bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of sex differences in cooperation: the role of trade-offs with dispersal
Authors: Capilla-Lasheras Pablo , Bircher Nina , Brown Antony M. , Harrison Xavier , Reed Thomas , York Jennifer E. , Cram Dominic L. , Rutz Christian , Walker Lindsay , Naguib Marc , Young Andrew J.
Published: September 2023

Abstract

Explaining the evolution of sex differences in cooperation remains a major challenge. Comparative studies highlight that offspring of the more philopatric sex tend to be more cooperative within their family groups than those of the more dispersive sex but we do not understand why. The leading ‘Philopatry hypothesis’ proposes that the more philopatric sex cooperates more because their higher likelihood of natal breeding increases the direct fitness benefits of natal cooperation. However, the ‘Dispersal trade-off hypothesis’ proposes that the more dispersive sex cooperates less because preparations for dispersal, such as extra-territorial prospecting, trade-off against natal cooperation. Here, we test both hypotheses in cooperatively breeding white-browed sparrow weavers (Plocepasser mahali), using a novel high-resolution automated radio-tracking method. First, we show that males are the more dispersive sex (a rare reversal of the typical avian sex-difference in dispersal) and that, consistent with the predictions of both hypotheses, females contribute substantially more than males to cooperative care while within the natal group. However, the Philopatry hypothesis cannot readily explain this female-biased cooperation, as females are not more likely than males to breed within their natal group. Instead, our radio-tracking findings support the Dispersal trade-off hypothesis: males conduct pre-dispersal extra-territorial prospecting forays at higher rates than females and prospecting appears to trade-off against natal cooperation. Our findings thus highlight that the evolution of sex differences in cooperation could be widely attributable to trade-offs between cooperation and dispersal; a potentially general explanation that does not demand that cooperation yields direct fitness benefits.
Genome-Scale Metabolic Modeling Identifies Causal Reactions Mediated by SNP-SNP Interactions Influencing Yeast Sporulation
Authors: Sasikumar Srijith , Kumar S Pavan , Bhatt Nirav , Sinha Himanshu
Published: September 2023

Understanding how genetic variations influence cellular function remains a major challenge in genetics. Genome-scale metabolic models (GEMs) are powerful tools used to understand the functional effects of genetic variants. While GEMs have illuminated genotype-phenotype relationships, the impact of single nucleotide polymorphisms (SNPs) in transcription factors and their interactions on metabolic fluxes remains largely unexplored. We used gene expression data from a yeast allele replacement panel to construct co-expression networks and SNP-specific GEMs. The analysis of these models helped us to understand how genetic interactions affect yeast sporulation efficiency, a quantitative trait. Our findings revealed that SNP-SNP interactions have a significant impact on the connectivity of key metabolic regulators involved in steroid biosynthesis, amino acid metabolism and histidine biosynthesis. By integrating gene expression data into GEMs and conducting genome-scale differential flux analysis, we were able to identify causal reactions within six major metabolic pathways, providing mechanistic explanations for variations in sporulation efficiency. Notably, we found that in specific SNP combinations, the pentose phosphate pathway was differentially regulated. In models where the pentose phosphate pathway was inactive, the autophagy pathway was activated, likely compensating by providing critical precursors such as nucleotides and amino acids. This compensatory mechanism may enhance sporulation efficiency by supporting processes that are dependent on the pentose phosphate pathway. Our study sheds light on how transcription factor polymorphisms interact to shape metabolic pathways in yeast and offers valuable insights into genetic variants associated with metabolic traits in genome-wide association studies.
Multi-omic profiling of pathogen-stimulated primary immune cells
Authors: Salz Renee , Vorsteveld Emil E. , van der Made Caspar I. , Kersten Simone , Stemerdink Merel , Riepe Tabea V. , Hsieh Tsung-han , Mhlanga Musa , Netea Mihai G. , Volders Pieter-Jan , Hoischen Alexander , ’t Hoen Peter A.C.
Published: September 2023

We performed long-read transcriptome and proteome profiling of pathogen-stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors to discover new transcript and protein isoforms expressed during immune responses to diverse pathogens. Long-read transcriptome profiling reveals novel sequences and isoform switching induced upon pathogen stimulation, including transcripts that are difficult to detect using traditional short-read sequencing. Widespread loss of intron retention occurs as a common result of all pathogen stimulations. We highlight novel transcripts ofNFKB1 and CASP1that may indicate novel immunological mechanisms. RNA expression differences did not result in differences in the amounts of secreted proteins. Clustering analysis of secreted proteins revealed a correlation between chemokine (receptor) expression on the RNA and protein levels inC. albicans-and Poly(I:C)-stimulated PBMCs. Isoform aware long-read sequencing of pathogen-stimulated immune cells highlights the potential of these methods to identify novel transcripts, revealing a more complex transcriptome landscape than previously appreciated.
Deep Learning of Ligand-bound RNA Tertiary Structures Diverges from Learning Unbound Ones: A Case Study Using The gRNAde Software
Authors: Dhesi Tajveer S. , Bannister Alyssa W. , Manzourolajdad Amirhossein
Published: September 2023

