bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Large Language Models for sentiment analysis of health-related social media data: empirical evaluation and practical tips
Authors: He Lu , Omranian Samaneh , McRoy Susan , Zheng Kai 
Published: March 2024

AbstractHealth-related social media data generated by patients and the public provide valuable insights into patient experiences and opinions toward health issues such as vaccination and medical treatments. Using Natural Language Processing (NLP) methods to analyze such data, however, often requires high-quality annotations that are difficult to obtain. The recent emergence of Large Language Models (LLMs) such as the Generative Pre-trained Transformers (GPTs) has shown promising performance on a variety of NLP tasks in the health domain with little to no annotated data. However, their potential in analyzing health-related social media data remains underexplored. In this paper, we report empirical evaluations of LLMs (GPT-3.5-Turbo, FLAN-T5, and BERT-based models) on a common NLP task of health-related social media data: sentiment analysis for identifying opinions toward health issues. We explored how different prompting and fine-tuning strategies affect the performance of LLMs on social media datasets across diverse health topics, including Healthcare Reform, vaccination, mask wearing, and healthcare service quality. We found that LLMs outperformed VADER, a widely used off-the-shelf sentiment analysis tool, but are far from being able to produce accurate sentiment labels. However, their performance can be improved by data-specific prompts with information about the context, task, and targets. The highest performing LLMs are BERT-based models that were fine-tuned on aggregated data. We provided practical tips for researchers to use LLMs on health-related social media data for optimal outcomes. We also discuss future work needed to continue to improve the performance of LLMs for analyzing health-related social media data with minimal annotations.
Reduced STMN2 and pathogenic TDP-43, two hallmarks of ALS, synergize to accelerate motor decline in mice
Authors: Krus Kelsey L. , Morales Benitez Ana , Strickland Amy , Milbrandt Jeffrey , Bloom A. Joseph , DiAntonio Aaron 
Published: March 2024

AbstractPathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients.Stathmin2(Stmn2)is a key target of TDP-43 regulation and aberrantly splicedStmn2mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer’s Disease. STMN2 participates in the axon injury response and its depletionin vivopartially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation. The interaction between STMN2 loss and TDP-43 dysfunction has not been studied in mice because TDP-43 regulates human but not murineStmn2splicing. Therefore, we generated trans-heterozygous mice that lack one functional copy ofStmn2and express one mutant TDP-43Q331Kknock-in allele to investigate whether reduced STMN2 function exacerbates TDP-43-dependent pathology. Indeed, we observe synergy between these two alleles, resulting in an early onset, progressive motor deficit. Surprisingly, this behavioral defect is not accompanied by detectable neuropathology in the brain, spinal cord, peripheral nerves or at neuromuscular junctions (NMJs). However, the trans-heterozygous mice exhibit abnormal mitochondrial morphology in their distal axons and NMJs. As both STMN2 and TDP-43 affect mitochondrial dynamics, and neuronal mitochondrial dysfunction is a cardinal feature of many neurodegenerative diseases, this abnormality likely contributes to the observed motor deficit. These findings demonstrate that partial loss of STMN2 significantly exacerbates TDP-43-associated phenotypes, suggesting that STMN2 restoration could ameliorate TDP-43 related disease before the onset of degeneration.
Persistent homology centrality improves link prediction performance in Pubmed co-occurrence networks
Authors: Brown Chase Alan , Wren Jonathan D. 
Published: March 2024

