Aerosol-Jet-Printable Covalent Organic Framework Colloidal Inks and Temperature-Sensitive Nanocomposite Films.

With molecularly well-defined and tailorable 2D structures, covalent organic frameworks (COFs) have emerged as leading material candidates for chemical sensing, storage, separation, and catalysis. In these contexts, the ability to directly and deterministically print COFs into arbitrary geometries will enable rapid optimization and deployment. However, previous attempts to print COFs have been restricted by low spatial resolution and/or post-deposition polymerization that limits the range of compatible COFs. Here, these limitations are overcome with a pre-synthesized, solution-processable colloidal ink that enables aerosol jet printing of COFs with micron-scale resolution. The ink formulation utilizes the low-volatility solvent benzonitrile, which is critical to obtaining homogeneous printed COF film morphologies. This ink formulation is also compatible with other colloidal nanomaterials, thus facilitating the integration of COFs into printable nanocomposite films. As a proof-of-concept, boronate-ester COFs are integrated with carbon nanotubes (CNTs) to form printable COF-CNT nanocomposite films, in which the CNTs enhance charge transport and temperature sensing performance, ultimately resulting in high-sensitivity temperature sensors that show electrical conductivity variation by 4 orders of magnitude between room temperature and 300 °C. Overall, this work establishes a flexible platform for COF additive manufacturing that will accelerate the incorporation of COFs into technologically significant applications.

Adjuvant chemotherapy following chemoradiotherapy as primary treatment for locally advanced cervical cancer versus chemoradiotherapy alone (OUTBACK): an international, open-label, randomised, phase 3 trial.

BACKGROUND: Standard treatment for locally advanced cervical cancer is chemoradiotherapy, but many patients relapse and die of metastatic disease. We aimed to determine the effects on survival of adjuvant chemotherapy after chemoradiotherapy. METHODS: The OUTBACK trial was a multicentre, open-label, randomised, phase 3 trial done in 157 hospitals in Australia, China, Canada, New Zealand, Saudi Arabia, Singapore, and the USA. Eligible participants were aged 18 year or older with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, II, IIIB, or IVA disease), Eastern Cooperative Oncology Group performance status 0-2, and adequate bone marrow and organ function. Participants were randomly assigned centrally (1:1) using a minimisation approach and stratified by pelvic or common iliac nodal involvement, requirement for extended-field radiotherapy, FIGO 2008 stage, age, and site to receive standard cisplatin-based chemoradiotherapy (40 mg/m2 cisplatin intravenously once-a-week for 5 weeks, during radiotherapy with 45·0-50·4 Gy external beam radiotherapy delivered in fractions of 1·8 Gy to the whole pelvis plus brachytherapy; chemoradiotherapy only group) or standard cisplatin-based chemoradiotherapy followed by adjuvant chemotherapy with four cycles of carboplatin (area under the receiver operator curve 5) and paclitaxel (155 mg/m2) given intravenously on day 1 of a 21 day cycle (adjuvant chemotherapy group). The primary endpoint was overall survival at 5 years, analysed in the intention-to-treat population (ie, all eligible patients who were randomly assigned). Safety was assessed in all patients in the chemoradiotherapy only group who started chemoradiotherapy and all patients in the adjuvant chemotherapy group who received at least one dose of adjuvant chemotherapy. The OUTBACK trial is registered with ClinicalTrials.gov, NCT01414608, and the Australia New Zealand Clinical Trial Registry, ACTRN12610000732088. FINDINGS: Between April 15, 2011, and June 26, 2017, 926 patients were enrolled and randomly assigned to the chemoradiotherapy only group (n=461) or the adjuvant chemotherapy group (n=465), of whom 919 were eligible (456 in the chemoradiotherapy only group and 463 in the adjuvant chemotherapy group; median age 46 years [IQR 37 to 55]; 663 [72%] were White, 121 [13%] were Black or African American, 53 [6%] were Asian, 24 [3%] were Aboriginal or Pacific islander, and 57 [6%] were other races) and included in the analysis. As of data cutoff (April 12, 2021), median follow-up was 60 months (IQR 45 to 65). 5-year overall survival was 72% (95% CI 67 to 76) in the adjuvant chemotherapy group (105 deaths) and 71% (66 to 75) in the chemoradiotherapy only group (116 deaths; difference 1% [95% CI -6 to 7]; hazard ratio 0·90 [95% CI 0·70 to 1·17]; p=0·81). In the safety population, the most common clinically significant grade 3-4 adverse events were decreased neutrophils (71 [20%] in the adjuvant chemotherapy group vs 34 [8%] in the chemoradiotherapy only group), and anaemia (66 [18%] vs 34 [8%]). Serious adverse events occurred in 107 (30%) in the adjuvant chemotherapy group versus 98 (22%) in the chemoradiotherapy only group, most commonly due to infectious complications. There were no treatment-related deaths. INTERPRETATION: Adjuvant carboplatin and paclitaxel chemotherapy given after standard cisplatin-based chemoradiotherapy for unselected locally advanced cervical cancer increased short-term toxicity and did not improve overall survival; therefore, it should not be given in this setting. FUNDING: National Health and Medical Research Council and National Cancer Institute.

