bluuebunny/crossref_metadata_2025_split huggingface dataset:
A diel multi-tissue genome-scale metabolic model ofVitis vinifera
Authors: Sampaio Marta , Rocha Miguel , Dias Oscar 
Published: February 2024

AbstractVitis 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.
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

AbstractEbola 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

AbstractBackground-Research questionChronic 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-Methodsused 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).ResultsWe 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.InterpretationGiven 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

AbstractAlzheimer’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

AbstractIntroductionLarger 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.MethodTo 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.ResultsComparative 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.ConclusionThe 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

AbstractSocial 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

AbstractObjectivesLongitudinal 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).SettingA 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.ParticipantsAdults and/or children of school age (≥5 years old), with clinician-diagnosed asthmaPrimary outcomesAsthma PROs, namely asthma exacerbations, asthma control, asthma-related quality of life and asthma severityResults24 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.DiscussionRoutinely 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 SummaryStrengths and limitations of this studyThis 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

AbstractIntroductionSelf-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.MethodsA 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.ResultsSingle 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.DiscussionThis 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

AbstractImmunological 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

AbstractNeuroinflammation 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

AbstractThis 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

AbstractBackgroundsMyelosuppression 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.ObjectiveThis study aims to analyze the post-chemotherapy myelosuppression in breast cancer patients and the chemotherapy regimen used during chemotherapy associated with blood parameters.MethodThis study was conducted in observational retrospective design. Data were taken from patients’ medical record that went on chemotherapy during January 2021-December 2022.ResultsThe 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%.ConclusionBased 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.