AbstractThis paper provides a novel approach to understanding the nature of innovation and scientific progress by analyzing large-scale datasets of scientific literature. A new measure of novelty potential or disruptiveness for a set of scientific entities is proposed, based in the mathematical formalism of algebraic topology via a method calledpersistent homology. In this framework, understanding where academic ideas depart from the existing body of knowledge tofill knowledge gapsis key to scoring a set of entities and their potential for filling future knowledge gaps. This framework is motivated by the assumption that scientific discovery has underlying regularities that can be modeled and predicted.Our method uses afiltration, which is a type of ranking of hypergraph components along a chosen parameter. In this work two different axes are used, which constructs a growing grid of sub-hypergraphs. The axes of time (scientific knowledge evolution) and normalized point-wise mutual information (network structure) affords the ability to succinctly represent the entire dynamic structure of the scientific literature network. We then find that using very simple and interpretable measures of centrality derived from this crudebifiltrationorvineyardaffords the ability to predict links within the dynamic scientific network.While several different methods of link prediction have been proposed in the past, the method presented hereextendsthe notion of link prediction to a higher dimension, as the boundary of the knowledge gap may be more than just 0-dimensional nodes.The system presented here not only suggests a mathematical basis, consistent with observations in cognitive neurosciences regarding early childhood language acquisition, but additionally provides useful applications for the scientific community in predicting and ranking hypothesis for scientific discovery.
Integrin conformation-dependent neutrophil slowing obstructs the capillaries of the pre-metastatic lung in a model of breast cancer
Authors: Fercoq Frédéric , Cairns Gemma S. , Donatis Marco De , Mackey John B. G. , Floerchinger Alessia , McFarlane Amanda , Raffo-Iraolagoitia Ximena L. , Whyte Declan , Arnott Lindsey W. G. , Nixon Colin , Wiesheu Robert , Kilbey Anna , Brown Leah , Al-Khalidi Sarwah , Norman Jim C. , Roberts Edward W. , Blyth Karen , Coffelt Seth B. , Carlin Leo M. 
Published: March 2024

AbstractNeutrophils are thought to be critical to the process whereby breast cancers establish an immunosuppressive and tumour cell nurturing ‘pre-metastatic’ niche before overt metastasis can be detected. However, the spatial localization of neutrophils and their interaction with other cell types in the lung pre-metastatic niche is not well described. We used a spontaneously metastatic mammary cancer model combined with a multiplexed three- and four-dimensional imaging approach to investigate the behaviour of neutrophils in the pre-metastatic niche. Volume fixed tissue three-dimensional imaging showed that approximately 40% of CD8+T cells are adjacent to neutrophils at this stage. In live tissue, we found neutrophils with impaired intravascular motility congested the capillaries of pre-metastatic lungs potentially obstructing CD8+T cells. Slowed neutrophil transit was dependent on the conformation of β2-integrin and could be recapitulated by treating non-tumour bearing mice with G-CSF, a potent systemic mediator of granulopoiesis. We found a decrease in L-selectin (CD62L) on neutrophils in the lungs of both mammary tumour bearing and G-CSF treated mice. Finally, we observed differential accumulation of intravenously injected micro-beads in the lung, suggestive of transient circulatory dead spaces which were also dependent on β2-integrin inactivation. Overall, our study proposes that integrin-mediated neutrophil congestion of the alveolar capillaries could contribute to the generation of the pulmonary pre-metastatic niche.
Atomistic Characterization of Beta-2-Glycoprotein I Domain V Interaction with Anionic Membranes
Authors: Hasdemir Hale S. , Pozzi Nicola , Tajkhorshid Emad 
Published: March 2024

AbstractBackgroundInteraction of beta-2-glycoprotein I (β2GPI) with anionic membranes is crucial in antiphospholipid syndrome (APS), implicating the role of it’s membrane bind-ing domain, Domain V (DV). The mechanism of DV binding to anionic lipids is not fully understood.ObjectivesThis study aims to elucidate the mechanism by which DV ofβ2GPI binds to anionic membranes.MethodsWe utilized molecular dynamics (MD) simulations to investigate the struc-tural basis of anionic lipid recognition by DV. To corroborate the membrane-binding mode identified in the HMMM simulations, we conducted additional simulations using a full mem-brane model.ResultsThe study identified critical regions in DV, namely the lysine-rich loop and the hydrophobic loop, essential for membrane association via electrostatic and hydrophobic interactions, respectively. A novel lysine pair contributing to membrane binding was also discovered, providing new insights intoβ2GPI’s membrane interaction. Simulations revealed two distinct binding modes of DV to the membrane, with mode 1 characterized by the insertion of the hydrophobic loop into the lipid bilayer, suggesting a dominant mechanism for membrane association. This interaction is pivotal for the pathogenesis of APS, as it facilitates the recognition ofβ2GPI by antiphospholipid antibodies.ConclusionThe study advances our understanding of the molecular interactions be-tweenβ2GPI’s DV and anionic membranes, crucial for APS pathogenesis. It highlights the importance of specific regions in DV for membrane binding and reveals a predominant bind-ing mode. These findings have significant implications for APS diagnostics and therapeutics, offering a deeper insight into the molecular basis of the syndrome.
Illuminating the Dark Cancer Phosphoproteome Through a Machine-Learned Co-Regulation Map of 26,280 Phosphosites
Authors: Jiang Wen , Jaehnig Eric J. , Liao Yuxing , Yaron-Barir Tomer M. , Johnson Jared L. , Cantley Lewis C. , Zhang Bing 
Published: March 2024

