bluuebunny/crossref_metadata_2025 huggingface dataset:
Immediate Hybrid Breast Reconstruction: Dual-plane approach using prepectoral implants and retro-pectoral fat grafting
Authors: Longo Benedetto , Giacalone Martina , D’Orsi Gennaro , Farcomeni Alessio , Gagliano Elettra , Vannucchi Lisa , Vanni Gianluca , Buonomo Claudio Oreste , Cervelli Valerio
Published: January 2025

Background:

Implant-based breast reconstruction (BR) is to date the most popular reconstructive modality. The aim of the study was to evaluate the immediate hybrid one-stage BR technique, with a dual-plane approach, using prepectoral implants and retro-pectoral autologous fat transfer (AFT).

Methods:

We prospectively enrolled patients scheduled for immediate BR using a hybrid approach, which included retro-pectoral AFT and prepectoral breast implants (Group-A). This cohort was compared with a retrospective control group of patients who underwent immediate direct-to-implant BR without AFT (Group-B). Complications, hospitalization days, number of AFT procedures for a complete BR, aesthetic outcomes and patient’s satisfaction were analysed. Fat survival rate was assessed through comparison of preoperative and 6-months postoperative MRI.

Results:

30 immediate BR were included in each group. The average amount of AFT in the retro-pectoral plane was 106.30 cc (SD 16.54), while the mean breast implant size was statistically higher in group B (p=0.00026). MRI assessment confirmed an average of 47.90 % (SD 0.14) retro-pectoral fat survival at 6 postoperative months. No statistically significant differences in term of complications and hospitalization days were observed (p>0.05), while a significant difference was observed regarding additional AFT sessions (p=0.00062). After a propensity score weighted analysis, surgeons and patients assessment showed a significant higher overall satisfaction in the active group.

Conclusions:

Immediate hybrid approach for one-stage BR, enabled the use of smaller breast implants, a decrease in AFT procedures with costs reduction, and yielded optimal breast shape and contour, by reducing step-off deformity and rippling alterations, without adding complications.

Level of Evidence II
Dedifferentiated Fat Cells (DFATs) combined with Acellular Dermal Matrix to Promote the Survival of Grafted Fat——A Basic Research
Authors: Dong Miao , Ma Xuan , Li Facheng
Published: January 2025

Background:

DFATs are derived from mature adipocytes that undergo dedifferentiation and regain proliferative and differentiation potential. Acellular Dermal Matrix (ADM) is used widely in plastic and reconstructive field. The effects of ADM combined with DFATs in fat transplantation has not been studied.

Methods:

In vitro, microstructure of ADM was tested. Adipogenic gene, and angiogenic factors secreted by ADSCs or DFATs seeded on ADM were measured. In vivo experiments involved pre-culturing DFATs on ADM and then mixing them with adipose tissue for transplantation into nude mice (1:2). Samples were collected at 4, 8, and 12 weeks for histological analysis, qRT-PCR, ELISA, and immunostaining.

Results:

ADM demonstrated good biocompatibility, and qRT-PCR showed that in vitro pre-culture enhanced the expression of adipogenic-related genes (PPARγ, CEBPα) in DFATs, and increased the secretion of VEGF (*P < 0.05). In the animal experiments, the fat grafts mixed with ADM exhibited better fat integrity, lower fibrosis levels and ELISA showed IL-1β、TNFα level was decreased. In DFATs+ADM group, the number of CD31+ cells and perilipin+ cells within the ADM were the largest (**P < 0.01). However, there was no significant difference in the expression of CD11b, iNOS/CD206 compared to the ADSCs+ADM group.

Conclusion:

ADM as a commercialized biomaterial enhances the paracrine function of seeded cells. When cultured on ADM and assisted fat transplantation, DFATs could better improve the angiogenesis and fat survival. The clinical application of 'cell-scaffold-fat transplantation' model in the future is promising.
Peer Audit and Feedback: A Documentation-Focused Quality Improvement Project
Authors: Glass Michal I. , Powers Kelly , Magennis Laura M. , Shaw Carmen L.
Published: January 2025

Background and Objectives:

Nurses’ documentation of communication, including notification of critical laboratory results (CLR), is important to ensure safe, high-quality care. Evidence supports peer audit with feedback as a quality improvement (QI) intervention to improve documentation. Nursing compliance with CLR documentation requirements was below goal for several years in an intensive care unit. To address this problem, a peer audit and feedback intervention was implemented and evaluated.

Methods:

Compliance with CLR documentation requirements was evaluated pre- and postintervention, for a total of 12 months. The evaluation also included data from the peer audits and a survey to assess nurses’ perceptions. The 5-month intervention was a timely peer audit and feedback of CLR events.

Results:

CLR documentation compliance improved from 6.4% to 9.6% (50% improvement), which was clinically meaningful but not statistically significant. Nurses had overall positive perceptions of the peer audit and feedback as a QI tool, perceiving it as nonpunitive and helpful for improving practice.

Conclusion:

Results support continued examination of peer audit and feedback to improve nursing documentation. Future projects should address the limited time for nurses to engage in QI projects.
Metabolic and Bariatric Operation and the Path to Kidney Transplantation
Authors: Attia Abdallah , Toraih Eman , Ardis Claire , Omar Mahmoud , Abdelmaksoud Ahmed , Tatum Danielle , Killackey Mary , Levy Shauna , Paramesh Anil
Published: January 2025

Background:

Obesity is a significant barrier to kidney transplantation for patients with end-stage renal disease (ESRD). We aimed to evaluate the long-term impact of metabolic and bariatric surgery (MBS) on kidney transplantation access and outcomes in individuals with obesity and ESRD patients.

