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Terrestrial Laser Scanning (TLS) greatly facilitates the acquisition of detailed and accurate 3D measurements of remote rock outcrops, at an operational range from several meters to a few kilometres. Reliable, quantitative measures of rock discontinuity roughness are necessary to characterize and evaluate the mechanical and hydraulic behavior of the rock mass. The aim of this research is to investigate the TLS potential and limitations for a reliable estimation of small scale roughness. TLS data noise and resolution define the level of extractable morphological detail, and therefore need to be known and associated with roughness value. The stationary variant of Discrete Wavelet Transform (SWT) was applied to estimate TLS noise level and perform wavelet denoising in direction of range measurements. Denoised TLS data were compared to reference surfaces of decreasing resolution (reference grids) in order to define the size of extractable surface detail. Noise and resolution effect on rock surface roughness, wavelet denoising success and extractable roughness scale were investigated with comparative analyses of TLS and reference surfaces. The developed methodology enabled reasonable TLS noise estimation, improved capabilities of TLS for modelling fine features of an irregular rock surface, and indicated the surface scale that can be reliably extracted from the TLS data.

Terrestrial Laser Scanning (TLS) is a well-known remote sensing tool that enables precise 3D acquisition of surface morphology from distances of a few meters to a few kilometres. The morphological representations obtained are important in engineering geology and rock mechanics, where surface morphology details are of particular interest in rock stability problems and engineering construction. The actual size of the discernible surface detail depends on the instrument range error (noise effect) and effective data resolution (smoothing effect). Range error can be (partly) removed by applying a denoising method. Based on the positive results from previous studies, two denoising methods, namely 2D wavelet transform (WT) and non-local mean (NLM), are tested here, with the goal of obtaining roughness estimations that are suitable in the context of rock engineering practice. Both methods are applied in two variants: conventional Discrete WT (DWT) and Stationary WT (SWT), classic NLM (NLM) and probabilistic NLM (PNLM). The noise effect and denoising performance are studied in relation to the TLS effective data resolution. Analyses are performed on the reference data acquired by a highly precise Advanced TOpometric Sensor (ATOS) on a 20x30 cm rock joint sample. Roughness ratio is computed by comparing the noisy and denoised surfaces to the original ATOS surface. The roughness ratio indicates the success of all denoising methods. Besides, it shows that SWT oversmoothes the surface and the performance of the DWT, NLM and PNLM vary with the noise level and data resolution. The noise effect becomes less prominent when data resolution decreases.

The precision of Terrestrial Laser Scanning (TLS) data depends mainly on the inherent random range error, which hinders extraction of small details from TLS measurements. New post processing algorithms have been developed that reduce or eliminate the noise and therefore enable modelling details at a smaller scale than one would traditionally expect. The aim of this research is to find the optimum denoising method such that the corrected TLS data provides a reliable estimation of small-scale rock joint roughness. Two wavelet-based denoising methods are considered, namely Discrete Wavelet Transform (DWT) and Stationary Wavelet Transform (SWT), in combination with different thresholding procedures. The question is, which technique provides a more accurate roughness estimates considering (i) wavelet transform (SWT or DWT), (ii) thresholding method (fixed-form or penalised low) and (iii) thresholding mode (soft or hard). The performance of denoising methods is tested by two analyses, namely method noise and method sensitivity to noise. The reference data are precise Advanced TOpometric Sensor (ATOS) measurements obtained on 20 × 30 cm rock joint sample, which are for the second analysis corrupted by different levels of noise. With such a controlled noise level experiments it is possible to evaluate the methods’ performance for different amounts of noise, which might be present in TLS data. Qualitative visual checks of denoised surfaces and quantitative parameters such as grid height and roughness are considered in a comparative analysis of denoising methods. Results indicate that the preferred method for realistic roughness estimation is DWT with penalised low hard thresholding.