SummaryMass spectrometry-based phosphoproteomics offers a comprehensive view of protein phosphorylation, but limited knowledge about the regulation and function of most phosphosites restricts our ability to extract meaningful biological insights from phosphoproteomics data. To address this, we combine machine learning and phosphoproteomic data from 1,195 tumor specimens spanning 11 cancer types to construct CoPheeMap, a network mapping the co-regulation of 26,280 phosphosites. Integrating network features from CoPheeMap into a machine learning model, CoPheeKSA, we achieve superior performance in predicting kinase-substrate associations. CoPheeKSA reveals 24,015 associations between 9,399 phosphosites and 104 serine/threonine kinases, including many unannotated phosphosites and under-studied kinases. We validate the accuracy of these predictions using experimentally determined kinase-substrate specificities. By applying CoPheeMap and CoPheeKSA to phosphosites with high computationally predicted functional significance and cancer-associated phosphosites, we demonstrate the effectiveness of these tools in systematically illuminating phosphosites of interest, revealing dysregulated signaling processes in human cancer, and identifying under-studied kinases as putative therapeutic targets.
Inverse and Postponed Impacts of Extracellular Tau PHF on Astrocytes and Neurons’ Mitochondrial Function
Authors: Zufferey Valentin , Parietti Enea , Barve Aatmika , Espourteille Jeanne , Varisco Yvan , Fabbri Kerstin , Capotosti Francesca , Preitner Nicolas , Richetin Kevin 
Published: March 2024

AbstractBackgroundTauopathies encompass a spectrum of neurodegenerative disorders which are marked by the pathological aggregation of tau protein into paired helical filaments (PHF-tau), neurofibrillary tangles (NFTs) and Glial-fibrillary tangles (GFTs). These aggregates impair cellular, mitochondrial, and synaptic functions. The emergence of extracellular tau (ePHF-tau), featuring a myriad of isoforms and phosphorylation states, presents a challenge in comprehending its nuanced effects on neural cells, particularly concerning synaptic and mitochondrial integrity.MethodsWe studied the impact of ePHF-tau (2N4R) on different states and ages of primary cultures of rat neuroglia. Using confocal microscopy and proteomic analysis of synaptosomes, we studied the impact of ePHF-tau on neurite and synapse number. We monitored mitochondrial responses in neurons and astrocytes over 72 hours using advanced fluorescence microscopy for dynamic, high-throughput analysis.ResultsTreatment with ePHF-tau has a strong effect on the neurites of immature neurons, but its toxicity is negligible when the neurons are more mature. At the mature stage of their development, we observed a substantial increase in the density of the PSD-95/vGlut1 zone in neurite, suggesting altered synaptic connectivity and ePHF-tau excitotoxicity. Proteomics revealed significant changes in mitochondrial protein in synaptosomes following exposure to ePHF-tau. In the neuronal compartment, real-time imaging revealed rapid and persistent mitochondrial dysfunction, increased ATP production, and reduced mitochondrial turnover. In contrast, we observed increased mitochondrial turnover and filamentation after treatment in the astrocyte processes, indicating cell-specific adaptive responses to ePHF-tau.ConclusionsThis study sheds light on the intricate effects of extracellular tau aggregates on neuronal and astrocytic mitochondrial populations, highlighting how tau pathology can lead to mitochondrial disturbances and synaptic alterations. By delineating the differential responses of neurons and astrocytes to ePHF-tau, our findings pave the way for developing targeted therapeutic interventions to mitigate the detrimental impacts of tau aggregates in neurodegenerative diseases.
Thoracic discopathy and thoracic-chest related pain: a scoping review
Authors: Lucia Ferrulli , Martina Zaninetti , Michele Margelli , Filippo Maselli , Galeoto Giovanni 
Published: March 2024

