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We demonstrate how tabletop settings combining hyperbolic lattices with nonlinear dynamics universally encode aspects of the bulk-boundary correspondence between gravity in anti-de-Sitter (AdS) space and conformal field theory (CFT). Our concrete and broadly applicable holographic toy model simulates gravitational self-interactions in the bulk and features an emergent CFT with nontrivial correlations on the boundary. We measure the CFT data contained in the two- and three-point functions and clarify how a thermal CFT is simulated through an effective black hole geometry. As a concrete example, we propose and simulate an experimentally feasible protocol to measure the holographic CFT using electrical circuits.

Objective: To evaluate the exposure frequency effect of 0.454% stannous fluoride (SnF 2 ) toothpaste in controlling gingivitis., Methods: Two randomized controlled trials enrolled generally healthy adults with gingivitis. The study duration was 1 mo (study 1) and 3 mo (study 2). Gingivitis was assessed using the Löe-Silness Gingival Index (LSGI) at baseline, 1 mo (both studies), and 3 mo (study 2); bleeding scores were derived from the LSGI. Study groups consisted of positive control (twice-daily use of 0.454% SnF 2 toothpaste), experimental group (brushing in the morning with SnF 2 toothpaste and in the evening with 0.76% sodium monofluorophosphate [SMFP] toothpaste), and negative control (twice-daily use of SMFP toothpaste). The primary endpoint was number of bleeding sites., Results: Study 1 and study 2 each enrolled and randomized 90 participants; 86 and 89 participants, respectively, completed the trials. At baseline, the mean (SD) number of bleeding sites was 47.6 (18.54) in study 1 and 41.5 (17.84) in study 2. At 3 mo (study 2), the positive control produced 51.3% fewer bleeding sites, and the experimental group produced 32.5% fewer bleeding sites versus the negative control ( P < 0.001 for both). At 1 mo, the positive control produced 45.1% (study 1) and 45.8% (study 2) fewer bleeding sites versus the negative control ( P < 0.001 for both), and the experimental group produced 33.0% (study 1) and 24.8% (study 2) fewer bleeding sites, respectively, versus the negative control ( P ≤ 0.002 for both). The benefit was observed as early as 1 mo and was consistent with 3-mo results., Conclusion: This research is to our knowledge the first to demonstrate a gingivitis-reduction response effect for the frequency of bioavailable SnF 2 toothpaste use, with maximum benefit from twice-daily use, followed by a single-daily exposure versus the negative control. Clinical trial registration numbers: NCT05916508 and NCT05916521., Knowledge Transfer Statement: The results of this study can be used by dental professionals to guide their recommendations for therapeutic toothpaste for gingival health. Emphasis on the importance of twice-daily brushing with bioavailable stannous fluoride dentifrice will help patients optimize gingival health benefits achieved via self-care., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. He, Dr. Zou, Dr. Grender, Dr. Kaminski, and Dr. Biesbrock are employees of The Procter & Gamble Company, the manufacturer of Crest Pro-Health Sensitive and Enamel Shield toothpaste. Dr. Amini declares no conflicts of interest.

Zenker's diverticulum (ZD), also known as a cricopharyngeal pouch, is a pulsion pseudodiverticulum located dorsally at the pharyngoesophageal junction. The pathophysiology of ZD involves cricopharyngeal spasm, incoordination, impaired upper esophageal sphincter opening, and structural changes in the cricopharyngeal muscle, leading to symptoms such as dysphagia, regurgitation of undigested food, foreign body sensation, halitosis, unintentional weight loss, and respiratory issues. Treatment for symptomatic ZD typically involves myotomy of the cricopharyngeal muscle. Endoscopic techniques, particularly flexible endoscopy septotomy (FES) and Zenker peroral endoscopic myotomy (Z-POEM), have become preferred options due to their minimally invasive nature. This review discusses the techniques and clinical outcomes of FES and Z-POEM, focusing on specific clinical scenarios to guide the choice between these methods. Additionally, the variability in FES techniques, the effectiveness of Z-POEM, and the impact of different diverticulum sizes on treatment outcomes are analyzed, providing a comprehensive overview of current therapeutic approaches for ZD., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Aim: We aim to determine the evolutionary origins and population genetics of mallard-like ducks of Oceania, greater Indonesia, and the Philippines., Location: Oceania, greater Indonesia, and the Philippines., Taxon: Mallard (Anas platyrhynchos), Pacific black duck (A. superciliosa spp.), and Philippine duck (A. luzonica) METHODS: Thousands of nuclear ddRAD-seq loci and the mitochondrial DNA control region were assayed across individuals representative of each species' range. We assessed population structure and phylogenetic relationships, as well as estimated demographic histories to reconstruct the biogeographical history of each species., Results: Philippine and Pacific black ducks represent unique genetic lineages that diverged from the mallard 1-2 million years ago. We find no support for the Philippine duck representing a hybrid species as once posited; however, their low levels of genetic diversity requires further attention. We find a lack of substructure among Philippine ducks. However, we found pronounced differentiation between subspecies of Pacific black ducks, especially between A. s. superciliosa from New Zealand and A. s. rogersi from Australia, Papua New Guinea, and Timor-Leste, Indonesia. Anas superciliosa pelewensis gave mixed results; individuals from the Solomon Islands were differentiated from the other subspecies, but those from the island of Aunu'u, American Samoa, were genetically more similar to A. s. rogersi than A. s. pelewensis samples from the Solomon Islands. Finally, we find limited evidence of interspecific gene flow at evolutionary scales, and mallard introgression among contemporary samples., Main Conclusions: Mallard-like ducks radiated across Oceania, greater Indonesia, and the Philippines within the last 2 million years. Only the Pacific black duck showed unique sub-structuring that largely followed known sub-species ranges, except for A. s. pelewensis. We posit that the high interrelatedness among Solomon Island samples suggests that their genetic distinctiveness may simply be the result of high levels of genetic drift. In contrast, we conclude that mainland Australian Pacific black ducks were the most likely source for the recent colonization of American Samoa. As a result, our findings suggest that either the A. s. pelewensis subspecies designations and/or its geographical range may require re-evaluation. Continued re-evaluation of evolutionary and taxonomic relationships is necessary when attempting to reconstruct and understand biogeographical histories, with important implications towards any attempts to implement conservation strategies., (Published by Elsevier Inc.)

Purpose: Inflammation plays a crucial role in the development of atherosclerotic plaques. Pentraxin 3 (PTX3) is produced at the site of inflammation and has been identified as a specific marker of atherosclerosis, vascular inflammation, and progression of the coronary artery disease (CAD). The aim of the study was to establish if PTX3 has potential relations with classical markers of cardiovascular risk, and if PTX3 may act as an independent risk factor of CAD occurrence and advancement., Materials and Methods: The study included 98 patients with stable CAD confirmed in coronary angiography (CAD group) (median age 65 interquartile range [IQR] 61-72 years; 72 ​% men). The control group consisted of 40 patients without CAD., Results: The CAD group had significantly higher PTX3 concentration compared to the control group. There was a correlation with age, male gender, lipid profile and intima-media thickness. There was no correlation between PTX3 concentration and the number of coronary vessels with significant atherosclerotic lesions and the advancement of atherosclerotic lesions on the Gensini scoring scale. The cut-off point was determined for 0.89 ​ng/ml for the exclusion of angiographically significant atherosclerotic lesions., Conclusions: Patients with CAD have significantly higher concentration of PTX3. There was no correlation between PTX3 and the advancement of angiographically significant atherosclerotic lesions in coronary arteries. Low PTX3 concentration may serve as an indicator for the absence of atherosclerosis., 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 © 2024. Published by Elsevier B.V.)

