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The paper provides an overview of recent modelling of global material erosion and deposition in the fusion devices Wendelstein 7-X (W7-X), JET and ITER using the Monte-Carlo code ERO2.0. For validating the modelling tool in a three-dimensional environment, W7-X simulations are performed to describe carbon erosion from the graphite test divertor units, which were equipped in operational phase OP 1.2 and analysed post-mortem. Synthetic spectroscopy of carbon line emission is compared with experimental results from the divertor spectrometer measurement system, showing a good agreement in the e-folding lengths in the radial intensity profiles of carbon. In the case of metallic wall materials, earlier modelling of the Be/W environment in JET and ITER is revisited and extended with an updated set of sputtering and reflection data, as well as including the mixing model for describing the Be/W dynamics in the divertor. Motivated by recent H/D/T isotope experiments in JET, limited and diverted configuration pulses are modelled, showing the expected trend of both Be and W erosion increasing with isotope mass. For the JET diverted configuration pulses, it is shown that Be migrates predominantly to the upper part of the inner divertor where it initially leads to strong W erosion. With longer exposure time, the growth of a Be deposited layer leads to a reduction of W erosion in that region. A similar trend is observed in simulations of the ITER baseline Q = 10 scenario, however with a more symmetric Be migration pattern leading to deposition also on the outer divertor.

An integral approach to plasma-wall interaction (PWI) modelling for DEMO is presented, which is part of the EUROfusion Theory and Advanced Simulation Coordination activities that were established to advance the understanding and predictive capabilities for the modelling of existing and future fusion devices using a modern advanced computing approach. In view of the DEMO design, the aim of PWI modelling activities is to assess safety-relevant information regarding the erosion of plasma-facing components (PFCs), including its impact on plasma contamination, dust production, fuel inventory, and material response to transient events. This is achieved using a set of powerful and validated computer codes that deal with particular PWI aspects and interact with each other by means of relevant data exchange. Steady state erosion of tungsten PFC and subsequent transport and re-deposition of eroded material are simulated with the ERO2.0 code using a DEMO plasma background produced by dedicated SOLPS-ITER simulations. Dust transport simulations in steady state plasma also rely on the respective SOLPS-ITER solutions and are performed with the MIGRAINe code. In order to improve simulations of tungsten erosion in the divertor of DEMO, relevant high density sheath models are being developed based on particle-in-cell (PIC) simulations with the state-of-the-art BIT code family. PIC codes of the SPICE code family, in turn, provide relevant information on multi-emissive sheath physics, such as semi-empirical scaling laws for field-assisted thermionic emission. These scaling laws are essential for simulations of material melting under transient heat loads that are performed with the recently developed MEMENTO code, the successor of MEMOS-U. Fuel retention simulations assess tritium retention in tungsten and structural materials, as well as fuel permeation to the coolant, accounting for neutron damage. Simulations for divertor monoblocks of different sizes are performed using the FESTIM code, while for the first wall the TESSIM code is applied. Respective code-code dependencies and interactions, as well as modelling results achieved to date are discussed in this contribution.

Purpose: The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. Methods: A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and 5 days, none for toxicities related to treatment. There were no grade 4 acute toxicities and 1 grade 3 acute toxicity (sensory neuropathy). The only 2 grade 3 late toxicities recorded, osteoradionecrosis and intranasal carotid blowout (mild and not emergently treated), occurred in a single patient. We report overall survival as 83% at 5 years, with local failure-free survival and progression-free survival rates of 72% and 68%, respectively. Five patients developed distant disease, and among the 9/54 patients who died, 4 deaths were not attributed to treatment or recurrence. Conclusions: Our findings suggest that high-dose proton therapy alone or in combination with IMRT is a safe and effective treatment option for chordomas and chondrosarcomas of the skull base and spine.

