Kumar , Dalal Ankit , Patil Gaurav Kumar , Maydeo Amit
Published: January 2025

Difficult biliary cannulation (DBC) is a marker for prolonged procedure time and a higher rate of adverse events (AEs) during endoscopic retrograde cholangiopancreatography (ERCP). We previously showed that endoscopic ultrasound-assisted rendezvous (EUS-RV) procedures had a higher single-session success rate than precut papillotomy (PCP) in cases of DBC. The present randomized study aimed to compare the technical success and AE rates of the two approaches

This was an open-label randomized controlled trial in a tertiary care setting. Patients with malignant distal biliary obstruction (MDBO) and DBC were enrolled. The patients were randomized to PCP with a needle-knife or EUS-RV. The primary outcome was technical success; secondary outcomes were the AE rate, procedure duration, and length of hospital stay (LOS).

208 patients were enrolled, 104 in each group. There were no statistically significant differences in technical success (93.3% PCP vs. 97.1% EUS-RV; P = 0.33; odds ratio [OR] 0.4, 95%CI 0.1–1.6) and overall AE rate (11.5% PCP vs. 5.8% EUS-RV; P=0.14; OR 0.5, 95%CI 0.8–5.9). Pancreatitis was higher in the PCP group (8.7% vs. 1.9%; P=0.06; OR 4.8, 95%CI 1.0–22.9). The mean duration of the procedure was significantly higher for EUS-RV (47 vs. 27 minutes; P<0.001). LOS was similar in the two groups (1.2 PCP vs. 1.1 days EUS-RV; P=0.25).

Both PCP and EUS-RV have comparable rates of success, AEs, mortality, and LOS. EUS-RV could be used as an alternative to PCP in patients with MDBO and DBC.
The red fox (Vulpes vulpes) as a potential invasive predator in a Critically Endangered sawfish nursery
Authors: Morgan David L. , Lear Karissa O. , Ingelbrecht Jack , Fazeldean Travis , Fleming Patricia A.
Published: January 2025

Although the red fox (Vulpes vulpes) is considered one of the most damaging and adaptive invasive carnivorous mammals that consumes a wide variety of vertebrate and invertebrate taxa, there are surprisingly few reports of red foxes hunting fish. We observed evidence of an attempted predation event by a red fox on a neonate green sawfish (Pristis zijsron) within a deltaic island in the Ashburton River estuary, a remote desert river in Western Australia. The site is a globally important nursery where newborn sawfish arrive annually in spring. Injuries to the sawfish included paw/claw marks on the head, damage to the rostrum, which is a formidable tool that is used for both defence against predators and for detecting and attacking prey, as well as a major hole in the head and damage to the gills, which are vital for respiration, osmoregulation, nitrogenous waste excretion, pH regulation, and hormone production. A series of tracks suggests at least one fox parades the shallow tidally influenced banks, with evidence of a green mud crab (Scylla serrata) having also been predated on. There have also been reports of red fox predation of sea turtle nests nearby. This is the first record of a red fox hunting in marine waters and one of the few identifying fish as prey. We suggest that a monitoring program for foxes, and possibly a control program, is warranted prior to the annual seasonal colonisation of this habitat by neonate green sawfish and nesting turtles, which may in turn reduce predation of sympatric species.
Exploring a new Biocultural Credit Assessment Framework: case study for Indigenous-led fauna management from the Laynhapuy Indigenous Protected Area, Australia
Authors: Smuskowitz Daniel G. , Ens Emilie J. , Campbell Bridget , Wunuŋmurra Bobby M. , Wunuŋmurra Bandipandi , Waṉambi Luḻparr George , Wunuŋmurra Brendan Banygada , Marrkula Butjiaŋanybuy Thomas , Waṉambi Darren G.
Published: January 2025

Warning This article contains names and/or images of deceased Aboriginal Peoples. Context The global biological-diversity crisis has resulted in a widespread uptake of market mechanisms to promote conservation. Despite widespread recognition of Indigenous-led contribution to biodiveristy conservation, market mechanisms are often derived from Western scientific approaches that do not appropriately incorporate Indigenous cultural values and objectives. Aims This research sought to produce a proof-of-concept case study for a novel ‘Biocultural Credit Assessment Framework’ (BCAF) to facilitate design of an Indigenous-led biocultural conservation project in response to ongoing decline of culturally significant fauna in north-eastern Arnhem Land, Australia. The BCAF is underpinned by Indigenous identification of project dimensions, combining biological and cultural values and aspirations, which could form assessable foundations of a potential Indigenous-led biocultural credit project. Methods Semi-structured interviews were conducted with nine Yolŋu Elders over 2 days. A three-stage thematic analysis using pre-defined coding categories and both latent and semantic level analysis were used to elucidate key components of a biocultural project from Elder responses, including biocultural concerns, actions, targets and indicators. Key results Yolŋu Elders expressed six key concerns about local fauna, including the following: that some animals were no longer seen; youth were not learning cultural knowledge; invasive-species impacts; reliance on shop food; and Western influences. These concerns were linked to three key targets, including improved cultural transmission, access and use of more bush foods, and seeing ‘species of decline’ again. Ten key indicator groups assessed by a mix of Indigenous and Western methodologies were identified and revolved around biophysical and cultural learning parameters to measure the impact of actions to progress targets. In total, six actions were identified, including spending more time on Country, science-based environmental management strategies and knowledge sharing. Conclusions The BCAF elucidated key components of an Indigenous-led biocultural conservation project as identified by Elders. A mix of biophysical and cultural learning indicators assessed both qualitatively and quantitatively could be used to feed into a potential biocultural credit market to enhance project delivery. Implications Further research is required to progress this conceptual framework with Cultural Advisors and real financial partners to further elucidate challenges, opportunities, and next steps towards an inclusive biocultural market.
Yarning up with Doc Reynolds: an interview about Country from an Indigenous perspective
Authors: Reynolds Doc , Cameron Liz
Published: January 2025