Aim: This study compared neurodevelopmental screening questionnaires completed when preterm-born children reached 2 years of corrected age with social communication skills at 5.5 years of age., Methods: Eligible subjects were born in 2011 at 24-34 weeks of gestation, participated in a French population-based epidemiological study and were free of motor and sensory impairment at 2 years of corrected age. The Ages and Stages Questionnaire (ASQ) and the Modified Checklist for Autism in Toddlers (M-CHAT) were used at 2 years and the Social Communication Questionnaire (SCQ) at 5.5 years of age., Results: We focused on 2119 children. At 2 years of corrected age, the M-CHAT showed autistic traits in 20.7%, 18.5% and 18.2% of the children born at 24-26, 27-31 and 32-34 weeks of gestation, respectively (p = 0.7). At 5.5 years of age, 12.6%, 12.7% and 9.6% risked social communication difficulties, with an SCQ score ≥90th percentile (p = 0.2). A positive M-CHAT score at 2 years was associated with higher risks of social communication difficulties at 5.5 years of age (odds ratio 3.46, 95% confidence interval 2.04-5.86, p < 0.001). Stratifying ASQ scores produced similar results., Conclusion: Using parental neurodevelopmental screening questionnaires for preterm-born children helped to identify the risk of later social communication difficulties., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objective: Epileptic Encephalopathy / Developmental Epileptic Encephalopathy with spike-and-wave activation during sleep (EE/DEE-SWAS) is a self-limiting childhood epilepsy syndrome but may cause permanent neurocognitive impairment. Surgical interventions have been controversial in the treatment of EE/DEE-SWAS. This systematic review aims to evaluate the efficacy of various surgical procedures on the outcomes of EE/DEE-SWAS., Methods: A systematic review was performed per the PRISMA guidelines. A total of 14 retrospective studies were identified, comprising 131 cases of EE/DEE-SWAS treated with epilepsy surgery. The review analyzed presurgical data, surgical interventions, as well as outcomes related to seizures, EEG, and neuropsychological assessments., Results: Epilepsy surgery was successfully performed in 131 cases with minor complications. The average age was 2.6 years at seizure onset and 5.0 years at diagnosis of SWAS. Excellent seizure control (Engel I and II) was achieved in 80.6 %, 78.6 %, 77.4 % and 27.2 % of patients receiving hemispherectomies, focal resections, multiple subpial transections (MSTs), and corpus callosotomies (CCTs), respectively. EEG SWAS resolution was seen in 79.7 % of hemispherectomy cases, 78.6 % in focal resections, 63.9 % in MSTs, and 8.3 % in CCTs. Neurocognitive and behavioral improvement was noted in 58.0 %, 71.4 %, 58.3 % and 16.7 % for patients receiving hemispherectomies, focal resections, MSTs, and CCTs, respectively. A correlation between improved seizure control and SWAS resolution was observed with improved neuropsychological outcomes., Conclusion: Epilepsy surgery is a safe and effective treatment for carefully selected children with drug-resistant EE/DEE-SWAS. Patients who underwent epilepsy surgery had reduction of seizure burden, SWAS resolution and improvements in neurocognitive and behavioral function., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

It is unclear whether metabolic health corresponds to reduced oncogenesis or vice versa. We study Tudor-interacting repair regulator (TIRR), an inhibitor of p53 binding protein 1 (53BP1)-mediated p53 activation, and the physiological consequences of enhancing tumor suppressor activity. Deleting TIRR selectively activates p53, significantly protecting against cancer but leading to a systemic metabolic imbalance in mice. TIRR-deficient mice are overweight and insulin resistant, even under normal chow diet. Similarly, reduced TIRR expression in human adipose tissue correlates with higher BMI and insulin resistance. Despite the metabolic challenges, TIRR loss improves p53 heterozygous (p53 HET ) mouse survival and correlates with enhanced progression-free survival in patients with various p53 HET carcinomas. Finally, TIRR's oncoprotective and metabolic effects are dependent on p53 and lost upon p53 deletion in TIRR-deficient mice, with glucose homeostasis and orexigenesis being primarily regulated by TIRR expression in the adipose tissue and the CNS, respectively, as evidenced by tissue-specific models. In summary, TIRR deletion provides a paradigm of metabolic deregulation accompanied by reduced oncogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Acrylamide (AA) is formed in foods due to thermal processes. AA was analysed in 230 foods in the first German Total Diet Study and the highest mean levels of AA were found in vegetable crisps (1430 μg/kg), followed by potato pancakes (558) μg/kg) and pan-fried potatoes (450 μg/kg). In various foods, e.g. French fries and sweet potatoes, AA was also tested for different browning degrees and cooking methods. French fries cooked to a browning degree of 3 in all cooking methods exceeded the benchmark level set by the European Union. French fries prepared in the oven and sweet potatoes in the air fryer had the lowest AA levels. In foods from the German market, AA was found also in foods such as popcorn (243 μg/kg), salty sticks (190 μg/kg), and dark chocolate (130 μg/kg). Levels of AA found in our study may support future dietary exposure and food safety assessments., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Objective: To assess the association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born preterm., Study Design: EPIPAGE 2 is a national, population-based cohort study of children born before 35 weeks of gestation in France in 2011. We included infants born alive between 24 0/7 and 34 6/7  weeks after preterm labor or preterm premature rupture of membranes. Clinical chorioamnionitis was defined as maternal fever before labor (>37.8°C) with ≥2 of the following criteria: maternal tachycardia, hyperleukocytosis, uterine contractions, purulent amniotic fluid, or fetal tachycardia. The primary outcome was a composite, including cerebral palsy, coordination disorders, cognitive disorders, sensory disorders, or behavioral disorders. We also analyzed each of these disorders separately as secondary outcomes. We performed a multivariable analysis using logistic regression models. We accounted for the nonindependence of twins and missing data by generalized estimating equation models and multiple imputations, respectively., Results: Among 2927 children alive at 5 years of age, 124 (3%) were born in a context of clinical chorioamnionitis. Overall, 8.2% and 9.6% of children exposed and unexposed, respectively, to clinical chorioamnionitis had moderate-to-severe neurodevelopmental disorders. After multiple imputations and multivariable analysis, clinical chorioamnionitis was not associated with the occurrence of moderate-to-severe neurodevelopmental disorders (aOR, 0.9; 95% CI, 0.5-1.8)., Conclusions: We did not find any association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born at <35 weeks of gestation after preterm labor or preterm premature rupture of membrane., Competing Interests: Declaration of Competing Interest The EPIPAGE 2 study was funded with support from the French Institute of Public Health Research/Institute of Public Health, and its partners. Partners include the French Health Ministry, National Institute of Health and Medical Research (INSERM), National Institute of Cancer, and National Solidarity Fund for Autonomy (CNSA); National Research Agency through the French EQUIPEX programme of investments in the future (reference ANR-11-EQPX-0038, ANR-19-COHO-001); PREMUP Foundation; Foundation of France (reference 11779); Foundation for Medical Research (SPF20160936356); and hospital clinical research programme Epinutri (DGOS13-040). Ministère de l'Enseignement Supérieur, De La Recherche et de L'Innovation (G13129KK); Apicil Foundation (R20065KK). The funding source had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval the manuscript; and the decision to submit the manuscript for publication. The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In a system with one conserved charge the charge diffusion is modified by nonlinear self-interactions within an effective field theory (EFT) of diffusive fluctuations. We include the slowest ultraviolet (UV) mode, constructing a UV-regulated EFT. The relaxation time of this UV mode is protected from renormalization, as supported by experimental data in a bad metal system. Furthermore, the retarded density-density Green's function acquires four branch points, eventually increasing the range of applicability. We discuss the fate of long time tails as well as implications for the quark gluon plasma.

