bluuebunny/crossref_metadata_2025_split huggingface dataset:
InterPLM: Discovering Interpretable Features in Protein Language Models via Sparse Autoencoders
Authors: Simon Elana , Zou James 
Published: November 2024

AbstractProtein language models (PLMs) have demonstrated remarkable success in protein modeling and design, yet their internal mechanisms for predicting structure and function remain poorly understood. Here we present a systematic approach to extract and analyze interpretable features from PLMs using sparse autoencoders (SAEs). By training SAEs on embeddings from the PLM ESM-2, we identify thousands of human-interpretable latent features per layer that highlight hundreds of known biological concepts such as binding sites, structural motifs, and functional domains. In contrast, examining individual neurons in ESM-2 reveals significantly less conceptual alignment, suggesting that PLMs represent most concepts in superposition. We further demonstrate that a larger PLM (ESM-2 with 650M parameters) captures substantially more interpretable concepts than a smaller PLM (ESM-2 with 8M parameters). Beyond capturing known annotations, we show that ESM-2 learns coherent concepts that do not map onto existing annotations and propose a pipeline using language models to automatically interpret novel latent features learned by the SAEs. As practical applications, we demonstrate how these latent features can fill in missing annotations in protein databases and enable targeted steering of protein sequence generation. Our results demonstrate that PLMs encode rich, interpretable representations of protein biology and we propose a systematic framework to uncover and understand these latent features. In the process, we recover both known biology and potentially new protein motifs. As community resources, we introduce InterPLM (interPLM.ai), an interactive visualization platform for investigating learned PLM features, and release code for training and analysis at github.com/ElanaPearl/interPLM.
The microbiota of wooden cheese ripening boards is a rich source of antimicrobial-producing bacteria againstListeria monocytogenes
Authors: Chen Yuxing , Chaves Ibrahim Zuniga , Suen Garret , Huynh TuAnh N. 
Published: November 2024

ABSTRACTWooden boards are essential tools in cheese ripening and there are accumulating observations suggesting their antimicrobial effect against foodborne bacterial pathogens, such asListeria monocytogenes. However, poor bacterial recovery of bacteria from wood can confound quantification of pathogen burdens. To assessL. monocytogenessurvival on wooden cheese boards, we applied a disruptive grinding method and tracked native board-associated bacterial counts as controls. Our data revealed thatL. monocytogenesdeclines on clean zones of wooden boards, but can replicate on areas where there is suitable cheese. Our microbiota analysis revealed diverse bacterial communities on wooden board surfaces, with a prominent presence ofBrevibacterium,Brachybacterium, andStaphylococcusgenera. We further identified seven bacterial species that inhibitL. monocytogenes, belonging toBacillus,Staphylococcus, andSerratiaphyla, as well asLactococcus lactis. We focused on aBacillus safensisisolate as a novel biocontrol agent candidate, and found it to potently inhibitL. monocytogenesvia secreted antimicrobial factors. Our genomic, bioinformatic, and biochemical analyses indicate that those factors are likely antimicrobial peptides encoded by multiple biosynthetic gene clusters, several of which are unique toB. safensisand have not been characterized. A sub-inhibitory concentration ofB. safensissupernatant induces a significant down-regulation of prophage elements and up-regulation antimicrobial stress response inL. monocytogenes. Taken together, our findings indicate that the wooden board microbiota is a rich source of antimicrobial-producing bacteria with potential applications in foodborne pathogen control strategies.IMPORTANCEDespite stringent food safety measures,L. monocytogenesfoodborne outbreaks remain frequent with high hospitalization and mortality rates. Removal ofL. monocytogenesfrom food processing environments is extremely challenging, because this pathogen is ubiquitous and encodes a wide array of stress response mechanisms that enable it to thrive under harsh conditions. Our study found that clean wooden boards used in cheese ripening inhibitL. monocytogenes, causing a noticeable decline in pathogen population following surface inoculation. Bacterial communities on wooden cheese boards are rich and diverse, and harbor many species that produce antimicrobial compounds againstL. monocytogenes, with the example of a newB. safensisisolate. Therefore, wooden board microbiota is a promising source for future antimicrobial discovery efforts.
Disordered glass nanowire substrates produce in vivo-like astrocyte morphology revealed by optical diffraction tomography
Authors: Anantha Pooja , Kim Joo Ho , Saracino Emanuela , Raj Piyush , Lucarini Ivano , Tanwar Swati , Chen Jessica , Gu Luo , Agrawal Jay , Convertino Annalisa , Barman Ishan 
Published: November 2024