Introduction: Stereotactic body radiation therapy (SBRT) is an emerging treatment modality for clinically localized prostate cancer (PCa). Online daily adaptive radiotherapy (ART) could potentially improve the therapeutic ratio of prostate SBRT by accounting for inter-fraction variation in target and OAR volumes. To our knowledge, no group has evaluated the clinical utility of a novel AI-augmented CT-based ART system for prostate SBRT. In this study we hypothesized that adaptive prostate SBRT plans would result in improved target coverage and lower dose to OARs in comparison to unadapted treatment plans. Methods: Seven patients with favorable intermediate to oligometastatic PCa treated with 5-fx prostate adaptive SBRT were retrospectively reviewed. Patients were treated with 3625 cGy to the prostate and seminal vesicles. 6 patients additionally received 2500 cGy to the pelvic nodes, 5 patients underwent a boost to 4000 cGy to the prostate. For each fraction, a CBCT was acquired and OARs (rectum, bladder, bowel, sigmoid, femurs) were segmented/deformed using AI. CTVs were rigidly registered. Volumes were adjusted manually and PTV expansions added. Adaptive treatment plans were developed based on the contoured targets and OARs and dose to these volumes for the adapted vs. initial plans were compared for each fraction. V100 and the D0.03 cc between scheduled and adapted treatment plans were compared using a Student’s t-test, with significance threshold of P

Sequential decision-making, where choices are made one after the other, is an important aspect of our daily lives. For example, when searching for a job, an apartment, or deciding when to buy or sell a stock, people often have to make decisions without knowing what future opportunities might arise. These situations, which are known as optimal stopping problems, involve a risk associated with the decision to either stop or continue searching. However, previous research has not consistently found a clear connection between individuals' search behavior in these tasks and their risk preferences as measured in controlled experimental settings. In this paper, we explore how particular characteristics of optimal stopping tasks affect people's choices, extending beyond their stable risk preferences. We find that (1) the way the underlying sampling distribution is presented (whether it is based on experience or description), (2) the sequential presentation of options, and (3) the unequal frequencies of choices to reject versus to accept significantly bias people choices. These results shed light on the complex nature of decisions that unfold sequentially and emphasize the importance of incorporating context factors when studying human decision behavior., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Metallothioneins (MTs) are small proteins that coordinate d-block metal ions in sulfur-metal clusters to control metal ion concentrations within the cell. Here we study metal cluster formation in the MT of the periwinkle Littorina littorea (LlMT) by nuclear magnetic resonance (NMR). We demonstrate that the three Cd 2+ ions in each domain are taken up highly cooperatively, that is, in an all-or-none fashion, with a four- to six-fold higher affinity for the C-terminal domain. During the transfer of metal ions from Cd 2+ -loaded MT to apo MT, Cd 2+ is most efficiently transferred from the metalated protein to the apo C-terminal domain. This behavior might be connected to unique structural motifs in the C-terminal domain, such as two double-CXC motifs and an increased proportion of positively charged residues. In Cd 2+ /Zn 2+ metal exchange experiments, the N-terminal domain displayed the most efficient inter-molecular metal exchange. Amide hydrogen exchange reveals fewer protected amides for the N-terminal domain, suggesting the structure might more easily "open up" to facilitate metal exchange. Experiments with a physical separation of donor and acceptor species demonstrate that metal exchange and transfer require protein-protein contacts. These findings provide insights into the mechanism of metal uptake and metal transfer, which are important processes during metal detoxification in snail MTs., (© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

