bluuebunny/crossref_metadata_2025 huggingface dataset:
Dysphagia screening among stroke patients in a tertiary hospital: a best practice implementation project
Authors: Shen Guojing , Xia Qingyi , Zhang XiaoLing , Xue Ping , Wang Ying , Wang Jue
Published: February 2024

Objectives:

The study aimed to promote nurses’ compliance with best practices for dysphagia screening in patients with stroke.

Introduction:

Dysphagia can significantly increase the risk of complications, especially aspiration pneumonia, leading to increased risk of disability, death, and high medical expenses. Dysphagia screening can reduce aspiration risk and is recommended as a crucial step in dysphagia management; however, not all patients with stroke undergo dysphagia screening in the neurology ward.

Methods:

The JBI Evidence Implementation Framework was used in this study. A baseline audit was conducted by interviewing 22 nurses and reviewing 48 medical records to evaluate current practice against best practice recommendations. The JBI Getting Research into Practice (GRiP) tool was used to identify barriers and strategies for practice change. A follow-up audit of 19 nurses and 48 medical records was conducted after implementation of improvement strategies.

Results:

The follow-up audit results showed improvement in three criteria compared with the baseline audit: for Criterion 1, compliance increased by 27.3%, rising from 72.7% to 100%; for Criteria 3 and 4, compliance increased by 77.1%, rising from 20.8% to 97.9%. The difference in nurses’ knowledge, attitude, and behavior scores for dysphagia screening between the baseline and follow-up audits was statistically significant (all p < 0.05).

Conclusions:

The project showed improvements in evidence-based practice in the dysphagia screening of stroke patients in a neurology ward. However, more work needs to be done to ensure the sustainability of best practices, such as regular training for nurses, supervision from managers, and regular audits of dysphagia screening.
Large-Scale Evaluation of Spatial Metabolomics Protocols and Technologies
Authors: Saharuka Veronika , Vieira Lucas M. , Stuart Lachlan , Ekelöf Måns , Molenaar Martijn R. , Bailoni Alberto , Ovchinnikova Katja , Soltwisch Jens , Bausbacher Tobias , Jakob Dennis , King Mary , Müller Max A. , Oetjen Janina , Pace Crystal , Pinto Fernanda E. , Strittmatter Nicole , Velickovic Dusan , Spengler Bernhard , Muddiman David C. , Liebeke Manuel , Janfelt Christian , Goodwin Richard , Eberlin Livia S. , Anderton Christopher R. , Hopf Carsten , Dreisewerd Klaus , Alexandrov Theodore
Published: February 2024

Spatial metabolomics using imaging mass spectrometry (MS) enables untargeted and label-free metabolite mapping in biological samples. Despite the range of available imaging MS protocols and technologies, our understanding of metabolite detection under specific conditions is limited due to sparse empirical data and predictive theories. Consequently, challenges persist in designing new experiments, and accurately annotating and interpreting data. In this study, we systematically measured the detectability of 172 biologically-relevant metabolites across common imaging MS protocols using custom reference samples. We evaluated 24 MALDI-imaging MS protocols for untargeted metabolomics, and demonstrated the applicability of our findings to complex biological samples through comparison with animal tissue data. We showcased the potential for extending our results to further analytes by predicting metabolite detectability based on molecular properties. Additionally, our interlaboratory comparison of 10 imaging MS technologies, including MALDI, DESI, and IR-MALDESI, showed extensive metabolite coverage and comparable results, underscoring the broad applicability of our findings within the imaging MS community. We share our results and data through a new interactive web application integrated with METASPACE. This resource offers an extensive catalogue of detectable metabolite ions, facilitating protocol selection, supporting data annotation, and benefiting future untargeted spatial metabolomics studies.
Aggregating Residue-Level Protein Language Model Embeddings with Optimal Transport
Authors: NaderiAlizadeh Navid , Singh Rohit
Published: February 2024

Protein language models (PLMs) have emerged as powerful approaches for mapping protein sequences into embeddings suitable for various applications. As protein representation schemes, PLMs generate per-token (i.e., per-residue) representations, resulting in variable-sized outputs based on protein length. This variability poses a challenge for protein-level prediction tasks that require uniform-sized embeddings for consistent analysis across different proteins. Previous work has typically used average pooling to summarize token-level PLM outputs, but it is unclear whether this method effectively prioritizes the relevant information across token-level representations. We introduce a novel method utilizing optimal transport to convert variable-length PLM outputs into fixed-length representations. We conceptualize per-token PLM outputs as samples from a probabilistic distribution and employ sliced-Wasserstein distances to map these samples against a reference set, creating a Euclidean embedding in the output space. The resulting embedding is agnostic to the length of the input and represents the entire protein. We demonstrate the superiority of our method over average pooling for several downstream prediction tasks, particularly with constrained PLM sizes, enabling smaller-scale PLMs to match or exceed the performance of average-pooled larger-scale PLMs. Our aggregation scheme is especially effective for longer protein sequences by capturing essential information that might be lost through average pooling.
The CoLab-score rapidly and efficiently excludes COVID-19 at the emergency department without need for SARS-CoV-2 testing: a multicenter case-control study
Authors: Boer Arjen-Kars , Deneer Ruben , Maas Maaike , Ammerlaan Heidi S. M. , van Balkom Roland H. H. , Leers Mathie P. G. , Martens Remy J.H. , Buijs Madelon M. , Kerremans Jos J. , Messchaert Muriël , van Suijlen Jeroen D.E. , van Riel Natal A.W. , Scharnhorst Volkher
Published: February 2024

Background

Rapid identification of emergency department (ED) patients with a possible COVID-19 infection is needed. PCR-testing all ED patients is neither feasible nor effective in most centers, therefore a rapid, objective, low-cost screening tool to triage ED patients is necessary.

