Search

Floricoccus penangensis ML061-4 was originally isolated from the leaf surface of an Assam tea plant (Camellia sinensis var. assamica) from Northern Thailand. To assess the functions encoded by the F. penangensis ML061-4 genome, gene identification and annotation were undertaken by in silico analysis. The complete genome of F. penangensis ML061-4 consists of single chromosome of 2,159,127 base pairs, containing a GC content of 33.2% and encompassing 2049 predicted protein-encoding genes. A total of 1195 genes (58.0%) in the F. penangensis ML061-4 genome have assignable functions based on BlastKOALA analysis. Furthermore, 1235 genes (59.9%) were classified into six KEGG functional categories with 187 associated pathways, while 1419 genes (68.8%) were assigned a putative function by the Clusters of Orthologous Groups (COGs) database. The ML061-4 genome was evaluated for genes associated with complex carbohydrate metabolism, bacterial adhesion, virulence factors, pathogenicity, bacteriophages, antiviral defence systems as well as toxin- and antibiotic-resistance associated genes, and genes involved in toxin production, secondary metabolite biosynthesis and xenobiotics biodegradation. The obtained results support the notion of F. penangensis ML061-4 being safe for biotechnological and food industry purposes. This is the first report outlining functional genomic insights regarding a member of the genus Floricoccus., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Bipolar disorder is a leading contributor to the global burden of disease 1 . Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown 2 . We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings 3 , and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder 4 , highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder., Competing Interests: Competing interests: T.E.T., H. Stefansson and K.S. are employed by deCODE Genetics/Amgen. E.A.S. is an employee of Regeneron Genetics Center and owns stocks of Regeneron Pharmaceutical. K.-H.L. and X.W. are employed by 23andMe. Multiple additional authors work for pharmaceutical or biotechnology companies in a manner directly analogous to academic co-authors and collaborators. A.H.Y. has given paid lectures and served on advisory boards relating to drugs used in affective and related disorders for several companies (AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allergan, Bionomics and Sumitomo Dainippon Pharma), was Lead Investigator for the Embolden study (AstraZeneca), BCI Neuroplasticity study and Aripiprazole Mania study, and is an investigator for Janssen, Lundbeck, Livanova and Compass. J.I.N. is an investigator for Janssen. P.F.S. is on the advisory committee and a shareholder of Neumora Therapeutics. G.B. reports consultancy and speaker fees from Eli Lilly and Illumina, and grant funding from Eli Lilly. M. Landén has received speaker fees from Lundbeck. O.A.A. has served as a speaker for Janssen, Lundbeck and Sunovion, and as a consultant for Cortechs.ai. A.M.D. is a founder of and holds equity interest in CorTechs Labs and serves on its scientific advisory board; is a member of the scientific advisory board of Human Longevity and the Mohn Medical Imaging and Visualization Center; and has received research funding from General Electric Healthcare. E.V. has received grants and served as a consultant, advisor or CME speaker for the following entities: AB-Biotics, Abbott, Allergan, Angelini, AstraZeneca, Bristol Myers Squibb, Dainippon Sumitomo Pharma, Farmindustria, Ferrer, Forest Research Institute, Gedeon Richter, GlaxoSmithKline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, SAGE, Sanofi-Aventis, Servier, Shire, Sunovion, Takeda, the Brain and Behaviour Foundation, the Catalan Government (AGAUR and PERIS), the Spanish Ministry of Science, Innovation, and Universities (AES and CIBERSAM), the Seventh European Framework Programme and Horizon 2020 and the Stanley Medical Research Institute. S.K.-S. received author’s, speaker’s and consultant honoraria from Janssen, Medice Arzneimittel Pütter GmbH and Takeda outside of the current work. A. Serretti is or has been a consultant and/or speaker for: Abbott, AbbVie, Angelini, AstraZeneca, Clinical Data, Boheringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi and Servier. J.R.D. has served as an unpaid consultant to Myriad-Neuroscience (formerly Assurex Health) in 2017 and 2019, and owns stock in CVS Health. B.M.N. is a member of the scientific advisory board at Deep Genomics, and consultant for Camp4 Therapeutics, Takeda Pharmaceutical and Biogen. B.-C.L., J.-W.K., Y.K.L., J.H.K., M. J. Cheon and D.J.K. are employed by Genoplan. I.B.H. is the Co-Director of Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to Headspace. I.B.H. is also the Chief Scientific Advisor to, and a 3.2% equity shareholder in, InnoWell. InnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to deliver the $30 M (AUD) Australian Government-funded Project Synergy (2017–2020; a 3-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative technologies. M.J.O. and M.C.O. have received funding from Takeda Pharmaceuticals and Akrivia Health outside the scope of the current work. P. B. Mitchell. has received remuneration from Janssen (Australia) and Sanofi (Hangzhou) for lectures or advisory board membership. J.A.R.-Q. was on the speakers’ bureau and/or acted as consultant for Biogen, Idorsia, Casen-Recordati, Janssen-Cilag, Novartis, Takeda, Bial, Sincrolab, Neuraxpharm, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Raffo in the past 3 years; has also received travel awards (airplane tickets and hotel) for taking part in psychiatric meetings from Idorsia, Janssen-Cilag, Rubió, Takeda, Bial and Medice; and the Department of Psychiatry chaired by J.A.R.