Interleukin (IL)-1 family cytokines are essential for host defense at epithelial barriers. The IL-1 family member IL-33 was recently linked to stress granules (SGs). Formation of SGs and other biomolecular condensates is promoted by proteins containing low-complexity regions (LCRs). Computational analysis predicts LCRs in six of the 11 IL-1 family members. Among these, IL-38 contains a long LCR including two amyloid cores. IL-38 localizes to intracellular granules in keratinocytes under oxidative stress (OS) and forms OS-induced amyloid aggregates in cells and in vitro. Interestingly, soluble and aggregated IL-38 are released from keratinocytes in an exosome-enriched extracellular vesicle fraction. Disulfide-bond mapping, in silico modeling, and mutational analysis suggest that oxidation-sensitive cysteines act as redox switches to alter IL-38 conformation and promote its aggregation. Finally, the presence of IL-38 granules in human epidermis facing environmental OS suggests that oxidation-induced amyloidogenesis, as an intrinsic property of IL-38, supports barrier function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

(1) Background: Long-term health effects after SARS-CoV-2 infections can manifest in a plethora of symptoms, significantly impacting the quality of life of affected individuals. (2) Aim: The present paper aimed to assess the effects of an individualized and controlled exercise intervention on fatigue and exercise capacity among Long-COVID (LC) patients in an ambulatory setting. (3) Methods: Forty-one (n = 41) LC patients performed an exercise protocol with an individualized control of the patients' training intensity during the study period based on the individual's ability to achieve the target criteria. The program was carried out two to three times a week, each session lasted 30 min, and the study parameters were recorded at the beginning of the program, as well as after 6 and 12 weeks, respectively. These included both patient-reported (PCFS questionnaire, FACIT-Fatigue questionnaire) and objective (one-minute sit-to-stand test (1MSTST), workload) outcomes. (4) Results: The exercise training intervention resulted in significant improvements in the FACIT-Fatigue (F(2, 80) = 18.08, p < 0.001), 1MSTST (χ2(2) = 19.35, p < 0.001) and workload scores (χ2(2) = 62.27, p < 0.001), while the PCFS scores remained unchanged. Changes in the workload scores were dependent on the frequency of the completed exercise sessions and were higher in the LC patients with a moderate Post COVID Syndrome Score (PCS) compared to a severe PCS. (5) Conclusions: The individualized and controlled training approach demonstrated efficacy in reducing fatigue and enhancing exercise capacity among outpatient LC patients. However, for complete regeneration, a longer, possibly indefinite, treatment is required, which in practice would be feasible within the framework of legislation.

