bluuebunny/crossref_metadata_2025_split huggingface dataset:
The antiviral activity of licensed therapeutics against Mpox clade Ib,in vitro; alternative options for the treatment of Mpox
Authors: Horton Amanda , Berryman Helen , Surani Yasmin M. , Bewley Kevin , Wand Matthew E. , Sutton J. Mark , Tree Julia A. 
Published: January 2025

AbstractClade Ib mpox is a newly emerged strain of the mpox virus (MPXV). The antiviral efficacy of 12 different therapeutic drugs was evaluated,in vitrousing a live-virus, foci reduction assay, against MPXV clade Ib. We report that antiviral activity is retained against clade Ib with inhibitory concentrations (required to reduce the viral foci count by 50% (IC50)) of 0.025 ± 0.018 and 43.8 ± 15.2 μM for tecovirimat and cidofovir, respectively. These values are not significantly different from those observed for clade IIb, when measured in the same foci reduction assay (IC50values of 0.010 ± 0.02 and 15.7 ± 14.3 μM for tecovirimat and cidofovir, respectively). Activity was also demonstrated for other antivirals, with the IC50of the active metabolites of molnupiravir (EIDD-1931; 4.47 ± 1.72 μM) and remdesivir (GS-441524; 11.8 ± 6.43 μM) and with other licensed antivirals such as ribavirin (34.4 ± 10.3 μM) and baloxavir marboxil (22.6 ± 10.5 μM). In contrast, no inhibitory activity was observed with acyclovir, L-valacyclovir hydrochloride or favipiravir (IC50>100 μM). Interestingly, the anti-parasitic drugs nitazoxanide, mefloquine hydrochloride and chloroquine diphosphate, showed inhibitory activity against the clade Ib virus, with IC50values of 14.5 ± 3.41, 5.37 ± 1.37 and 24.7 ± 2.38 μM, respectively. This study shows that several therapeutics, including several licensed antivirals, may offer alternative treatment options for mpox clade Ib.
miR-379-3p counteracts cancer cachexia through regulation of pyrimidinergic receptor, mitochondrial stress and interferon response
Authors: Borja-Gonzalez Maria , González-Ojeda Raúl , Sannicandro Anthony J , Su Chao , McCarthy Elan C , Sanz-Nogués Clara , Dwyer Roisin M , McDonagh Brian , Goljanek-Whysall Katarzyna 
Published: January 2025

AbstractCancer cachexia is a highly prevalent wasting syndrome in cancer patients. Inflammation is hallmarks of symptomatic cachexia, however early stages of cachexia are not well understood, including differences between biological sexes. In a mouse model of early cachexia, muscle from males showed strong mitochondrial defects, whereas females were characterized by inflammatory and stress response. We demonstrate a novel link between the increase in purinergic receptor P26Y, and dysregulated Ca2+homeostasis, mitochondrial dysfunction and damage, and inflammation during early stages of cancer cachexia. Low levels of miR-379-3p were associated with poor survival of patients with lung cancer. Restoring miR-379-3p levels in mice prevented loss of muscle mass and function. miR-379-3p targeted P2r6y and restored mitochondrial content and function, inhibited type II interferon response, and regulated the expression of Ca2+-related and apoptotic markers. This supports miR-379-3p as a hub regulating multiple processes underlying cachexia and represent a therapeutic target for cancer patients.
Estimating the effects of exercise-based cardiac rehabilitation on health-related quality of life in patients with myocardial infarction in Sweden: A registry-based study using non-experimental methods
Authors: Stanke Anja N. , Leósdóttir Margrét , Bäck Maria , Ekman Björn 
Published: January 2025