Purpose: To evaluate OCT features for vitreomacular traction (VMT) release and change in macular hole (MH) size after treatment with ocriplasmin., Methods: Patients who had undergone treatment with ocriplasmin for VMT with or without MH ≤400 µm were included. The main outcomes were VMT release and changes in minimum linear diameter MH size at 4 weeks in MHs that persisted. OCT features evaluated were central retinal thickness, vitreomacular adhesion length, posterior vitreous cortex (PVC) insertion angles 500 µm from the insertion points, and minimum linear diameter size., Results: Sixty patients were included: 37 had isolated VMT and 23 VMT with a MH. Four weeks after ocriplasmin injection, the overall VMT release rate was 66.7% (40/60); 64.9% (24/37) in eyes with isolated VMT and 69.6% (16/23) in eyes with MH. VMT release was associated with younger age (P = 0.02). Macular hole closure was achieved in 26.1% (6/23) and was associated with a smaller ratio of the temporal to the nasal PVC angle (P < 0.01). Of the 17 persistent MHs, 76.5% (13/17) increased in minimum linear diameter size from baseline 186 (±78) to 358 (±133) µm (P < 0.001). Progression in minimum linear diameter size showed a negative linear association with the size of the nasal PVC angle (R2 = 0.39, P = 0.002) and a positive linear association with the ratio of the temporal to nasal PVC angle (R2 = 0.39, P = 0.002)., Conclusion: In patients with VMT-associated MHs, the risk of MH enlargement following ocriplasmin is negatively correlated with the nasal PVC angle size and is increased if the ratio of the temporal to nasal angle is >1.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are advancing cardiovascular development and disease modeling, drug testing, and regenerative therapies. However, hPSC-CM production is hindered by significant variability in the differentiation process. Establishment of early quality markers to monitor lineage progression and predict terminal differentiation outcomes would address this robustness and reproducibility roadblock in hPSC-CM production. An integrated transcriptomic and epigenomic analysis assesses how attributes of the cardiac progenitor cell (CPC) affect CM differentiation outcome. Resulting analysis identifies predictive markers of CPCs that give rise to high purity CM batches, including TTN, TRIM55, DGKI, MEF2C, MAB21L2, MYL7, LDB3, SLC7A11, and CALD1. Predictive models developed from these genes provide high accuracy in determining terminal CM purities at the CPC stage. Further, insights into mechanisms of batch failure and dominant non-CM cell types generated in failed batches are elucidated. Namely EMT, MAPK, and WNT signaling emerge as significant drivers of batch divergence, giving rise to off-target populations of fibroblasts/mural cells, skeletal myocytes, epicardial cells, and a non-CPC SLC7A11+ subpopulation. This study demonstrates how integrated multi-omic analysis of progenitor cells can identify quality attributes of that progenitor and predict differentiation outcomes, thereby improving differentiation protocols and increasing process robustness., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The COVID-19 pandemic has impacted adolescent mental health worldwide. The current study aims to assess the feelings of French adolescents and the factors related to anxiety among these adolescents during the first lockdown due to COVID-19. A sample of 284 French adolescents from the Grand Est region aged 12-18 years completed an online survey evaluating their pandemic-related anxiety symptoms, behaviors, and feelings regarding the contingent strategies of lockdown that were taken and their living and learning conditions, family relationships, and social support. The Generalized Anxiety Disorder Scale (GAD-6) was used to assess anxiety. Data on parents' mental health status were also collected. A word cloud was generated to visualize respondents' feelings according to word use frequency. Cross-sectional analysis with linear regression was performed to identify the factors associated with a higher level of anxiety in adolescents. Higher anxiety scale scores were observed among females than among males (β = 1.2; P = 0.0005), among adolescents experiencing conflicts at home (β = 0.9; P = 0.03) and difficulties in isolation (β = 1.1; P = 0.02) than among those who did not report any difficulty, and among those working less than 2 h a day (β = 1.1; P = 0.003) than among those working more. Anxiety scale scores were lower in adolescents with higher family social support (β = -0.66; P < 0.001) and those with parents with no anxiety (β = -2.28; P < 0.001), lower anxiety (β = -1.38; P = 0.018), and higher mental health-related quality of life (β = -0.04; P = 0.03). These findings suggest a need to support interventions targeting parents' anxiety, develop strategies to increase family support, and establish consistent work schedules for children., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

For a better understanding of cadmium (Cd) accumulation over long time periods in cereals, Cd levels of the German wheat and rye harvest from 1975 to 2021 were analyzed. Overall, wheat had higher grain Cd concentrations than rye. Comparing mean values from different time periods showed that Cd levels in winter rye have stabilized, while Cd concentrations in winter wheat have decreased. Furthermore, Cd concentrations in almost all samples were below the newly introduced European Commission limits specifying the maximum permissible contaminant levels in foodstuffs (Cd in grains: rye 50 μg/kg FW; wheat 100 μg/kg FW). However, it is important to note that Cd is still ubiquitous in the German wheat and rye harvest. Although there has been a significant reduction in emissions and imissions for around 30 years, the extraordinarily long biological half-life and carcinogenicity of Cd still make it a relevant substance to food safety and human health.

