Tumour Size and Overall Survival in a Cohort of Patients with Unifocal Glioblastoma: A Uni- and Multivariable Prognostic Modelling and Resampling Study.

Published models inconsistently associate glioblastoma size with overall survival (OS). This study aimed to investigate the prognostic effect of tumour size in a large cohort of patients diagnosed with GBM and interrogate how sample size and non-linear transformations may impact on the likelihood of finding a prognostic effect. In total, 279 patients with a IDH-wildtype unifocal WHO grade 4 GBM between 2014 and 2020 from a retrospective cohort were included. Uni-/multivariable association between core volume, whole volume (CV and WV), and diameter with OS was assessed with (1) Cox proportional hazard models +/- log transformation and (2) resampling with 1,000,000 repetitions and varying sample size to identify the percentage of models, which showed a significant effect of tumour size. Models adjusted for operation type and a diameter model adjusted for all clinical variables remained significant (p = 0.03). Multivariable resampling increased the significant effects (p < 0.05) of all size variables as sample size increased. Log transformation also had a large effect on the chances of a prognostic effect of WV. For models adjusted for operation type, 19.5% of WV vs. 26.3% log-WV (n = 50) and 69.9% WV and 89.9% log-WV (n = 279) were significant. In this large well-curated cohort, multivariable modelling and resampling suggest tumour volume is prognostic at larger sample sizes and with log transformation for WV.

After wounding, a G-protein coupled receptor promotes the restoration of tension in epithelial cells.

The maintenance of epithelial barrier function involves cellular tension, with cells pulling on their neighbors to maintain epithelial integrity. Wounding interrupts cellular tension, which may serve as an early signal to initiate epithelial repair. To characterize how wounds alter cellular tension we used a laser-recoil assay to map cortical tension around wounds in the epithelial monolayer of the Drosophila pupal notum. Within a minute of wounding, there was widespread loss of cortical tension along both radial and tangential directions. This tension loss was similar to levels observed with Rok inactivation. Tension was subsequently restored around the wound, first in distal cells and then in proximal cells, reaching the wound margin ∼10 min after wounding. Restoring tension required the GPCR Mthl10 and the IP3 receptor, indicating the importance of this calcium signaling pathway known to be activated by cellular damage. Tension restoration correlated with an inward-moving contractile wave that has been previously reported; however, the contractile wave itself was not affected by Mthl10 knockdown. These results indicate that cells may transiently increase tension and contract in the absence of Mthl10 signaling, but that pathway is critical for fully resetting baseline epithelial tension after it is disrupted by wounding.

Characterisation and agronomic evaluation of acidified food waste anaerobic digestate products.

Raw liquid anaerobic digestate was synthesised into nutrient-dense solid digestates via acidification and evaporation. Acidification retained ammonium in the digestate whilst also donating the anion to free ammonium to form an ammonium salt. Digestate was treated with the addition of sulphuric, nitric, and phosphoric acid resulting in the formation of ammonium sulphate, ammonium nitrate and ammonium phosphate, respectively then evaporated into a solid fertiliser product. FTIR, XRD and SEM-EDS collectively confirm that the addition of acids completely converted the free ammonium in the raw digestate into their respective ammonium salt counterparts. Compounds of potassium chloride, silicon dioxide, calcium carbonate, magnesium ammonium phosphate, sodium nitrate, and sodium chloride were identified in all solid digestate samples. Plant growth and grain yield was higher in urea ammonium nitrate, raw liquid digestate and acidified digestate products compared to control and unacidified solid digestate. Urea ammonium nitrate and ammonium nitrate solid digestate had the highest dry shoot, likely due to the high available nitrogen found in both fertilisers. Overall, acidification and evaporation of liquid digestate can efficiently transform it into a valuable solid fertiliser with a high nutrient density. This process not only has the potential to mitigate handling and storage constraints of low nutrient density digestate in anaerobic digestion facilities but also offers a sustainable alternative to conventional fertilisers.

After wounding, a G-protein coupled receptor promotes the restoration of tension in epithelial cells.

