bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel method for detection of Aβ and Iso-D7-Aβ N-terminus-specific B cells and Iso-D7-Aβ-specific antibodies
Authors: Kolobova Elizaveta A , Petrushanko Irina Yu , Mitkevich Vladimir A , Makarov Alexander A , Grigorova Irina L
Published: January 2025

Alzheimer’s disease (AD) is a multifactorial systemic disease that is triggered, at least in part, by the accumulation of β-amyloid (Aβ) peptides in the brain, but it also depends on immune system-mediated regulation. Recent studies suggest that B cells may play a role in AD development and point to the accumulation of clonally expanded B cells in AD patients. However, the specificity of the clonally expanded B cells is unknown, and the contribution of Aβ-specific B cells to AD pathology development is unclear. In this study, we have developed a novel method to identify Aβ-specific B cells by flow cytometry using fluorescent tetramers. The suggested method also enables the identification of B-cell clones specific to a more pathology-provoking form of Aβ with an isomerized Asp7 residue (Iso-D7-Aβ) that accumulates in elderly people and in AD patients. The method has been verified using mice immunized with antigens containing the isomerized or non-isomerized Aβ N-terminus peptides. In addition, we describe a new method for the detection of Iso-D7-Aβ-specific antibodies, which was tested on mouse serum. These methods are of potential importance in research aimed at studying AD and may be also utilized for diagnostic and therapeutic purposes.
Weighted Q-learning for optimal dynamic treatment regimes with nonignorable missing covariates
Authors: Sun Jian , Fu Bo , Su Li
Published: January 2025

Dynamic treatment regimes (DTRs) formalize medical decision-making as a sequence of rules for different stages, mapping patient-level information to recommended treatments. In practice, estimating an optimal DTR using observational data from electronic medical record (EMR) databases can be complicated by nonignorable missing covariates resulting from informative monitoring of patients. Since complete case analysis can provide consistent estimation of outcome model parameters under the assumption of outcome-independent missingness, Q-learning is a natural approach to accommodating nonignorable missing covariates. However, the backward induction algorithm used in Q-learning can introduce challenges, as nonignorable missing covariates at later stages can result in nonignorable missing pseudo-outcomes at earlier stages, leading to suboptimal DTRs, even if the longitudinal outcome variables are fully observed. To address this unique missing data problem in DTR settings, we propose 2 weighted Q-learning approaches where inverse probability weights for missingness of the pseudo-outcomes are obtained through estimating equations with valid nonresponse instrumental variables or sensitivity analysis. The asymptotic properties of the weighted Q-learning estimators are derived, and the finite-sample performance of the proposed methods is evaluated and compared with alternative methods through extensive simulation studies. Using EMR data from the Medical Information Mart for Intensive Care database, we apply the proposed methods to investigate the optimal fluid strategy for sepsis patients in intensive care units.
Efficacy of extracorporeal photopheresis in treating severe erosive lichen planus: a case series
Authors: Loretan Audrey , Cortes Begonia
Published: January 2025

There are currently no good, evidence-based recommendations for any systemic treatment of erosive lichen planus (ELP). Extracorporeal photopheresis (ECP) may be an effective treatment for recalcitrant forms of this disease. We report three patients with severe ELP who were treated with ECP. Objective clinical responses as assessed by a dermatologist, subjective responses as reported by the patients, and recorded adverse events were monitored. Each patient showed a partial response of cutaneous, oral and genital lesions. Oesophageal lesions were more resistant to the treatment. The findings in the patients reported here, in addition to the 38 other cases reported in the literature, strongly support the value of ECP in the treatment of ELP. ECP may be effective as a salvage treatment option for ELP refractory to current treatments. Owing to the lack of side-effects of ECP, in contrast to other treatments, ECP is a potentially useful treatment option when immunosuppressive drugs are contraindicated.
Paediatrics and genetics
Authors: Boyle Aoife , Moloney Fergal J
Published: January 2025

We present the case of a 40-year-old man who was referred to dermatology for the evaluation of cutaneous manifestations of a genetic disorder with known ocular involvement.
Mission P(D)ossible: peritoneal dialysis in difficult cases
Authors: Lehmann Kijanosh , Reubke Benjamin , Wanninger Reinhard , Lindgren Manuela , Glowka Tim R , Kielstein Jan T , Eden Gabriele
Published: January 2025

Indications for peritoneal dialysis (PD) have undergone a paradigm shift in recent years. Medical barriers previously viewed as contraindications for PD such as anuria, autosomal dominant polycystic kidney disease, cardiovascular diseases or advanced age are increasingly re-examined. We learned that establishing a safe, functional and durable catheter access can be established even in patients with a variety of co-morbidities. Moreover, conditions that predispose to catheter-related infections and peritonitis are not as obvious as we thought. In this case-based review we present patients who have been performing PD for a long time and in whom PD might still be viewed unfeasible. The aim of the paper is to underline the importance of PD as a kidney replacement therapy with fewer medical limits than previously thought. It is also a plaidoyer for interdisciplinary and interprofessional collaboration. This ‘Mission PD-possible’ should be accompanied by a coordinated approach aligning policy, organizational structures and financial resources.
Toxic effects of eight azole fungicides on the growth, photosynthetic activity, and oxidative stress of Raphidocelis subcapitata
Authors: Huang Yongxiang , Guo Dijie , Qin Litang , Mo Lingyun , Zhao Yuqing
Published: January 2025