Study Objectives: Wearable devices that monitor sleep stages and heart rate offer the potential for longitudinal sleep monitoring in patients with neurodegenerative diseases. Sleep quality reduces with disease progression in Huntington's disease (HD). However, the involuntary movements characteristic of HD may affect the accuracy of wrist-worn devices. This study compares sleep stage and heart rate data from the Fitbit Charge 4 (FB) against polysomnography (PSG) in participants with HD., Methods: Ten participants with manifest HD wore an FB during overnight hospital-based PSG, and 9 of these participants continued to wear the FB for 7 nights at home. Sleep stages (30-second epochs) and minute-by-minute heart rate were extracted and compared against PSG data., Results: FB-estimated total sleep and wake times and sleep stage times were in good agreement with PSG, with intraclass correlations of 0.79-0.96. However, poor agreement was observed for wake after sleep onset and the number of awakenings. FB detected waking with 68.6 ± 15.5% sensitivity and 93.7 ± 2.5% specificity, rapid eye movement sleep with high sensitivity and specificity (78.7 ± 31.9%, 95.6 ± 2.3%), and deep sleep with lower sensitivity but high specificity (56.4 ± 28.8%, 95.0 ± 4.8%). FB heart rate was strongly correlated with PSG, and the mean absolute error between FB and PSG heart rate data was 1.16 ± 0.42 beats/min. At home, longer sleep and shorter wake times were observed compared with hospital data, whereas percentage sleep stage times were consistent with hospital data., Conclusions: Results suggest the potential for long-term monitoring of sleep patterns using wrist-worn wearable devices as part of symptom management in HD., Citation: Doheny EP, Renerts K, Braun A, et al. Assessment of Fitbit Charge 4 for sleep stage and heart rate monitoring against polysomnography and during home monitoring in Huntington's disease. J Clin Sleep Med . 2024;20(7):1163-1171., (© 2024 American Academy of Sleep Medicine.)

Strain ZW T0&#95;25 T was isolated from an onion sample (Allium cepa var. Hytech F1) within a storage trial and proofed to be a novel, aerobic, Gram-stain negative, rod-shaped bacterial strain. Analyses of the 16S rRNA gene sequence and of the whole draft genome sequences, i.e., digital DNA-DNA hybridization (dDDH), Average Nucleotide Identity (ANI) and Average Amino Acid Identity (AAI) showed that this strain represents a new species of the genus Bosea. The genome size of strain ZW T0&#95;25 T is 6.19 Mbp, and the GC content is 66.9%. As whole cell sugars, rhamnose, ribose and glucose were identified. Ubiquinone Q-10 is the major respiratory quinone with 97.8%. Polar lipids in strain ZW T0&#95;25 T are composed of one phosphatidylethanolamine, one phosphatidylglycerol, one aminophospholipid, two aminolipids, one glycolipid and two phospholipids whereas the fatty acid profile predominantly consists of C18:1 w7c (63.3%), C16:1 w7c (19.5%) and C16:0 (7.1%). Phenotypic traits were tested in the wet lab as well as predicted in silico from genome data. Therefore, according to this polyphasic approach, the new name Bosea rubneri sp. nov. with the type strain ZW T0&#95;25 T (= DSM 116094  T  = LMG 33093  T ) is proposed., (© 2024. The Author(s).)

