bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Trade-Off Between Torque and Power with Speed: A Study of Shoulder Performance During an Isokinetic and Multiplanar Task
Authors: Lee Kayla D.L , Lee Erin C.S , Rainbow Michael J. 
Published: November 2024

AbstractThe human shoulder likely evolved under selective pressures favouring diverse tasks that require high mobility, speed, and torque. For example, humans are uniquely adept at high-speed and accurate throwing. Prior work has aimed to quantify the kinematics and kinetics of upper limb movements in isometric or uniplanar motions. However, we still do not fully understand the trade-offs of shoulder torque and power with angular velocity during functional tasks that are reflective of demands that may be relevant to the shoulder’s evolution. We developed a novel approach for upper limb 3D inverse dynamic calculations by integrating motion capture with an instrumented cable machine. Twenty-five participants performed a crossbody, isokinetic upper limb motion at various cable speeds in a rigid and free torso condition (self-imposed). Shoulder torque decreased significantly (p < 0.05) with increasing angular velocity in 19 and 16 participants for the constrained and unconstrained conditions, respectively. Shoulder power increased significantly (p < 0.05) with angular velocity for 6 and 11 participants for constrained and unconstrained, respectively. T-tests revealed no statistical difference between the torso conditions for torque and power against angular velocity. Our findings suggest that despite having a trade-off in torque and velocity, the shoulder may be tuned to produce power over a wide range of velocities independent of energy transfer from the lower extremities.
A Multi-Modal Deep Learning Framework with Both Sequence and Structure for Tumor Antigens Prediction
Authors: Jin Ruofan , Ge Jingxuan , Zhang Guanqiao , Deng Ziyan , Hsieh Kim , Hou Tingjun , Zhou Ruhong 
Published: November 2024

AbstractTumor antigens are key targets in cancer immunotherapies that can be recognized by T cell receptor and induce immune responses. However, precision screening of immunogenic tumor antigens remains a great challenge due to human leukocyte antigen (HLA) restriction and tumor antigen escape. Here, we introduce MultiTAP (Multi-modal Tumor Antigen Predictor), a pioneering multi-modal framework with TCR-peptide-HLA sequence and structure features incorporating an attention mechanism designed to accurately identify tumor antigens with immunogenic properties. By constructing the multi-modal TCR-peptide-HLA Dataset (TPHD) and integrating its sequence and structure, we perform antigen feature enhancement using peptide-HLA (pHLA) structural features at the residue level, achieving interpretable prediction of immunogenicity for tumor antigens. Relative to existing baseline models, the MultiTAP framework has exhibited superior efficacy in predicting the immunogenicity of tumor antigens. Through comprehensive out-of-distribution (OOD) assessments, MultiTAP has maintained predictive robustness across diverse HLA phenotypes and the continuously evolving landscape of epitope distributions. Overall, MultiTAP presents a brand-new and promising approach for cancer immunotherapies that target tumor antigens.
A Contribution To The Anatomy Of Two Rare Cetacean Species: The Hourglass Dolphin (Lagenorhynchus Cruciger) And The Spectacled Porpoise (Phocoena dioptrica)
Authors: Graïc Jean-Marie , Gerussi Tommaso , Cozzi Bruno , Kot Brian Chin Wing , Boys Rebecca M. , Perrott Matthew R. , Fleury Kane , Burns Emma , Webster Trudi , Betty Emma L. , Howarth Odette , Loch Carolina , White Sophie , Dawson Steve , Rayment William , Hunter Stuart , Cole Ros , Cox Derek , Young Melanie , Roberts Joseph , Waterhouse Tom , Smith Robin , Ogle Mike , Fyfe Jim , Hendriks Hannah , van Helden Anton , Johnstone Muriel , Stewart Ramari Oliphant , Fordyce R. Ewan , Stockin Karen A. 
Published: November 2024

