bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural variability and individuality of walking behavior inDrosophila
Authors: Godesberg Vincent , Bockemühl Till , Büschges Ansgar 
Published: November 2023

AbstractInsects use walking behavior in a large number of contexts, such as exploration, foraging, escape and pursuit, or migration. A lot is known on how nervous systems produce this behavior in general and also how certain parameters vary with regard to walking direction or speed, for instance. An aspect that has not received much attention is if and how walking behavior varies across individuals of a particular species. To address this, we created a large corpus of kinematic walking data of many individuals of the fruit flyDrosophila. We only selected instances of straight walking in a narrow range of walking speeds to minimize the influence of these high-level parameters, aiming to uncover more subtle aspects of variability. Using high-speed videography and automated annotation we captured the positions of the six leg tips for thousands of steps and used principal components analysis to characterize the postural space individuals used during walking. Our analysis shows that the largest part of walking kinematics can be described by five principal components (PCs). Separation of these five PCs into a 2-dimensional and a 3-dimensional subspace was found to divide the description of walking behavior into invariant features shared across individuals and features that relate to the specifics of individuals; the latter features can be regarded as idiosyncrasies. We also demonstrate that this approach can detect the effects of experimental interventions in an unbiased manner and that general aspects of individuality, such as the average width of the individual walking posture, can be described.Summary statementThe kinematics of walking behavior inDrosophilacan be decomposed into general aspects of motor output and idiosyncrasies of individual flies.
VaxSeer: Selecting influenza vaccines through evolutionary and antigenicity models
Authors: Shi Wenxian , Wohlwend Jeremy , Wu Menghua , Barzilay Regina 
Published: November 2023

AbstractCurrent vaccines provide limited protection against rapidly evolving viruses. For example, the flu vaccine’s effectiveness has averaged below 40% for the past five years. Today, clinical outcomes of vaccine effectiveness can only be assessed retrospectively. Since vaccine strains are selected at least six months ahead of flu season, prospective estimation of their effectiveness is crucial but remains under-explored. In this paper, we propose anin-silicomethod named VaxSeer that selects vaccine strains based on their coverage scores, which quantifiesexpectedvaccine effectiveness in future seasons. This score considers both the future dominance of circulating viruses and antigenic profiles of vaccine candidates. Based on historical WHO data, our approach consistently selects superior strains than the annual recommendations. Finally, the prospective coverage score exhibits a strong correlation with retrospective vaccine effectiveness and reduced disease burden, highlighting the promise of this framework in driving the vaccine selection process.
Capturing cell heterogeneity in representations of cell populations for image-based profiling using contrastive learning
Authors: van Dijk Robert , Arevalo John , Babadi Mehrtash , Carpenter Anne E. , Singh Shantanu 
Published: November 2023

AbstractImage-based cell profiling is a powerful tool that compares perturbed cell populations by measuring thousands of single-cell features and summarizing them into profiles. Typically a sample is represented by averaging across cells, but this fails to capture the heterogeneity within cell populations. We introduce CytoSummaryNet: a Deep Sets-based approach that improves mechanism of action prediction by 30-68% in mean average precision compared to average profiling on a public dataset. CytoSummaryNet uses self-supervised contrastive learning in a multiple-instance learning framework, providing an easier-to-apply method for aggregating single-cell feature data than previously published strategies. Interpretability analysis suggests that the model achieves this improvement by downweighting small mitotic cells or those with debris and prioritizing large uncrowded cells. The approach requires only perturbation labels for training, which are readily available in all cell profiling datasets. CytoSummaryNet offers a straightforward post-processing step for single-cell profiles that can significantly boost retrieval performance on image-based profiling datasets.
AI-Driven Insights into the complexities of Chinese hamster ovary cells death in order to optimize production processes
Authors: Moshfeghnia Mohammad 
Published: November 2023