This study investigates the 96 hours toxicity and physiological effects of eight azole fungicides on Raphidocelis subcapitata (R. subcapitata). The findings revealed significant differences in toxicity levels among these fungicides, with the hierarchy of toxicity as follows: Difenoconazole (DIF) ≈ Tetraconazole (TET) ≈ Fuberidazole (FUB) > Metconazole (MET) > Terrazole (TER) ≈ Triflumizole (TRI) > Flutriafol (FLU) > Hymexazol (HYM). Increased concentrations of azole fungicides corresponded with decreased cellular activity and inhibited algal growth, highlighting the concentration-dependent nature of toxicity. The toxicological mechanisms involved include reduced levels of chlorophyll (Chla, Chlb) and carotenoids (Car), disrupting the photosynthetic process. Additionally, exposure to these fungicides resulted in decreased total protein (TP) levels, increased reactive oxygen species (ROS) and malondialdehyde (MDA), and elevated activity of antioxidant enzymes like superoxide dismutase (SOD) and catalase (CAT). Consequently, there was a significant rise in apoptosis rates among algal cells. These findings provide important insights for assessing the ecological impact of azole fungicides on aquatic ecosystems and aquatic life.
Dimensionality reduction for visualizing spatially resolved profiling data using SpaSNE
Authors: Zhou Yuansheng , Tang Chen , Xiao Xue , Zhan Xiaowei , Wang Tao , Xiao Guanghua , Xu Lin
Published: January 2025

Background

Spatially resolved profiling technologies to quantify transcriptomes, epigenomes, and proteomes have been emerging as groundbreaking methods for comprehensive molecular characterizations. Dimensionality reduction and visualization is an essential step to analyze and interpret spatially resolved profiling data. However, state-of-the-art dimensionality reduction methods for single-cell sequencing data, such as the t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), were not tailored for spatially resolved profiling data.

Results

Here we developed a spatially resolved t-SNE (SpaSNE) method to integrate both spatial and molecular information. We applied it to a variety of public spatially resolved profiling datasets that were generated from 3 experimental platforms and consisted of cells from different diseases, tissues, and cell types. To compare the performances of SpaSNE, t-SNE, and UMAP, we applied them to 4 spatially resolved profiling datasets obtained from 3 distinct experimental platforms (Visium, STARmap, and MERFISH) on both diseased and normal tissues. Comparisons between SpaSNE and these state-of-the-art approaches reveal that SpaSNE achieves more accurate and meaningful visualization that better elucidates the underlying spatial and molecular data structures.

Conclusions

This work demonstrates the broad application of SpaSNE for reliable and robust interpretation of cell types based on both molecular and spatial information, which can set the foundation for many subsequent analysis steps, such as differential gene expression and trajectory or pseudotime analysis on the spatially resolved profiling data.
Elevated LINC00115 expression correlates with aggressive endometrial cancer phenotypes via JAK/STAT pathway modulation
Authors: Zhao Zheqi , Liu Yangyang , Wang Mengyao , Wei Aiwu
Published: January 2025

This study systematically explores the oncogenic role of the long non-coding RNA (lncRNA) LINC00115 in endometrial cancer (EC) and reveals its unique mechanism in promoting proliferation, invasion, and metastasis via the JAK/STAT signaling pathway. LINC00115 is significantly upregulated in EC tissues and closely associated with advanced TNM staging and lymph node metastasis. Functional assays showed that knockdown of LINC00115 suppressed EC cell proliferation, invasion, and metastasis, while overexpression enhanced these malignant behaviors. In vivo models confirmed that LINC00115 overexpression accelerates tumor growth and metastasis. Our study is the first to identify LINC00115 as a key activator of the JAK/STAT pathway through direct interaction with KH-type Splicing Regulatory Protein (KHSRP), a previously unrecognized mechanism in EC. This finding provides new insights into lncRNA-mediated signaling regulation and highlights LINC00115 as a novel biomarker and promising therapeutic target for EC, offering a theoretical basis for developing targeted therapies.
Monitoring molecular markers associated with antimalarial drug resistance in south-east Senegal from 2021 to 2023
Authors: Wade Alioune , Sene Seynabou D , Caspar Emanuelle , Diallo Fatoumata , Platon Lucien , Thiebaut Lucas , Pouye Mariama N , Ba Aboubacar , Thiam Laty Gaye , Fall Magal , Sadio Bacary Djilocalisse , Desamours Ife , Guerra Noemi , Hagadorn Kelly , Amambua-Ngwa Alfred , Bei Amy K , Vigan-Womas Ines , Ménard Didier , Mbengue Alassane
Published: January 2025

Background

Since 2006, artemisinin-based combination therapies (ACTs) have been introduced in Senegal in response to chloroquine resistance (CQ-R) and have shown high efficacy against Plasmodium falciparum. However, the detection of the PfKelch13R515K mutation in Kaolack, which confers artemisinin resistance in vitro, highlights the urgency of strengthening antimalarial drug surveillance to achieve malaria elimination by 2030.

