bluuebunny/crossref_metadata_2025_split huggingface dataset:
An assessment of evidence to inform best practice for the communication of acute venous thromboembolism diagnosis: a scoping review
Authors: Mishra Samarth , Klok Frederikus A. , Gal Grégoire Le , de Wit Kerstin , Schwartz Aviva , Luijten Dieuwke , Sadeghipour Parham , Bayley Julie , Woller Scott C. 
Published: October 2024

AbstractBackgroundPhysician communication with patients is a key aspect of excellent care. Scant evidence exists to inform best practice for physician communication in patients diagnosed with pulmonary embolism and deep vein thrombosis, collectively referred to as venous thromboembolism (VTE). The aim of this study was to summarize the existing literature on best practices for communication between healthcare providers and patients newly diagnosed with VTE.MethodsWe performed a scoping review of the extant literature on best practice for physician patient communication and the diagnosis and management of VTE. Manuscripts on communication between healthcare professionals and patients with acute vascular diseases, including VTE, were eligible. Two authors independently reviewed titles, and consensus determined article inclusion. The manuscripts were further categorized into two main categories: best practice in communication and unmet needs in communication. Data aggregation was achieved by a modified thematic synthesis.ResultsAmong 345 initial publications, 22 manuscripts met inclusion criteria with 11 that addressed VTE, five pulmonary embolism, four deep vein thrombosis, one atrial fibrillation, and one acute coronary syndrome. Eleven manuscripts addressed communication of VTE diagnosis, while 12 focused on communication of VTE treatment. Eleven manuscripts identified unmet communication needs, and 14 addressed best practice. Our review shows that good communication surrounding the VTE diagnosis and treatment can enhance satisfaction while suboptimal communication can incur emotional, cognitive, behavioral, social, and health-systems adverse effects.ConclusionScant literature guides best practices for communicating VTE diagnosis and treatment. Further research is necessary to establish practices for improving communication with VTE patients.
Spatial and temporal signatures of cell competition revealed by K-function analysis
Authors: Day Nathan , Michalowska Jasmine , Kelkar Manasi , Vallardi Giulia , Charras Guillaume , Lowe Alan R. 
Published: November 2024

AbstractIt is generally hypothesised that in MDCK wild-type versus ScrKDco-cultures mechanical competition leads to the physical elimination of ScrKDcells, while in MDCK wild-type versus RasV12co-cultures biochemical competition results in the non-apoptotic extrusion of RasV12cells. However, the exact spatiotemporal signatures of competitive interactions in these systems remains largely unknown. Utilising advanced single-cell image analysis, this research quantifies the spatiotemporal dynamics of these competitive interactions. Time-lapse microscopy, combined with cellular segmentation, tracking, cell-state classification, and K-function clustering analysis provide detailed insights into how wild-type cell proliferation relates to the elimination of mutant cells. We find striking differences in the underlying processes of each competition type. In the ScrKDcompetition, elimination seems driven by diffuse proliferative forces unrelated to the immediate elimination site. In contrast, RasV12cell elimination is closely linked to local increases in wild-type cell mitoses prior to the RasV12extrusion. Both competitions trigger an increase in local wild-type cell proliferation post-elimination, although the timing of these responses vary. This study not only sheds light on the diverse mechanisms of cell competition but also underscores the complexity of cellular interactions in tissue dynamics, providing new perspectives on cellular quality control and a new quantitative approach to characterise these interactions.
PAM-flexible adenine base editing rescues hearing loss in a humanizedMPZL2mouse model harboring an East Asian founder mutation
Authors: Hu Shao Wei , Jeong Sohyang , Jiang Luoying , Koo Hansol , Wang Zijing , Choi Won Hoon , Zhu Biyun , Seok Heeyoung , Zhou Yi , Kim Min Gu , Mu Dan , Guo Huixia , Zhou Ziyi , Jung Sung Ho , Zhang Yingting , Chae Ho Byung , Chen Liheng , Lee Sung-Yeon , Guo Luo , Suh Myung-Whan , Xiao Yang , Park Moo Kyun , Tang Honghai , Song Jae-Jin , Chen Xi , Chen Ai , Lee Jun Ho , Bae Sangsu , Lee Sang-Yeon , Shu Yilai 
Published: November 2024