AbstractChinese hamster ovary (CHO) cells are a multipurpose and high-performance cell line for recombinant protein production in biopharmaceutical industry. They have proven their ability to produce a wide range of therapeutic proteins with high efficiency and quality. Designing novel and high-performance CHO cell lines has an incredible impact in biopharmaceutical industry that can reduce prices and increase product efficiency. One of the best ways is to prevent CHO cells death during Bioprocessing. Apoptosis is the most common form of CHO cells death during Bioprocessing. Analyzing Apoptosis and cell-cycle complex signaling pathways are necessary for the control of cell growth, efficiency, and the death of CHO cells. Therefore, analyzing and understanding interactions of these pathways and their interactions with other cellular processes can help optimize the performance and quality of CHO cell lines. AI-driven insight solutions and Advanced machine learning algorithms like GAT (Graph Attention Network) used in this project indicate most important Targets in complex signaling pathways. Pathways such as the TNF signaling pathway, and also viruses like: Hepatitis C, HIV1 and Bacteria like: Salmonella have High intersection size and Low P-value with complex signaling pathways. These microorganisms should be used to design high-performance CHO cell lines because they are master in these pathways. This method can be used to find novel and high efficiency targets for curing cancer in humans.
Counter-gradient variation in gene expression between fish populations facilitates colonization of low-dissolved oxygen environments
Authors: Fox Janay A. , Hunt David A. G. A. , Hendry Andrew P. , Chapman Lauren J. , Barrett Rowan D. H. 
Published: November 2023

AbstractThe role of phenotypic plasticity during colonization remains unclear due to the shifting importance of plasticity across timescales. Over time, genetic responses can reduce plasticity such that species in a novel environment show higher levels of plasticity than those with a longer evolutionary timescale in the environment. Therefore, comparing species in the early stages of colonization to long-established species provides a powerful approach for uncovering the role of phenotypic plasticity during different stages of colonization. We compared gene expression between the cyprinid fishEnteromius apleurogramma, a species that has undergone a recent range expansion, andE. neumayeri, a long-established native species in the same region, caught from low-dissolved oxygen (DO) and high-DO habitats. We sampled tissue either immediately after capture from the field or after a two-week acclimation under high-DO conditions, allowing us to test for both evolved and plastic differences in low-DO vs high-DO populations of each species. We found that most genes showing evolved differences in gene expression did not overlap with those showing plastic differences in gene expression. However, in the genes that did overlap, there was counter-gradient variation such that plastic and evolved gene expression responses were in opposite directions in both species. Additionally,E. apleurogrammahad higher levels of plasticity and evolved divergence in gene expression between field populations. We suggest that the higher level of plasticity and counter-gradient variation may have allowed rapid genetic adaptation inE. apleurogrammaand facilitated colonization. This study shows how counter-gradient variation may impact colonization of divergent oxygen environments.
TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma
Authors: Tian Maojin , Yang Le , Zhao Ziqian , Li Jigang , Wang Lianqing , Yin Qingqing , Hu Wei , Lou Yunwei , Du Jianxin , Zhao Peiqing 
Published: November 2023

AbstractTIPE (TNFAIP8) has been identified as an oncogene and participates in tumor biology. However, how its role in the metabolism of tumor cells during melanoma development remains unclear. Here, we demonstrated that TIPE promoted glycolysis by interacting with pyruvate kinase M2 (PKM2) in melanoma. We found that TIPE induced PKM2 dimerization, thereby facilitating its translocation from the cytoplasm to the nucleus. TIPE-mediated PKM2 dimerization consequently promoted HIF-1α activation and glycolysis, which contributed to melanoma progression and increased its stemness features. Notably, TIPE specifically phosphorylated PKM2 at Ser 37 in an ERK-dependent manner. Consistently, the expression of TIPE was positively correlated with the levels of PKM2 Ser37 phosphorylation and cancer stem cell markers in melanoma tissues from clinical samples and tumor bearing mice. In summary, our findings indicate that the TIPE/PKM2/HIF-1α signaling pathway plays a pivotal role in promoting cancer stem cell properties by facilitating the glycolysis, which would provide a promising therapeutic target for melanoma intervention.
Dynamic establishment and maintenance of the human intestinal B cell population and repertoire following transplantation
Authors: Fu Jianing , Hsiao Thomas , Waffarn Elizabeth , Meng Wenzhao , Long Katherine D. , Frangaj Kristjana , Jones Rebecca , Gorur Alaka , Shtewe Areen , Li Muyang , Muntnich Constanza Bay , Rogers Kortney , Jiao Wenyu , Velasco Monica , Matsumoto Rei , Kubota Masaru , Wells Steven , Danzl Nichole , Ravella Shilpa , Iuga Alina , Vasilescu Elena-Rodica , Griesemer Adam , Weiner Joshua , Farber Donna L. , Luning Prak Eline T. , Martinez Mercedes , Kato Tomoaki , Hershberg Uri , Sykes Megan 
Published: November 2023