The maintenance of epithelial barrier function involves cellular tension, with cells pulling on their neighbors to maintain epithelial integrity. Wounding interrupts cellular tension, which may serve as an early signal to initiate epithelial repair. To characterize how wounds alter cellular tension, we used a laser-recoil assay to map cortical tension around wounds in the epithelial monolayer of the Drosophila pupal notum. Within a minute of wounding, there was widespread loss of cortical tension along both radial and tangential directions. This tension loss was similar to levels observed with Rok inactivation. Tension was subsequently restored around the wound, first in distal cells and then in proximal cells, reaching the wound margin about 10 minutes after wounding. Restoring tension required the GPCR Mthl10 and the IP3 receptor, indicating the importance of this calcium signaling pathway known to be activated by cellular damage. Tension restoration correlated with an inward-moving contractile wave that has been previously reported; however, the contractile wave itself was not affected by Mthl10 knockdown. These results indicate that cells may transiently increase tension and contract in the absence of Mthl10 signaling, but that pathway is critical for fully resetting baseline epithelial tension after it is disrupted by wounding.

Independent component analysis (ICA) applied to dynamic oxygen-enhanced MRI (OE-MRI) for robust functional lung imaging at 3 T.

PURPOSE: Dynamic lung oxygen-enhanced MRI (OE-MRI) is challenging due to the presence of confounding signals and poor signal-to-noise ratio, particularly at 3 T. We have created a robust pipeline utilizing independent component analysis (ICA) to automatically extract the oxygen-induced signal change from confounding factors to improve the accuracy and sensitivity of lung OE-MRI. METHODS: Dynamic OE-MRI was performed on healthy participants using a dual-echo multi-slice spoiled gradient echo sequence at 3 T and cyclical gas delivery. ICA was applied to each echo within a thoracic mask. The ICA component relating to the oxygen-enhancement signal was automatically identified using correlation analysis. The oxygen-enhancement component was reconstructed, and the percentage signal enhancement (PSE) was calculated. The lung PSE of current smokers was compared with nonsmokers; scan-rescan repeatability, ICA pipeline repeatability, and reproducibility between two vendors were assessed. RESULTS: ICA successfully extracted a consistent oxygen-enhancement component for all participants. Lung tissue and oxygenated blood displayed the opposite oxygen-induced signal enhancements. A significant difference in PSE was observed between the lungs of current smokers and nonsmokers. The scan-rescan repeatability and the ICA pipeline repeatability were good. CONCLUSION: The developed pipeline demonstrated sensitivity to the signal enhancements of the lung tissue and oxygenated blood at 3 T. The difference in lung PSE between current smokers and nonsmokers indicates a likely sensitivity to lung function alterations that may be seen in mild pathology, supporting future use of our methods in patient studies.

Feasibility of dynamic T2 *-based oxygen-enhanced lung MRI at 3T.

PURPOSE: To demonstrate proof-of-concept of a T2 *-sensitized oxygen-enhanced MRI (OE-MRI) method at 3T by assessing signal characteristics, repeatability, and reproducibility of dynamic lung OE-MRI metrics in healthy volunteers. METHODS: We performed sequence-specific simulations for protocol optimisation and acquired free-breathing OE-MRI data from 16 healthy subjects using a dual-echo RF-spoiled gradient echo approach at 3T across two institutions. Non-linear registration and tissue density correction were applied. Derived metrics included percent signal enhancement (PSE), ∆R2 * and wash-in time normalized for breathing rate (τ-nBR). Inter-scanner reproducibility and intra-scanner repeatability were evaluated using intra-class correlation coefficient (ICC), repeatability coefficient, reproducibility coefficient, and Bland-Altman analysis. RESULTS: Simulations and experimental data show negative contrast upon oxygen inhalation, due to substantial dominance of ∆R2 * at TE > 0.2 ms. Density correction improved signal fluctuations. Density-corrected mean PSE values, aligned with simulations, display TE-dependence, and an anterior-to-posterior PSE reduction trend at TE1 . ∆R2 * maps exhibit spatial heterogeneity in oxygen delivery, featuring anterior-to-posterior R2 * increase. Mean T2 * values across 32 scans were 0.68 and 0.62 ms for pre- and post-O2 inhalation, respectively. Excellent or good agreement emerged from all intra-, inter-scanner and inter-rater variability tests for PSE and ∆R2 *. However, ICC values for τ-nBR demonstrated limited agreement between repeated measures. CONCLUSION: Our results demonstrate the feasibility of a T2 *-weighted method utilizing a dual-echo RF-spoiled gradient echo approach, simultaneously capturing PSE, ∆R2 * changes, and oxygen wash-in during free-breathing. The excellent or good repeatability and reproducibility on intra- and inter-scanner PSE and ∆R2 * suggest potential utility in multi-center clinical applications.