Background: Healthcare spending represents a large portion of the GDP of the United States. Value-based care (VBC) seeks to decrease waste in health care spending, yet this concept is insufficiently taught to medical students. The Choosing Wisely Students and Trainees Advocating for Resource Stewardship (STARS) campaign promotes initiatives that integrate knowledge of VBC into undergraduate medical education (UME). This study sought to determine the most effective strategy to educate medical students on key principles of VBC as taught by the STARS campaign., Methods: Choosing Wisely principles were incorporated into the UME curriculum of an academic medical institution via the creation of eight new learning objectives (LOs) for case-based learning (CBL) sessions and lectures. Medical students completed an annual 10-question survey from 2019 to 2022 and 10 formal examination questions during the preclinical (years 1 and 2) curriculum after exposure to varying quantities of LOs. Pearson correlation, chi-square, and logistic regression were employed to determine the association between increased LOs in the curriculum and (1) campaign awareness and (2) knowledge of VBC principles., Results: A total of 700 survey responses over a four-year period (2019 to 2022) were analyzed. Student awareness of the campaign and knowledge of VBC principles increased year over year during the survey period (39% to 92% and 64% to 74%, respectively). There were significant associations between increased LOs in the curriculum and (1) campaign awareness (0.828, p<0.0001) and (2) knowledge of VBC principles (0.934, p<0.001). Students also performed well on formal examination questions related to VBC principles (mean: 81.5% and mean discrimination index: 0.18)., Conclusion: Integration of VBC-focused LOs is significantly associated with awareness of the Choosing Wisely STARS campaign and knowledge of VBC principles taught by the campaign. Collaborative initiatives to increase exposure to VBC education may improve students' knowledge of these principles during medical school., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, El Fadel et al.)

Background: Very preterm (VP) birth is associated with a considerable risk for cognitive impairment, putting children at a disadvantage in academic and everyday life. Despite lower cognitive ability on the group level, there are large individual differences among VP born children. Contemporary theories define intelligence as a network of reciprocally connected cognitive abilities. Therefore, intelligence was studied as a network of interrelated abilities to provide insight into interindividual differences. We described and compared the network of cognitive abilities, including strength of interrelations between and the relative importance of abilities, of VP and full-term (FT) born children and VP children with below-average and average-high intelligence at 5.5 years., Methods: A total of 2,253 VP children from the EPIPAGE-2 cohort and 578 FT controls who participated in the 5.5-year-follow-up were eligible for inclusion. The WPPSI-IV was used to measure verbal comprehension, visuospatial abilities, fluid reasoning, working memory, and processing speed. Psychometric network analysis was applied to analyse the data., Results: Cognitive abilities were densely and positively interconnected in all networks, but the strength of connections differed between networks. The cognitive network of VP children was more strongly interconnected than that of FT children. Furthermore, VP children with below average IQ had a more strongly connected network than VP children with average-high IQ. Contrary to our expectations, working memory had the least central role in all networks., Conclusions: In line with the ability differentiation hypothesis, children with higher levels of cognitive ability had a less interconnected and more specialised cognitive structure. Composite intelligence scores may therefore mask domain-specific deficits, particularly in children at risk for cognitive impairments (e.g., VP born children), even when general intelligence is unimpaired. In children with strongly and densely connected networks, domain-specific deficits may have a larger overall impact, resulting in lower intelligence levels., (© 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Maternal problems in the postpartum period may lead to suboptimal long-term health for women and could affect mother-child attachment. Social disadvantage is a risk factor for preterm birth, which carries its own burden of health issues and stress. The main aim of this study was to investigate the role for social factors in mothers' physical and emotional health-related quality of life (HRQoL) at 1 year after a preterm birth., Methods: EPIPAGE-2 is a French nationwide, prospective, population-based cohort of preterm children born before 35 weeks' gestation (N=3614 women). At birth, detailed data on the family's social status were collected. At 1 year after birth, mothers completed a mailed questionnaire to report information on their HRQoL, assessed by the Medical Outcomes Study 12-item Short Form. We used multivariate linear regression models to assess the association between social factors and maternal HRQoL., Results: At 1 year after childbirth, the emotional HRQoL of mothers of preterm children was worse than their physical HRQoL, even in women without any previous signs of psychological distress at the infant's discharge from hospital. Baseline social characteristics were the most important factors influencing the physical component of HRQoL. None of the studied social factors had any clear association with the mental component of HRQoL., Conclusion: Our study underlines the importance of social disadvantage during pregnancy as risk factors for poor physical HRQoL at 1 year after a preterm birth., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Declaration of Competing Interest There are no conflicts of interest

Background and study aims In patients with familial adenomatous polyposis (FAP), endoscopic resection of duodenal adenomas is commonly performed to prevent cancer and prevent or defer duodenal surgery. However, based on studies using different resection techniques, adverse events (AEs) of polypectomy in the duodenum can be significant. We hypothesized that cold snare polypectomy (CSP) is a safe technique for duodenal adenomas in FAP and evaluated its outcomes in our centers. Patients and methods We performed a prospective international cohort study including FAP patients who underwent CSP for one or more superficial non-ampullary duodenal adenomas of any size between 2020 and 2022. At that time, this technique was common practice in our centers for superficial duodenal adenomas. The primary outcome was the occurrence of intraprocedural and post-procedural AEs. Results In total, 133 CSPs were performed in 39 patients with FAP (1-18 per session). Median adenoma size was 10 mm (interquartile range 8-15 mm), ranging from 5 to 40 mm; 27 adenomas were ≥20 mm (20%). Of the 133 polypectomies, 109 (82%) were performed after submucosal injection. Sixty-one adenomas (46%) were resected en bloc and 72 (54%) piecemeal. Macroscopic radical resection was achieved for 129 polypectomies (97%). Deep mural injury type II occurred in three polyps (2%) with no delayed perforation after prophylactic clipping. There were no clinically significant bleeds, perforations or other post-procedural AEs. Histopathology showed low-grade dysplasia in all 133 adenomas. Conclusions CSP for (multiple) superficial non-ampullary duodenal adenomas in FAP seems feasible and safe. Long-term prospective research is needed to evaluate whether protocolized duodenal polypectomies prevent cancer and surgery., Competing Interests: Conflict of Interest Arthur S. Aelvoet: none to declare. John G. Karstensen: JGK consultancy for SNIPR BIOME, Boston Scientific, and AMBU and speaker's fee from Norgine. Barbara A.J. Bastiaansen: speaker's fee from Olympus, Tillotts Pharma AG and Ovesco Endoscopy AG. Monique van Leerdam: review and editorial fee from Elsevier Francesc Balaguer: FB has received an honorarium for consultancy from Sysmex, CPP Pharmaceuticals, and One-Two Therapeutics, speaker's fees from Norgine, and editorial fee from Elsevier. Michal Kaminski: speaker’s fee from Olympus, Fujifilm, Boston Scientific, Medtronic, AlfaSigma, IPSEN, consultancy fee from Olympus, ERBE, AlfaSigma. Roel Hompes: none to declare. Patrick M.M. Bossuyt: none to declare. Luigi Ricciardiello: consultancy and unrestricted research grant from SLA Pharma AG. Andrew Latchford: none to declare. Rodrigo Jover: consultancy for CPP Pharmaceuticals Maria Daca-Alvarez: none to declare. Maria Pellise: endoscopic equipment on loan of FujiFilm, research grant from FujiFilm, ZiuZ and Casen Recordati, consultancy for FujiFilm, Olympus and speaker's fee from Olympus, Medtronic and FujiFilm. Evelien Dekker: endoscopic equipment on loan of FujiFilm and Olympus, research grant from FujiFilm, consultancy for FujiFilm, Olympus, Ambu and InterVenn, and speaker's fee from Olympus, GI Supply, Norgine, IPSEN, PAION and FujiFilm., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Aim: To describe the circumstances, causes and timing of death in extremely preterm infants., Methods: We included from the EPIPAGE-2 study infants born at 24-26 weeks in 2011 admitted to neonatal intensive care units (NICU). Vital status and circumstances of death were used to define three groups of infants: alive at discharge, death with or without withholding or withdrawing life-sustaining treatment (WWLST). The main cause of death was classified as respiratory disease, necrotizing enterocolitis, infection, central nervous system (CNS) injury, other or unknown., Results: Among 768 infants admitted to NICU, 224 died among which 89 died without WWLST and 135 with WWLST. The main causes of death were respiratory disease (38%), CNS injury (30%) and infection (12%). Among the infants who died with WWLST, CNS injury was the main cause of death (47%), whereas respiratory disease (56%) and infection (20%) were the main causes in case of death without WWLST. Half (51%) of all deaths occurred within the first 7 days of life, and 35% occurred within 8 and 28 days., Conclusion: The death of extremely preterm infants in NICU is a complex phenomenon in which the circumstances and causes of death are intertwined., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