This article uses Yarning with Country as a methodological approach where Country plays a pivotal role as an active participant. Our focus is on examining how we learn from and establish respectful, reciprocal, and accountable relationships with Country, as told through the eyes and experiences of knowledge holders, in this case, Doc Reynolds. The knowledge shared about the importance and meaning of Country contributes to advancing ecological-research methodologies to better acknowledge and learn from Indigenous knowledge systems, offering insights into sustainable practices and community engagement within landscapes. This body of knowledge serves as an invitation for Australians to reconceptualise Country, envisioning it both as a noun and a verb. As a noun, Country represents the physical landscape and environment, imbued with cultural significance and history. As a verb, it highlights the dynamic and interactive relationships that exist between people and their environment. This dual understanding encourages a deeper engagement with Country, that it is not merely a backdrop for human activity but a living entity that requires care, respect, and ongoing dialogue.
Nonclassicality of photons in mean-field anisotropic quantum light-matter interacting lattices: Two-photon correlation function and quadrature squeezing
Authors: Xu-Min Chen , Pei-Yao Chen , Chen Wang
Published: January 2025

The generation of nonclassical photons via quantum light-matter interactions is of fundamental importance in quantum optics. Here we investigate steady-state two-photon correlation function and photon squeezing in an open anisotropic Rabi lattice by applying quantum dressed master equation embedded with the mean-field approximation. The expanded antibunching effect of photons due to anisotropic qubit-photon interaction, is strongly suppressed by including inter-site photon tunneling, whereas the giant photon bunching keeps robust with weak inter-site photon tunneling strength. The microscopic processes for photon antibunching and bunching effects are presented based on incoherent transitions between eigenstates. The photon squeezing is also analyzed under the influences of qubit-photon coupling and anisotropic factor. The quadrature squeezing shows persistency by tuning on the inter-site photon tunneling, and becomes dramatically pronounced at the small anisotropic factor. Moreover, the increasing number of qubits significantly enhances quadrature squeezing with strong qubit-photon interaction. We hope such results may provide physical insights into efficient generation and manipulation of nonclassical features of photons in quantum light-matter interacting lattice systems.
Controlled propagation and particle manipulation of off-axis-rotating elliptical Gaussian beams in strong nonlocal media
Authors: Chen Rong-Quan , Xiao Rui-Lin , Wang Wei , Chu Xi-Xi , Song Yu-Qing , Hu Xu-Dong , Chen Ming
Published: January 2025

Off-axis-rotating elliptical Gaussian beams(OareGB) oblique incidence in strong nonlocal medium exhibit novel propagation properties.The analytical expressions of semi-axial beamwidths, and center-of-mass trajectory equations for transmitting off-axis-rotating elliptical Gaussian beams in strong nonlocal media are obtained using the ABCD transfer matrix method. The study revealed that the trajectory of the mass’s center in the cross-section can be controlled by changing the sizes of the OareGB parameters c, d, ζ, and f. The gradient force of the light field causes the spot region to form a spatial potential well in the media, and this spatial potential well can effectively capture nanoparticles. The particles captured by the light field can move along with the beam, realizing the effective manipulation of the particle trajectory. These laws may be applied to modulating the propagation path of light beams and optical tweezer technology.
The co-excitation of electrostatic ion-cyclotron wave and ion Bernstein-like wave launched from a grid
Authors: Sun Hongyu , Ma Jinxiu , Zhao Yaodong , Tao Wan , Liu Qi
Published: January 2025

Electrostatic ion-cyclotron wave (EICW) and ion-Bernstein wave (IBW) are two typical normal modes of plasma propagating vertically to a magnetic field. These modes satisfy the extreme conditions $\omega \ll k_{\parallel} v_{\rm te}$ and $\omega \gg k_{\parallel} v_{\rm te}$, where $\omega$, $k_{\parallel}$, and $v_{\rm te}$ are the wave angular frequency, wave number parallel to the magnetic field, and the electron thermal speed. Between these extremities, there exist IBW-like waves that have not been studied. In this paper, the co-excitation of the EICW and IBW-like wave in an experiment is presented. It is shown that, in an argon (Ar) discharge, the EICW appears in the fundamental and second harmonic frequency bands of the ion-cyclotron frequency. In contrast, the IBW-like wave appears in the higher harmonic frequency bands and in the case of a relatively strong magnetic field. In a helium (He) discharge, the IBW-like wave is excited in the fundamental frequency band, but the wave behaviour becomes complicated in the harmonic frequency bands. The measured dispersion relations of the excited EICW are in agreement with the results of the fluid and kinetic models in some range of frequencies, but those of the excited IBW-like wave are only in qualitative agreement with the kinetic model of the IBW. This study is important for identifying the IBW-like mode that may have potential application in plasma heating via Landau damping.
Integrated Assessment and Policy Optimization: A Brief Introduction
Authors: Kelleher J Paul
Published: January 2025