Methods

Results from all routine lab tests from ED patients at the Catharina Hospital were collected from July 2019 to July 2020 and used in a statistical model to obtain the CoLab-score. The score was validated temporally and externally in three independent centers.

Results

The CoLab-score consists of 10 routine lab results and can be used to safely rule-out a COVID-19 infection in more than one third of ED presentations with a negative predictive value of 0.997 (95% CI: 0.994 – 0.999).

Conclusions

The CoLab-score is a valuable tool to rule out COVID-19, guide PCR testing and is available to any center with access to routine laboratory tests.
Determination of prevalence of HLA-B27 in patients with backache at Armed Forces Institute of Pathology (AFIP), Rawalpindi
Authors: Haris Abdul Rehman , Maqsood Furqan , Tipu Hamid Nawaz , Ahmed Dawood
Published: February 2024

Background

HLA-B27 is a class I MHC protein that is associated with different diseases collectively called, spondyloarthropathies. It includes;

2.

Ankylosing spondylitis, which causes inflammation of the bones in your spine

3.

Reactive arthritis, which causes inflammation of your joints, urethra, and eyes, and in some cases lesions on your skin

4.

Juvenile rheumatoid arthritis

5.

Anterior Uveitis, which causes swelling and irritation in the middle layer of your eye

Objectives

To determine the prevalence of HLA-B27 in patients with backache at the Armed Forces Institute of Pathology in Rawalpindi. This descriptive cross-sectional study was conducted between June 2020 and Nov 2020.

Material and methods

Of the 243 patients, 167 males and 76 females were tested for HLA-B27 during the study period. Venous blood samples (3 mL) were collected in EDTA tubes and processed for HLA-B27 gene identification on the cell surface. A two-color flow cytometry panel was used to analyze samples using a BD FACS Canto II flow cytometer on BD FACS Diva software. The dot plot was created using an isotype control in four quadrants, and positive and negative populations of cells were identified.

Results

A total of 243 patients were analyzed for the presence of HLA-B27 using flow cytometry. Of the 243 patients, 167 were male and 76 were female patient.51 male patients tested positive, with a positivity rate of 30.53% among the male population and 20.98% among the general population. In contrast to the male population, 12 female patients tested positive for the HLA-B27 gene, with a positivity rate of 15.78% among the female population and 4.93% among the general population. The total positivity rate was 25.92%, with a higher prevalence in the male population included in this study.

Conclusion

All individuals tested for HLA B27 were included in this study. This study showed that positivity rate of HLA-B27 is more in males with a percentage of 20.98% as compared to female population (4.93%).
A novel and efficient machine learning Mendelian randomization estimator applied to predict the safety and efficacy of sclerostin inhibition
Authors: Legault Marc-André , Hartford Jason , Arsenault Benoît J. , Yang Archer Y. , Pineau Joelle
Published: February 2024

1

Mendelian Randomization (MR) enables estimation of causal effects while controlling for unmeasured confounding factors. However, traditional MR’s reliance on strong parametric assumptions can introduce bias if these are violated. We introduce a new machine learning MR estimator named Quantile Instrumental Variable (IV) that achieves low estimation error in a wide range of plausible MR scenarios. Quantile IV is distinctive in its ability to estimate nonlinear and heterogeneous causal effects and offers a flexible approach for subgroup analysis. Applying Quantile IV, we investigate the impact of circulating sclerostin levels on heel bone mineral density, osteoporosis, and cardiovascular outcomes in the UK Biobank. Employing various MR estimators and colocalization techniques that allow multiple causal variants, our analysis reveals that a genetically predicted reduction in sclerostin levels significantly increases heel bone mineral density and reduces the risk of osteoporosis, while showing no discernible effect on ischemic cardiovascular diseases. Quantile IV contributes to the advancement of MR methodology, and the case study on the impact of circulating sclerostin modulation contributes to our understanding of the on-target effects of sclerostin inhibition.
Toward a more comprehensive understanding of network centrality disruption in amnestic Mild Cognitive Impairment: a MEG multilayer approach
Authors: Taguas Ignacio , Doval Sandra , Maestú Fernando , López-Sanz David
Published: February 2024