Modeling the relationship between the native RNA sequence and itsin-vivostructure is challenging, partly due to the flexible nature of the RNA molecular structure. In addition, the RNA structure can take on different conformations in the presence of specific molecules, metabolites, temperatures or other signaling and environmental factors, making it difficult to construct a universal statistical model for the sequence-structure relationship of the RNA. Using a Geometric-Vector-Perceptron Graph Neural Network architecture, Joshi, et al. predict the RNA sequence from its given 3D structure with good performance and on a dataset including RNA structures of different type and length, namely RNAsolo. In this work, using the Authors open-source software package, gRNAde, we confirm their results on a more updated version of RNAsolo and for structure of different resolution, confirming the ability of the algorithm to capture RNA structural features and generalize to sequences of different lengths. We did observe, however, that performance on riboswitches is lower than expected that RNAs whose structure has been resolved while being bound to a ligand, such as riboswitches, may require a statistical model that diverges from those of native structures.
Searching for Structure: Characterizing the Protein Conformational Landscape with Clustering-based Algorithms
Authors: Macke Amanda C. , Stump Jacob E. , Kelly Maria S. , Rowley Jamie , Herath Vageesha , Mullen Sarah , Dima Ruxandra I.
Published: September 2023

The identification and characterization of the main conformations from a protein population is a challenging, inherently high-dimensional problem. We introduce the Secondary sTructural Ensembles with machine LeArning (StELa) double clustering method, which clusters protein structures based on the underlying Ramachandran plot. Our approach takes advantage of the relationship between the phi and psi dihedral angles in a protein backbone and the secondary structure of the protein. The classification of states as vectors composed of the clusters’ indices arising naturally from the Ramachandran plot, followed by the hierarchical clustering of the vectors, enables the identification of the minima from the corresponding free energy landscape (FEL) by lifting the high structure degeneracy found with existing approaches such as the RMSD-based clustering GROMOS. We compare the performance of StELa with not only GROMOS but also with CATS, the combinatorial averaged transient structure clustering method based on distributions of the phi and psi dihedral angle coordinates. Using ensembles of conformations from molecular dynamics (MD) simulations of either intrinsically disordered proteins (IDPs) of various lengths (tau protein fragments) or from local structures from a globular protein, we show that StELa is the only clustering method that identifies nearly all the minima from the corresponding FELs. In contrast, GROMOS yields a large number of clusters that cover the entire FEL and CATS, even with an additional clustering step, is unable to sample well the FEL for long IDPs and for fragments from globular proteins as it misses important minima.

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Deep-learning and transfer learning identify new breast cancer survival subtypes from single-cell imaging data
Authors: Yadav Shashank , Zhou Shu , He Bing , Du Yuheng , Garmire Lana X
Published: September 2023

Quantitative models that explicitly capture single-cell resolution cell-cell interaction features to predict patient survival at population scale are currently missing. Here, we computationally extracted hundreds of features describing single-cell based cell-cell interactions and cellular phenotypes from a large, published cohort of cyto-images of breast cancer patients. We applied these features to a neural-network based Cox-nnet survival model and obtained high accuracy in predicting patient survival in test data (Concordance Index > 0.8). We identified seven survival subtypes using the top survival features, which present distinct profiles of epithelial, immune, fibroblast cells, and their interactions. We identified atypical subpopulations of TNBC patients with moderate prognosis (marked by GATA3 over-expression) and Luminal A patients with poor prognosis (marked by KRT6 and ACTA2 over-expression and CDH1 under-expression). These atypical subpopulations are validated in TCGA-BRCA and METABRIC datasets. This work provides important guidelines on bridging single-cell level information towards population-level survival prediction.

STATEMENT OF TRANSLATIONAL RELEVANCE

Our findings from a breast cancer population cohort demonstrate the clinical utility of using the single-cell level imaging mass cytometry (IMC) data as a new type of patient prognosis prediction marker. Not only did the prognosis prediction achieve high accuracy with a Concordance index score greater than 0.8, it also enabled the discovery of seven survival subtypes that are more distinguishable than the molecular subtypes. These new subtypes present distinct profiles of epithelial, immune, fibroblast cells, and their interactions. Most importantly, this study identified and validated atypical subpopulations of TNBC patients with moderate prognosis (GATA3 over-expression) and Luminal A patients with poor prognosis (KRT6 and ACTA2 over-expression and CDH1 under-expression), using multiple large breast cancer cohorts.
Perspectives on health, illness, disease and management approaches among Baganda traditional spiritual healers in Central Uganda
Authors: Sekagya Yahaya H. K. , Muchunguzi Charles , Unnikrishnan Payyappallimana , Mulogo Edgar M.
Published: September 2023

In Uganda, spirituality is closely associated with traditional healthcare; however, though prevalent, it is considered controversial, mystical, less-documented and often misunderstood. There is a paucity of literature on the description of health, illness, disease, and management approaches among traditional spiritual healers. This article examines perspectives on health, illness, disease and management approaches among Baganda traditional spiritual healers, theBalubaale, in central Uganda, who engage ancestral spirits in health care and management.

The study used a qualitative study design in particular grounded theory. Unstructured, qualitative interviews and observation were used on 12 male and female purposively selectedBalubaalein Central Uganda. Data was transcribed, coded and thematically analyzed using ATLAS ti. 22 Computer software based on an inductive approach.

Findings show that the words and concepts describing health, illness, disease and management approaches are descriptive and contextualized to include the problem, the prospected root-causes, and therapeutic approaches involved. The words for illness “olumbe”,disease“obulwadde”and the management approaches such as divination (kulagula), ritual cleansing(kwambulula), amulets (ensiribaandyirizi), and scarification (kusandaga)have spiritual and social dimensions, contextual meanings and attachments.

