bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individualized dynamic risk assessment for multiple myeloma
Authors: Murie Carl , Turkarslan Serdar , Patel Anoop , Coffey David G. , Becker Pamela S. , Baliga Nitin S. 
Published: April 2024

AbstractBackgroundIndividualized treatment decisions for patients with multiple myeloma (MM) requires accurate risk stratification that takes into account patient-specific consequences of genetic abnormalities and tumor microenvironment on disease outcome and therapy responsiveness.MethodsPreviously, SYstems Genetic Network AnaLysis (SYGNAL) of multi-omics tumor profiles from 881 MM patients generated the mmSYGNAL network, which uncovered different causal and mechanistic drivers of genetic programs associated with disease progression across MM subtypes. Here, we have trained a machine learning (ML) algorithm on activities of mmSYGNAL programs within individual patient tumor samples to develop a risk classification scheme for MM that significantly outperformed cytogenetics, International Staging System, and multi-gene biomarker panels in predicting risk of PFS across four independent patient cohorts.ResultsWe demonstrate that, unlike other tests, mmSYGNAL can accurately predict disease progression risk at primary diagnosis, pre- and post-transplant and even after multiple relapses, making it useful for individualized dynamic risk assessment throughout the disease trajectory.ConclusionmmSYGNAL provides improved individualized risk stratification that accounts for a patient’s distinct set of genetic abnormalities and can monitor risk longitudinally as each patient’s disease characteristics change.
Concordance of whole-genome long-read sequencing with standard clinical testing for Prader-Willi and Angelman syndromes
Authors: Paschal Cate R. , Zalusky Miranda P. G. , Beck Anita E. , Gillentine Madelyn A. , Narayanan Jaya , Damaraju Nikhita , Goffena Joy , Storz Sophie H. R. , Miller Danny E. 
Published: April 2024

AbstractCurrent clinical testing approaches for individuals with suspected imprinting disorders are complex, often requiring multiple tests performed in a stepwise fashion to make a precise molecular diagnosis. We investigated whether whole-genome long-read sequencing (LRS) could be used as a single data source to simultaneously evaluate copy number variants (CNVs), single nucleotide variants (SNVs), structural variants (SVs), and differences in methylation in a cohort of individuals known to have either Prader-Willi or Angelman syndrome. We evaluated 25 individuals sequenced to an average depth of coverage of 36x on an Oxford Nanopore PromethION. A custom one-page report was generated that could be used to assess copy number, SNVs, and methylation patterns at select CpG sites within the 15q11.2-q13.1 region and prioritize candidate pathogenic variants inUBE3A. After training with three positive controls, three analysts blinded to the known clinical diagnosis arrived at the correct molecular diagnosis for 22 out of 22 cases (20 true positive, 2 negative controls). Our findings demonstrate the utility of LRS as a single, comprehensive data source for complex clinical testing, offering potential benefits such as reduced testing costs, increased diagnostic yield, and shorter turnaround times in the clinical laboratory.
Three-dimensional multi-target super-resolution microscopy of cells using Metal-Induced Energy Transfer and DNA-PAINT
Authors: Oleksiievets Nazar , Mougios Nikolaos , Jans Daniel C. , Hauke Lara , Thiele Jan Christoph , Basak Samrat , Jakobs Stefan , Opazo Felipe , Enderlein Jörg , Tsukanov Roman 
Published: April 2024

