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Abstract Tracer tests are an important tool for characterizing and monitoring subsurface reservoir properties. However, they are limited both because of the tracer molecules constraining factors such as irreversible adsorption, retention, and degradations, i.e. interaction processes of fluorophore molecule with surrounding media resulting in a large variation in transport properties. Elaborate tests utilizing more than one tracer to distinguish time or location of injection are complex and interpretation is ambiguous because each tracer interacts differently. In this study, we present an approach to increase tracer stability and enhance the transport uniformity of different tracers, thus making tests utilizing multiple tracers simpler and more feasible. We present this concept of tracer multiplicity by encapsulating an anionic, cationic or amphoteric fluorophore inside mesoporous silica nanoparticle carriers coated with a protective titania layer. Upon encapsulation, increased thermal resistance and drastically lowered sorption affinity towards quartz sand was detected in batch and flow-through experiments. An additional advantage of the presented nanoparticle tracers over molecular tracers is their modularity, which is demonstrated by surface modifications and application of additives that greatly reduce sorption and increase recovery rates in the flow experiments. With the here presented concept of tracer multiplicity, we introduce a new approach for colloidal tracer design that has the potential to expand and enhance measurable parameters, measurement accuracy and simplicity of analysis.

Summary: Autosomal-dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by the formation of fluid-filled renal cysts, loss of mitochondrial function, decreased fatty acid oxidation, increased glycolysis, and likely renal failure. We previously demonstrated that inducing a state of ketosis ameliorates or reverses PKD progression in multiple animal models. In this study, we compare time-restricted feeding and 48-h periodic fasting regimens in both juvenile and adult Cy/+ rats. Both fasting regimens potently prevent juvenile disease progression and partially reverse PKD in adults. To explore the mechanism of fasting, we administered β-hydroxybutyrate (BHB) to Cy/+ rats and orthologous mouse models of PKD (Pkd1RC/RC, Pkd1-Ksp:Cre). BHB recapitulated the effects of fasting in these models independent of stereoisomer, suggesting the effects of BHB are largely due to its signaling functions. These findings implicate the use of ketogenic metabolic therapy and BHB supplementation as potential disease modifiers of PKD and point toward underlying mechanisms.

One of the deficits of knowledge on bone remodelling, is to what extent cells that are driven towards osteogenic differentiation can contribute to osteoclast formation. The periodontal ligament fibroblast (PdLFs) is an ideal model to study this, since they play a role in osteogenesis, and can also orchestrate osteoclastogenesis.when co-cultured with a source of osteoclast-precursor such as peripheral blood mononuclear cells (PBMCs). Here, the osteogenic differentiation of PdLFs and the effects of this process on the formation of osteoclasts were investigated. PdLFs were obtained from extracted teeth and exposed to osteogenic medium for 0, 7, 14, or 21 out of 21 days. After this 21-day culturing period, the cells were co-cultured with peripheral blood mononuclear cells (PBMCs) for an additional 21 days to study osteoclast formation. Alkaline phosphatase (ALP) activity, calcium concentration, and gene expression of osteogenic markers were assessed at day 21 to evaluate the different stages of osteogenic differentiation. Alizarin red staining and scanning electron microscopy were used to visualise mineralisation. Tartrate-resistant acid phosphatase (TRAcP) activity, TRAcP staining, multinuclearity, the expression of osteoclastogenesis-related genes, and TNF-α and IL-1β protein levels were assessed to evaluate osteoclastogenesis. The osteogenesis assays revealed that PdLFs became more differentiated as they were exposed to osteogenic medium for a longer period of time. Mineralisation by these osteogenic cells increased with the progression of differentiation. Culturing PdLFs in osteogenic medium before co-culturing them with PMBCs led to a significant decrease in osteoclast formation. qPCR revealed significantly lower DCSTAMP expression in cultures that had been supplemented with osteogenic medium. Protein levels of osteoclastogenesis stimulator TNF-α were also lower in these cultures. The present study shows that the osteogenic differentiation of PdLFs reduces the osteoclastogenic potential of these cells. Immature cells of the osteoblastic lineage may facilitate osteoclastogenesis, whereas mature mineralising cells may suppress the formation of osteoclasts. Therefore, mature and immature osteogenic cells may have different roles in maintaining bone homeostasis.

The aim of this study was to examine the relationship between an American English Digits in Noise (DIN) test and commonly used audiological measures to evaluate the DIN test’s ability to detect hearing loss and validate hearing aid fitting. QuickSIN and DIN tests were completed by participants with untreated hearing loss (n = 46), prescription hearing aids (n = 15), and over-the-counter (OTC) hearing aids (n = 12). Performance on the QuickSIN showed moderate positive correlations with DIN for untreated hearing loss participants and prescription hearing aid users, but not for OTC hearing aid users. For untreated hearing loss participants, both QuickSIN and DIN tests showed positive moderate to strong correlations with high frequency puretone averages. In OTC users, DIN scores did not significantly change over a 6-month time period and were better when conducted remotely compared to in-person testing. Our results suggest that the DIN test may be a feasible monitoring option for individuals with hearing loss and those fitted with hearing aids. However, due to small sample size in this pilot study, future research is needed to examine DIN test’s utility for fitting and validating OTC hearing aids.

Abstract Background By 2035, the number of newly diagnosed cancer cases will double and over 50% will be in older adults. Given this rapidly growing demographic, a need exists to understand how age influences oncology patients’ symptom burden. The study purposes were to evaluate for differences in the occurrence, severity, and distress of 38 symptoms in younger (

ABSTRACTBorna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies.ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1act: general activation of microglial cells; Iba1nod: formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; patearly: patients treated with early high dose steroid shot; patlate: patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum

ABSTRACTBackground Teacher identity is defined as a continuum of a person’s self-conviction (‘Identity is something I have’) and a context-dependent action (‘Identity is something I do in a context’) (Lankveld et al. 2021). It has been identified a relevant contributor to physicians’ teaching commitment. In this study, we further improve the currently only existing questionnaire instrument (37 items) measuring physicians’ teacher identity.Methods Survey data on 147 clinicians at a German university hospital were (1) analyzed by confirmatory factor analysis (CFA). We tested (a) the model fits of the originally suggested scales and (b) potential for improvement of model fits by item reduction. As this could not reveal satisfactory fits for all scales, we (2) applied a principal axis factoring as an exploratory approach. Last, we combined findings from (1) and (2) with a theoretical item content discussion and suggest (3) reassembled scales which were again checked using CFA.Findings (1a) Two scales from the original instrument were successfully confirmed. (1b) Some scales benefited from item reduction. (2) The exploratory analysis identified three factors that explained at least 5% variance. (3) By integrating confirmatory and exploratory findings with a content analysis of the items, we propose a partially rearranged questionnaire instrument, comprising seven scales: (1) Feeling intrinsic satisfaction from teaching; (2) Feeling responsibility to teach; (3) Exchange of teaching experience; (4) Identification and enjoyment of the teaching role; (5) Development of teaching; (6) Teaching self-concept of ability; (7) Desired rewards for teaching. Four items were kept as single items.Conclusion We suggest that when assessing teacher identity in physicians, all items should be constructed to allow for responses, even from physicians who are presently not actively involved in teaching. The scales benefited from categorizing items based on the continuum of teacher identity as outlined by van Lankveld et al. (2021).

