bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term impact of early identification of cerebral palsy
Authors: Rojas Ana-Marie
Published: January 2025

Purpose of review

Early identification of cerebral palsy (CP), as in all neurologic conditions, has a profound impact on the ability to initiate interventions, support the education and empowerment of parents, ameliorate the effect of the conditions, and importantly identifies cohorts for neuroprotection or repair to address the primary injury. CP is a life span condition. Rapid initiation of services, support and anticipatory guidance is essential to maximize functional outcomes, prevent or manage complications and improve quality of life.

Recent findings

CP diagnosis should not be delayed. Early imaging as well as motor and neurologic evaluation can aid in early detection of CP before age 5 months. Early therapeutic intervention can influence function and assist in prevention of complications that can impact abilities. There is important ongoing research with efforts to prevent CP or alter the phenotype of the condition.

Literature review provides evidence to change in standard of care in diagnosing CP. There are published guidelines on how to pursue the diagnosis during early infancy. Early identification results in early intervention with the purpose of enhancing functional skill development, prevention of complications, and establishing parental support. Early identification provides an optimistic view and opportunity to intervene immediately in hopes to have an impact in the functional outcome and improving quality of life.
Reducing Employee Injuries from Aggressive Patient Behavior at Children’s Hospital by Implementing a Behavioral Response Team
Authors: Martorana Julia A. , Griffith Debrea M. , Eiger Carmel , Maurer James J. , Burnside Amanda , Janssen Aron C. , Pergjika Alba , Hoffmann Jennifer A.
Published: January 2025

Background:

Among hospitalized children, episodes of aggressive patient behavior place healthcare staff at risk for serious injuries. By implementing a behavioral response team at a children’s hospital, we aimed to reduce monthly employee injuries related to aggressive patient behavior from 3.4 to 2.4 per 1,000 acute care visits during 12 months.

Methods:

At a children’s hospital, a multidisciplinary team used quality improvement methodology to implement a behavioral response team that provided proactive and reactive support to staff caring for children at risk for aggressive behavior. Full-scale implementation occurred in July 2022. We measured days between Occupational Health and Safety Administration (OSHA)-recordable employee injuries related to aggressive patient behavior and total monthly employee injuries related to aggressive patient behavior per 1,000 acute care visits (emergency department visits and/or hospitalizations) by patients 3 years of age or older.

Results:

In the year after full-scale implementation, an average of 101 BRT rounds and 17 reactive responses occurred per month. The maximum number of days between OHSA-recordable employee injuries related to aggressive patient behavior increased from 163 days in the year before full-scale implementation to 271 days in the following year. Monthly employee injuries related to aggressive patient behavior decreased from 3.4 to 1.7 injuries per 1,000 acute care visits by patients 3 years of age or older.

Conclusions:

The BRT model, which provides proactive and reactive support to hospital staff caring for children at risk for aggressive behavior, should be considered a strategy to reduce employee injuries and promote workplace safety.
Trypstatin as a Novel TMPRSS2 Inhibitor with Broad-Spectrum Efficacy Against Corona and Influenza Viruses
Authors: Lawrenz Jan , Wettstein Lukas , Alfonso Armando Rodríguez , Nchioua Rayhane , von Maltitz Pascal , Albers Dan P.J. , Zech Fabian , Vandeput Julie , Naesens Lieve , Fois Giorgio , Preising Nico , Schmierer Emilia , Almeida-Hernandez Yasser , Petersen Moritz , Ständker Ludger , Wiese Sebastian , Braubach Peter , Frick Manfred , Barth Eberhard , Sauter Daniel , Kirchhoff Frank , Sanchez-Garcia Elsa , Stevaert Annelies , Münch Jan
Published: January 2025

Respiratory viruses, such as SARS-CoV-2 and influenza, exploit host proteases like TMPRSS2 for entry, making TMPRSS2 a prime antiviral target. Here, we report the identification and characterization of Trypstatin, a 61-amino acid Kunitz-type protease inhibitor derived from human hemofiltrate. Trypstatin inhibits TMPRSS2 and related proteases, with IC50values in the nanomolar range, comparable to the small molecule inhibitor camostat mesylate.In vitroassays demonstrated that Trypstatin effectively blocks spike-driven entry of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and hCoV-NL63, as well as hemagglutinin-mediated entry of influenza A and B viruses. In primary human airway epithelial cultures, Trypstatin significantly reduced SARS-CoV-2 replication and retained activity in the presence of airway mucus.In vivo, intranasal administration of Trypstatin to SARS-CoV-2-infected Syrian hamsters reduced viral titers and alleviated clinical symptoms. These findings highlight Trypstatin’s potential as a broad-spectrum antiviral agent against TMPRSS2-dependent respiratory viruses.

