Influence of chemistry and topography on the wettability of copper.

To understand the complex interplay of topography and surface chemistry in wetting, fundamental studies investigating both parameters are needed. Due to the sensitivity of wetting to miniscule changes in one of the parameters it is imperative to precisely control the experimental approach. A profound understanding of their influence on wetting facilitates a tailored design of surfaces with unique functionality. We present a multi-step study: The influence of surface chemistry is analyzed by determining the adsorption of volatile carbonous species (A) and by sputter deposition of metallic copper and copper oxides on flat copper substrates (B). A precise surface topography is created by laser processing. Isotropic topography is created by ps laser processing (C), and hierarchical anisotropic line patterns are produced by direct laser interference patterning (DLIP) with different pulse durations (D). Our results reveal that the long-term wetting response of polished copper surfaces stabilizes with time despite ongoing accumulation of hydrocarbons and is dominated by this adsorption layer over the oxide state of the substrate (Cu, CuO, Cu2O). The surfaces' wetting response can be precisely tuned by tailoring the topography via laser processing. The sub-pattern morphology of primary line-like patterns showed great impact on the static contact angle, wetting anisotropy, and water adhesion. An increased roughness inside the pattern valleys combined with a minor roughness on pattern peaks favors air-inclusions, isotropic hydrophobicity, and low water adhesion. Increasing depth of the primary topography can also induce air-inclusions despite increasing peak roughness while time dependent wetting transitions were observed.

DNA double-strand break-capturing nuclear envelope tubules drive DNA repair.

Current models suggest that DNA double-strand breaks (DSBs) can move to the nuclear periphery for repair. It is unclear to what extent human DSBs display such repositioning. Here we show that the human nuclear envelope localizes to DSBs in a manner depending on DNA damage response (DDR) kinases and cytoplasmic microtubules acetylated by α-tubulin acetyltransferase-1 (ATAT1). These factors collaborate with the linker of nucleoskeleton and cytoskeleton complex (LINC), nuclear pore complex (NPC) protein NUP153, nuclear lamina and kinesins KIF5B and KIF13B to generate DSB-capturing nuclear envelope tubules (dsbNETs). dsbNETs are partly supported by nuclear actin filaments and the circadian factor PER1 and reversed by kinesin KIFC3. Although dsbNETs promote repair and survival, they are also co-opted during poly(ADP-ribose) polymerase (PARP) inhibition to restrain BRCA1-deficient breast cancer cells and are hyper-induced in cells expressing the aging-linked lamin A mutant progerin. In summary, our results advance understanding of nuclear structure-function relationships, uncover a nuclear-cytoplasmic DDR and identify dsbNETs as critical factors in genome organization and stability.

Structured Exposure Achieves High Acceptance of Immersive Technology Among Medical Students and Educators.

Virtual reality (VR) is a potent educational tool with untapped potential in medical training. However, its integration into medical schools faces challenges such as cybersickness and hesitancy among medical students and professionals. Notably, there has been no systematic assessment of the acceptance of medical educational VR applications by both students and educators. In our single-center study, we enrolled 133 medical students and 14 medical educators. Following a practical demonstration of the established VR anatomy application, Sharecare YOU VR, participants completed a self-reporting survey based on the Technology Acceptance Model (TAM), exploring user acceptance of information technologies and focusing on perceived usefulness (PU), perceived ease of use (PEU), and attitude toward using (ATU). We also sought insights into potential future applications of VR in medical education. Our findings indicate a high level of acceptance among medical students and educators upon structured exposure to VR with significantly positive responses for all three TAM variables (PU, PEU, and ATU). Intriguingly, hands-on experience influenced acceptance. Students envisioned VR's benefits in anatomy, surgery, emergency medicine, and communication skill training with patients. Both students and educators believed that VR could enhance traditional approaches and complement the existing curriculum, anticipating improved preparedness for medical students through VR training applications. In conclusion, our results demonstrate the receptivity of both students and educators to immersive technologies, including VR, in medical education. Importantly, the data suggest that the adoption of VR in this field would be welcomed rather than resisted, potentially enhancing students' self-efficacy and enriching the medical school curriculum.

Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.

Complemental Value of Microstructural and Macrostructural MRI in the Discrimination of Neurodegenerative Parkinson Syndromes.

PURPOSE: Various MRI-based techniques were tested for the differentiation of neurodegenerative Parkinson syndromes (NPS); the value of these techniques in direct comparison and combination is uncertain. We thus compared the diagnostic performance of macrostructural, single compartmental, and multicompartmental MRI in the differentiation of NPS. METHODS: We retrospectively included patients with NPS, including 136 Parkinson's disease (PD), 41 multiple system atrophy (MSA) and 32 progressive supranuclear palsy (PSP) and 27 healthy controls (HC). Macrostructural tissue probability values (TPV) were obtained by CAT12. The microstructure was assessed using a mesoscopic approach by diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and diffusion microstructure imaging (DMI). After an atlas-based read-out, a linear support vector machine (SVM) was trained on a training set (n = 196) and validated in an independent test cohort (n = 40). The diagnostic performance of the SVM was compared for different inputs individually and in combination. RESULTS: Regarding the inputs separately, we observed the best diagnostic performance for DMI. Overall, the combination of DMI and TPV performed best and correctly classified 88% of the patients. The corresponding area under the receiver operating characteristic curve was 0.87 for HC, 0.97 for PD, 1.0 for MSA, and 0.99 for PSP. CONCLUSION: We were able to demonstrate that (1) MRI parameters that approximate the microstructure provided substantial added value over conventional macrostructural imaging, (2) multicompartmental biophysically motivated models performed better than the single compartmental DTI and (3) combining macrostructural and microstructural information classified NPS and HC with satisfactory performance, thus suggesting a complementary value of both approaches.

Assessing hypo-arousal during reward anticipation with pupillometry in patients with major depressive disorder: replication and correlations with anhedonia.

Major depressive disorder (MDD) is a devastating and heterogenous disorder for which there are no approved biomarkers in clinical practice. We recently identified anticipatory hypo-arousal indexed by pupil responses as a candidate mechanism subserving depression symptomatology. Here, we conducted a replication and extension study of these findings. We analyzed a replication sample of 40 unmedicated patients with a diagnosis of depression and 30 healthy control participants, who performed a reward anticipation task while pupil responses were measured. Using a Bayesian modelling approach taking measurement uncertainty into account, we could show that the negative correlation between pupil dilation and symptom load during reward anticipation is replicable within MDD patients, albeit with a lower effect size. Furthermore, with the combined sample of 136 participants (81 unmedicated depressed and 55 healthy control participants), we further showed that reduced pupil dilation in anticipation of reward is inversely associated with anhedonia items of the Beck Depression Inventory in particular. Moreover, using simultaneous fMRI, particularly the right anterior insula as part of the salience network was negatively correlated with depressive symptom load in general and anhedonia items specifically. The present study supports the utility of pupillometry in assessing noradrenergically mediated hypo-arousal during reward anticipation in MDD, a physiological process that appears to subserve anhedonia.

Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures.

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.

Free-viewing gaze patterns reveal a mood-congruency bias in MDD during an affective fMRI/eye-tracking task.

Major depressive disorder (MDD) has been related to abnormal amygdala activity during emotional face processing. However, a recent large-scale study (n = 28,638) found no such correlation, which is probably due to the low precision of fMRI measurements. To address this issue, we used simultaneous fMRI and eye-tracking measurements during a commonly employed emotional face recognition task. Eye-tracking provide high-precision data, which can be used to enrich and potentially stabilize fMRI readouts. With the behavioral response, we additionally divided the active task period into a task-related and a free-viewing phase to explore the gaze patterns of MDD patients and healthy controls (HC) and compare their respective neural correlates. Our analysis showed that a mood-congruency attentional bias could be detected in MDD compared to healthy controls during the free-viewing phase but without parallel amygdala disruption. Moreover, the neural correlates of gaze patterns reflected more prefrontal fMRI activity in the free-viewing than the task-related phase. Taken together, spontaneous emotional processing in free viewing might lead to a more pronounced mood-congruency bias in MDD, which indicates that combined fMRI with eye-tracking measurement could be beneficial for our understanding of the underlying psychopathology of MDD in different emotional processing phases.Trial Registration: The BeCOME study is registered on ClinicalTrials (gov: NCT03984084) by the Max Planck Institute of Psychiatry in Munich, Germany.