Numerous neurosurgical (NSG) conditions entail high morbidity, mortality, and prolonged ICU stays. Palliative care (PC) serves to alleviate suffering, align treatment with patient preferences, and is linked to enhanced patient and family outcomes as well as reduced care costs. Notably, no studies have addressed demographic and clinical factors associated with PC receipt in NSG patients. Our aim is to identify characteristics and outcomes, particularly end of life outcomes, of hospitalized NSG patients associated with a PC consult compared with usual NSG care. A retrospective chart review was performed of patients admitted to the NSG service from January 1, 2017 to December 31, 2018 at the University of Iowa Hospitals & Clinics. Data regarding demographics, clinical outcomes, and GOC and ACP documentation were collected. The most common reasons for a PC consult were goals of care, end of life issues, and comfort care. Of 121 total decedent patients, 97 (80.2%) had PC referrals. Patients with a PC referral had longer hospital stays (10.3 days vs 4 days) and had the majority of care in the ICU (90.7% vs 83.3%). However, fewer PC patients died in the ICU (42.3% vs 75%) and more had PCA/NCA use (51.5% vs 8.3%), code status changes to DNR (90.7% vs 62.5%), GOC documented (78.4% vs 0%) and ACP documentation (35.1% vs 16.7%). In conclusion, in NSG patients, the integration of PC may contribute to improved end-of-life care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Supportive oncology (SO) care reduces symptom severity, admissions, and costs in patients with advanced cancer. This study examines the impact of SO care on utilization and costs., Methods: Retrospective analysis of utilization and costs comparing patients enrolled in SO versus three comparison cohorts who did not receive SO. Using claims, the authors estimated differences in health care utilization and cost between the treatment group and comparison cohorts. The treatment group consisting of patients treated for cancer at an National Cancer Institute-designated cancer center who received SO between January 2018 and December 2019 were compared to an asynchronous cohort that received cancer care before January 2018 (n = 60), a contemporaneous cohort with palliative care receiving SO care from other providers in the Southeastern Pennsylvania region during the program period (n = 86), and a contemporaneous cohort without palliative care consisting of patients at other cancer centers who were eligible for but did not receive SO care (n = 393)., Results: At 30, 60, and 90 days post-enrollment into SO, the treatment group had between 27% and 70% fewer inpatient admissions and between 16% and 54% fewer emergency department visits (p < .05) compared to non-SO cohorts. At 90 days following enrollment in SO care, total medical costs were between 4.4% and 24.5% lower for the treatment group across all comparisons (p < .05)., Conclusions: SO is associated with reduced admissions, emergency department visits, and total costs in advanced cancer patients. Developing innovative reimbursement models could be a cost-effective approach to improve care of patients with advanced cancer., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Introduction: Each individual touches the own body several 100 times a day. While some researchers propose a self-regulatory function of self-touch, others report that self-touching increases nervousness. This controversy appears to be caused by the fact that researchers did not define the kind of self-touch they examined and actually, referred to different types of self-touch. Thus, kinematically defining different types of self-touch, such as phasic (discrete), repetitive , and irregular , and exploring the neural correlates of the different types will provide insight into the neuropsychological function of self-touching behavior., Methods: To this aim, we assessed hemodynamic responses in prefrontal brain areas using functional near-infrared spectroscopy (fNIRS) and behavioral responses with NEUROGES®. Fifty-two participants were recorded during three specific kinematically types of self-touch ( phasic, irregular, repetitive ) that were to be performed on command. The recently developed toolbox Satori was used for the visualization of neuronal processes., Results: Behaviorally, the participants did not perform irregular self-touch reliably. Neurally, the comparison of phasic, irregular and repetitive self-touch revealed different activation patterns. Repetitive self-touch is associated with stronger hemodynamic responses in the left Orbitofrontal Cortex and the Dorsolateral Prefrontal Cortex than phasic self-touch., Discussion: These brain areas have been reported to be associated with self-regulatory processes. Furthermore, irregular self-touch appears to be primarily generated by implicit neural control. Thus, by distinguishing kinematically different types of self-touch, our findings shed light on the controverse discussion on the neuropsychological function of self-touch., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 von Au, Helmich, Kieffer and Lausberg.)

In a scenario where the discovery of new molecules to fight antibiotic resistance is a public health concern, ribosomally synthesized and post-translationally modified peptides constitute a promising alternative. In this context, the Gram-positive human gut symbiont Ruminococcus gnavus E1 produces five sactipeptides, Ruminococcins C1 to C5 (RumC1-C5), co-expressed with two radical SAM maturases. RumC1 has been shown to be effective against various multidrug resistant Gram-positives clinical isolates. Here, after adapting the biosynthesis protocol to obtain the four mature RumC2-5 we then evaluate their antibacterial activities. Establishing first that both maturases exhibit substrate tolerance, we then observed a variation in the antibacterial efficacy between the five isoforms. We established that all RumCs are safe for humans with interesting multifunctionalities. While no synergies where observed for the five RumCs, we found a synergistic action with conventional antibiotics targeting the cell wall. Finally, we identified crucial residues for antibacterial activity of RumC isoforms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (© 2023 The Author(s).)

The automotive industry is working toward driving automation and driver-assistance technology is becoming a norm in modern cars. Warning alert systems support the driver-car interaction and inform drivers about automation system status, upcoming obstacles, or dangers ahead. However, older drivers' needs are not always addressed in research studies, although they make up a large segment of drivers. Therefore, we conducted a qualitative three-round formative evaluation of a warning alert system using video prototypes in lab and remote settings. The goal was to evaluate visual-, sound-, and speech-based alerts based on: (a) their efficiency in informing drivers about the road situation ahead, and (b) participants' subjective opinions. We evaluated the system's efficiency using self-reported data measuring participants' cognitive load, usability, UX, and ease of use. Also, we conducted interviews to collect subjective feedback about proposed prototypes. In this article, we describe the design of warning alerts and report on their evaluation results. Our results show that speech-based warnings, especially when coupled with visual warnings, are efficient and accepted well by the participants. This article illustrates older drivers' attitude toward the use of different warning modalities in the driving context., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