ABSTRACTDNA-points accumulation for imaging in nanoscale topography (DNA-PAINT) is a potent variant of single-molecule localization microscopy (SMLM) which is highly effective for multiplexed super-resolution imaging. It achieves localization precision down to nanometers in the lateral direction. However, its routine axial localization precision is approximately three-fold lower as compared to the lateral localization precision. Recently, a technique known as Metal-Induced Energy Transfer (MIET) has been introduced, offering excellent axial resolution at the nanometer scale up to 200 nm above a surface. MIET is characterized by a low entry barrier, as its sole technical requirement is the availability of a fluorescence lifetime imaging modality. In this study, we harness the synergy between the exceptional axial resolution provided by MIET and the lateral resolution achieved with DNA-PAINT (MIET-PAINT) to accomplish multitarget 3D super-resolution imaging. We implemented MIET-PAINT using a wide-field fluorescence lifetime imaging microscope. We validated our technique by measuring the height of emitters placed on top of spacers of known thicknesses. We then demonstrated multiplexed MIET-PAINT imaging of fixed cells to visualize mechanotransduction proteins in the focal adhesion complex (FAC) and the cytoskeleton. We explored the structural arrangement of paxillin, zyxin, and actin stress fibers in U2OS cells and discovered that MIET-PAINT can reliably address multiple targets, providing lateral and axial nanometerscale resolution.
Advancing knowledge of West African morning glories: a taxonomic revision ofIpomoeaL. (Convolvulaceae) from Ghana
Authors: Williams Benjamin Darko , Francisco Ruth Cristóvão , Mewded Befkadu , Oppong Christiana Peprah , Bosomtwi-Ayensu Claudia , Masinde Collins Wafula , Chukwuma Deborah Moradeke , Gadisa Deresa Abetu , Yeboah Doreen Donkor , Ahossou Enangnon Oscar Doré , Rasaminirina Fitiavana , Precious Igho-Osagie Uhunwa , Korir Mercy Jebiwott , Antwi-Boasiako Kwasi Boateng , Mfodwo Raymond Attah , Musa Mutegeki Alislam Said , Atta-Adjei Peter , Akomatey Peter Kwasi , Kumordzie Seyiram , Borosova Renata , Tang Cheung , Asase Alex , Ameka Gabriel , Simões Ana Rita Giraldes 
Published: April 2024

AbstractGhana’s plant diversity is estimated at 2,974 plant species, belonging to 1,077 genera and 173 plant families. However, a Flora of Ghana is yet inexistent: targeted floristic and taxonomic studies are still much needed to document the plant diversity of the country fully at the family, generic and species levels. This is essential for identifying priority conservation areas in the country and support further research in crop wild relatives or medicinal plants, which will help tackle food insecurity and improve livelihoods. In this study, we provide a taxonomic revision of theIpomoea spp.in Ghana to enhance their identification, conservation and sustainable utilization as food and medicine among other uses. An extensive literature review was carried out, including historical references and online taxonomic databases, to recover information on accepted names, type specimens and synonyms, followed by consultation of herbarium specimens at GC herbaria, to retrieve morphological information and database specimens. Specimen locality information was georeferenced, and records plotted onto distribution maps. As a result, this work provides an identification key to the species ofIpomoeaof Ghana, nomenclatural information, comprehensive morphological descriptions, detailed list of examined specimens, distribution maps and notes on conservation status and traditional plant uses. In total, 28 species are fully described, 20 of which are native and eight introduced from the Americas; five are new records to Ghana.
Evaluating Large Language Models for Drafting Emergency Department Discharge Summaries
Authors: Williams Christopher Y.K. , Bains Jaskaran , Tang Tianyu , Patel Kishan , Lucas Alexa N. , Chen Fiona , Miao Brenda Y. , Butte Atul J. , Kornblith Aaron E. 
Published: April 2024

AbstractImportanceLarge language models (LLMs) possess a range of capabilities which may be applied to the clinical domain, including text summarization. As ambient artificial intelligence scribes and other LLM-based tools begin to be deployed within healthcare settings, rigorous evaluations of the accuracy of these technologies are urgently needed.ObjectiveTo investigate the performance of GPT-4 and GPT-3.5-turbo in generating Emergency Department (ED) discharge summaries and evaluate the prevalence and type of errors across each section of the discharge summary.DesignCross-sectional study.SettingUniversity of California, San Francisco ED.ParticipantsWe identified all adult ED visits from 2012 to 2023 with an ED clinician note. We randomly selected a sample of 100 ED visits for GPT-summarization.ExposureWe investigate the potential of two state-of-the-art LLMs, GPT-4 and GPT-3.5-turbo, to summarize the full ED clinician note into a discharge summary.Main Outcomes and MeasuresGPT-3.5-turbo and GPT-4-generated discharge summaries were evaluated by two independent Emergency Medicine physician reviewers across three evaluation criteria: 1) Inaccuracy of GPT-summarized information; 2) Hallucination of information; 3) Omission of relevant clinical information. On identifying each error, reviewers were additionally asked to provide a brief explanation for their reasoning, which was manually classified into subgroups of errors.ResultsFrom 202,059 eligible ED visits, we randomly sampled 100 for GPT-generated summarization and then expert-driven evaluation. In total, 33% of summaries generated by GPT-4 and 10% of those generated by GPT-3.5-turbo were entirely error-free across all evaluated domains. Summaries generated by GPT-4 were mostly accurate, with inaccuracies found in only 10% of cases, however, 42% of the summaries exhibited hallucinations and 47% omitted clinically relevant information. Inaccuracies and hallucinations were most commonly found in the Plan sections of GPT-generated summaries, while clinical omissions were concentrated in text describing patients’ Physical Examination findings or History of Presenting Complaint.Conclusions and RelevanceIn this cross-sectional study of 100 ED encounters, we found that LLMs could generate accurate discharge summaries, but were liable to hallucination and omission of clinically relevant information. A comprehensive understanding of the location and type of errors found in GPT-generated clinical text is important to facilitate clinician review of such content and prevent patient harm.
Multi-SpinX: An Advanced Framework for Automated Tracking of Mitotic Spindles and Kinetochores in Multicellular Environments
Authors: Chai Binghao , Efstathiou Christoforos , Choudhury Muntaqa S. , Kuniyasu Kinue , Jain Saakshi Sanjay , Maharea Alexia-Cristina , Tanaka Kozo , Draviam Viji M. 
Published: April 2024