AbstractHearing loss is one of the most prevalent sensory disorders, but no commercial biological treatments are currently available. Here, we identified an East Asia-specific founder mutation, the homozygous c.220C>T mutation inMPZL2, that contributes to a significant proportion of hereditary deafness cases in our cohort study. We found that the disease-causing mutation could be targetable by adenine base editors (ABEs) that enable A·T-to-G·C base corrections without DNA double-strand breaks. To demonstrate this, we developed a humanized mouse model (hMPZL2Q74X/Q74X) that recapitulates humanMPZL2deafness and leads to progressive hearing loss. A PAM-flexible ABE variant with reduced bystander and off-target effects (ABE8eWQ-SpRY:sgRNA3) was packaged in dual adeno-associated viruses (AAVs) and injected into the inner ear ofhMPZL2Q74X/Q74Xmice and effectively corrected the mutation. This treatment significantly restored hearing function, improved inner ear structural integrity, and reversed altered gene expression. Base editing may hold therapeutic potential for hereditary deafness, including most cases ofMPZL2deafness.
Self-Documenting Plasmids
Authors: Hernandez Sarah I. , Peccoud Samuel J. , Berezin Casey-Tyler , Peccoud Jean 
Published: October 2024

SummaryPlasmids are the workhorse of biotechnology. These small DNA molecules are used to produce recombinant proteins and to engineer living organisms. They can be regarded as the blueprints of many biotechnology products. It is, therefore, critical to ensure that the sequences of these DNA molecules match their intended designs. Yet, plasmid verification remains challenging. To secure the exchange of plasmids in research and development workflows, we have developed self-documenting plasmids that encode information about themselves in their own DNA molecules. Users of self-documenting plasmids can retrieve critical information about the plasmid without prior knowledge of the plasmid identity. The insertion of documentation in the plasmid sequence does not adversely affect their propagation in bacteria and does not compromise protein expression in mammalian cells. This technology simplifies plasmid verification, hardens supply chains, and has the potential to transform the protection of intellectual property in the life sciences.
Structural-Functional Brain Network Coupling During Task Performance Reveals Intelligence-Relevant Communication Strategies
Authors: Popp Johanna L. , Thiele Jonas A. , Faskowitz Joshua , Seguin Caio , Sporns Olaf , Hilger Kirsten 
Published: October 2024

AbstractIntelligence is a broad mental capability influencing human performance across tasks. Individual differences in intelligence have been linked to characteristics of structural and functional brain networks. Here, we consider their alignment, the structural-functional brain network coupling (SC-FC coupling) during resting state and during active cognition, to predict general intelligence. Using DWI and fMRI data from 764 participants of the Human Connectome Project (Replication:N1=126,N2=180), we modelled SC-FC coupling with similarity and communication measures that capture functional interactions unfolding on top of structural brain networks. By accounting for variations in brain region-specific neural signaling strategies, we show that individual differences in SC-FC coupling patterns predict individual intelligence scores. Most accurate predictions resulted from cognitively demanding tasks and task combinations. Our study suggests the existence of an intrinsic SC-FC coupling organization enabling fine-drawn intelligence-relevant adaptations that support efficient information processing by facilitating brain region-specific adjustment to external task demands.
Vimentin molecular linkages with nesprin-3 enhance nuclear deformations by cell geometric constraints
Authors: Swoger Maxx , Thanh Minh Tri Ho , Byfield Fitzroy J. , Dam Van , Williamson Jessica , Frank Bronson , Hehnly Heidi , Conway Daniel , Patteson Alison E. 
Published: November 2024

AbstractThe nucleus is the organelle of the cell responsible for controlling protein expression, which has a direct effect on cellular biological functions. Here we show that the cytoskeletal protein vimentin plays an important role in increasing cell-generated forces transmitted to the cell nucleus, resulting in increased nuclear deformations in strongly polarized cells. Using micropatterned substrates to geometrically control cell shape in wild-type and vimentin-null cells, we show vimentin increases polarization and deformation of the cell nucleus. Loss of nesprin-3, which physically couples vimentin to the nuclear envelope, phenotypically copies the loss of vimentin, suggesting vimentin transmits forces to the cell nucleus through direct molecular linkages. Use of a fluorescence resonance energy transfer (FRET) sensor that binds to the nuclear envelope through lamin-A/C suggests vimentin increases the tension on the nuclear envelope. Our results indicate that nuclear shape and deformation can be modified by the vimentin cytoskeleton and its specific crosslinks to the cell nucleus.
Seasonal and daily variation in indoor light and temperature associate with sleep disturbance in dementia
Authors: Skeldon Anne C , Rodriguez Garcia Thalia ,   Centre for Care Research & Technology, Soreq Eyal , Walsh Chloe , Dijk Derk-Jan 
Published: November 2024