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Single-cell morphological profiling reveals insights into cell death
Authors: Frey Benjamin , Holmberg David , Byström Petter , Bergman Ebba , Georgiev Polina , Johansson Martin , Hennig Patrick , Rietdijk Jonne , Rosén Dan , Carreras-Puigvert Jordi , Spjuth Ola
Published: January 2025

Abstract

Analysis of single-cell data has emerged as a powerful tool for studying biological processes and response to perturbations. However, its application in morphological profiling is less explored. In this study we profile six cell death subtypes induced by 50 small molecule drugs across six concentrations using the Cell Painting assay. We evaluate the performance of three feature extraction methods at single-cell and aggregated level and apply supervised and unsupervised analyses to uncover factors contributing to cell death mechanisms. Our results show that a bagged LightGBMXT model, trained on single-cell DeepProfiler achieved classification accuracy of 77.23%, with a top overall performance of 89.97% for corresponding aggregated profiles. Furthermore, self-supervised learning using the transformer-based DINO network revealed highly resolved and biologically meaningful subpopulations, shedding light on perturbation- and concentration-specific molecular targets and dose-dependant morphological changes. Our findings demonstrate the potential of studying phenomic data on single-cell level to enhance the characterization of cell death pathways, advancing our understanding of perturbation effects at a granular level.
3D-Printed Magnetic Levitation Device with Deep Learning-Assisted Particle Tracking and Analysis for High-Throughput Sorting
Authors: Ramarao Malavika , Ozaltin Alfa , Yaman Sena , Ozbozduman Kaan , Loc Irem , Ertok Nil , Gao Aria , Unlu Mehmet Burcin , Durmus Naside Gozde
Published: January 2025

Intrinsic density-based particle separation is fundamental to biomedical research and materials science. Magnetic levitation offers an accessible and label-free approach; however, current platforms are limited by throughput, complex fabrication requirements, and manual analysis methods. Here, we demonstrate a high-throughput magnetic levitation-based microfluidic device fabricated using commercial 3D printing, integrated with dual automated analysis systems. The device features optimized magnet configurations and wide channel design (1 mm × 1 mm) that enables gentle separation (<1 PSI) at throughputs of 66 mL/hr–– a ten-fold improvement over existing levitation platforms. We developed two complementary analysis tools: “Phase” for static levitation height measurements, and a deep learning pipeline combining CNN-based particle classification (>95% accuracy) with SORT (Simple Online and Realtime Tracking) algorithm for dynamic analysis. The automated system showed excellent correlation with manual counting (Pearson coefficients: 0.91-0.99, p<0.001). Through systematic optimization of magnet spacing and paramagnetic medium concentration (150 mM Gd), the platform achieved robust continuous-flow sorting while maintaining exceptional purity (>90%) and resolving density differences as small as 0.03 g/mL. This work establishes a versatile platform for particle sorting, enabling sophisticated analysis without specialized facilities or extensive operator training, with broad applications in biomedical research and diagnostics.
IL-27 limits HSPC differentiation during infection and protects from stem cell exhaustion
Authors: Aldridge Daniel L. , Lanzar Zachary , Phan Anthony T. , Christian David A. , Pardy Ryan , Min Booki , Kedl Ross M. , Hunter Christopher A.
Published: January 2025

Many inflammatory stimuli can induce progenitor cells in the bone marrow to produce increased numbers of myeloid cells as part of the process of emergency myelopoiesis. These events are associated with innate training and can have long-term impacts on hematopoietic stem and progenitor cell (HSPC) development but can also compromise their function. While many cytokines support emergency myelopoiesis, less is known about the mechanisms that temper these events. When mice that lack the cytokine IL-27 were infected withToxoplasma gondii, there was enhanced generation of monocyte progenitors and increased numbers of inflammatory monocytes. In the bone marrow of infected mice there was increased production of IL-27 that localized with HSPCs and a survey of cytokine receptor expression highlighted that HSPCs were uniquely poised to respond to IL-27. Furthermore, the use ofin vitrodifferentiation assays and mixed bone marrow chimeras revealed that HSPCs from IL-27 deficient mice are pre-disposed towards the monocyte lineage. Additional studies highlighted that after infection loss of the IL-27R resulted in reduced HSPC fitness that manifested as reduced proliferative responses and a decreased ability to reconstitute the hematopoietic system. Thus, the ability of IL-27 to act on HSPC provides a regulatory brake on differentiation to limit monocyte induction and preserve HSPC stemness.
Oligodendroglia vulnerability in the human dorsal striatum in Parkinson’s disease
Authors: Barba-Reyes Juan M. , Harder Lisbeth , Salas Sergio Marco , Jaisa-aad Methasit , Muñoz-Castro Clara , Rafati Nima , Nilsson Mats , Hyman Bradley T. , Serrano-Pozo Alberto , Muñoz-Manchado Ana B.
Published: January 2025

Oligodendroglia are the responsible cells for myelination in the central nervous system and their involvement in Parkinson’s disease (PD) is poorly understood. We performed snRNA-seq and image-based spatial transcriptomics of human caudate nucleus and putamen (dorsal striatum) from PD and Control brain donors to elucidate the diversity of oligodendroglia and how they are affected by the disease. We have defined fifteen subclasses, from precursor to mature cells, four of which are disease-associated. These PD-specific populations are characterized by the overexpression of heat shock proteins and distinct expression signatures, including immune responses and myelination alterations. We have also identified disruptions in cell communication and oligodendrocyte development, evidenced by changes in neurotransmitter receptors expression and cell adhesion molecules. These transcriptomic changes correlated with impaired myelin integrity and altered oligodendrocyte distribution in the striatum. Thus, we uncover oligodendroglia as a critical cell type in PD and a potential new therapeutic target.
Towards a Generative Paradigm for Large-scale Microbiome Analysis by Generative Language Model
Authors: Zhang Haohong , Kang Zixin , Zhang Yuli , Yang Ronghua , Ning Kang
Published: January 2025