Current online adaptive radiotherapy (oART) workflows require dedicated equipment. Our aim was to develop and implement an oART workflow for a C-arm linac which can be performed using standard clinically available tools. A workflow was successfully developed and implemented. Three patients receiving palliative radiotherapy for bladder cancer were treated, with 33 of 35 total fractions being delivered with the cone-beam computed tomography (CBCT)-guided oART workflow. Average oART fraction duration was 24 min from start of CBCT acquisition to end of beam on. This work shows how oART could be performed without dedicated equipment, broadening oART availability for application at existing treatment machines.

BACKGROUND:. Tracheostomy-related acquired pressure injuries (TRPIs) are one of the hospital-acquired conditions. We hypothesize that an uneven ventilator circuit load, leading to non-neutral tracheostomy tube positioning in the immediate post-tracheostomy period, leads to an increased incidence of TRPIs. Does switching the ventilator circuit load daily, in addition to standard post-tracheostomy care, lead to a decreased incidence of TRPIs? METHODS:. This is a prospective quality improvement study. Study was conducted at two academic hospital sites within tertiary care hospitals at Emory University in different ICUs. Consecutive patients undergoing bedside percutaneous tracheostomy by the interventional pulmonary service were included. The flip the ventilator circuit (FLIC) protocol was designed and implemented in selected ICUs, with other ICUs as controls. RESULTS:. Incidence of TRPI in intervention and control group were recorded at post-tracheostomy day 5. A total of 99 patients were included from October 22, 2019, to May 22, 2020. Overall, the total incidence of any TRPI was 23% at post-tracheostomy day 5. Incidence of stage I, stage II, and stages III–IV TRPIs at postoperative day 5 was 11%, 12%, and 0%, respectively. There was a decrease in the rate of skin breakdown in patients following the FLIC protocol when compared with standard of care (13% vs. 36%; p = 0.01). In a multivariable analysis, interventional group had decreased odds of developing TRPI (odds ratio, 0.32; 95% CI, 0.11–0.92; p = 0.03) after adjusting for age, albumin, body mass index, diabetes mellitus, and days in hospital before tracheostomy. CONCLUSIONS:. The incidence of TRPIs within the first week following percutaneous tracheostomy is high. Switching the side of the ventilator circuit to evenly distribute load, in addition to standard bundled tracheostomy care, may decrease the overall incidence of TRPIs.

Objectives: Teaching communication skills plays a pivotal role in medical curricula. The aim of this article is to describe and evaluate a new communication curriculum developed at the Faculty of Medicine, University of Augsburg (KomCuA), which was conceptualized by an interdisciplinary team based on recommended quality standards (i.e., helical, integrated, longitudinal).Methods: A total of 150 medical students enrolled in the 1, 3, and ≥5 semester participated in the study. They completed an online survey (numerical rating scales and validated questionnaires) evaluating their current communication skills, how these developed across the curriculum in terms of quality and self-confidence, and how helpful they considered practicing in small group tutorials with simulated patients. The students’ attitudes towards communication and empathy in the context of medical care were additionally assessed. The students’ responses were compared across semesters using one-way univariate analysis of variance (ANOVA).Results: Overall, students reported improved communications skills due to attending the KomCuA and further considered practicing with simulated patients as being very helpful (large effect sizes). Compared to 1 semester students, 3 and ≥5 semester students reported better communication skills (medium to large effect sizes). Additionally, ≥5 semester students showed stronger agreement towards the relevance of empathy in the context of medical care (medium effect size) compared to both 1 and 3 semester students. Conclusion: The KomCuA has shown to be an effective communication curriculum to support medical students in the development of their communication skills and positive attitudes towards empathy. Additional studies assessing students’ communication skills and empathic attitudes longitudinally are warranted to confirm the present results and to gain further knowledge on how these essential skills and attitudes develop across medical curricula.

Summary: Small intestine (SI) maturation during early life is pivotal in preventing the onset of gut diseases. In this study we interrogated the milestones of SI development by gene expression profiling and ingenuity pathway analyses. We identified a set of cytokines as main regulators of changes observed across different developmental stages. Upon cytokines stimulation, with IFNγ as the most contributing factor, human fetal organoids (HFOs) increase brush border gene expression and enzyme activity as well as trans-epithelial electrical resistance. Electron microscopy revealed developed brush border and loss of fetal cell characteristics in HFOs upon cytokine stimulation. We identified T cells as major source of IFNγ production in the fetal SI lamina propria. Co-culture of HFOs with T cells recapitulated the major effects of cytokine stimulation. Our findings underline pro-inflammatory cytokines derived from T cells as pivotal factors inducing functional SI maturation in vivo and capable of modulating the barrier maturation of HFOs in vitro.

BackgroundPhysical capacity and physical activity are important aspects of physical functioning and quality of life in people with a chronic disease such as Parkinson disease (PD) or chronic obstructive pulmonary disease (COPD). Both physical capacity and physical activity are currently measured in the clinic using standardized questionnaires and tests, such as the 6-minute walk test (6MWT) and the Timed Up and Go test (TUG). However, relying only on in-clinic tests is suboptimal since they offer limited information on how a person functions in daily life and how functioning fluctuates throughout the day. Wearable sensor technology may offer a solution that enables us to better understand true physical functioning in daily life. ObjectiveWe aim to study whether device-assisted versions of 6MWT and TUG, such that the tests can be performed independently at home using a smartwatch, is a valid and reliable way to measure the performance compared to a supervised, in-clinic test. MethodsThis is a decentralized, prospective, observational study including 100 people with PD and 100 with COPD. The inclusion criteria are broad: age ≥18 years, able to walk independently, and no co-occurrence of PD and COPD. Participants are followed for 15 weeks with 4 in-clinic visits, once every 5 weeks. Outcomes include several walking tests, cognitive tests, and disease-specific questionnaires accompanied by data collection using wearable devices (the Verily Study Watch and Modus StepWatch). Additionally, during the last 10 weeks of this study, participants will follow an aerobic exercise training program aiming to increase physical capacity, creating the opportunity to study the responsiveness of the remote 6MWT. ResultsIn total, 89 people with PD and 65 people with COPD were included in this study. Data analysis will start in April 2024. ConclusionsThe results of this study will provide information on the measurement properties of the device-assisted 6MWT and TUG in the clinic and at home. When reliable and valid, this can contribute to a better understanding of a person’s physical capacity in real life, which makes it possible to personalize treatment options. Trial RegistrationClinicalTrials.gov NCT05756075; https://clinicaltrials.gov/study/NCT05756075 International Registered Report Identifier (IRRID)DERR1-10.2196/55452

