bluuebunny/crossref_metadata_2025_split huggingface dataset:
A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders
Authors: Lee Arthur S. , Ayers Lauren J. , Kosicki Michael , Chan Wai-Man , Fozo Lydia N. , Pratt Brandon M. , Collins Thomas E. , Zhao Boxun , Rose Matthew F. , Sanchis-Juan Alba , Fu Jack M. , Wong Isaac , Zhao Xuefang , Tenney Alan P. , Lee Cassia , Laricchia Kristen M. , Barry Brenda J. , Bradford Victoria R. , Jurgens Julie A. , England Eleina M. , Lek Monkol , MacArthur Daniel G. , Lee Eunjung Alice , Talkowski Michael E. , Brand Harrison , Pennacchio Len A. , Engle Elizabeth C. 
Published: September 2024

AbstractUnsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN) cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generate single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers. We evaluate enhancer activity for 59 elements using an in vivo transgenic assay and validate 44 (75%), demonstrating that single cell accessibility can be a strong predictor of enhancer activity. Applying our cMN atlas to 899 whole genome sequences from 270 genetically unsolved CCDD pedigrees, we achieve significant reduction in our variant search space and nominate candidate variants predicted to regulate known CCDD disease genes MAFB, PHOX2A, CHN1, and EBF3 – as well as candidates in recurrently mutated enhancers through peak- and gene-centric allelic aggregation. This work delivers non-coding variant discoveries of relevance to CCDDs and a generalizable framework for nominating non-coding variants of potentially high functional impact in other Mendelian disorders.
Causal involvement of dorsomedial prefrontal cortex in learning the predictability of observable actions
Authors: Kang Pyungwon , Moisa Marius , Lindström Björn , Soutschek Alexander , Ruff Christian C. , Tobler Philippe N. 
Published: September 2024

AbstractSocial learning is well established across species. While recent neuroimaging studies show that dorsomedial prefrontal cortex (DMPFC/preSMA) activation correlates with observational learning signals, the precise computations that are implemented by DMPFC/preSMA have remained unclear. To identify whether DMPFC/preSMA supports learning from observed outcomes or observed actions, or possibly encodes even a higher order factor (such as the reliability of the demonstrator), we downregulate DMPFC/preSMA excitability with continuous theta burst stimulation (cTBS) and assess different forms of observational learning. Relative to a vertex-cTBS control condition, DMPFC/preSMA downregulation decreases performance during action-based learning but has no effect on outcome-based learning. Computational modeling reveals that DMPFC/preSMA cTBS disrupts learning the predictability, a proxy of reliability, of the demonstrator and modulates the rate of learning from observed actions. Thus, our results suggest that the DMPFC is causally involved in observational action learning, mainly by adjusting the speed of learning about the predictability of the demonstrator.
Revealing real-time 3D in vivo pathogen dynamics in plants by label-free optical coherence tomography
Authors: de Wit Jos , Tonn Sebastian , Shao Mon-Ray , Van den Ackerveken Guido , Kalkman Jeroen 
Published: September 2024

AbstractMicroscopic imaging for studying plant-pathogen interactions is limited by its reliance on invasive histological techniques, like clearing and staining, or, for in vivo imaging, on complicated generation of transgenic pathogens. We present real-time 3D in vivo visualization of pathogen dynamics with label-free optical coherence tomography. Based on intrinsic signal fluctuations as tissue contrast we image filamentous pathogens and a nematode in vivo in 3D in plant tissue. We analyze 3D images of lettuce downy mildew infection (Bremia lactucae) to obtain hyphal volume and length in three different lettuce genotypes with different resistance levels showing the ability for precise (micro) phenotyping and quantification of the infection level. In addition, we demonstrate in vivo longitudinal imaging of the growth of individual pathogen (sub)structures with functional contrast on the pathogen micro-activity revealing pathogen vitality thereby opening a window on the underlying molecular processes.
Private benefit of β-lactamase dictates selection dynamics of combination antibiotic treatment
Authors: Ma Helena R. , Xu Helen Z. , Kim Kyeri , Anderson Deverick J. , You Lingchong 
Published: September 2024