RNA polymerases (RNAPs) are found in all living organisms. In the chloroplasts, the plastid-encoded RNA polymerase (PEP) is a prokaryotic-type multimeric RNAP involved in the selective transcription of the plastid genome. One of its active states requires the assembly of nuclear-encoded PEP-Associated Proteins (PAPs) on the catalytic core, producing a complex of more than 900 kDa, regarded as essential for chloroplast biogenesis. In this study, sequence alignments of the catalytic core subunits across various chloroplasts of the green lineage and prokaryotes combined with structural data show that variations are observed at the surface of the core, whereas internal amino acids associated with the catalytic activity are conserved. A purification procedure compatible with a structural analysis was used to enrich the native PEP from Sinapis alba chloroplasts. A mass spectrometry (MS)-based proteomic analysis revealed the core components, the PAPs and additional proteins, such as FLN2 and pTAC18. MS coupled with crosslinking (XL-MS) provided the initial structural information in the form of protein clusters, highlighting the relative position of some subunits with the surfaces of their interactions. Using negative stain electron microscopy, the PEP three-dimensional envelope was calculated. Particles classification shows that the protrusions are very well-conserved, offering a framework for the future positioning of all the PAPs. Overall, the results show that PEP-associated proteins are firmly and specifically associated with the catalytic core, giving to the plastid transcriptional complex a singular structure compared to other RNAPs.

Well-organized protein assemblies offer many properties that justify their use for the design of innovative bionanomaterials. Herein, crystals of the oligomerization domain of the LEAFY protein from Ginkgo biloba, organized in a honeycomb architecture, were used as a modular platform for the selective grafting of a ruthenium-based complex. The resulting bio-hybrid crystalline material was fully characterized by UV-visible and Raman spectroscopy and by mass spectrometry and LC-MS analysis after selective enzymatic digestion. Interestingly, insertion of complexes within the tubular structure affords an impressive increase in stability of the crystals, eluding the use of stabilizing cross-linking strategies.

(1) Background: The proteomic analysis of histones constitutes a delicate task due to the combination of two factors: slight variations in the amino acid sequences of variants and the multiplicity of post-translational modifications (PTMs), particularly those occurring on lysine residues. (2) Methods: To dissect the relationship between both aspects, we carefully evaluated PTM identification on lysine 27 from histone H3 (H3K27) and the artefactual chemical modifications that may lead to erroneous PTM determination. H3K27 is a particularly interesting example because it can bear a range of PTMs and it sits nearby residues 29 and 31 that vary between H3 sequence variants. We discuss how the retention times, neutral losses and immonium/diagnostic ions observed in the MS/MS spectra of peptides bearing modified lysines detectable in the low-mass region might help validate the identification of modified sequences. (3) Results: Diagnostic ions carry key information, thereby avoiding potential mis-identifications due to either isobaric PTM combinations or isobaric amino acid-PTM combinations. This also includes cases where chemical formylation or acetylation of peptide N-termini artefactually occurs during sample processing or simply in the timeframe of LC-MS/MS analysis. Finally, in the very subtle case of positional isomers possibly corresponding to a given mass of lysine modification, the immonium and diagnostic ions may allow the identification of the in vivo structure.

Background: Global health systems are shifting toward value-based health care to improve patient outcomes in the face of rising health care costs. The challenge is to identify standardized outcome measurements that allow optimal quality-of-care monitoring and comparison to optimize medical practices and patient pathways. A common outcomes definition is required, including medical results (Clinical Reported Outcomes Measurements [CROMs]) and quality-of-life components that matter most to patients (Patient-Reported Outcomes Measurements [PROMs]), which are particularly important for severe pathologies with short life expectancy such as pancreatic cancer. This study aimed to create standardized metrics that could be used for outcomes analysis of pancreatic cancer care., Methods: A multidisciplinary working group (WG) was assembled. A systematic review was performed to collect the most used outcomes in clinical studies of pancreatic cancers. The study reviewed 570 studies published in the last 10 years. From these studies, 3370 outcomes, including CROMs, and PROMs, were listed and prioritized. The WG reached a consensus on key outcomes, proposed groupings for CROMs and PROMs, identified existing questionnaires that could be used for PROMs collection, and set the timeline for data collection. To refine and validate the final outcomes set, an international external committee completed a Delphi process (two rounds for both CROMS and PROMs)., Results: After the systematic literature review, the WG selected 102 outcomes (92 CROMs and 10 PROMs) for submission to the international Delphi vote committee. The committee retrained 89 outcomes (78 CROMs and 11 PROMs). For the PROMs, the WG and the international external committee chose a validated questionnaire, the Functional Assessment of Cancer Therapy-Hepatobiliary, which covers all of the 11 selected PROMs., Conclusions: A standardized set of outcome measures that need to be validated through international health outcome comparisons and quality-of-care assessments was built. Pilot projects are underway to test and optimize the approach in real-life conditions.