AbstractParticipation in exercise-based cardiac rehabilitation (EBCR) improves long-term prognosis for patients following myocardial infarction (MI). Evaluating the effects of EBCR is challenging due to the voluntary nature of participation in the program. Using register data on 18,978 patients hospitalized for MI in 2011 to 2013 in Sweden, a non-experimental study design is employed to evaluate the effects of EBCR on the health-related quality of life (HRQoL). Conditional independence from non-random treatment assignment is considered through set of potential-outcome (PO) models to estimate the average treatment effect (ATE) and the ATE on the treated (ATET) of EBCR on HRQoL using the EQ-5D-3L instrument. Changes in the EuroQoL Visual Analogue Scale (EQ-VAS; range 0 to 100) and the EQ5D-Index (range -0.594 to 1) between 6-10 weeks and one-year post-MI are compared between two groups of participants in EBCR (complete participants [≥3 months] and non-complete participants [<3 months]) and non-participants (control group). In total, 43% of patients participated in EBCR to some extent (12% complete, 31% non-complete). Participants showed greater improvement on the EQ-VAS scale compared with non-participants. Patients who completed an EBCR program had a larger improvement (ATE of between 1.851-1.917 points; p < 0.001) compared with participants who did not complete the full program (0.974-1.017 points; p < 0.01). Full participation in the program increased the EQ5D-Index of between 0.014 and 0.017 points (p < 0.05), while no statistically significant effect was observed among non-completers. The effect of EBCR on HRQoL was more pronounced among younger patients and those reporting dyspnea and angina than older and non-symptomatic patients. Participating in EBCR may improve the health-related quality of life of patients post-MI. The clinical relevance of the observed impact of EBCR on HRQoL warrants further investigation. The effects of EBCR participation can be readily estimated using broadly applicable non-experimental approaches and commonly available register data.
The benefits of palliative care follow-up combining day hospital and telemedicine
Authors: Saffon Valerie Mauries , Faya-Robles Alfonsina , Bourgouin Marie , Lamy Sebastien , Caunes-Hilary Nathalie , Couderc Bettina 
Published: January 2025

AbstractThe objective of the present study is to evaluate the impact of remote consultations (telemedicine) conducted on a monthly basis, in conjunction with quarterly inpatient follow-ups conducted by a team specialising in palliative care for cancer patients, in terms of anticipating potential deterioration in patients’ general condition and enhancing their quality of life. The study also investigates whether there is a specific profile of patients who could benefit from teleconsultation and identifies patients’ expectations and concerns regarding teleconsultation.The study enrolled 36 patients on their initial admission to a palliative care day hospital (HDJ), and they completed a questionnaire regarding their demographics, expectations, and reservations concerning teleconsultation. Patients were then scheduled for two monthly teleconsultations and were advised to return to the HDJ at D = 3 months. However, only 13 out of the 36 patients enrolled were able to benefit from the two teleconsultations and return to the HDJ after 3 months. This finding underscores the critical issue of patients being referred to the mobile palliative care team at a late stage. Our study revealed that factors such as age, gender, socio-economic status, and pathology did not influence patient compliance or the efficacy of the teleconsultations. The study emphasised the benefits of monthly teleconsultations for the clinical and psychological management of patients, highlighting that patients had minimal negative preconceptions upon enrolment and expressed a strong desire to continue these monthly consultations after the initial 3-month period. The findings underscore the significance of leveraging teleconsultations for patients receiving palliative care in oncology, particularly in scenarios where face-to-face consultations are not feasible. Telemedicine holds immense potential to enhance the monitoring of a larger patient population, thereby promoting greater equity in healthcare delivery.
Rationale design of peptide inhibitors forα-Synuclein liquid condensates and fibrillar aggregates using multiscale modelling approach
Authors: Ekambaram Srinivasan , Prajapati Santosh , Srivastava Anand 
Published: January 2025