Study Design:

A retrospective cohort study using data from 64 US healthcare organizations included 132,989 individuals with obesity (BMI ≥30kg/m²) and ESRD requiring dialysis, of whom 6,263 (4.6%) underwent MBS. Propensity score matching produced 1:1 matched groups of 6,238 patients each, analyzed over 10 years. Primary outcomes included rates of kidney transplant waitlist placement, transplantation, and overall mortality. Secondary outcomes focused on 22,979 transplant recipients, including 1,701 (7.4%) MBS patients, to evaluate post-transplant adverse events.

Results:

Over a median follow-up of 33.3 months (MBS) and 28.5 months (controls), MBS patients demonstrated higher rates of waitlist placement (19.12% vs 10.53%, HR=1.800, 95%CI=1.636-1.980, p<0.001) and transplantation (27.06% vs 16.09%, HR=1.712, 95%CI=1.584-1.852, p<0.001) at 10 years, with benefits evident within 1-month postoperation. Mortality was lower in the MBS group (30.55% vs 36.44%, HR=0.768, 95%CI=0.723-0.817, p<0.001). In transplant recipients, MBS patients had lower cardiovascular complications (37.3% vs 40.6%, RR=0.92, p=0.007) and all-cause mortality (16.70% vs 20.88%, HR=0.82, p<0.001), with no significant differences in graft rejection or failure.

Conclusion:

MBS significantly improves access to kidney transplantation and long-term survival for obese ESRD patients. Patients who underwent MBS demonstrated notable improvements in cardiovascular health, potentially leading to a better quality of life and survival.

These findings suggest that MBS should be considered as part of the comprehensive care for this high-risk population.
Potential role of Gut Bacteria in the development of hepatocellular carcinoma
Authors: Yan bingqing , Wang Yuchao , Wang Ziqi , Huang Ailong , Jin Xiuxiu , Jiang Tiantian , Xue Hong , Shen Zheyu , Wang Shifang , Xu Haiyan , Zhu Renfei
Published: January 2025

Liver cancer is the fourth most deadly cancer and early detection and timely treatment apparently play a crucial role in it. Intestinal bacteria affect the development of liver cancer through various pathways. In this study, the gut bacteria of liver cancer patients is analyzed in detail by using macro-genome sequencing technology, and some of the bacterial species and metabolic pathways that may affect the development of liver cancer have been identified, in addition, the bacterial factors that may affect the tumor size and other important clinical indicators have also been identified, which provides a scientific basis for the research related to the development of liver cancer and new insights for the clinical treatment of liver cancer.
Retinal optical coherence tomography angiography imaging in population studies
Authors: Kashani Amir H , Berendschot Tos TJM , Bonnin Sophie , Sobrin Lucia , Andrade de Jesus Danilo , Sanchez Brea Luisa , Collazo Martinez Ana , Raman Rajiv , de Vries Victor AV , Huang Haifan ,   E3 consortium, Macgillivray Tom , Ramdas Wishal , Webers Carroll , van Asten Freekje , Baiser Alexandra , Klaver Caroline , Breteler Monique , Finger Robert , Khan Rehana , Liu Renee , Susarla Gayatri , Rizza Azzi , Li Ashley , Han Samuel , Chan Weilin , Lains Ines , Yang Janine , Brustoki Kim , Khetan Vikas , Iyengar Sudha , Benchek Penelope , Sinnakaruppan Mathavan , Chan Ricky , van der Heide Frank CT
Published: January 2025

Abstract Background Widespread use of retinal optical coherence tomography angiography (OCT-A) imaging in population-based studies requires methodological and analytical consensus to ensure reproducible and accurate results. Objective Development of a consensus framework for assessment of OCT-A image quality and working with OCT-A-derived variables in population studies. Methods Criteria for image quality were developed for fovea-centered, 3x3-mm OCT-A images acquired with three commercially available devices. Inter- and intragrader agreements for overall image quality, vessel density (VD) and foveal avascular zone (FAZ) area were evaluated among five graders (% agreement). Intergrader agreement was validated on 6x6-mm OCT-A images. Recommendations for grading and use of OCT-A images in epidemiological studies were developed. Results Mean intergrader agreements for overall Unusable, Usable, and Excellent 3x3-mm OCT-A image quality (52 images) were 82.3%, 70.8%, and 87.1%; for Unusable VD and FAZ area agreements were 80.0% and 81.9%, respectively. Mean intragrader agreements for overall Unusable, Usable and Excellent 3x3-mm OCT-A image quality (27 images) were 91.1%, 82.2%, and 81.9%; agreements for Unusable VD and FAZ area were 89.6%; and 92.6%, respectively. Mean intergrader agreements for assessment of overall Unusable, Usable and Excellent 6x6-mm OCT-A images (21 images) were 73.3 %, 57.1% and 83.8%, agreements for Unusable VD and FAZ area were 60.0 % and 84.8 %, respectively. Three analytic scenarios were developed to account for common types of bias related to suboptimal OCT-A image quality and ocular comorbidities. Conclusion These recommendations provide a framework for working with OCT-A imaging in population studies.
Bayesian optimization of cortical neuroprosthetic vision using perceptual feedback
Authors: Kucukoglu Burcu , Soo Leili , Leeftink David , Grani Fabrizio , Soto Sanchez Cristina , Guclu Umut , van Gerven Marcel , Fernandez Eduardo
Published: January 2025