AbstractIt is unknown how intestinal B cell populations and B cell receptor (BCR) repertoires are established and maintained over time in humans. Following intestinal transplantation (ITx), surveillance ileal mucosal biopsies provide a unique opportunity to map the dynamic establishment of gut lymphocyte populations. Using polychromatic flow cytometry that includes HLA allele group-specific mAbs distinguishing donor from recipient cells along with high throughput BCR sequencing, we tracked the establishment of recipient B cell populations and BCR repertoire in the allograft mucosa of ITx recipients. We confirm the early presence of naïve donor B cells in the circulation and, for the first time, document the establishment of recipient B cell populations, including B resident memory cells, in the intestinal allograft mucosa. Recipient B cell repopulation of the allograft was most rapid in infant (<1 year old)-derived allografts and, unlike T cell repopulation, did not correlate with rejection rates. While recipient memory B cell populations were increased in graft mucosa compared to circulation, naïve recipient B cells remained detectable in the graft mucosa for years. Comparisons of peripheral and intra-mucosal B cell repertoires in the absence of rejection revealed increased BCR mutation rates and clonal expansion in graft mucosa compared to circulating B cells, but these parameters did not increase markedly after the first year post-transplant. Furthermore, clonal mixing between the allograft mucosa and the circulation was significantly greater in ITx recipients, even years after transplantation, than in healthy control adults. Collectively, our data demonstrate intestinal mucosal B cell repertoire establishment from a circulating pool, a process that continues for years without evidence of establishment of a stable mucosal B cell repertoire.
‘Whose quality of life is it anyway?’ – Evaluation of quality of life tools for children with complex needs accessing specialist leisure provision
Authors: Astill Fiona , Collins Bethan , McGrath Nicole , Kemp Alison , Hurt Lisa , Maguire Sabine 
Published: November 2023

AbstractStudies of quality of life (QoL) routinely exclude children with complex needs. These children struggle to access leisure activities, particularly those with severe communication needs or challenging behaviour. Sparkle provides specialised leisure services to children and young people (0-17 years) with complex needs in South Wales, UK. We aimed to evaluate previously validated tools to measure QoL with this population.Three tools were assessed over a 6-year period – PedsQL, KINDLRand QI-Disability. PedsQL (41) and KINDLR(10) were attempted by the children attending the clubs (5-17 years old), and QI-Disability by caregivers (96). The majority of child participants had a neurodevelopmental diagnosis, a proportion of whom were non-verbal.Neither KINDLRnor PedsQL were appropriate for the population, with children unable to understand the questions and answers. The QI-Disability scores showed a statistically significant improvement in parents’ estimate of their child’s positive emotions, but results were severely limited by drop off.Existing validated QoL tools cannot be meaningfully used by children with complex needs. While the caregiver tool showed some benefit of specialist leisure provision, it is recognised that caregivers may perceive a child’s QoL differently to the child themselves, and caregivers clearly found repeat measurements onerous.
75 years’ journey of malaria publications: what and where?
Authors: Deora Nimita , Kar Sonalika , Pande Veena , Sinha Abhinav 
Published: November 2023