High-throughput functional analysis of regulatory variants using a massively parallel reporter assay.

Association studies describe genetic associations between noncoding variants and disease susceptibility; however, they do not provide functional insight into the underlying molecular mechanisms of these variants. We present a protocol to assay the regulatory potential of thousands of noncoding variants using massively parallel reporter assays. We describe steps for oligo design, generating a plasmid pool, and extracting tag-seq libraries from cells to quantify the tested sequences. For complete details on the use and execution of this protocol, please refer to Oliveros and Delfosse et al.1.

Stress-induced brain responses are associated with BMI in women.

Overweight and obesity are associated with altered stress reactivity and increased inflammation. However, it is not known whether stress-induced changes in brain function scale with BMI and if such associations are driven by peripheral cytokines. Here, we investigate multimodal stress responses in a large transdiagnostic sample using predictive modeling based on spatio-temporal profiles of stress-induced changes in activation and functional connectivity. BMI is associated with increased brain responses as well as greater negative affect after stress and individual response profiles are associated with BMI in females (pperm < 0.001), but not males. Although stress-induced changes reflecting BMI are associated with baseline cortisol, there is no robust association with peripheral cytokines. To conclude, alterations in body weight and energy metabolism might scale acute brain responses to stress more strongly in females compared to males, echoing observational studies. Our findings highlight sex-dependent associations of stress with differences in endocrine markers, largely independent of peripheral inflammation.

Unveiling the tribological potential of MXenes-current understanding and future perspectives.

Reducing energy consumption and CO2 emissions by improving the tribological performance of mechanical systems relies on the development of new lubrication concepts. Two-dimensional (2D) materials have been the subject of extensive tribological research due to their unique physical and chemical properties. 2D transition metal carbides, nitrides, and carbonitrides (MXenes), with their tuneable chemistry and structure, are a relatively new addition to the family of 2D materials. MXenes' good strength and stiffness, easy-to-shear ability, capability to form wear-resistant tribofilms, and the possibility to control their surface chemistry make them appealing candidates to be explored for tribological purposes. This review provides a comprehensive overview of MXenes' tribology, covering their structure-property relationship, synthesis approaches, deposition methods to generate MXene coatings for tribological purposes, and their fundamental tribological mechanisms. Furthermore, detailed insights into studies exploring MXenes' tribological performance from the nano- to the macro-scale are presented with special emphasis on their use as self-lubricating solid lubricants, lubricant additives, and reinforcement phases in composites.

Systematic characterization of regulatory variants of blood pressure genes.

High blood pressure (BP) is the major risk factor for cardiovascular disease. Genome-wide association studies have identified genetic variants for BP, but functional insights into causality and related molecular mechanisms lag behind. We functionally characterize 4,608 genetic variants in linkage with 135 BP loci in vascular smooth muscle cells and cardiomyocytes by massively parallel reporter assays. High densities of regulatory variants at BP loci (i.e., ULK4, MAP4, CFDP1, PDE5A) indicate that multiple variants drive genetic association. Regulatory variants are enriched in repeats, alter cardiovascular-related transcription factor motifs, and spatially converge with genes controlling specific cardiovascular pathways. Using heuristic scoring, we define likely causal variants, and CRISPR prime editing finally determines causal variants for KCNK9, SFXN2, and PCGF6, which are candidates for developing high BP. Our systems-level approach provides a catalog of functionally relevant variants and their genomic architecture in two trait-relevant cell lines for a better understanding of BP gene regulation.