The electrical and physical properties of the SiC/SiO 2 interfaces are critical for the reliability and performance of SiC-based MOSFETs. Optimizing the oxidation and post-oxidation processes is the most promising method of improving oxide quality, channel mobility, and thus the series resistance of the MOSFET. In this work, we analyze the effects of the POCl 3 annealing and NO annealing processes on the electrical properties of metal-oxide-semiconductor (MOS) devices formed on 4H-SiC (0001). It is shown that combined annealing processes can result in both low interface trap density (D it ), which is crucial for oxide application in SiC power electronics, and high dielectric breakdown voltage comparable with those obtained via thermal oxidation in pure O 2 . Comparative results of non-annealed, NO-annealed, and POCl 3 -annealed oxide-semiconductor structures are shown. POCl 3 annealing reduces the interface state density more effectively than the well-established NO annealing processes. The result of 2 × 10 11 cm -2 for the interface trap density was attained for a sequence of the two-step annealing process in POCl 3 and next in NO atmospheres. The obtained values D it are comparable to the best results for the SiO 2 /4H-SiC structures recognized in the literature, while the dielectric critical field was measured at a level ≥9 MVcm -1 with low leakage currents at high fields. Dielectrics, which were developed in this study, have been used to fabricate the 4H-SiC MOSFET transistors successfully.

Background: To evaluate the association between exposure to early skin-to-skin contact (SSC) and incidence of late-onset sepsis (LOS) in extremely and very preterm infants., Methods: Observational study using the national population-based EPIPAGE-2 cohort in 2011. A propensity score for SSC exposure was used to match infants with and without exposure to SSC before day 4 of life and binomial log regression used to estimate risk ratios and CIs in the matched cohort. The primary outcome was at least one episode of LOS during hospitalization. Secondary outcomes were the occurrence of any late-onset neonatal infection (LONI), LOS with Staphylococcus or Staphylococcus aureus, incidence of LOS and LONI per 1000 central venous catheter days., Results: Among the 3422 included infants, 919 were exposed to early SSC. The risk ratio (RR) for LOS was 0.86 (95% CI, 0.67-1.10), for LONI was 1.00 (95% CI, 0.83-1.21), and for LOS with Coagulase-negative Staphylococcus or Staphylococcus aureus infection was 0.91 (95% CI, 0.68-1.21) and 0.77 (95% CI, 0.31-1.87). The incidence RR for LOS per-catheter day was 0.87 (95% CI, 0.64-1.18)., Conclusion: Early SSC exposure was not associated with LOS or LONI risk. Thus, their prevention should not be a barrier to a wider use of SSC., Impact: Kangaroo Mother Care decreased neonatal infection rates in middle-income countries. Skin-to-skin contact is beneficial for vulnerable preterm infants but barriers exist to its implementation. In a large population-based study using a propensity score methods, we found that skin-to-skin contact before day 4 of life was not associated with a decreased risk of late-onset-sepsis in very and extremely preterm infants. Early skin-to-skin contact was not associated with an increased risk of any late-onset-neonatal-infection, in particular with staphylococcus. The fear of neonatal infection should not be a barrier to a wider use of early skin-to-skin contact in this population., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Arterial stiffness (AS) and non-dipping pattern are early predictors of cardiovascular diseases but are not used in clinical practice. We aimed to assess if AS and the non-dipping pattern are more prevalent in the erectile dysfunction (ED) group than in the non-ED group among subjects with type 1 diabetes (T1DM). The study group consisted of adults with T1DM. Aortic pulse wave velocity (PWV Ao)-a marker of increased AS, central systolic blood pressure, and heart rate (HR) were measured with a brachial oscillometric device (Arteriograph 24). Erectile dysfunction (ED) was assessed by the International Index of Erectile Function-5. A comparison between the groups with and without ED was performed. Of 34 investigated men with T1DM, 12 (35.3%) suffered from ED. The group with ED had higher mean 24 h HR (77.7 [73.7-86.5] vs 69.9 [64.0-76.8]/min; p = 0.04, nighttime PWV Ao (8.1 [6.8-8.5] vs 6.8 [6.1-7.5] m/s; p = 0.015) and prevalence of non-dipping SBP Ao pattern (11 [91.7] vs 12 [54.5]%; p = 0.027) than individuals without ED. The presence of ED detected a central non-dipping pattern with a sensitivity of 47.8% and a specificity of 90.9%. The central non-dipping pattern was more prevalent and the nighttime PWV was higher in T1DM subjects with ED than in those without ED., (© 2023. The Author(s).)

Background: Respiratory sinus arrhythmia (RSA) denotes decrease of cardiac beat-to-beat intervals (RRI) during inspiration and RRI increase during expiration, but an inverse pattern (termed negative RSA) was also found in healthy humans with elevated anxiety. It was detected using wave-by-wave analysis of cardiorespiratory rhythms and was considered to reflect a strategy of anxiety management involving the activation of a neural pacemaker. Results were consistent with slow breathing, but contained uncertainty at normal breathing rates (0.2-0.4 Hz)., Objectives and Methods: We combined wave-by-wave analysis and directed information flow analysis to obtain information on anxiety management at higher breathing rates. We analyzed cardiorespiratory rhythms and blood oxygen level-dependent (BOLD) signals from the brainstem and cortex in 10 healthy fMRI participants with elevated anxiety., Results: Three subjects with slow respiratory, RRI, and neural BOLD oscillations showed 57 ± 26% negative RSA and significant anxiety reduction by 54 ± 9%. Six participants with breathing rate of ~0.3 Hz showed 41 ± 16% negative RSA and weaker anxiety reduction. They presented significant information flow from RRI to respiration and from the middle frontal cortex to the brainstem, which may result from respiration-entrained brain oscillations, indicating another anxiety management strategy., Conclusions: The two analytical approaches applied here indicate at least two different anxiety management strategies in healthy subjects.