This chapter provides a brief introduction to climate change economics and to the integrated assessment models (IAMs) it employs. It then describes the main features of policy-optimization IAMs, which have social cost of carbon estimates as one of their main outputs. The chapter explains the role of objective functions in policy-optimization IAMs and warns against reading too much into the fact that an IAM incorporates an objective function. For example, philosophers tend to assume that the presence of an objective function makes an IAM essentially normative. But that might be a mistake, as it is possible to derive seemingly identical objective functions from within radically different analytical frameworks.
The Social Cost of Carbon in Social Choice Climate Economics
Authors: Kelleher J Paul
Published: January 2025

This chapter explains the basis and methods of what the book calls social choice climate economics. This framework uses a social welfare function to place intertemporal paths of consumption into a ranked ordering. The chapter explains that the framework requires two key assumptions: that individual well-being is cardinally measurable and that it is interpersonally comparable. It also explains how two different social cost of carbon (SCC) concepts emerge from the framework, and how the economic technique of discounting is involved in this. Finally, it relates each SCC concept to its own distinct task in climate economics. One of these tasks concerns climate change cost-benefit analysis, while the other concerns the identification of so-called optimal climate policy.
The Social Cost of Carbon in General Equilibrium Climate Economics
Authors: Kelleher J Paul
Published: January 2025

This chapter explains the basis and methods of what the book calls general equilibrium climate economics. This framework is concerned to study Pareto efficient intertemporal allocations of goods, services, and environmental amenities, and the decentralized policy instruments that can steer the world toward any pre-selected Pareto efficient allocation. It explains that each Pareto efficient allocation is the solution to a policy-optimization problem whose objective function looks like a social choice social welfare function, but which is fundamentally different. The mathematics of these new functions—which the chapter terms character functions—permits the derivation of two new social cost of carbon concepts, only one of which is useful for policy analysis.
A Foundation for (Discounted) Utilitarian Social Welfare Functions
Authors: Kelleher J Paul
Published: January 2025

This chapter discusses two different approaches to deriving discounted and undiscounted utilitarian social welfare functions in social choice climate economics. It explains and critically evaluates Tjalling Koopmans’s axiomatic derivation of discounted utilitarianism, as well as his exploration of undiscounted utilitarianism. It then sympathetically explicates John Harsanyi’s derivation of a social welfare function that is consistent with weighted and unweighted versions of utilitarianism and its rival prioritarianism. Drawing heavily on work by John Broome, the chapter explains assumptions required to vindicate an unweighted utilitarian social welfare function. These assumptions concern the possibility of interpersonal comparisons of well-being, and the ability to aggregate well-being across times within each person’s life and then across different lives within a given intertemporal outcome. In the Harsanyi-Broome framework, the ability to aggregate in these ways turns on the ability to aggregate across different possible states of the world.
The Social Cost of Carbon in Applied Climate Change Policy Analysis
Authors: Kelleher J Paul
Published: January 2025

This chapter summarizes the book’s central arguments and then puts some of its principal conclusions to work. It explicates and evaluates efforts by the U.S. federal government to produce official social cost of carbon estimates for use by federal agencies. And it criticizes guidelines that had—until very recently—forbidden the use of social choice climate economics in these federal SCC efforts. Invoking normative abridgement, the chapter then rebuts several objections to social choice climate economics that were lodged by economists who peer-reviewed the recent policy change. The chapter ends with a brief but sympathetic discussion of Pareto-improving climate policy.
Introduction
Authors: Catala Amandine
Published: January 2025

The Introduction presents the aim of the book, namely, to develop a systematic account of epistemic power and agency by turning to the dynamics of epistemic injustice, or the many forms epistemic injustice can take, the different sites and mechanisms through which it operates, and the various transformations consequently required to move toward greater epistemic justice. The Introduction explains the choice of standpoint theory as the book’s methodology in order to ground theory in practice by centering the lived experience and experiential knowledge of non-dominant groups. It further explains how the book will highlight the problematic dynamics that generate and maintain unjust credibility and intelligibility economies by focusing on important social issues such as deliberative impasses, colonial memory, academic migration, the underrepresentation of members of non-dominant groups in certain fields, the marginalization of minoritized minds like intellectually disabled people, and the transformative experience of receiving an autism diagnosis in adulthood. The Introduction also provides basic definitions of key terms and clarifies the distinction between epistemic injustice and epistemic oppression. Finally, the Introduction offers an overview of each chapter, surveying some of the key points developed in the book, such as a pluralist account of knowledge and epistemic agency, meta-epistemic injustice, structural explanation, testimonial domination, hermeneutical domination, epistemic affordances, meta-epistemic filters, linguistic epistemic injustice, and existential hermeneutical injustice.
Colonial Memory, Epistemic Affordances, and Political Equality
Authors: Catala Amandine
Published: January 2025