Objective

To assess the proportion of P. falciparum parasites carrying molecular signatures associated with antimalarial resistance (PfKelch13, Pfmdr1, Pfcrt, dhfr and dhps) in isolates collected at Kédougou using multiplex amplicon deep sequencing.

Methods

Venous blood samples were collected from patients diagnosed with P. falciparum infection over a 3-year period (2021, 2022 and 2023). Parasite DNA was extracted, and multiplex amplicon sequencing was used to investigate gene polymorphisms.

Results

Analysis of PfKelch13 did not reveal any non-synonymous mutations. Pfcrt mutations were present in 45% of the samples, mainly K76T (44%) and I356T (36%). The dominant Pfmdr-1 allele was Y184F (62%). The sextuple mutant 51I/59R/108N + 436A/437G/613S dhfr/dhps was observed in 10% of the samples.

Conclusion

The absence of PfKelch13 mutants suggests that ACT efficacy remains uncompromised, although clinical outcome studies are required to confirm this. Analysis of Pfcrt and Pfmdr-1 shows that CQ-R alleles, probably from previous CQ use, are slowly decreasing. Likewise, the detection of the dhfr/dhps sextuple mutant highlights the need to monitor sulfadoxine-pyrimethamine resistance and the emergence of 581G. There is therefore a need for continued antimalarial resistance surveillance in Senegal.
Assessing Artificial Intelligence (AI) Implementation for Assisting Gene Linking (at the National Library of Medicine)
Authors: Islamaj Rezarta , Wei Chih-Hsuan , Lai Po-Ting , Huston Melanie , Coss Cathleen , Kochar Preeti Gokal , Miliaras Nicholas , Mork James G , Rodionov Oleg , Sekiya Keiko , Trinh Dorothy , Whitman Deborah , Wallin Craig , Lu Zhiyong
Published: January 2025

Objectives

The National Library of Medicine (NLM) currently indexes close to a million articles each year pertaining to more than 5300 medicine and life sciences journals. Of these, a significant number of articles contain critical information about the structure, genetics, and function of genes and proteins in normal and disease states. These articles are identified by the NLM curators, and a manual link is created between these articles and the corresponding gene records at the NCBI Gene database. Thus, the information is interconnected with all the NLM resources, services which bring considerable value to life sciences. National Library of Medicine aims to provide timely access to all metadata, and this necessitates that the article indexing scales to the volume of the published literature. On the other hand, although automatic information extraction methods have been shown to achieve accurate results in biomedical text mining research, it remains difficult to evaluate them on established pipelines and integrate them within the daily workflows.

Materials and Methods

Here, we demonstrate how our machine learning model, GNorm2, which achieved state-of-the art performance on identifying genes and their corresponding species at the same time handling innate textual ambiguities, could be integrated with the established daily workflow at the NLM and evaluated for its performance in this new environment.

Results

We worked with 8 biomedical curator experts and evaluated the integration using these parameters: (1) gene identification accuracy, (2) interannotator agreement with and without GNorm2, (3) GNorm2 potential bias, and (4) indexing consistency and efficiency. We identified key interface changes that significantly helped the curators to maximize the GNorm2 benefit, and further improved the GNorm2 algorithm to cover 135 species of genes including viral and bacterial genes, based on the biocurator expert survey.

Conclusion

GNorm2 is currently in the process of being fully integrated into the regular curator’s workflow.
Challenges Facing the Appeal to Practical Wisdom in Medicine and Beyond
Authors: Miller Christian B
Published: January 2025

As work on practical wisdom and medicine accelerates, now is a good time to outline some important challenges that any approach to developing an account of this virtue faces. More specifically, I develop five challenges having to do with the existence and nature of practical wisdom, and whether it connects with objective and general normative truths. The main goal is to provide a guide to the challenges themselves and some of the options available for tackling them, rather than trying to resolve them here.
Perianal abscess complicated by histiocytic necrotizing lymphadenitis postoperatively: a case report
Authors: Zhang Liman , Yang Jie , Wang Lili , Zhang Tianpeng , Ju Fei , Wu Yanjang
Published: January 2025

Histiocytic necrotizing lymphadenitis (HNL) is a rare condition presenting with lymphadenopathy and fever. We report a case of a 61-year-old male with a history of perianal abscess surgery who developed HNL postoperatively. The patient was treated with corticosteroids, leading to resolution of fever and alleviation of symptoms. This case emphasizes the need for clinical vigilance for HNL in patients with a history of perianal abscess surgery and postoperative fever with lymph node enlargement.
Study protocol for the development of a pouch anal and vaginal fistula core outcome measurement set (PAVFCOMS)
Authors: Anand Easan , Joshi Shivani , Reza Lillian , Sahnan Kapil , Lung Phillip , Hart Ailsa , Tozer Phil
Published: January 2025