Abstract Background Swine are frequently used as animal model for cardiovascular research, especially in terms of representativity of human anatomy and physiology. Reference values for the most common species used in research are important for planning and execution of animal testing. Transesophageal echocardiography is the gold standard for intraoperative imaging, but can be technically challenging in swine. Its predecessor, epicardial echocardiography (EE), is a simple and fast intraoperative imaging technique, which allows comprehensive and goal-directed assessment. However, there are few echocardiographic studies describing echocardiographic parameters in juvenile swine, none of them using EE. Therefore, in this study, we provide a comprehensive dataset on multiple geometric and functional echocardiographic parameters, as well as basic hemodynamic parameters in swine using EE. Methods The data collection was performed during animal testing in ten female swine (German Landrace, 104.4 ± 13.0 kg) before left ventricular assist device implantation. Hemodynamic data was recorded continuously, before and during EE. The herein described echocardiographic measurements were acquired according to a standardized protocol, encompassing apical, left ventricular short axis and long axis as well as epiaortic windows. In total, 50 echocardiographic parameters and 10 hemodynamic parameters were assessed. Results Epicardial echocardiography was successfully performed in all animals, with a median screening time of 14 min (interquartile range 11–18 min). Referring to left ventricular function, ejection fraction was 51.6 ± 5.9% and 51.2 ± 6.2% using the Teichholz and Simpson methods, respectively. Calculated ventricular mass was 301.1 ± 64.0 g, as the left ventricular end-systolic and end-diastolic diameters were 35.3 ± 2.5 mm and 48.2 ± 3.5 mm, respectively. The mean heart rate was 103 ± 28 bpm, mean arterial pressure was 101 ± 20 mmHg and mean flow at the common carotid artery was 627 ± 203 mL/min. Conclusion Epicardial echocardiography allows comprehensive assessment of most common echocardiographic parameters. Compared to humans, there are important differences in swine with respect to ventricular mass, size and wall thickness, especially in the right heart. Most hemodynamic parameters were comparable between swine and humans. This data supports study planning, animal and device selection, reinforcing the three R principles in animal research. Graphical Abstract

A new accessory was developed to allow implantation of left ventricular assist devices (LVADs) without requiring an anastomosis to the ascending aorta. The accessory combines the LVAD inflow and outflow into a dual-lumen device. Initial prototypes encountered reduced pump performance in vitro, but a second-generation prototype successfully addressed this issue. This feasibility study aimed to demonstrate the anatomic fit, safe implantation, and hemodynamic effectiveness of the LVAD with the accessory. The accessory was implanted in ten female pigs (104 ± 13 kg). Following sternotomy and apical coring under cardiopulmonary bypass, a balloon catheter was retrogradely inserted and exteriorized through the coring site, where it was inflated within the distal third of the outflow graft. It was utilized to pull the accessory’s outflow across the aortic valve. After LVAD attachment, the catheter was removed. Echocardiography revealed no relevant valve regurgitation post-implantation. During ramp testing, pump flow increased from 3.7 ± 1.2 to 5.4 ± 1.2 L/min. Necropsy confirmed correct accessory placement in nine animals. No valve lesions or device thrombosis were observed. The accessory enabled LVAD implantation without compromising pump performance. Future work includes design refinements for implantation without cardiopulmonary bypass and long-term testing in a chronic heart failure model.

Ambient noise correlation analyses are largely used to monitor temporal medium changes generally associated with stress field variations and/or fluid movement. Here, we analyze the 2021 eruption of La Palma, the most active island in the Canary archipelago, to study its effects on the structure in a post-eruptive stage. To date, most of the studies, whether in volcanic environments or other geological systems, focus on determining seismic velocity changes that can be associated with precursory signals. In our study, we are interested in localizing the medium changes that permit constraining the depth of the most affected structure and suggesting possible mechanisms capable of inducing such alterations. The auto- and cross-correlation functions were computed using the phase cross-correlation strategy. The correlations were linearly stacked using a 3-day sliding window. The combination of these two approaches proved to render the best results. The analysis of 3 years of data resulted in the detection of occasional decorrelation before the eruption, followed by a well-defined decoherence period after the eruption. In addition, the relationship between the waveform correlation and lag time, using autocorrelations from before and after the eruption, permits identifying phase shifts and waveform distortion, which are sensitive to different parameters and, thus, have great importance in inferring the possible mechanism. Phase shifts occur when there is only velocity change without changing the structure, whereas waveform distortion is caused by a structural (geological) change. We also inferred the depths at which the most significant medium alterations occur. We observed that the decorrelation occurs at lag times corresponding to changes localized in depth. The surface structure appears to not have undergone significant medium changes for depths until approximately 8 km, either before or after the eruption.

The binary Fe–Ni system offers alloys with notably low linear coefficients of thermal expansion (CTE), contingent upon their Ni content. In this respect twin-wire arc additive manufacturing (T-WAAM) presents the opportunity of in-situ alloying through the simultaneous feeding of two metal wires into a weld pool to obtain desired alloy compositions. This study aims to deposit a graded wall with Ni contents targeted at 42, 46, and 52 wt% in the building direction of the wall, along with a block comprising of 46 wt% Ni, employing the T-WAAM approach. The results show effective incorporation of additional Ni into the weld pool and geometrically stable weld beads in the continuous metal transfer mode during the T-WAAM process. This mode led to the defect-free and chemically stable deposition of the graded wall and the block with average Ni contents of 42.3 ± 1.1, 45.8 ± 1.4, 52.6 ± 0.8 wt%, and 46.4 ± 0.9 wt%, respectively. The measured Curie temperatures of the as-deposited alloys and the mean CTE values of alloy 46 were found to be comparable to the commercial alloys. In summary, this study validates the feasibility of in-situ deposition of low thermal expansion alloy compositions, thereby enabling the possibility of on-demand thermal expansion properties.

Summary: Background: Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites. Methods: Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded. Findings: Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19–2.25]), 26 months (1.20 [95% CI 0.48–1.91]), and 38 months (1.52 [95% CI 0.74–2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43–1.07]), 26 months (mean difference 0.65 [95% CI 0.27–1.03]), and 38 months (mean difference 0.72 [95% CI 0.25–1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34–43.38]), 26 months (mean difference 29.26 m [95% CI 14.87–43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32–54.09]). No new safety signals were identified. Interpretation: Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA. Funding: Financial support for the registry from Biogen, Novartis and Roche.

Abstract The immunity conferred by SARS-CoV-2 vaccines and infections reduces the transmission of the virus. To answer how the effect of immunity is shared between a reduction of infectiousness and an increased protection against infection, we examined >50,000 positive cases and >110,000 contacts from Geneva, Switzerland (June 2020 to March 2022). We assessed the association between secondary attack rate (i.e. proportion of new cases among contacts) and immunity from natural infection and/or vaccination, stratifying per four SARS-CoV-2 variants and adjusting for index cases and contacts’ socio-demographic characteristics and the propensity of the contacts to be tested. Here we show that immunity protected contacts from infection, rather than reducing infectiousness of index cases. Natural infection conferred the strongest immunity. Hybrid immunity did not surpass recent infection. Although of smaller amplitude, the reduction in infectiousness due to vaccination was less affected by time and by the emergence of new SARS-CoV-2 variants than the susceptibility to infection. These findings support the role of vaccine in reducing infectiousness and underscore the complementary role of interventions reducing SARS-CoV-2 propagation, such as mask use or indoor ventilation.