Data-Driven Pupil Response Profiles as Transdiagnostic Readouts for the Detection of Neurocognitive Functioning in Affective and Anxiety Disorders.

BACKGROUND: Neurocognitive functioning is a relevant transdiagnostic dimension in psychiatry. As pupil size dynamics track cognitive load during a working memory task, we aimed to explore if this parameter allows identification of psychophysiological subtypes in healthy participants and patients with affective and anxiety disorders. METHODS: Our sample consisted of 226 participants who completed the n-back task during simultaneous functional magnetic resonance imaging and pupillometry measurements. We used latent class growth modeling to identify clusters based on pupil size in response to cognitive load. In a second step, these clusters were compared on affective and anxiety symptom levels, performance in neurocognitive tests, and functional magnetic resonance imaging activity. RESULTS: The clustering analysis resulted in two distinct pupil response profiles: one with a stepwise increasing pupil size with increasing cognitive load (reactive group) and one with a constant pupil size across conditions (nonreactive group). A larger increase in pupil size was significantly associated with better performance in neurocognitive tests in executive functioning and sustained attention. Statistical maps of parametric modulation of pupil size during the n-back task showed the frontoparietal network in the positive contrast and the default mode network in the negative contrast. The pupil response profile of the reactive group was associated with more thalamic activity, likely reflecting better arousal upregulation and less deactivation of the limbic system. CONCLUSIONS: Pupil measurements have the potential to serve as a highly sensitive psychophysiological readout for detection of neurocognitive deficits in the core domain of executive functioning, adding to the development of valid transdiagnostic constructs in psychiatry.

Nationwide analysis of hospital admissions and outcomes of patients with SARS-CoV-2 infection in Austria in 2020 and 2021.

This retrospective study evaluated temporal and regional trends of patient admissions to hospitals, intensive care units (ICU), and intermediate care units (IMCU) as well as outcomes during the COVID-19 pandemic in Austria. We analysed anonymous data from patients admitted to Austrian hospitals with COVID-19 between January 1st, 2020 and December 31st, 2021. We performed descriptive analyses and logistic regression analyses for in-hospital mortality, IMCU or ICU admission, and in-hospital mortality following ICU admission. 68,193 patients were included, 8304 (12.3%) were primarily admitted to ICU, 3592 (5.3%) to IMCU. Hospital mortality was 17.3%; risk factors were male sex (OR 1.67, 95% CI 1.60-1.75, p < 0.001) and high age (OR 7.86, 95% CI 7.07-8.74, p < 0.001 for 90+ vs. 60-64 years). Mortality was higher in the first half of 2020 (OR 1.15, 95% CI 1.04-1.27, p = 0.01) and the second half of 2021 (OR 1.11, 95% CI 1.05-1.17, p < 0.001) compared to the second half of 2020 and differed regionally. ICU or IMCU admission was most likely between 55 and 74 years, and less likely in younger and older age groups. We find mortality in Austrian COVID-19-patients to be almost linearly associated with age, ICU admission to be less likely in older individuals, and outcomes to differ between regions and over time.

Se Nanopowder Conversion into Lubricious 2D Selenide Layers by Tribochemical Reactions.

Transition metal dichalcogenide (TMD) coatings have attracted enormous scientific and industrial interest due to their outstanding tribological behavior. The paradigmatic example is MoS2 , even though selenides and tellurides have demonstrated superior tribological properties. Here, an innovative in operando conversion of Se nanopowders into lubricious 2D selenides, by sprinkling them onto sliding metallic surfaces coated with Mo and W thin films, is described. Advanced material characterization confirms the tribochemical formation of a thin tribofilm containing selenides, reducing the coefficient of friction down to below 0.1 in ambient air, levels typically reached using fully formulated oils. Ab initio molecular dynamics simulations under tribological conditions reveal the atomistic mechanisms that result in the shear-induced synthesis of selenide monolayers from nanopowders. The use of Se nanopowder provides thermal stability and prevents outgassing in vacuum environments. Additionally, the high reactivity of the Se nanopowder with the transition metal coating in the conditions prevailing in the contact interface yields highly reproducible results, making it particularly suitable for the replenishment of sliding components with solid lubricants, avoiding the long-lasting problem of TMD-lubricity degradation caused by environmental molecules. The suggested straightforward approach demonstrates an unconventional and smart way to synthesize TMDs in operando and exploit their friction- and wear-reducing impact.