Pouch-related fistulae, such as pouch-anal and pouch-vaginal fistulae, are serious complications that impact ⁓5% of patients undergoing ileoanal pouch surgery, frequently leading to pouch failure. Research on treatment options is limited by small studies with inconsistent outcome reporting. To address this, the Pouch Anal and Vaginal Fistula Core Outcome Set (PAVFCOS) was developed, identifying seven key outcomes through stakeholder consensus. This study aims to create a core outcome measurement set (PAVFCOMS) to standardize how outcomes are measured in pouch fistula treatment, in line with Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines. PAVFCOMS will incorporate validated patient-reported (PROMs) and clinician-reported (ClinROMs) outcome measures to provide a standardized tool for future clinical research. The study follows a two-phase process per COSMIN guidance. Phase one involves a systematic review to identify and assess current measurement instruments used in pouch fistula research and has been prospectively registered on PROSPERO (CRD42024505563). The second phase uses a Delphi process with international stakeholders, including patients, surgeons, gastroenterologists, radiologists and nurses, to reach consensus on the final measurement set. This will identify measurement instrument gaps and select the best available tools for each outcome. Reporting will adhere to ACCORD guidelines. This is the first international consensus to establish a core outcome measurement set for pouch fistula research. Standardized outcome measurement will enhance trial quality and facilitate stronger systematic reviews and meta-analyses. A key strength of this study is its patient-centred approach, ensuring the relevance of outcomes to the patient community, reflecting their lived experiences with pouch fistulae.
Performance of chest CT-based artificial intelligence models in distinguishing pulmonary mucormycosis, invasive pulmonary aspergillosis, and pulmonary tuberculosis
Authors: Li Yun , Chen Deyan , Zhang Youwen , Liu Shuyi , Liang Lina , Tan Lunfang , Yang Fan , Li Yuyan , Peng Chengbao , Ye Feng , Zhang Xia , Hu Guodong , Chen Huai , Zheng Jinping
Published: January 2025

In clinical practice, differentiating among pulmonary mucormycosis (PM), invasive pulmonary aspergillosis (IPA), and pulmonary tuberculosis (PTB) can be challenging. We aimed to evaluate the performance of chest CT-based artificial intelligence (AI) models in distinguishing among these three diseases. Patients with confirmed PM, IPA, or PTB were retrospectively recruited from three tertiary hospitals. Two models were developed: the unannotated supervised training (UST) model, trained with original CT images and the annotated supervised training (AST) model, trained with manually annotated lesion images. A network questionnaire with 20 cases was designed to assess the performance of clinicians. Sensitivity, specificity, and accuracy were calculated for both models and clinicians. A total of 61 PM cases, 136 IPA cases, and 155 PTB cases were included in the study. In the internal validation set, both models had an accuracy of 66.1%. The UST model had sensitivities of 27.3%, 73.9%, and 76.0% for PM, IPA, and PTB, while the AST model had sensitivities of 9.1%, 69.6%, and 88.0% for the same conditions. In the external validation set, both models had an accuracy of 57.6%. The UST model had sensitivities of 0, 85.7%, and 53.3% for PM, IPA, and PTB, respectively, while AST model had sensitivities of 0, 42.9% and 83.3%. A total of 112 clinicians had an accuracy of 42.9%, with sensitivities of 31.5%, 43.4%, and 48.0% for PM, IPA, and PTB. We demonstrated that two AI models showed comparable performance in diagnosing three diseases. Both models effectively detected IPA and PTB but struggled to identify PM.
Reionization morphology and intrinsic velocity offsets allow transmission of Lyman-α emission from JADES-GS-z13-1-LA
Authors: Qin Yuxiang , Wyithe J Stuart B
Published: January 2025

We investigate the detectability of Lyman-$\alpha$ (Ly $\alpha$) emission from galaxies at the onset of cosmic reionization, aiming to understand the conditions necessary for detecting high-redshift sources like JADES-GS-z13-1-LA at $z=13$. By integrating galaxy formation models with detailed intergalactic medium (IGM) reionization simulations, we construct high-redshift galaxy catalogues to model intrinsic Ly $\alpha$ profiles and assess their transmission through the IGM. For a galaxy with $M_{\rm UV}\sim -18.5$ like JADES-GS-z13-1-LA, our fiducial model predicts a Ly $\alpha$ transmission of ${\sim }13$ per cent and there is a probability of observing Ly $\alpha$ emission with an equivalent width $\gt 40$ Å of up to 10 per cent. We also explore how variations in the UV ionizing escape fraction, dependent on host halo mass or specific star formation rate, impact Ly $\alpha$ detectability. Our findings reveal that reionization morphology significantly influences detection chances – models where reionization is driven by low-mass galaxies can boost the detection probability to as much as 12 per cent, while those driven by massive galaxies tend to reduce ionized regions around faint emitters, limiting their detectability. Our findings remain robust when further accounting for stochastic star formation with the detection probability still spanning 3 per cent to 12 per cent. This study underscores the interplay between reionization morphology and intrinsic galaxy properties in interpreting high-redshift Ly $\alpha$ observations.
Faithful Interpretation of Protein Structures through Weighted Persistent Homology Improves Evolutionary Distance Estimation
Authors: Bou Dagher Léa , Madern Dominique , Malbos Philippe , Brochier-Armanet Céline
Published: January 2025