Objectives: Neurocysticercosis (NCC) is a parasitic disease caused by the larval stage of the tapeworm Taenia solium. NCC mainly occurs in Africa, Latin America and South-East Asia and can cause a variety of clinical signs/symptoms. Although it is a rare disease in Europe, it should nonetheless be considered as a differential diagnosis. The aim of this study was to describe clinical characteristics and management of patients with NCC diagnosed and treated in Europe., Methods: We conducted a systematic search of published and unpublished data on patients diagnosed with NCC in Europe (2000-2019) and extracted demographic, clinical and radiological information on each case, if available., Results: Out of 293 identified NCC cases, 59% of patients presented initially with epileptic seizures (21% focal onset); 52% presented with headache and 54% had other neurological signs/symptoms. The majority of patients had a travel or migration history (76%), mostly from/to Latin America (38%), Africa (32%) or Asia (30%). Treatment varied largely depending on cyst location and number. The outcome was favorable in 90% of the cases., Conclusions: Management of NCC in Europe varied considerably but often had a good outcome. Travel and migration to and from areas endemic for T. solium will likely result in continued low prevalence of NCC in Europe. Therefore, training and guidance of clinicians is recommended for optimal patient management., (© International Society of Travel Medicine 2022. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Vestibular dysfunction is a disturbance of the body's balance system. The control of balance and gait has a particular influence on the quality of life. Currently, assessing patients with these problems is mainly subjective. New assessment options using wearables may provide complementary and more objective information. Posturography makes it possible to determine the extent and type of posture dysfunction, which makes it possible to plan and monitor the effectiveness of physical rehabilitation therapy. This study evaluates the effectiveness of non-instrumental clinical tests and the instrumental mobile posturography MediPost device for patients with unilateral vestibular disorders. The study group included 40 patients. A subjective description of the symptoms was evaluated using a questionnaire about the intensity of dizziness using the Dizziness Handicap Inventory (DHI) and Vertigo Syndrome Scale-short form (VSS-sf). The clinical protocol contained clinical tests and MediPost measurements using a Modified Clinical Test of Sensory Interaction on Balance. All patients underwent vestibular rehabilitation therapy (VRT) for four weeks. The non-instrumental measurement results were statistically significant, and the best was in the Timed Up and Go test (TUG). In MediPost, condition 4 was the most valuable. This research demonstrated the possibilities of using an instrumental test (MediPost) as an alternative method to assess balance.

Brain-body interactions can be studied by using directed coupling measurements of fMRI oscillations in the low (0.1-0.2 Hz) and high frequency bands (HF; 0.2-0.4 Hz). Recently, a preponderance of oscillations in the information flow between the brainstem and the prefrontal cortex at around 0.15/0.16 Hz was shown. The goal of this study was to investigate the information flow between BOLD-, respiratory-, and heart beat-to-beat interval (RRI) signals in the HF band in healthy subjects with high anxiety during fMRI examinations. A multivariate autoregressive model was concurrently applied to the BOLD signals from the middle frontal gyrus (MFG), precentral gyrus and the brainstem, as well as to respiratory and RRI signals. Causal coupling between all signals was determined using the Directed Transfer Function (DTF). We found a salience of fast respiratory waves with a period of 3.1 s (corresponding to ~ 0.32 Hz) and a highly significant (p < 0.001) top-down information-flow from BOLD oscillations in the MFG to the brainstem. Additionally, there was a significant (p < 0.01) information flow from RRI to respiratory oscillations. We speculate that brain oscillations around 0.32 Hz, triggered by nasal breathing, are projected downwards to the brainstem. Particularly interesting is the driving force of cardiac to respiratory waves with a ratio of 1:1 or 1:2. These results support the binary hierarchy model with preferred respiratory frequencies at 0.32 Hz and 0.16 Hz., (© 2023. The Author(s).)

Objective: To evaluate, in very preterm infants, the hemoglobin (Hb) levels during the first 24 h and the neurodevelopment outcomes at 24 months of corrected age., Design, Setting, and Patients: We conducted a secondary analysis of the French national prospective and population-based cohort EPIPAGE-2. The eligible study participants were live-born singletons who were born before 32 weeks of gestational age, with early Hb levels who were admitted to the neonatal intensive care unit., Main Outcome Measures: The early Hb levels for an outcome survival at 24 months of corrected age without neurodevelopmental impairment were measured. The secondary outcomes were survival at discharge and without severe neonatal morbidity., Results: Of the 2158 singletons of <32 weeks with mean early Hb levels of 15.4 (±2.4) g/dL, 1490 of the infants (69%) had a follow-up at two years of age. An early Hb of 15.2 g/dL is the minimum receiving operating characteristic curve at the 24 months risk-free level, but the area under the curve at 0.54 (close to 50%) indicates that this rate was not informative. In logistic regression, no association was found between early Hb levels and outcomes at two years of age (aOR 0.966; 95% CI [0.775-1.204]; p = 0.758) but rather there was a correlation found with severe morbidity (aOR 1.322; 95% CI [1.003-1.743]; p = 0.048). A risk stratification tree showed that male newborns of >26 weeks with Hb of <15.5 g/dL (n = 703) were associated with a poor outcome at 24 months (OR 1.9; CI: [1.5-2.4] p < 0.01)., Conclusions: Early low Hb levels are associated with major neonatal morbidities in VP singletons, but not with neurodevelopment outcomes at two years of age, except in male infants of >26 Weeks GA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines drive the generation of affinity-matured B cell responses through germinal center (GC) reactions in vaccine draining lymph nodes. Herein, we describe a procedure for the acquisition of human lymph node samples via an ultrasound-guided fine needle aspiration-based approach. Additionally, we outline a suggested approach for the analysis of CD4 T helper cell subsets as well as antigen-specific GC B cells, memory B cells, and plasmablasts by high-parameter spectral flow cytometry. For complete details on the use and execution of this protocol, please refer to Lederer et al. (2022). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To explore adolescent perspectives on the content and delivery of anticipatory guidance (AG), both during and after outpatient visits, in order to develop targeted resources and educational material for adolescent patients., Methods: Semi-structured phone interviews among patients ages 12 to 21 seen between May-July 2021 at four outpatient sites of NewYork Presbyterian Hospital were recorded, transcribed and analyzed using thematic analysis. Content domains included attitudes toward and preferences around AG, discharge instructions and patient education resources., Results: Twenty-eight of 156 recruited patients completed interviews; 52% received an After Visit Summary (AVS); of the 48% who did not receive it, half of them expressed interest in receiving one. Themes included positive perceptions of the AVS, patient-physician communication, multimodal delivery of educational materials, and critical discussion topics such as mental health and nutrition., Conclusion: Adolescents value the AVS and prefer multimodal materials and topics that are specifically geared towards them, rather than their caregivers., Innovation: This study is the first to explore adolescent perspectives on AG and after-visit informational materials. These findings may help more effectively reach, educate and engage adolescent patients in the primary care setting by guiding the focused development of patient-centered instructions and resources., Competing Interests: 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., (© 2022 The Authors. Published by Elsevier B.V.)

The article describes the problem of geometric synthesis of the inspection robot suspension system, designed for operation in difficult conditions with the presence of scattered obstacles. The exemplary application of a mine infrastructure inspection robot is developed and supported by the ideas. The brief introduction presents current trends, requirements and known design approaches of platforms enabled to cross the obstacles. The idea of a nature-inspired wheel-legged robot is given, and the general outline of its characteristics is provided. Then the general idea of kinematic system elements selection is discussed. The main subject of geometrical synthesis of the chosen four-bar mechanism is described in detail. The mathematical model of the suspension and connections between the parts of the structure is clarified. The well-known analytical approach of brute force search is analyzed and validated. Then the method inspired by the branch and bound algorithm is developed. Finally, a novel application of the nature-inspired algorithm (the Chameleon Swarm Algorithm) to synthesis is proposed. The obtained results are analyzed, and a brief comparison of methods is given. The successful implementation of the algorithm is presented. The obtained results are effectively tested with simulations and experimental tests. The designed structure developed with the CSA is assembled and attached to the prototype of a 14-DOF wheel-legged robot. Furthermore, the principles of walking and the elements forming the control structure were also discussed. The paper is summarized with the description of the developed wheel-legged robot LegVan 1v2.