AbstractMechanisms regulating human sleep and physiology have evolved in response to rhythmic variation in environmental variables driven by the Earth’s rotation around its axis and the sun. To what extent these mechanisms are operable in vulnerable people who are primarily exposed to the indoor environment remains unknown. We analysed 26,523 days of data from environmental sensors and a contactless behaviour-and-physiology sensor tracking bed occupancy, heart and breathing rate in 70 people living with dementia (PLWD). Indoor light and temperature, sleep timing, duration and fragmentation as well as the timing of the heart rate minimum all varied across seasons. Beyond the effects of season, higher bedroom temperature and less bright indoor daytime light associated with more disrupted sleep and higher respiratory rate. This sensitivity of sleep and physiology to ecologically relevant variations in indoor environmental variables implies that implementing approaches to control indoor light and temperature can improve sleep.
Exploring Intersectionality of Race and Newcomer Status with Material and Social Deprivation in Ontario Census Data: A Comparative Analysis of the ON-MARG Deprivation Index and Machine-Learning Derived Demographic Clusters
Authors: Calderon Anyosa Renzo , Anderson Geoffrey 
Published: November 2024

AbstractBackgroundThe Ontario Marginalization Index (ON-MARG) is widely used to assess health inequalities in Ontario by measuring four dimensions of marginalization at the dissemination area (DA) level. However, averaging these dimensions into an overall deprivation score can obscure important information, in particular information on intersectionality of material and social deprivation and race and immigrant status.ObjectiveTo use machine learning algorithms to uncover relationships among the four ON-MARG dimensions across DAs as demographic clusters and to compare the use of these clusters to understand and map marginalization and to describe health inequities.MethodsWe applied K-means clustering to 2021 ON-MARG data on the four On-MARG dimensions — Households and Dwellings (HD), Material Resources (MR), Age and Labour Force (AL), and Racialized and Newcomer Populations (RN) across 20,123 DAs. We then compared these clusters to ON-MARG average index scores in terms of mapping marginalization in Toronto and examined how these clusters were associated with inequities in mental health service as compared specific dimensions of the ON-MARG index.ResultsWe identified four clusters: (1) Advantaged White Canadians, (2) Disadvantaged White Canadians, (3) Advantaged Visible Minorities and Immigrants, and (4) Disadvantaged Visible Minorities and Immigrants. The clustering approach revealed nuanced patterns not captured by the ON-MARG summary scores alone. Disadvantaged White Canadians exhibited the highest outpatient mental health visit rates, particularly among females (250–300 visits per 100,000). Disadvantaged Visible Minorities and Immigrants followed with elevated rates, while both advantaged clusters showed significantly lower utilization. The clusters provided better discrimination of health service disparities than ON-MARG quintiles alone, highlighting that disadvantaged groups, regardless of racial composition, had higher rates of mental health service use.ConclusionsCombining ON-MARG with machine learning clustering offers a more comprehensive understanding of marginalization’s intersectionality, revealing disparities in health service utilization not apparent from the index alone. This approach underscores the need for targeted, intersectional policies to address the specific needs of diverse populations, ultimately contributing to more equitable healthcare interventions in Ontario.
Touch to text: Spatiotemporal evolution of braille letter representations in blind readers
Authors: Teng Santani , Cichy Radoslaw , Pantazis Dimitrios , Oliva Aude 
Published: November 2024