Abstract Animal mitochondrial gene expression relies on specific interactions between nuclear-encoded aminoacyl-tRNA synthetases and mitochondria-encoded tRNAs. Their evolution involves an antagonistic interplay between strong mutation pressure on mtRNAs and selection pressure to maintain their essential function. To understand the molecular consequences of this interplay, we analyze the human mitochondrial serylation system, in which one synthetase charges two highly divergent mtRNASer isoacceptors. We present the cryo-EM structure of human mSerRS in complex with mtRNASer(UGA), and perform a structural and functional comparison with the mSerRS-mtRNASer(GCU) complex. We find that despite their common function, mtRNASer(UGA) and mtRNASer(GCU) show no constrain to converge on shared structural or sequence identity motifs for recognition by mSerRS. Instead, mSerRS evolved a bimodal readout mechanism, whereby a single protein surface recognizes degenerate identity features specific to each mtRNASer. Our results show how the mutational erosion of mtRNAs drove a remarkable innovation of intermolecular specificity rules, with multiple evolutionary pathways leading to functionally equivalent outcomes.

Gingival fibroblasts (GFs) can differentiate into osteoblast-like cells and induce osteoclast precursors to differentiate into osteoclasts. As it is unclear whether these two processes influence each other, we investigated how osteogenic differentiation of GFs affects their osteoclast-inducing capacity. To establish step-wise mineralization, GFs were cultured in four groups for 3 weeks, without or with osteogenic medium for the final 1, 2, or all 3 weeks. The mineralization was assessed by ALP activity, calcium concentration, scanning electron microscopy (SEM), Alizarin Red staining, and quantitative PCR (qPCR). To induce osteoclast differentiation, these cultures were then co-cultured for a further 3 weeks with peripheral blood mononuclear cells (PBMCs) containing osteoclast precursors. Osteoclast formation was assessed at different timepoints with qPCR, enzyme-linked immunosorbent assay (ELISA), TRAcP activity, and staining. ALP activity and calcium concentration increased significantly over time. As confirmed with the Alizarin Red staining, SEM images showed that the mineralization process occurred over time. Osteoclast numbers decreased in the GF cultures that had undergone osteogenesis. TNF-α secretion, a costimulatory molecule for osteoclast differentiation, was highest in the control group. GFs can differentiate into osteoblast-like cells and their degree of differentiation reduces their osteoclast-inducing capacity, indicating that, with appropriate stimulation, GFs could be used in regenerative periodontal treatments.

The state-of-the-art ammonothermal method for the growth of nitrides is reviewed here, with an emphasis on binary and ternary nitrides beyond GaN. A wide range of relevant aspects are covered, from fundamental autoclave technology, to reactivity and solubility of elements, to synthesized crystalline nitride materials and their properties. Initially, the potential of emerging and novel nitrides is discussed, motivating their synthesis in single crystal form. This is followed by a summary of our current understanding of the reactivity/solubility of species and the state-of-the-art single crystal synthesis for GaN, AlN, AlGaN, BN, InN, and, more generally, ternary and higher order nitrides. Investigation of the synthesized materials is presented, with a focus on point defects (impurities, native defects including hydrogenated vacancies) based on GaN and potential pathways for their mitigation or circumvention for achieving a wide range of controllable functional and structural material properties. Lastly, recent developments in autoclave technology are reviewed, based on GaN, with a focus on advances in development of in situ technologies, including in situ temperature measurements, optical absorption via UV/Vis spectroscopy, imaging of the solution and crystals via optical (visible, X-ray), along with use of X-ray computed tomography and diffraction. While time intensive to develop, these technologies are now capable of offering unprecedented insight into the autoclave and, hence, facilitating the rapid exploration of novel nitride synthesis using the ammonothermal method.

Purpose: To analyse the association of masticatory performance and oral health-related quality of life in a representative population of individuals residing in communities in Switzerland aged ≥ 45 years. Materials and Methods: In total, 100 subjects completed two dedicated and validated questionnaires on their demographic data and the Geriatric Oral Health Assessment Index. A mixing ability test was performed for assessing masticatory performance. The qualitative analysis of the test was performed by categorizing the images into five categories, while the quantitative analysis was performed via a validated custom-made software. Results: Sixty-six samples could be analysed. Participants younger than 65 years of age showed significantly less frequent chewing deficiencies (17%) compared to those 65 years and older (50%, p < 0.01). However, retired participants had chewing deficiencies significantly more frequently (8%) compared to workers (51%, p < 0.01). A statistically significant positive association of having chewing deficiency was found between employment status (p < 0.01) and the presence of restorations (p = 0.04), while GOHAI did not show any statistically significant association. Overall, the enrolled subjects displayed moderate chewing function. Masticatory performance was positively associated with the number of present restorations. Conclusions: The enrolled subjects residing in communities in Switzerland aged ≥ 45 years displayed moderate chewing function. Their masticatory performance was positively associated with the number of present restorations but not associated with oral health related quality of life (GOHAI).

Invar alloys exhibit low thermal expansion and are useful in applications requiring dimensional stability when subject to temperature changes. Conventional production of Invar faces certain challenges that can be offset by exploiting additive manufacturing processes. This study employed pulsed gas tungsten arc welding (GTAW) to deposit Invar 36 alloy blocks at five heat inputs (HI) ranging from 200 to 550 J mm−1. The results show that the microstructure comprised of columnar grains and remained in the austenitic phase regardless of the HI. Ductility dip cracking was found to prevail in all the blocks except the block deposited at the lowest HI. The decreased susceptibility to cracking with a reduction in the HI was due to the preservation of the grain boundary area, consequently leading to an improved partitioning of strain among the grain boundaries. On lowering the HI from 550 to 200 J mm−1 the average yield strength, tensile strength and elongation improved by 16%, 23% and 38%, respectively. The HI had a negligible effect on the mean linear coefficient of thermal expansion (CTE) in different temperature ranges as the CTE values were nearly identical between the blocks deposited at 200 and 550 J mm−1. In general, the CTE in the building direction was slightly higher than the travel direction, with a maximum difference between the CTE of the two directions being 15%. In summary, this work demonstrates the application of the cold wire GTAW process as an alternative to conventional/laser based methods for realizing the functional properties of Invar.

Abstract Evidence from cross-sectional human studies, and preliminary microbial-based intervention studies, have implicated the microbiota-gut-brain axis in the neurobiology of autism spectrum disorder (ASD). Using a prospective longitudinal study design, we investigated the developmental profile of the fecal microbiota and metabolome in infants with (n = 16) and without (n = 19) a family history of ASD across the first 36 months of life. In addition, the general developmental levels of infants were evaluated using the Mullen Scales of Early Learning (MSEL) test at 5 and 36 months of age, and with ADOS-2 at 36 months of age. At 5 months of age, infants at elevated-likelihood of ASD (EL) harbored less Bifidobacterium and more Clostridium and Klebsiella species compared to the low-likelihood infants (LL). Untargeted metabolic profiling highlighted that LL infants excreted a greater amount of fecal γ-aminobutyric acid (GABA) at 5 months, which progressively declined with age. Similar age-dependent patterns were not observed in the EL group, with GABA being consistently low across all timepoints. Integrated microbiome-metabolome analysis showed a positive correlation between GABA and Bifidobacterium species and negative associations with Clostridium species. In vitro experiments supported these observations demonstrating that bifidobacteria can produce GABA while clostridia can consume it. At the behavioral level, there were no significant differences between the EL and LL groups at 5 months. However, at 36 months of age, the EL group had significantly lower MSEL and ADOS-2 scores compared to the LL group. Taken together, the present results reveal early life alterations in gut microbiota composition and functionality in infants at elevated-likelihood of ASD. These changes occur before any behavioral impairments can be detected, supporting a possible role for the gut microbiota in emerging behavioral variability later in life.