ABSTRACTBackgroundThoracic discopathy refers to the degeneration or herniation of one or more discs in the thoracic spine, which can cause thoracic-chest related pain. Thoracic-chest related pain can be challenging to diagnose and treat, as it can have various causes, including musculoskeletal, neurological, and visceral.ObjectivesThis scoping review aims to provide an overview of the current scientific literature on the thoracic discopathy and the thoracic-chest related pain, by examining the available scientific research, as well as to identify any existing gaps in knowledge.Eligibility criteriaThe databases of Medline, Cinahl, Cochrane, Prospero were searched using key terms: “thoracic”, “chest”, “dorsal”, “disc”, “hernia”, “radiculopathy”, “myelopathy”, and “pain”.We also have searched for Grey literature onclinicaltrial.govand google scholar.Inclusion criteriaadult population (over 18 years old); thoracic discopathy or thoracic-chest related pain; Italian or English language; no context, geographical or temporal limits. Exclusion criteria: unspecified pathologies and symptoms (as non-specific back pain, low back pain) and specific pathologies without any interest of thoracic disc (as spinal synovial cysts, spinal arachnoid webs, lung herniation ecc).
Emergence and ongoing outbreak of ST80 vancomycin-resistantEnterococcus faeciumin Guangdong province, China from 2021 to 2023: a multicenter, time-series and genomic epidemiological study
Authors: Shen Cong , Luo Li , Zhou Hongyun , Xiao Yinglun , Zeng Jinxiang , Zhang Liling , Pu Jieying , Zeng Jianming , Zhang Ni , Jiang Yueting , Xu Lingqing , Chen Dingqiang , Li Gang , Wu Kuihai , Yu Hua , Wang Min , Guo Xuemin , Wang Juan , Huang Bin , Chen Cha 
Published: March 2024

AbstractBackgroundThe surveillance system revealed that the prevalence of vancomycin-resistantEnterococcus faecium(VREfm) has increased. We aim to investigate the epidemiological and genomic characteristics of VREfm in China.MethodsWe collected 20747 non-redundantE. faeciumisolates from inpatients across 19 hospitals in six provinces between Jan 2018 and June 2023. VREfm was confirmed by antimicrobial susceptibility testing. The prevalence was analyzed using changepoint package in R. Genomic characteristics were explored by whole-genome sequencing and bioinformatic analysis.Results5.59% (1159/20747) ofE. faeciumisolates were resistant to vancomycin. The prevalence of VREfm increased in Guangdong province from 5% before 2021 to 20%-50% in 2023 (p<0.0001), but not in the other five provinces. The two predominant clones before 2021, ST17 and ST78, were substituted by an emerging clone, ST80, from 2021 to 2023 (88.63%, 195/220). All ST80 VREfm from Guangdong formed a single lineage (SC11) and were genetically distant from the ST80 VREfm from other countries, suggesting a regional outbreak. All ST80 VREfm in SC11 carried a new type of plasmid which harbored avanAcassette (vanRSHAXYZ) flanked by Tn1546/Tn3clusters. However, no conjugation-related gene was detected and no transconjugant was obtained in conjugation experiment, indicating that the outbreak of ST80 VREfm could be attributed to clonal transmission.ConclusionsWe revealed an ongoing outbreak of ST80 VREfm with a newvanA-harboring plasmid in Guangdong, China. This clone has also been identified in other provinces and countries, foreboding a risk of wider spreading shortly. Continuous surveillance is needed to inform public health interventions.
Disentangling mechanisms behind the pleiotropic effects of proximal 16p11.2 BP4-5 CNVs
Authors: Auwerx Chiara , Moix Samuel , Kutalik Zoltán , Reymond Alexandre 
Published: March 2024