AbstractAstrocytes, integral components of the central nervous system (CNS), fulfill crucial roles such as maintaining ion homeostasis, providing neuroprotection, and contributing to the blood-brain barrier. Their distinctive, star-like morphology is essential to these functions, and abnormalities in astrocyte structure are linked to numerous neurological disorders. However, our understanding of astrocyte morphology, particularlyin vivo, remains limited. Traditional imaging methods, such as fluorescence microscopy, introduce challenges like restricting continuous observation and comprehensive morphological analysis. In this study, we present a novel approach utilizing optical diffraction tomography (ODT), an advanced imaging technique that generates 3D refractive index profiles, to image and quantify detailed astrocyte morphology. We demonstrate, for the first time, the application of ODT to image samples through and on disordered glass nanowire (NW) substrates, overcoming the typical challenges posed by nanostructures, which can disrupt phase reconstruction. Crucially, we show that disordered glass nanowire (NW) substrates can inducein vivo-like astrocyte morphology in cultured rat cortical astrocytes. Compared to traditional glass substrates, astrocytes grown on disordered glass NWs substrates exhibited enhanced process branching and greater total arbor length—features typically observed in their natural,in vivostate, a state of advanced maturation. This finding underscores the significant influence of substrate topography on astrocyte structure and highlights the unique potential of nanostructured environments to mimic physiological conditions. By leveraging ODT, we were able to monitor astrocyte behavior on these substrates, providing unprecedented insights into their morphological dynamics. Our study pioneers the use of nanostructured substrates for reconstructing astrocyte morphology and sets the stage for further exploration of how microenvironmental cues shape astrocyte morphology and behavior.
The D15 color arrangement test retains its diagnostic value regardless of display accuracy: A modeling study
Authors: Árpádffy-Lovas Tamás , Tóth-Molnár Edit 
Published: November 2024

AbstractColor vision testing is often considered a resource-intensive examination, requiring an anomaloscope, or at least color plates and specialized lighting equipment. Multiple novel, digital color vision testing algorithms have also been described, but were only verified using calibrated displays. In this work, we assessed if color vision testing could be performed with any computer display using two arrangement type color vision tests, the D15 and desaturated D15 panels. Established mathematical models of human color vision deficiencies (CVDs) and publicly available colorimetric data of real world computer screens were used to model how the panel colors would be displayed on computer screens and then perceived and arranged by subjects with varying levels of CVD. A total of 627,431 arrangements were evaluated. We found that all of the modeled displays, including ones with a low color accuracy of deltaE=6, were characterized by specificity above 86%, and the sensitivity of the desaturated D15 panel remained above 85% as well, with negative predictive values above 90% to detect any form of CVD compared to using the unmodifed colors. These findings suggest that any digital screen could be utilized for color vision screening, even without calibration, enabling reliable high-throughput screening utilizing equipment that is already present at virtually all healthcare providers. Since 8% of the population is affected by some form of CVD, simplifeid screening would unlock notable benefits for all stakeholders. Furthermore, the described algorithm could also be used to optimize other digital color vision tests for general use.
Consumption of legumes and risk of hepatobiliary diseases among humans aged 2+ years: a scoping review
Authors: Langmann Fie , Jensen Christopher Fisker , Mortensen Vibeke Lie , Rosendal Line , Bock Niels , Dahm Christina C. 
Published: November 2024