Abstractα-Synuclein is an intrinsically disordered protein (IDP) whose aggregation is implicated in Parkinson’s disorder. Herein, we computationally design aα-Synuclein derived potential peptide inhibitor against the protein’s monomeric, fibrillar and liquid condensate forms using multi-scale molecular modelling approaches. Since the conventional structure-based design paradigm often is not applicable to these highly labile IDPs, we first develop a pipeline to generate an exhaustive library of small candidate peptides from an available repository ofα-Synuclein 70µs all-atom molecular dynamics (AAMD) trajectory data. We then use high throughput screening techniques such as PATCHDOCK and HPEPDOCK as well as AAMD simulations to arrive at a single candidate peptide. AAMD simulations data show thatα-Synuclein bound peptide chain leads to an expanded conformational ensemble for the chain and also reduces theβ-sheet propensity of the protein’s fibrillar amylogenic aggregates. Coarse-grained simulations using HPS-Cation forcefield with 100 chains ofα-Synuclein and varying levels of candidate peptides shows decreased density and increased apparent critical temperature of the condensate system. Our detailed molecular interactions analyses show that peptides bind to theα-Synucleins through the “dynamic shuttling mechanism” where interaction are frequently made and broken around a given set of structurally proximal residues, which likely softens the dynamic interaction network in the condensates. Together, we could illustrate the inhibitory effect of the final designed peptide against distinct forms ofα-Synuclein monomer and aggregates. Our work provides a multiscale simulation based prescription towards the futuristic development of therapeutic strategies against the disordered proteins.
Transcranial Magnetic Stimulation Depression Treatment Induces Positive Bias in Task-Related Brain Function: Results From the BRAEN-MAP Trial
Authors: Sarrazin Verena , Suen Paulo , Cavendish Beatriz , Martens Marieke , da Silva Pedro Henrique Rodrigues , Britto Anne , Rassi Matheus , Baptista Mariana , Brunoni Andre R , O’Shea Jacinta 
Published: January 2025

AbstractAntidepressant treatments are theorised to act by inducing a positive bias in information processing early on during treatment. Here, we tested for the first time whether this theory generalises to transcranial magnetic stimulation (TMS) treatment, an effective therapy for treatment-resistant depression. 49 patients with major depression received 20 sessions of open-label intermittent theta-burst stimulation applied to left dorsolateral prefrontal cortex. At baseline and after eight stimulation sessions, positive bias was assessed using behavioural and functional magnetic resonance imaging tasks presenting emotional faces. Clinical improvement at the end of treatment was related to an early increase in positive bias (1) in misclassification of emotional faces, (2) in the response of the default mode network (DMN) to emotional faces including rostral anterior cingulate cortex (ACC), and (3) in connectivity between rostral ACC and DMN. These neural changes predicted clinical improvement at the end of treatment beyond early symptom reduction. The results suggest that TMS treatment increases positive bias early on during treatment, and that the neural mechanisms might differ from that of antidepressant drugs.
SYSTEMS AND NETWORK BIOLOGY ANALYSIS COMBINED WITH MACHINE LEARNING IDENTIFIES KEY IMMUNE RESPONSE PROFILES AND POTENTIAL CORRELATES OF PROTECTION FOR THE M72/AS01E TUBERCULOSIS VACCINE
Authors: Taofeek Oluwaseun oluwatosin , Alile Solomon Osarumwense , Elcanah Evans Mauta , Ezediuno Louis Odinakaose , George Ifeoluwa Adeniyi , Oyewole Olawale Moses , Owiti Peter Ngo’la , Sulaimon Lateef Adegboyega 
Published: January 2025

AbstractTuberculosis claims around 1.5 million lives annually. The M72/AS01E vaccine candidate is an innovative effort demonstrating a 50% reduction in the incidence of active TB in adults. However, optimization and effective immunization strategies against TB depends heavily on precise identification of specific molecular signatures active in vaccine protection. In this study, we employed weighted gene co-expression network analysis, machine learning and network biology to investigate the gene expression patterns of peripheral blood mononuclear cells, identifying transcriptomic markers of vaccine protection. Our comprehensive exploration of publicly available gene expression dataset comprising samples from subjects vaccinated twice with 10μg of M72/AS01E vaccine one day post-second dose (D31) and one week post-second dose (D37) in a Phase IIA clinical trial revealed intense induction of multiple gene modules, indicative of acute/immediate immune response at D31 that subsided by D37. Thirty-one hub genes with significant elevation/correlation with immune protection were identified significantly mediating key events in immunity to TB. The more selective profile at D37 involved additional adaptive immunity pathways including Th1/Th2/Th17 differentiation, T cell receptor and cytokine signaling. The functional relevance of these biomarkers in predicting vaccine response was further analyzed using the random forest classifier demonstrating high accuracy in distinguishing between vaccinated and non-vaccinated samples. Additionally, the study pinpointed a miRNAs-transcription factors (TF)-target regulatory network excavating key TF, miRNA, mRNAs mediating vaccine protection. Our results provided new insights into immune protection of M72/AS01E vaccine meriting further study aiming to advance its optimization and informing development of future TB vaccines.
Respiratory virus infection dynamics and genomic surveillance to detect seasonal influenza subtypes in wastewater: a longitudinal study in Bengaluru, India
Authors: Daroch Namrta , Subash KK , Srikantaiah Vishwanath , Mishra Rakesh , Ishtiaq Farah 
Published: January 2025