Chapter 4, titled “Colonial Memory, Epistemic Affordances, and Political Equality,” starts from the observation that most Western democracies have been, or continue to be, involved in colonialism. Yet, whether in Europe, North America, or Australasia, colonial memory is either severely distorted or lacking entirely—a situation that this chapter characterizes as colonial erasure. Focusing on the case of colonial memory in the context of Belgium’s colonization of the Congo, this chapter argues that (i) colonial erasure is a problem of epistemic injustice; that (ii) this situation of epistemic injustice undermines political equality in contemporary societies because of what this chapter calls meta-epistemic filtering; and that (iii) securing epistemic justice and political equality therefore requires, among other things, a collective duty of colonial memory. To make its case, this chapter introduces the concepts of epistemic affordance, disaffordance, dysaffordance, and misaffordance—all of which track the differential epistemic opportunities and obstacles that individuals face based on their social position and thereby capture different ways in which epistemic agency can be constrained or facilitated.
Mistaking Linguistic Privilege for Epistemic Privilege
Authors: Catala Amandine
Published: January 2025

Chapter 5, titled “Mistaking Linguistic Privilege for Epistemic Privilege: Academic Migration and Linguistic Epistemic Injustice,” focuses on undue differentials in epistemic power as they arise in the philosophically understudied case of academic migration. This chapter develops a systematic account of the various ways in which the spread of English as a lingua franca in academia produces linguistic epistemic injustice for academic migrants who are non-native English users. The chapter begins by proposing a broad conception of academic migration, spelling out what it encompasses and why it normatively matters, before focusing the discussion on the specific academic context of Anglo-American analytic philosophy. Next, it outlines the normative significance of a politicized conception of language, including linguistic privilege, for understanding linguistic epistemic injustice. The chapter then proceeds to show how academic migrants who are non-native English users face several types of linguistic epistemic injustice in both agential and institutional forms. Finally, it considers possible avenues to move toward greater epistemic justice in Anglophone academia. The chapter adopts an intersectional perspective, with an emphasis on the interaction between racial and linguistic biases that is captured in linguistic racism and raciolinguistic ideologies. This chapter thereby contributes to theories of epistemic injustice, which mostly have not discussed the rise of English as a lingua franca; to theories of linguistic justice, which mostly have not identified the rise of English as a lingua franca as a source of epistemic injustice; and to theories of migration, which mostly have not focused on academic migration.
Becoming Who You Are
Authors: Catala Amandine
Published: January 2025

Chapter 6, titled “Becoming Who You Are: Hermeneutical Breakthroughs, Transformative Experience, and Epistemic Empowerment,” addresses the process of epistemic empowerment by connecting the literature on epistemic injustice to the literature on transformative experience. In contrast to the predominant focus on the implications of transformative experience for rational choice and decision theory, this chapter focuses on some of the normative, justice-oriented aspects of transformative experience by turning to the philosophically neglected intersection of gender and neurodiversity. This chapter argues that accessing an autism diagnosis constitutes a hermeneutical breakthrough that is the source of a transformative experience for previously undiagnosed Autistic women, and that accessing a diagnosis is a matter of both epistemic and social justice. After some terminological clarifications, this chapter begins by showing how hermeneutical breakthroughs give rise to transformative experience and epistemic empowerment, and how hermeneutical breakthroughs can impact Autistic women’s social, economic, and mental well-being. It then shows how hermeneutical injustice can preempt hermeneutical breakthroughs, which involve hermeneutical representativeness and improved self-understanding. This chapter identifies a new type of epistemic injustice, which it terms existential hermeneutical injustice, which specifically affects a person’s sense of identity or who they take themselves to be, by preventing a person from knowing and becoming who they are. Finally, the chapter shows that moving toward hermeneutical justice, so that Autistic women may access a diagnosis and become who they are, requires attending to the gender biases that pervade both the social and the medical spheres.
Conclusion
Authors: Catala Amandine
Published: January 2025

The conclusion provides a review that both summarizes the main contributions of the book while showing how they all fit together. These contributions include: a pluralist account of epistemic agency and injustice that identifies their non-propositional, experiential (practical, tacit, embodied, and affective) dimensions in addition to their propositional ones; a structural explanation of epistemic agency that identifies its individual and structural dimensions; the concepts of meta-epistemic injustice; of testimonial and hermeneutical domination, of epistemic affordances, disaffordances, dysaffordances, and misaffordances, of meta-epistemic filters, of linguistic epistemic injustice, of existential hermeneutical injustice; a detailed account of hermeneutical breakthroughs and their connection to transformative experience and epistemic empowerment; and a systematic account of epistemic power, including epistemic power-to, power-over, and power-with.
Optimizing Closed-Approach Preservation Rhinoplasty by Ultrasonic Piezo-assisted Techniques for Enhanced Precision
Authors: Guilarte Ruben , Malzone Gerardo
Published: January 2025

Background

Preservation rhinoplasty, particularly dorsal preservation, has gained prominence with the advent of piezoelectric instruments, which minimize trauma and enhance precision in bone reshaping. This approach presents unique challenges, especially in closed techniques, where spatial limitations complicate the use of piezotomes.

Objectives

The aim of this study was to evaluate outcomes of piezo-assisted preservation rhinoplasty performed with specialized instrumentation to enhance visibility, precision, and postoperative recovery in closed rhinoplasty procedures.