Background: Preterm delivery is a risk factor for suboptimal neurodevelopment. Pregnancies conceived after medically assisted reproduction-which includes in vitro fertilization, with or without intracytoplasmic insemination, and induction of ovulation followed by intrauterine insemination or timed intercourse-have a higher risk of preterm delivery. Few studies have evaluated the outcome at >2 years of age of such preterm-born children., Objective: To evaluate neurodevelopmental outcome at 5½ years of age of children born preterm according to the mode of conception (spontaneous vs medically assisted reproduction)., Study Design: A total of 4349 children born between 24 and 34 weeks of gestation who survived to 5½ years of age in the 2011 French prospective national cohort study "EPIPAGE-2" were included: 814 in the medically assisted reproduction group (433 by in vitro fertilization, with or without intracytoplasmic insemination, and 381 by induction of ovulation) and 3535 in the spontaneously conceived group. The studied neurodevelopmental outcomes were sensory (hearing and vision) impairments, cerebral palsy, cognition, and developmental coordination disorders. Multivariate analyses were performed with generalized estimating equation models adjusted for gestational age, antenatal steroids, and social characteristics. All analyses were performed following multiple imputation. Sensitivity analyses were performed with the populations of singletons and cases with complete data., Results: No differences in cerebral palsy (adjusted odds ratio, 1.00; 95% confidence interval, 0.67-1.49), neurodevelopmental impairment (adjusted odds ratio, 1.09; 95% confidence interval, 0.82-1.45), or developmental coordination disorders (adjusted odds ratio, 0.75; 95% confidence interval, 0.50-1.12) were found between children born following medically assisted reproduction and children born following spontaneous conception after adjustment for sociodemographic factors. For proportions of children with an intelligence quotient below 1 and 2 standard deviations, there were no differences between those born after medically assisted reproduction and those born after spontaneous pregnancy (respectively, adjusted odds ratio, 0.99; 95% confidence interval, 0.80-1.23 and adjusted odds ratio, 1.14; 95% confidence interval, 0.83-1.56). In subgroup analyses, no differences were observed between children born following induction of ovulation or in vitro fertilization and those conceived spontaneously. Sensitivity analyses were consistent with the main results., Conclusion: In this cohort of preterm-born children, there was no evidence of an impact of the mode of conception on neurodevelopmental outcomes at 5½ years of age., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: The 2017 international PACIFIC trial established a role for immunotherapy after chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC). However, in the US, patients with NSCLC commonly differ from clinical trial populations in terms of age, health, access to care, and treatment course, which may all factor into the efficacy of immunotherapy., Objective: To determine the outcomes of immunotherapy use in unresectable stage III NSCLC in the general US population., Design, Setting, and Participants: This cohort study analyzed the National Cancer Database for patients diagnosed with clinical stage III NSCLC between 2015 and 2017 with follow-up through the end of 2018 who were treated with chemotherapy and radiation. Data were analyzed January 2022., Main Outcomes and Measures: Mortality hazard in a multivariable Cox proportional hazards model and survival among a propensity-matched sample treated with chemotherapy and radiation, with and without immunotherapy., Results: A total of 23 811 patients with clinical stage III NSCLC with median (IQR) age 66 (59-72) years met inclusion criteria (10 454 [43.9%] women; 564 [2.4%] Asian, 2930 [12.3%] Black, 20 077 [84.3%] White patients), including 209 (16.1%) patients with multiple comorbidities and 1297 (5.4%) immunotherapy recipients. Immunotherapy after chemotherapy and radiation was associated with reduced mortality (hazard ratio [HR], 0.74; 95% CI, 0.67-0.82; P < .001). Among a propensity-matched sample, immunotherapy was associated with superior 3-year survival (52% [1297 patients at 0 months, 56 patients at 36 months] vs 44% [2594 patients at 0 months, 173 patients at 36 months]; P < .001). The treatment of 833 patients who received immunotherapy (64.2%) differed from the PACIFIC trial protocol, including 221 patients (17.0%) who received radiation doses outside of the protocol range and 731 patients (56.4%) who started immunotherapy more than 6 weeks after radiation was completed. The survival advantage of immunotherapy persisted when initiated up to 12 weeks after radiation was completed (HR, 0.75; 95% CI, 0.61-0.92). Among patients who received radiation outside the PACIFIC protocol range, the survival advantage of immunotherapy was not significant (HR, 0.87; 95% CI, 0.69-1.01)., Conclusions and Relevance: In this cohort study, immunotherapy after chemotherapy and radiation for stage III NSCLC was associated with a survival advantage in the general US population despite two-thirds of patients treated differently than the PACIFIC protocol. The findings suggest there may be flexibility in the timing of immunotherapy initiation after radiation; further study is warranted to clarify the clinical benefits of immunotherapy.

Following these guidelines to order fewer tests can improve health care quality and patient experience, while reducing wasteful costs.

Objective: Very preterm born children are at risk for impairments in multiple neurodevelopmental domains, but outcomes vary between individuals. The present study aimed to distinguish subgroups with distinct profiles of functioning across motor, cognitive, behavioral, and psychosocial domains. These profiles were related to neonatal and social/environmental factors., Method: The sample included 1977 children born very preterm (<32 weeks' gestation) in 2011 from the French population-based EPIPAGE-2 cohort. Using latent profile analysis, subgroups of children were distinguished based on their functioning at 5.5 years. The relation between outcome profiles and neonatal and social/environmental factors was tested using multivariable multinomial logistic regression analysis., Results: Four subgroups with distinct outcome profiles were distinguished: no deficit in any domain (45%); motor and cognitive deficits without behavioral/psychosocial deficits (31%); primarily behavioral and psychosocial deficits (16%); and deficits in multiple domains (8%). Male sex (odds ratio [OR] = 2.1-2.7), bronchopulmonary dysplasia (OR = 2.1-2.8), low parental education level (OR = 1.8-2.1), and parental non-European immigrant status (OR = 2.3-3.0) were independently associated with higher odds for all suboptimal outcome profiles compared to the favorable outcome profile., Conclusion: Among 5.5-year-old very preterm born children, subgroups can be distinguished with distinct outcome profiles that vary in severity, type, and combinations of deficits. This information is important for the development of interventions that are tailored to the needs of large subgroups of children across multiple domains of functioning. General neonatal and social/environmental factors may be useful for early identification of very preterm born children at risk for general rather than domain-specific impairments., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Slow oscillations of different center frequencies and their coupling play an important role in brain-body interactions. The crucial question analyzed by us is, whether the low frequency (LF) band (0.05-0.15 Hz) or the intermediate frequency (IMF) band (0.1-0.2 Hz) is more eminent in respect of the information flow between body (heart rate and respiration) and BOLD signals in cortex and brainstem. A recently published study with the LF band in fMRI-naïve subjects revealed an intensive information flow from the cortex to the brainstem and a weaker flow from the brainstem to the cortex. The comparison of both bands revealed a significant information flow from the middle frontal gyrus (MFG) to the precentral gyrus (PCG) and from brainstem to PCG only in the IMF band. This pattern of directed coupling between slow oscillations in the cortex and brainstem not only supports the existence of a pacemaker-like structure in brainstem, but provides first evidence that oscillations centered at 0.15/0.16 Hz can also emerge in brain networks. BOLD oscillations in resting states are dominating at ~ 0.08 Hz and respiratory rates at ~ 0.32 Hz. Therefore, the frequency component at ~ 0.16 Hz (doubling-halving 0.08 Hz or 0.32 Hz) is of special interest, because phase coupled oscillations can reduce the energy demand., (© 2022. The Author(s).)