Metasurface-Enhanced Raman Spectroscopy (mSERS) for Oriented Molecular Sensing.

Surface-enhanced Raman spectroscopy (SERS) is a widely used sensing technique for ultrasensitivity chemical sensing, biomedical detection, and environmental analysis. Because SERS signal is proportional to the fourth power of the local electric field, several SERS applications have focused on the design of plasmonic nanogaps to take advantage of the extremely strong near-field enhancement that results from plasmonic coupling, but few designs have focused on how SERS detection is affected by molecular orientation within these nanogaps. Here, we demonstrate a nanoparticle-on-metal metasurface designed for near-perfect optical absorption as a platform for Raman detection of highly oriented molecular analytes, including two-dimensional materials and aromatic molecules. This metasurface platform overcomes challenges in nanoparticle aggregation, which commonly leads to low or fluctuating Raman signals in other colloidal nanoparticle platforms. Our metasurface-enhanced Raman spectroscopy (mSERS) platform is based on a colloidal Langmuir-Schaefer deposition, with up to 32% surface coverage density of nanogaps across an entire sensor chip. In this work, we perform both simulations of the local electric field and experimental characterization of the mSERS signal obtained for oriented molecular layers. We then demonstrate this mSERS platform for the quantitative detection of the drinking-water toxin polybrominated diphenyl ether (BDE-15), with a limit of detection of 0.25 µM under 530 µW excitation. This detection limit is comparable to other SERS-based sensors operating at laser powers over 3 orders of magnitude higher, indicating the promise of our mSERS platform for nondestructive and low-level analyte detection.

Co-doping of iron and copper ions in nanosized bioactive glass by reactive laser fragmentation in liquids.

Bioactive glass (BG) is a frequently used biomaterial applicable in bone tissue engineering and known to be particularly effective when applied in nanoscopic dimensions. In this work, we employed the scalable reactive laser fragmentation in liquids method to produce nanosized 45S5 BG in the presence of light-absorbing Fe and Cu ions. Here, the function of the ions was twofold: (i) increasing the light absorption and thus causing a significant increase in laser fragmentation efficiency by a factor of 100 and (ii) doping the BG with bioactive metal ions up to 4 wt%. Our findings reveal an effective downsizing of the BG from micrometer-sized educts into nanoparticles having average diameters of <50 nm. This goes along with successful element-specific incorporation of the metal ions into the BG, inducing co-doping of Fe and Cu ions as verified by energy-dispersive X-ray spectroscopy (EDX). In this context, the overall amorphous structure is retained, as evidenced by X-ray powder diffraction (XRD). We further demonstrate that the level of doping for both elements can be adjusted by changing the BG/ion concentration ratio during laser fragmentation. Consecutive ion release experiments using inductively-coupled plasma mass spectrometry (ICP-MS) were conducted to assess the potential bioactivity of the doped nanoscopic BG samples, and cell culture experiments using MG-63 osteoblast-like cells demonstrated their cytocompatibility. The elegant method of in situ co-doping of Fe and Cu ions during BG nanosizing may provide functionality-advanced biomaterials for future studies on angiogenesis or bone regeneration, particularly as the level of doping may be adjusted by ion concentrations and ion type in solution.

Thermally conductive ultra-low-k dielectric layers based on two-dimensional covalent organic frameworks.

As the features of microprocessors are miniaturized, low-dielectric-constant (low-k) materials are necessary to limit electronic crosstalk, charge build-up, and signal propagation delay. However, all known low-k dielectrics exhibit low thermal conductivities, which complicate heat dissipation in high-power-density chips. Two-dimensional (2D) covalent organic frameworks (COFs) combine immense permanent porosities, which lead to low dielectric permittivities, and periodic layered structures, which grant relatively high thermal conductivities. However, conventional synthetic routes produce 2D COFs that are unsuitable for the evaluation of these properties and integration into devices. Here, we report the fabrication of high-quality COF thin films, which enable thermoreflectance and impedance spectroscopy measurements. These measurements reveal that 2D COFs have high thermal conductivities (1 W m-1 K-1) with ultra-low dielectric permittivities (k = 1.6). These results show that oriented, layered 2D polymers are promising next-generation dielectric layers and that these molecularly precise materials offer tunable combinations of useful properties.