AbstractBackgroundMalaria is a life-threatening and ancient disease that has inflicted serious morbidity and mortality across the globe. The major brunt of the disease has been on African, South East Asian and South American countries. Proportionally, malaria has attracted global research priorities amongst infectious diseases and this is evident from the number of publications directly or indirectly related to malaria from across the globe, irrespective of the endemicity of the disease. However, formal and exhaustive analyses of these ‘malaria publications’ are rarely done and published.MethodsWe therefore did a systematic analyses of the literature published on malaria with an intent to retrieve information on what has been published on malaria, where is it published and which countries are major contributors in malaria research. The study presents malaria publications from 1945 to 2020 retrieved using three global databases: Web of Science™, Embase® and Scopus®. Exported data was examined to determine the number of publications over time, their subject areas, contributions from various countries/organizations, and top publishing journals.ResultsThe total number of published records on malaria ranged from 90,282-1,12,698. On the basis of the number of publications, the United States, United Kingdom, France, and India were identified as the top four countries. Malaria Journal, American Journal of Tropical Medicine & Hygiene and PLoS One were the most preferred journals whereas the University of London, the London School of Hygiene and Tropical Medicine, and the University of Oxford appeared to be the top contributing organizations.ConclusionThe study concluded that a disproportional contribution to malaria research was observed with non-malaria endemic countries making the largest contribution. Databases were found to be incomparable and must be standardized on multiple dimensions before making a comparison. There are still some pertinent outstanding questions that need to be addressed: why there is still a research mismatch between endemic and non-endemic regions? why a standardized and comparable information is still not available for direct and quick analyses? is less case-based research conducted as compared to in-vitro or in animal models?
Iron status, thyroid dysfunction and iron deficiency anemia: a two-sample Mendelian randomization study
Authors: Huang Xianjun , Guo Tianhong , Wu Yuqin , Xu Qi , Dai Junliang , Huang Yuanshuai 
Published: November 2023

AbstractObjectiveGiven the clinical association between thyroid dysfunction and iron deficiency anemia (IDA), as well as their shared association with iron status, this study aims to investigate the causal relationship between iron status and thyroid dysfunction, while also examining the risk of IDA in relation to thyroid dysfunction.MethodsA two-sample Mendelian randomization (MR) study was conducted to identify the causal relationship of iron status on thyroid dysfunction, as well as thyroid dysfunction on IDA. Large-scale European population-based GWAS databases were utilized (Genetics of Iron Status consortium, ThyroidOmics consortium, FinnGen consortium, and UK biobank). Inverse variance weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results.ResultsThe IVW estimates did not reveal any significant causal relationship between serum iron status markers and thyroid dysfunction. However, a significant causal relationship was observed between hypothyroidism and IDA (OR = 1.101, 95% CI = 1.048-1.157,p< 0.001). Repeated analyses also demonstrated a similar trend (OR = 1.023, 95% CI = 1.011-1.035,p< 0.001). Sensitivity analysis supported that the MR estimates were robust.ConclusionIn our MR study, an upregulation of the hypothyroidism-associated gene was found to be significantly associated with an elevated risk of IDA in the European population. These findings may offer novel therapeutic insights for clinicians managing patients with hypothyroidism, IDA, or their comorbidities.
Portrait of Mental Health Identified by People with the Post-Covid Syndrome
Authors: Mayo Nancy , Hum Stanley , Matout Mohamad , Fellows Lesley K , Brouillette Marie-Josée 
Published: November 2023