The challenge in cortical neuroprosthetic vision is determining the optimal, safe stimulation patterns for the visual cortex in order to evoke the desired perception in blind individuals - specifically, light perceptions known as phosphenes. Currently, clinical studies gain insights into the perceptual characteristics of the perceived phosphenes by asking for descriptions of provided stimulation protocols. However, the huge parameter space for multi-electrode stimulation settings makes it difficult to draw conclusions about the optimality of the stimulation patterns that lead to well-perceived phosphenes. A systematic search in the parameter space of the electrical stimulation is needed to achieve good perception. Bayesian optimization (BO) is a framework for finding optimal parameters efficiently. Using the patient's scoring of the perception as feedback, a model of the patient's response based on iteratively generated stimulation protocols can be built to maximize perception quality. A patient implanted with an intracortical 96-channel microelectrode array in their visual cortex was tested by iteratively presenting stimulation protocols, generated via BO for the first and random generation (RG) for the second experiment. Whereas standard BO methods do not scale well to problems with over a dozen inputs, we propose to optimize a set of 40 electrode currents using trust region-based BO. The generated protocols determine which electrodes are concurrently stimulated from the set and with how much current from a range of 0-50 uA, on a maximum total current constraint of 500 uA. The patient provided feedback for each stimulation based on their liking of the perception quality on a Likert scale, where a score of 7 indicated the highest quality and 0 no perception. In the BO experiment, the patient perception quality ratings gradually converged on higher values compared to the RG experiment. Similarly, gradually higher total current values were chosen by BO, in line with the observed preference of patients for higher currents due to brighter phosphenes. Finally, the electrodes that were observed to be more effective in producing phosphene perception in previous studies were gradually chosen more by BO also with the allocation of higher current values. This study demonstrates the power of BO in converging to optimal stimulation protocols based on patient feedback, providing a more efficient search for stimulation parameters for clinical studies.
ViFIT-assisted Histopathology: From H&E Style Standardization to Virtual Fiber Image Transformation
Authors: Wang Shu , Zhang Xiao , Wang Xingfu , Lv Chenyong , Han Xiahui , Lin Xiong , Kang Deyong , Lin Ruolan , Hu Liwen , Huang Feng , Liu Wenxi , Chen Jianxin
Published: January 2025

Deep learning-based virtual fiber staining provides a promising complement to routine H&E pathology. However, the reliance on predefined staining style inputs and manual intervention limits the clinical applicability of existing methods. To address these challenges, we introduce ViFIT-assisted histopathology, a two-stage diagnostic approach that integrates our proposed unsupervised deep learning-based virtual fiber transformation model (ViFIT). This approach enables the conversion of H&E-stained images with diverse styles into pathologist-preferred H&E images, while simultaneously generating content-consistent virtual fiber images containing label-free collagen fibers and stained reticular and elastic fibers. ViFIT-assisted histopathology reveals tumor-associated fibers and provides quantitative metrics across multiple intraoperative and postoperative cases. Experimental results demonstrate that ViFIT significantly outperforms state-of-the-art unsupervised methods in both style standardization and virtual staining, across various downstream tasks and cancer types. By eliminating the need for staining variation and manual annotation, ViFIT-assisted histopathology streamlines histopathology workflows, making it well-suited for multi-center consultations and differential diagnosis.
Expanding Chemical Space: Developing a Compound Generative Pre-trained Transformer for De Novo Drug Design
Authors: Chen Tze Shin , Chu Jhih Wei , Yang Jinn Moon
Published: January 2025

The drug development process is time-consuming and costly. With the success of attention mechanism models across various domains, including drug development, their adoption has significantly increased. pre-trained a model on large datasets enhances its ability to understand the vast chemical space, enabling effective drug design. However, despite numerous generative models for drug discovery, challenges remain: (i) Most current models utilize less than 2 million compounds, which are insufficient to cover the vast chemical space and often results in limited interpretability. (ii) Existing pre-trained models for compound generation struggle to represent the full diversity of potential molecular structures due to restricted training data. Here, we developed a generic compound generator leveraging extensive chemical spaces. Training data derived from 200 million compounds in the ZINC20 database enabled the model to capture and represent the SMILES syntax and the key features of compounds. Using the attention mechanisms of the generative model, we achieved an interpretable understanding of chemical structures, ensuring robust performance in diverse chemical spaces. Our approach demonstrated 99% novelty, surpassing state-of-the-art methods to generating chemically valid and unique compounds.
RNAbpFlow: Base pair-augmented SE(3)-flow matching for conditional RNA 3D structure generation
Authors: Tarafder Sumit , Bhattacharya Debswapna
Published: January 2025