Ambient seismic noise acquired in the Cerdanya Basin (eastern Pyrenees) is used to assess the capability of different methodologies to map the geometry of a small-scale sedimentary basin. We present results based on a 1-year-long broad-band deployment covering a large part of the eastern Pyrenees and a 2-month-long high-density deployment covering the basin with interstation distances around 1.5 km. The explored techniques include autocorrelations, ambient noise Rayleigh wave tomography, horizontal-to-vertical-spectra ratio (HVSR) and band-pass-filtered ambient noise amplitude mapping. The basement depth estimations retrieved from each of these approaches, based on independent datasets and different implicit assumptions, are consistent, showing that the deeper part of the basin is located in its central part, reaching depths of 600–700 m close to the Têt fault trace bounding the Cerdanya Basin to the NE. The overall consistency between the results from all the methodologies provides solid constraints to our basement depth estimation, although significant differences arise in some areas. The results also show that, when high-density seismic data are available, HVSR and ambient noise amplitude analysis in a selected frequency band are useful tools to quickly map the sedimentary 3D geometry. Beside this methodological aspect, our results help to improve the geological characterization of the Cerdanya Basin and will provide further constraints to refine the seismic risk maps of an area of relevant touristic and economic activity.

Abstract Fiber optic infrastructure is essential in the transmission of data of all kinds, both for the long haul and shorter distances in cities. Optical fibers are also preferred for data infrastructures inside buildings, especially in highly secured organizations and government facilities. This paper focuses on a reference measurement and analysis of optical fiber cables sensitivity to acoustic waves. Measurement was carried out in an anechoic chamber to ensure stable conditions of acoustic pressure in the range from 20 Hz to 20 kHz. The frequency response, the signal-to-noise ratio per frequency, and the Speech Transmission Index are evaluated for various types of optical fiber cables and different ceiling tiles, followed by their comparison. The influence of the means of fixing the cable is also studied. The results prove that optical fiber-based infrastructure in buildings can be exploited as a sensitive microphone.

Abstract Background Perioperative echocardiography is of paramount importance during cardiac surgery. Nonetheless, in the experimental large‐animal setting, it might be challenging obtaining optimal imaging when using conventional imaging acquisition techniques, such as transthoracic and transesophageal screenings. Open‐chest surgery allows epicardial echocardiographic assessment with direct contact between probe and heart, thus providing superior quality. Standard protocols regarding the use of epicardial ultrasound in swine for research purposes are lacking. Methods Epicardial echocardiography was performed in 10 female German Landrace pigs undergoing cardiac surgery. A structured and comprehensive protocol for epicardial echocardiography was elaborated including apical, ventricular long and short axis, as well as epiaortic planes. All experiments were approved by the local board for animal welfare and conducted in accordance with the German animal protection law (TierSchG) and the ARRIVE guidelines. Conclusions Systematic protocols using epicardial echocardiography may serve as an additional tool to assess cardiac dimensions and function in experimental scenarios with swine models.

The role of resting state functional MRI (rsfMRI) is increasing in the field of epilepsy surgery because it is possible to interpolate network connectivity patterns across the brain with a high degree of spatial resolution. Prior studies have shown that by rsfMRI with scalp electroencephalography (EEG), an epileptogenic network can be modeled and visualized with characteristic patterns of connectivity that are relevant to both seizure-related and neuropsychological outcomes after surgery. The aim of this study is to show that a 5-min acquisition time provides reproducible results related to the relevant connectivity metrics when compared to a separately acquired 5-min scan. Fourteen separate rsfMRI sessions from ten different patients were used for comparison, comprised of patients with temporal lobe epilepsy both pre- and post-operation. Results showed that there was no significant difference in any of the connectivity metrics when comparing both 5-min scans to each other. These data support the continued use of a 5-min scan for epileptogenic network modeling in future studies because the inter-scan variability is sufficiently low as not to alter the output metrics characterizing the network connectivity.

ABSTRACT In this study, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins and virus particles can be detected (i) in post-mortem kidney of fatal coronavirus disease 2019 (COVID-19) patients and (ii) in renal biopsy of patients suffering from kidney failure months after combating a SARS-CoV-2 infection. Using fluorescence microscopy, antibodies against viral proteins [nucleocapsid, membrane (M), non-structural proteins (nsp) 3, 4, and 13] and double-stranded RNA (dsRNA) were validated on SARS-CoV-2-infected Vero cells. dsRNA was detected in lipid-filled electron-lucent (white) compartments in SARS-CoV-2-producing cells. In the kidney of a patient with acute kidney failure, accumulation of SARS-CoV-2 nucleocapsid N protein was detected in tubular epithelium. In contrast, none of the other viral proteins (M, nsp3, 4, 13) nor dsRNA was detected in these regions, suggesting that no viral replication takes place in the kidney of these patients. High-resolution immunoelectron microscopy demonstrated N protein accumulation in Golgi-like structures but absence of intracellular virus particles. The presence of the N protein in Golgi-like structures in kidney of patients suggests that this protein may have an unforeseen role in post-COVID-19 renal complications. IMPORTANCE Even though the coronavirus disease 2019 (COVID-19) pandemic is slowly developing into a conventional infectious disease, the long-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection are still not well understood. One of the problems is that many COVID-19 cases develop acute kidney injuries. Still, it is heavily debated whether SARS-CoV-2 virus enters and actively replicates in kidney tissue and if SARS-CoV-2 virus particles can be detected in kidney during or post-infection. Here, we demonstrated that nucleocapsid N protein was detected in kidney tubular epithelium of patients that already recovered form COVID-19. The presence of the abundantly produced N protein without signs of viral replication could have implications for the recurrence of kidney disease and have a continuing effect on the immune system.

ABSTRACTDiet shapes our gut microbiome from the day we are born. The contribution of dietary non-protein nitrogen to normal and healthy nitrogen cycling in the infant gut is scarcely described. Herein, we review in vitro and in vivo findings that show the impact of Human Milk Nitrogen (HMN) on the gut microbiota that colonizes the gut in early human life. We describe that several non-protein nitrogen sources, that include creatine, creatinine, urea, polyamines and free amino acids, are key in establishing the bifidobacterium-dominated microbiome and thus are bifidogenic. Furthermore, several parts of HMN-related metabolism are associated with a healthy infant gut and commensal microbiota. We illustrate an overlap and great diversity in accessibility of HMN by large parts of the infant gut microbiota. This review nonetheless shows the importance of research on HMN and its effects on the activity and composition of the infant gut microbiota and its potential effect on early life infant health.