Methods

In a cohort of 734 patients undergoing primary rhinoplasty between May 2021 and April 2023, piezoelectric instruments facilitated closed preservation techniques. Cases were documented with a focus on instrument adaptation, bone reshaping precision, and the mitigation of postoperative complications.

Results

A 6% revision rate was observed, predominantly for dorsal contour adjustments, with minimal intraoperative bleeding, swelling, and postoperative pain, demonstrating the effectiveness of piezoelectric assistance. Woodpecker (Guilin, China) SS18 and SS4 inserts were specifically optimized to enhance cutting efficiency for removal of the perpendicular plate of the ethmoid, and for lateral and transverse osteotomies.

Conclusions

Piezo-assisted rhinoplasty improves precision and reduces trauma, supporting advanced closed preservation rhinoplasty techniques. Although all osteotomies can now be performed with ultrasonic piezotomes, enhanced instrument design may further refine outcomes, facilitating minimally invasive, aesthetically superior results.

Level of Evidence: 4 (Therapeutic)
Tetragonia tetragonioides extract prevented high-fat-diet-induced obesity and changed hepatic and adipose transcriptomic signatures in C57BL/6J male mice
Authors: Oh Hea Ry , Park Yong Hyun , Hong Hye Ryeong , Kim Hyun Jin , Park Jinbong , Han Yohan , Ko Seong-Gyu , Shin Eui Cheol , Kim Tae Gyun , Cho Hyung Taek , Pan Jeong Hoon , Shin Hyo Ri , Shim Youn Young , Reaney Martin J T , Cho Tae Jin , Hong Ji Youn , Kim Young Jun , Han Bok Kyung , Lee Geung-Joo , Lee Kangwook , Do Seon Gil , Kim Jae Kyeom
Published: January 2025

Obesity, often driven by high-fat diets (HFDs), is a major global health issue, necessitating effective preventive measures. Tetragonia tetragonoides, a plant with known medicinal properties, has not been extensively studied for its effects on HFD-induced obesity and related genetic changes in mice. This study explores the impact of T. tetragonoides extract (TTE; 300 mg/kg) on obesity-related traits in C57BL/6J male mice, with a focus on transcriptomic changes in the liver and white adipose tissue (WAT). Over 8 weeks, TTE supplementation led to significant reductions in obesity-related phenotypes and modulated gene expression altered by HFD. Key genes like Cd180 and MUPs, linked to immune responses and lipid metabolism, were notably influenced by TTE. The study highlighted TTE’s effects on lipid metabolism pathways in the liver and immune processes in WAT, underscoring its potential as an anti-obesity agent, while advocating for further research into its bioactive components.
PbsNRs: predict the potential binders and scaffolds for nuclear receptors
Authors: Zheng Genhui , Wu Dingfeng , Wei Xiuxia , Xu Dongpo , Mao Tiantian , Yan Deyu , Han Wenhao , Shang Xiaoxiao , Chen Zikun , Qiu Jingxuan , Tang Kailin , Cao Zhiwei , Qiu Tianyi
Published: January 2025

Nuclear receptors (NRs) are a class of essential proteins that regulate the expression of specific genes and are associated with multiple diseases. In silico methods for prescreening potential NR binders with predictive binding ability are highly desired for NR-related drug development but are rarely reported. Here, we present the PbsNRs (Predicting binders and scaffolds for Nuclear Receptors), a user-friendly web server designed to predict the potential NR binders and scaffolds through proteochemometric modeling. The utility of PbsNRs was systemically evaluated using both chemical compounds and natural products. Results indicated that PbsNRs achieved a good prediction performance for chemical compounds on internal (ROC-AUC = 0.906, where ROC is Receiver-Operating Characteristic curve and AUC is the Area Under the Curve) and external (ROC-AUC = 0.783) datasets, outperforming both compound–ligand interaction tools and NR-specific predictors. PbsNRs also successfully identified bioactive chemical scaffolds for NRs by screening massive natural products. Moreover, the predicted bioactive and inactive natural products for NR2B1 were experimentally validated using biosensors. PbsNRs not only aids in screening potential therapeutic NR binders but also helps discover the essential molecular scaffold and guide the drug discovery for multiple NR-related diseases. The PbsNRs web server is available at http://pbsnrs.badd-cao.net.
Supervised analysis of alternative polyadenylation from single-cell and spatial transcriptomics data with spvAPA
Authors: Zhang Qinglong , Kang Liping , Yang Haoran , Liu Fei , Wu Xiaohui
Published: January 2025

Alternative polyadenylation (APA) is an important driver of transcriptome diversity that generates messenger RNA isoforms with distinct 3′ ends. The rapid development of single-cell and spatial transcriptomic technologies opened up new opportunities for exploring APA data to discover hidden cell subpopulations invisible in conventional gene expression analysis. However, conventional gene-level analysis tools are not fully applicable to APA data, and commonly used unsupervised dimensionality reduction methods often disregard experimentally derived annotations such as cell type identities. Here, we proposed a supervised analytical framework termed spvAPA, specifically used for APA analysis from both single-cell and spatial transcriptomics data. First, an iterative imputation method based on weighted nearest neighbor was designed to recover missing APA signatures, by integrating both gene expression and APA modalities. Second, a supervised feature selection method based on sparse partial least squares discriminant analysis was devised to identify APA features distinguishing cell types or spatial morphologies. Additionally, spvAPA improves the visualization of high-dimensional data for discovering novel cell subtypes, which considers APA features and dual modalities of gene expression and APA. Evaluations across nine single-cell and spatial transcriptomics datasets demonstrate the effectiveness and applicability of spvAPA. spvAPA is available at https://github.com/BMILAB/spvAPA.
PhyloMix: enhancing microbiome-trait association prediction through phylogeny-mixing augmentation
Authors: Jiang Yifan , Liao Disen , Zhu Qiyun , Lu Yang Young
Published: January 2025