Motivation: Despite the groundbreaking advances in deep learning-enabled methods for bimolecular modeling, predicting accurate three-dimensional (3D) structures of RNA remains challenging due to the highly flexible nature of RNA molecules combined with the limited availability of evolutionary sequences or structural homology. Results: We introduce RNAbpFlow, a novel sequence- and base-pair-conditioned SE(3)-equivariant flow matching model for generating RNA 3D structural ensemble. Leveraging a nucleobase center representation, RNAbpFlow enables end-to-end generation of all-atom RNA structures without the explicit or implicit use of evolutionary information or homologous structural templates. Experimental results show that base pairing conditioning leads to broadly generalizable performance improvements over current approaches for RNA topology sampling and predictive modeling in large-scale benchmarking. Availability: RNAbpFlow is freely available at https://github.com/Bhattacharya-Lab/RNAbpFlow.
Functional characterization of immune cells in a cnidarian reveals an ancestral antiviral program
Authors: Kozlovski Itamar , Sharoni Ton , Levy Shani , Jaimes-Becerra Adrian , Talice Shani , Kwak Hee-Jin , Aleshkina Daria , Grau-Bove Xavier , Karmi Ola , Rosental Benyamin , Sebe-Pedros Arnau , Moran Yehu
Published: January 2025

Examining early-branching animal phyla can help reconstructing the evolutionary origin of animal immune cells. Here we characterized the immune related cell program in the sea anemone Nematostella vectensis, a model organism representing the phylum Cnidaria that diverged ~600 million years ago from the rest of animals. By using a Nematostella transgenic reporter line expressing mCherry under the RLRb antiviral promoter we show that cells fluorescent upon stimulation with the viral mimic poly(I:C) are morphologically and transcriptomically distinct. These cells exhibit upregulation of immune effector and regulator genes. Cellular assays revealed an increase in phagocytic activity upon poly(I:C) treatment in this cell population. Lastly, we used a combination of immunofluorescent staining followed by FACS and bulk RNA sequencing, accompanied by single-cell transcriptomic analysis, to reveal the gene regulatory programs associated with immune cells in Nematostella. Comparing the sea anemone immune expression profile with gene expression of stony corals treated with the immunostimulant 2′3′-Cyclic GMP-AMP revealed remarkable similarity, suggesting that the immune response to viral challenge is conserved across the cnidarian class Hexacorallia. Altogether, this research uncovers the characteristics of a novel cnidarian immune cell type involved in antiviral immunity and offers insights into the evolutionary history of the innate immune system.
Estimating the effect of tissue- and blood-derived cell reference matrices on deconvolving bulk transcriptomic datasets
Authors: Sun Siqi , Yadav Shweta , Pingili Mulini , Chang Dan , Wang Jing
Published: January 2025

Background

Cell deconvolution is a method used to characterize the composition of the mixed cell population in bulk transcriptomic datasets. Tissue- and blood-derived cell reference matrices (CRMs) are typically used, but their impact on deconvolution has yet to be evaluated.

Methods

Recursive feature elimination and random forest methods were applied to build tissue- and blood-derived CRMs using single-cell RNA sequencing (scRNA-seq) datasets of inflammatory bowel disease (IBD) which comprises two subtypes (Crohn’s disease (CD) and ulcerative colitis (UC)). Combining with three published blood-derived CRMs (IRIS, LM22, and ImmunoStates), public bulk transcriptomes datasets and simulated datasets generated from scRNA-Seq were used to evaluate the deconvolution performance by goodness-of-fit and cell fractions correlation. Additionally, two infliximab-treated bulk datasets were used to compare the treatment-related cell types revealed by tissue- and blood-derived CRMs. Lung adenocarcinoma (LUAD) single-cell and TCGA bulk transcriptomic datasets were also used for evaluation.

Results

For CD and UC tissue bulk datasets, tissue-derived CRMs showed better deconvolution goodness-of-fit scores compared to blood-derived CRMs. Meanwhile, tissue-derived CRMs represented more accurate cellular proportion estimates for most cell types, such as immune and stromal cells in tissue pseudobulk datasets. They also revealed more treatment-related cell types. Additionally, CRMs derived from the scRNA-seq datasets from CD and UC colon samples had similar performance. In contrast, CRMs derived from CD ileum scRNA-seq dataset had better performance in the ileum bulk datasets. All CRMs yielded consistent deconvolution performance when deconvolving blood bulk transcriptomics. The similar results have also been shown using LUAD datasets.

Conclusions

Our results emphasize the importance of selecting appropriate CRMs for cell deconvolution, particularly in bulk tissue transcriptomes in immunology and oncology. Such considerations can be extended to encompass other disease implications.

AbbVie Disclosure statement

All authors are current employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.

Key Points

Tissue-derived CRMs showed higher goodness-of-fit compared to blood-derived CRMs for deconvolving bulk tissue transcriptomics.

All CRMs yield consistent goodness-of-fit for deconvolving bulk blood transcriptomics.

Tissue-derived CRMs represent more accurate cellular proportion estimates and reveal more treatment-related cell types, and the specific tissue type is relevant to the deconvolution performance.
A fluid dynamics-model system for advancing Tissue Engineering and Cancer Research studies: Dynamic Culture with the innovative BioAxFlow Bioreactor
Authors: Gramigna Giulia , Liguori Federica , Filippini Ludovica , Mastantuono Maurizio , Pistillo Michele , Scamarcio Margherita , Lisi Antonella , Falvo D’Urso Labate Giuseppe , Ledda Mario
Published: January 2025