Alzheimer’s Disease (AD) is the most common form of dementia. Its early stage, amnestic Mild Cognitive Impairment (aMCI), is characterized by disrupted information flow in the brain. Previous studies using electrophysiological techniques to investigate AD’s functional connectivity changes have yielded inconsistent results; contributing factors may include the specific metric employed and the separate study of brain activity in each frequency band. Our study addresses this by employing a cross-frequency approach to compare functional networks in 172 healthy subjects and 105 aMCI patients. Using magnetoencephalography, we constructed source-based multilayer graphs considering both intra- and inter-band functional connectivity across the five classical frequency bands. We assessed network changes through three centrality measures (strength, eigenvector centrality, and betweenness centrality), and combined them into a unified centrality score for a comprehensive assessment of centrality disruption in aMCI. Results revealed a notable shift in centrality distribution in aMCI patients spatially and across frequencies. Posterior brain regions decrease synchrony between high-frequency oscillations and other regions’ activity across all frequencies, while anterior regions increase synchrony between low-frequency oscillations and other regions’ activity across all bands. Thus, posterior regions reduce their relative importance in favor of anterior regions. This study demonstrates that considering the interplays between different frequency bands enhances understanding of AD network dynamics and sets a precedent for multilayer functional network studies. Our findings provide valuable insights into the intricate changes that occur in functional brain networks during the early stages of AD, offering a framework for developing interventions aimed at modifying the disease trajectory.

Significance statement

Over 55 million people worldwide suffer from Alzheimer’s Disease. The brain changes causing the symptoms begin around 20 years before their onset, so characterizing these changes in the early stage, mild cognitive impairment, is of utmost importance. Magnetoencephalography and electroencephalography (M/EEG) are two commonly used techniques to assess changes in functional networks; however, the existing studies yield inconsistent results. Our study applies a novel methodology for the analysis of M/EEG data that addresses two factors contributing to this effect: the metric employed to assess network changes and the use of a cross-frequency approach. Results show that posterior regions reduce their relative importance in favor of anterior regions. This study sets a precedent for the functional study of all brain disorders.
Age-Related RPE changes in Wildtype C57BL/6J Mice between 2 and 32 Months
Authors: Shelton Debresha A. , Gefke Isabelle , Summers Vivian , Kim Yong-Kyu , Yu Hanyi , Getz Yana , Ferdous Salma , Donaldson Kevin , Liao Kristie , Papania Jack T. , Chrenek Micah A. , Boatright Jeffrey H. , Nickerson John M.
Published: February 2024

Purpose

This study provides a systematic evaluation of age-related changes in RPE cell structure and function using a morphometric approach. We aim to better capture nuanced predictive changes in cell heterogeneity that reflect loss of RPE integrity during normal aging. Using C57BL6/J mice ranging from P60-P730, we sought to evaluate how regional changes in RPE shape reflect incremental losses in RPE cell function with advancing age. We hypothesize that tracking global morphological changes in RPE is predictive of functional defects over time.

Methods

We tested three groups of C57BL/6J mice (young: P60-180; Middle-aged: P365-729; aged: 730+) for function and structural defects using electroretinograms, immunofluorescence, and phagocytosis assays.

Results

The largest changes in RPE morphology were evident between the young and aged groups, while the middle-aged group exhibited smaller but notable region-specific differences. We observed a 1.9-fold increase in cytoplasmic alpha-catenin expression specifically in the central-medial region of the eye between the young and aged group. There was an 8-fold increase in subretinal, IBA-1-positive immune cell recruitment and a significant decrease in visual function in aged mice compared to young mice. Functional defects in the RPE corroborated by changes in RPE phagocytotic capacity.

Conclusions

The marked increase of cytoplasmic alpha-catenin expression and subretinal immune cell deposition, and decreased visual output coincide with regional changes in RPE cell morphometrics when stratified by age. These cumulative changes in the RPE morphology showed predictive regional patterns of stress associated with loss of RPE integrity.
Structural dynamics and immunogenicity of the recombinant and outer membrane vesicle-embedded Meningococcal antigen NadA
Authors: Calvaresi Valeria , Dello Iacono Lucia , Borghi Sara , Luzzi Enrico , Biolchi Alessia , Benucci Barbara , Ferlenghi Ilaria , Peschiera Ilaria , Giusti Fabiola , Fontana Lucia E. , Kan Zhong-Yuan , Spinello Zaira , Merola Marcello , Delany Isabel , Rand Kasper D. , Norais Nathalie
Published: February 2024

The structure and conformation adopted by protein vaccine antigens significantly influence the exposure of their antigenic determinants. Structural knowledge of antigens in native state could drive the design of recombinant vaccines that resemble their cognate native forms, although such information is often difficult to obtain, particularly for membrane proteins. Here, we assessed the structural and functional features of the native Neisseria Adhesin A (NadA), a meningococcal trimeric outer membrane protein included as soluble recombinant antigen in the 4CMenB vaccine. We used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to generate a structural model of NadA and to compare the fold and structural dynamics of the recombinant NadA as soluble vaccine form, and the native NadAin situ, as embedded in meningococcal outer membrane vesicles (OMVs), complementing the HDX data with electron microscopy imaging. While their overall structures are similar, conformational differences between the two forms were observed. Especially, OMV- embedded NadA appears more susceptible to trimer opening than its cognate soluble antigen, suggesting that NadA in its native membrane could display a larger antigenic surface. Accordingly, we show that mice immunized with OMV-embedded NadA elicited antibodies with superior bactericidal activity and capable of better preventing bacterial adhesion compared to the soluble antigen. Collectively, these data support the hypothesis that protein vaccine antigens presented in native-like environments can elicit a more potent immune response than recombinant forms.
3D-ARM-Gaze: a public dataset of 3D Arm Reaching Movements with Gaze information in virtual reality
Authors: Lento Bianca , Segas Effie , Leconte Vincent , Doat Emilie , Danion Frederic , Péteri Renaud , Benois-Pineau Jenny , de Rugy Aymar
Published: February 2024