AbstractAimsThe Post-COVID-19 syndrome (PCS) represents an epidemic within the COVID-19 pandemic, with potentially serious consequences for affected individuals, the healthcare system, and society at large. Facing a new and poorly understood health condition, this study aimed to produce a patient-centered understanding of mental health symptom patterns, functional impact, and intervention priorities.MethodsA cross-sectional analysis of the first 414 participants in a longitudinal study recruited over a 5- month from September 2022 to January 2023 was carried out involving people from Quebec who self-identified as having symptoms of PCS. People were asked to name areas of their mental health affected by PCS using the structure of the Patient Generated Index (PGI), an individualized measure suited to eliciting the most frequent and most bothersome symptoms. The PGI was supplemented with a set of patient-reported outcome measures across the rubrics of the Wilson- Cleary model. The text threads from the PGI were grouped into topics using BERTopic analysis.ResultsTwenty topics were identified from 818 text threads referring to PCS mental health symptoms nominated using the PGI format. 35% of threads were identified as relating to anxiety, discussed in terms of five topics: generalized/social anxiety, fear/worry, post-traumatic stress, panic, and nervous. 29% of threads were identified as relating to low mood, represented by five topics: depression, discouragement, emotional distress, sadness, and loneliness. A cognitive domain (22% of threads) was covered by four topics referring to concentration, memory, brain fog, and mental fatigue. Topics related to frustration, anger, irritability. and mood swings (7%) were considered as one domain and there were separate topics related to motivation, insomnia, and isolation.ConclusionThis novel method of digital transformation of unstructured text data uncovered different ways in which people think about classical mental health domains. This information could be used to evaluate the extent to which existing measures cover the content identified by people with PCS or to justify the development of a new measure of the mental health impact of PCS.
Delivery of mRNA encoding an anti-tau monoclonal antibody and engineered scFv intrabody results in functional antibody expression in SH-SY5Y cells
Authors: Wongsodirdjo Patricia , Caruso Alayna C. , Yong Alicia , Lester Madeleine A. , Vella Laura J. , Hung Ya Hui , Nisbet Rebecca M. 
Published: November 2023

AbstractMonoclonal antibodies have emerged as a leading therapeutic agent for the treatment of disease, including Alzheimer’s disease. In the last year, two anti-amyloid monoclonal antibodies, lecanemab and aducanumab, have been approved in the USA for the treatment of Alzheimer’s disease, whilst several tau-targeting monoclonal antibodies are currently in clinical trials. Such antibodies, however, are expensive and timely to produce and require frequent dosing regimens to ensure disease-modifying effects. Syntheticin vitro-transcribed mRNA encoding antibodies for endogenous protein expression holds the potential to overcome many of the limitations associated with protein antibody production. Here, we have generated syntheticin vitro-transcribed mRNA encoding a tau specific monoclonal antibody as a full-sized IgG and as a single chain variable fragment (scFv).In vitrotransfection of human neuroblastoma SH-SY5Y cells demonstrated the ability of the synthetic mRNA to be translated into functional tau-specific antibodies. Furthermore, we show that the translation of the tau-specific scFv as an intrabody results in the specific engagement of intracellular tau. This work highlights the utility of mRNA for the delivery of antibody therapeutics, including intrabodies, for the targeting of tau in tauopathies.
Tissue-specific sex difference in the metabolism of fatty acid esters of hydroxy fatty acids
Authors: Riecan Martin , Domanska Veronika , Lupu Cristina , Patel Maulin , Vondrackova Michaela , Rossmeisl Martin , Saghatelian Alan , Lupu Florea , Kuda Ondrej 
Published: November 2023

AbstractFatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous bioactive lipids known for their anti-inflammatory and anti-diabetic properties. Despite their therapeutic potential, little is known about the sex-specific variations in FAHFA metabolism. This study investigated the role of Androgen Dependent TFPI Regulating Protein (ADTRP), a FAHFA hydrolase. Additionally, tissue-specific differences in FAHFA levels, focusing on the perigonadal white adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), brown adipose tissue (BAT), plasma, and liver, were evaluated using metabolomics and lipidomics. We found that female mice exhibited higher FAHFA levels in pgWAT, scWAT, and BAT compared to males. FAHFA levels were inversely related toAdtrpmRNA, which showed significantly lower expression in females compared with males in pgWAT and scWAT. However, no significant differences between the sexes were observed in plasma and liver FAHFA levels.Adtrpdeletion had minimal impact on both sexes’ metabolome and lipidome of pgWAT. However, we discovered higher endogenous levels of triacylglycerol estolides containing FAHFAs, a FAHFA metabolic reservoir, in the pgWAT of female mice. These findings suggest that sex-dependent differences in FAHFA levels occur primarily in specific WAT depots and may modulate local insulin sensitivity in adipocytes. However, further investigations are warranted to fully comprehend the underlying mechanisms and implications of sex effects on FAHFA metabolism in humans.