AbstractSpinX, an AI-guided spindle tracking software, allows the 3-dimensional (3D) tracking of metaphase spindle movements in mammalian cells. Using over 900 images of dividing cells, we create the Multi-SpinX framework to significantly expand SpinX’s applications: a) to track spindles and cell cortex in multicellular environments, b) to combine two object tracking (spindle with kinetochores marked by centromeric probes) and c) to extend spindle tracking beyond metaphase to prometaphase and anaphase stages where spindle morphology is different. We have used a human-in-the-loop approach to assess our optimisation steps, to manually identify challenges and to build a robust computational pipeline for segmenting kinetochore pairs and spindles. Spindles of both H1299 and RPE1 cells have been assessed and validated for use through Multi-SpinX, and we expect the tool to be versatile in enabling quantitative studies of mitotic subcellular dynamics.
Causal role of frontocentral beta oscillation in comprehending linguistic communicative functions
Authors: Chang Wenshuo , Zhao Xiaoxi , Wang Lihui , Zhou Xiaolin 
Published: April 2024

AbstractLinguistic communication is often considered as an action serving the function of conveying the speaker’s goal to the addressee. Although neuroimaging studies have suggested a role of the motor system in comprehending communicative functions, the underlying mechanism is yet to be specified. Here, by 2 EEG experiments and a tACS experiment, we demonstrate that the frontocentral beta oscillation, which represents action states, plays a crucial part in linguistic communication understanding. Participants read scripts involving 2 interlocutors and rated the interlocutors’ attitudes. Each script included a critical sentence said by the speaker expressing a context-dependent function of either promise, request, or reply to the addressee’s query. These functions were behaviorally discriminated, with higher addressee’s will rating for the promise than for the reply and higher speaker’s will rating for the request than for the reply. EEG multivariate analyses showed that different communicative functions were represented by different patterns of frontocentral beta activity but not by patterns of alpha activity. Further tACS results showed that, relative to alpha tACS and sham stimulation, beta tACS improved the predictability of communicative functions of request or reply, as measured by the speaker’s will rating. These results convergently suggest a causal role of the frontocentral beta activities in comprehending linguistic communications.HighlightsThe frontocentral beta activity patterns discriminate communicative functions.The frontocentral beta activity plays a causal role in comprehending the functions.The comprehension could be subserved by the mental simulation of the communication.Our findings connect the idea of embedded semantics with the speech act theory.
Elucidating role of long non-coding RNAs ofTamarindus indicaLinn. in post-transcriptional gene regulation
Authors: Roy Chowdhury Moumita , Kumar Aman , Besra Alfred , Basak Jolly 
Published: April 2024