Visuospatial short-term and working memory disturbance in the primary progressive aphasias: Neuroanatomical and clinical implications.

INTRODUCTION: Primary progressive aphasia (PPA) comprises three main variants: logopenic (lv-PPA), non-fluent (nfv-PPA) and semantic variant (sv-PPA). Differentiating the language profiles of the PPA variants remains challenging, especially for lv-PPA and nfv-PPA. As such, diagnostic tools that do not rely on speech and language may offer some utility. Here, we investigated the short-term and working memory profiles of the PPA variants and typical Alzheimer's disease (AD), with a particular interest in the visuospatial system. We hypothesised visuospatial short-term and working memory would be more compromised in lv-PPA and AD than in the other PPA variants, and that this would relate to degeneration of posterior temporoparietal brain regions. METHOD: Thirty-three lv-PPA, 26 nfv-PPA, 31 sv-PPA and 58 AD patients, and 45 matched healthy controls were recruited. All participants completed the WMS-III Spatial and Digit Span tasks and underwent a structural brain MRI for voxel-based morphometry analyses. RESULTS: Relative to Controls, Spatial Span Forward (SSF) performance was impaired in lv-PPA and AD but not in nfv-PPA or sv-PPA. In contrast, Digit Span Forward (DSF) performance was impaired in lv-PPA and nfv-PPA (to a similar level), and AD, but was relatively intact in sv-PPA. As expected, most backward span scores across both modalities were lower than forward span scores. Neuroimaging analyses revealed that SSF and SSB performance in all patients combined correlated with grey matter intensity decrease in several clusters located in temporo-parieto-occipital brain regions. Post-hoc group comparisons of these regions showed that grey matter loss was more extensive in the lv-PPA and AD groups than in the nfv-PPA and sv-PPA groups. CONCLUSIONS: The findings suggest that the visuospatial short-term and working memory profiles of the PPA variants are separable and likely reflect their distinct patterns of temporo-parieto-occipital brain atrophy.

High-Sensitivity Acoustic Molecular Sensors Based on Large-Area, Spray-Coated 2D Covalent Organic Frameworks.

2D covalent organic frameworks (2D COFs) are a unique materials platform that combines covalent connectivity, structural regularity, and molecularly precise porosity. However, 2D COFs typically form insoluble aggregates, thus limiting their processing via additive manufacturing techniques. In this work, colloidal suspensions of boronate-ester-linked 2D COFs are used as a spray-coating ink to produce large-area 2D COF thin films. This method is synthetically general, with five different 2D COFs prepared as colloidal inks and subsequently spray-coated onto a diverse range of substrates. Moreover, this approach enables the deposition of multiple 2D COF materials simultaneously, which is not possible by polymerizing COFs on substrates directly. When combined with stencil masks, spray-coated 2D COFs are rapidly deposited as thin films larger than 200 cm2 with line resolutions below 50 µm. To demonstrate that this deposition scheme preserves the desirable attributes of 2D COFs, spray-coated 2D COF thin films are incorporated as the active material in acoustic sensors. These 2D-COF-based sensors have a 10 ppb limit-of-quantification for trimethylamine, which places them among the most sensitive sensors for meat and seafood spoilage. Overall, this work establishes a scalable additive manufacturing technique that enables the integration of 2D COFs into thin-film device architectures.

Sustained attention failures on a 3-min reaction time task is a sensitive marker of dementia.

The objective of the study is to determine the utility of a simple reaction time task as a marker of general cognitive decline across the frontotemporal lobar degeneration (FTLD) spectrum and in Alzheimer's disease (AD). One hundred and twelve patients presenting with AD or FTLD affecting behaviour (behavioural-variant frontotemporal dementia), language (progressive non fluent aphasia, logopenic progressive aphasia, semantic dementia) or motor function (corticobasal syndrome, progressive supranuclear palsy, frontotemporal dementia-motor neuron disease) and 25 age-matched healthy controls completed the Psychomotor Vigilance Task (PVT), a 3-min reaction time (RT) task. The proportion of lapses (RT > 500 ms) was significantly increased in dementia patients compared to healthy controls, except for semantic dementia, and correlated with all cognitive functions except language. Discrimination of individuals (dementia patients versus healthy controls) based on the proportion of lapses yielded the highest classification performance (Area Under the Curve, AUC, 0.90) compared to standard neuropsychological tests. Only the complete and lengthy neuropsychological battery had a higher predictive value (AUC 0.96). The basic ability to sustain attention is fundamental to perform any cognitive task. Lapses, interpreted as momentary shifts in goal-directed processing, can therefore, be used as a marker of general cognitive decline indicative of possible dementia.