The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): Results from the OSIPI-Dynamic Contrast-Enhanced challenge.

PURPOSE: K trans $$ {K}^{\mathrm{trans}} $$ has often been proposed as a quantitative imaging biomarker for diagnosis, prognosis, and treatment response assessment for various tumors. None of the many software tools for K trans $$ {K}^{\mathrm{trans}} $$ quantification are standardized. The ISMRM Open Science Initiative for Perfusion Imaging-Dynamic Contrast-Enhanced (OSIPI-DCE) challenge was designed to benchmark methods to better help the efforts to standardize K trans $$ {K}^{\mathrm{trans}} $$ measurement. METHODS: A framework was created to evaluate K trans $$ {K}^{\mathrm{trans}} $$ values produced by DCE-MRI analysis pipelines to enable benchmarking. The perfusion MRI community was invited to apply their pipelines for K trans $$ {K}^{\mathrm{trans}} $$ quantification in glioblastoma from clinical and synthetic patients. Submissions were required to include the entrants' K trans $$ {K}^{\mathrm{trans}} $$ values, the applied software, and a standard operating procedure. These were evaluated using the proposed OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score defined with accuracy, repeatability, and reproducibility components. RESULTS: Across the 10 received submissions, the OSIP I gold $$ \mathrm{OSIP}{\mathrm{I}}_{\mathrm{gold}} $$ score ranged from 28% to 78% with a 59% median. The accuracy, repeatability, and reproducibility scores ranged from 0.54 to 0.92, 0.64 to 0.86, and 0.65 to 1.00, respectively (0-1 = lowest-highest). Manual arterial input function selection markedly affected the reproducibility and showed greater variability in K trans $$ {K}^{\mathrm{trans}} $$ analysis than automated methods. Furthermore, provision of a detailed standard operating procedure was critical for higher reproducibility. CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within K trans $$ {K}^{\mathrm{trans}} $$ estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with different benchmarking methodology.

Ultrafast Charge Transfer Dynamics in a Slip-Stacked Donor-Acceptor-Acceptor System.

Photoexcitation of molecular electron donor and/or acceptor chromophore aggregates can greatly affect their charge-transfer dynamics. Excitonic coupling not only alters the energy landscape in the excited state but may also open new photophysical pathways, such as symmetry-breaking charge separation (SB-CS). Here, we investigate the impact of excitonic coupling on a covalent donor-acceptor-acceptor system comprising a perylene donor (Per) and two perylenediimide (PDI) acceptor chromophores in which the three components are π-stacked in a geometry that is slipped along their long axes (Per-PDI2). Following selective photoexcitation of PDI, femtosecond transient absorption data for Per-PDI2 is compared to that for the single-donor, single-acceptor Per-PDI system, and the PDI2 dimer, which both have the same interchromophore geometry as Per-PDI2. The data show that electron transfer from Per to the lower exciton state of the PDI dimer is slower than that of the single PDI acceptor system. This is due to the lower free energy of the reaction for charge separation because of the electronic stabilization afforded by the excitonic coupling between the PDIs. While PDI2 was shown previously to undergo ultrafast SB-CS, the strong π-π electronic interaction of Per with the adjacent PDI in Per-PDI2 breaks the electronic symmetry of the PDI dimer, resulting in the oxidation of Per rather than SB-CS. These results show that the electronic coupling between molecules designed to accept charges produced by SB-CS in molecular dimers and the chromophores comprising the dimer must be balanced to favor SB-CS.

Tracheobronchomalacia: an unusual cause of debilitating dyspnoea and its surgical management.

Tracheobronchomalacia (TBM) is a progressive weakening of the airways, leading to collapse and dyspnoea. TBM can be misdiagnosed when multiple chronic conditions accompany it. Tracheobronchoplasty (TBP) is indicated for severe symptomatic TBM, diagnosed by bronchoscopy and CT thorax. We report the case of a patient who underwent tracheal resection and reconstruction for continuing dyspnoea post argon therapy, TBP and a failure to tolerate extracorporeal membrane oxygenation-assisted Y-stent insertion. Relevant background history includes asthma, sleep apnoea, reflux, cardiomyopathy and a high body mass index. Bronchoscopy postreconstruction showed patent airways. Airway reconstruction was a viable management option for this patient's TBM. TBP is a treatment option for TBM. In this case, tracheal resection was required to sustain benefit. In addition, surveillance bronchoscopies will be carried out every year.