AbstractTamarindus indica, commonly known as tamarind, is a rich source of carbohydrates, proteins, lipids, fatty acids, vitamins, minerals and different bioactive compounds. It is well established that long non-coding RNAs (lncRNAs) play important role in transcriptional, post-transcriptional and epigenetic regulation. In spite of the tamarind genome information available, handful of studies have been done on its non-coding genome. In this study, 320 tamarind lncRNAs have been predicted by computational methods. Along with the experimental validation of seven randomly chosen lncRNAs, functional analysis of the predicted lncRNAs along with their targets elucidated their roles in various biological pathways. Sequence analysis of these predicted lncRNAs reveals the presence of different motifs and TRs. Our analysis provides information about the non-coding genome of tamarind and their involvement in gene regulation, which may be used to gain more knowledge about the medicinal properties of tamarind.
Similar, but not the same: multi-omics comparison of human valve interstitial cells and osteoblast osteogenic differentiation expanded with an estimation of data-dependent and data-independent PASEF
Authors: Lobov Arseniy , Kuchur Polina , Boyarskaya Nadezhda , Perepletchikova Daria , Taraskin Ivan , Ivashkin Andrei , Kostina Daria , Khvorova Irina , Uspensky Vladimir , Repkin Egor , Denisov Evgeny , Gerashchenko Tatiana , Tikhilov Rashid , Bozhkova Svetlana , Karelkin Vitaly , Wang Chunli , Xu Kang , Malashicheva Anna 
Published: April 2024

AbstractOsteogenic differentiation is crucial in normal bone formation and pathological calcification, such as calcific aortic valve disease (CAVD). Understanding the proteomic and transcriptomic landscapes underlying this differentiation can unveil potential therapeutic targets for CAVD. In this study, we employed the timsTOF Pro platform to explore the proteomic profiles of valve interstitial cells (VICs) and osteoblasts during osteogenic differentiation, utilizing three data acquisition/analysis techniques: Data-Dependent Acquisition (DDA-PASEF) and Data-Independent Acquisition (DIA-PASEF) with a classic library based and machine learning-based “library-free” search (DIA-ML). RNA-seq complemented comparative proteome coverage analysis to provide a comprehensive biological reference. We reveal distinct proteomic and transcriptomic profiles between VICs and osteoblasts, highlighting specific biological processes in their osteogenic differentiation pathways. Furthermore, the study identified potential therapeutic targets for CAVD, including the differential expression of proteins such as MAOA and ERK1/2 pathway in VICs. From a technical perspective, the DIA-ML offers significant advantages and seems the method of choice for routine proteomics.
Expansion of a neural crest gene signature following ectopic MYCN expression in sympathoadrenal lineage cells in vivo
Authors: Ibarra-García-Padilla Rodrigo , Nambiar Annika , Hamre Thomas A. , Singleton Eileen W. , Uribe Rosa A. 
Published: April 2024

AbstractNeural crest cells (NCC) are multipotent migratory stem cells which originate from the neural tube during early vertebrate embryogenesis. NCC give rise to a variety of cell types within the developing organism, including neurons and glia of the sympathetic nervous system. It has been suggested that failure in correct NCC differentiation leads to several diseases, including neuroblastoma (NB). During normal NCC development, MYCN is transiently expressed to promote NCC migration, and its downregulation precedes neuronal differentiation. Overexpression of MYCN has been linked to high-risk and aggressive NB progression. For this reason, understanding the effect overexpression of this oncogene has on development of NCC-derived sympathoadrenal progenitors (SAP), which later give rise to sympathetic nerves, will help elucidate the developmental mechanisms that may prime the onset of NB. Here, we found that overexpressing human EGFP-MYCN within SAP lineage cells in zebrafish led to the transient formation of an abnormal SAP population which displayed expanded and elevated expression of NCC markers, while paradoxically also co-expressing SAP and neuronal differentiation markers. The aberrant NCC signature was corroborated within vivotime lapse confocal imaging in zebrafish larvae, which revealed transient expansion ofsox10reporter expression in MYCN overexpressing SAPs during the early stages of SAP development. In these aberrant MYCN overexpressing SAP cells, we also found evidence of dampened BMP signaling activity, indicating that BMP signaling disruption occurs following elevated MYCN expression, and suggesting BMP is functionally important for the NCC to SAP differentiation transition. In agreement, we discovered that pharmacological inhibition of BMP signaling was sufficient to create an aberrant NCC gene signature in SAP cells, phenocopying MYCN overexpression. Together, our results suggest that MYCN overexpression in SAPs disrupts their differentiation by eliciting abnormal NCC gene expression programs, and dampening BMP signaling response, having developmental implications for the priming of NBin vivo.
Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections
Authors: Arévalo-Jaimes Betsy Veronica , Salinas-Pena Mónica , Ponte Inmaculada , Jordan Albert , Roque Alicia , Torrents Eduard 
Published: April 2024