Further research is recommended among other tribes and larger sample size to compare findings and terminologies to facilitate communication and policy considerations.
The predictive value of arterial stiffness combined with hypertension in the index of atherosclerotic cardiovascular disease
Authors: Qin Qian , Yang Yang , Li Jiaoyan , Yang Hang , Chen Jingfeng , Zheng Yansong , Ding Suying
Published: September 2023

Objective

This study was conducted to investigate the hypertension and arterial stiffness (AS) in predicting future atherosclerotic cardiovascular disease (ASCVD) risk.Methods:We included 6530 participants from Chinese People′s Liberation Army General Hospital. AS was assessed by measuring brachial-ankle pulse wave velocity (baPWV) and participants were stratified into two groups: ASCVD≥10% or ASCVD<10% by a risk threshold of 10%. The Kaplan-Meier survival analysis and Cox proportional risk model were evaluated the risk of ASCVD between participants with ideal vascular function (IVF defined as normal AS with normotension), normotension with AS (NTAS), hypertension with normal baPWV (HTNAS) and hypertension with AS (HTAS). C statistics were used to compare hypertension and AS status in determining ASCVD risk.

Results

After a median follow-up of 2.17 years, 672 participants with high risk of ASCVD were identified. Compared to the IVF group, the highest risk of ASCVD was exhibited in the HTAS group (HR=2.252,95%CI=1.733∽2.927), followed by the NTAS group (HR=1.888,95%CI=1.583∽2.252) and HTNAS group (HR=1.827,95%CI=1.144∽2.916). Multiple sensitivity and subgroup analyses yielded similar results. Additionally, compared to the addition of hypertension in the traditional model, the addition of AS elevated the incremental effect on the predicted value of ASCVD (the C statistic was 0.824 vs 0.817, integrated discrimination improvement was 0.80% vs 0.20%, and net reclassification index was 25.00% vs 12.20%).

Conclusions

The individuals with AS had a higher risk of ASCVD, and hypertension amplified these associations after adjusting for cardiovascular confounders. Otherwise, AS showed better predictive power than hypertension in determining ASCVD risk.
Development of a search filter to retrieve reports of interrupted time series studies from MEDLINE and PubMed
Authors: Nguyen Phi-Yen , McKenzie Joanne E. , Turner Simon L. , Page Matthew J. , McDonald Steve
Published: September 2023

Background

Interrupted time series (ITS) studies contribute importantly to systematic reviews of population-level interventions. However, there is no search filter designed to identify only ITS studies from bibliographic databases. We aimed to develop and validate search filters to retrieve ITS studies in MEDLINE and PubMed.

Methods

A set of 1,017 known ITS studies (published 2013-2017) were analysed using text mining to generate candidate terms. A population set of 1,398 time-series studies were used to select discriminating terms. Various combinations of candidate terms were iteratively tested to generate three search filters. An independent set of 700 ITS studies were used to validate the filters’ sensitivities. The filters were test-run in Ovid MEDLINE; their retrieved records were randomly screened for ITS studies to determine their precision. Finally, all three MEDLINE filters were translated to PubMed format and their sensitivities in PubMed were estimated.

Results

Three search filters were created: aprecision-maximisingfilter with high precision (78%; 95% CI 74%-82%) but moderate sensitivity (63%; 59%-66%), useful for rapid reviews; asensitivity- and-precision-maximisingfilter with high sensitivity (81%; 77%-83%) but lower precision (32%; 28%-36%), useful when a balance of expediency and comprehensiveness is required; and a sensitivity-maximisingfilter with high sensitivity (88%; 85%-90%) but likely very low precision, useful for search strategies accompanying specific content terms.

Conclusion

Our filters strike different balances between comprehensiveness and screening workload and suit different research needs. To improve retrieval of ITS studies, authors need to identify ITS designs in titles more frequently.
Cooperativity and induced oligomerisation control the interaction of SARS-CoV-2 with its cellular receptor and patient-derived antibodies
Authors: Asor Roi , Olerinyova Anna , Burnap Sean A. , Kushwah Manish S. , Soltermann Fabian , Rudden Lucas Powell , Hensen Mario , Vasiljevic Snežana , Brun Juliane , Hill Michelle , Chang Liu , Dejnirattisa Wanwisa , Supasa Piyada , Mogkolsapaya Juthatip , Zhou Daming , Stuart David I. , Screaton Gavin R. , Degiacomi Matteo , Zitzmann Nicole , Benesch Justin L. P. , Struwe Weston B. , Kukura Philipp
Published: September 2023

Viral entry is mediated by oligomeric proteins on the virus and cell surfaces. The association is therefore open to multivalent interactions between these proteins, yet such recognition is typically rationalised as affinity between monomeric equivalents. As a result, assessment of the thermodynamic mechanisms that control viral entry has been limited. Here, we use mass photometry to overcome the analytical challenges consequent to multivalency. Examining the interaction between the spike protein of SARS-CoV-2 and the ACE2 receptor, we find that ACE2 induces oligomerisation of spike in a variant-dependent fashion. We also demonstrate that patient-derived antibodies use induced-oligomerisation as a primary inhibition mechanism or to enhance the effects of receptor-site blocking. Our results reveal that naive affinity measurements are poor predictors of potency, and introduce a novel antibody-based inhibition mechanism for oligomeric targets.