Phylogenetic inference is mainly based on sequence analysis and requires reliable alignments. This can be challenging, especially when sequences are highly divergent. In this context, the use of three-dimensional protein structures is a promising alternative. In a recent study, we introduced an original topological data analysis method based on persistent homology to estimate the evolutionary distances from structures. The method was successfully tested on 518 protein families representing 22,940 predicted structures. However, as anticipated, the reliability of the estimated evolutionary distances was impacted by the quality of the predicted structures and the presence of indels in the proteins. This paper introduces a new topological descriptor, called bio-topological marker (BTM), which provides a more faithful description of the structures, a topological analysis for estimating evolutionary distances from BTMs, and a new weight-filtering method adapted to protein structures. These new developments significantly improve the estimation of evolutionary distances and phylogenies inferred from structures.
Specifying cellular context of transcription factor regulons for exploring context-specific gene regulation programs
Authors: Minaeva Mariia , Domingo Júlia , Rentzsch Philipp , Lappalainen Tuuli
Published: January 2025

Understanding the role of transcription and transcription factors (TFs) in cellular identity and disease, such as cancer, is essential. However, comprehensive data resources for cell line-specific TF-to-target gene annotations are currently limited. To address this, we employed a straightforward method to define regulons that capture the cell-specific aspects of TF binding and transcript expression levels. By integrating cellular transcriptome and TF binding data, we generated regulons for 40 common cell lines comprising both proximal and distal cell line-specific regulatory events. Through systematic benchmarking involving TF knockout experiments, we demonstrated performance on par with state-of-the-art methods, with our method being easily applicable to other cell types of interest. We present case studies using three cancer single-cell datasets to showcase the utility of these cell-type-specific regulons in exploring transcriptional dysregulation. In summary, this study provides a valuable pipeline and a resource for systematically exploring cell line-specific transcriptional regulations, emphasizing the utility of network analysis in deciphering disease mechanisms.
vClean: assessing virus sequence contamination in viral genomes
Authors: Wagatsuma Ryota , Nishikawa Yohei , Hosokawa Masahito , Takeyama Haruko
Published: January 2025

Recent advancements in viral metagenomics and single-virus genomics have improved our ability to obtain the draft genomes of environmental viruses. However, these methods can introduce virus sequence contaminations into viral genomes when short, fragmented partial sequences are present in the assembled contigs. These contaminations can lead to incorrect analyses; however, practical detection tools are lacking. In this study, we introduce vClean, a novel automated tool that detects contaminations in viral genomes. By applying machine learning to the nucleotide sequence features and gene patterns of the input viral genome, vClean could identify contaminations. Specifically, for tailed double-stranded DNA phages, we attempted accurate predictions by defining single-copy-like genes and counting their duplications. We evaluated the performance of vClean using simulated datasets derived from complete reference genomes, achieving a binary accuracy of 0.932. When vClean was applied to 4693 genomes of medium or higher quality derived from public ocean metagenomic data, 1604 genomes (34.2%) were identified as contaminated. We also demonstrated that vClean can detect contamination in single-virus genome data obtained from river water. vClean provides a new benchmark for quality control of environmental viral genomes and has the potential to become an essential tool for environmental viral genome analysis.
ProPr54 web server: predicting σ54 promoters and regulon with a hybrid convolutional and recurrent deep neural network
Authors: Achterberg Tristan , de Jong Anne
Published: January 2025

σ54 serves as an unconventional sigma factor with a distinct mechanism of transcription initiation, which depends on the involvement of a transcription activator. This unique sigma factor σ54 is indispensable for orchestrating the transcription of genes crucial to nitrogen regulation, flagella biosynthesis, motility, chemotaxis and various other essential cellular processes. Currently, no comprehensive tools are available to determine σ54 promoters and regulon in bacterial genomes. Here, we report a σ54 promoter prediction method ProPr54, based on a convolutional neural network trained on a set of 446 validated σ54 binding sites derived from 33 bacterial species. Model performance was tested and compared with respect to bacterial intergenic regions, demonstrating robust applicability. ProPr54 exhibits high performance when tested on various bacterial species, highly surpassing other available σ54 regulon identification methods. Furthermore, analysis on bacterial genomes, which have no experimentally validated σ54 binding sites, demonstrates the generalization of the model. ProPr54 is the first reliable insilico method for predicting σ54 binding sites, making it a valuable tool to support experimental studies on σ54. In conclusion, ProPr54 offers a reliable, broadly applicable tool for predicting σ54 promoters and regulon genes in bacterial genome sequences. A web server is freely accessible at http://propr54.molgenrug.nl.
PSAURON: a tool for assessing protein annotation across a broad range of species
Authors: Sommer Markus J , Zimin Aleksey V , Salzberg Steven L
Published: January 2025