3D-ARM-Gaze is a public dataset designed to provide natural arm movements together with visual and gaze information when reaching objects in a wide reachable space from a precisely controlled, comfortably seated posture. Participants were involved in picking and placing objects in various positions and orientations in a virtual environment, whereby a specific procedure maximized the workspace explored while ensuring a consistent seated posture. The dataset regroups more than 2.5 million samples recorded from 20 healthy participants performing 14 000 single pick-and-place movements (700 per participant). While initially designed to explore novel prosthesis control strategies based on natural eye-hand and arm coordination, this dataset will also be useful to researchers interested in core sensorimotor control, humanoid robotics, human-robot interactions, as well as for the development and testing of associated solutions in gaze-guided computer vision.
Gastric microbiomes ofCassiopeain the Florida Keys are low diversity andEndozoicomonas-,Vibrio-andMycoplasma-dominated
Authors: Muffett Kaden M , Labonté Jessica M , Miglietta Maria Pia
Published: February 2024

Interactions with microbial communities fundamentally shape metazoans’ physiology, development, and health across marine ecosystems. This is especially true in zooxanthellate (symbiotic algae-containing) cnidarians. In photosymbiotic anthozoans (eg. shallow water anemones and corals), the key members of the associated microbiota are increasingly well studied, however there is limited data on photosymbiotic scyphozoans (true jellyfish). Using 16S rRNA barcoding, we sampled the internal and external mucus of the zooxanthellate Upside- Down Jellyfish,Cassiopea xamachanathroughout eight sites covering the full length of the Florida Keys. We find that across sites, these medusae to have low-diversity internal microbial communities distinct from the communities of their external surfaces and their environment.

These internal communities are dominated by only three taxa:Endozoicomonascf.atrinae, an uncultured novelMycoplasma, andVibriocf. coralliilyticus.Cassiopeabell mucosal samples conform largely to the communities of surrounding sediment with the addition ofEndozoicomonascf.atrinae. The microbial taxa we identify associated with wild Florida KeysCassiopeabear a strong resemblance to those found within photosymbiotic anthozoans, increasing the known links in ecological position between these groups.
Structural basis of the Integrator complex assembly and association with transcription factors
Authors: Razew Michal , Fraudeau Angelique , Pfleiderer Moritz M. , Galej Wojciech P.
Published: February 2024

Integrator is a multi-subunit protein complex responsible for premature transcription termination of coding and non-coding RNAs in Metazoans. This is achieved via Integrator’s two enzymatic activities, RNA endonuclease and protein phosphatase, acting on the promoter-proximally paused RNA Polymerase II (RNAPII). Yet, it remains unclear how Integrator assembly and recruitment are regulated and what are the functions of many of its core subunits. Here we report two cryo-EM reconstructions of large Integrator sub-complexes: INTS10/13/14/15 (Arm module) and INTS5/8/10/15, which allowed integrative modelling of the fully-assembled Integrator bound to the RNAPII paused elongating complex (PEC). INTS13/14 are positioned near the DNA upstream from the transcription pause site, suggesting a potential role in the chromatin context. Anin silicoprotein interaction screen of over 1500 transcription factors (TFs), identified Zinc Finger Protein 655 (ZNF655) as a direct interacting partner of INTS13 that associates with a fully assembled, 17-subunit Integrator complex. We propose a model wherein the Arm module acts as a platform for the recruitment of TFs that could modulate the stability of the Integrator’s association at specific loci and modulate transcription attenuation of the target genes.
Cell-material interactions in 3D bioprinted plant cells
Authors: Madison Imani , Tahir Maimouna , Van den Broeck Lisa , Phan Linh , Horn Timothy , Sozzani Rosangela
Published: February 2024

3D bioprinting is an additive manufacturing technology with promise towards facilitating tissue engineering and single-cell investigations of cellular development and microenvironment responses. 3D bioprinting is still a new technology in the field of plant biology so its optimization with plant cells is still widely needed. Here, we present a study in which 3D bioprinting parameters, such as needle gauge, extrusion pressure, and scaffold type, were all tested in 3D bioprinted Tobacco BY-2 cells to evaluate how cell viability is responsive to each parameter. As a result, this study revealed an optimal range of extrusion pressures and needle gauges that resulted in an optimum cell viability. Furthermore, this study applied the identified optimal 3D bioprinting parameters to a different cell line,Arabidopsisroot protoplasts, and stress condition, phosphate starvation, to confirm that the identified parameters were optimal in a different species, cell type, and cellular microenvironment. This suggested that phosphate-starved bioprintedArabidopsiscells were less viable by 7 days, which was consistent with whole root phosphate starvation responses. As a result, the 3D bioprinter optimization yielded optimal cell viabilities in both BY-2 and Arabidopsis cells and facilitated an applied investigation into phosphate starvation stress.
A diel multi-tissue genome-scale metabolic model ofVitis vinifera
Authors: Sampaio Marta , Rocha Miguel , Dias Oscar
Published: February 2024