Microbiome analysis has traditionally relied on taxonomic abundance tables, which, while effective, often constrain the exploration of deeper contextual relationships. In this study, we present MGM 2.0, a novel framework that applies advanced natural language processing (NLP) techniques to microbiome research. By reimagining microbiome samples as sentences and microbial species as words, MGM 2.0 enabled the extraction of nuanced patterns and relationships. The model demonstrated robust predictive performance in identifying exogenous species colonization (AUROC = 0.86). Additionally, through prompt-guided microbiome data generation, MGM 2.0 produced realistic microbial profiles conditioned on disease labels. The framework further revolutionized donor selection in fecal microbiota transplantation (FMT) by framing it as a sequence-to-sequence prediction task, enabling the prediction of post-transplantation community compositions and the identification of super donors for personalized treatments (average increase in C2R = 0.52). This innovative integration of NLP and microbiome science provides a versatile toolkit for predictive modeling, data generation, and personalized medicine.

Highlights

Introduced MGM 2.0, a generative language model utilizing sentence-like representation for microbiome analysis and generation.

Demonstrated that sentence-like representation preserves sample distinctions, enabling accurate microbial sample classification tasks, such as colonization prediction.

Generated realistic, disease-specific microbiome profiles using a prompt-guided approach, validated by a novel “Microbiome Turing Test.”

Applied MGM 2.0 to fecal microbiota transplantation (FMT) donor selection, accurately predicting post-transplant community compositions and identifying potential “super donors” for personalized treatment strategies.
Metadata Harmonization from Biological Datasets with Language Models
Authors: Verbitsky Alexander , Boutet Patrick , Eslami Mohammed
Published: January 2025

Biomedical research faces significant challenges in harmonizing metadata across diverse datasets due to inconsistent labeling and the lack of universally adopted ontologies. Conventional solutions, such as Common Data Elements, face adoption difficulties as they impede scientific progress by requiring researchers to navigate through thousands of standardized terms with subtle variations. Tools such as laboratory information management systems, while designed to enforce standardization, can hinder research progress when their rigid standards conflict with domain-specific documentation needs and evolving research practices. As a result of these challenges, researchers maintain their own annotation systems, leading to disconnected datasets that are difficult to integrate across studies.

This study presents a novel approach using large language models to automatically standardize researcher annotations to standards within ontologies. The approach is applied to multiple domains such as oncology, alcohol research, and infectious disease. Data augmentation strategies are presented to align training data with the space of human representations. These strategies generate realistic variations of standard terms to simulate how researchers naturally document their work, especially valuable in domains lacking the extensive terminology mappings needed for training language models. Experiments with fine-tuned GPT-2 variants show up to 96% accuracy on in-dictionary tasks and 17% on out-of-dictionary tasks, outperforming traditional techniques and zero-shot GPT-4o applications. This implies that there can be up to a 96% reduction in metadata standardization labor if a term exists in an ontology. We also show a significant trade-off between domain-specific models versus those that aim to generalize across domains such as infectious disease or alcohol research. While larger models excel at generalization, fine-tuned models consistently outperform on domain-specific terminology. This approach enables more efficient and accurate research data integration across biomedical fields, though out-of-dictionary generalization remains a challenge across all model sizes.
Single cell resolved spatial immune repertoire unveils spatial heterogeneity of lymphoid aggregates in human immune disorders
Authors: Zhan Xiaojuan , Liu Yi , Guo Yanying , Zhou Wenwen , Yan Yixin , Zeng Hui , Dong Xuan , Chen Xiaoyu , Ma Rong , Liu Zhong , Zhu Fan , Zheng Xubin , Li Xinxing , Yin Jinwen , Chan Francis Ka-ming , Liu Chuanyu , Liu Longqi , Xu Xun , Hou Yong , Tao Haoran , Dong Yuliang , Zeng Tao , Li Young , Zhou Jingying , Zeng Zexian , Feng Yu
Published: January 2025

Adaptive immunity, mediated by T and B cell responses, is essential for defending against infections and cancers while also being implicated in autoimmune diseases. Tracking T and B cell repertoiresin situat single-cell resolution is essential for understanding adaptive immune responses. To address the lack of tools forin situsingle-cell T/BCR (XCR) sequencing, we developed Stereo-XCR-seq, an efficient strategy for retrieving and sequencing TCR and BCR from Stereo-seq cDNA libraries at subcellular resolution. Stereo-XCR-seq provides unbiased full-length XCR reads alongside spatial transcriptomics, enabling the identification of heterogeneous lymphoid aggregates with distinct clonal activities in cancers and inflammatory bowel disease (IBD). We identified plasma cell aggregates that differ from tertiary lymphoid structures (TLSs) in both transcriptomic profiles and clonal activities, with spatial positioning potentially mediating unique immune responses. Collectively, Stereo-XCR-seq enablesin situsingle-cell profiling of T and B cell clonal activities within tissue microenvironments, providing insights into lymphocyte adaption to environmental stimuli. This technology provides potential for advancing our understanding of tissue immunity and the development of therapeutic strategies for immune disorders.
Phylogeny, ethnomedicinal use and the distribution of phytoestrogens in the Fabaceae
Authors: Thaweepanyaporn Kongkidakorn , Thompson Jamie B. , Vasudevan Nandini , Hawkins Julie A.
Published: January 2025

Aim of the study

Ethnomedicinal knowledge is a critical resource for drug discovery, and when combined with phylogenetic analysis, it increases the precision of bioprospecting. Phytoestrogens, compounds from plants with estrogenic activity, are commonly found across the Fabaceae family and hold the potential for managing menopause-related symptoms. This study focuses on methods to identify novel sources of phytoestrogens from the Fabaceae.

