Dissociative photoionization of phenyl triflate, a photoacid generator for photolithography, at 92 eV.

The dissociative photoionization of phenyl triflate (C6H5OSO2CF3), a neutral photoacid generator used in photolithography, was investigated in a gas phase experiment employing extreme ultraviolet (EUV) synchrotron radiation at 92 eV and photoelectron-photoion coincidence detection. The interaction of EUV photons with the molecule leads almost exclusively to dissociation, which is dominated by a sequential fragmentation mechanism, in which SO2, CF3, CO, and C2H2 are lost. For lithographic purposes, the lack of the observation of a fragment that could serve as a precursor for the formation of triflic acid means that the effective photoacid generator concentration in a photoresist is reduced, impacting its patterning performance in EUV lithography. A better understanding of the dissociative photoionization of photoresist components and proxies thereof can provide a crucial handle that guides the design of photoresists for the upcoming technology nodes with ever decreasing feature sizes for more powerful computer chips.

Efficient Indirect Interatomic Coulombic Decay Induced by Photoelectron Impact Excitation in Large Pure Helium Nanodroplets.

Ionization of matter by energetic radiation generally causes complex secondary reactions that are hard to decipher. Using large helium nanodroplets irradiated by extreme ultraviolet (XUV) photons, we show that the full chain of processes ensuing primary photoionization can be tracked in detail by means of high-resolution electron spectroscopy. We find that elastic and inelastic scattering of photoelectrons efficiently induces interatomic Coulombic decay (ICD) in the droplets. This type of indirect ICD even becomes the dominant process of electron emission in nearly the entire XUV range in large droplets with radius ≳40 nm. Indirect ICD processes induced by electron scattering likely play an important role in other condensed-phase systems exposed to ionizing radiation as well, including biological matter.

Complete Genome Sequence of an Escherichia coli Strain Isolated from Laboratory Mouse Stool for Use as a Chassis for Transgene Delivery to the Murine Microbiome.

Tools to explore functional changes in the microbiome are limited. Here, we report the complete genome sequence of a strain of Escherichia coli that was isolated from murine stool. This sequence will provide essential information to further develop this tool, and similar tools, to explore the complex murine microbiome.

Electron and ion spectroscopy of azobenzene in the valence and core shells.

Azobenzene is a prototype and a building block of a class of molecules of extreme technological interest as molecular photo-switches. We present a joint experimental and theoretical study of its response to irradiation with light across the UV to x-ray spectrum. The study of valence and inner shell photo-ionization and excitation processes combined with measurement of valence photoelectron-photoion coincidence and mass spectra across the core thresholds provides a detailed insight into the site- and state-selected photo-induced processes. Photo-ionization and excitation measurements are interpreted via the multi-configurational restricted active space self-consistent field method corrected by second order perturbation theory. Using static modeling, we demonstrate that the carbon and nitrogen K edges of azobenzene are suitable candidates for exploring its photoinduced dynamics thanks to the transient signals appearing in background-free regions of the NEXAFS and XPS.

Core-shell excitation of isoxazole at the C, N, and O K-edges - an experimental NEXAFS and theoretical TD-DFT study.

The near-edge X-ray absorption fine structure (NEXAFS) spectra of the gas-phase isoxazole molecule have been measured by collecting total ion yields at the C, N, and O K-edges. The spectral structures have been interpreted using time-dependent density functional theory (TD-DFT) with the short-range corrected SRC2-BLYP exchange-correlation functional. Experimental and calculated energies of core excitations are generally in good agreement, and the nature of observed core-excitation transitions has been elucidated. The experimental C 1s, N 1s, and O 1s core electron binding energies (CEBEs) have additionally been estimated from another yield measurement where the neutral fragments in high-Rydberg (HR) states were ionized by the electric field. For comparison, theoretical CEBEs have been calculated at the ΔM06-2X//mixed basis set level. We have also calculated the vibrationally resolved spectra pertaining to the lowest C 1s and N 1s core-excited roots in the Franck-Condon-Herzberg-Teller (FCHT) approximation. These spectra correlate well with the observed spectral features and have proven useful in resolving certain ambiguities in the assignment of the low-lying C 1s NEXAFS bands.

Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes.

Live bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e., chassis) have difficulty in colonizing the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli bacteria isolated from the stool cultures of CR mice were modified to express functional genes. The reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E. coli can induce functional changes that affect physiology of and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to "knock in" specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts and enables LBT with curative intent.