Evaluating the accuracy of protein-coding sequences in genome annotations is a challenging problem for which there is no broadly applicable solution. In this manuscript, we introduce PSAURON (Protein Sequence Assessment Using a Reference ORF Network), a novel software tool developed to help assess the quality of protein-coding gene annotations. Utilizing a machine learning model trained on a diverse dataset from over 1000 plant and animal genomes, PSAURON assigns a score to coding DNA or protein sequence that reflects the likelihood that the sequence is a genuine protein-coding region. PSAURON scores can be used for genome-wide protein annotation assessment as well as the rapid identification of potentially spurious annotated proteins. Validation against established benchmarks demonstrates PSAURON’s effectiveness and correlation with recognized measures of protein quality, highlighting its potential use as a widely applicable method to evaluate precision in gene annotation. PSAURON is open source and freely available at https://github.com/salzberg-lab/PSAURON.
Indigenous Science Education and STEM-related Education
Authors: Marin Ananda , Barry Nikki , White Eyes Renee , DeerInWater Kathy , Bang Megan , Bruce Forrest Hunter
Published: January 2025

Education broadly conceived includes the when, where, why, and how of teaching, learning, and maturation. From this perspective education takes shape and evolves across many contexts, including familial and kin relations; informal settings such as community-based organizations, museums, and libraries; and school settings from early childhood to post-secondary. Science, like education, is concerned with the how and why of things. Indigenous science education is grounded in the philosophical, intellectual, emotional, and spiritual traditions and practices of Indigenous knowledge systems (IKS). IKS is holistic, relational, and informed by experience in and with the natural world. Although IKS are tribally specific, there are commonalities and shared practices across communities. Indigenous knowledge systems ground much of Indigenous science education. While some principles of IKS and Indigenous science education that we discuss will apply to Indigenous peoples globally, there are also important differences to hold across geopolitical contexts. Rather than collapsing the vast heterogeneity of global indigeneity into a single category, we found it important to limit our scope. Furthermore, it may be inappropriate for the authors—Indigenous people from nations who largely reside within the borders of what is currently considered the United States and Canada—to reach beyond this scope. At the same time, we would be remiss if we did not acknowledge that there is important research within the field of comparative Indigenous education that speaks to connections between the local and the global. In addition, Indigenous peoples globally have traded, collaborated, and exchanged knowledge since time immemorial, and they continue to do so. IKS has taught us, the authors, to view reading and writing as activities that carry with them responsibilities for being in a relation with knowledge. Thus, this article is structured to provide relevant studies, reports, and resources on Indigenous science education and STEM-related education contextualized within what is currently known as the United States and Canada. And in this context, the authors use both Native and Indigenous interchangeably throughout this bibliography. The article is organized around four main sections: (1) Paradigms for Indigenous Science Education, (2) Indigenous Science Education across the Life-Span, (3) Curriculum and Assessments within Indigenous Science Education, and (4) Professional Organizations, Key Reports, and Books.
Environmental Justice
Authors: Wells E. Christian
Published: January 2025

The unfolding global environmental crises ushered in by late industrialism—from contamination to climate change—pose grave threats to human and environmental health, and yet not everyone shares these burdens and risks equally. An extensive body of scholarship on “health disparities” and “environmental inequalities” has emerged since the 1980s that demonstrates unequivocally how people of color, Indigenous and tribal communities, and other marginalized groups are disproportionately exposed to environmental pollutants and contaminants and suffer the consequences of these conditions for their health and well-being. These conditions exist as an integral and deeply embedded component of structural racism, as expressed and experienced through, for example, residential segregation and the social determinants of health. Following on the successful tactics deployed in the US civil rights movement in the 1950s-1960s, including coalition building, community empowerment, litigation, and other forms of nonviolent direct action, scholars and activists have leveraged these practices to demand that everyone, regardless of race or class, has a right to the same environmental protections and meaningful involvement in shaping environmental policies in their communities. This process is often referred to as “environmental justice” and has evolved over the past half century to integrate both a social movement and a scholarly mode of inquiry. For many, this merger has catalyzed new forms of “liberation science” that leverage community-based, participatory approaches to advance health equity by emancipating people from toxic environments. While the environmental justice movement started in the United States, it has grown to become a global, postcolonial effort aimed at advancing the wellbeing of Black, Indigenous, and People of the Global Majority (BIPGM) including disadvantaged racial and ethnic groups, Indigenous peoples, and those living in poverty. Since 2008, the journal Environmental Justice has provided a key source of scholarship for the field.
Collaborative governance in politicized times: the battle over asylum policies in Italian cities
Authors: Bazurli Raffaele , Campomori Francesca
Published: January 2025

Collaborative governance has gained momentum for its promise to deliver social inclusion, with municipalities viewed as ideal spaces for its success. However, little research critically examines the political conditions under which this is the case. This article theorizes why and how collaborative local governance succeeds or fails in today’s divided democracies. It argues that politicization manifests in three dimensions of local governance—among stakeholders, across government levels, and in the framing of policy target groups. These dynamics often incentivize the exclusion of marginalized populations. For collaboration to succeed, it must be anchored in an ideologically cohesive network of stakeholders, with civil society organizations acting as political advocates for disadvantaged groups. Drawing on fieldwork conducted in 2018–2022, we compare asylum policies in two Italian cities: Bologna and Venice. Despite rising far-right politics nationally, Bologna’s collaborative governance persisted thanks to the sustained commitment of local officials and civil society actors, all sharing ideological and strategic motivations in promoting refugee rights. In contrast, anti-migrant politics has increasingly informed the policy agenda of Venice elected officials. The politicization of immigration offered them powerful incentives to wipe out long-established collaborations and to frame refugees as undeserving policy targets, leading to their exclusion from public services. These findings extend to other geographical contexts and policy sectors, calling for a more political understanding of collaborative local governance.
Who’s to blame for the Brazilian nuclear program never coming of age?
Authors: Nicolini Gabriel João Paulo , Belém Lopes Dawisson
Published: January 2025