T-cell acute lymphoblastic leukemia (T-ALL) is commonly driven by activating mutations in NOTCH1 that facilitate glutamine oxidation. Here we identify oxidative phosphorylation (OxPhos) as a critical pathway for leukemia cell survival and demonstrate a direct relationship between NOTCH1, elevated OxPhos gene expression, and acquired chemoresistance in pre-leukemic and leukemic models. Disrupting OxPhos with IACS-010759, an inhibitor of mitochondrial complex I, causes potent growth inhibition through induction of metabolic shut-down and redox imbalance in NOTCH1-mutated and less so in NOTCH1-wt T-ALL cells. Mechanistically, inhibition of OxPhos induces a metabolic reprogramming into glutaminolysis. We show that pharmacological blockade of OxPhos combined with inducible knock-down of glutaminase, the key glutamine enzyme, confers synthetic lethality in mice harboring NOTCH1-mutated T-ALL. We leverage on this synthetic lethal interaction to demonstrate that IACS-010759 in combination with chemotherapy containing L-asparaginase, an enzyme that uncovers the glutamine dependency of leukemic cells, causes reduced glutaminolysis and profound tumor reduction in pre-clinical models of human T-ALL. In summary, this metabolic dependency of T-ALL on OxPhos provides a rational therapeutic target., (© 2022. The Author(s).)

The paper concerns the development of methods of EEG functional connectivity estimation including short overview of the currently applied measures describing their advantages and flaws. Linear and non-linear, bivariate and multivariate methods are confronted. The performance of different connectivity measures in respect of robustness to noise, common drive effect and volume conduction is considered providing a guidance towards future developments in the field, which involve evaluation not only functional, but also effective (causal) connectivity. The time-varying connectivity measure making possible estimation of dynamical information processing in brain is presented. The methods of post-processing of connectivity results are considered involving application of advanced graph analysis taking into account community structure of networks and providing hierarchy of networks rather than the single, binary networks currently used., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kaminski and Blinowska.)

Introduction: Children born very preterm have an immature sucking reflex at birth and are exposed to neonatal care that can impede proper palate growth., Objectives: We aimed to describe the frequency of high-arched palate and posterior crossbite at the age of 5 in children born very preterm and to identify their respective risk factors., Methods: Our study was based on the data from EPIPAGE-2, a French national prospective cohort study, and included 2,594 children born between 24- and 31-week gestation. Outcomes were high-arched palate and posterior crossbite. Multivariable models estimated by generalized estimation equations with multiple imputation were used to study the association between the potential risk factors studied and each outcome., Results: Overall, 8% of children born very preterm had a high-arched palate and 15% posterior crossbite. The odds of high-arched palate were increased for children with low gestational age (24-29 vs. 30-31 weeks of gestation) [adjusted odds ratio (aOR) 1.76, 95% confidence interval (CI) 1.17, 2.66], thumb-sucking habits at the age of 2 (aOR 1.53, 95% CI 1.03, 2.28), and cerebral palsy (aOR 2.18, 95% CI 1.28, 3.69). The odds of posterior crossbite were increased for children with pacifier-sucking habits at the age of 2 (aOR 1.75, 95% CI 1.30, 2.36)., Conclusions: Among very preterm children, low gestational age and cerebral palsy are the specific risk factors for a high-arched palate. High-arched palate and posterior crossbite share non-nutritive sucking habits as a common risk factor. The oro-facial growth of these children should be monitored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Herrera, Pierrat, Kaminski, Benhammou, Marchand-Martin, Morgan, Le Norcy, Ancel and Germa.)

Introduction: Available guidelines are inconsistent as to whether patients with newly diagnosed clinical stage II NSCLC should receive routine brain imaging., Methods: The National Cancer Database was queried for the prevalence of isolated brain metastases among patients with newly diagnosed NSCLC in 2016 and 2017. Patients with metastases in locations other than the brain were excluded. The prevalences were then stratified by clinical T and N classifications and further stratified into a summary stage, which was calculated based on T and N classifications. The summary stage represents the clinical stage that would have been available at the time of decision for brain imaging., Results: A total of 6,949 of 149,958 patients (4.6%) with clinical stages I, II, III, or brain-limited stage IV NSCLC had dissemination limited to the brain. As T and N stages increased, prevalence of brain metastases generally increased. Among patients with node-negative (N0) NSCLC, the prevalence of brain-only metastases increased from 1.2% in patients with T1a to 3.8% among patients with T4 ( p < 0.001). Among patients with T1a, the prevalence of brain-only metastases increased from 1.2% for patients with N0 to 7.9% for patients with N3 ( p < 0.001). The prevalence of brain-limited metastases generally increased with increasing summary stage. The prevalence of brain-only metastases among patients with stage IA was 1.7% whereas that among patients with stage IIIA was 6.7% ( p < 0.001). Of note, the prevalence of brain-limited metastases was approximately 6% for both summary stages II and III., Conclusions: Considering the similarity in prevalence of isolated brain metastases and the potential hazards associated with brain imaging in early stage NSCLC, practitioners may consider a more liberal use of brain imaging when interpreting conflicting guidelines., (© 2022 The Authors.)

Infections due to extended-spectrum β-lactamase (ESBL)-producing Enterobacterales are an increasingly common problem. For many of these infections, no oral treatment options are available. The activity of amoxicillin-clavulanate combined with ceftibuten or cefpodoxime was evaluated against a group of Escherichia coli and Klebsiella pneumoniae clinical isolates possessing a variety of CTX-M- and SHV-type ESBLs; some possessed bla TEM1 as well. In time-kill studies, the combination of subinhibitory concentrations of amoxicillin-clavulanate with ceftibuten was bactericidal and synergistic for all strains with an amoxicillin-clavulanate MIC ≤32 μg/mL, regardless of the type of ESBL and the cephalosporin minimal inhibitory concentration (MIC). The combination with cefpodoxime was also bactericidal and synergistic against all but one of these strains. These combinations were further tested against two strains of K. pneumoniae and one E. coli in a sepsis model using Galleria mellonella larvae. The combination of amoxicillin-clavulanate with ceftibuten demonstrated a synergistic survival benefit against all three strains. The combination with cefpodoxime also improved survival against the two K. pneumoniae strains, but not the E. coli strain. These findings support combining amoxicillin-clavulanate with ceftibuten, and possibly cefpodoxime, for the treatment of infections due to ESBL producers and suggest that having an amoxicillin-clavulanate MIC of 32 μg/mL or less may predict activity at clinically achievable concentrations. Clinical studies are warranted to further evaluate this therapeutic approach.