Local density dependent potentials for an underlying van der Waals equation of state: A simulation and density functional theory analysis.

There is an ever increasing use of local density dependent potentials in the mesoscale modeling of complex fluids. Questions remain, though, about the dependence of the thermodynamic and structural properties of such systems on the cutoff distance used to calculate these local densities. These questions are particularly acute when it comes to the stability and structure of the vapor/liquid interface. In this article, we consider local density dependent potentials derived from an underlying van der Waals equation of state. We use simulation and density functional theory to examine how the bulk thermodynamic and interfacial properties vary with the cutoff distance, rc, used to calculate the local densities. We show quantitatively how the simulation results for bulk thermodynamic properties and vapor-liquid equilibrium approach the van der Waals limit as rc increases and demonstrate a scaling law for the radial distribution function in the large rc limit. We show that the vapor-liquid interface is stable with a well-defined surface tension and that the interfacial density profile is oscillatory, except for temperatures close to critical. Finally, we show that in the large rc limit, the interfacial tension is proportional to rc and, therefore, unlike the bulk thermodynamic properties, does not approach a constant value as rc increases. We believe that these results give new insights into the properties of local density dependent potentials, in particular their unusual interfacial behavior, which is relevant for modeling complex fluids in soft matter.

Enhancing nutrient recovery from food waste anaerobic digestate.

The study synthesised the raw liquid fraction of digestate into a nutrient rich solid digestate through acidification whilst preventing nitrogen loss through ammonium volatilisation during evaporation. To stabilise ammonium in the digestate, it was acidified with sulphuric, nitric, and phosphoric acid to produce solid digestate with ammonium sulphate, ammonium nitrate and ammonium phosphate, respectively. These treatments were compared against urea ammonium nitrate, raw digestate, and unacidified solid digestate. To evaluate the effect of these transformed digestate products in soil, a plant growth experiment (Kikuyu; Cenchrus clandestinus) was conducted, and characterised, plant growth, soil chemistry, and rhizosphere bacterial communities. Plant growth was enhanced by all digestate treatments compared to control and urea ammonium nitrate. Ammonium phosphate solid digestate plant growth was significantly higher than all other acidified treatments due to the high P content. Moreover, digestate-amended soil had elevated Proteobacteria and putative denitrification genes.

Operative Management of Aerodigestive Injuries: Improved Survival Over two Decades.

INTRODUCTION: Non-iatrogenic aerodigestive injuries are infrequent but potentially fatal. We hypothesize that advances in management and adoption of innovative therapies resulted in improved survival. METHODS: Trauma registry review at a university Level 1 center from 2000 to 2020 that identified adults with aerodigestive injuries requiring operative or endoluminal intervention. Demographics, injuries, operations, and outcomes were abstracted. Univariate analysis was performed, P < .05 was statistically significant. RESULTS: 95 patients had 105 injuries: 68 tracheal and 37 esophageal (including 10 combined). Mean age 30.9 (± 14), 87.4% male, 82.1% penetrating, and 28.4% with vascular injuries. Median ISS, chest AIS, admission BP, Shock Index, and lactate were 26 (16-34), 4 (3-4), 132 (113-149) mmHg, .8 (.7-1.1), and 3.1 (2.4-5.6) mmol/L, respectively. There were 46 cervical and 22 thoracic airway injuries; 5 patients in extremis required preoperative ECMO. 66 airway injuries were surgically repaired and 2 definitively managed with endobronchial stents. There were 24 cervical, 11 thoracic, 2 abdominal esophageal injuries-all repaired surgically. Combined tracheoesophageal injuries were individually managed and buttressed. 4 airway complications were successfully managed, and 11 esophageal complications managed conservatively, stented, or resected. Mortality was 9.6%, half from intraoperative hemorrhage. Specific mortality: tracheobronchial 8.8%, esophageal 10.8%, and combined 20%. Mortality was significantly associated with higher ISS (P = .01), vascular injury (P = .007), blunt mechanism (P = .01), bronchial injury (P = .01), and years 2000-2010 (P = .03), but not combined tracheobronchial injury. CONCLUSION: Mortality is associated with several variables, including vascular trauma and years 2000-2010. The use of ECMO and endoluminal stents in highly selected patients and institutional experience may account for 97.8% survival over the past decade.