ABSTRACTVisual deprivation does not silence the visual cortex, which is responsive to auditory, tactile, and other nonvisual tasks in blind persons. However, the underlying functional dynamics of the neural networks mediating such crossmodal responses remain unclear. Here, using braille reading as a model framework to investigate these networks, we presented sighted (N=13) and blind (N=12) readers with individual visual print and tactile braille alphabetic letters, respectively, during MEG recording. Using time-resolved multivariate pattern analysis and representational similarity analysis, we traced the alphabetic letter processing cascade in both groups of participants. We found that letter representations unfolded more slowly in blind than in sighted brains, with decoding peak latencies ∼200 ms later in braille readers. Focusing on the blind group, we found that the format of neural letter representations transformed within the first 500 ms after stimulus onset from a low-level structure consistent with peripheral nerve afferent coding to high-level format reflecting pairwise letter embeddings in a text corpus. The spatiotemporal dynamics of the transformation suggest that the processing cascade proceeds from a starting point in somatosensory cortex to early visual cortex and then to inferotemporal cortex. Together our results give insight into the neural mechanisms underlying braille reading in blind persons and the dynamics of functional reorganization in sensory deprivation.
Diminished placental Factor XIIIA1 expression associates with pre-conception antiretroviral treatment and preterm birth in pregnant people living with HIV
Authors: Ojwach Doty , Annels Nicola , Sunshine Sunny , Simpkin Daniel , Duruanyanwu Justin , Webber Tariq , Alinde Berenice , Ikumi Nadia , Zulu Michael , Madlala Hlengiwe , Myer Landon , Malaba Thoko , Newell Marie-Louise , Campagnolo Paolo , Gordon Siamon , Jaspan Heather , Gray Clive M. , Martinez Estrada Fernando 
Published: November 2024

SummaryWe previously showed a link between maternal vascular malperfusion and pre-term birth (PTB) in pregnant people living with HIV (PPLH) initiating antiretroviral treatment (ART) before pregnancy, indicating poor placental vascularisation. After measuring antenatal plasma angiogenic factors to seek mechanistic insights, low levels of plasma Factor XIIIA1 (FXIIIA1) and vascular-endothelial-growth-factor (VEGF) was significantly associated with PTB at the time closest to delivery (median 34 weeks) in PPLH initiating ART before pregnancy. Knowing that FXIIIA1 is crucial for haemostasis, angiogenesis, implantation and pregnancy maintenance and that expression is found on placental macrophages (Hofbauer cells), we examined placentae at delivery from matching participants who either initiating ART before pregnancy or during gestation. Highest FXIIIA1 expression was on Hofbauer cells but was significantly lower in PTB regardless of HIV infection, but was significantly lower in PPLH in PTB from women who initiated ART before pregnancy. To test the hypothesis that antiretroviral drugs may disrupt vascularisation in the placenta, we used a human umbilical vein endothelial cell (HUVEC) matrigel angiogenesis assay. We identified that addition of pre-treated FXIIIA1-expressing MCSF-and IL-10-induced placenta-like macrophages with physiological concentrations of tenofovir, 3TC, and efavirenz resulted in significantly inhibited angiogenesis; akin to the inhibition observed with titratable concentrations of ZED1301, an inhibitor of FXIIIA1. Overall, an efavirenz-containing ART combination inhibits vasculogenesis without causing toxicity and likely does so through inhibition of a FXIIIA1-mediated-placental macrophage pathway.
IL-17A Alters Human Cortical Development in a 3D Ex Vivo Model of Maternal Immune Activation
Authors: Assir Muhammad Z. K. , Yanakiev Mario , Gim Do Hyeon , Valkila Sara S. M. , Muscolino Paola , Peng Liu , Fowler Paul A. , Berg Daniel A. , Kang Eunchai 
Published: October 2024

AbstractHuman brain development depends on the coordinated interaction of diverse cell types and extracellular matrix (ECM) components, which are essential for proper neurogenesis and cortical organization. Epidemiological and animal studies have demonstrated that maternal immune activation (MIA) disrupts brain development, leading to impaired neurogenesis and increased risk of neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD) and schizophrenia. However, the cellular and molecular mechanisms by which MIA impacts human cortical development remain poorly understood. Here we introduce a 3D ex vivo culture system, termed ‘cerebroids,’ derived from dorsolateral prefrontal cortex of human fetal brain tissue, which faithfully preserves key developmental processes, along with critical cellular diversity and structural integrity of the developing human cortex. Using this platform, we show that IL-17A, a cytokine strongly implicated in NDDs, induces premature cortical folding, increases cortical thickness, and accelerates neurogenesis and neuronal maturation. Transcriptomic and proteomic analyses reveal significant dysregulation of ECM-related pathways, including the upregulation of proteoglycans such as brevican and versican. Notably, treatment with the anti-inflammatory agent parthenolide, an inhibitor of NF-κB and HDAC1 pathways, reverses IL-17A-induced cortical abnormalities, restoring normal cortical thickness, folding, and neurogenesis. These findings provide valuable insights into how IL-17A disrupts human cortical development during MIA, advancing our understanding of NDD-associated structural cortical alterations.
AlphaFold 2, but not AlphaFold 3, predicts confident but unrealistic β-solenoid structures for repeat proteins
Authors: Pratt Olivia S. , Elliott Luc G. , Haon Margaux , Mesdaghi Shahram , Price Rebecca M. , Simpkin Adam J. , Rigden Daniel J. 
Published: October 2024