One-Sentence Summary

Multivalent interactions between viral proteins, cell-surface receptors, and anti-viral antibodies regulate infection and inhibition.
MixOmics Integration of Biological Datasets Identifies Highly Correlated Key Variables of COVID-19 severity
Authors: Harriott Noa C. , Chimenti Michael S. , Ryan Amy L.
Published: September 2023

Background

Despite several years since the COVID-19 pandemic was declared, challenges remain in understanding the factors that can predict the severity of COVID-19 disease and complications of SARS-CoV-2 infection. While many large-scale Multiomic datasets have been published, integration of these datasets has the potential to substantially increase the biological insight gained allowing a more complex comprehension of the disease pathogenesis. Such insight may improve our ability to predict disease progression, detect severe cases more rapidly and develop effective therapeutics.

Methods

In this study we have applied an innovative machine learning algorithm to delineate COVID-severity based on integration of paired samples of proteomic and transcriptomic data from a small cohort of patients testing positive for SARS-CoV-2 infection with differential disease severity. Targeted plasma proteomics and an onco-immune targeted transcriptomic panel was performed on sequential samples from a cohort of 23 severe, 21 moderate and 10 mild COVID-19 patients. We applied DIABLO, a new integrative method, to identify multi-omics biomarker panels that can discriminate between multiple phenotypic groups, such as the varied severity of disease in COVID-19 patients.

Results

As COVID-19 severity is known among our sample group, we can train models using this as the outcome variable and calculate features that are important predictors of severe disease. In this study, we detect highly correlated key variables of severe COVID-19 using transcriptomic discriminant analysis and multi-omics integration methods.

Conclusions

This approach highlights the power of data integration from a small cohort of patients offering a better biological understanding of the molecular mechanisms driving COVID-19 severity and an opportunity to improve prediction of disease trajectories and targeted therapeutics.
Two disparity channels in human visual cortex with different contrast and blur sensitivity
Authors: Kaestner Milena , Chen Yulan D. , Clement Caroline , Hodges Alex , Norcia Anthony M.
Published: September 2023

Purpose

Our goal is to describe the contrast and blur sensitivity of multiple horizontal disparity sub-systems and to relate them to the contrast and spatial sensitivities of their monocular inputs.

Methods

Steady-State Visual Evoked Potentials (SSVEPs) amplitudes were recorded in response to Dynamic Random Dot Stereograms (DRDS) alternating at 2 Hz between zero disparity and varying magnitudes of crossed disparity for disparity plane and disparity grating stimuli. Half-image contrasts ranged between 2.5 and 80% and over a range of Gaussian blurs from 1.4 to 12 arcmin. Separate experiments measured contrast and blur sensitivity for the monocular half-images.

Results

The first and second harmonics disparity responses were maximal for disparity gratings and for the disparity plane condition, respectively. The first harmonic of the disparity grating response was more affected by both contrast and blur than was the second harmonic of the disparity plane response which had higher contrast sensitivity than the first harmonic.

Conclusion

The corrugation frequency, contrast and blur tuning of the first harmonic suggest that it reflects activity of neurons tuned to higher luminance spatial frequencies that are selective for relative disparity, whereas the second harmonic reflects the activity of neurons sensitive to absolute disparity that are driven by low monocular spatial spatial frequencies.

Translational Relevance

SSVEPs to DRDS provide two objective neural measures of disparity processing, the first harmonic – whose stimulus preferences are similar to those of behavioral stereoacuity – and the second harmonic that represents an independent disparity-specific, but not necessarily stereoscopic mechanism.
Towards a mechanistic understanding of the role of error monitoring and memory in social anxiety
Authors: Hosseini Kianoosh , Pettit Jeremy W. , Soto Fabian A. , Mattfeld Aaron T. , Buzzell George A.
Published: September 2023

Cognitive models state social anxiety (SA) involves biased cognitive processing that impacts what is learned and remembered within social situations, leading to the maintenance of SA. Neuroscience work links SA to enhanced error monitoring, reflected in error-related neural responses arising from mediofrontal cortex (MFC). Yet, the role of error monitoring in SA remains unclear, as it is unknown whether error monitoring can drive changes in memory, biasing what is learned or remembered about social situations. Thus, we developed a novel paradigm to investigate the role of error-related MFC theta oscillations (associated with error monitoring) and memory biases in SA. EEG was collected while participants completed a novel Face-Flanker task, involving presentation of task-unrelated, trial-unique faces behind target/flanker arrows on each trial. A subsequent incidental memory assessment evaluated memory biases for error events. Severity of SA symptoms were associated with greater error-related theta synchrony over MFC, as well as between MFC and sensory cortex. SA was positively associated with memory biases for error events. Consistent with a mechanistic role in biased cognitive processing, greater error-related MFC-sensory theta synchrony during the Face-Flanker predicted subsequent memory biases for error events. Our findings suggest high SA individuals exhibit memory biases for error events, and that this behavioral phenomenon may be driven by error-related MFC-sensory theta synchrony associated with error monitoring. Moreover, results demonstrate the potential of a novel paradigm to elucidate mechanisms underlying relations between error monitoring and SA.
Developmental Mouse Brain Common Coordinate Framework
Authors: Kronman Fae A. , Liwang Josephine K. , Betty Rebecca , Vanselow Daniel J. , Wu Yuan-Ting , Tustison Nicholas J. , Bhandiwad Ashwin , Manjila Steffy B. , Minteer Jennifer A. , Shin Donghui , Lee Choong Heon , Patil Rohan , Duda Jeffrey T. , Puelles Luis , Gee James C. , Zhang Jiangyang , Ng Lydia , Kim Yongsoo
Published: September 2023

