Light-activated ferroelectric transition in layer dependent Bi2O2Se films

Bi2O2Se has attracted intensive attention due to its potential in electronics, optoelectronics, as well as ferroelectric applications. Despite that, there have only been a handful of experimental studies based on ultrafast spectroscopy to elucidate the carrier dynamics in Bi2O2Se thin films, Different groups have reported various ultrafast timescales and associated mechanisms across films of different thicknesses. A comprehensive understanding in relation to thickness and fluence is still lacking. In this work, we have systematically explored the thickness-dependent Raman spectroscopy and ultrafast carrier dynamics in chemical vapor deposition (CVD)-grown Bi2O2Se thin films on mica substrate with thicknesses varying from 22.44 nm down to 4.62 nm at both low and high pump fluence regions. Combining the thickness dependence and fluence dependence of the slow decay time, we demonstrate a ferroelectric transition in the thinner (< 8 nm) Bi2O2Se films, influenced by substrate-induced compressive strain and non-equilibrium states. Moreover, this transition can be manifested under highly non-equilibrium states. Our results deepen the understanding of the interplay between the ferroelectric phase and semiconducting characteristics of Bi2O2Se thin films, providing a new route to manipulate the ferroelectric transition

Whole blood RNA signatures in tuberculosis patients receiving H56:IC31 vaccine as adjunctive therapy

IntroductionTherapeutic vaccination in tuberculosis (TB) represents a Host Directed Therapy strategy which enhances immune responses in order to improve clinical outcomes and shorten TB treatment. Previously, we have shown that the subunit H56:IC31 vaccine induced both humoral and cellular immune responses when administered to TB patients adjunctive to standard TB treatment (TBCOX2 study, NCT02503839). Here we present the longitudinal whole blood gene expression patterns in H56:IC31 vaccinated TB patients compared to controls receiving standard TB treatment only.MethodsThe H56:IC31 group (N=11) and Control group (N=7) underwent first-line TB treatment for 182 days. The H56:IC31 group received 5 micrograms of the H56:IC31 vaccine (Statens Serum Institut; SSI, Valneva Austria GmbH) intramuscularly at day 84 and day 140. Total RNA was extracted from whole blood samples collected in PAXgene tubes on days 0, 84, 98, 140, 154, 182 and 238. The expression level of 183 immune-related genes was measured by high-throughput microfluidic qPCR (Biomark HD system, Standard BioTools).ResultsThe targeted gene expression profiling unveiled the upregulation of modules such as interferon (IFN) signalling genes, pattern recognition receptors and small nucleotide guanosine triphosphate (GTP)-ases in the vaccinated group compared to controls two weeks after administration of the first H56:IC31 vaccine. Additionally, the longitudinal analysis of the Adolescent Cohort Study-Correlation of Risk (ACS-COR) signature showed a progressive downregulation in both study arms towards the end of TB treatment, in congruence with reported treatment responses and clinical improvements. Still, two months after the end of TB treatment, vaccinated patients, and especially those developing both cellular and humoral vaccine responses, showed a lower expression of the ACS-COR genes compared to controls.DiscussionOur data report gene expression patterns following H56:IC31 vaccination which might be interpreted as a lower risk of relapse in therapeutically vaccinated patients. Further studies are needed to conclude if these gene expression patterns could be used as prognostic biosignatures for therapeutic TB vaccine responses

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Modelling, inference and simulation of personalised breast cancer treatment

Mathematical modelling and simulation tools are an attractive and time- and cost- effective approach to determine optimal therapy for individual cancer patients. Current models can address pharmacokinetics and pharmacodynamics of anticancer medicine at various spatial and temporal scales. Simulations can then be performed to explore many treatment regimens to identify optimal plans with minimal toxicity. To individualise a model to each individual patient, its parameters require separate estimation and validation, and the runtime of simulations remains too slow for a practical clinical use. In this project, I demonstrate that - a mathematical model designed for a specific type of cancer, integrating routinely-collected data from a clinical trial is feasible, - the model is robust enough to simulate and predict various responses using individual data, and - the collected data are sufficient for the purpose of validation and personalisation of the model We use data from a recently published neoadjuvant clinical phase II trial in patients with advanced breast tumours where histological, magnetic resonance imaging (MRI) and molecular data were collected before, during and at the end of neoadjuvant treatment. Overall, our study demonstrates the effectiveness and the potential of simulation-based personal treatment optimisation. It lays the basis for future program in delivering robust clinic companion diagnostic tool

Personalized computer simulations of a NeoAva non-responder patient: comparison of standard and alternative schedules

The videos show personalized computer simulation of a breast tumor portion under the combined effect of chemotherapy and anti-angiogenic treatment. The simulations corresponds to 12 weeks of therapy in a luminal non-responder patient of the NeoAva clinical trial using standard and alternative schedules. Cancer, stroma cells and oxygen tension are shown. To produce the simulations we use a multiscale pharmacokinetic and pharmacodynamic model informed by individual, multisource clinical data, including histological, molecular and magnetic resonance imaging data. See reference below

Accrual and statistical power failure in published adjuvant phase III oncology trials: a comprehensive analysis from 2013 to 2023