In this study, we test an innovative bioreactor, particularly suitable for tissue engineering applications, named BioAxFlow. Unlike traditional bioreactors, it does not rely on mechanical components to agitate the culture medium, but on the fluid-dynamics generated thanks to the unique geometry of the culture chamber. The flow generated within ensures continuous medium movement, promoting consistent cell exposure to nutrients and growth factors. Using the human osteosarcoma cell line SAOS-2, the bioreactor’s ability to enhance cell adhesion and proliferation on polylactic acid scaffolds, mimicking bone tissue matrix architecture, is tested. The findings show that the bioreactor significantly improved cell adhesion and growth compared to static cultures, promoting a homogeneous cell distribution across the scaffold surfaces, which is crucial for developing functional tissue constructs. The bioreactor preserves the osteogenic potential of SAOS-2 cells as assessed by the expression of key osteogenic markers. Additionally, it retains the tumorigenic characteristics of SAOS-2 cells, including the expression of pro-angiogenic factors and apoptosis-related genes. These results indicate that the BioAxFlow bioreactor is an effective platform for tissue engineering and cancer research, offering a promising tool for both regenerative medicine applications and drug testing.
N-terminal modification of Histone H3 inhibits H3K27M-mediated loss of H3K27 trimethylation
Authors: Poux Nicolas , Zhang Daren F , Kebede Adam F , Gainey Isabella , Famous Olohireme E , Beroukhim Rameen , Bandopadhayay Pratiti
Published: January 2025

The use of short epitope tags is widespread in the study of histone H3 biology as they allow for the antibody-mediated detection and pulldown of particular histone post-translational modifications (PTM) or exogenous histone transgenes. However, H3 is particularly sensitive to sequence modification and the addition of epitope tags may interfere with the native function of H3. Here, we use the known relationship between lysine-to-methionine K27M mutations and the loss of trimethylation at the H3 K27 residue to test whether the addition of epitope tags to the N or C terminus of H3 affects the levels of histone H3 PTMs. We find that all tested N-terminal tags abrogate the H3K27M-mediated loss of H3K27 trimethylation. These results suggest that the addition of epitope tags to the N-terminus of H3 should be performed with caution, and these findings may be of particular interest for the study of H3-driven cancers, like diffuse midline gliomas.
Fast tumor phylogeny regression via tree-structured dual dynamic programming
Authors: Schmidt Henri , Qi Yuanyuan , Raphael Benjamin J. , El-Kebir Mohammed
Published: January 2025

Motivation

Reconstructing the evolutionary history of tumors from bulk DNA sequencing of multiple tissue samples remains a challenging computational problem, requiring simultaneous deconvolution of the tumor tissue and inference of its evolutionary history. Recently, phylogenetic reconstruction methods have made significant progress by breaking the reconstruction problem into two parts: a regression problem over a fixed topology and a search over tree space. While effective techniques have been developed for the latter search problem, the regression problem remains a bottleneck in both method design and implementation due to the lack of fast, specialized algorithms.

Results

Here, we introducefastppm, a fast tool to solve the regression problem viatree-structured dual dynamic programming. fastppmsupports arbitrary, separable convex loss functions including theℓ2, piecewise linear, binomial and beta-binomial loss and provides asymptotic improvements for theℓ2and piecewise linear loss over existing algorithms. We find thatfastppmempirically outperforms both specialized and general purpose regression algorithms, obtaining 50-450×speedups while providing as accurate solutions as existing approaches.

Incorporatingfastppminto several phylogeny inference algorithms immediately yields up to 400×speedups, requiring only a small change to the program code of existing software. Finally,fastppmenables analysis of low-coverage bulk DNA sequencing data on both simulated data and in a patient-derived mouse model of colorectal cancer, outperforming state-of-the-art phylogeny inference algorithms in terms of both accuracy and runtime.

Availability

fastppmis implemented in C++and available as both a command-line interface and Python library at github.com/elkebir-group/fastppm.git.
Vertical transmission of chronic wasting disease in free-ranging white-tailed deer populations
Authors: Sandoval Audrey M. , Nalls Amy V. , McNulty Erin E. , Denkers Nathaniel D. , Trujillo Devon J. , Olmstead Zoe , Barton Ethan , Ballard Jennifer R. , Grove Daniel M. , Dennison Jeremy S. , Stilwell Natalie , Cleveland Christopher A. , Crum James M. , Ruder Mark G. , Mathiason Candace K.
Published: January 2025

Chronic wasting disease (CWD) is a fatal neurodegenerative disease affecting cervids across North America, Northern Europe, and Asia. Disease transmission among cervids has historically been attributed to direct animal-to-animal contact with ‘secreta’ (saliva, blood, urine, and feces) containing the infectious agent, and indirect contact with the agent shed to the environment in these bodily components. Mounting evidence provides another mechanism of CWD transmission, that from mother-to-offspring, including during pregnancy (vertical transmission). Here we describe the detection of the infectious CWD agent and prion seeding in fetal and reproductive tissues collected from healthy-appearing free-ranging white-tailed deer (Odocoileus virginianus) from multiple U.S. states by mouse bioassay andin vitroprion amplification assays. This is the first report of the infectious agent in severalin uteroderived fetal and maternal-fetal reproductive tissues, providing evidence that CWD infections are propagated within gestational fetal tissues of white-tailed deer populations. This work confirms previous experimental and field findings in several cervid species supporting vertical transmission as a mechanism of CWD transmission and helps to further explain the facile dissemination of this disease among captive and free-ranging cervid populations.
Antimullerian Hormone Levels by Phenotypes in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
Authors: de Carvalho Patrícia Jorge Schwenck , De Nardo Maffazioli Giovana , Simões Ricardo Santos , Macchione Renata Ferri , de Medeiros Sebastião Freitas , Soares José Maria , Baracat Edmund Chada , Maciel Gustavo Arantes Rosa
Published: January 2025

Structured abstract

Objective

This study aims to evaluate antimüllerian hormone (AMH) levels across Polycystic Ovary Syndrome (PCOS) phenotypes (A, B, C, D) based on the Rotterdam diagnostic criteria.