Today's biodiversity crisis fundamentally threatens the habitability of the planet, thus ranking among the primary human challenges of our time. Much emphasis is currently placed on the loss of biodiversity in the Anthropocene, yet these debates often portray biodiversity as a purely natural phenomenon without much consideration of its human dimensions and frequently lack long-term vistas. This paper offers a deep-time perspective on the key role of the evolving human niche in ecosystem functioning and biodiversity dynamics. We summarize research on past hunter-gatherer ecosystem contributions and argue that human-environment feedback systems with important biodiversity consequences are probably a recurrent feature of the Late Pleistocene, perhaps with even deeper roots. We update current understandings of the human niche in this light and suggest that the formation of palaeo-synanthropic niches in other animals proffers a powerful model system to investigate recursive interactions of foragers and ecosystems. Archaeology holds important knowledge here and shows that ecosystem contributions vary greatly in relation to different human lifeways, some of which are lost today. We therefore recommend paying more attention to the intricate relationship between biodiversity and cultural diversity, contending that promotion of the former depends on fostering the latter. This article is part of the theme issue 'Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere'.

Background: Accurately assessing the severity and frequency of fluctuating motor symptoms is important at all stages of Parkinson's disease management. Contrarily to time-consuming clinical testing or patient self-reporting with uncertain reliability, recordings with wearable sensors show promise as a tool for continuously and objectively assessing PD symptoms. While wearables-based clinical assessments during standardised and scripted tasks have been successfully implemented, assessments during unconstrained activity remain a challenge., Methods: We developed and implemented a supervised machine learning algorithm, trained and tested on tremor scores. We evaluated the algorithm on a 67-hour database comprising sensor data and clinical tremor scores for 24 Parkinson patients at four extremities for periods of about 3 hours. A random 25% subset of the labelled samples was used as test data, the remainder as training data. Based on features extracted from the sensor data, a Support Vector Machine was trained to predict tremor severity. Due to the inherent imbalance in tremor scores, we applied dataset rebalancing techniques., Results: Our classifier demonstrated robust performance in detecting tremor events with a sensitivity of 0.90 on the test-portion of the resampled dataset. The overall classification accuracy was high at 0.88., Conclusion: We implemented an accurate classifier for tremor monitoring in free-living environments that can be trained even with modestly sized and imbalanced datasets. This advancement offers significant clinical value in continuously monitoring Parkinson's disease symptoms beyond the hospital setting, paving the way for personalized management of PD, timely therapeutic adjustments, and improved patient quality of life., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Fernando Rodriguez et al.)

Purpose: This research seeks to extend previous research into student discipline and competitiveness, at the macro or national level, to the micro or individual level. The role of factors with the potential to impact individual competitiveness, namely the expectations of the mother and the father, the importance of school discipline played in primary and secondary schools, and past participation in sport and music were examined., Design/methodology/approach: Data from a sample of current university students and recent graduates representing Western (the United States) and Asian regions (South Korea and China) were analysed using multiple regressions to establish the explanatory power of independent variables in the competitiveness model, including testing for moderation effects of country of birth., Results: The study found that personal discipline is significantly associated with individual competitiveness. The importance placed on discipline in primary schools was found to predict individual competitiveness as were parents' expectations, yet with nuances in terms of maternal and paternal expectations. Surprisingly, neither participation in music nor discipline at secondary school was found to significantly associate with individual competitiveness. At the same time, the study did find moderating effects of country of birth and the number of years students played sport in predicting competitiveness., Originality/value: Guided by the Ecological Systems Theory and the notion of the Pygmalion effect, we develop a framework of factors that shape an individual's competitiveness. The results make several theoretical contributions by establishing new drivers of individual competitiveness, and as such illuminating the importance of discipline during schooling and how parental expectations drive performance. Implications for employers, educational institutions, and parents are outlined and directions for further research are offered., Competing Interests: No potential conflict of interest was reported by the authors., (© 2024 The Authors.)