AbstractHistones possess significant antimicrobial potential, yet their activity against biofilms remains underexplored. Moreover, concerns regarding adverse effects limit their clinical implementation. We investigated the antibacterial efficacy of human recombinant histone H1 subtypes againstPseudomonas aeruginosaPAO1, both planktonic and in biofilms. After thein vitrotests, toxicity and efficacy were assessed in aP. aeruginosaPAO1 infection model usingGalleria mellonellalarvae. Histones were also evaluated in combination with ciprofloxacin and gentamicin. Our results demonstrate antimicrobial activity against of all three histones againstP. aeruginosaPAO1, with H1.0 and H1.4 showing efficacy at lower concentrations. The bactericidal effect was associated with a mechanism of membrane disruption.In vitrostudies using static and dynamic models showed that H1.4 had antibiofilm potential by reducing cell biomass. Neither H1.0 nor H1.4 showed toxicity inG. mellonellalarvae, and both increased larvae survival when infected withP. aeruginosaPAO1. Althoughin vitrosynergism was observed between ciprofloxacin and H1.0, no improvement over the antibiotic alone was notedin vivo. Differences in antibacterial and antibiofilm activity were attributed to sequence and structural variations among histone subtypes. Moreover, the efficacy of H1.0 and H1.4 was influenced by the presence and strength of the extracellular matrix. These findings suggest histones hold promise for combating acute and chronic infections caused by pathogens such asP. aeruginosa.ImportanceThe constant increase of multidrug-resistant bacteria is a critical global concern. The inefficacy of current therapies to treat bacterial infections is attributed to multiple mechanisms of resistance, including the capacity to form biofilms. Therefore, the identification of novel and safe therapeutic strategies is imperative. This study confirms the antimicrobial potential of three histone H1 subtypes against both Gram-negative and Gram-positive bacteria. Furthermore, histones H1.0 and H1.4 demonstratedin vivoefficacy without associated toxicity in an acute infection model ofPseudomonas aeruginosaPAO1 inGalleria mellonellalarvae. The bactericidal effect of these proteins also resulted in reduction in biomass ofP. aeruginosaPAO1 biofilms. Given the clinical significance of this opportunistic pathogen, our research provides a comprehensive initial evaluation of the efficacy, toxicity, and mechanism of action of a potential new therapeutic approach against acute and chronic bacterial infections.
CINner: modeling and simulation of chromosomal instability in cancer at single-cell resolution
Authors: Dinh Khanh N. , Vázquez-García Ignacio , Chan Andrew , Malhotra Rhea , Weiner Adam , McPherson Andrew W. , Tavaré Simon 
Published: April 2024

ABSTRACTCancer development is characterized by chromosomal instability, manifesting in frequent occurrences of different genomic alteration mechanisms ranging in extent and impact. Mathematical modeling can help evaluate the role of each mutational process during tumor progression, however existing frameworks can only capture certain aspects of chromosomal instability (CIN). We present CINner, a mathematical framework for modeling genomic diversity and selection during tumor evolution. The main advantage of CINner is its flexibility to incorporate many genomic events that directly impact cellular fitness, from driver gene mutations to copy number alterations (CNAs), including focal amplifications and deletions, missegregations and whole-genome duplication (WGD). We apply CINner to find chromosome-arm selection parameters that drive tumorigenesis in the absence of WGD in chromosomally stable cancer types. We found that the selection parameters predict WGD prevalence among different chromosomally unstable tumors, hinting that the selective advantage of WGD cells hinges on their tolerance for aneuploidy and escape from nullisomy. Direct application of CINner to model the WGD proportion and fraction of genome altered (FGA) further uncovers the increase in CNA probabilities associated with WGD in each cancer type. CINner can also be utilized to study chromosomally stable cancer types, by applying a selection model based on driver gene mutations and focal amplifications or deletions. Finally, we used CINner to analyze the impact of CNA probabilities, chromosome selection parameters, tumor growth dynamics and population size on cancer fitness and heterogeneity. We expect that CINner will provide a powerful modeling tool for the oncology community to quantify the impact of newly uncovered genomic alteration mechanisms on shaping tumor progression and adaptation.