AbstractThe anatomical description of the hourglass dolphin (Lagenorhynchus cruciger) and the spectacled porpoise (Phocoena dioptrica) remains largely unexplored, due to limited specimen availability and preservation challenges. This study employed digital imaging techniques, conventional histology and computed tomography to provide three-dimensional visualisation of anatomical structures for detailed volumetric analysis prior to necropsy. We present a comprehensive analysis of the gross macroscopical and microscopical morphology of two hourglass dolphins and four spectacled porpoises. The hourglass dolphins were characterised by their distinctive black and white pigmentation and a hooked dorsal fin, while the spectacled porpoises were distinguished for their large dorsal fin and unique eye markings. Morphometric measurements and skeletal characteristics were similar to those present in literature, while the anatomy and topography of internal organs and systems were similar to those found in other odontocetes. The respiratory systems showed an absence of lobation and a rightbronchus trachealis. Although precise lung measurements were challenging, qualitative assessments indicate relatively large lungs for their body size, supporting the “short dive, big lung” hypothesis and suggesting that these species are not deep divers. The spectacled porpoise dorsal fin is uniquely large accompanied by a developed blood supply. This organ is hypothesised to act as a thermoregulatory window, helping to manage body heat. Overall, this study provides new data on the anatomy of the hourglass dolphin and spectacled porpoise, providing insights that may influence future research on these rare species. The findings highlighted the importance of anatomical studies in explaining in detail the evolutionary relationships within cetaceans and their ecological roles in the Southern Ocean ecosystems.
Are we serologically prepared against an avian influenza pandemic and could seasonal flu vaccines help us?
Authors: Sanz-Muñoz Iván , Sánchez-Martínez Javier , Rodríguez-Crespo Carla , Concha-Santos Corina S. , Hernández Marta , Rojo-Rello Silvia , Domínguez-Gil Marta , Mostafa Ahmed , Martinez-Sobrido Luis , Eiros Jose M. , Nogales Aitor 
Published: November 2024

AbstractThe current situation with H5N1 highly pathogenic avian influenza virus (HPAI) is causing a worldwide concern due to multiple outbreaks in wild birds, poultry, and mammals. Moreover, multiple zoonotic infections in humans have been reported. Importantly, HPAI H5N1 viruses with genetic markers of adaptation to mammals have been detected. Together with HPAI H5N1, avian influenza viruses H7N9 (high and low pathogenic) stand out due to their high mortality rates in humans. This raises the question of how prepared we are serologically and whether seasonal vaccines are capable of inducing protective immunity against these influenza subtypes. An observational study was conducted in which sera from people born between years 1925-1967, 1968-1977, and 1978-1997 were collected before or after 28 days or 6 months post-vaccination with an inactivated seasonal influenza vaccine. Then, haemagglutination inhibition, viral neutralization, and immunoassays were performed to assess the basal protective immunity of the population as well as the ability of seasonal influenza vaccines to induce protective responses. Our results indicate that subtype-specific serological protection against H5N1 and H7N9 in the representative Spanish population evaluated was limited or nonexistent. However, seasonal vaccination was able to increase the antibody titers to protective levels in a moderate percentage of people, probably due to cross-reactive responses. These findings demonstrate the importance of vaccination and suggest that seasonal influenza vaccines could be used as a first line of defense against an eventual pandemic caused by avian influenza viruses, to be followed immediately by the use of more specific pandemic vaccines.ImportanceInfluenza A viruses (IAV) can infect and replicate in multiple mammalian and avian species. Avian influenza virus (AIV) is a highly contagious viral disease that occurs primarily in poultry and wild water birds. Due to the lack of population immunity in humans and ongoing evolution of AIV, there is a continuing risk that new IAV could emerge and rapidly spread worldwide causing a pandemic, if the ability to transmit efficiently among humans was gained. The aim of this study is to analyze the basal protection and presence of antibodies against IAV H5N1, and H7N9 subtypes in the population from different ages. Moreover, we have evaluated the h humoral response after immunization with a seasonal influenza vaccine. This study is strategically important to evaluate the level of population immunity that is a major factor when assessing the impact that an emerging IAV strain would have, and the role of seasonal vaccines to mitigate the effects of a pandemic.
Unsupervised Deep Disentangled Representation of Single-Cell Omics
Authors: Moinfar Amir Ali , Theis Fabian J. 
Published: November 2024