Motivation

Understanding the associations between traits and microbial composition is a fundamental objective in microbiome research. Recently, researchers have turned to machine learning (ML) models to achieve this goal with promising results. However, the effectiveness of advanced ML models is often limited by the unique characteristics of microbiome data, which are typically high-dimensional, compositional, and imbalanced. These characteristics can hinder the models’ ability to fully explore the relationships among taxa in predictive analyses. To address this challenge, data augmentation has become crucial. It involves generating synthetic samples with artificial labels based on existing data and incorporating these samples into the training set to improve ML model performance.

Results

Here, we propose PhyloMix, a novel data augmentation method specifically designed for microbiome data to enhance predictive analyses. PhyloMix leverages the phylogenetic relationships among microbiome taxa as an informative prior to guide the generation of synthetic microbial samples. Leveraging phylogeny, PhyloMix creates new samples by removing a subtree from one sample and combining it with the corresponding subtree from another sample. Notably, PhyloMix is designed to address the compositional nature of microbiome data, effectively handling both raw counts and relative abundances. This approach introduces sufficient diversity into the augmented samples, leading to improved predictive performance. We empirically evaluated PhyloMix on six real microbiome datasets across five commonly used ML models. PhyloMix significantly outperforms distinct baseline methods including sample-mixing-based data augmentation techniques like vanilla mixup and compositional cutmix, as well as the phylogeny-based method TADA. We also demonstrated the wide applicability of PhyloMix in both supervised learning and contrastive representation learning.

Availability and implementation

The Apache-licensed source code is available at (https://github.com/batmen-lab/phylomix).
Funmap: integrating high-dimensional functional annotations to improve fine-mapping
Authors: Li Yuekai , Xiao Jiashun , Ming Jingsi , Zeng Yicheng , Cai Mingxuan
Published: January 2025

Motivation

Fine-mapping aims to prioritize causal variants underlying complex traits by accounting for the linkage disequilibrium of genome-wide association study risk locus. The expanding resources of functional annotations serve as auxiliary evidence to improve the power of fine-mapping. However, existing fine-mapping methods tend to generate many false positive results when integrating a large number of annotations.

Results

In this study, we propose a unified method to integrate high-dimensional functional annotations with fine-mapping (Funmap). Funmap can effectively improve the power of fine-mapping by borrowing information from hundreds of functional annotations. Meanwhile, it relates the annotation to the causal probability with a random effects model that avoids the over-fitting issue, thereby producing a well-controlled false positive rate. Paired with a fast algorithm, Funmap enables scalable integration of a large number of annotations to facilitate prioritizing multiple causal single nucleotide polymorphisms. Our comprehensive simulations across a wide range of annotation relevance settings demonstrate that Funmap is the only method that produces well-calibrated false discovery rate under the setting of high-dimensional annotations while achieving better or comparable power gains as compared to existing methods. By integrating genome-wide association studies of 4 lipid traits with 187 functional annotations, Funmap consistently identified more variants that can be replicated in an independent cohort, achieving 15.5%–26.2% improvement over the runner-up in terms of replication rate.

Availability and implementation

The Funmap software and all analysis code are available at https://github.com/LeeHITsz/Funmap.
PUPMCR: an R package for image-based identification of color based on Rayner’s (1970) terminology and known fungal pigments
Authors: Zapanta Niña Rose , Santos Rhenz Hannah , Pineda Jericho Ivan , Pedrosa Jireh Sealtiel , Rabelas Kristine Joyce , Samontan Charina , Alvarez Lourdes , Deocaris Chester
Published: January 2025

Fungi are eukaryotic organisms grouped based on different traits of their morphology. In 1970, R. W. Rayner published A Mycological Colour Chart to provide a standardized system for identifying color in fungi. While its terminologies have contributed a standard way of color matching for taxonomic diagnoses, this method using the personal color perception of the observer does not guarantee accuracy. Considering the diversity of fungi, visual color matching is expected to be challenging without a standard assisting instrument. In this study, the R package PUPMCR is developed to approximate the color name and associated pigments of fungal species based on the pixel coordinates of its uploaded image. This software utilizes CIELAB and RGB color spaces as well as Euclidean and Chi-square distance metric systems. The package is tested and validated using 300 fungal images as a dataset for conducting interrater reliability tests. Results showed the highest agreement for parameters utilizing the RGB color space (Cohen’s kappa values: 0.655 ± 0.013 for RGB and Euclidean; 0.658 ± 0.004 for RGB and Chi-square), attributed to its computational efficiency, which facilitates more uniform binning and universally scaled distance metrics. The produced color-identifying tool is also available as a Shiny web application (https://pupmcr.shinyapps.io/PUPMCR/) to allow better accessibility for users on the World Wide Web. The development of PUPMCR not only benefits a variety of users from its free accessibility but also provides a more reliable color identification system in the field of mycology.
Robust Bayesian graphical regression models for assessing tumor heterogeneity in proteomic networks
Authors: Yao Tsung-Hung , Ni Yang , Bhadra Anindya , Kang Jian , Baladandayuthapani Veerabhadran
Published: January 2025