Abstract Background Neonatal intensive care unit (NICU) admission among term neonates is a rare event. The aim of this study was to study the association of the NICU admission of term neonates on the risk of long-term childhood mortality. Methods A single-center case–control retrospective study between 2005 and 2019, including all in-hospital ≥ 37 weeks’ gestation singleton live-born neonates. The center perinatal database was linked with the birth and death certificate registries of the Israeli Ministry of Internal Affairs. The primary aim of the study was to study the association between NICU admission and childhood mortality throughout a 15-year follow-up period. Results During the study period, 206,509 births were registered; 192,527 (93.22%) term neonates were included in the study; 5292 (2.75%) were admitted to NICU. Throughout the follow-up period, the mortality risk for term neonates admitted to the NICU remained elevated; hazard ratio (HR), 19.72 [14.66, 26.53], (p

This study presents the first 10-year follow-up investigation of the implant survival and peri-implant outcomes of one-piece mini dental implants (MDIs) retaining mandibular implant overdentures (IODs), including marginal bone level alterations (ΔMBLs), clinical peri-implant parameters, and complications. Twenty participants with horizontally atrophied mandibles received complete dentures and four MDIs (diameter 1.8 mm) at baseline. The dentures were converted into IODs with O-ring attachments. The 10-year follow-up comprised a radiological assessment of ΔMBLs, peri-implant parameters, as well as biological and technical complications. Results from a 10-year follow-up of 14 participants showed a 100% implant survival rate for all 56 implants. The mean ΔMBL after 10 years was −1.12 ± 0.80 mm, with 49 implants classified as successful (ΔMBL < 2 mm) and 7 implants with satisfactory survival (ΔMBL 2–4 mm). Time after implant placement significantly influenced ΔMBL, with stable MBLs after 5 years. The prosthetic survival rate after 10 years was 93%. ΔMBLs were not influenced by implant position or gender but were significantly smaller in subjects older than 65 years. Conclusively, one-piece MDIs with O-ring attachments offer a reliable treatment option for horizontally atrophied mandibles after 10 years, with high implant and prosthetic survival rates, potentially benefiting from advanced age regarding peri-implant bone stability.

Headache is a frequent comorbidity in patients with epilepsy. Data are sparse regarding the distribution of headache types in children with epilepsy (CWE). We aimed to assess the prevalence of primary headache types and their influence on health-related quality of life (QoL) in CWE. CWE filled out a validated headache questionnaire to assess migraine (MIG), tension-type headache (TTH), trigeminal–autonomic cephalalgia (TAC), or, if the criteria were not fulfilled, non-classifiable headache (NCH). QoL was measured using both patient and parent versions of a validated questionnaire. Of 119 CWE (59 female; 11.5 ± 3.1 y), headache was found in 46 (38.7%). Sixteen (34.8%) patients showed MIG, 9 (19.6%) patients TTH, and 21 (45.7%) patients described NCH. More girls reported headache (χ2 = 5.4, p = 0.02) when compared to boys. Overall, QoL was reduced in patients with headache from both the patients’ and parents’ points of view (70.8% [39.6; 87.5] vs. 77.0% [46.9; 95.8], p = 0.002; 71,9% [33.3; 87.5] vs. 78,1% [54.2; 95.8], p = 0.003). Headache is common among CWE with MIG as the most prevalent primary headache type and higher rates in female patients. Importantly, patients and their parents perceive a reduced overall QoL when suffering from headache.

Abstract Rayleigh wave ellipticity measurements from seismic ambient noise recorded on the Greenland Ice Sheet (GrIS) show complex and anomalous behavior at wave periods sensitive to ice (T

Abstract For the first time, we measured the ellipticity of direct Rayleigh waves at intermediate periods (15–35 s) on Mars using the recordings of three large seismic Martian events, including S1222a, the largest event recorded by the InSight mission. These measurements, together with P‐to‐s receiver functions and P‐wave reflection times, were utilized for performing a joint inversion of the local crustal structure at the InSight landing site. Our inversion results are compatible with previously reported intra‐crustal discontinuities around 10 and 20 km depths, whereas the preferred models show a strong discontinuity at ∼37 km, which is interpreted as the crust‐mantle interface. Additionally, we support the presence of a shallow low‐velocity layer of 2–3 km thickness. Compared to nearby regions, lower seismic wave velocities are derived for the crust, suggesting a higher porosity or alteration of the whole local crust.

Dyslipidemia in obesity results from excessive production and impaired clearance of triglyceride-rich (TG-rich) lipoproteins, which are particularly pronounced in the postprandial state. Here, we investigated the impact of Roux-en-Y gastric bypass (RYGB) surgery on postprandial VLDL1 and VLDL2 apoB and TG kinetics and their relationship with insulin-responsiveness indices. Morbidly obese patients without diabetes who were scheduled for RYGB surgery (n = 24) underwent a lipoprotein kinetics study during a mixed-meal test and a hyperinsulinemic-euglycemic clamp study before the surgery and 1 year later. A physiologically based computational model was developed to investigate the impact of RYGB surgery and plasma insulin on postprandial VLDL kinetics. After the surgery, VLDL1 apoB and TG production rates were significantly decreased, whereas VLDL2 apoB and TG production rates remained unchanged. The TG catabolic rate was increased in both VLDL1 and VLDL2 fractions, but only the VLDL2 apoB catabolic rate tended to increase. Furthermore, postsurgery VLDL1 apoB and TG production rates, but not those of VLDL2, were positively correlated with insulin resistance. Insulin-mediated stimulation of peripheral lipoprotein lipolysis was also improved after the surgery. In summary, RYGB resulted in reduced hepatic VLDL1 production that correlated with reduced insulin resistance, elevated VLDL2 clearance, and improved insulin sensitivity in lipoprotein lipolysis pathways.

Purpose: Men with advanced prostate cancer experience a wide range of side effects from the cancer and its therapies, which have a negative effect on their quality of life (QOL). Few studies have evaluated supportive care needs in these individuals. The purpose of this study was to conduct a holistic supportive care needs assessment among these survivors guided by the Supportive Care Framework for Cancer Care. Methods: Using a convergent parallel mixed-methods approach, prostate cancer survivors with advanced disease (n = 188) completed a cross-sectional survey. A subset of these survivors (n = 20) participated in an interview to further explore their experience of unmet needs.Results: Survivors reported unmet supportive care needs in every domain of the framework. Up to 95.2% of the survivors had at least one unmet need, with a mean of 14.9 (range: 0–42). Several areas of convergence among the quantitative and qualitative data (fatigue, sexual dysfunction, practical, and emotional/psychological domains), as well as divergence (informational and spiritual domains, depression, urinary dysfunction) were found through the integration process. Conclusions: This study confirms that prostate cancer survivors with advanced disease experience high rates of unmet supportive care needs. The findings also highlight the diversity of those unmet needs. These results may assist with future development of patient-centered supportive care interventions that better meet the specific needs of this vulnerable group of cancer survivors.Keywords: prostate cancer; advanced disease; survivors; supportive care; unmet needs; quality of life; mixed-methods