AbstractSingle-cell genomics allows for the unbiased exploration of cellular heterogeneity. Representation learning methods summarize high-dimensional single-cell data into a manageable latent space in a typically nonlinear fashion, allowing cross-sample integration or generative modeling. However, these methods often produce entangled representations, limiting interpretability and downstream analyses. Existing disentanglement methods instead either require supervised information or impose sparsity and linearity, which may not capture the complexity of biological data. We, therefore, introduce Disentangled Representation Variational Inference (DRVI), an unsupervised deep generative model that learns nonlinear, disentangled representations of single-cell omics. This is achieved by combining recently introduced additive decoders with nonlinear pooling, for which we theoretically prove disentanglement under reasonable assumptions. We validate DRVI’s disentanglement capabilities across diverse relevant biological problems, from development to perturbational studies and cell atlases, decomposing, for example, the Human Lung Cell Atlas into meaningful, interpretable latent dimensions. Moreover, we demonstrate that if applied to batch integration, DRVI’s integration quality does not suffer from the disentanglement constraints and instead is on par with entangled integration methods. With its disentangled latent space, DRVI is inherently interpretable and facilitates the identification of rare cell types, provides novel insights into cellular heterogeneity beyond traditional cell types, and highlights developmental stages.
Ophiostomatalean fungi associated withCyrtogenius luteusinfestedPinus massoniana, including characterization ofMasuyamyces qingyuanensissp. nov. in China
Authors: Liu Kun , Gao Xiang , Wang Ya-Jie , Yin Ming-Liang 
Published: November 2024

AbstractOphiostomatalean fungi refers to the species in the order Ophiostomatales of Ascomycota. This group of fungi comprises wood blue-stain agents and some species that are important pathogens of trees, nematodes, or humans. Most species in the Ophiostomatales have beneficial relationships with wood-boring insects such as bark beetles. Recent surveys were conducted to investigate the diversity of Ophiostomatoid fungi associated withCyrtogenius luteusinfestingPinus massonianain some areas of Guangdong, China. This study, 382 fungal strains were obtained, and 224 were identified as belonging to the Ophiostomatales order. Identification of these strains revealed that they spanned seven distinct genera. A new species,Masuyamyces qingyuanensis sp. nov., was discovered and identified through a combination of morphological and phylogenetic analyses across four gene regions: beta-tubulin (TUBB), internal transcribed spacer (ITS), large subunit ribosomal RNA (LSU), and translation elongation factor 1 alpha (EF1A).
Multiplexed perturbation of yew reveals cryptic proteins that enable a total biosynthesis of baccatin III and Taxol precursors
Authors: McClune Conor James , Liu Jack Chun-Ting , Wick Chloe , De La Peña Ricardo , Lange Bernd Markus , Fordyce Polly M. , Sattely Elizabeth S. 
Published: November 2024