Diet and feeding pattern modulate diurnal dynamics of the ileal microbiome and transcriptome.

Compositional oscillations of the gut microbiome are essential for normal peripheral circadian rhythms, both of which are disrupted in diet-induced obesity (DIO). Although time-restricted feeding (TRF) maintains circadian synchrony and protects against DIO, its impact on the dynamics of the cecal gut microbiome is modest. Thus, other regions of the gut, particularly the ileum, the nexus for incretin and bile acid signaling, may play an important role in entraining peripheral circadian rhythms. We demonstrate the effect of diet and feeding rhythms on the ileal microbiome composition and transcriptome in mice. The dynamic rhythms of ileal microbiome composition and transcriptome are dampened in DIO. TRF partially restores diurnal rhythms of the ileal microbiome and transcriptome, increases GLP-1 release, and alters the ileal bile acid pool and farnesoid X receptor (FXR) signaling, which could explain how TRF exerts its metabolic benefits. Finally, we provide a web resource for exploration of ileal microbiome and transcriptome circadian data.

Fragmentation dynamics of doubly charged camphor molecule following C 1s Auger decay.

The fragmentation dynamics of the gas-phase, doubly charged camphor molecule, formed by Auger decay following carbon 1s ionisation, using soft X-ray synchrotron radiation, is presented in this work. The technique of velocity map imaging combined with a photoelectron-photoion-photoion coincidence (VMI-PEPIPICO) is used for both electron energy and ion momentum (in-sequence) measurements. The experimental study is complemented by molecular dynamics simulation, performed with an NVT (moles, volume, and temperature) ensemble. Velocity Verlet algorithms were used for time integration at various internal energies. These simulations validate observed dissociation pathways. From these, we successfully deduce that the internal energy of the doubly charged molecular ion has a significant contribution to the fragmentation mechanism. Notably, a prominent signature of the internal energy was observed in the experimentally determined energies of the neutral fragment in these deferred charge separation pathways, entailing a more detailed theoretical study to uncover the exact dissociation dynamics.

Revealing the electronic properties of the B-B bond: the bis-catecholato diboron molecule.

The electronic properties of a diboron molecule, namely bis(catecholato)diboron (2-(1,3,2-benzodioxaborol-2-yl)-1,3,2-benzodioxaborole) (B2Cat2), have been studied by comparing the results of photoemission (XPS) and near edge X-ray absorption spectroscopy (NEXAFS) experiments with the outcome of DFT calculations. The B 1s, C 1s and O 1s K-edges have been investigated for both the isolated gas phase molecule and the adsorbed one on the Au(111) surface. The main features of the polarized NEXAFS spectra at each of the three edges considered are not significantly affected by the presence of the substrate, with respect to the isolated molecule, indicating that the molecule-gold interaction is weak. Moreover, the comparison between the observed dichroism in the NEXAFS spectra of the adsorbed B2Cat2 and that in the NEXAFS spectra of the isolated molecule has confirmed the orbital symmetry assigned in the gas phase absorption spectra. The transitions to π(B-B) bonding and π*(B-B) anti-bonding final states represent the most relevant probe of the chemistry of the B2Cat2 molecule. We show that their theoretical description requires that the treatment of the relaxation changes among different excited state configurations, which we successfully implemented by using ΔSCF-DFT (ΔSCF) calculations.

Influence of migrant background on patient preference and expectations in breast and gynecological malignancies (NOGGO-expression V study): results of a prospective multicentre study in 606 patients in Germany.

BACKGROUND: An effective cross-cultural doctor-patient communication is vital for health literacy and patient compliance. Building a good relationship with medical staff is also relevant for the treatment decision-making process for cancer patients. Studies about the role of a specific migrant background regarding patient preferences and expectations are lacking. We therefore conducted a multicentre prospective survey to explore the needs and preferences of patients with a migrant background (PMB) suffering from gynecological malignancies and breast cancer to evaluate the quality of doctor-patient communication and cancer management compared to non-migrants (NM). METHODS: This multicentre survey recruited patients with primary or recurrence of breast, ovarian, peritoneal, or fallopian tube cancer. The patients either filled out a paper form, participated via an online survey, or were interviewed by trained staff. A 58-item questionnaire was primarily developed in German and then translated into three different languages to reach non-German-speaking patients. RESULTS: A total of 606 patients were included in the study: 54.1% (328) were interviewed directly, 9.1% (55) participated via an online survey, and 36.8% (223) used the paper print version. More than one quarter, 27.4% (166) of the participants, had a migrant background. The majority of migrants and NM were highly satisfied with the communication with their doctors. First-generation migrants (FGM) and patients with breast cancer were less often informed about participation in clinical trials (p < 0.05) and 24.5% of them suggested the help of an interpreter to improve the medical consultation. Second and third-generation migrants (SGM and TGM) experienced more fatigue and nausea than expected. CONCLUSIONS: Our results allow the hypothesis that training medical staff in intercultural competence and using disease-related patient information in different languages can improve best supportive care management and quality of life in cancer patients with migrant status.