Mechanical ventilation with ten versus twenty breaths per minute during cardio-pulmonary resuscitation for out-of-hospital cardiac arrest: A randomised controlled trial.

AIM OF THE STUDY: This study sought to assess the effects of increasing the ventilatory rate from 10 min-1 to 20 min-1 using a mechanical ventilator during cardio-pulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) on ventilation, acid-base-status, and outcomes. METHODS: This was a randomised, controlled, single-centre trial in adult patients receiving CPR including advanced airway management and mechanical ventilation offered by staff of a prehospital physician response unit (PRU). Ventilation was conducted using a turbine-driven ventilator (volume-controlled ventilation, tidal volume 6 ml per kg of ideal body weight, positive end-expiratory pressure (PEEP) 0 mmHg, inspiratory oxygen fraction (FiO2) 100%), frequency was pre-set at either 10 or 20 breaths per minute according to week of randomisation. If possible, an arterial line was placed and blood gas analysis was performed. RESULTS: The study was terminated early due to slow recruitment. 46 patients (23 per group) were included. Patients in the 20 min-1 group received higher expiratory minute volumes [8.8 (6.8-9.9) vs. 4.9 (4.2-5.7) litres, p < 0.001] without higher mean airway pressures [11.6 (9.8-13.6) vs. 9.8 (8.5-12.0) mmHg, p = 0.496] or peak airway pressures [42.5 (36.5-45.9) vs. 41.4 (32.2-51.7) mmHg, p = 0.895]. Rates of ROSC [12 of 23 (52%) vs. 11 of 23 (48%), p = 0.768], median pH [6.83 (6.65-7.05) vs. 6.89 (6.80-6.97), p = 0.913], and median pCO2 [78 (51-105) vs. 86 (73-107) mmHg, p > 0.999] did not differ between groups. CONCLUSION: 20 instead of 10 mechanical ventilations during CPR increase ventilation volumes per minute, but do not improve CO2 washout, acidaemia, oxygenation, or rate of ROSC. CLINICALTRIALS: gov Identifier: NCT04657393.

Association of immediate versus delayed extubation of patients admitted to intensive care units postoperatively and outcomes: A retrospective study.

AIM OF THIS STUDY: This study seeks to investigate, whether extubation of tracheally intubated patients admitted to intensive care units (ICU) postoperatively either immediately at the day of admission (day 1) or delayed at the first postoperative day (day 2) is associated with differences in outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of data from an Austrian ICU registry. Adult patients admitted between January 1st, 2012 and December 31st, 2019 following elective and emergency surgery, who were intubated at the day 1 and were extubated at day 1 or day 2, were included. We performed logistic regression analyses for in-hospital mortality and over-sedation or agitation following extubation. RESULTS: 52 982 patients constituted the main study population. 1 231 (3.3%) patients extubated at day 1 and 958 (5.9%) at day 2 died in hospital, 464 (1.3%) patients extubated at day 1 and 613 (3.8%) at day 2 demonstrated agitation or over-sedation after extubation during ICU stay; OR (95% CI) for in-hospital mortality were OR 1.17 (1.01-1.35, p = 0.031) and OR 2.15 (1.75-2.65, p<0.001) for agitation or over-sedation. CONCLUSIONS: We conclude that immediate extubation as soon as deemed feasible by clinicians is associated with favourable outcomes and may thus be considered preferable in tracheally intubated patients admitted to ICU postoperatively.