Materials and Methods

We identified 183 Fabaceae species traditionally used as aphrodisiacs or with application to control fertility to create a cross-cultural dataset of ethnomedicinal use. Phylogenetic analysis revealed “hot nodes”—lineages with a higher-than-expected number of species with these traits. The known distribution of estrogenic flavonoids was used to test whether the frequency of phytoestrogen-containing species was higher in “hot nodes”. Additionally, we examined the overlap of aphrodisiac-fertility uses with neurological applications, hypothesising that such species may have bioactive compounds with estrogenic properties. Lastly, the “hot-node” lineages without previously known estrogenic flavonoids were identified.

Results

Species in hot nodes were more likely to contain estrogenic flavonoids (21% of species), a major group of phytoestrogens, compared to Fabaceae as a whole (7% of species). Moreover, aphrodisiac-fertility species with neurological applications showed even higher search efficiency, with 62% of such species confirmed to contain estrogenic flavonoids. Furthermore, we identified 43 high-priority hot nodes including several notable genera such asDelonixandIndigofera.

These lineages might represent promising targets for future studies on phytoestrogens.

Conclusions

The results demonstrated the predictive power of combining phylogenetic and ethnomedicinal data to guide the discovery of novel drugs with therapeutic potential for menopause, fertility, and neurological health.
Plakophilin-2 Coordinates Energy Metabolism and Contractility in Cardiomyocytes, Revealing Its Roles beyond Desmosomes
Authors: Aycinena J. Alex , Tefera Anley E. , Perea-Gil Isaac , Holbrook-Smith Duncan , Williams Kevin , Shenwai Reva , Farshidfar Farshad , Ryback Brendan , Foppe Katelyn , Wu Iris , Zeng Aliya , Pell Melissa Van , Xu Emma , Woods Joseph , Jones Samantha , Hatter Yolanda , Dee-Hoskins Cristina , Madariaga Jessie , Robinson Kevin , Greer-Short Amara , Song Xiaomei , Ivey Kathryn N. , Priest James , Argast Gretchen , Hoey Timothy , Driggers Edward , Yang Zhihong Jane
Published: January 2025

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease associated with ventricular arrhythmias and an increased risk of sudden cardiac death. Mutations in the desmosome genePlakophilin-2,PKP2, lead to reduction in PKP2 protein and collapse of desmosomes that is known to compromise contractility and electrical stability of cardiomyocytes. Our previous studies demonstrated the efficacy of adeno-associated virus 9 (AAV9)-mediated restoration of PKP2 expression in a cardiac specific knock-out mouse model ofPkp2and revealed profound changes in mRNA signatures of metabolic enzymes that were reversed by the gene replacement approach. In this study, we used PKP2-deficient mouse hearts and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to identify changes in steady-state metabolite levels associated with impaired lipid homeostasis, glycolysis, and glucose oxidation. These metabolic phenotypes align with human ARVC metabolic data and reflect an intrinsic impairment of cellular energy metabolism. Here we showed for the first time that these intracellular metabolic defects were associated specifically with poor contractility of cardiomyocytes. AAV9:PKP2 restored contractility, improved electrophysiological properties and Ca2+transients. In contrast, we observed that treating PKP2-deficient cardiomyocytes pharmacologically with small molecule metabolic enhancers improved contractility but not electrophysiological properties and Ca2+transients, suggesting differential sensitivity of structure-mediated functions in response to metabolic perturbance. Our study modeled and revealed a direct intracellular connection between compromised PKP2 function and metabolic impairment. We proposed that an increased risk of decoupling energy-responsive contractility from less energy-responsive electrical activities can be a new arrhythmogenic mechanism, potentially responsible for exercise-triggered cardiac adversity in ARVC disease development and progression.
Histone deacetylase-1 is required for epigenome stability inNeurospora crassa
Authors: Ebot-Ojong Felicia , Ferraro Aileen R. , Kaddar Farh , Hull-Crew Clayton , Scadden Ashley W. , Klocko Andrew D. , Lewis Zachary A.
Published: January 2025