Vitis vinifera, also known as grapevine, is widely cultivated and commercialized, particularly to produce wine. As wine quality is directly linked to fruit quality, studying grapevine metabolism is important to understand the processes underlying grape composition. Genome-scale metabolic models (GSMMs) have been used for the study of plant metabolism and advances have been made, allowing the integration of omics datasets with GSMMs. On the other hand, Machine learning (ML) has been used to analyze omics data, and while the combination of ML with GSMMs has shown promising results, it is still scarcely used to study plants. Here, the first GSSM ofV. viniferawas reconstructed and validated, comprising 7199 genes, 5399 reactions, and 5141 metabolites across 8 compartments. Tissue-specific models for stem, leaf, and berry of the Cabernet Sauvignon cultivar were generated from the original model, through the integration of RNA-Seq data. These models have been merged into diel multi-tissue models to study the interactions between tissues at light and dark phases. The potential of combining ML with GSMMs was explored by using ML to analyze the fluxomics data generated by green and mature grape GSMMs, helping to understand the factors influencing grape quality at different developmental stages.
Rapid QC-MS – Interactive Dashboard for Synchronous Mass Spectrometry Data Acquisition Quality Control
Authors: Sandhu Wasim , Gray Ira J , Lin Sarah , Elias Joshua E , DeFelice Brian C
Published: February 2024

Consistently collecting high quality liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) data is a time consuming hurdle for untargeted workflows. Analytical controls such as internal and biological standards are commonly included in high throughput workflows, helping researchers recognize low integrity specimens regardless of their biological source. However, evaluating these standards as data are collected has remained a considerable bottleneck – in both person hours and accuracy. Here we present Rapid QC-MS, an automated, interactive dashboard for assessing LC-MS/MS data quality. Minutes after a new data file is written, a browser-viewable dashboard is updated with quality control results spanning multiple performance dimensions such as instrument sensitivity, in-run retention time shifts, and mass accuracy drift. Rapid QC-MS provides interactive visualizations that help users recognize acute deviations in these performance metrics, as well as gradual drifts over periods of hours, days, months, or years. Rapid QC-MS is open-source, simple to install, and highly configurable. By integrating open source python libraries and widely used MS analysis software, it can adapt to any LC-MS/MS workflow. Rapid QC-MS runs locally and offers optional remote quality control by syncing with Google Drive. Furthermore, Rapid QC-MS can operate in a semiautonomous fashion, alerting users to specimens with potentially poor analytical integrity via frequently used messaging applications. Rapid QC-MS offers a fast, straightforward approach to help users collect high quality untargeted LC-MS/MS data by eliminating many of the most time consuming steps in manual data curation. Download for free: https://github.com/czbiohub-sf/Rapid-QC-MS
Minor changes in electrostatics robustly increase VP40 membrane binding, assembly, and budding of Ebola virus matrix protein derived virus-like particles
Authors: Motsa Balindile B. , Sharma Tej , Chapagain Prem P. , Stahelin Robert V.
Published: February 2024

Ebola virus (EBOV) is a filamentous negative-sense RNA virus which causes severe hemorrhagic fever. There are limited vaccines or therapeutics for prevention and treatment of EBOV, so it is important to get a detailed understanding of the virus lifecycle to illuminate new drug targets. EBOV encodes for the matrix protein, VP40, which regulates assembly and budding of new virions from the inner leaflet of the host cell plasma membrane (PM). In this work we determine the effects of VP40 mutations altering electrostatics on PM interactions and subsequent budding. VP40 mutations that modify surface electrostatics affect viral assembly and budding by altering VP40 membrane binding capabilities. Mutations that increase VP40 net positive charge by one (e.g., Gly to Arg or Asp to Ala) increase VP40 affinity for phosphatidylserine (PS) and PI(4,5)P2in the host cell PM. This increased affinity enhances PM association and budding efficiency leading to more effective formation of virus-like particles (VLPs). In contrast, mutations that decrease net positive charge by one (e.g., Gly to Asp) lead to a decrease in assembly and budding because of decreased interactions with the anionic PM. Taken together our results highlight the sensitivity of slight electrostatic changes on the VP40 surface for assembly and budding. Understanding the effects of single amino acid substitutions on viral budding and assembly will be useful for explaining changes in the infectivity and virulence of different EBOV strains, VP40 variants that occur in nature, and for long-term drug discovery endeavors aimed at EBOV assembly and budding.
Disentangling Predictors of COPD Mortality with Probabilistic Graphical Models
Authors: Lovelace Tyler C. , Ryu Min Hyung , Jia Minxue , Castaldi Peter , Sciurba Frank C. , Hersh Craig P. , Benos Panayiotis V.
Published: February 2024

Background-Research question

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of mortality. Predicting mortality risk in COPD patients can be important for disease management strategies. Although scores for all-cause mortality have been developed previously, there is limited research on factors that may directly affect COPD-specific mortality.

Study design-Methods

used probabilistic (causal) graphs to analyze clinical baseline COPDGene data, including demographics, spirometry, quantitative chest imaging, and symptom features, as well as gene expression data (from year-5).

Results

We identified factors linked to all-cause and COPD-specific mortality. Although many were similar, there were differences in certain comorbidities (all-cause mortality model only) and forced vital capacity (COPD-specific mortality model only). Using our results, we developedVAPORED, a 7-variable COPD-specific mortality risk score, which we validated using the ECLIPSE 3-yr mortality data. We showed that the new model is more accurate than the existing ADO, BODE, and updated BODE indices. Additionally, we identified biological signatures linked to all-cause mortality, including a plasma cell mediated component. Finally, we developed a web page to help clinicians calculate mortality risk using VAPORED, ADO, and BODE indices.