AbstractRecent global pandemics have been caused by respiratory viruses found in both humans and animals with zoonotic spillover potential. Many respiratory viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), influenza A virus (IAV), and influenza B virus (IBV), have overlapping ecology and share similar symptoms. However, respiratory disease surveillance is often passive and relies on testing clinical specimens. Wastewater surveillance has been widely used as an epidemiological tool for early detection of SARS-CoV-2 variants and can differentiate between respiratory virus infections and SARS-CoV-2 peaks at a community level. In this retrospective longitudinal study covering three SARS-CoV-2 Omicron waves, we conducted a monthly sampling for 28 months (812 samples) between August 2021 and December 2023 at 28 sewershed sites in Bengaluru city (∼11 million inhabitants). Using RT-qPCR kits, we quantified SARS-CoV-2 RNA concentrations, IAV, IBV and RSV to understand community viral infection occurrences. We provide evidence of changes in the relative abundance of influenza subtypes and SARS-CoV-2 variants driving emerging peaks in wastewater data. We found 86% of samples positive for SARS-CoV-2, while the positivity rates for influenza virus and RSV were lower (37% for IAV, 16 % for IBV, and 15% for RSV). We observed an increase in influenza viruses in the post monsoon season (August to December) and remained present in January and February, while being practically absent the rest of the year. RSV showed a similar trend to IAV, with comparable quantities. Furthermore, we identified all eight segments of influenza virus genomes and emerging SARS-CoV-2 variants in wastewater samples. Wastewater surveillance provides data on the abundance of respiratory viruses in urban Bengaluru that would not be reported otherwise. Under the One Health framework, wastewater surveillance can offer early warning signs and enhance the traceability of infectious diseases in both wildlife and humans.
Estimating malaria antigen dynamics and the time to negativity of next-generation malaria rapid diagnostic tests
Authors: Sheahan William , Golden Allison , Barney Rebecca , Das Smita , Jang Ihn-Kyung , Ntuku Henry , Wu Xue , Whittemore Brooke , Dausab Lucille , Mumbengegwi Davis , Slater Hannah , Domingo Gonzalo J , Hsiang Michelle S 
Published: January 2025

AbstractBackgroundRapid diagnostic tests (RDTs) used to diagnosePlasmodium falciparum(Pf) predominantly target the antigen Histidine Rich Protein 2 (HRP2) exclusively. With the emergence ofhrp2/hrp3gene deletions, RDTs targeting other antigens such as the essential enzyme Lactate Dehydrogenase (LDH) are needed. The dynamics of LDH relative to HRP2 are currently not well described but are needed to inform the use of next-generation (NG-) LDH and HRP2 RDTs that are designed to addresshrp2/hrp3gene deletions.MethodsA longitudinal cohort study conducted in a low transmission setting in Namibia was leveraged to compare HRP2 and LDH decay rates. Passive and active case detection were used to recruit individuals with positive HRP2-RDT results. Study participants were treated and subsequently followed weekly until they received two consecutive HRP2-RDT negative results. Blood specimens were characterized for antigen concentration and parasite density. Antigen decay rates were calculated and used to estimate time to negativity (TTN) of NG-RDTs: two HRP2 and LDH-based RDTs (Rapigen Pf and a WHO prequalified Pf/Pv RDT) and an LDH-only RDT (Rapigen Pf/Pv).ResultsIn 135 participants, the starting geometric mean concentrations for HRP2 and LDH were 899 ng/mL and 344 ng/mL respectively. Both antigens followed a biphasic decay rate, with a faster decay rate in the first phase. For current RDTs with an analytical sensitivity of 1 ng/mL for HRP2 and 5 ng/mL for LDH, TTN was 44 and 4 days, respectively. With a NG-RDT with LDH analytical sensitivity of 0.37 ng/mL, average TTN was 9 days. Multiple levels of analytical sensitivity were also modeled.ConclusionsIn the detection of Pf malaria, LDH versus HRP2-based RDTs had a faster TTN due to a combination of lower accumulated antigen concentrations and faster decay rates, even for more sensitive LDH-based RDTs. Detection of LDH versus HRP2 by RDT is more likely to reflect a new or very recent infection. For NG-RDTs that target both antigens, HRP2 is likely to contribute more to the test signal than LDH in recently treated infections unless the infection hashrp2/hrp3gene deletions. Antigen decay data combined with analytical sensitivity of RDTs contributes to our understanding of their performance and interpretation.
Evaluation of stochastic trajectory-based epidemic models using the energy score
Authors: Bay Clara , Mu Kunpeng , St-Onge Guillaume , Chinazzi Matteo , Davis Jessica T. , Vespignani Alessandro 
Published: January 2025