Polycomb group (PcG) proteins form chromatin modifying complexes that stably repress lineage- or context-specific genes in animals, plants, and some fungi. Polycomb Repressive Complex 2 (PRC2) catalyzes trimethylation of lysine 27 on histone H3 (H3K27me3) to assemble repressive chromatin. In the model fungusNeurospora crassa,H3K27me3 deposition is controlled by the H3K36 methyltransferase ASH1 and components of constitutive heterochromatin including the H3K9me3-binding protein HETEROCHROMATIN PROTEIN 1 (HP1). Hypoacetylated histones are a defining feature of both constitutive heterochromatin and PcG-repressed chromatin, but how histone deacetylases (HDACs) contribute to normal H3K27me3 and transcriptional repression within PcG-repressed chromatin is poorly understood. We performed a genetic screen to identify HDACs required for repression of PRC2-methylated genes. In the absence of HISTONE DEACETYLASE-1 (HDA-1), PRC2-methylated genes were activated and H3K27me3 was depleted from typical PRC2-targeted regions. At constitutive heterochromatin, HDA-1 deficient cells displayed reduced H3K9me3, hyperacetylation, and aberrant enrichment of H3K27me3 and H3K36me3. CHROMODOMAIN PROTEIN-2 (CDP-2) is required to target HDA-1 to constitutive heterochromatin and was also required for normal H3K27me3 patterns. Patterns of aberrant H3K27me3 were distinct in isogenic Δhda-1strains, suggesting that loss of HDA-1 causes stochastic or progressive epigenome dysfunction. To test this, we constructed a newΔhda-1strain and performed a laboratory evolution experiment. Deletion ofhda-1led to progressive epigenome decay over hundreds of nuclear divisions. Together, our data indicate that HDA-1 is a critical regulator of epigenome stability inN. crassa.
Research advancements on the application of sterile insect technique for the control of lepidopteran pests over the past two decades: A Systematic Review
Authors: Karabo Bambo , Malinga LN
Published: January 2025

Many lepidopterans’ species, such as fruit borer (Helicoverpa armigera) on tomato, apple mothCydia pomonella(codling moth), and orange mothThaumatotibia leucotreta(false codling moth), are among many lepidopterans that are crop pests. In the early 1930s, the concept of the sterile insect technique was conceived in response to the global threat of insect pests and the excessive use of insecticides, which were proven to pose a health risk to humans. This pest control tactic has gained and is currently gaining more traction in all regions where it is implemented on both small and large scales. This systematic review looks at the recent research advances in the application of sterile insect techniques for the control of lepidopteran pests. The paper analyses publications, focusing on the geographic distribution of studies, target species, irradiation source, and the year of publication. It highlights the growing interest in SIT as an environmentally friendly pest management strategy compared to insecticide use. The paper compiles and summarises information over the last two decades on the lepidopteran species studied, the study approach, the country where the study was performed, the source of irradiation, and the year of publication. It also analysed the suitability of each lepidopteran species as an SIT candidate and the effectiveness of this control strategy. The review resulted in 2 537, from which 24 publications matched the search criteria. From the results, 14 species were identified, and the most studied lepidopteran wasT. leucotreta. The review discusses the effectiveness of SIT in controlling various lepidopteran species and explores the potential for further development and implementation of SIT programmes globally.
Feeder-free culture of naive human pluripotent stem cells retaining embryonic, extraembryonic and blastoid generation potential
Authors: Rossignoli Giada , Oberhuemer Michael , Brun Ida Sophie , Zorzan Irene , Osnato Anna , Wenzel Anne , van Genderen Emiel , Drusin Andrea , Panebianco Giorgia , Magri Nicolo , Solis Mairim Alexandra , Colantuono Chiara , van Knippenberg Sam Samuel Franciscus Allegonda , Pham Thi Xuan Ai , Khodeer Sherif , Grumati Paolo , Cacchiarelli Davide , Martini Paolo , Rivron Nicolas C , Pasque Vincent , Zylicz Jan Jakub , Leeb Martin , Martello Graziano
Published: January 2025

Conventional human pluripotent stem cells (hPSCs) are widely used to study early embryonic development, generate somatic cells, and model diseases, with differentiation potential aligned to a post-implantation epiblast identity. In the past decade, naive hPSCs, representing a pre-implantation stage, have been derived. Naive hPSCs efficiently differentiate towards embryonic and extraembryonic lineages such as trophectoderm, primitive endoderm, and extraembryonic mesoderm, and also self-organize into blastocyst-like structures called blastoids. However, their culture typically relies on mouse embryonic fibroblasts (MEFs), which are variable, resource-intensive, and can confound analyses. We report the long-term maintenance of naive hPSCs in a feeder-free, serum-coated system. We successfully expanded for up to 25 passages 8 different naive hPSCs lines across 5 laboratories. Growth rate, clonogenicity, and gene expression profiles on serum coating were comparable to MEF-based cultures, but serum coating eliminated fibroblast contamination. Naive hPSCs cultured on serum exhibited more efficient germ layer specification, retained trophectoderm potential and high blastoid formation efficiency. Exome sequencing revealed fewer mutations in serum-cultured cells, and mass spectrometry identified extracellular matrix proteins such as vitronectin, fibronectin, and collagens in the serum coating. Overall, serum coating offers a scalable, cost-effective and therefore widely applicable alternative for naive hPSC culture, maintaining developmental potential, reducing DNA mutations, and eliminating MEF-related confounding factors. We believe serum coating will expand the use of naive hPSCs to large-scale studies and facilitate the investigation of mechanistic insights into developmental and disease modelling.
Hsp70 chaperones, Ssa1 and Ssa2, limit poly(A) binding protein aggregation
Authors: Buchholz Hannah E. , Martin Sean A. , Dorweiler Jane E. , Radtke Claire M. , Knier Adam S. , Beans Natalia B. , Manogaran Anita L.
Published: January 2025