Interpretation

Given the importance of predicting COPD-specific and all-cause mortality risk in COPD patients, we showed that probabilistic graphs can identify the features most directly affecting them, and be used to build new, more accurate models of mortality risk. Novel biological features affecting mortality were also identified. This is an important step towards improving our identification of high-risk patients and potential biological mechanisms that drive COPD mortality.
PRE-DIAGNOSTIC MANIFESTATIONS OF ALZHEIMER’S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF LONGITUDINAL STUDIES
Authors: Zabihi Sedigheh , Espinoza Jeraldo Rosario Isabel , Anjum Rifah , Carter Christine , Roche Moïse , Bestwick Jonathan P , Morgan-Trimmer Sarah , Birks Yvonne , Wilberforce Mark , Walter Fiona M. , Cooper Claudia , Marshall Charles R
Published: February 2024

Alzheimer’s disease (AD) is associated with a range of non-cognitive symptoms that can be early or even presenting features. Better recognition of pre-diagnostic symptoms of AD would support improved early detection and diagnosis.

To identify possible prodromal symptoms of AD, we systematically searched electronic databases for prospective longitudinal studies to March 2023, that reported the risk of AD diagnosis associated with non-cognitive symptoms. We conducted random-effects meta-analyses to obtain pooled odds of subsequent AD.

Thirty studies met eligibility criteria. Most studies (n=18) reported on the association of depression with subsequent AD diagnosis (pooled OR= 1.80; 95% CI: 1.29 to 2.50; I2=95.8%). Hearing loss, weight loss, spondylosis and hypotension also predicted a subsequent AD diagnosis.

This evidence suggests that these features that may be recorded during routine healthcare encounters are risk markers for incident AD and could therefore support improved early detection and diagnosis.
Relationship between fill volume and transport in peritoneal dialysis
Authors: Öberg Carl M.
Published: February 2024

Introduction

Larger fill volumes in peritoneal dialysis (PD) typically improve small solute clearance and water removal, andvice versa– but the relationship between intra-peritoneal volume and the capacities for solute and water transport in PD has been little studied. Here, it is proposed that this relative relationship is described by a simple ratio (Volumenew/Volumeold)2/3up to a critical break-point volume, beyond which further volume increase is less beneficial in terms of transport.

Method

To scrutinize this hypothesis, experiments were conducted in a rat model of PD alongside a retrospective analysis of clinical data from a prior study. Rats underwent PD with either three consecutive fills of 8+8+8 mL (n=10) or 12+12+12 mL (n=10), with 45-minute dwell time intervals. This approach yielded sixty estimations of water and solute transport, characterized by osmotic conductance to glucose (OCG) and solute diffusion capacities, respectively.

Results

Comparative analysis of the predictive efficacy of the two models — the simple ratioversusthe break-point model — was performed using Monte Carlo cross-validation. The break-point model emerged as a superior predictor for both water and solute transport, demonstrating its capability to characterize both experimental and clinical data.

Conclusion

The present analysis indicates that relatively simple calculations can be used to approximate clinical effects on transport when prescribing a lower or higher fill volume to patients on PD.
Neural processing of social reciprocity in autism
Authors: Bierlich A. M. , Plank I. S. , Scheel N. T. , Keeser D. , Falter-Wagner C. M.
Published: February 2024

Social reciprocity and interpersonal synchrony implicitly mediate social interactions to facilitate natural exchanges. These processes are altered in autism, but it is unclear how such alterations manifest at the neural level during social interaction processing. Using task-based fMRI, we investigated the neural correlates of interpersonal synchrony during basic reciprocal interactions in a preregistered study. Participants communicated with a virtual partner by sending visual signals. Analyses showed comparable activation patterns and experienced synchrony ratings between autistic and non-autistic participants, as well as between interactions with virtual partners who had high or low synchronous responses. An exploratory whole brain analysis for the effect of task revealed significant activation of the right inferior frontal gyrus (IFG) and left anterior inferior parietal lobe (IPL); areas associated with cognitive control, temporal coordination, and action observation. This activation was independent of the virtual partner’s response synchrony and was similar for autistic and non-autistic participants. These results provide an initial look into the neural basis of processing social reciprocity in autism, particularly when individuals are part of an interaction, and hint that the neural processing of social reciprocity may be spared in autism when their partners’ behavior is predictable.
A systematic review of multi-variate time series approaches to extract predictive asthma biomarkers from routinely collected diary data
Authors: Clemeno Franz Aaron , Richardson Matthew , Siddiqui Salman
Published: February 2024

Objectives

Longitudinal data is commonly acquired in asthma studies, to help assess asthma progression in patients, and to determine predictors of future outcomes, including asthma exacerbations and asthma control. Different methods exist for quantifying temporal behaviour in routinely collected diary variables to obtain meaningful predictive biomarkers of asthma outcomes. The aims of this systematic review were to evaluate the methods for extracting biomarkers from longitudinally collected diary data in asthma and investigate associations between the extracted measures and asthma patient reported outcomes (PROs).