3D standard reference brains serve as key resources to understand the spatial organization of the brain and promote interoperability across different studies. However, unlike the adult mouse brain, the lack of standard 3D reference atlases for developing mouse brains has hindered advancement of our understanding of brain development. Here, we present a multimodal 3D developmental common coordinate framework (DevCCF) spanning mouse embryonic day (E) 11.5, E13.5, E15.5, E18.5, and postnatal day (P) 4, P14, and P56 with anatomical segmentations defined by a developmental ontology. At each age, the DevCCF features undistorted morphologically averaged atlas templates created from Magnetic Resonance Imaging and co-registered high-resolution templates from light sheet fluorescence microscopy. Expert-curated 3D anatomical segmentations at each age adhere to an updated prosomeric model and can be explored via an interactive 3D web-visualizer. As a use case, we employed the DevCCF to unveil the emergence of GABAergic neurons in embryonic brains. Moreover, we integrated the Allen CCFv3 into the P56 template with stereotaxic coordinates and mapped spatial transcriptome cell-type data with the developmental ontology. In summary, the DevCCF is an openly accessible resource that can be used for large-scale data integration to gain a comprehensive understanding of brain development.
Distributions of Recorded Pain in Mental Health Records: A Natural Language Processing Based Study
Authors: Chaturvedi Jaya , Stewart Robert , Ashworth Mark , Roberts Angus
Published: September 2023

Objective

The objective of this study is to determine demographic and diagnostic distributions of physical pain recorded in the clinical notes of a mental health electronic health records database by utilising natural language processing and to examine the level of overlap in recorded physical pain between primary and secondary care.

Design, Setting and Participants

The data were extracted from an anonymised version of the electronic health records from a large mental community and secondary healthcare provider serving a catchment of 1.3M residents in south London. These included patients under active referral and aged 18+ at the index date of July 1, 2018, and had at least one clinical document (>=30 characters) associated with their record between July 1, 2017 and July 1, 2019. This cohort was compared to linked primary care records from one of the four catchment boroughs.

Outcome

The primary outcome of interest was the presence or absence of recorded physical pain within the clinical notes of the patients. This does not include mental, psychological or metaphorical pain.

Results

A total of 27,211 patients were retrieved based on the extraction criteria. Of these, 52% (14,202) had narrative text containing relevant mentions of physical pain. Patients who were older (OR 1.17, 95% CI 1.15-1.19), female (OR 1.42, 95% CI 1.35-1.49), of Asian (OR 1.30, 95% CI 1.16-1.45) or Black (OR 1.49, 95% CI 1.40-1.59) ethnicities, and living in deprived neighbourhoods (OR 1.64, 95% CI 1.55-1.73) showed higher odds of recorded pain. Patients with an SMI diagnosis were found to be less likely to report pain (OR 0.43, 95% CI 0.41-0.46, p<0.001). When comparing the overlap between primary and secondary care, 17% of the CRIS cohort also had records within LDN, and 31% of these had recorded pain in both records.

Conclusion

The findings of this study show the sociodemographic and diagnostic differences in recorded pain, and have significant implications for the assessment and management of physical pain in patients with mental health disorders.

Strengths and Limitations of this study

This study utilises natural language processing on clinical notes to access a large sample with information about pain.

This is the first cross-sectional study to summarise and describe the distribution of recorded pain within the clinical notes of mental health records.

The recorded mentions of pain within clinical notes clearly depend on the patient sharing and the clinician recording their experiences.

The findings are not generalisable to the general population since this study only looks at patients receiving mental healthcare within a specific geographic catchment.
Development and Performance Assessment of a Novel Plasma p-Tau181 Assay Reflecting Tau Tangle Pathology in Alzheimer’s Disease
Authors: Tagai Kenji , Tatebe Harutsugu , Matsuura Sayo , Hong Zhang , Kokubo Naomi , Matsuoka Kiwamu , Endo Hironobu , Oyama Asaka , Hirata Kosei , Shinotoh Hitoshi , Kataoka Yuko , Matsumoto Hideki , Oya Masaki , Kurose Shin , Takahata Keisuke , Ichihashi Masanori , Kubota Manabu , Seki Chie , Shimada Hitoshi , Takado Yuhei , Kawamura Kazunori , Zhang Ming-Rong , Soeda Yoshiyuki , Takashima Akihiko , Higuchi Makoto , Tokuda Takahiko
Published: September 2023

Several blood-based assays for phosphorylated tau (p-tau) have been developed to detect brain tau pathologies in Alzheimer’s disease (AD). However, plasma p-tau measured by currently available assays is influenced by brain amyloid and, therefore, could not accurately reflect brain tau deposits. Here, we devised a novel immunoassay that can quantify N- and C-terminally truncated p-tau fragments (mid-p-tau181) in human plasma. We measured plasma p-tau181 levels in 164 participants who underwent both amyloid and tau positron emission tomography (PET) scans using mid-p-tau181 and conventional p-tau181 assays. The mid-p-tau181 assay displayed stronger correlations with tau PET accumulation than the conventional assay in the AD continuum and accurately distinguished between tau PET-positive and -negative cases. Furthermore, the mid-p-tau181 assay demonstrated a trajectory similar to tau PET alongside cognitive decline. Consequently, our mid-p-tau181 assay could be useful in evaluating the extent of brain tau burden in AD.
Refining COVID-19 retrospective diagnosis with continuous serological tests: a Bayesian mixture model
Authors: Glemain Benjamin , de Lamballerie Xavier , Zins Marie , Severi Gianluca , Touvier Mathilde , Deleuze Jean-François ,   SAPRIS-SERO study group, Lapidus Nathanaël , Carrat Fabrice
Published: September 2023