Impact of health-related quality of life (HRQoL) on short-term mortality in patients with recurrent ovarian, fallopian or peritoneal carcinoma (the NOGGO-AGO QoL Prognosis-Score-Study): results of a meta-analysis in 2209 patients.

OBJECTIVE: Recurrent ovarian cancer is an incurable disease with variable but poor prognosis. Health-related quality of life (HRQoL) is a patient-reported outcome measure generally applied to measure effects of therapies. Our aim was the development and validation of a risk score for the prediction of short-term mortality using the combination of sociodemographic and clinical factors and HRQoL. METHODS: For exploratory and validation analysis, the North-Eastern German Society of Gynecological Oncology (NOGGO) and Working Group Gynecological Oncology (AGO) study databases were screened for trials. Only trials which obtained defined HRQoL measurements were included in the final analysis. Multivariable logistic regression analyses were used to identify risk factors and their weighting for the risk score. Modulation with cubic regression analyses revealed median survival and short-term mortality defined as 1-year mortality for each value. RESULTS: For exploration, 974 patients from three clinical studies of the NOGGO and for validation, 1235 patients from several clinical studies of the AGO were eligible. The risk score included platinum-free interval, performance status, age, global QoL and nausea/vomiting. Receiver operating characteristic analysis showed a good predictive value with an area under the curve of 0.81 for model 1 in the exploration and 0.74 in the validation. Short-term mortality in model 1 was 8.2%, 23.5% and 58.4% in the exploration sample, and 19.7%, 38.1% and 63.4% in the validation sample for patients under low, medium and high risk, respectively. CONCLUSIONS: This risk score discriminates well between recurrent ovarian cancer patients under low, medium and high risk of short-term mortality. It may help to identify a risk group under high risk for short-term mortality that can be used for randomization in clinical trials and may support decision making for palliative chemotherapy.

Coincident angle-resolved state-selective photoelectron spectroscopy of acetylene molecules: a candidate system for time-resolved dynamics.

The acetylene-vinylidene system serves as a benchmark for investigations of ultrafast dynamical processes where the coupling of the electronic and nuclear degrees of freedom provides a fertile playground to explore the femto- and sub-femto-second physics with coherent extreme-ultraviolet (EUV) photon sources both on the table-top as well as free-electron lasers. We focus on detailed investigations of this molecular system in the photon energy range 19-40 eV where EUV pulses can probe the dynamics effectively. We employ photoelectron-photoion coincidence (PEPICO) spectroscopy to uncover hitherto unrevealed aspects of this system. In this work, the role of excited states of the C2H2+ cation, the primary photoion, is specifically addressed. From photoelectron energy spectra and angular distributions, the nature of the dissociation and isomerization channels is discerned. Exploiting the 4π-collection geometry of the velocity map imaging spectrometer, we not only probe pathways where the efficiency of photoionization is inherently high but also perform PEPICO spectroscopy on relatively weak channels.

Genetic diversity of clinical and environmental Mucorales isolates obtained from an investigation of mucormycosis cases among solid organ transplant recipients.