AbstractPlants make complex and potent therapeutic molecules, but difficulties in sourcing from natural producers or chemical synthesis can challenge their use in the clinic. A prominent example is the anti-cancer therapeutic paclitaxel (Taxol®). Identification of the full paclitaxel biosynthetic pathway would enable heterologous drug production, but it has eluded discovery despite a half century of intensive research. Within the search space ofTaxus’large, enzyme-rich genome, we suspected the complex paclitaxel pathway would be difficult to resolve using conventional gene co-expression analysis and small sample sets. To improve the resolution of gene set identification, we developed a multiplexed perturbation strategy to transcriptionally profile cell states spanning tissues, cell types, developmental stages, and elicitation conditions. This approach revealed a set of paclitaxel biosynthetic genes that segregate into expression modules that suggest consecutive biosynthetic sub-pathways. These modules resolved seven new genes that, when combined with previously known enzymes, are sufficient for thede novobiosynthesis and isolation of baccatin III, an industrial precursor for Taxol, inNicotiana benthamianaleaves at levels comparable to the natural abundance inTaxusneedles. Included are taxane 1β-hydroxylase (T1βH), taxane 9α-hydroxylase (T9αH), taxane 7β-O-acyltransferase (T7ΑΤ), taxane 7β-O-deacetylase (T7dA), taxane 9α-O-deacetylase (T9dA), and taxane 9-oxidase (T9ox). Importantly, the T9αH we discovered is distinct and independently evolved from those recently reported, which failed to yield baccatin III with downstream enzymes. Unexpectedly, we also found a nuclear transport factor 2 (NTF2)-like protein (FoTO1) crucial for high yields of taxanes; this gene promotes the formation of the desired product during the first taxane oxidation step, resolving a longstanding bottleneck in paclitaxel pathway reconstitution. Together with a new β-phenylalanine-CoA-ligase, the eight genes discovered in this study enables the complete reconstitution of 3’-N-debenzoyl-2’-deoxy-paclitaxel with a 20-enzyme pathway inNicotianaplants. More broadly, we establish a generalizable approach for pathway discovery that scales the power of co-expression studies to match the complexity of specialized metabolism, enabling discovery of gene sets responsible for high-value biological functions.
Mitomycin C eliminates cyanobacterial transcription without detectable lysogen induction in aMicrocystis-dominated bloom in Lake Erie
Authors: Martin Robbie M. , Denison Elizabeth R. , Pound Helena L. , Barnes Ellen A. , Chaffin Justin D. , Wilhelm Steven W. 
Published: November 2024

AbstractAlthough evidence indicates that viruses are important in the ecology ofMicrocystisspp., many questions remain. For example, how doesMicrocystisexist at high, bloom-associated cell concentrations in the presence of viruses that infect it? The phenomenon of lysogeny and associated homoimmunity offer possible explanations to this question. Virtually nothing is known about lysogeny inMicrocystis, but a metatranscriptomic study suggests that widespread, transient lysogeny is active during blooms. These observations lead us to posit that lysogeny is important in modulatingMicrocystisblooms. Using a classic mitomycin C-based induction study, we tested for lysogeny in aMicrocystis-dominated community in Lake Erie in 2019. Treated communities were incubated with 1 mg L-1mitomycin C for 48 h alongside unamended controls. We compared direct counts of virus-like-particles (VLPs) and examined community transcription for active infection by cyanophage. Mitomycin C treatment did not increase VLP count. Mitomycin C effectively eliminated transcription in the cyanobacterial community, while we detected no evidence of induction. Metatranscriptomic analysis demonstrated that the standard protocol of 1 mg L-1was highly-toxic to the cyanobacterial population, which likely inhibited induction of any prophage present. Follow-up lab studies indicated that 0.1 mg L-1may be more appropriate for use in freshwater cyanobacterial studies. These findings will guide future efforts to detect lysogeny inMicrocystisblooms.ImportanceHarmful algal blooms dominated byMicrocystisspp. occur throughout the world’s freshwater ecosystems leading to detrimental effects on ecosystem services that are well documented. After decades of research, the scientific community continues to struggle to understand the ecology ofMicrocystisblooms. The phenomenon of lysogeny offers an attractive, potential explanation to several ecological questions surrounding blooms. However, almost nothing is known about lysogeny inMicrocystis. We attempted to investigate lysogeny in aMicrocystisbloom in Lake Erie and found that the standard protocols used to study lysogeny in aquatic communities are inappropriate for use inMicrocystisstudies, and perhaps freshwater cyanobacterial studies more broadly. This work can be used to design better methods to study the viral ecology ofMicrocystisblooms.
Microbiome impact of ibezapolstat and otherClostridioides difficileinfection relevant antibiotics using humanized mice
Authors: Wolfe Trenton M. , Jo Jinhee , Pinkham Nick V. , Garey Kevin W. , Walk Seth T. 
Published: November 2024

AbstractBackgroundIbezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for treatment ofClostridioides difficileinfection (CDI). Previous studies demonstrated IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics.MethodsGroups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare gut microbiome perturbation between treatment and no-drug control groups.ResultsAmong the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversity following FDX- and IBZ-treated groups were less pronounced compared to those observed in VAN-or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of Bacteroidota (phylum), with IBZ additionally increasing the relative abundance of Actinomycetota (phylum).ConclusionIn microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity compared to VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.
Impact of Paraben on Uterine Collagen: An Integrated and Targeted Correlative Approach Using Second Harmonic Generation Microscopy, Nanoindentation, and Atomic Force Microscopy
Authors: Arshee Mahmuda R. , Shukla Ritwik , Li Jie , Bagchi Indrani C. , Ziv-Gal Ayelet , Johnson A. J. Wagoner 
Published: November 2024

AbstractThis study investigates the structural and mechanical changes in uterine collagen following exposure to propylparaben (PP), using a combined methodology of Second Harmonic Generation (SHG) microscopy, Nanoindentation (NI), and Atomic Force Microscopy (AFM). SHG analysis identified significant disorganization in collagen fibril orientation in the circumferential layer and heterogeneous distribution of regions with elevated forward to backward ratios (F/B) across all uterine layers due to PP exposure. High F/B can indicate multiple potential fibril-level changes like thickened fibrils, higher crosslinking, fibril disorganization - changes not fully decipherable by SHG alone. Recognizing this limitation, the study employs NI and AFM to provide complementary mechanical and nanoscale insights. NI revealed increased indentation modulus in the exposed uteri, suggesting increased stiffness. Co-registration of the indentation response with SHG parameters uncovered that elevated F/B regions show enhanced mechanical stiffness, suggesting a fibrotic transformation following PP exposure. AFM was specifically performed on regions identified by SHG as having low or high F/B, providing the necessary nanoscale resolution to elucidate the structural changes in fibrils that are likely responsible for the observed alterations. This approach confirmed the presence of disordered and entangled collagen fibrils in the circumferential layer in all regions and an increase in fibril diameter in the high F/B regions in the exposed uteri. Together, these findings demonstrate significant alterations in collagen architecture due to PP exposure, revealing disruptions at both the fiber and fibril levels and highlighting the potential for broader applications of the multi-scale, multi-modal approach in collagenous tissue studies.
LUMIC: Latent diffUsion for Multiplexed Images of Cells
Authors: Hung Albert , Zhang Charles J. , Sexton Jonathan Z. , O’Meara Matthew J. , Welch Joshua D. 
Published: November 2024

AbstractThe rapid advancement of high-content, single-cell technologies like robotic confocal microscopy with multiplexed dyes (morphological profiling) can be leveraged to reveal fundamental biology, ranging from microbial and abiotic stress to organ development. Specifically, heterogeneous cell systems can be perturbed genetically or with chemical treatments to allow for inference of causal mechanisms. An exciting strategy to navigate the high-dimensional space of possible perturbation and cell type combinations is to use generative models as priors to anticipate high-content outcomes in order to design informative experiments. Towards this goal, we present the Latent diffUsion for Multiplexed Images of Cells (LUMIC) framework that can generate high quality and high fidelity images of cells. LUMIC combines diffusion models with DINO (self-Distillation with NO labels), a vision-transformer based, self-supervised method that can be trained on images to learn feature embeddings, and HGraph2Graph, a hierarchical graph encoder-decoder to represent chemicals. To demonstrate the ability of LUMIC to generalize across cell lines and treatments, we apply it to a dataset of∼27,000 images of two cell lines treated with 306 chemicals and stained with three dyes from the JUMP Pilot dataset and a newly-generated dataset of∼3,000 images of five cell lines treated with 61 chemicals and stained with three dyes. To quantify prediction quality, we evaluate the DINO embeddings, Kernel Inception Distance (KID) score, and recovery of morphological feature distributions. LUMIC significantly outperforms previous methods and generates realistic out-of-sample images of cells across unseen compounds and cell types.