Data Sources

A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Embase, ScienceDirect, and Web of Science were searched for studies published between January 2009 and June 2024.

Study Eligibility Criteria

Studies reporting AMH levels stratified by PCOS phenotypes based on the Rotterdam criteria, along with population characteristics and AMH measurement methods, were included. Animal studies, reviews, case reports, opinion articles, letters to the editor, other non-original research. and those lacking complete phenotype stratification were excluded.

Study Appraisal and Synthesis Methods

Study quality was assessed using the ROBINS-E tool. Primary outcomes included mean AMH levels across phenotypes, analyzed as tAMH (without assay differentiation) and bcAMH (Beckman Coulter Gen II assay). Secondary outcomes included age and BMI by phenotype. Random-effects meta-analysis was used to calculate mean levels and standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic.

Results

Forty-nine studies involving 15,535 subjects revealed that AMH levels vary significantly by phenotype, being highest in A, followed by D, C, and B. For phenotype A: tAMH=9.87 ng/mL (SMD 2.97, CI 9.29–10.48); bcAMH=11.49 ng/mL (SMD 3.06, CI 10.47–12.61). For phenotype B: tAMH=5.71 ng/mL (SMD 0.98, CI 4.96–6.57); bcAMH=6.25 ng/mL (SMD 1.36, CI 5.20–7.51). There were no significant differences in age or BMI among phenotypes. High heterogeneity suggests additional factors influence AMH levels beyond phenotypic categories.

Conclusions

AMH levels are elevated in PCOS and vary across phenotypes, underscoring their potential to improve PCOS subtype characterization and guide management strategies. The findings highlight the need for standardizing AMH measurement techniques for consistent clinical application.
Staphylococcus haemolyticusis a reservoir of antibiotic resistance genes in the preterm infant gut
Authors: Lamberte Lisa E. , Darby Elizabeth M. , Kiu Raymond , Moran Robert A. , Acuna-Gonzalez Antia , Sim Kathleen , Shaw Alexander G. , Kroll J. Simon , Belteki Gusztav , Clarke Paul , Felgate Heather , Webber Mark A. , Rowe William , Hall Lindsay J. , van Schaik Willem
Published: January 2025

Among coagulase-negative staphylococci,Staphylococcus haemolyticusis a primary cause of bloodstream infections in preterm infants, with gut colonisation being recognised as a risk factor for subsequent infection. Through a re-analysis of a 16S rRNA gene sequencing dataset (n=497 preterm infants), we found thatS. haemolyticuswas abundant and prevalent in the gut in the first month of life. To better understand the diversity ofS. haemolyticusamong preterm infants, we generated genome sequences ofS. haemolyticusstrains (n=140), which were isolated from 44 stool samples of 22 preterm infants from four different hospitals in the United Kingdom. Core genome phylogenetic analyses, incorporating 126 publicly availableS. haemolyticusgenome sequences, showed that 85/140 (60.1%) of the isolates, from three different hospitals, formed a clonal group with 79/85 (92.9%) strains being assigned to Multi-Locus Sequence Type (ST) 49. Antibiotic resistance genes were highly prevalent in the genome sequences. Using logistic regression, we found a strong association between the presence of the genemecAand phenotypic resistance to oxacillin (odds ratio [OR]: 158.00, p<0.0001), and theaacA-aphDgene and phenotypic resistance to gentamicinaacA-aphD(OR: 162.00, p<0.001). None of the strains from the preterm infant cohort had a complete Staphylococcal Cassette Chromosomemec(SCCmec) element. TheaacA-aphDgene was associated with the transposon Tn4001.Using hybrid genome assemblies, we found it to be present on the chromosome (54.5% of strains) or on diverse plasmids (27.3%). Four strains (18.2%) had Tn4001copies on both plasmid and chromosome. Our data suggest the existence of a distinct sub-population ofS. haemolyticusthat has adapted to colonise the gut of preterm infants. Prevalent resistance to antibiotics is of clinical concern and the diversity of genetic contexts ofmecAand Tn4001suggests widespread horizontal gene transfer and recombination in this species.
Centriole Loss in Embryonic Development Disrupts Axonal Pathfinding and Muscle Integrity
Authors: González Beatriz , Sellés-Altés Júlia , Pla-Parron Jèrica , Castro-Ribera Judith , Araújo Sofia J.
Published: January 2025

Centrosomes, the primary microtubule-organizing centers (MTOCs), are crucial for early neuronal development, particularly in establishing polarity and promoting axon formation. Traditionally considered non-essential in terminally differentiated cells, recent evidence suggests that centrosomes play vital roles in specialized cellular contexts. In mammalian neurons, centrosome-mediated microtubule remodeling is essential for axon elongation, with centrosome dysfunction leading to axonal misrouting and growth defects. Although active centrosomes have been detected in the tracheal terminal cells ofDrosophila melanogaster, their activity in neuronsin vivohas not been observed. Their gradual loss during embryogenesis has been reported as non-essential for organogenesis, as adult flies can eclose without centrioles.