Mucormycoses are invasive infections by Rhizopus species and other Mucorales. Over 10 months, four solid organ transplant (SOT) recipients at our centre developed mucormycosis due to Rhizopus microsporus (n=2), R. arrhizus (n=1) or Lichtheimia corymbifera (n=1), at a median 31.5 days (range: 13-34) post-admission. We performed whole genome sequencing (WGS) on 72 Mucorales isolates (45 R. arrhizus, 19 R. delemar, six R. microsporus, two Lichtheimia species) from these patients, from five patients with community-acquired mucormycosis, and from hospital and regional environments. Isolates were compared by core protein phylogeny and global genomic features, including genome size, guanine-cytosine percentages, shared protein families and paralogue expansions. Patient isolates fell into six core phylogenetic lineages (clades). Phylogenetic and genomic similarities of R. microsporus isolates recovered 7 months apart from two SOT recipients in adjoining hospitals suggested a potential common source exposure. However, isolates from other patients and environmental sites had unique genomes. Many isolates that were indistinguishable by core phylogeny were distinct by one or more global genomic comparisons. Certain clades were recovered throughout the study period, whereas others were found at particular time points. In conclusion, mucormycosis cases could not be genetically linked to a definitive environmental source. Comprehensive genomic analyses eliminated false associations between Mucorales isolates that would have been assigned using core phylogenetic or less extensive genomic comparisons. The genomic diversity of Mucorales mandates that multiple isolates from individual patients and environmental sites undergo WGS during epidemiological investigations. However, exhaustive surveillance of fungal populations in a hospital and surrounding community is probably infeasible.

Penning spectroscopy and structure of acetylene oligomers in He nanodroplets.

Embedded atoms or molecules in a photoexcited He nanodroplet are well-known to be ionized through inter-atomic relaxation in a Penning process. In this work, we investigate the Penning ionization of acetylene oligomers occurring from the photoexcitation bands of He nanodroplets. In close analogy to conventional Penning electron spectroscopy by thermal atomic collisions, the n = 2 photoexcitation band plays the role of the metastable atomic 1s2s 3,1S He*. This facilitates electron spectroscopy of acetylene aggregates in the sub-Kelvin He environment, providing the following insight into their structure: the molecules in the dopant cluster are loosely bound van der Waals complexes rather than forming covalent compounds. In addition, this work reveals a Penning process stemming from the n = 4 band where charge-transfer from autoionized He in the droplets is known to be the dominant relaxation channel. This allows for excited states of the remnant dopant oligomer Penning-ions to be studied. Hence, we demonstrate Penning ionization electron spectroscopy of doped droplets as an effective technique for investigating dopant oligomers which are easily formed by attachment to the host cluster.

Electron transfer mediated decay of alkali dimers attached to He nanodroplets.

Alkali metal dimers attached to the surface of helium nanodroplets are found to be efficiently doubly ionized by electron transfer mediated decay (ETMD) when photoionizing the helium droplets. This process is evidenced by detecting in coincidence two energetic ions created by Coulomb explosion and one low-kinetic energy electron. The kinetic energy spectra of ions and electrons are reproduced by simple model calculations based on diatomic potential energy curves, and are in agreement with ab initio calculations for the He-Na2 and He-KRb systems. This work demonstrates that ETMD is an important decay channel in heterogeneous nanosystems exposed to ionizing radiation.

Methylcellulose - a versatile printing material that enables biofabrication of tissue equivalents with high shape fidelity.

With the aid of biofabrication, cells can be spatially arranged in three dimensions, which offers the opportunity to guide tissue maturation in a better way compared to traditional tissue engineering approaches. A prominent technique allowing biofabrication of tissue equivalents is extrusion-based 3D (bio)printing, also called 3D (bio)plotting or robocasting, which comprises cells embedded in the biomaterial (bioink) during the fabrication process. First bioprinting studies introduced bioinks allowing either good cell viability or good shape fidelity. Concepts enabling printing of cell-laden constructs with high shape fidelity were developed only rarely. Recent studies showed the great potential of the polysaccharide methylcellulose (mc) as supportive biomaterial that can be utilized in various ways to enable biofabrication and especially extrusion-based bioprinting of bioinks. This minireview highlights the multiple applications of mc for biofabrication: it was successfully used as sacrificial ink to enable 3D shaping of cell sheets or biomaterial inks as well as as internal stabilizing component of various bioinks. Moreover, a brief overview about first bioprinted functional tissue equivalents is given, which have been fabricated by using mc. Based on these studies, future research should consider mc as an auxiliary material for bioinks and biofabricated constructs with high shape fidelity.

Ultrafast relaxation of photoexcited superfluid He nanodroplets.