The article examines Brazil’s attempt to establish a national nuclear industry during its military regime (1964–85), focusing on the 1975 nuclear agreement with West Germany. Based on extensive document analysis and interviews, this study reveals that despite the agreement’s goal of reducing dependence on US technology, it reinforced Brazil’s reliance on foreign sources and highlighted flaws in its Science and Technology strategy. The technocratic elite, or “nucleocracy,” prioritized rapid development over nurturing domestic research, sidelining academic and industrial stakeholders. The article employs the National Innovation Systems framework, particularly the triple helix model, to demonstrate how insufficient collaboration between academia, industry, and government hindered the establishment of a self-sufficient nuclear sector. The findings underscore that international scientific collaborations, while intended to foster technological autonomy, can paradoxically entrench dependence when domestic capacity-building is neglected.
A point mutation in the pepper veinal mottle virus 6K1 protein yields a stable attenuated strain for engineering virus resistance in pepper plants
Authors: Deng Changhui , Hu Weiyao , Shen Wen-tao , Li Fangfang , Dai Zhaoji , Cui Hongguang
Published: January 2025

A total of 164 viruses have been identified in peppers worldwide. To combat viruses, pathogen-derived resistance (PDR) has been employed by expressing a viral genomic segment or a viral protein in host plants. Unfortunately, peppers are recalcitrant to genetic transformation and regeneration. An alternative strategy is to generate PDR in pepper plants by using an attenuated virus-based expression vector. In a previous study on the function of pepper veinal mottle virus (PVMV) 6K1 protein, we mutated a conserved Ala with Arg (A15R), and a second mutation R15G was observed in virus progeny. In this study, we demonstrated that mutating Ala to Gly (A15G) in the 6K1 yield a stable attenuated strain (named PVMV-G-A15G). PVMV-G-A15G can cross-protect pepper plants against a severe strain of PVMV and its close relative, chilli veinal mottle virus. We then engineered PVMV-G-A15G into a viral expression vector that has the Golden Gate cloning feature. To examine if the PVMV vector can be used to mediate PDR, we inserted the complete CP sequence of potato virus X (PVX) into the engineered PVMV-G-A15G. Pre-inoculated plants with the recombinant PVMV-G-A15G that carries the PVX CP sequence are resistant to PVX infection. Taken together, our research demonstrates that the attenuated PVMV can be employed for delivering target virus sequence to mediate PDR.
Signaling via retinoic acid receptors mediates decidual angiogenesis in mice and human stromal cell decidualization
Authors: Zhao Qingshi , Samuels Cherie‐Ann , Timmins Patrick , Massri Noura , Chemerinski Anat , Wu Tracy , Loia Rachel , Cheung Emma K. , Zhang Xusheng , Arora Ripla , Babwah Andy V. , Douglas Nataki C.
Published: January 2025

At the maternal‐fetal interface, tightly regulated levels of retinoic acid (RA), the physiologically active metabolite of vitamin A, are required for embryo implantation and pregnancy success. Herein, we utilize mouse models, primary human cells, and pharmacological tools to demonstrate how depletion of RA signaling via RA receptor (RAR) disrupts implantation and progression of early pregnancy. To inhibit RAR signaling during early pregnancy, BMS493, an inverse pan‐RAR agonist that prevents RA‐induced differentiation, was administered to pregnant mice during the peri‐implantation period. Attenuation of RA/RAR signaling prior to embryo implantation results in implantation failure, whereas attenuation of RA/RAR signaling after embryo implantation disrupts the post‐implantation decidual vasculature and results in pregnancy failure by mid‐gestation. To inhibit RAR signaling during human endometrial stromal cell (HESC) decidualization, primary HESCs and decidualized primary HESCs were transfected with silencing RNA specific for human RARA. Inhibition of RA/RARA signaling prevents initiation of HESC decidualization, but not maintenance of the decidualized HESC phenotype. These data show that RA/RAR signaling is required for maintenance of the decidual vasculature that supports early pregnancy in mice, and distinct RAR signaling is required for initiation, but not maintenance of primary HESC decidualization in vitro.
Mechanical Failure of the Stryker T2 Alpha Retrograde Femoral Nail
Authors: Lopas Luke A. , Soni Chirag , Natoli Roman M. , Jang Yohan , Milburn Mason , McKinley Todd O. , Mullis Brian , Szatkowski Jan P.
Published: January 2025

OBJECTIVE:

To evaluate mechanical failure rates of retrograde femoral nails in the treatment of distal femur fractures.

METHODS:

Design: Retrospective chart review.

Setting:

Urban Academic Level 1 Trauma Center.

Patient Selection Criteria:

Included were adult patients who sustained a distal femur fracture (AO/OTA 33) who were treated with a retrograde intramedullary nail from August 2021 through September 2022.