To investigate centrosome activity in neurons, we revisitedDrosophila Sas-4mutants, which exhibit centrosome loss (CL), and observed that 50% of homozygous mutant individuals fail to hatch as larvae. We analysed their development, focusing on the expressivity and penetrance of nervous system phenotypes, and examined centriole localization in neurons. Our findings confirm the presence of centrosomes in motor and sensory neurons inDrosophilaand their localization near the nascent axon. CL conditions resulted in axonal misrouting and muscle developmental abnormalities. Targeted downregulation of Sas-4 in the pioneer motor neurons aCC and RP2 induced axon guidance errors, indicating an autonomous role for centrosomes in axonal navigation. Colocalization of acetylated- and γ-tubulin with centrioles in motor neurons further confirmed the presence of functional centrosomes in these cells. Analysis of motor axons revealed that CL leads to axonal tortuosity, a characteristic associated with neurodegeneration. This is the first direct association of CL with axonal morphological phenotypes, highlighting the role of centrosomes in neuronal development and their broader influence on nervous system structure and function.
LAM/TREM2+ macrophages release extracellular vesicles and extracellular lipid droplets which modulate the phenotype of recipient macrophages and homeostasis of skeletal muscle cells
Authors: Tacconi Stefano , Giudetti Anna Maria , Blangero Ferdinand , Meugnier Emmanuelle , El-jaafari Assia , Longo Serena , Angile Federica , Fanizzi Francesco Paolo , Canaple Laurence , Jalabert Audrey , Errazuriz-Cerda Elizabeth , Cassin Christel , Zuccotti Maurizio , Alfieri Andrea , Da Silva Claire Crola , Brun Camille , Gillet Benjamin , Hughes Sandrine , Rieusset Jennifer , Vidal Hubert , dini luciana , Rome Sophie
Published: January 2025

The polarization of tissue-resident macrophages is influenced by a variety of signals from the immune system and the local tissue environment, including nutrition. Although it is known that the quality and quantity of ingested lipids have a significant effect on the lipid composition of extracellular vesicles and their fate, it is unknown how the nutritional environment modifies the release and the function of macrophage-derived EVs. In this study, we used a combination of palmitate and oleate (1:2, FFA) to generate lipid-associated TREM2-expressing macrophages (LAM/TREM2+) in vitro. Using various electron microscopy techniques (TEM, SEM, CryoEM) and fluorophores, we found that FFA overload not only induces lipid storage in LAM/TREM2+ macrophages, but also alters their morphology and reduces the diversity and the number of the lipid-derived structures they release. In addition, LAM/TREM2+ macrophages accumulated lipid droplets (LDs) below the plasma membrane and we discovered for the first time that they export and disseminate full LDs into their environment, in addition to extracellular vesicles, by using a cellular pathway associated to CD81. The use of 14C-palmitate confirmed the presence of 14C-triacylglycerols in the large extracellular vesicle pellet. LAM/TREM2+ macrophage-derived EVs induced TREM2 and Il-10 expression in recipient M0 macrophages. These data provide potential insights into how dietary factors and metabolic perturbations can shape the functions of macrophage-derived EVs in the context of metabolic diseases such as diabetes and obesity. In addition, LAM/TREM2+ macrophage-derived EVs modulated insulin-sensitivity, mitochondrial oxidative capacity, lipid profiles and the expressions of genes encoding extracellular matrix components in recipient skeletal muscle cells. Although previously postulated but never demonstrated, these data also highlight the LAM/TREM2+ macrophage-derived EVs as important players in SkM tissue renewal and metabolic homeostasis.
Analysis oflhx8a, isl1, pax6a/b, calb2aandsst7Reveals that Dopaminergic Neurons in the Zebrafish Subpallium Belong to the Extended Amygdala
Authors: Armbruster Daniel , Mueller Thomas , Driever Wolfgang
Published: January 2025

The amygdala is a heterogenous multinuclear telencephalic structure critical for motivated and emotion-related behaviors in vertebrates. In ray-finned fish (actinopterygii) like the teleost zebrafish, a telencephalic outward growing process called eversion makes defining amygdaloid territories particularly challenging. Teleosts are also peculiar in that they develop prominent dopaminergic neuron groups in the subpallium, which are absent from tetrapods. To shed light on amygdala organization in teleosts, we pursued an evolutionary-developmental approach focusing on the topological origin of subpallial dopaminergic neurons. Specifically, we analyzed developmental expression patterns of Tyrosine hydroxylase in conjunction withpax6a+b,isl1a,nkx2.1,lhx8a, calb2aas telencephalic topology markers in brains of 5- and 30-day-old zebrafish (Danio rerio, Teleostei). Our results reveal, that the subpallial dopaminergic neurons develop within apax6anegative dorsal subpallial domain (Vdd), which forms a primordial portion of the extended amygdala, including the medial amygdala and the anterior bed nucleus of the stria terminalis. Moreover, these dopaminergic neurons differentially coexpresscalb2aandsst7, indicating population heterogeneity and potentially functional diversity. Our data also show that the zebrafish extended amygdala is formed by the dorsal LGE-like Vdd, which is subdivided into a Vdd2 subdivision that may correspond to the extended medial amygdala, including the bed nucleus of the stria terminalis, and forms the pallial-subpallial border region, and a more ventral Vdd1 that ispax6apositive and that corresponds to the central amygdala. Our work contributes to understanding development and evolution of the amygdala, and provides a foundation for functional analysis of the newly defined dopaminergic subtypes of the extended amygdala.
Causality in the presence of stacked shockwaves
Authors: Chen Calvin Y.-R. , Margalit Aoibheann , de Rham Claudia , Tolley Andrew J.
Published: January 2025