COVID-19 serological tests with a “positive”, “intermediate” or “negative” result according to predefined thresholds cannot be directly interpreted as a probability of having been infected with SARS-CoV-2. Based on 81,797 continuous anti-spike tests collected in France after the first wave, a Bayesian mixture model was developed to provide a tailored infection probability for each participant. Depending on the serological value and the context (age and administrative region), a negative or a positive test could correspond to a probability of infection as high as 61.9% or as low as 68.0%, respectively. In infected individuals, the model estimated a proportion of “non-responders” of 14.5% (95% CI, 11.2-18.1%), corresponding to a sub-group of persons who exhibited a weaker serological response to SARS-CoV-2. This model allows for an individual interpretation of serological results as a probability of infection, depending on the context and without any notion of threshold.
Predictors of COVID-19 Vaccine Acceptability Among Refugees and Other Migrant Populations: A Systematic Scoping Review
Authors: Yazdani Yasaman , Pai Poojitha , Sayfi Shahab , Mohammadi Arash , Perdes Saber , Spitzer Denise , Fabreau Gabriel E. , Pottie Kevin
Published: September 2023

Objective

This study aimed to map the existing literature to identify predictors of COVID-19 vaccine acceptability among refugees, immigrants, and other migrant populations.

Methods

A systematic search of Medline, Embase, APA PsycInfo and Cumulative Index of Nursing and Allied Health Literature (CINAHL) was conducted up to 31 January 2023 to identify the relevant English peer-reviewed observational studies. Two independent reviewers screened, selected studies, and extracted data.

Results

We identified 34 cross-sectional studies, primarily conducted in high income countries (76%). Lower vaccine acceptance was associated with mistrust in the host countries’ government and healthcare system, concerns about the safety and effectiveness of COVID-19 vaccines, limited knowledge of COVID-19 infection and vaccines, lower COVID-19 risk perception, and lower integration level in the host country. Female gender, younger age, lower education level, and being single were associated with lower vaccine acceptance in most studies. Additionally, sources of information about COVID-19 and vaccines and previous history of COVID-19 infection, also influence vaccine acceptance. Vaccine acceptability towards COVID-19 booster doses and various vaccine brands were not adequately studied.

Conclusions

Vaccine hesitancy and lack of trust in COVID-19 vaccines became significant public health concerns within migrant populations. These findings may help in providing information for current and future vaccine outreach strategies among migrant populations.
Epidemiology and clinical profile of sports injuries treated in the Douala General Hospital and the Douala Laquintinie Hospital
Authors: Tanko Tankeng Leonard , William Ngatchou Djomo , Nana Theophile Chunteng , Bill-Erich Mbianyor , Gilbert Akwa , Kange Lifafa Kinge , Bonny Aimé
Published: September 2023

Background

A sport injury is any body tissue damage that results from the practice of sports or exercise. Despite the number of cases treated at hospitals, very little is reported. Regarding the rising participation in sports and as a consequence sports injuries, this study aimed to present the epidemiology and clinical profile of sport injuries treated at two tertiary hospitals in Douala Cameroon.

Methods

This was a hospital based cross sectional descriptive study during nine months, carried out in the Douala General hospital and the Douala Laquintinie Hospital. Medical records of patients who were treated for sports injuries from January 2012 to April 2022 were included in the study. Severe injury was considered to be an injury score of greater than or equal to three according to the abbreviated injury scale of the injured body region.

Results

Among 72 consecutive eligible records, there was a male predominance (86.1%) with a 6.2 M:F sex ratio. The mean age 24.97±13.8 years and the modal age range was 11-21 years. The prevalence of sports injuries was 1.12% amongst all trauma cases. 48.6% of injured persons were students, 36.1 % employed, 8.3% athletes and 6.9% unemployed. 59.7% of injuries occurred during recreational sports while 22.2% occurred during physical education, 11.1% during trainings and 6.9% during competitions. Football accounted for 66.7% injuries, running 13.9% and 12.5% in jumping. 59.7% of injuries were fractures, 6.9% dislocations, 27.7% soft tissue injuries and 5.6% head injuries. 47.2% of injuries occurred on the lower extremities, 29.2% on the upper extremities, 6.9% on the face, 5.6% abdominopelvic, 4.2% on the thorax, 5.6% head injuries and 1.4% on the neck. Overall 73.7% of sports injuries were severe injuries.

Conclusion

Sports injuries treated in hospitals are severe injuries. The majority of sports injuries treated in hospitals are fractures. Most sports injuries occur in the lower extremity. Football records the highest number of injuries.
Epidemiological findings and estimates of the instantaneous reproduction number and control strategies of the first Mpox outbreak in Latin America
Authors: Díaz-Brochero Cándida , Cucunubá Zulma M.
Published: September 2023

Background and objective

since 2022, the world has experienced the largest Mpox outbreak in history. The region of the Americas has been especially affected, accounting for 67% of the cumulative cases worldwide. Key epidemiological characteristics of the outbreak for the Latin American region remain understudied. Here we provide estimations of R(t) and describe the key epidemiological trends, and vaccination strategies of the Mpox outbreak in six Latin American countries.