Abstractβ-lactam antibiotics have been prescribed for most bacterial infections since their discovery. However, resistance to β-lactams, mediated by β-lactamase (Bla) enzymes such as extended spectrum β-lactamases (ESBLs), has become widespread. Bla inhibitors can restore the efficacy of β-lactams against resistant bacteria, an approach which preserves existing antibiotics despite declining industry investment. However, the effects of combination treatment on selection for β-lactam resistance are not well understood. Bla production confers both private benefits for resistant cells and public benefits which faster-growing sensitive cells can also exploit. These benefits may be differentially impacted by Bla inhibitors, leading to non-intuitive selection dynamics. In this study, we demonstrate strain-to-strain variation in effective combination doses, with complex growth dynamics in mixed populations. Using modeling, we derive a criterion for the selection outcome of combination treatment, dependent on the burden and effective private benefit of Bla production. We then use engineered strains and natural isolates to show that strong private benefits of Bla are associated with increased selection for resistance. Finally, we demonstrate that this parameter can be coarsely estimated using high-throughput phenotyping of clonal populations. Our analysis shows that quantifying the phenotypic responses of bacteria to combination treatment can facilitate resistance-minimizing optimization of treatment.
The role of water mobility on water-responsive actuation of silk
Authors: Podbevšek Darjan , Jung Yeojin , Khan Maheen K. , Yu Honghui , Tu Raymond S. , Chen Xi 
Published: September 2024

AbstractBiological water-responsive materials that deform with changes in relative humidity have recently demonstrated record-high actuation energy densities, showing promise as high-performance actuators for various engineering applications. However, there is a lack of theories capable of explaining or predicting the stress generated during water-responsiveness. Here, we show that the nanoscale confinement of water dominates the macroscopic dehydration-induced stress of the regenerated silk fibroin. We modified silk fibroin’s secondary structure, which leads to various distributions of bulk-like mobile and tightly bound water populations. Interestingly, despite these structure variations, all silk samples start to exert force when the bound-to-mobile (B/M) ratio of confined water reaches the same level. This critical B/M water ratio suggests a common threshold above which the chemical potential of water instigates the actuation. Our findings serve as guidelines for predicting and engineering silk’s WR behavior and suggest the potential of describing the WR behavior of biopolymers through confined water.
Pixel to practice: multi-scale image data for calibrating remote-sensing-based winter wheat monitoring methods
Authors: Anderegg Jonas , Tschurr Flavian , Kirchgessner Norbert , Treier Simon , Graf Lukas Valentin , Schmucki Manuel , Caflisch Nicolin , Minguely Camille , Streit Bernhard , Walter Achim 
Published: September 2024

AbstractSite-specific crop management in heterogeneous fields has emerged as a promising avenue towards increasing agricultural productivity whilst safeguarding the environment. However, successful implementation is hampered by insufficient availability of accurate spatial information on crop growth, vigor, and health status at large scales. Challenges persist particularly in interpreting remote sensing signals within commercial crop production due to the variability in canopy appearance resulting from diverse factors. Recently, high-resolution imagery captured from unmanned aerial vehicles has shown significant potential for calibrating and validating methods for remote sensing signal interpretation. We present a comprehensive multi-scale image dataset encompassing 35,000 high-resolution aerial RGB images, ground-based imagery, and Sentinel-2 satellite data from nine on-farm wheat fields in Switzerland. We provide geo-referenced orthomosaics, digital elevation models, and shapefiles, enabling detailed analysis of field characteristics across the growing season. In combination with rich meta data such as detailed records of crop husbandry, crop phenology, and yield maps, this data set enables key challenges in remote sensing-based trait estimation and precision agriculture to be addressed.
The impact of group membership on punishment versus partner rejection
Authors: Loustau Trystan , Glassman Jacob , Martin Justin W. , Young Liane , McAuliffe Katherine 
Published: September 2024