By investigating wet and dry age-related ripening of beef, Pseudomonas strains V3/3/4/13 T and V3/K/3/5 T were isolated. Strain V3/3/4/13 T exhibited more than 99 % 16S rRNA gene-based similarity to Pseudomonas fragi and other members of this group, while isolate V3/K/3/5 T was very close to Pseudomonas veronii and a number of relatives within the Pseudomonas fluorescens group. Additional comparisons of complete rpoB sequences and draft genomes allowed us to place isolate V3/3/4/13 T close to Pseudomonas deceptionensis DSM 26521 T . In the case of V3/K/3/5 T the closest relative was P. veronii DSM 11331 T . Average nucleotide identity (ANIb) and digital DNA-DNA hybridization (dDDH) values calculated from the draft genomes of V3/3/4/13 T and P. deceptionensis DSM 26521 T were 88.5 and 39.8 %, respectively. For V3/K/3/5 T and its closest relative P. veronii DSM 11331 T , the ANIb value was 95.1 % and the dDDH value was 60.7 %. The DNA G+C contents of V3/3/4/13 T and V3/K/3/5 T were 57.4 and 60.8 mol%, respectively. Predominant fatty acids were C 16 : 0 , C 18 : 1  ω7 c , C 17 : 0 cyclo and summed feature C 16 : 1 ω7 ct /C 15 : 0 iso 2OH. The main respiratory quinones were Q9, with minor proportions of Q8 and, in the case of V3/K/3/5 T , additional Q10. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and, in the case of V3/K/3/5 T , additional phosphatidylcholine. Based on the combined data, isolates V3/3/4/13 T and V3/K/3/5 T should be considered as representatives of two novel Pseudomonas species. The type strain of the newly proposed Pseudomonas kulmbachensis sp. nov. is V3/3/4/13 T (=DSM 113654 T =LMG 32520 T ), a second strain belonging to the same species is FLM 004-28 (=DSM 113604=LMG 32521); the type strain for the newly proposed Pseudomonas paraveronii sp. nov. is V3/K/3/5 T (=DSM 113573 T =LMG 32518 T ) with a second isolate FLM 11 (=DSM 113572=LMG 32519).

Prior data from our group showed that first-lactation cows under organic management in United States have a high prevalence of Staphylococcus aureus, Streptococcus spp., and Staphylococcus chromogenes intramammary infections (IMI) in early lactation. Nonetheless, the relationship between IMI, udder health, and milk production in organically reared primiparous cows remains elusive. The objectives of this observational study were to investigate the relationship between presence and persistence of IMI in the first 35 d in milk (DIM) and somatic cell count (SCC) and milk production during the first 6 mo of lactation on first-lactation organic dairy cows. The analysis included a total of 1,348 composite milk samples collected during the first 35 DIM that were submitted for milk culture and 1,674 Dairy Herd Improvement Association (DHIA) tests during the first 180 DIM from 333 heifers in 4 organic dairy farms, enrolled between February 2019 and January 2020. The association between IMI in the first 35 DIM and new high SCC (SCC > 200,000 cells/mL) and milk production during the first 6 mo of lactation was investigated using Cox proportional hazards regression and mixed linear regression, respectively. The association between IMI persistence (harboring the same microorganism as reported by the laboratory for 2 or more samples) in the first 35 DIM and number of DHIA tests with high SCC during the first 6 mo of lactation was modeled using negative binomial regression. The presence of IMI by Staph. aureus (hazard ratio [HR] [95% confidence interval {CI}]: 3.35 [2.64, 4.25]) or Streptococcus spp. (HR [95% CI]: 2.25 [2.12, 2.39]) during the first 35 DIM was associated with an increased risk of new high SCC during the first 6 mo of lactation. Milk production was reduced when Streptococcus spp. were identified in milk samples. However, there was no evidence of a difference in milk production in Staph. aureus IMI. Isolation of non-aureus staphylococci and mammaliicocci was related to a mild increase in the hazards of high SCC (HR [95% CI]: 1.34 [0.97, 1.85]) and a decrease in milk production during one or more postpartum tests. Presence of gram-negative or Streptococcus-like organisms IMI was not associated with either high SCC or milk production. Presence of Bacillus IMI was associated with a lower hazard of new high SCC (HR [95% CI]: 0.45 [0.30, 0.68]), and higher milk production during the first 180 d of lactation (overall estimate [95% CI]: 1.7 kg/d [0.3, 3.0]). The persistence of IMI in the first 35 DIM was associated with the number of tests with high SCC during the lactation for all microorganisms except for Staphylococcus chromogenes. Therefore, our results suggest that the persistence of IMI in the first 35 DIM could be an important factor to understand the association between IMI detected in early lactation and lactational SCC and milk production in organic dairy heifers. Our study described associations between IMI, udder health, and milk production in first-lactation organic dairy cows that are consistent with findings from conventional dairy farms., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Sleep abnormalities may represent an independent risk factor for neurodegeneration. An international expert group convened in 2021 to discuss the state-of-the-science in this domain. The present article summarizes the presentations and discussions concerning the importance of a strategy for studying sleep- and circadian-related interventions for early detection and prevention of neurodegenerative diseases. An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years; discussed the current challenges in the field of relationships among sleep, sleep disorders, and neurodegeneration; and identified future priorities. Sleep efficiency and slow wave activity during non-rapid eye movement (NREM) sleep are decreased in cognitively normal middle-aged and older adults with Alzheimer's disease (AD) pathology. Sleep deprivation increases amyloid-β (Aβ) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases Aβ. Obstructive sleep apnea (OSA) is a risk factor for dementia. Studies indicate that positive airway pressure (PAP) treatment should be started in patients with mild cognitive impairment or AD and comorbid OSA. Identification of other measures of nocturnal hypoxia and sleep fragmentation could better clarify the role of OSA as a risk factor for neurodegeneration. Concerning REM sleep behavior disorder (RBD), it will be crucial to identify the subset of RBD patients who will convert to a specific neurodegenerative disorder. Circadian sleep-wake rhythm disorders (CSWRD) are strong predictors of caregiver stress and institutionalization, but the absence of recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying sleep-circadian-related interventions for early detection/prevention of neurodegenerative diseases are required. CSWRD evaluation may help to identify additional biomarkers for phenotyping and personalizing treatment of neurodegeneration., (© 2023. Fondazione Società Italiana di Neurologia.)