Molecular chaperones play a central role in maintaining protein homeostasis. The highly conserved Hsp70 family of chaperones have major functions in folding of nascent peptides, protein refolding, and protein aggregate disassembly. In yeast, loss of two Hsp70 proteins, Ssa1 and Ssa2, is associated with decreased cellular growth and shortened lifespan. While heterologous or mutant temperature sensitive proteins form anomalous large cytoplasmic inclusions inssa1Δssa2Δstrains, it is unclear how endogenous wildtype proteins behave and are regulated in the presence of limiting Hsp70s. Using the wildtype yeast Poly A binding protein (Pab1), which is involved in mRNA binding and forms stress granules (SGs) upon heat shock, Pab1 forms large inclusions in approximately half ofssa1Δssa2Δcells in the absence of stress. Overexpression of Ssa1, Hsp104, and Sis1 almost completely limits the formation of these large inclusions inssa1Δssa2Δ, suggesting that excess Ssa1, Hsp104 and Sis1 can each compensate for the lower levels of Ssa proteins. Upon heat shock, SGs also form in cells whether large Pab1 inclusions are present or not. Surprisingly, cells containing only SGs disassemble faster than wildtype, whereas cells with both large inclusions disassemble slower albeit completely. We suspect that disassembly of these large inclusions is linked to the elevated heat shock response and elevated Hsp104 and Sis1 levels inssa1Δssa2Δstrains. We also observed that wildtype cultures grown to saturation also form large Pab1-GFP inclusions. These inclusions can be partially rescued by overexpression of Ssa1. Taken together, our data suggests that Hsp70 not only plays a role in limiting unwanted protein aggregation in normal cells, but as cells age, the depletion of active Hsp70 possibly underlies the age-related aggregation of endogenous proteins.
A Novel COE-D8-Fosfomycin Conjugate Effectively Against First-line Antibiotic ResistantUropathogenic Escherichia coli
Authors: Ruan Lin , Fan Cun , Chen Jingjie , Wang Yingxia , Ren Yuji , Yuan Wenli , Xiong Xiaozhe , Guo Chunming
Published: January 2025

Recurrent urinary tract infections (UTIs) are increasingly associated with antibiotic resistance, posing significant clinical challenges. This study evaluates the antimicrobial efficacy of the membrane-intercalating conjugated oligoelectrolyte COE-D8 against uropathogenic Escherichia coli (UPEC). Among 93 clinical UPEC isolates, over 50% demonstrated resistance to first-line antibiotics, with compound sulfamethoxazole showing the highest resistance (75% at a minimum inhibitory concentration (MIC) >512 μg/mL). COE-D8 significantly reduced resistance rates, achieving less than 50% at 32 μg/mL and below 5% at 512 μg/mL, while demonstrating at least fourfold faster bacterial elimination than standard antibiotics.

Mechanistic studies revealed that COE-D8 disrupts bacterial membranes, inducing rapid lysis. However, its cytotoxicity in mammalian cells at 2 μg/mL limits clinical application. To address this, a combination therapy with fosfomycin was explored, significantly reducing COE-D8 toxicity by at least fourfold in vitro. In mouse models, fosfomycin co-administration mitigated COE-D8-induced toxicity and prevented mortality at higher doses without compromising antimicrobial efficacy.

These findings highlight the potential of COE-D8, particularly in combination with fosfomycin, as a promising strategy to combat antibiotic-resistant UPEC while addressing toxicity challenges.
Shared and individual tuning curves for social vision
Authors: Varrier Rekha S. , Su Zishan , Liang Qi , Benson Tory , Jolly Eshin , Finn Emily S.
Published: January 2025

A stimulus with light is clearly visual; a stimulus with sound is clearly auditory. But what makes a stimulus “social”, and how do judgments of socialness differ across people? Here, we characterize both group-level and individual thresholds for perceiving the presence and nature of a social interaction. We take advantage of the fact that humans are primed to see social interactions—e.g., chasing, playing, fighting—even in very un-lifelike stimuli such as animations of geometric shapes. Unlike prior work using these stimuli, we exploit their most advantageous property, which is that their visual features are fully parameterizable. We use this property to construct psychophysics-inspired “social tuning curves” for individual subjects. Social tuning curves are stable within individuals, unique across individuals, and show some relationship to socio-affective traits. Results support the view that social information processing begins early in the perceptual hierarchy. Further, our approach lays the foundation for a generative account of social perception in single subjects.
A simulation-based approach to optimizing resource allocation and logistics in construction projects: a case study
Authors: Nikoukar Shayan , Tavakolan Mehdi
Published: January 2025

Purpose

This research aims to address the challenge of inefficient decision-making in site layout planning and resource allocation for construction projects. Existing approaches often rely on mathematical models that produce unrealistic results or encounter limitations confined to the site itself. To overcome these constraints, this study proposes a simulation-based approach with a focus on automatically optimizing tower crane placement, depot locations, and supplier selection. The primary objective is to minimize project costs while enhancing overall efficiency and productivity.