But : Les hommes souffrant d’un cancer avancé de la prostate connaissent un large éventail d’effets secondaires découlant du cancer et de ses traitements qui nuisent à leur qualité de vie (QDV). Peu d’études ont évalué les besoins de soins de soutien chez ces personnes. Cette étude a été réalisée pour effectuer une évaluation globale des besoins en soins de soutien chez ces survivants en se fondant sur un cadre de soins de soutien en oncologie (Supportive Care Framework for Cancer Care, ou SCFCC). Méthodes : Dans le cadre d’une recherche menée selon une approche mixte, parallèle et convergente, des survivants du cancer de la prostate à un stade avancé (n = 188) ont répondu à un questionnaire d’enquête transversale. Quelques-uns de ces survivants (n = 20) ont participé à un entretien afin de mieux évaluer leurs besoins non satisfaits.Résultats : Les survivants ont déclaré des besoins non satisfaits de soins de soutien dans tous les domaines du cadre d’évaluation utilisé. Pas moins de 95,2 % des survivants avaient au moins un besoin non satisfait, avec une moyenne de 14,9 besoins (fourchette : 0–42). Plusieurs domaines de convergence entre les données quantitatives et qualitatives (fatigue, dysfonctionnement sexuel, domaines pratique et émotionnel/psychologique) et de divergence (domaines informationnel et spirituel, dépression, dysfonctionnement urinaire) ont été trouvés durant le processus d’intégration. Conclusion : Cette étude confirme que les survivants du cancer de la prostate à un stade avancé présentent des taux élevés de besoins non satisfaits en soins de soutien. Les résultats soulignent également une grande diversité dans ces besoins non satisfaits. Ces résultats pourraient contribuer au développement de plans de soins de soutien centrés sur le patient, adaptés aux besoins particuliers de ce groupe vulnérable de survivants du cancer.Mots-clés : cancer de la prostate; stade avancé; survivants; soins de soutien; besoins non satisfaits; qualité de vie; méthodes mixtes

Abstract Introduction An understanding of the long‐term psychosocial impact of paediatric haematopoietic stem cell transplantation (HSCT) for nonmalignant diseases is needed to optimize pre‐HSCT counselling, supportive care and long‐term follow‐up programmes after HSCT for this group of patients and caregivers. Methods This qualitative study included 14 patients who underwent transplantation for a nonmalignant disease during childhood. In‐depth interviews were held online to explore patients' perspectives on the long‐term psychosocial impact of HSCT on their lives. The results were analysed based on the Grounded Theory approach. Results Patients' median age at the time of the interview was 19 years (range: 14–49), and the median years after HSCT was 12 years (range: 3–33). Four main themes were identified: (1) doing okay, (2) experiencing persistent involvement with healthcare services, (3) influence on relationships with loved ones and (4) impact on the patient's life course. Subthemes extracted were doing okay, feeling of being cured, health limitations, sense of vulnerability, ongoing connection to the hospital, acceptance, friendship, family relations, development of own identity, not taking life for granted, social development, impact on (school) career and thinking about the future. Conclusions Patients reported active coping strategies and resilience after this high‐impact treatment. The data highlight the need for patient‐adjusted supportive care, indicating more need for supportive care in the long‐term outpatient clinic. Patient Contribution This study included patients as participants. Caregivers were approached if patients were below a certain age. Additionally, preliminary results were presented during a patient conference day.

Seismic Rayleigh wave ellipticity measurements are the horizontal-to-vertical ratio of the Rayleigh wave particle motion, and are sensitive to the subsurface structure beneath a seismic station. H/V ratios measured from the ambient vibrations of the Earth are being increasingly used in glaciological applications to determine glacier and ice sheet thickness, seismic velocities and firn properties. Using the newly developed degree-of-polarisation (DOP-E) method which exploits the polarisation properties of seismic noise, we identify and extract Rayleigh waves from seismic stations in Greenland, and relate them to sea ice processes and the geology of the upper crust. Finally, we provide some suggestions for future applications of DOP-E method to gain greater insight into seasonal and long-term variability of sea ice formation and breakup as well as the monitoring of ice sheet thickness, subglacial environment and firn layers in the poles.

In mixed-phase clouds, the variable mass ratio between liquid water and ice as well as the spatial distribution within the cloud plays an important role in cloud lifetime, precipitation processes, and the radiation budget. Data sets of vertically pointing Doppler cloud radars and lidars provide insights into cloud properties at high temporal and spatial resolution. Cloud radars are able to penetrate multiple liquid layers and can potentially be used to expand the identification of cloud phase to the entire vertical column beyond the lidar signal attenuation height, by exploiting morphological features in cloud radar Doppler spectra that relate to the existence of supercooled liquid. We present VOODOO (reVealing supercOOled liquiD beyOnd lidar attenuatiOn), a retrieval based on deep convolutional neural networks (CNNs) mapping radar Doppler spectra to the probability of the presence of cloud droplets (CD). The training of the CNN was realized using the Cloudnet processing suite as supervisor. Once trained, VOODOO yields the probability for CD directly at Cloudnet grid resolution. Long-term predictions of 18 months in total from two mid-latitudinal locations, i.e., Punta Arenas, Chile (53.1∘ S, 70.9∘ W), in the Southern Hemisphere and Leipzig, Germany (51.3∘ N, 12.4∘ E), in the Northern Hemisphere, are evaluated. Temporal and spatial agreement in cloud-droplet-bearing pixels is found for the Cloudnet classification to the VOODOO prediction. Two suitable case studies were selected, where stratiform, multi-layer, and deep mixed-phase clouds were observed. Performance analysis of VOODOO via classification-evaluating metrics reveals precision > 0.7, recall ≈ 0.7, and accuracy ≈ 0.8. Additionally, independent measurements of liquid water path (LWP) retrieved by a collocated microwave radiometer (MWR) are correlated to the adiabatic LWP, which is estimated using the temporal and spatial locations of cloud droplets from VOODOO and Cloudnet in connection with a cloud parcel model. This comparison resulted in stronger correlation for VOODOO (≈ 0.45) compared to Cloudnet (≈ 0.22) and indicates the availability of VOODOO to identify CD beyond lidar attenuation. Furthermore, the long-term statistics for 18 months of observations are presented, analyzing the performance as a function of MWR–LWP and confirming VOODOO's ability to identify cloud droplets reliably for clouds with LWP > 100 g m−2. The influence of turbulence on the predictive performance of VOODOO was also analyzed and found to be minor. A synergy of the novel approach VOODOO and Cloudnet would complement each other perfectly and is planned to be incorporated into the Cloudnet algorithm chain in the near future.