Objective: To evaluate the impact of antenatal corticosteroid therapy (ACS) on birth outcomes in term infants exposed during pregnancy., Study Design: Exposed newborns were compared with non-exposed controls in a 1 to 2 design. Multivariate analysis was used to assess the effect of ACS exposure on neonatal outcomes., Result: 408 newborns were included (136 exposed to ACS, 272 non-exposed). Mean ± SD head circumference (HC) was 33.7 ± 1.4 vs 34.3 ± 1.6 cm, p = 0.001 in exposed vs controls; birth weight was 3.1 ± 0.4 vs 3.3 ± 0.4 kg, p = 0.0001; and birth height was 47.9 ± 2.1 vs. 49.1 ± 2.0 cm, p < 0.0001. Hypocalcemia (4.4 vs 0.7%, p = 0.019) and feeding difficulties (5.1 vs 1.5%, p = 0.047) were significantly more common in exposed newborns. Multivariate analysis for HC showed a significant independent association with ACS exposure (β = -0.5, p = 0.009)., Conclusion: Term newborns exposed to ACS have lower birth HC and higher risk of neonatal complications., Clinical Trial Registration: NCT05640596., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Integrin α 1 β 1 is an adhesion receptor that binds to collagen and laminin. It regulates cell adhesion, cytoskeletal organization, and migration. The cytoplasmic tail of the α 1 subunit consists of 15 amino acids and contains six positively charged lysine residues. In this study, we present evidence that the α 1 integrin cytoplasmic tail (α 1 CT) directly associates with phosphoinositides, preferentially with phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P 3 ). Since the association was disrupted by calcium, magnesium and phosphate ions, this interaction appears to be in ionic nature. Here, the peptide-lipid interaction was driven by the conserved KIGFFKR motif. The exchange of both two potential phospholipid-binding lysines for glycines in the KIGFFKR motif increased α 1 β 1 integrin-specific adhesion and F-actin cytoskeleton formation compared to cells expressing the unmodified α 1 subunit, whereas only mutation of the second lysine at position 1171 increased levels of constitutively active α 1 β 1 integrins on the cell surface. In addition, enhanced focal adhesion formation and increased phosphorylation of focal adhesion kinase, but decreased phosphorylation of AKT was observed in these cells. We conclude that the KIGFFKR motif, and in particular lysine1171 is involved in the dynamic regulation of α 1 β 1 integrin activity and that the interaction of α 1 CT with phosphoinositides may contribute to this process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Whole-genome sequencing (WGS) represents the main technology for SARS-CoV-2 lineage characterization in diagnostic laboratories worldwide. The rapid, near-full-length sequencing of the viral genome is commonly enabled by high-throughput sequencing of PCR amplicons derived from cDNA molecules. Here, we present a new approach called NASCarD (Nanopore Adaptive Sampling with Carrier DNA), which allows a low amount of nucleic acids to be sequenced while selectively enriching for sequences of interest, hence limiting the production of non-target sequences. Using COVID-19 positive samples available during the omicron wave, we demonstrate how the method may lead to >99% genome completeness of the SARS-CoV-2 genome sequences within 7 h of sequencing at a competitive cost. The new approach may have applications beyond SARS-CoV-2 sequencing for other DNA or RNA pathogens in clinical samples.