Outcome Measures and Comparisons:

The primary outcome was the rate of mechanical failure of the intramedullary nail defined as deformation and/or breakage of the intramedullary nail. The rate of mechanical failure was compared amongst retrograde femoral nails used at the same institution during the same time period.

RESULTS:

One hundred and twenty distal femur fractures were identified (77 native distal femur, 43 periprosthetic) that were treated with a retrograde intramedullary nail. Average patient age was 67 years (SD 15.1, range 18-96 years). Eighty-three (69.2%) of patients were female. Four mechanical nail failures (deformation and/or breakage of the intramedullary nail) were observed within six months of surgery, two in patients with native distal femur fractures, and two in patients with periprosthetic distal femur fractures. All failures occurred among forty-nine fractures treated with a newly released retrograde femoral nail, the T2 Alpha Retrograde Femoral Nail (Stryker, Mahwah, NJ). This represents an 8.2% mechanical failure rate of distal femur fractures treated with this new nail compared to no failures observed with any other nail (p=0.03).

CONCLUSIONS:

Mechanical nail failures, within six months of surgery for distal femur fracture, of a new retrograde femoral nail were observed to be higher than seen with other nails. Further evaluation is needed to determine if this experience represents factors related to patient, injury, or surgical characteristics, an anomaly, or a safety signal.

Level Of Evidence:

Therapeutic Level III. See instructions for authors for a complete description of levels of evidence.
Inpatient Multimodal Pain Regimens Do Not Impact Hospital Length of Stay or Long-term Postoperative Opioid Use Following 1 and 2-Level Lumbar Fusion
Authors: Carter Michael , Narayanan Rajkishen , Toci Gregory , Lee Yunsoo , Fras Sebastian , Hammelef Emma , Mumtaz Shiraz , Garayo Tasha , Kurd Mark , Kaye Ian David , Canseco Jose , Hilibrand Alan , Vaccaro Alexander , Kepler Christopher , Schroeder Gregory
Published: January 2025

Study Design:

Retrospective cohort study.

Objective:

To determine hospital length of stay (LOS) and long-term opioid consumption among patients who received inpatient multimodal analgesia following lumbar spine surgery, as opposed to those who received opioids alone.

Summary of Background Data:

Opioids have long been the historical choice for managing postoperative pain. The use of multimodal analgesia has become more commonplace in recent years as it is thought to achieve similar levels of pain control while simultaneously diminishing opioid consumption and decreasing LOS.

Materials and Methods:

Patients who underwent 1 or 2-level lumbar fusion from 2018 to 2019 were included. Patients who received opioids on an as-needed basis were propensity-matched to a cohort who received multimodal analgesia based on demographics, surgical approach, and levels fused. LOS was collected for each patient. One year preoperative to 2 postoperative opioid use was obtained from the Pennsylvania Prescription Drug Monitoring Program and included total prescriptions and total morphine milligram equivalents (MMEs). A subanalysis was also performed comparing preoperative, perioperative, and postoperative tramadol consumption during this time frame.

Results:

A total of 69 patients received an opioid-only pain regimen, while 207 patients received multimodal analgesia. Patients receiving a multimodal pain regimen consumed a higher daily tramadol MME but a comparable total in-hospital MME to patients in the opioid-only cohort. No statistically significant differences existed between cohorts with regards to LOS, preoperative, perioperative, and postoperative opioid consumption, though multimodal patients consumed more tramadol from 0 to 30 days postoperatively.

Conclusions:

Patients who received a multimodal pain regimen consumed comparable quantities of opioids to those who received opioids alone and did not have a longer LOS following 1 and 2-level lumbar fusion.
Efficacy and Safety of 730-nm Picosecond Laser for the Treatment of Acquired Bilateral Nevus of Ota-like Macules
Authors: Han Rui , Sun Yifang , Su Mingshan
Published: January 2025

BACKGROUND

The effectiveness and safety of 730-nm picosecond laser for treating acquired bilateral nevus of Ota-like macules remain uncertain.

OBJECTIVE

This study aims to evaluate the potential benefits and risks of using the 730-nm picosecond laser for ABNOM removal.

METHODS

This is a retrospective review of patients who were presented to the clinic between January 2020 and January 2024 for the treatment of ABNOM with 730-nm picosecond laser alone. The efficacy of the laser was assessed based on the Quartile Improvement Scale, using high-resolution photographs evaluated by blinded dermatologists.

RESULTS

A total of 72 Chinese participants with Fitzpatrick skin types III to IV were included in the study. The overall effective rate of the treatment was 75%, achieved after an average of 2.42 ± 0.75 sessions. A subgroup analysis of 41 patients who completed 3 treatment sessions showed statistically significant differences in outcomes across the sessions. The mean improvement scores for sessions 1, 2, and 3 were 1.63 ± 1.04, 2.66 ± 1.22, and 3.29 ± 1.17, respectively (p < .01). No cases of hypopigmentation were observed. The incidence of postinflammatory hyperpigmentation was 5.56%.

CONCLUSION

The 730-nm picosecond laser is a safe and effective treatment for ABNOM in Chinese patients.