Graphical models are powerful tools to investigate complex dependency structures in high-throughput datasets. However, most existing graphical models make one of two canonical assumptions: (i) a homogeneous graph with a common network for all subjects or (ii) an assumption of normality, especially in the context of Gaussian graphical models. Both assumptions are restrictive and can fail to hold in certain applications such as proteomic networks in cancer. To this end, we propose an approach termed robust Bayesian graphical regression (rBGR) to estimate heterogeneous graphs for non-normally distributed data. rBGR is a flexible framework that accommodates non-normality through random marginal transformations and constructs covariate-dependent graphs to accommodate heterogeneity through graphical regression techniques. We formulate a new characterization of edge dependencies in such models called conditional sign independence with covariates, along with an efficient posterior sampling algorithm. In simulation studies, we demonstrate that rBGR outperforms existing graphical regression models for data generated under various levels of non-normality in both edge and covariate selection. We use rBGR to assess proteomic networks in lung and ovarian cancers to systematically investigate the effects of immunogenic heterogeneity within tumors. Our analyses reveal several important protein–protein interactions that are differentially associated with the immune cell abundance; some corroborate existing biological knowledge, whereas others are novel findings.
The pathogenesis and management of heatstroke and heatstroke-induced lung injury
Authors: Liu Jian , Li Qin , Zou Zhimin , Li Li , Gu Zhengtao
Published: January 2025

In the past two decades, record-breaking heat waves have caused an increasing number of heat-related deaths, including heatstroke, globally. Heatstroke is a life-threatening systemic condition characterized by a core body temperature >40°C and the subsequent development of multiple organ dysfunction syndrome. Lung injury is a well-documented complication of heatstroke and is usually the secondary cause of patient death. In recent years, extensive research has been conducted to investigate the underlying causes of heatstroke and heatstroke-induced lung injury. This review aims to consolidate and present the current understanding of the key pathogenic mechanisms involved in heatstroke and heatstroke-induced lung injury. In addition, systemic factors such as heat cytotoxicity, systemic inflammation, oxidative stress, endothelial cell dysfunction, and other factors are involved in the pathogenesis of lung injury in heatstroke. Furthermore, we also established current management strategies for heatstroke and heatstroke-induced lung injury. However, further investigation is required to fully understand the detailed pathogenesis of heatstroke so that potentially effective means of treating and preventing heatstroke and heatstroke-induced lung injury can be developed and studied.
Childhood-onset inflammatory bowel disease and chronic non-bacterial osteomyelitis: a Swedish nationwide cohort study 2002-2022
Authors: Malmquist Marianne , Voghera Siri ,   The SWIBREG Study Group, Berg Stefan , Saalman Robert , Olén Ola
Published: January 2025

Background and Aims

Nationwide, population-based studies of chronic non-bacterial osteomyelitis (CNO) in patients with childhood-onset inflammatory bowel disease (IBD) are lacking.

Methods

We used nationwide registers to identify all children in Sweden diagnosed with IBD during 2002-2022 and the occurrence of CNO in this IBD cohort and general population non-IBD comparators. To estimate the temporal associations between IBD and CNO we used Cox regression. We compared clinical data for IBD patients with CNO (IBD+CNO) and the IBD patients without CNO.

Results

We identified 8244 children with IBD and 82 400 non-IBD comparators. At IBD diagnosis, CNO had been diagnosed in 0.13% (11/8244) of the IBD cohort and 0.03% (26/82 400) of the non-IBD comparators. During follow-up, 13 additional CNO cases occurred in the IBD cohort and 22 in the non-IBD comparators (adjusted hazard ratio = 5.87 [95% CI 2.95-11.66]). The prevalence of CNO among all prevalent children with IBD and prevalent matched non-IBD comparators December 31, 2022 was 0.48% (9/1885) and 0.02% (4/18 567), respectively. Median age at IBD diagnosis was lower in IBD + CNO compared to IBD without CNO (11 vs 14 years [−3 years, 95% CI −5 to −1]). Extraintestinal manifestations (except CNO) were more frequent in IBD + CNO (62% vs 21%, P < .0001). Treatment with biologics was more common in the IBD + CNO group (78% vs 44%, P = .004), prescribed for IBD and/or CNO.