Purpose: To investigate the effect of an inverted internal limiting membrane flap (IF) and other factors on metamorphopsia after macular hole surgery., Methods: Prospective case series of patients undergoing pars plana vitrectomy with gas tamponade, with either conventional internal limiting membrane peeling (CP) or an IF, for primary idiopathic macular holes ≤ 500 µ m. Vertical and horizontal metamorphopsia were measured as M-scores (degrees) using M-charts preoperatively and at 2, 6, and 12 months postoperatively., Results: Fifty-three eyes of 53 patients were included of whom 27 underwent CP and 26 were treated with an IF. After macular hole surgery, all patients were pseudophakic. Vertical and horizontal metamorphopsia improved from 1.08 (±0.51) and 0.98 (±0.70) preoperatively to 0.58 (±0.37) and 0.45 (±0.36) at 2 months ( P < 0.01), with no further significant improvement at 6 months (0.39 [±0.31], P = 0.07 and 0.31 [±0.28], P = 0.18) or at 12 months (0.37 [±0.30], P = 0.72 and 0.28 [±0.28], P = 0.99). There was no significant difference in the mean vertical and horizontal metamorphopsia between patients with CP and with an IF at 2 months ( P = 0.063, P = 0.10), 6 months ( P = 0.25, P = 0.16), or 12 months ( P = 0.62, P = 0.22). Preoperative vertical M-score improved at 12 months after macular hole surgery by 61% and 64% in the CP and IF groups, respectively ( P = 0.84), and the horizontal M-score by 65% and 71%, respectively ( P = 0.98)., Conclusion: The use of an IF has no evident bearing on the degree of postoperative metamorphopsia 12 months after surgical repair of macular holes ≤ 500 µ m.

Leucine and Isoleucine are two amino acids that differ only by the positioning of one methyl group. This small difference can have important consequences in α-helices, as the β-branching of Ile results in helix destabilization. We set out to investigate whether there are general trends for the occurrences of Leu and Ile residues in the structures and sequences of class A GPCRs (G protein-coupled receptors). GPCRs are integral membrane proteins in which α-helices span the plasma membrane seven times and which play a crucial role in signal transmission. We found that Leu side chains are generally more exposed at the protein surface than Ile side chains. We explored whether this difference might be attributed to different functions of the two amino acids and tested if Leu tunes the hydrophobicity of the transmembrane domain based on the Wimley-White whole-residue hydrophobicity scales. Leu content decreases the variation in hydropathy between receptors and correlates with the non-Leu receptor hydropathy. Both measures indicate that hydropathy is tuned by Leu. To test this idea further, we generated protein sequences with random amino acid compositions using a simple numerical model, in which hydropathy was tuned by adjusting the number of Leu residues. The model was able to replicate the observations made with class A GPCR sequences. We speculate that the hydropathy of transmembrane domains of class A GPCRs is tuned by Leu (and to some lesser degree by Lys and Val) to facilitate correct insertion into membranes and/or to stably anchor the receptors within membranes., (© 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)