Materials and methods

we investigated the public health response to the Mpox outbreak in six Latin American countries from official sources. The surveillance data were obtained from the official Mpox report of the Pan American Health Organization. We calculated cumulative and incident confirmed cases according to the report date for each country and represented these findings in epidemic curves. The R(t) was estimated on weekly sliding windows for each country.

Results

The maximum means of R(t) ranged from 2.28 to 3.15 from May to July 2022. At epidemiological week 42, the R(t) estimates were as follows: Argentina: 0.94 (95% Credible interval -CrI-0.77 to 1.12), Chile: 0.83 (95% CrI: 0.64 to 1.05), Colombia: 0.60 (95% CrI: 0.52 to 0.69), Mexico: 0.75 (95% CrI: 0.67 to 0.84). For Peru and Brazil, R(t) decreased to less than 1 in weeks 32 and 33, with estimates between 0.89 (95% CrI: 0.82 to 0.96) and 0.94 (95% CrI: 0.89 to 0.98), respectively.

Conclusion

our results provide relevant information about current trends and future scenarios of the Mpox outbreak in Latin America. From late August to early September 2022, R(t) started to decrease to values less than 1, despite the limited delivery of vaccination programs implemented across the region. However, a large population remains at risk, and there is a possibility of new waves of the disease as the epidemic continues its course.
CCR2-targeting pepducins reduce T cell-nociceptor interaction driving bone cancer pain
Authors: Midavaine Élora , Brouillette Rebecca L. , Théberge Élizabeth , Mona Christine E. , Kashem Sakeen W. , Côté Jérôme , Zeugin Vera , Besserer-Offroy Élie , Longpré Jean-Michel , Marsault Éric , Sarret Philippe
Published: September 2023

Inhibition of the CCL2/CCR2 chemokine signaling represents a promising avenue for the development of non-opioid pain treatment, particularly for painful bone metastases. To investigate the involvement of CCR2 in cancer-induced bone pain, we generated and characterized the functional activities of a novel cell-penetrating pepducin, namely PP101, acting as an intracellular negative allosteric modulator of CCR2.In vivo, PP101 was effective in relieving neuropathic and bone cancer pain. By targeting CCR2, PP101 reduced bone cancer pain by preventing infiltration of CD4+and CD8+T cells and by decreasing the neuroimmune communication network within the dorsal root ganglia. Importantly, reduced neuroinflammatory milieu in the dorsal root ganglia induced by PP101 did not result in deleterious tumor progression or behavioral adverse effects. Thus, targeting the neuroimmune crosstalk through allosteric inhibition of CCR2 may represent an effective and safe avenue for the management of bone cancer pain.

Graphical Abstract

Highlights

Breast cancer bone metastases induce pain by activating CCR2 on sensory neurons.

DRG-infiltrating CD4+and CD8+T cells promote the development of bone cancer pain.

CCR2 inhibition by PP101 suppresses DRG neuroinflammation and neuronal excitability.

PP101 alleviates bone cancer pain without behavioral or physiological side effects.
Sensory neuron population expansion enhances odor tracking without sensitizing projection neurons
Authors: Takagi Suguru , Sancer Gizem , Abuin Liliane , Stupski S. David , Arguello J. Roman , Prieto-Godino Lucia L. , Stern David L. , Cruchet Steeve , Álvarez-Ocaña Raquel , Wienecke Carl F. R. , van Breugel Floris , Jeanne James M. , Auer Thomas O. , Benton Richard
Published: September 2023

The evolutionary expansion of sensory neuron populations detecting important environmental cues is widespread, but functionally enigmatic. We investigated this phenomenon through comparison of homologous neural pathways ofDrosophila melanogasterand its close relativeDrosophila sechellia, an extreme specialist forMorinda citrifolianoni fruit.D. sechelliahas evolved species-specific expansions in select, noni-detecting olfactory sensory neuron (OSN) populations, through multigenic changes. Activation and inhibition of defined proportions of neurons demonstrate that OSN population increases contribute to stronger, more persistent, noni-odor tracking behavior. These sensory neuron expansions result in increased synaptic connections with their projection neuron (PN) partners, which are conserved in number between species. Surprisingly, having more OSNs does not lead to greater odor-evoked PN sensitivity or reliability. Rather, pathways with increased sensory pooling exhibit reduced PN adaptation, likely through weakened lateral inhibition. Our work reveals an unexpected functional impact of sensory neuron expansions to explain ecologically-relevant, species-specific behavior.
NGAL deficiency elicits Hemophilia-like bleeding and clotting disorder
Authors: Xue Min , Wang Shaoying , Li Changjiang , Wang Yuewei , Liu Ming , Xiao Dandan , Yin Qikai , Niu Liyuan , Shen Chuanbin , Wang Jianxun , Tang Xiaopeng
Published: September 2023