AbstractPeople often display ingroup bias in punishment, punishing outgroup members more harshly than ingroup members. However, the impact of group membership may be less pronounced when people are choosing whether to stop interacting with someone (i.e., partner rejection). In two studies (N = 1667), we investigate the impact of group membership on both response types. Participants were assigned to groups based on a “minimal” groups paradigm (Study 1) or their self-reported political positions (Study 2) and played an incentivized economic game with other players. In this game, participants (Responders) responded to other players (Deciders). In the Punishment condition, participants could decrease the Decider’s bonus pay. In the Partner Rejection condition, participants could reject future interactions with the Decider. Participants played once with an ingroup member and once with an outgroup member. To control for the effects of intent and outcome, scenarios also differed based on the Decider’s Intent (selfish versus fair) and the Outcome (equal versus unequal distribution of resources). Participants punished outgroup members more than ingroup members, however group membership did not influence decisions to reject partners. These results highlight partner rejection as a boundary condition for the impact of group on responses to transgressions.
Modulating the unfolded protein response with ISRIB mitigates cisplatin ototoxicity
Authors: Li Jiang , Rouse Stephanie L. , Matthews Ian R. , Park Yesai , Eltawil Yasmin , Sherr Elliott H. , Chan Dylan K. 
Published: September 2024

AbstractCisplatin is a commonly used chemotherapy agent with a nearly universal side effect of sensorineural hearing loss. The cellular mechanisms underlying cisplatin ototoxicity are poorly understood. Efforts in drug development to prevent or reverse cisplatin ototoxicity have largely focused on pathways of oxidative stress and apoptosis. An effective treatment for cisplatin ototoxicity, sodium thiosulfate (STS), while beneficial when used in standard risk hepatoblastoma, is associated with reduced survival in disseminated pediatric malignancy, highlighting the need for more specific drugs without potential tumor protective effects. The unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways have been shown to be involved in the pathogenesis of noise-induced hearing loss and cochlear synaptopathy in vivo, and these pathways have been implicated broadly in cisplatin cytotoxicity. This study sought to determine whether the UPR can be targeted to prevent cisplatin ototoxicity. Neonatal cochlear cultures and HEK cells were exposed to cisplatin, and UPR marker gene expression and cell death measured. Treatment with ISRIB (Integrated Stress Response InhIBitor), a drug that activates eif2B and downregulates the pro-apoptotic PERK/CHOP pathway of the UPR, was tested for its ability to reduce apoptosis in HEK cells, hair-cell death in cochlear cultures, and hearing loss using an in vivo mouse model of cisplatin ototoxicity. Finally, to evaluate whether ISRIB might interfere with cisplatin chemoeffectiveness, we tested it in head and neck squamous cell carcinoma (HNSCC) cell-based assays of cisplatin cytotoxicity. Cisplatin exhibited a biphasic, non-linear dose–response of cell death and apoptosis that correlated with different patterns of UPR marker gene expression in HEK cells and cochlear cultures. ISRIB treatment protected against cisplatin-induced hearing loss and hair-cell death, but did not impact cisplatin’s cytotoxic effects on HNSCC cell viability, unlike STS. These findings demonstrate that targeting the pro-apoptotic PERK/CHOP pathway with ISRIB can mitigate cisplatin ototoxicity without reducing anti-cancer cell effects, suggesting that this may be a viable strategy for drug development.
Detection of breast cancer in digital breast tomosynthesis with vision transformers
Authors: Kassis Idan , Lederman Dror , Ben-Arie Gal , Giladi Rosenthal Maia , Shelef Ilan , Zigel Yaniv 
Published: September 2024