AbstractObjectivesTo identify and map the literature regarding human consumption of legumes and potential relationships with hepatobiliary diseases.BackgroundConsuming legumes might reduce lipid accumulation in the liver while potentially impeding the functionality of the bile duct and gallbladder. As dietary trends shift toward promoting legume consumption, exploring the positive and negative impacts on hepatobiliary health becomes crucial.MethodsThis scoping review explored the intake of dietary pulses and legumes (excluding broader dietary patterns) and their relation to hepatobiliary diseases like non-alcoholic fatty liver disease, gallstones, and gallbladder removal among individuals above the age of two years. The review included textbooks, expert opinions, and searches in four databases (PubMed, CINAHL Complete, Embase, and Web of Science). Two reviewers extracted data independently from each article. The synthesis of results was presented narratively by hepatobiliary outcomes. Unpublished studies and grey literature sources were sought out.ResultsFrom 19,881 records retrieved, 29 were included - 17 on non-alcoholic fatty liver disease and 12 on gallbladder diseases. Most studies were observational, but a few were narrative reviews. Some studies found a protective association between legume consumption and non-alcoholic liver disease, while others found no association. Overall, there was no clear association between legume consumption and gallbladder diseases. The studies varied in methodological quality, and confidence in the findings was low.ConclusionThe association between legume consumption and non-alcoholic fatty liver disease was inverse or non-significant. The association between legume consumption and gallbladder disease was inconclusive. Further research is needed to draw firmer conclusions.Keywords: Dietary pulses; Gallstone; Hepatobiliary health; Legumes; Non-alcoholic fatty liver disease
Genome-wide DNA methylation markers associated with metabolic liver cancer
Authors: Antwi Samuel O. , Siaw Ampem Darko Jnr. , Armasu Sebastian M. , Frank Jacob A. , Yan Irene K. , Ahmed Fowsiyo Y. , Izquierdo-Sanchez Laura , Boix Loreto , Rojas Angela , Banales Jesus M. , Reig Maria , Stål Per , Gómez Manuel Romero , Wangensteen Kirk J. , Singal Amit G. , Roberts Lewis R. , Patel Tushar 
Published: November 2024

ABSTRACTBackground and AimsMetabolic liver disease is the fastest rising cause of hepatocellular carcinoma (HCC) worldwide, but the underlying molecular processes that drive HCC development in the setting of metabolic perturbations are unclear. We investigated the role of aberrant DNA methylation in metabolic HCC development in a multicenter international study.MethodsWe used a case-control design, frequency-matched on age, sex, and study site. Genome-wide profiling of peripheral blood leukocyte DNA was performed using the 850k EPIC array. Cell type proportions were estimated from the methylation data. The study samples were split 80% and 20% for training and validation. Differential methylation analysis was performed with adjustment for cell type, and we generated area under the receiver-operating curves (ROC-AUC).ResultsWe enrolled 272 metabolic HCC patients and 316 control patients with metabolic liver disease from six sites. Fifty-five differentially methylated CpGs were identified; 33 hypermethylated and 22 hypomethylated in cases versus controls. The panel of 55 CpGs discriminated between cases and controls with AUC=0.79 (95%CI=0.71-0.87), sensitivity=0.77 (95%CI=0.66-0.89), and specificity=0.74 (95%CI=0.64-0.85). The 55-CpG classifier panel performed better than a base model that comprised age, sex, race, and diabetes mellitus (AUC=0.65, 95%CI=0.55-0.75, sensitivity=0.62 (95%CI=0.49-0.75) and specificity=0.64 (95%CI=0.52-0.75). A multifactorial model that combined the 55 CpGs with age, sex, race, and diabetes, yielded AUC=0.78 (95%CI=0.70-0.86), sensitivity=0.81 (95%CI=0.71-0.92), and specificity=0.67 (95%CI=0.55-0.78).ConclusionsA panel of 55 blood leukocyte DNA methylation markers differentiates patients with metabolic HCC from control patients with benign metabolic liver disease, with a slightly higher sensitivity when combined with demographic and clinical information.
Research on female breast and gynaecologic cancers in the Democratic Republic of Congo: a scoping review
Authors: Kalay Anifa , Madiata Eric , Lebwaze Bienvenu , Donzo Médard , Botomwito John , Tshiabo Delly , Ntambwe Mireille L. 
Published: November 2024