Design/methodology/approach

The implementation integrates a genetic algorithm and a discrete event simulation model featuring a central control kernel. Key considerations include project boundaries, site layout features, depot locations, and manufacturing and transportation capabilities. The simulation process assesses each solution, encompassing critical stages like manufacturing, transfer to depot, site transportation, and installation. The proposed approach is tested using an actual steel structure project in Tehran, Iran.

Findings

Results demonstrate substantial cost reductions compared to the contractor plan, showcasing the superiority of the proposed simulation-based optimization approach. The findings underscore the practical applicability of the research, providing valuable insights for industry professionals to make informed decisions and enhance project outcomes in real-world construction projects.

Originality/value

This integrated simulation-based optimization approach offers a robust framework for realistic and effective site layout planning and resource allocation in general steel construction projects. Its general simulation mechanism allows for easy expansion and application to similar projects, capable of assessing a large number of alternatives. The research contributes to the field by presenting a novel and effective method for addressing decision-making challenges in construction project planning and resource allocation.
Contextualizing the ethical behaviour of professional accountants in a developing country: do their personal idiosyncrasies matter?
Authors: Serwaa Owusu Mensah Ewurama , Ahomka Yeboah Moses , Ansong Abraham
Published: January 2025

Purpose

The study aims to investigate the influence of critical socio-cultural factors common in developing countries on the ethical behaviour of professional accountants and the extent to which their self-control strengthens or weakens the relationships.

Design/methodology/approach

This paper relied on the quantitative approach to collect data from 366 professional accountants and used the partial least squares structural equation modelling technique to test hypotheses in the study.

Findings

This paper established that susceptibility to positive peer influence, materialism and political trust influence the ethical behaviour of professional accountants. Also, self-control moderates the relationship between susceptibility to positive peer influence and ethical behaviour of professional accountants. However, self-control does not moderate the relationships between materialism and ethical behaviour as well as political trust and ethical behaviour of professional accountants.

Practical implications

The regulatory institutions should review the existing ethical codes and standards to clarify the guidelines on conflicts of interest, financial temptations, materialistic influence and other related matters. Further, training programs must integrate self-control lessons. These programs should focus on enhancing self-control skills, particularly in situations where peer influence and political mistrust are entrenched.

Originality/value

This paper demonstrates the novelty in how critical socio-cultural factors could be contingent on individual circumstances and personal idiosyncrasies in influencing ethical behaviour.
Influential factors for effective facilities management practices in public special economic zones (PSEZ): a case study of Benjamin Mkapa and Hifadhi SEZs in Dar es Salaam, Tanzania
Authors: Kongela Sophia Marcian , Mugeta Nyaganya Donald , Lucian Charles A.
Published: January 2025

Purpose

Special economic zones (SEZs) typically require high-quality service and infrastructure, as well as the presence of skilled and experienced facilities managers. However, the zones face several challenges in terms of facility management, such as poor infrastructure and an unprofessional approach to facilities management (FM). Using two public SEZs, this study aims to examine the drivers of effective facilities management practices, evaluate management strategies and explore challenges that prevent the zones’ effective facilities management.

Design/methodology/approach

The study uses a mixed-method research approach to collect data from selected investors and facilities managers, with primary data collected through a questionnaire to 101 respondents and interviews conducted with 8 facilities managers. Interpretive analysis was used to analyse qualitative data, while descriptive analysis was used to analyse data collected through a survey.

Findings

The results show that FM in the zones is highly in-house, with facilities managers’ roles only seen as critical during the occupation stage, little involvement during the construction stage and no involvement at all during the design stage. The analysis of the drivers for effective FM practices reveals a disparity between what is occurring on the ground and best practices. Furthermore, investors were dissatisfied with the quality of facilities management practices, the competence of facilities managers in carrying out their facilities management responsibilities and the time required to deliver services.

Originality/value

This study proposed a conceptual framework that guides policymakers and other stakeholders on properly managing PSEZs to attract investors’ interest. The study also calls for professional FM in PSEZs, policy intervention to separate government ownership from Zone management and addressing problems that impede zone competitiveness.
Driving unlegislated social value through local-government operated construction procurement
Authors: Mensah Sarfo , Ameyaw Collins
Published: January 2025

Purpose

Social value (SV) is gaining traction worldwide. However, there are no clear strategies to drive SV where there is limited or no formal SV legislation. The purpose of this study is to determine the key drivers of SV through construction procurement practices in regions without formal SV laws.

Design/methodology/approach

Quantitative data on the SV drivers of construction projects were obtained from local government construction procurement operatives using a survey questionnaire. The analytic hierarchy process was applied to prioritise SV drivers. A one-sample t-test was used to determine the significance of the SV drivers. Subsequently, the Pareto technique was deployed to determine the key drivers of SV.

Findings

The key drivers of SV to consider during construction procurement are investment by project clients, the education and training of contractors and consultants and organisational planning and policy reformation.

Social implications

The findings of this study will engender investment in sustainable projects and the integration of SV into construction practices to elevate industry standards, enhance corporate reputation and meet social expectations. The strategies identified in this study for promoting SV will foster community development through improved infrastructure, job creation and economic growth while supporting long-term sustainability and resilience.