AbstractDigital Breast Tomosynthesis (DBT) has revolutionized more traditional breast imaging through its three-dimensional (3D) visualization capability that significantly enhances lesion discernibility, reduces tissue overlap, and improves diagnostic precision as compared to conventional two-dimensional (2D) mammography. In this study, we propose an advanced Computer-Aided Detection (CAD) system that harnesses the power of vision transformers to augment DBT’s diagnostic efficiency. This scheme uses a neural network to glean attributes from the 2D slices of DBT followed by post-processing that considers features from neighboring slices to categorize the entire 3D scan. By leveraging a transfer learning technique, we trained and validated our CAD framework on a unique dataset consisting of 3,831 DBT scans and subsequently tested it on 685 scans. Of the architectures tested, the Swin Transformer outperformed the ResNet101 and vanilla Vision Transformer. It achieved an impressive AUC score of 0.934 ± 0.026 at a resolution of 384 $$\times$$
×
384. Increasing the image resolution from 224 to 384 not only maintained vital image attributes but also led to a marked improvement in performance (p-value = 0.0003). The Mean Teacher algorithm, a semi-supervised method using both labeled and unlabeled DBT slices, showed no significant improvement over the supervised approach. Comprehensive analyses across different lesion types, sizes, and patient ages revealed consistent performance. The integration of attention mechanisms yielded a visual narrative of the model’s decision-making process that highlighted the prioritized regions during assessments. These findings should significantly propel the methodologies employed in DBT image analysis by setting a new benchmark for breast cancer diagnostic precision.
Enzymatic modification of cotton fibre polysaccharides as an enabler of sustainable laundry detergents
Authors: Yau Hamish C. L. , Byard James , Thompson Lily E. , Malekpour Adam K. , Robson Timothy , Bakshani Cassie R. , Lelanaite Ieva , Willats William G. T. , Lant Neil J. 
Published: September 2024

AbstractCotton is the most common natural fibre used in textile manufacture, used alone or with other fibres to create a wide range of fashion clothing and household textiles. Most of these textiles are cleaned using detergents and domestic or commercial washing machines using processes that require many chemicals and large quantities of water and energy. Enzymes can reduce this environmental footprint by enabling effective detergency at reduced temperatures, mostly by directly attacking substrates present in the soils. In the present study, we report the contribution of a cleaning cellulase enzyme based on the family 44 glycoside hydrolase (GH) endo-beta-1,4-glucanase from Paenibacillus polymyxa. The action of this enzyme on textile fibres improves laundry detergent performance in several vectors including soil anti-redeposition, dye transfer inhibition and stain removal. Molecular probes are used to study how this enzyme is targeting both amorphous cellulose and xyloglucan on textile fibres and the relationship between textile surface effects and observed performance benefits.
Understanding inter-individual variability of experimental pain habituation and conditioned pain modulation in healthy individuals
Authors: De Schoenmacker Iara , Scheuren Paulina S. , Sirucek Laura , Lütolf Robin , Gorrell Lindsay M. , Rosner Jan , Curt Armin , Schweinhardt Petra , Hubli Michèle 
Published: September 2024

AbstractAlthough reduced experimental pain habituation is proposed as a proxy of diminished endogenous pain modulatory capacity in chronic pain, prior studies show contradictory findings. Even across healthy participants, pain habituation varies substantially, which may relate to another measure of endogenous pain modulation, i.e., conditioned pain modulation (CPM). Hence, this study investigated the relationship between pain habituation and CPM. Pain habituation was assessed in 45 healthy participants between two blocks of 15–20 contact-heat stimuli applied to the hand. Habituation of subjective pain ratings and objective neurophysiological readouts (contact-heat evoked potential (CHEP) and palmar sympathetic skin response (SSR)) was investigated. CPM was assessed by comparing heat pain thresholds before and after hand immersion in a noxious cold (9 °C) and lukewarm water bath (32 °C, to control for repeated measures effects). Pain habituation showed a large variability, with subjective but not objective pain habituation correlating with cold-induced CPM effects (r = 0.50; p = 0.025). This correlation was not observed for ‘true’ CPM effects (corrected for repeated measures effects) nor for CPM effects induced by a lukewarm water bath. These findings suggest that the observed variability in subjective pain habituation may be influenced by both descending endogenous pain modulation and peripheral adaptation processes associated with repeated measures. Objective pain habituation readouts, i.e., CHEPs and SSRs, capture different, complementary aspects of endogenous pain modulation.
A privacy-preserving expert system for collaborative medical diagnosis across multiple institutions using federated learning
Authors: Markkandan S. , Bhavani N. P. G. , Nath Srigitha S. 
Published: September 2024