Conclusions

We found a 6-fold increased risk of CNO in childhood-onset IBD compared to non-IBD comparators. Patients with IBD + CNO are characterized by younger age at IBD onset, more frequent extraintestinal manifestations, and higher usage of biologics.
Conserved ancillary residues situated proximally to the VIM-2 active-site affect its metallo β-lactamase activity
Authors: Jain Diamond , Ajith Tejavath , Verma Jyoti , Chatterjee Debasmita , Ghosh Anindya S
Published: January 2025

Verona-integron-metallo-β-lactamase (VIM-2) is one of the most widespread class B β-lactamase responsible for β-lactam resistance. Although active-site residues help in metal binding, the residues nearing the active-site possess functional importance. Here, to decipher the role of such residues in the activity and stability of VIM-2, the residues E146, D182, N210, S207, and D213 were selected through in-silico analyses and substituted with alanine using site-directed mutagenesis. The effects of substitution mutations were assessed by comparing the changes in β-lactam susceptibility pattern of Escherichia coli host cell expressing VIM-2 and its mutated proteins. VIM-2_N210A enhanced the susceptibility of the host by ∼4–8 folds against penicillins and cephalosporins, while the expression of VIM-2_D182A radically increased the susceptibility of host. However, expression of VIM-2_E146A reduced the susceptibility of host by 2-fold. Further, proteins were purified to homogeneity, and VIM_N210A and VIM_D182A displayed reduced thermal stability than VIM-2. Moreover, in vitro catalytic efficiencies of VIM-2_D182A were drastically reduced against all the β-lactams tested whereas the same were moderately reduced for VIM-2_N210A. Conversely, the catalytic efficiency was marginally altered for VIM_E146A. Overall, we infer that both N210A and D182A substitutions negatively affect the performance of VIM-2 by influencing substrate specificity and stability, respectively.
Similar, but not the same: multiomics comparison of human valve interstitial cells and osteoblast osteogenic differentiation expanded with an estimation of data-dependent and data-independent PASEF proteomics
Authors: Lobov Arseniy , Kuchur Polina , Boyarskaya Nadezhda , Perepletchikova Daria , Taraskin Ivan , Ivashkin Andrei , Kostina Daria , Khvorova Irina , Uspensky Vladimir , Repkin Egor , Denisov Evgeny , Gerashchenko Tatiana , Tikhilov Rashid , Bozhkova Svetlana , Karelkin Vitaly , Wang Chunli , Xu Kang , Malashicheva Anna
Published: January 2025

Osteogenic differentiation is crucial in normal bone formation and pathological calcification, such as calcific aortic valve disease (CAVD). Understanding the proteomic and transcriptomic landscapes underlying this differentiation can unveil potential therapeutic targets for CAVD. In this study, we employed RNA sequencing transcriptomics and proteomics on a timsTOF Pro platform to explore the multiomics profiles of valve interstitial cells (VICs) and osteoblasts during osteogenic differentiation. For proteomics, we utilized 3 data acquisition/analysis techniques: data-dependent acquisition (DDA)–parallel accumulation serial fragmentation (PASEF) and data-independent acquisition (DIA)–PASEF with a classic library-based (DIA) and machine learning–based library-free search (DIA-ML). Using RNA sequencing data as a biological reference, we compared these 3 analytical techniques in the context of actual biological experiments. We use this comprehensive dataset to reveal distinct proteomic and transcriptomic profiles between VICs and osteoblasts, highlighting specific biological processes in their osteogenic differentiation pathways. The study identified potential therapeutic targets specific for VICs osteogenic differentiation in CAVD, including the MAOA and ERK1/2 pathway. From a technical perspective, we found that DIA-based methods demonstrate even higher superiority against DDA for more sophisticated human primary cell cultures than it was shown before on HeLa samples. While the classic library-based DIA approach has proved to be a gold standard for shotgun proteomics research, the DIA-ML offers significant advantages with a relatively minor compromise in data reliability, making it the method of choice for routine proteomics.
Enhancing inbreeding estimation and global conservation insights through chromosome-level assemblies of the Chinese and Malayan pangolin
Authors: Lan Tianming , Tian Yinping , Shi Minhui , Liu Boyang , Lin Yu , Xia Yanling , Ma Yue , Sahu Sunil Kumar , Wang Qing , Li Jun , Chen Jin , Hou Fanghui , Yin Chuanling , Wang Kai , Fu Yuan , Que Tengcheng , Liu Wenjian , Liu Huan , Li Haimeng , Hua Yan
Published: January 2025

A high-quality reference genome coupled with resequencing data is a promising strategy to address issues in conservation genomics. This has greatly enhanced the development of conservation plans for endangered species. Pangolins are fascinating animals with a variety of unique features. Unfortunately, they are the most trafficked wild animal in the world. In this study, we assembled a chromosome-scale genome with HiFi long reads and Hi-C short reads for the Chinese and Malayan pangolin and provided two new representative reference genomes for the pangolin species. We found a great improvement in the evaluation of genetic diversity and inbreeding based on these high-quality genomes and obtained different results for the detection of genome-wide extinction risks compared with genomes assembled using short reads. Moderate inbreeding and genetic diversity were reverified in these two pangolin species, except for one Malayan pangolin population with high inbreeding and low genetic diversity. Moreover, we identified a much higher inbreeding level (FROH = 0.54) in the Chinese pangolin individual from Taiwan Province compared with that from Mainland China, but more than 99.6% runs of homozygosity (ROH) fragments were restricted to less than 1 Mb, indicating that the high FROH in Taiwan Chinese pangolins may have accumulated from historical inbreeding events. Furthermore, our study is the first to detect relatively mild genetic purging in pangolin populations. These two high-quality reference genomes will provide valuable genetic resources for future studies and contribute to the protection and conservation of pangolins.