Originality/value

The originality of this research lies in its context-specific insights into a country without formal SV legislation. The proactive measures identified, such as education and policy alignment, demonstrate a bottom-up approach for integrating SV into construction procurement. This contrasts with top-down legislative approaches seen in other contexts, providing a unique perspective on how SV can be driven in the absence of formal laws.
Factors influencing donor giving behaviours in charitable donations
Authors: Allah Pitchay Anwar Bin , Mohd Hashim Nur Syazni Arina , Ganesan Yuvaraj , Shaharudin Muhammad Shabir
Published: January 2025

Purpose

The post-disaster effect is an essential for countries to rebuild an affected place and provide basic needs for victims. However, the government fund alone is insufficient to cover the total loss of victims. Hence, most of the non-government organisations (NGOs) will play an essential role in raising donation funds from the public. Therefore, this study aims to examine the relationship between information disclosures and giving behaviour.

Design/methodology/approach

A total of 215 responses were gathered through a self-administered questionnaire. The data is analysed using structural equation modelling technique.

Findings

The study result shows that background information, financial information, non-financial information and governance information directly affect trust. Trust is a significant mediator between background, financial, non-financial and governance information towards giving behaviour. Besides, the results illustrated that religious belief does not moderate the relationship between trust and giving behaviour.

Originality/value

This study provides significant knowledge that may be useful for NGOs to be aware of the importance of information disclosures revealed by organisations and make required decisions for potential donors to have trust in organisations handling donations and will be engaging in giving behaviour.
Exploring learner and environmental factors in facilitating networked learning within the workplace
Authors: Khor Ean Teng , Looi Chee Kit , Lian Zixuan , Darshan Dave
Published: January 2025

Purpose

Networked learning facilitates collaboration and learning interactions. This study aims to explore networked learning in the workplace (knowledge sharing and connection building) and gain insights into the contextual factors (learner and environmental) of learning interactions.

Design/methodology/approach

Thematic analysis was conducted to explore how learning interactions were facilitated among healthcare workers in a large hospital in Singapore. This study examined both the learner and environmental factors of learning interactions. Interview and focus group discussions qualitative data were included in the analysis.

Findings

The findings of this study reveal that more emphasis can be placed on the environmental factors, and targeting these factors would provide a good foundation for networked learning in the workplace, whereas learner factors could be promoted to enhance additional learning interactions. This study also found that workers learn most frequently from experienced seniors, indicating the value of mentorship programmes in fostering high-quality learning interactions.

Originality/value

This paper sheds light on the comprehensive set of factors that encourage networked learning among healthcare professionals and provides empirical findings that might direct future studies in similar domains.
Tenapanor: A novel therapeutic agent for dialysis patients with hyperphosphatemia
Authors: Akizawa Tadao , Urano Natsuki , Ikejiri Kazuaki , Nakanishi Kaoru , Fukagawa Masafumi
Published: January 2025

Patients on dialysis often develop hyperphosphatemia, contributing to an increased risk of cardiovascular events and mortality. Currently, several types of phosphate binders (PBs) exist for the treatment of hyperphosphatemia, but they are sometimes associated with drug‐specific side effects and high pill burden, making it difficult to control serum phosphorus appropriately. Tenapanor, which has a novel mechanism to reduce serum phosphorus via selective sodium/proton exchange transporter 3 inhibition, was approved for hyperphosphatemia in Japan in 2023. Four phase 3 studies of tenapanor have been performed in Japan and have demonstrated its efficacy and safety as a single‐agent drug, add‐on effects to PBs for patients with refractory hyperphosphatemia that cannot be improved with PBs alone, and reduction of the pill burden associated with PBs. This review provides an overview of the characteristics and previous clinical studies of tenapanor and describes the clinical benefits of tenapanor over current therapy in patients on dialysis.
Production of nondairy fermented products with chestnut puree as substrate and milk kefir grains or two lactic acid bacteria
Authors: Afonso Maria João , Ramalhosa Elsa , del Río Pablo G. , Martins Fátima , Baptista Paula , Pereira Ermelinda L. , Guerra Nelson P.
Published: January 2025

This work aimed to study the production, for the first time, of three fermented products of chestnut puree (CP) with milk kefir grains, a higher nisin‐producing (Lactococcus (L.) lactis CECT 539) and a higher lactic acid‐producing (Lactobacillus (Lb.) casei CECT 4043) lactic acid bacteria (LAB). After studying the CP rheology, the ability of the two LAB to assimilate the carbon sources (starch, sucrose, glucose, and fructose) present in the CP was assayed. The two LAB grew well on glucose, fructose, and sucrose, but they did not use starch. Fermentation of CP with the two LAB and kefir grains allowed us to obtain three fermented products that contained no alcohol and low levels of sugars, lactic, and acetic acids, as well as viable cell counts. After 24 h of fermentation, bacterial counts increased by 2.12 log10 cycles for Lb. casei and 2.44 log10 cycles for L. lactis. Although the final counts for both LAB were very similar (p > 0.05), L. lactis grew faster than Lb. casei and produced a higher concentration of lactic acid. The total microbial counts for kefir increased by 1.16 log10 cycles, after 28 h of incubation, indicating that the microorganisms of the kefir grains adapted well to the composition of the CP. As no ethanol was detected, these results suggest the possibility of producing healthy, nonalcoholic, and low‐calorie CPs.