AbstractExpert system recommendation assists the healthcare system to develop in real-time monitoring and diagnosis of patient conditions over several healthcare institutions. Privacy concerns, however, present significant problems since patient data leaks can lead to big effects including financial losses for hospitals and invasions of personal privacy for people. To address these issues, the research introduces a privacy-preserving collaborative medical diagnosis (CMD) method on a federated learning (FL). FL maintains patient privacy and data localization by spreading only model parameters, therefore enabling training models on remote datasets. The combination of Partially Homomorphic Cryptosystem (PHC) and Residual Learning based Deep Belief Network (RDBN) ensures an accurate and safe classification of patient physiological data. Experimental results show that the proposed method is successful in maintaining the diagnostic accuracy over numerous healthcare institutions and protecting privacy. The results show that the RDBN and PHC computations requires around 1000 ms and 150 ms, respectively for classification and privacy; the data transmission from the user to server and from server to user is 5 MB and 4 MB, respectively. Finally with a 30% reduction in overhead, the proposed approach offers an average increase in classification accuracy of 10% over multiple datasets.
Population density as the attractor of business to the place
Authors: Kopczewska Katarzyna , Kubara Maria , Kopyt Mateusz 
Published: September 2024

AbstractFirm location studies traditionally assume that this is business that attracts other business to a given location. They focus on knowledge transfers between the most productive and innovative firms and analyse agglomeration economies arising from matching, learning and sharing mechanisms. We argue that the population density also attracts firms to the place. Therefore, we extend this stream of research by using the concept of economies of density to discuss the effects of the attraction of firms by population. Our study explores the existence of the hierarchical causal mechanism that occurs when 2nd line firms understood as non-innovative, less productive retail and service businesses together with human settlement create an environment that attracts 1st line firms - the most innovative and productive businesses. We show that population density and business agglomeration jointly affect the location of firms in different sectors and should be considered as complementary rather than substitutable attraction factors.
Galectin-9 as a new biomarker of acute-on-chronic liver failure
Authors: Ling Jun , You Shaoli , Chen Weiwei , Yang Xinxin , Xv Yiwen , Zhu Bing 
Published: September 2024

AbstractGalectin-9 (Gal-9) expression in patients with acute-on-chronic liver failure and its correlation with prognosis remain unclear. This study investigated the relationship between liver failure prognosis and Gal-9 expression analysis in patients with acute-on-chronic liver failure. Patients with acute-on-chronic liver failure attributable to hepatitis B and those with chronic hepatitis B were included in this single-center prospective cohort study. The Gal-9 levels in the acute-on-chronic liver failure group were significantly higher than those in the chronic hepatitis B group, and there was an upregulation of Gal-9 and T-cell immunoglobulin domain and mucin domain-3 expressions in peripheral blood T cells. Gal-9 was localized in the regenerative areas of liver tissues in patients with acute-on-chronic liver failure, co-localizing with Kupffer cells. Kaplan–Meier survival curves showed that patients with Gal-9 levels < 9.6 ng/ml had a worse prognosis, with the area under the receiver operating characteristic curve (AUC-ROC) being similar to that of the Model for End-Stage Liver Disease score. The combined ROC curve of the two had better predictive performance, with an AUC of 0.945. High Gal-9 levels in liver regenerative areas can serve as a prognostic marker, indicating a better prognosis for patients with hepatitis B virus-acute-on-chronic liver failure.