Pectin is synthesized in a highly methylesterified form in the Golgi cisternae and partially de-methylesterified in muro by pectin methylesterases (PMEs). Arabidopsis thaliana produces a local and strong induction of PME activity during the infection of the necrotrophic fungus Botrytis cinerea. AtPME17 is a putative A. thaliana PME highly induced in response to B. cinerea. Here, a fine tuning of AtPME17 expression by different defence hormones was identified. Our genetic evidence demonstrates that AtPME17 strongly contributes to the pathogen-induced PME activity and resistance against B. cinerea by triggering jasmonic acid-ethylene-dependent PDF1.2 expression. AtPME17 belongs to group 2 isoforms of PMEs characterized by a PME domain preceded by an N-terminal PRO region. However, the biochemical evidence for AtPME17 as a functional PME is still lacking and the role played by its PRO region is not known. Using the Pichia pastoris expression system, we demonstrate that AtPME17 is a functional PME with activity favoured by an increase in pH. AtPME17 performs a blockwise pattern of pectin de-methylesterification that favours the formation of egg-box structures between homogalacturonans. Recombinant AtPME17 expression in Escherichia coli reveals that the PRO region acts as an intramolecular inhibitor of AtPME17 activity., (© 2020 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues., Competing Interests: The authors declare no competing interest.

Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acyl-coenzymes A. We investigated the dynamics of lysine acetylation and crotonylation on histones H3 and H4 during mouse spermatogenesis. Lysine crotonylation appeared to be of significant abundance compared to acetylation, particularly on Lys27 of histone H3 (H3K27cr) that accumulates in sperm in a cleaved form of H3. We identified the genomic localization of H3K27cr and studied its effects on transcription compared to the classical active mark H3K27ac at promoters and distal enhancers. The presence of both marks was strongly associated with highest gene expression. Assessment of their co-localization with transcription regulators (SLY, SOX30) and chromatin-binding proteins (BRD4, BRDT, BORIS and CTCF) indicated systematic highest binding when both active marks were present and different selective binding when present alone at chromatin. H3K27cr and H3K27ac finally mark the building of some sperm super-enhancers. This integrated analysis of omics data provides an unprecedented level of understanding of gene expression regulation by H3K27cr in comparison to H3K27ac, and reveals both synergistic and specific actions of each histone modification., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Seed extracts from Moringa oleifera are of wide interest for use in water purification where they can play an important role in flocculation; they also have potential as anti-microbial agents. Previous work has focused on the crude protein extract. Here we describe the detailed biophysical characterization of individual proteins from these seeds. The results provide new insights relating to the active compounds involved. One fraction, designated Mo-CBP3, has been characterized at a molecular level using a range of biochemical and biophysical techniques including liquid chromatography, X-ray diffraction, mass spectrometry, and neutron reflection. The interfacial behavior is of particular interest in considering water purification applications and interactions with both charged (e.g. silica) and uncharged (alumina) surfaces were studied. The reflection studies show that, in marked contrast to the crude extract, only a single layer of the purified Mo-CBP3 binds to a silica interface and that there is no binding to an alumina interface. These observations are consistent with the crystallographic structure of Mo-CBP3-4, which is one of the main isoforms of the Mo-CBP3 fraction. The results are put in context of previous studies of the properties of the crude extract. This work shows possible routes to development of separation processes that would be based on the specific properties of individual proteins., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)