Coagulation is related to inflammation, but the key pathways, especially innate immunity inflammatory response-coagulation, hemostasis, and thrombosis regulation is poorly understood and need to be further explored. In the current study, we showed that innate immunity inflammatory mediator neutrophil gelatinase-associated apolipoprotein (NGAL) which was upregulated in plasma of deep vein thrombosis patients interacted with and potentiated thrombin, kallikrein, FXIa, and FVIIa and suppressed antithrombin to induce coagulation, hemostasis, and thrombosis. Furthermore, NGAL can augment thrombin-induced platelet aggregation. In multiple mice hemostasis and thrombosis models, NGAL overexpression or intravenous administration promoted coagulation and hemostasis and aggravated thrombus, whereas NGAL knockout or treatment with anti-NGAL monoclonal antibody significantly prolonged bleeding time and alleviated thrombus formation. Notably, NGAL knockout prolonged both mice tail bleeding time and artery occlusion time to over 40 min, resembling uncontrollable bleeding and clotting disorder seen in Hemophilia mice. Furthermore, anti-NGAL monoclonal antibody treatment markedly reduced the formation of blood clots in a mouse-tail thrombosis model induced by carrageenan, which is linked to inflammation. Collectively, these findings suggest NGAL is a crucial coagulation regulator and mediates the crosstalk between innate immunity inflammation and coagulation, hemostasis, and thrombus, and provide new target and strategy for the development of innovative antithrombotic drugs.
Endothelial-fibroblast interactions during Scarb1 accelerate heart failure
Authors: Katsuki Toshiomi , Kusumoto Dai , Akiba Yohei , Kimura Mai , Komuro Jin , Nakamura Takahiro , Hashimoto Hisayuki , Kuoka Thukaa , Suzuki Yutaka , Kubota Yoshiaki , Fukuda Keiichi , Yuasa Shinsuke , Ieda Masaki
Published: September 2023

Endothelial cells (ECs) maintain cardiac homeostasis and EC dysfunction causes heart failure progression. Moreover, pathological changes occur via interactions between multiple cells, including ECs. Here, we conducted single-cell RNA-seq analysis of non-cardiomyocytes in mouse hearts during heart failure progression to elucidate the pathological changes in ECs and fibroblasts (FBs) mediated by cell-cell interactions. We show that capillary and arterial ECs exhibit mesenchymal gene expression changes with heart failure progression, indicating that endothelial-to-mesenchymal transition (EndMT) is a major pathological alteration in ECs. We also found that the interaction between ECs and FBs was enriched during heart failure, particularly when involving Scavenger Receptor Class B Member 1 (Scarb1) in ECs. FBs induce mesenchymal gene alterations in ECs in the EC-FB co-culture system, which is inhibited by blocking SCARB1. RNA-seq analysis showed that administration of a SCARB1 inhibitor blocked mesenchymal gene expression, and inflammatory changes, suggesting that the EC-FB interaction via Scarb1 is important for EndMT induction in ECs. Systemic administration of a SCARB1 inhibitor attenuated heart failure progression and cardiac fibrosis. EC-specificScarb1knockout mouse showed improved cardiac function, suggesting a crucial role of Scarb1 in heart failure progression. Our results suggest that Scarb1 is a promising candidate for novel heart failure treatments that target ECs.
The asynchrony in the exit from naive pluripotency cannot be explained by differences in the cell cycle phase
Authors: Jayaram Swathi , Romeike Merrit , Buecker Christa
Published: September 2023

Development is characterized by consecutive cell state transitions that build on each other and ultimately lead to the generation of the numerous different cell types found in the organism. During each of these transitions, cells change their gene expression profiles and take on new identities. Cell state transitions have to be tightly coordinated with proliferation to ensure simultaneous growth and differentiation. The exit from naive pluripotency is an ideal model system for studying the temporal coordination of proliferation and differentiation. Individual cells initiate differentiation earlier compared to others, thereby leading to an asynchronous exit from naive pluripotency. One of the major differences among the cells of the starting population of mouse embryonic stem cells (mESCs) is the cell cycle status, and could therefore be an underlying cause of the differences in the onset of the exit from naive pluripotency. However, through comprehensive analysis including single cell RNA sequencing (scRNA-seq), cell cycle synchronization, and perturbation experiments, we demonstrate here that the cell cycle phase at the initiation of differentiation does not influence the timing of the exit from naive pluripotency.
Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype
Authors: Marichannegowda Manukumar Honnayakanahalli , Setua Saini , Bose Meera , Sanders-Buell Eric , King David , Zemil Michelle , Wieczorek Lindsay , Diaz-Mendez Felisa , Chomont Nicolas , Thomas Rasmi , Francisco Leilani , Eller Leigh Anne , Polonis Victoria R. , Tovanabutra Sodsai , Tagaya Yutaka , Michael Nelson L. , Robb Merlin L. , Song Hongshuo
Published: September 2023

Nearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, detection was not at the earliest stages of acute infection. Here, we identified an X4-tropic T/F HIV-1 in a participant in acute infection cohort. Coreceptor assays demonstrated that this T/F virus is strictly CXCR4 tropic. The participant experienced significantly faster CD4 depletion compared with R5 virus infected participants in the same cohort. Naïve and central memory CD4 subsets declined faster than effector and transitional memory subsets. All CD4 subsets, including naïve, were productively infected. Increased CD4+T cell activation was observed over time. This X4-tropic T/F virus is resistant to broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 regions. These findings demonstrate that X4-tropic HIV-1 is transmissible through the mucosal route in people with the wild-type CCR5 genotype and have implications for understanding the transmissibility and immunopathogenesis of X4-tropic HIV-1.