Development of a controlled release fertilizer by incorporating lauric acid into microalgal biomass: Dynamics on soil biological processes for efficient utilisation of waste resources.

Utilisation of microalgae to extract nutrients from the effluent of anaerobic digestion of food waste is an emerging technology. A by-product of this process is the microalgal biomass which has potential to be used as an organic bio-fertilizer. However, microalgal biomass are rapidly mineralized when applied to soil which may result in N loss. One solution is to emulsify microalgal biomass with lauric acid (LA) to delay the release of mineral N. This study aimed to investigate whether combining LA with microalgae to develop a new fertilizer product with a controlled release function of mineral N when applied to soil, and any potential impacts the bacterial community structure and activity. The treatments were applied to soil emulsified with LA and were combined with either microalgae or urea at rates of 0%, 12.5%, 25% and 50% LA, untreated microalgae or urea and unamended control were incubated at 25 °C and 40% water holding capacity for 28 days. Quantification of soil chemistry (NH4+-N, NO3--N, pH and EC), microbial biomass carbon, CO2 production and bacterial diversity were characterised at 0, 1, 3, 7, 14 and 28 days. The NH4+-N and NO3--N concentration decreased with increasing rate of LA combined microalgae indicating that both N mineralization and nitrification were impacted. As a function of time, NH4+-N concentration increased up to 7 days for the microalgae at lower rates of LA, and then slowly decreased for 14 and 28 days, with an inverse relationship with soil NO3-N. Aligning with soil chemistry, an observed decrease in the predicted nitrification genes amoA·amoB and relative abundance of ammonia oxidizing bacteria (Nitrosomonadaceae) and nitrifying bacteria (Nitrospiraceae) with an increasing rate of LA with microalgae provides further support for possible inhibition of nitrification. The MBC and CO2 production was higher in the soil amended with increasing rates of LA combined microalgae and there was an increase in the relative abundance of fast-growing heterotrophs. Treating microalgae by emulsification with LA has the potential to control the release of N by increasing immobilization over nitrification and therefore it might be possible to engineer microalgae to match plant nutrient growth requirements whilst recovering waste from waste resources.

Export pathways of biosolid derived microplastics in soil systems - Findings from a temperate maritime climate.

The environmental fate of microplastics (MPs) added to agricultural soils remains poorly understood, particularly regarding their mobility in soils. Here we investigate the potential for MP export from soil to surface waters and groundwater in two agricultural settings with a 20-year history of biosolid treatment. A third site where biosolids had never been applied served as a reference (Field R). The potential for MP export along overland and interflow pathways to surface waters was determined from MP abundances in shallow surface cores (10 cm) along ten down-slope transects (five each for Field A and B), and through MP abundances in effluent from a sub-surface land drain. The risk of vertical MP migration was assessed from 2 m cores, and from MP abundances in groundwater sampled from the core boreholes. XRF Itrax core scanning was conducted on two of the deep cores to capture high-resolution optical and 2-D radiographic imaging. Results suggest limited MP mobility at depths >35 cm, with MPs largely recovered in surface soils characterised by lower compaction. Furthermore, abundances of MPs across the surface cores were comparable, with no evidence of MP accumulations observed. Average MP abundance in the top 10 cm of soil across Field A and B was 365 ± 302 MP kg-1, with 0.3 MP l-1 and 1.6 MP l-1 recovered from the groundwater and field drainpipe water samples, respectively. MP abundances were significantly higher in fields treated with biosolids than in Field R (90 ± 32 MP kg-1 soil). Findings suggest ploughing is the most significant driver of MP mobility in upper soil layers, however the potential for overland or interflow movement cannot be excluded, particularly for fields that may be artificially drained.