Abstract Purpose To determine the clinical and radiological outcomes of hybrid-design- (HD) and bone-level (BL) implants for bar-retained mandibular implant-overdentures (IODs). Methods For this retrospective study, edentulous patients who had received maxillary complete dentures and mandibular bar-retained IODs were invited for a follow-up assessment. Implant survival, implant success and health of peri-implant tissues were assessed on an implant level-based analysis. Patient-based parameters served to identify risk factors for peri-implant bone loss, presence of peri-implantitis and success. Results Eighty patients (median age 72.72 [67.03; 78.81] years, 46 females) with 180 implants (median follow-up 12.01 [10.82; 21.04] years) were assessed. There was no difference concerning the rate of implant failure (p = 0.26), or peri-implantitis (p = 0.97) between HD and BL implants. Solely in one study group, there was the presence of peri-implant pus. Implant success was higher in BL implants with one group being notably higher than the comparing groups (p = 0.045). For bone loss, a width of keratinized mucosa (KM) ≤ 1 mm (p = 0.0006) and the presence of xerostomia (p = 0.09) were identified as risk factors. Smoking (p = 0.013) and a higher body mass index (BMI) (p = 0.03) were a risk factor for peri-implantitis. As risk factors for reduced implant success, a small width of KM (p = 0.003) and the presence of xerostomia (p = 0.007) were identified. Conclusions For mandibular bar-retained IODs, both BL and HD implants are mostly successful. A minimum of 1 mm KM around implants and normal salivary flow are relevant factors for implant success and stable peri-implant bone levels. Smoking and a high BMI are potential risk factors for peri-implantitis.

Mitochondrial tRNAs are indispensable and yet underwent an extreme mutational erosion. The authors report the structures of a mitochondrial aaRS-tRNA complex and show how the most degenerated of all human mtRNAs is recognized by its cognate synthetase to maintain mitochondrial gene expression.

Abstract We present the first detection of normal modes on Mars using the vertical records from InSight's broad‐band seismometer following the marsquake that occurred on sol 1222. The proposed catalog lists 60 potential eigenfrequencies between 3 and 12 mHz. Due to their low signal‐to‐noise ratio, these normal modes were detected using the phasor walkout approach. The normal modes amplitudes are consistent with the upper limit of the S1222a magnitude and with high quality factors. Additionally, we provide the first detection of a Martian hum before the quake for several of these frequencies. The proposed frequencies are at about 1‐sigma of those predicted by published models based on body wave travel time inversions. Our detection of normal modes is the first made on a terrestrial planet other than Earth and opens the way for future interior models that incorporate both normal modes frequencies, surface waves velocities and body wave travel times.

Background: The impact of bifurcations at the proximal or distal cap on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. Methods: We analyzed the clinical, angiographic, and procedural data of 4,584 cases performed in patients between 2012 and 2020 in a global CTO PCI registry. We compared 4 groups according to the bifurcation location: “proximal cap,” “distal cap,” “proximal and distal cap,” and “no bifurcation.” Results: The CTO involved a bifurcation in 67% cases, as follows: proximal cap (n = 1451, 33%), distal cap (n = 622, 14%), or both caps (n = 954, 21%). “Proximal and distal cap” cases had higher J-CTO compared with “proximal cap,” “distal cap,” and “no bifurcation” cases (2.9 ± 1.1 vs 2.5 ± 1.1 vs 2.4 ± 1.2 vs 2.0 ± 1.2, P

The estimation of debris flow velocity and volume is a fundamental task for the development of early warning systems and the design of control structures and of other mitigation measures. Debris flow velocity can be calculated using seismic data recorded at two monitoring stations located along the channel, and previous analysis of the seismic energy produced by debris flows showed that the peak discharge of each surge can be estimated based on the maximum amplitude of the seismic signal. This work provides a first approach for estimating the total volume of debris flows from the integrated seismic energy detected with simple, low-cost geophones installed along a debris flow channel. The developed methods were applied to seismic data collected from 2014 to 2018 in three different test sites in the European Alps: Gadria and Cancia (Italy) and Lattenbach (Austria). An adaptable cross-correlation time window was used to calculate the velocity of the different surges, which can offer a better estimation of the velocity compared to a constant window length. The analyses of the seismic data of 14 debris flows show the strong control of the sampling rate and of the inter-station distance on velocity estimation. A linear relationship between the squares of seismic amplitudes – a proxy for seismic energy – and independent measurements of the debris flow volume is proposed for a first-order estimation of the latter. Uncertainties in the volume estimations are controlled by flow properties – such as liquid or viscous surges generating low-amplitude signals and thus underestimating the calculated volume – but in most cases (9 out of 11 events of the test dataset of the Illgraben basin, CH) the order of magnitude of the debris flow volume is correctly predicted.

Cláudio Rodrigues Leles,1 Jésio Rodrigues Silva,1 Thalita Fernandes Fleury Curado,1 Martin Schimmel,2,3 Gerald McKenna4 1School of Dentistry, Federal University of Goias, Goiania, Brazil; 2Department of Reconstructive Dentistry and Gerodontology, School of Dental Medicine, University of Bern, Bern, Switzerland; 3Division of Gerodontology and Removable Prosthodontics, University Clinics of Dental Medicine, University of Geneva, Geneva, Switzerland; 4Centre for Public Health, Queen’s University, School of Medicine Dentistry & Biomedical Sciences, Institute of Clinical Science, Belfast, UKCorrespondence: Cláudio Rodrigues Leles, Faculdade de Odontologia, Universidade Federal de Goiás, Praça Universitária, s/n, Setor Universitário, Goiania, Goias, 74605-220, Brazil, Tel +55 62 32096052, Email claudio_leles@ufg.brAbstract: Oral health problems are associated with poor quality of life, with the potential to cause functional, aesthetic, nutritional, and psychological difficulties, in addition to pain and suffering. Traditionally, dental treatment outcomes are measured using purely clinical parameters; however, this may be ineffective as these parameters cannot adequately capture the full impact of poor oral health on the patient, or their respective coping strategies. From this perspective, there are significant benefits when the patient’s perception of their care is considered, and included in treatment planning and delivery. The impacts perceived by the patient on their treatment outcomes can be measured using patient-reported outcomes (PROS), or more specifically with dPROS, focused on dental patient-reported outcomes. Although there are some instruments available for measuring these outcomes in clinical trials, very little information is available for explaining the context in which these outcomes are considered, and also how to capture this information using appropriate instruments, specially in evidence-based dental practice. This article aims to review the literature, seeking to describe what has been considered about assessing patient’s outcomes, as well as how to measure them, and explore the potential benefits of using dPROS in evidence-based prosthodontics and clinical care of partially and fully edentulous patients.Keywords: evidence-based practice, dentistry, prosthodontics, patient-reported outcomes

Abstract Knowledge of Martian crust and uppermost mantle aid us studying the planet's evolution. NASA's InSight mission provides seismic data being used to reveal the interior structure. Most studies have focused on the crustal structure beneath InSight lander, but the seismic structure of other regions has remained poorly known. We use surface‐wave data to investigate the crustal structure of a large region along the Medusa Fossae Formation and the dichotomy. We adopt the largest‐magnitude marsquake (S1222a) that has been recorded, which provides both Rayleigh‐ and Love‐wave signals. We measure and jointly invert these surface‐wave fundamental‐mode group velocities from ∼15 to 40 s to estimate the average 1D isotropic velocity models. These models includes a high‐velocity layer at ∼7‐km depth, which could be due to a regional basaltic activity or regional stress. Our models also indicate that a common intra‐crustal structure (∼12–40 km depth) may exist in this region along the dichotomy.