The relaxation of photoexcited nanosystems is a fundamental process of light-matter interaction. Depending on the couplings of the internal degrees of freedom, relaxation can be ultrafast, converting electronic energy in a few fs, or slow, if the energy is trapped in a metastable state that decouples from its environment. Here, we study helium nanodroplets excited resonantly by femtosecond extreme-ultraviolet (XUV) pulses from a seeded free-electron laser. Despite their superfluid nature, we find that helium nanodroplets in the lowest electronically excited states undergo ultrafast relaxation. By comparing experimental photoelectron spectra with time-dependent density functional theory simulations, we unravel the full relaxation pathway: Following an ultrafast interband transition, a void nanometer-sized bubble forms around the localized excitation (He[Formula: see text]) within 1 ps. Subsequently, the bubble collapses and releases metastable He[Formula: see text] at the droplet surface. This study highlights the high level of detail achievable in probing the photodynamics of nanosystems using tunable XUV pulses.

Prognostic role of chemotherapy-induced nausea and vomiting in recurrent ovarian cancer patients: results of an individual participant data meta-analysis in 1213.

BACKGROUND: The aim of this study was to analyze the potential impact of chemotherapy-induced nausea and vomiting (CINV) on dose reductions, discontinuation of chemotherapy, and survival. PATIENTS AND METHODS: This study was designed as individual participant data meta-analysis with the original study data of three phase II/III trials that were conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) including 1213 patients with recurrent ovarian cancer. Logistic and Cox regression analyses were used to estimate odds and hazard ratios after adjusting for age, ECOG, amount of delivered cycles, amount of recurrences, and amount of comedications and study. RESULTS: The majority of patients developed nausea (58.1%) and almost one third experienced vomiting (31.0%). CINV was not associated with FIGO stage, grading, histology, and number of recurrences. The necessity of dose reduction and discontinuation of chemotherapy did not correlate to nausea and vomiting (p = 0.88, p = 0.39 and p = 0.25, p = 0.54 respectively). Progression-free survival was shorter in patients with grade III/IV nausea and vomiting (p = 0.02; hazard ratio (HR) for grade III/IV nausea 1.58, 95% CI 1.14-2.20, and p = 0.02; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CINV grade III/IV was also associated with poorer overall survival (p < 0.001; HR for grade III/IV nausea 2.35, 95% CI 1.64-3.37, and p < 0.001; HR for grade III/IV vomiting 1.67, 95% CI 1.15-2.42 respectively). CONCLUSION: CINV is significantly associated with poorer prognosis in recurrent ovarian cancer patients while there was no correlation found with the necessity of dose reduction and prior discontinuation of treatment. This study underlines the importance of prevention and treatment of CINV as part of early best supportive care.

The prognostic and predictive role of pain before systemic chemotherapy in recurrent ovarian cancer: an individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO) of 1226 patients.

BACKGROUND: Aim of this study was to analyze the impact of pain on quality of life and survival in recurrent OC patients. METHODS: Raw data including the QLQ-C30 questionnaire from three phase II/III trials ("Topotecan phase III," "Hector," and "TRIAS") conducted by the North-Eastern German Society of Gynecological Oncology (NOGGO) were synthesized and analyzed using logistic and Cox regression analyses. RESULTS: Data on pain was available for 952 patients out of 1226. Moderate to severe pain, which was defined as pain ≥ 50 in the QLQ-C30 symptom scale, was experienced by more than one-third of patients (36.6%). A total of 31% were taking non-opioid pain medication and 16% opioids. Median age at randomization was 61 years (range 25-84). Most patients (84.7%) were diagnosed in FIGO III/IV. Pain was independent from age, FIGO stage, grading, amount of recurrences, and chemotherapy-free interval. ECOG was significantly worse in patients with pain (p < 0.001). Fatigue, nausea/vomiting, sleeping disorders, and abdominal symptoms such as loss of appetite, diarrhea, and constipation were more frequently found in patients with pain (all p < 0.001). Quality of life was significantly diminished (p < 0.001). Pain was also an independent marker for overall survival (OS). Median OS was 18.2 months in patients with pain compared with 22.0 months in patients without pain (p = 0.013, HR 1.25, 95% confidence interval 1.05-1.48). OS was shorter in patients with pain and without pain medication compared with those on sufficient pain medication, whereas OS was mostly decreased in patients having pain despite pain medication (18.5, 19.6, and 15.0 months respectively; p = 0.026). Progression-free survival and prior treatment discontinuation were not associated with pain. CONCLUSION: Best supportive care including sufficient pain medication should be delivered as early as possible because effective pain management is crucial for both quality of life and overall survival in patients with recurrent ovarian cancer.