Relativistic causality constrains the S-matrix both through its analyticity, and by imposing lower bounds on the scattering time delay. These bounds are easiest to determine for spacetimes which admit either a timelike or null Killing vector. We revisit a class of pp-wave spacetimes and carefully determine the scattering time delay for arbitrary incoming states in the eikonal, semiclassical, and Born approximations. We apply this to the effective field theory of gravity in arbitrary dimensions. It is well-known that higher-dimension operators such as the Gauss-Bonnet term, when treated perturbatively at low energies, can appear to make both positive and negative contributions to the time delays of the background geometry. We show that even when multiple shockwaves are stacked, the corrections to the scattering time delay relative to the background are generically unresolvable within the regime of validity of the effective field theory so long as the Wilson coefficients are of order unity. Phrased the other way, this can be read as a bound on the Wilson coefficient from infrared causality which are consistent with positivity/bootstrap bounds.

Published by the American Physical Society
2025
Two transitions in complex eigenvalue statistics: Hermiticity and integrability breaking
Authors: Akemann Gernot , Balducci Federico , Chenu Aurélia , Päßler Patricia , Roccati Federico , Shir Ruth
Published: January 2025

Open quantum systems have complex energy eigenvalues which are expected to follow non-Hermitian random matrix statistics, when chaotic, or two-dimensional (2d) Poisson statistics, when integrable. We investigate the spectral properties of a many-body quantum spin chain, i.e., the Hermitian Heisenberg model with imaginary disorder. Its rich complex eigenvalue statistics is found to separately break both Hermiticity and integrability at different scales of the disorder strength. With no disorder, the system is integrable and Hermitian, with spectral statistics corresponding to the 1d Poisson point process. At very small disorder, we find a transition from 1d Poisson statistics to an effective D-dimensional Poisson point process, showing Hermiticity breaking. At intermediate disorder, we find integrability breaking, as inferred from the statistics matching that of non-Hermitian complex symmetric random matrices in class AI†. For large disorder, as the spins align, we recover the expected integrability (now in the non-Hermitian setup), indicated by 2d Poisson statistics. These conclusions are based on fitting the spin-chain data of numerically generated nearest- and next-to-nearest-neighbor spacing distributions to an effective 2d Coulomb gas description at inverse temperature β. We confirm that such an effective description of random matrices also applies in classes AI† and AII† up to next-to-nearest-neighbor spacings.

Published by the American Physical Society
2025
Crystal structure of submicron-sized sulfur particles using 3D ED obtained in atmospheric conditions
Authors: Rahimisheikh Sepideh , Hajizadeh Amirhossein , Quintelier Matthias , Stulens Sander , Hardy An , Hadermann Joke
Published: January 2025

Lithium–sulfur batteries are a promising candidate for the next generation of rechargeable batteries. Despite extensive research on this system over the last decade, a complete understanding of the phase transformations has remained elusive. Conventional in-situ powder X-ray diffraction has struggled to determine the unit cell and space group of the polysulfides formed during charge and discharge cycles due to the high solubility of these solid products in the liquid electrolyte. With the improvement in in-situ electrochemical set-ups dedicated to transmission electron microscopes, three-dimensional electron diffraction (3D ED) has the potential to capture the crystal structures of the polysulfides during cycling. In this work, the structure solution and refinement from 3D ED data of elemental sulfur, known to sublimate in the vacuum of transmission electron microscopes, is enabled through the use of an environmental cell with a micro-electromechanical system. This work represents the first step in characterizing sulfur's transformation into lithium polysulfides using in-situ 3D ED.
Framework for systematic adoption of ERP systems in the Sri Lankan construction industry
Authors: Hewavitharana Sachindra , Perera Asoka , Perera Srinath , Perera Prasad , Nanayakkara Samudaya
Published: January 2025

Purpose

Despite the benefits of enterprise resource planning (ERP) systems, construction organisations in Sri Lanka fail to adopt ERP systems successfully due to functional issues. Functional issues arise because of the gap between ERP protocols and construction practices. The purpose of this study is to identify the functional issues in ERP implementation and to propose a framework for the systematic adoption of ERP in the construction industry in Sri Lanka.

Design/methodology/approach

A comprehensive literature review was carried out to identify the issues when adopting ERP protocols into construction practices. These were classified into ten knowledge modules using PMBOK-Version 6 (Project Management Body of Knowledge). Then a questionnaire was developed and validated through an expert forum with five experts. The validated questionnaire was distributed among ERP users in C1-C5 grade construction enterprises in Sri Lanka. Those enterprises were simultaneously operating in multiple construction sites and already experienced ERP implementation. The estimated population was 210 from which 174 responses were received indicating an 82% response rate. Data was analysed using the Chi-Square test.

Findings

The analysis established that there is a significant gap level between ERP protocols and construction practices. The highest significant gap with a Chi-square value of 158.766 exists in the area of inventory management. Other areas such as human resource management (HRM) (142.366), asset management (130.264), finance (126.267), site operations (103.793), project management (53.88), purchasing (34.324), petty cash (28.337), estimating and tendering (22.148) and subcontract management (20.492) show a significant gap level respectively.

Originality/value

The paper establishes comprehensive strategies and a framework developed using the protocols prescribed in webERP (TM) and adopting it to onsite construction practices. webERP (TM) system was developed based on best practices defined in PMBOK (Version 6) and CIDA (Construction Industry Development Authority) specifications for efficient construction practices in Sri Lanka.