Setting

A systematic review of MEDLINE, EMBASE, CINAHL and the Cochrane Library was conducted, using index terms relating to diary variables and asthma outcomes. Studies that focused on preschool children were excluded, to avoid confounding asthma with multi-factorial preschool wheeze. Study quality and risk of bias were assessed using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) and the Prediction model Risk Of Bias ASessment Tool (PROBAST), respectively.

Participants

Adults and/or children of school age (≥5 years old), with clinician-diagnosed asthma

Primary outcomes

Asthma PROs, namely asthma exacerbations, asthma control, asthma-related quality of life and asthma severity

Results

24 full-text articles met the inclusion criteria and were included in the review. Generally, higher levels of variability in the diary variables were associated with poorer outcomes, especially increased asthma exacerbation risk, and poor asthma control. There was increasing interest in nonparametric methods to quantify complex behaviour of diary variables (6/24). TRIPOD and PROBAST highlighted a lack of consistent reporting of model performance measures and potential for model bias.

Discussion

Routinely collected diary variables aid in generating asthma assessment tools, including surrogate endpoints, for clinical trials, and predictive biomarkers of adverse outcomes, warranting monitoring through remote sensors. Studies consistently lacked robust reporting of model performance. Future research should utilise diary variable-derived biomarkers.

Article Summary

Strengths and limitations of this study

This is the first systematic review that explores the different methods applied to time series of diary variables, namely peak flow, reliever use, symptom scores and awakenings.

The scope of this review included multiple patient-reported outcomes, including asthma exacerbations, asthma control and asthma severity.

Only one reviewer was involved in screening the titles and abstracts for inclusion into the systematic review.
Environmental risk factors for self-harm during imprisonment: a prospective cohort study
Authors: Stephenson T , Harris I , Armstrong C , Fazel S , Short R , Blackwood N
Published: February 2024

Introduction

Self-harm is a major public health issue in the imprisoned population. Limited high-quality evidence exists for the potential impact of prison environmental factors such as solitary confinement. This pilot prospective cohort study in a large male remand prison in England sought to estimate effect sizes of a comprehensive range of prison environmental factors on self-harming behaviours.

Methods

A random sample of all prisoners (N=149) starting a period of imprisonment at the study prison took part in a clinical research interview, which assessed a range of known risk factors for self-harm in prison. Information concerning environmental factors, including staff numbers, cell placement and movements, and engagement in work and activities were collected from prison records. Incidents of self-harm behaviour in the 3 months after entering prison were measured using medical records and self-report at end of follow-up. Multivariable logistic regression models were calculated individually for each predictor.

Results

Single cell placement (OR 4.31, 95% CI 1.06-18.24, p=0.041) and more frequent cellmate (OR 1.52, CI 1.14-2.17, p=0.009) and cell (OR 1.83, 95% CI 1.28-2.86, p=0.003) changes were associated with an increased risk of self-harming behaviour. Unexpectedly, a lower staff-to-prisoner ratio (OR 0.89, CI 0.78-0.99, p=0.039) was also associated with an increased risk of self-harming behaviour. Following sensitivity analyses, the associations between frequent cell changes and self-harm behaviour, and between single cell placement and self-harm ideation, remained statistically significant.

Discussion

This pilot study provides prospective longitudinal data regarding relationships between prison environmental factors and self-harm behaviour. Findings regarding single cell accommodation and frequent cell changes are consistent with the prior evidence base largely derived from case-control study data. The finding regarding frequent cellmate changes predicting self-harm is novel. Findings regarding staff-prisoner ratio and self-harm most likely reflect a reverse causal relationship. Replication in larger cohort studies is required to address the limitations of this pilot study.
The impact of antigenic distance on Orthopoxvirus Vaccination and Mpox Infection for cross-protective immunity
Authors: Crandell Jameson , Monteiro Valter Silva , Pischel Lauren , Fang Zhenhao , Zhong Yi , Lawres Lauren , Conde Luciana , Meira de Asis Gustavo , Maciel Gabriela , Zaleski Agnieszka , Lira Guilherme S. , Higa Luiza M. , Breban Mallery I. , Vogels Chantal B. F. , Grubaugh Nathan D. , Aoun-Barakat Lydia , Grifoni Alba , Sette Alessandro , Castineiras Terezinha M. , Chen Sidi , Yildirim Inci , Vale Andre M. , Omer Saad B. , Lucas Carolina
Published: February 2024