AbstractBackgroundIn the last decades, the incidence of female breast and gynecologic cancers has been increasing in sub-Saharan African countries including in the Democratic Republic of the Congo (DRC). Although DRC has taken some steps in addressing cancer issues, cancer control is not yet efficiently organized. The DRC national strategy for the fight against cervical and female breast cancers stresses that research conducted on female breast and cervical cancers in DRC is not leveraged to support the Ministry of Health. There is a clear and urgent need to identify the type and extend of research conducted in DRC about female breast cancer and cervical cancers to inform the operational cancer research agenda in DRC. Thus, the purpose of this scoping review is to describe current research and identify research gaps related to research on female breast and gynaecologic cancers in DRCMethodsA scoping review was conducted through search of several electronic databases. We included peer-reviewed articles and grey literature resources reporting primary or secondary studies about female breast cancer or gynaecologic cancers in DRC.ResultsA total of 448 articles were retrieved. After screening, 32 articles were retained for review. Twenty-one articles pertained to cervical cancer, 12 to female breast cancer and 2 to vulva cancer. Five articles focused on several cancer types. There was no article retrieved for the other gynaecologic cancers (uterine, Fallopian tube and ovarian cancers). Most of the studies (60%) used a cross-sectional design. The studies were conducted in six provinces.ConclusionThis scoping review has demonstrated significant gaps in female breast and gynaecologic cancer research in DRC. The review’s findings support the need for further research in all areas of the continuum of cancer care, the establishment of a clear and adapted research agenda, advocacy and providers’ capacity development.
Investigating the Impact of Social Determinants of Health on Diagnostic Delays and Access to Antifibrotic Treatment in Idiopathic Pulmonary Fibrosis
Authors: Li Rui , Lu Qiuhao , Wen Andrew , Wang Jinlian , Fu Sunyang , Ruan Xiaoyang , Wang Liwei , Liu Hongfang 
Published: November 2024

AbstractIdiopathic pulmonary fibrosis (IPF) is a rare disease that is challenging to diagnose. Patients with IPF often spend years awaiting a diagnosis after the onset of initial respiratory symptoms, and only a small percentage receive antifibrotic treatment. In this study, we examine the associations between social determinants of health (SDoH) and two critical factors: time to IPF diagnosis following the onset of initial respiratory symptoms, and whether the patient receives antifibrotic treatment. To approximate individual SDoH characteristics, we extract demographic-specific averages from zip code-level data using the American Community Survey (via the U.S. Census Bureau API). Two classification models are constructed, including logistic regression and XGBoost classification. The results indicate that for time-to-diagnosis, the top three SDoH factors are education, gender, and insurance coverage. Patients with higher education levels and better insurance are more likely to receive a quicker diagnosis, with males having an advantage over females. For antifibrotic treatment, the top three SDoH factors are insurance, gender, and race. Patients with better insurance coverage are more likely to receive antifibrotic treatment, with males and White patients having an advantage over females and patients of other ethnicities. This research may help address disparities in the diagnosis and treatment of IPF related to socioeconomic status.
Ultrafast elastocapillary fans control agile maneuvering in ripple bugs and robots
Authors: Ortega-Jimenez Victor M. , Kim Dongjin , Kumar Sunny , Kim Changhwan , Koh Je-Sung , Bhamla Saad 
Published: November 2024