AbstractScoring rules are critical for evaluating the predictive performance of epidemic models by quantifying how well their projections and forecasts align with observed data. In this study, we introduce the energy score as a robust performance metric for stochastic trajectory-based epidemic models. As a multivariate extension of the continuous ranked probability score (CRPS), the energy score provides a single, unified measure for time-series predictions. It evaluates both calibration and sharpness by considering the distances between individual trajectories and observed data, as well as the inter-trajectory variability. We provide an overview of how the energy score can be applied to assess both scenario projections and forecasts in this format, with a particular focus on a detailed analysis of the Scenario Modeling Hub results for the 2023-2024 influenza season. By comparing the energy score to the widely used weighted interval score (WIS), we demonstrate its utility as a powerful tool for evaluating epidemic models, especially in scenarios requiring integration of predictions across multiple target outcomes into a single, interpretable metric.Author summaryEpidemic model predictions are often evaluated using scoring rules, such as the weighted interval score (WIS), which require outputs in interval or quantile formats. However, epidemic models often produce outputs as collections of stochastic trajectories, which are then summarized into quantiles for evaluation. In this study, we introduce the energy score as a scoring metric specifically designed for evaluating stochastic trajectories without requiring conversion to other formats. The energy score provides a rigorous assessment by accounting for both the variability among trajectories and their alignment with observed data. Using publicly available data, we demonstrate that the energy score is a reliable and effective metric for evaluating epidemic model predictions in their native stochastic trajectory format.
Artificial Intelligence Generated Computed Tomography Segmentation of the Thoracoabdominal Aorta
Authors: Chatterjee Devina , Obey Nicholas T. , Shou Benjamin , Singh Sangmita , Acuna Higaki Adrian R. , Ahmed Adham , Erez Ely , Cupo Michela , Price Nathaniel , Hameed Irbaz , Schneider Eric B. , Vallabhajosyula Prashanth , Ong Chin Siang 
Published: January 2025

AbstractObjectivesThe rising global burden of cardiovascular diseases (CV) highlights the critical need for efficiency in disease diagnosis and management. An important area for such improvement is utilization of artificial intelligence (AI) for streamlining time and resources in CV imaging workflow. We evaluate the performance of artificial intelligence (AI) segmentation for aortic segmentation on clinical computed tomography angiography (CTA) images and compare accuracy to manual methods. Such automation would markedly improve efficiency and accuracy of aortic surveillance.MethodsThis retrospective study included 27 scans from 20 patients who underwent thoracic endovascular aortic repair (TEVAR) between January 2020 and March 2022. An open-source AI model was applied to segment the aorta, and its performance was assessed by comparing AI-generated segmentations with manual segmentations using Dice similarity coefficients, volumetric analysis, and aortic dimensions. Centerline reconstructed images of thoracoabdominal aorta were processed to extract radiomic features, including maximum diameter and cross-sectional area, for analysis.ResultsThe AI tool achieved a median Dice coefficient of 0.96 (0.02), indicating a high degree of concordance with manual segmentation. Multiplanar reconstruction was performed to visualize the aorta and extract measurements along its length using the automated centerline, and radiomic features, including maximum diameter and cross-sectional area, were subsequently extracted for analysis.ConclusionsAI segmentation demonstrates strong potential for improving efficiency and consistency in thoracoabdominal aortic segmentation, achieving high accuracy compared to manual methods. These findings highlight the feasibility of AI integration into clinical practice for diagnosis and surveillance of aortopathies, warranting further validation on larger datasets to enable clinical translation.Graphical Abstract