Accrual failure; Oncology; Phase IIIFallo de acumulación; Oncología; Fase IIIFalla d'acumulació; Oncologia; Fase IIIBackground In a competitive landscape with many ongoing adjuvant randomised controlled trials (RCTs), the prevalence of trials that failed to recruit their targeted sample size and were inadequately powered is unclear. The aims of the study are (i) to determine the percentage of trials with accrual and statistical power failure and (ii) to evaluate their potential impact on the drug development process. Materials and methods A systematic review was carried out to identify adjuvant phase III oncology RCTs reported between 2013 and 2023 across all solid tumours. No restrictions were applied regarding the type of intervention or journal of publication. The percentage of trials with accrual failure and power failure was estimated as well as their association with the efficacy endpoints. Logistic regression models were used to estimate the odds ratio (OR) and its 95% confidence interval (CI). Results A total of 282 RCTs met the inclusion criteria with a median sample size of 661 patients and a median accrual period of 4.3 years. Most of these studies were superiority trials (83.0%). Accrual failure was observed in 22.0% of the studies, finishing recruitment without achieving the targeted sample size. Overall, 39.7% of the studies experienced power failure, having less power than specified in the protocol at the date of the read-out. Among superiority RCTs evaluating intermediate survival endpoints, only 31.1% presented statistically significant results. Trials with power failure were less likely to present statistically significant results (37.9% versus 21.9%, P = 0.04). The association was consistent across all cancer types. In the subset of non-inferiority trials, 35.0% formally demonstrated non-inferiority of the experimental arm. Conclusions Nearly 40% of adjuvant phase III RCTs experienced power failure, and the reduction in power significantly impacted the final study results. There is a need for procedural refinements in the design and implementation of future adjuvant RCTs to mitigate these fallacies.This work was supported by the National Institute for Health Research (NIHR) Senior Investigator Award [grant number NF-SI-0616-10107]. ICR-CTSU also receives programme grant funding from Cancer Research UK [grant number C1491/A25351]. The findings, interpretations and conclusions expressed in this paper are entirely those of the authors. The funding source did not have a role in the writing or decision to submit for publication. All authors have full access to the full data in the study and accept responsibility to submit for publication

Ocular findings and ocular graft-versus-host disease after allogeneic stem cell transplantation without total body irradiation

Patients treated with allogeneic stem cell transplantation (allo-SCT) often develop ocular complications. To investigate the ocular findings in young long-term survivors after allo-SCT without TBI, we examined 96 patients more than 5 years after transplantation. All patients were under 30 years of age at transplantation. The mean follow-up time was 16.8 years (range 6.0–26.1 years). The study was a part of the Norwegian Allo Survivorship Study investigating health impairments in young survivors after allo-SCT. Ophthalmological examination included visual acuity, tear break-up time, corneal fluorescein staining, Schirmer I test, tear film osmolarity, biomicroscopy and dilated ophthalmoscopy. In patients with known systemic chronic GVHD (cGVHD), ocular GVHD (oGVHD) diagnosed by clinical examination was compared with diagnosis using National Institutes of Health (NIH) or International Chronic Ocular Graft-vs-Host-Disease (ICCGVHD) Consensus Group criteria. We diagnosed dry eye disease (DED) in 52 patients (54%), cataract in 3 patients (3%) and retinopathy in 1 patient (1%). Systemic cGVHD was a risk factor for DED (OR 4.40, CI 1.33–14.56, p = 0.02). Comparison of diagnostic criteria suggests that the more stringent ICCGVHD criteria can better differentiate DED from oGVHD after allo-SCT as compared with the NIH criteria

Change in Ocular Surface Staining during Eyelid Warming Is Related to Tear Cytokine Levels

Purpose. To investigate the changes in the tear cytokine profile of patients with meibomian gland dysfunction (MGD) treated with eyelid warming and to correlate these changes with clinical parameters for dry eye disease (DED). Methods: Seventy patients with MGD were included and treated with the warming of eyelids. Of these, 61 still used the treatment three months after baseline, while 48 completed the whole treatment period of six months. The concentrations of 39 cytokines in the tear fluid were measured at baseline and after three and six months of treatment. All participants were examined with tests for DED, including tear film break-up time (TBUT), ocular surface staining (OSS), and the self-reporting Ocular Surface Disease Index (OSDI). Changes in cytokine concentrations were assessed from baseline to three months, from three to six months, and from baseline to six months. Correlation analyses were performed between changes in the cytokine concentrations and changes in TBUT, OSS, and OSDI during the same time intervals. Results: No significant changes were found in the concentrations of the 39 cytokines during any of the three treatment intervals. However, several correlations were detected between changes in the level of cytokines and OSS from baseline to three months of treatment. Decreasing concentrations of granulocyte chemotactic protein 2 (GCP-2/CXCL6, mean effect 2.36, p = 0.042), interleukin 10 (IL-10, mean effect 1.04, p = 0.045), and IL-16 (mean effect 1.36, p = 0.035) were associated with decreasing OSS. Decreasing concentrations of granulocyte macrophage colony-stimulating factor (GM-CSF, mean effect −2.98, p = 0.024), IL-8 (IL-8/CXCL8, mean effect −1.35, p = 0.026), and macrophage migration inhibitory factor (MIF, mean effect −2.44, p = 0.033) were related to increasing OSS. Conclusions: Warming of eyelids did not change the concentration of cytokines in the tear fluid of patients with MGD significantly. However, alterations in the level of several cytokines were associated with changes in the OSS. This finding indicates a close connection between tear cytokines and OSS in MGD patients treated with eyelid warming

Breast MRI as a building block for patient-specific simulations of drug effect

Poster presented in the 4th Symposium of Nordic Association for Clinical Physics, Bridging Imaging and Therapy, February 6 – 8, 2017 Oslo, Norwa