Early veno-venous extracorporeal membrane oxygenation is an effective strategy for traumatically injured patients presenting with refractory respiratory failure.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV ECMO) is used for respiratory failure when standard therapy fails. Optimal trauma care requires patients be stable enough to undergo procedures. Early VV ECMO (EVV) to stabilize trauma patients with respiratory failure as part of resuscitation could facilitate additional care. As VV ECMO technology is portable and prehospital cannulation possible, it could also be used in austere environments. We hypothesize that EVV facilitates injury care without worsening survival. METHODS: Our single center, retrospective cohort study included all trauma patients between January 1, 2014, and August 1, 2022, who were placed on VV ECMO. Early VV was defined as cannulation ≤48 hours from arrival with subsequent operation for injuries. Data were analyzed with descriptive statistics. Parametric or nonparametric statistics were used based on the nature of the data. After testing for normality, significance was defined as a p < 0.05. Logistic regression diagnostics were performed. RESULTS: Seventy-five patients were identified and 57 (76%) underwent EVV. There was no difference in survival between the EVV and non-EVV groups (70% vs. 61%, p = 0.47). Age, race, and gender did not differ between EVV survivors and nonsurvivors. Time to cannulation (4.5 hours vs. 8 hours, p = 0.39) and injury severity scores (34 vs. 29, p = 0.74) were similar. Early VV survivors had lower lactic acid levels precannulation (3.9 mmol/L vs. 11.9 mmol/L, p < 0.001). A multivariable logistic regression analysis examining admission and precannulation laboratory and hemodynamic values demonstrated that lower precannulation lactic acid levels predicted survival (odds ratio, 1.2; 95% confidence interval, 1.02-1.5; p = 0.03), with a significant inflection point of 7.4 mmol/L corresponding to decreased survival at hospital discharge. CONCLUSION: Patients undergoing EVV did not have increased mortality compared with the overall trauma VV ECMO population. Early VV resulted in ventilatory stabilization that allowed subsequent procedural treatment of injuries. LEVEL OF EVIDENCE: Therapeutic Care/Management; Level III.

Steps on the Path to Clinical Translation: A workshop by the British and Irish Chapter of the ISMRM.

The British and Irish Chapter of the International Society for Magnetic Resonance in Medicine (BIC-ISMRM) held a workshop entitled "Steps on the path to clinical translation" in Cardiff, UK, on 7th September 2022. The aim of the workshop was to promote discussion within the MR community about the problems and potential solutions for translating quantitative MR (qMR) imaging and spectroscopic biomarkers into clinical application and drug studies. Invited speakers presented the perspectives of radiologists, radiographers, clinical physicists, vendors, imaging Contract/Clinical Research Organizations (CROs), open science networks, metrologists, imaging networks, and those developing consensus methods. A round-table discussion was held in which workshop participants discussed a range of questions pertinent to clinical translation of qMR imaging and spectroscopic biomarkers. Each group summarized their findings via three main conclusions and three further questions. These questions were used as the basis of an online survey of the broader UK MR community.

Coherent Vibronic Wavepackets Show Structure-Directed Charge Flow in Host-Guest Donor-Acceptor Complexes.

Designing and controlling charge transfer (CT) pathways in organic semiconductors are important for solar energy applications. To be useful, a photogenerated, Coulombically bound CT exciton must further separate into free charge carriers; direct observations of the detailed CT relaxation pathways, however, are lacking. Here, photoinduced CT and relaxation dynamics in three host-guest complexes, where a perylene (Per) electron donor guest is incorporated into two symmetric and one asymmetric extended viologen cyclophane acceptor hosts, are presented. The central ring in the extended viologen is either p-phenylene (ExV2+) or electron-rich 2,5-dimethoxy-p-phenylene (ExMeOV2+), resulting in two symmetric cyclophanes with unsubstituted or methoxy-substituted central rings, ExBox4+ and ExMeOBox4+, respectively, and an asymmetric cyclophane with one of the central viologen rings being methoxylated ExMeOVBox4+. Upon photoexcitation, the asymmetric host-guest ExMeOVBox4+ ⊃ Per complex exhibits directional CT toward the energetically unfavorable methoxylated side due to structural restrictions that facilitate strong interactions between the Per donor and the ExMeOV2+ side. The CT state relaxation pathways are probed using ultrafast optical spectroscopy by focusing on coherent vibronic wavepackets, which are used to identify CT relaxations along charge localization and vibronic decoherence coordinates. Specific low- and high-frequency nuclear motions are direct indicators of a delocalized CT state and the degree of CT character. Our results show that the CT pathway can be controlled by subtle chemical modifications of the acceptor host in addition to illustrating how coherent vibronic wavepackets can be used to probe the nature and time evolution of the CT states.

Two-Dimensional Electronic Spectroscopy Reveals Vibrational Modes Coupled to Charge Transfer in a Julolidine-BODIPY Dyad.