AbstractAlphaFold 2 has revolutionised protein structure prediction but, like any new tool, its performance on specific classes of targets, especially those potentially under- represented in its training data, merits attention. Prompted by a highly confident prediction for a biologically meaningless, scrambled repeat sequence, we assessed AF2 performance on sequences comprised perfect repeats of random sequences of different lengths. AF2 frequently folds such sequences into β-solenoids which, while ascribed high confidence, contain unusual and implausible features such as internally stacked and uncompensated charged residues. A number of sequences confidently predicted as β-solenoids are predicted by other advanced methods as intrinsically disordered. The instability of some predictions is demonstrated by Molecular Dynamics. Importantly, other Deep Learning-based structure prediction tools predict different structures or β-solenoids with much lower confidence suggesting that AF2 alone has an unreasonable tendency to predict confident but unrealistic β-solenoids for perfect repeat sequences. The potential implications for structure prediction of natural (near-)perfect sequence repeat proteins are also explored.
Acetylation of RORβ by histone acetyltransferase p300 and deacetylation by SIRT1 modulates receptor stability, turnover and transcriptional activity
Authors: O’Leary Timothy , Shutin Denis , Edwards Dean P. , Griffin Patrick R. , Chang Mi Ra 
Published: October 2024

AbstractRORβ is an understudied nuclear receptor recently implicated in numerous pathologies. Using immunoprecipitation mass spectrometry, the transcription factor coregulatory protein and histone acetyltransferase p300 (EP300) was identified as a direct interacting protein of RORβ. Crosslinking mass spectrometry (XL-MS) confirmed that p300 interacts with the DNA binding domain (DBD), hinge region, and ligand binding domain (LBD) of RORβ. Both p300 and SIRT1 impact the turnover rate and transcriptional activity of RORβ. p300-dependent acetylation sites were found to be constrained to the DBD and hinge region of RORβ and were deacetylated by SIRT1. Sites that were ubiquitinated in the presence of p300 and SIRT1 were also discovered, with some sites sensitive to proteasome inhibitor. A constitutively acetylated mimic at K176 in the hinge prevented ubiquitination of RORβ at distal sites. Uncovering regulatory mechanisms of RORβ via protein interactions and PTMs will provide strategies for development of therapeutics targeting the receptor.Teaserp300 and SIRT1 work in concert to coordinate posttranslational modifications of the nuclear receptor RORβ.Graphical Abstract
Different serotonergic neurons regulate appetite for sucrose and hunger for proteins
Authors: Dorn Katharina , Gompert Magdalena , He Jianzheng , Scholz Henrike 
Published: October 2024

ABSTRACTFor the organism it is important to replenish internal energy storages selectively and selective appetite for nutrients might uncover internal energy requirements. How is the selective uptake of a specific nutrient regulated? Here we show that inDrosophila melanogasterdifferent sets of serotonergic neurons regulate appetite for sucrose and hunger for proteins. Increased neuronal activity in specific subsets of serotonergic neurons and interfering with serotonin reuptake using a mutated serotonin transporter reduced the appetite for sucrose selectively, but not the hunger for proteins. The insulin receptor together with the serotonin transporter regulates the selective sucrose appetite. We provide evidence that the cellular location of the serotonin transporter depends on the insulin receptor. This mechanism might allow optimizing nutrient intake and in turn might prevent overconsumption by repressing appetite for sucrose. Given the conserved nature of the molecules involved it is likely that the mechanism is conserved in higher organisms.