AbstractMillimeter-sized ripple bugs in the genusRhagoveliaexhibit exceptional agility and rapid maneuvers in fast, unsteady streams, comparable to animal fliers. Their remarkable interfacial transit and turning skills stem from a specialized fan structure on their middle legs. While researchers have suggested active fan actuation, the role of capillary forces and unique microstructure in self-spreading remains unclear. We reveal thatRhagovelia’sfans possess a flat-ribbon architecture with directional stiffness, enabling ultrafast elastocapillary morphing for passive actuation in under 10 ms, independent of muscle control, while producing high-thrust momentum through unsteady vortical wakes. These self-morphing fans allowRhagoveliato execute ∼90 ° turns at a rate of ∼4200 °/s, in ∼50 ms, with speeds reaching ∼120 BL/s – on par with the fastest recorded turns in animal fliers like fruit flies. Inspired by these, we develop an ultralight, ultrafast elastocapillary robotic fan (∼1 mg, ∼100 ms opening/closing time) and integrate it into an insect-scaled robot (Rhagobot, ∼0.2 g). The engineered fans passively balance surface tension and water drag through stiffness anisotropy, enabling the robot to achieve high agility with speeds up to ∼2 BL/s and turning rates of 206 °/sec. Experiments with both insects and robots, with and without fans, show that a self-spreading passive fan significantly improves thrust, braking, and turning – key factors for controlled, high-speed maneuvers. This elastocapillary innovation enables ripple bugs to survive and thrive in turbulent streams and offers new insights for agile aquatic robotics.
Anti-HIV-1 B cell antigen receptor signaling and structure
Authors: Thakur Bhishem , Alam Jahangir , Cronin Kenneth , Patel Parth , Anasti Kara , Kane Advaiti Pai , Hossain Alamgir , Do Hung , Mansouri Katayoun , Spence Taylor N. , Edwards Robert J. , Janowska Katarzyna , Lella Muralikrishna , Cook Aaron , Saunders Kevin , Gnanakaran Sandrasegaram , Haynes Barton F. , Acharya Priyamvada , Alam S. Munir 
Published: November 2024

AbstractThe B cell antigen receptor (BCR) complex, comprised of antigen recognition and signaling components, functions in initiating B cell activation. While structural studies have described BCR domain organization, gaps remain in our understanding of its antigen binding domain (Fab, fragment antigen-binding) disposition, and how antigen binding is sensed to initiate signaling. Here, we report antigen affinity and signaling of the immunoglobulin (Ig) class IgM and IgG BCRs and define conformational states of full-length BCRs of two human broadly neutralizing antibodies, the glycan-specific, heavy chain domain-swapped, I-shaped 2G12, and a canonical Y-shaped antibody, CH31, that recognizes the CD4-binding site on the HIV-1 Envelope protein (Env). The BCRs adopted the shapes (I or Y) of their respective soluble antibodies, and both Ig class of BCRs of the same specificity bound Env trimers with similar affinities. We observed antigen-valenc y dependent differential signaling by the 2G12 IgM and IgG BCRs with trimeric Envs. Cryo-electron microscopy of the 2G12 IgG and CH31 IgM BCRs revealed varied Fab orientations. Structural comparisons revealed hinge points and regions of flexibility in the BCRs suggesting a highly dynamic structure of the BCR complex. Taken together, our results provide an integrated understanding of BCR structure, conformation, antigen recognition and signaling, and provide the basis for understanding antigen induced BCR signal transmission.One Sentence SummaryCryo-electron microscopy structures of full-length B cell antigen receptor complex provide a novel dynamic BCR model and a basis for understanding antigen binding induced signal transmission.
Steroid receptor-assisted loading modulates transcriptional responses in prostate cancer cells
Authors: Hiltunen Johannes , Helminen Laura , Aaltonen Niina , Launonen Kaisa-Mari , Laakso Hanna , Malinen Marjo , Niskanen Einari A. , Palvimo Jorma J. , Paakinaho Ville 
Published: November 2024

ABSTRACTSteroid receptors are involved in a wide array of crosstalk mechanisms that regulate diverse biological processes, with significant implications in diseases, particularly in cancers. In prostate cancer, indirect crosstalk between androgen receptor (AR) and glucocorticoid receptor (GR) is well-documented, where GR replaces antiandrogen-inactivated AR becoming the disease driver. However, the existence and impact of direct chromatin crosstalk between AR and GR in prostate cancer have remained elusive. Our genome-wide investigations reveal that AR activation significantly expands GR chromatin binding. Mechanistically, AR induces remodeling of closed chromatin sites, facilitating GR binding to inaccessible sites. Importantly, coactivation of AR and GR results in distinct transcriptional responses at both the cell population and single-cell levels. Intriguingly, pathways affected by these transcriptional changes are generally associated with improved patient survival. Thus, the direct crosstalk between AR and GR yields markedly different outcomes from the known role of GR in circumventing AR blockade by antiandrogens.