Understanding charge transfer (CT) dynamics in molecular donor-acceptor (D-A) dyads can provide insight into developing efficient D-A molecules for capturing solar energy. Here, we characterize the excited-state evolution of a julolidine-BODIPY (Jul-BD) D-A system with an emissive CT state using time-resolved fluorescence, femtosecond transient absorption, and two-dimensional electronic spectroscopies. Comparison of these results with those from phenyl-BODIPY (Ph-BD) allows us to identify the dynamics at play during CT state formation and its subsequent conversion to either a fully charge-separated or triplet state. Photoexcitation of Jul-BD in tetrahydrofuran results in the formation of an initial emissive CT state that relaxes before fully charge-separating. In contrast, Jul-BD in toluene exhibits similar CT state dynamics, albeit at slower timescales, before decaying to a terminal triplet species. Quantum beat analysis at early times in both solvents shows several vibronic modes, which are corroborated using density functional theory (DFT) calculations. For Ph-BD, a single 220 cm-1 compression mode about the single bond linking the phenyl to BODIPY modulates their orbital overlap. Three active vibronic modes, 147, 174, and 214 cm-1, are found in Jul-BD, regardless of the dielectric constant of the medium. These motions correspond to compression and torsional motions along the single bond joining Jul to BD and are responsible for the evolution of the spontaneous and stimulated emission features in the time-resolved spectroscopic data, which is further supported by time-dependent DFT calculations of the steady-state absorption spectrum of the Jul-BD as a function of increasing D-A dihedral core angle. These findings show how torsional and compression motions can play a pivotal role in intramolecular CT between a D and an A linked by a single bond.

First-in-human technique translation of oxygen-enhanced MRI to an MR Linac system in patients with head and neck cancer.

BACKGROUND AND PURPOSE: Tumour hypoxia is prognostic in head and neck cancer (HNC), associated with poor loco-regional control, poor survival and treatment resistance. The advent of hybrid MRI - radiotherapy linear accelerator or 'MR Linac' systems - could permit imaging for treatment adaptation based on hypoxic status. We sought to develop oxygen-enhanced MRI (OE-MRI) in HNC and translate the technique onto an MR Linac system. MATERIALS AND METHODS: MRI sequences were developed in phantoms and 15 healthy participants. Next, 14 HNC patients (with 21 primary or local nodal tumours) were evaluated. Baseline tissue longitudinal relaxation time (T1) was measured alongside the change in 1/T1 (termed ΔR1) between air and oxygen gas breathing phases. We compared results from 1.5 T diagnostic MR and MR Linac systems. RESULTS: Baseline T1 had excellent repeatability in phantoms, healthy participants and patients on both systems. Cohort nasal concha oxygen-induced ΔR1 significantly increased (p < 0.0001) in healthy participants demonstrating OE-MRI feasibility. ΔR1 repeatability coefficients (RC) were 0.023-0.040 s-1 across both MR systems. The tumour ΔR1 RC was 0.013 s-1 and the within-subject coefficient of variation (wCV) was 25% on the diagnostic MR. Tumour ΔR1 RC was 0.020 s-1 and wCV was 33% on the MR Linac. ΔR1 magnitude and time-course trends were similar on both systems. CONCLUSION: We demonstrate first-in-human translation of volumetric, dynamic OE-MRI onto an MR Linac system, yielding repeatable hypoxia biomarkers. Data were equivalent on the diagnostic MR and MR Linac systems. OE-MRI has potential to guide future clinical trials of biology guided adaptive radiotherapy.

Encapsulating Semiconductor Quantum Dots in Supramolecular Cages Enables Ultrafast Guest-Host Electron and Vibrational Energy Transfer.

In the field of supramolecular chemistry, host-guest systems have been extensively explored to encapsulate a wide range of substrates, owing to emerging functionalities in nanoconfined space that cannot be achieved in dilute solutions. However, host-guest chemistry is still limited to encapsulation of small guests. Herein, we construct a water-soluble metallo-supramolecular hexagonal prism with a large hydrophobic cavity by anchoring multiple polyethylene glycol chains onto the building blocks. Then, assembled prisms are able to encapsulate quantum dots (QDs) with diameters of less than 5.0 nm. Furthermore, we find that the supramolecular cage around each QD strongly modifies the photophysics of the QD by universally increasing the rates of QD relaxation processes via ultrafast electron and vibrational energy transfer. Taken together, these efforts expand the scope of substrates in host-guest systems and provide a new approach to tune the optical properties of QDs.