AbstractWhereas 16p11.2 BP4-5 copy-number variants (CNVs) represent one of the most pleiotropic etiologies of genomic syndromes in both clinical and population cohorts, the mechanisms leading to such pleiotropy remain understudied. Identifying 73 deletion and 89 duplication carriers among unrelated white British UK Biobank participants, we performed a phenome-wide association study between the region’s copy number and 117 complex traits and diseases, mimicking four dosage models. Forty-six phenotypes (39%) were affected by 16p11.2 BP4-5 CNVs, with the deletion-only, mirror, U-shape, and duplication-only models being the best fit for thirty, ten, four, and two phenotypes, respectively, aligning with the stronger deleteriousness of the deletion. Upon individually adjusting CNV effects for either body mass index (BMI), height, cognitive function, or socio-economic status as potential mediators, we found that sixteen testable deletion-driven associations (61%) – primarily with cardiovascular and metabolic traits – were BMI-dependent, with other mediators playing a more subtle role. Bidirectional Mendelian randomization supported that 13 out of these 16 associations (81%) were secondary consequences of the CNV’s impact on BMI. For the 22 traits that remained significantly associated upon individual adjustment for mediators, matched-control analyses found that eleven phenotypes, including musculoskeletal traits, liver enzymes, fluid intelligence, platelet count, pulmonary capacity, pneumonia, and acute kidney injury, remained associated under strict Bonferroni correction, with eight additional nominally significant associations. These results paint a complex picture of 16p11.2 BP4-5’s pleiotropic pattern that involves direct effects on multiple physiological systems and indirect co-morbidities consequential to the CNV’s impact on BMI and cognition, acting through trait-specific dosage mechanisms.
Otoferlin requires a free intravesicular C-terminal end for synaptic vesicle docking and fusion
Authors: Dulon Didier , Boutet de Monvel Jacques , Plion Baptiste , Mallet Adeline , Condamine Steven , Bouleau Yohan , Safieddine Saaid 
Published: March 2024

SUMMARYOur understanding of how otoferlin, the major calcium sensor in inner hair cells (IHCs) synaptic transmission, contributes to the overall dynamics of synaptic vesicle (SV) trafficking remains limited. To address this, we generated a knock-in mouse model expressing an otoferlin-GFP protein, where GFP was fused to its C-terminal transmembrane domain. Similar to the wild type protein, the GFP-tagged otoferlin showed normal expression and was associated with IHC SV. Surprisingly, while the heterozygoteOtof+/GFPmice exhibited a normal hearing function, homozygoteOtofGFP/GFPmice were profoundly deaf attributed to severe reduction in SV exocytosis. Fluorescence recovery after photobleaching revealed a markedly increased mobile fraction of the otof-GFP-associated SV inOtofGFP/GFPIHCs. Correspondingly, 3D-electron tomographic of the ribbon synapses indicated a reduced density of SV attached to the ribbon active zone. Collectively, these results indicate that otoferlin requires a free intravesicular C-terminal end for normal SV docking and fusion.
Cell-Type Specific Reductions in Interneuron Gene Expression within Subregions of the Anterior and Posterior Cingulate Gyrus of Schizophrenia and Bipolar Disorder Subjects
Authors: Krolewski David M. , Waselus Maria , Bunney Blynn G. , Myers Richard M. , Barchas Jack D. , Lee Francis S.Y. , Schatzberg Alan F. , Bunney William E. , Akil Huda , Watson Stanley J. 
Published: March 2024

AbstractSchizophrenia (SZ) and bipolar disorder (BP) patients share overlapping and distinct neurocognitive deficits. Neuroimaging of these patients and postmortem gene expression analyses suggest that compromised cingulate gyrus GABA-ergic interneurons may contribute to cognitive impairments in SZ and BP. Therefore, we investigated potential gene expression signatures for SZ and BP using interneuron cell-type specific markers including glutamic acid decarboxylase (GAD67), parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP) within cingulate Brodmann’s areas (BA). We report reduced GAD67 mRNA in anterior midcingulate cortex (aMCC) of SZ and BP subjects with BA24c’ being most dysregulated across disorders, demonstrating reduced PV (SZ), SST (BP), and VIP mRNA (SZ and BP). Dorsal posterior cingulate (dPCC) displayed decreased SST (BP) whereas retrosplenial cortex (RSC) showed reduced PV (SZ and BP) and SST mRNA (BP). Our results show shared and unique transcription signatures of two disorders in specific cingulate gyrus regions and cell types. SZ and BP show a similar profile of aMCC gene expression reductions suggesting subregional dysregulation within areas associated with error/action monitoring and the saliency network. In dPCC/RSC, transcriptional changes are associated with disease-specific gene/subregion signatures, possibly underlying differential effects on allocation of attentional resources and visuospatial memory processing unique to each disorder.