Objective: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors for early-onset sepsis (EOS)., Study Design: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of EOS (ie, born after preterm labor or preterm premature rupture of membranes or from a mother who had clinical chorioamnionitis or had received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotic therapy started at day 0 or day 1 of life, irrespective of the duration and type of antibiotics. We compared treated and untreated patients using inverse probability of treatment weighting based on estimated propensity scores., Results: Among 648 very preterm infants at low risk of EOS, 173 (26.2%) had received early antibiotic treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR, 1.04; 95% CI, 0.72-1.50); however, it was associated with higher odds of severe cerebral lesions (OR, 2.71; 95% CI, 1.25-5.86) and moderate-severe bronchopulmonary dysplasia (BPD) (OR, 2.30; 95% CI, 1.21-4.38)., Conclusions: Early empirical antibiotic therapy administrated in very preterm infants at low risk of EOS was associated with a higher risk of severe cerebral lesions and moderate-severe BPD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: We investigated the timing of survival differences and effects on morbidity for foetuses alive at maternal admission to hospital delivered at 22 to 26 weeks' gestational age (GA)., Methods: Data from the EXPRESS (Sweden, 2004-07), EPICure-2 (England, 2006) and EPIPAGE-2 (France, 2011) cohorts were harmonised. Survival, stratified by GA, was analysed to 112 days using Kaplan-Meier analyses and Cox regression adjusted for population and pregnancy characteristics; neonatal morbidities, survival to discharge and follow-up and outcomes at 2-3 years of age were compared., Results: Among 769 EXPRESS, 2310 EPICure-2 and 1359 EPIPAGE-2 foetuses, 112-day survival was, respectively, 28.2%, 10.8% and 0.5% at 22-23 weeks' GA; 68.5%, 40.0% and 23.6% at 24 weeks; 80.5%, 64.8% and 56.9% at 25 weeks; and 86.6%, 77.1% and 74.4% at 26 weeks. Deaths were most marked in EPIPAGE-2 before 1 day at 22-23 and 24 weeks GA. At 25 weeks, survival varied before 28 days; differences at 26 weeks were minimal. Cox analyses were consistent with the Kaplan-Meier analyses. Variations in morbidities were not clearly associated with survival., Conclusion: Differences in survival and morbidity outcomes for extremely preterm births are evident despite adjustment for background characteristics. No clear relationship was identified between early mortality and later patterns of morbidity., (© 2021 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Brain-heart synchronization is fundamental for emotional-well-being and brain-heart desynchronization is characteristic for anxiety disorders including specific phobias. Recording BOLD signals with functional magnetic resonance imaging (fMRI) is an important noninvasive diagnostic tool; however, 1-2% of fMRI examinations have to be aborted due to claustrophobia. In the present study, we investigated the information flow between regions of interest (ROI's) in the cortex and brain stem by using a frequency band close to 0.1 Hz. Causal coupling between signals important in brain-heart interaction (cardiac intervals, respiration, and BOLD signals) was studied by means of Directed Transfer Function based on the Granger causality principle. Compared were initial resting states with elevated anxiety and final resting states with low or no anxiety in a group of fMRI-naïve young subjects. During initial high anxiety the results showed an increased information flow from the middle frontal gyrus (MFG) to the pre-central gyrus (PCG) and to the brainstem. There also was an increased flow from the brainstem to the PCG. While the top-down flow during increased anxiety was predominant, the weaker ascending flow from brainstem structures may characterize a rhythmic pacemaker-like activity that (at least in part) drives respiration. We assume that these changes in information flow reflect successful anxiety processing., (© 2021. The Author(s).)

Background: Healthcare facility-onset Clostridioides difficile infection is associated with adverse clinical outcomes and hospital reimbursement. A four-year review involving eleven hospitals of the NYC Health + Hospital system was undertaken., Methods: From 2016-2019, infection rates and standardized infection ratios (SIRs) were gathered from National Healthcare Safety Network. The C. difficile testing scheme at each facility was recorded., Results: For the eleven hospitals, declines in rates of C. difficile infection and SIRs were documented. However, this decline was driven by two hospitals that had high rates of infection in 2016; for the remaining nine hospitals, rates of infection and SIRs were at a plateau. Most hospitals used a testing scheme that fell into the nucleic acid amplification test (NAAT) category for SIR risk adjustment. Hospitals that used the algorithm glutamate dehydrogenase (GDH) and toxin A/B immunoassay (EIA) followed by NAAT for discrepant results had significantly lower rates of C. difficile infection but similar SIRs., Conclusions: For most hospitals in this system, rates of C. difficile remained level. Within the NAAT test categories, SIRs may not correlate with infection rates. Given the controversies regarding testing and calculation of SIRs, alternatives to C. difficile infection should be sought as a hospital quality measurement., (Copyright © 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Very preterm children generally perform poorly in executive functions and particularly in working memory. Adaptive training tasks encouraging these children to work continuously on their personal working memory capacity can be very useful. Above all in preschool-age children, several cognitive training programs focused on improving working memory capacity. Cogmed is a computerized visuospatial cognitive training program that improves working memory in children and adolescents with attention-deficit/hyperactivity disorder. The main objective is to assess the long-term effects (18 months) of cognitive training (Cogmed) on visuospatial processing in preschool-age very preterm children with working memory impairment., Methods: The EPIREMED study is a prospective, randomized, controlled, multicentric trial nested in a population based epidemiological survey. An intervention group (Cogmed cognitive training) and a control group (standard care management) will compare children aged 5½ to 6 years, born between 24- and 34-weeks' gestational age, with a global intelligence quotient > 70 and a working memory index < 85. The study will include 166 children from national study EPIPAGE-2 (Epidemiological Study on Small Gestational Ages). The intervention consists of 25 sessions administered over a 5- to 8-week period. The primary endpoint will be the visuospatial processing, assessed by the score of the visuospatial index: score of the WPPSI-IV (Wechsler Preschool and Primary Scale of Intelligence). The secondary endpoints will allow to assess the executive functions, language and abilities, infant behavior, quality of life assessment, school performance and parental anxiety., Discussion: This project's primary goal is to demonstrate the necessity of early visuospatial memory assessment within the vulnerable population of very preterm children, and to prove the feasibility and efficacy of computerized cognitive training using online software programs. A better global neuropsychological development improvement (visuospatial processing and other far transfer) can be expected with an improvement in learning and decreased behavioral problems. In the long term, these improvements might also reduce those global costs linked to the consequences of extreme prematurity., Trial Registration: NCT02757794 (registered on 2nd May 2016 at ClinicalTrial.gov)., (© 2021. The Author(s).)

Introductions and invasions provide opportunities for interaction and hybridization between colonists and closely related native species. We investigate this phenomenon using the mitochondrial DNA COI and 81,416 base-pairs of overlapping nuclear variation to examine the evolutionary histories and signatures of hybridization among introduced feral Rock Pigeon and Eurasian Collared-Dove and native White-winged and Mourning doves in southwestern North America. First, we report all four species to be highly divergent across loci (overall pair-wise species Φ ST range = 0.17-0.70) and provide little evidence for gene flow at evolutionary timescales. Despite this, evidence from multiple population genetics analyses supports the presence of six putative contemporary late-stage hybrids among the 182 sampled individuals. These putative hybrids contain various ancestry combinations, but all involve the most populous species, the Mourning Dove. Next, we use a novel method to reconstruct demographic changes through time using partial genome sequence data. We identify recent, species-specific fluctuations in population size that are likely associated with changing environments since the Miocene and suggest that these fluctuations have influenced the genetic diversity of each dove species in ways that may impact their future persistence. Finally, we discuss the importance of using multiple marker types when attempting to infer complex evolutionary histories and propose important considerations when analyzing populations that were recently established or of domestic origins.

The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and "interrelatedness" at posterior alpha (8-12 Hz) and widespread delta (< 4 Hz) and theta (4-8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact-free rsEEG periods are needed; (2) power density and "interrelatedness" rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes., (© 2021 the Alzheimer's Association.)