Immunological memory mediates rapid protection following infection or vaccination including heterologous exposure. However, cross-reactive memory responses in humans remain poorly characterized. We explored the longevity and specificity of cross-protective responses to orthopoxviruses through smallpox vaccination and Mpox virus (MPXV) infection. Smallpox vaccination using Vaccinia virus (VACV)-based vaccines provides a unique opportunity to study long-term cross-protective immunity without antigen re-exposure. We assessed systemic and mucosal responses in four human cohorts, including first-(Dryvax) and/or third-generation (JYNNEOS) smallpox vaccine recipients (vaccinated 1 week-80 years ago), along with Mpox-infected individuals. First-and third-generation smallpox vaccines elicited strong VACV- and MPXV-specific antibodies. VACV-neutralizing antibodies persisted for decades in first-generation vaccine recipients and were further enhanced after JYNNEOS vaccination. However, despite the high levels of anti-MPXV-specific antibodies in the plasma, cross-neutralization activity was directly correlated with the antigenic distance. Higher neutralization was observed for the cowpox virus (CWPXV) than for MPXV, which showed lower antigenic conservation with VACV. Similarly, Mpox-infected patients had lower neutralization titers for VACV than for CWPXV. Individuals who received vaccination boosters showed more robust, diverse, and prolonged cross-neutralizing responses. Long-term memory analysis revealed an increase in neutralization capacity for VACV over decades, with 80-years-old displaying the most robust humoral response, although this trend was not observed for cross-reactive antigens. Finally, T-cell reactivity to VACV and MPXV epitopes was detected decades post-vaccination, suggesting a role of long-lasting cross-reactive T-cell memory responses in vaccine efficacy. Our findings underscore the pivotal influence of antigenic distance on vaccine effectiveness with implications for cross-protective vaccine design.
Peripheral inflammatory markers relate to central inflammation and survival in syndromes associated with frontotemporal lobar degeneration
Authors: Malpetti Maura , Swann Peter , Tsvetanov Kamen A , Chouliaras Leonidas , Strauss Alexandra , Chikaura Tanatswa , Murley Alexander G , Ashton Nicholas , Barker Peter , Jones P Simon , Fryer Tim D. , Hong Young T. , Cope Thomas E , Savulich George , Street Duncan , Bevan-Jones W Richard , Rittman Timothy , Blennow Kaj , Zetterberg Henrik , Aigbirhio Franklin I. , O’Brien John T. , Rowe James B.
Published: February 2024

Neuroinflammation is an important pathogenic mechanism in many neurodegenerative diseases, including those caused by frontotemporal lobar degeneration (FTLD). There is a pressing need for scalable and mechanistically relevant blood markers of inflammation to facilitate drug development and experimental medicine. We assessed inflammatory profiles of serum cytokines from 214 patients with FTLD-associated syndromes (behavioural and language variants of frontotemporal dementia, progressive supranuclear palsy, corticobasal syndrome). We tested the association with brain microglial activation (by positron emission tomography) and survival. A pro-inflammatory profile across the FTLD spectrum (including TNF-α, TNF-R1, M-CSF, IL-17A, IL-12, IP-10 and IL-6) differentiated patients (all syndromes) from controls. A higher pro-inflammatory profile scores was associated with higher microglial activation in frontal and brainstem regions, and with lower survival. Blood-based markers of inflammation could increase the scalability and access to neuroinflammatory assessment of people with dementia, to facilitate clinical trials and experimental medicine studies.
Optimal vaccination strategies on networks and in metropolitan areas
Authors: Moschen Lucas Machado , Aronna María Soledad
Published: February 2024

This study presents a mathematical model for optimal vaccination strategies in interconnected metropolitan areas, considering commuting patterns. It is a compartmental model with a vaccination rate for each city, acting as a control function. The commuting patterns are incorporated through a weighted adjacency matrix and a parameter that selects day and night periods. The optimal control problem is formulated to minimize a functional cost that balances the number of hospitalizations and vaccines, including restrictions of a weekly availability cap and an application capacity of vaccines per unit of time. The key findings of this work are bounds for the basic reproduction number, particularly in the case of a metropolitan area, and the study of the optimal control problem. Theoretical analysis and numerical simulations provide insights into disease dynamics and the effectiveness of control measures. The research highlights the importance of prioritizing vaccination in the capital to better control the disease spread, as we depicted in our numerical simulations. This model serves as a tool to improve resource allocation in epidemic control across metropolitan regions.
ANALYSIS OF MYELOSUPPRESSION IN POST-CHEMOTHERAPY BREAST CANCER PATIENTS (A Study at Division of Hematology and Medical Oncology Airlangga University Hospital)
Authors: Yulistiani  , Utomo Febriansyah Nur , Romadhon Pradana Zaky , Nareswari Andwynanda Bhadra
Published: February 2024

Backgrounds

Myelosuppression is decreased bone marrow activity that can be caused by chemotherapy which lowers the formation of blood cells and manifests as anaemia, neutropenia, leukopenia, and thrombocytopenia.

Objective

This study aims to analyze the post-chemotherapy myelosuppression in breast cancer patients and the chemotherapy regimen used during chemotherapy associated with blood parameters.

Method

This study was conducted in observational retrospective design. Data were taken from patients’ medical record that went on chemotherapy during January 2021-December 2022.

Results

The result showed that 97% patients had myelosuppression with the significance statistic’s analysis P<0,05. The chemotherapy regimens used in breast cancer patients are AC-T, TAC, Paclitaxel-Carboplatin, TC, AC-TH, and TCH. This study found myelosuppression in several regimens: anaemia grade I-II in patients with AC-T regimen, neutropenia grade I-IV in patients with TCH regimen, leukopenia grade I-IV in patients with TC regimen, and thrombocytopenia grade I in patients with Paclitaxel-Carboplatin regimen. The incidence of delayed chemotherapy in patients due to myelosuppression is 18%.

Conclusion

Based on this study, all the regimens used had myelosuppression side effect. The highest incidence of myelosuppression occurred in patient with TAC and TCH regimen. Myelosuppression can cause delayed therapy, dose reduction, and drug substitution.