-Q. received unrestricted educational and research support from the following companies in the past 3 years: Exeltis, Idorsia, Janssen-Cilag, Neuraxpharm, Oryzon, Roche, Probitas and Rubió. All other authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Rapid advancements in long-read sequencing have facilitated species-level microbial profiling through full-length 16S rRNA sequencing (~ 1500 bp), and more notably, by the newer 16S-ITS-23S ribosomal RNA operon (RRN) sequencing (~ 4500 bp). RRN sequencing is emerging as a superior method for species resolution, exceeding the capabilities of short-read and full-length 16S rRNA sequencing. However, being in its early stages of development, RRN sequencing has several underexplored or understudied elements, highlighting the need for a critical and thorough examination of its methodologies. Key areas that require detailed analysis include understanding how primer pairs, sequencing platforms, and classifiers and databases affect the accuracy of species resolution achieved through RRN sequencing. Our study addresses these gaps by evaluating the effect of primer pairs using four RRN primer combinations, and that of sequencing platforms by employing PacBio and Oxford Nanopore Technologies (ONT) systems. Furthermore, two classification methods (Minimap2 and OTU clustering), in combination with four RRN reference databases (MIrROR, rrnDB, and two versions of GROND) were compared to identify consistent and accurate classification methods with RRN sequencing. Here we demonstrate that RRN primer pair choice and sequencing platform do not substantially bias taxonomic profiles for most of the tested mock communities, while classification methods significantly impact the accuracy of species-level assignments. Of the classification methods tested, Minimap2 classifier in combination with the GROND database most consistently provided accurate species-level classification across the communities tested, irrespective of sequencing platform., Competing Interests: Declarations. Ethics approval and consent to participate: No ethics approval or consent to participate was required. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The assessment of research performance is widely seen as a vital tool in upholding the highest standards of quality, with selection and competition believed to drive progress. Academic institutions need to take critical decisions on hiring and promotion, while facing external pressure by also being subject to research assessment 1-4 . Here we present an outlook on research assessment for career progression with specific focus on promotion to full professorship, based on 314 policies from 190 academic institutions and 218 policies from 58 government agencies, covering 32 countries in the Global North and 89 countries in the Global South. We investigated how frequently various promotion criteria are mentioned and carried out a statistical analysis to infer commonalities and differences across policies. Although quantitative methods of assessment remain popular, in agreement with what is found in more geographically restricted studies 5-9 , they are not omnipresent. We find differences between the Global North and the Global South as well as between institutional and national policies, but less so between disciplines. A preference for bibliometric indicators is more marked in upper-middle-income countries. Although we see some variation, many promotion policies are based on the assumption of specific career paths that become normative rather than embracing diversity. In turn, this restricts opportunities for researchers. These results challenge current practice and have strategic implications for researchers, research managers and national governments., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: This study aims to outline sleep strategies grounded in scientific research and endorsed by sleep experts, integrating parental input into the evaluation process, to assist parents in supporting infant sleep after discharge from a neonatal ward., Methods: A Delphi method, consisting of three rounds, was employed. Sleep strategies based on scientific literature were presented to sleep experts and parents of infants discharged from a neonatal ward., Results: A literature search identified 11 sleep strategies. These strategies were incorporated in Delphi round 1. Out of 17 sleep experts, 13 reviewed and revised these 11 sleep strategies, resulting in a list of 8 sleep strategies. In round 2, these strategies were ranked by 14 out of 17 sleep experts, with "knowledge gathering" being ranked the most important sleep strategy. In round 3, the same list of 8 sleep strategies was ranked by 35 parents. They found "sleep hygiene" and "swaddling" the most important strategies., Conclusion: This study offers 8 sleep strategies that are grounded in scientific research, supported by experts, and evaluated by parents. Experts and parents prioritize sleep strategies differently. Therefore, healthcare professionals should offer practical and customized sleep strategies that align with the unique needs of each family., Impact: Experts and parents prioritize sleep strategies differently. This study offers a summary of sleep strategies that are grounded in scientific research, supported by experts, and include parental feedback in the evaluation process. Healthcare professionals can use these strategies to offer practical and customized sleep advise that aligns with the unique needs of each family., Competing Interests: Competing interests: The authors declare no competing interests. Patient consent: Sleep experts and parents were asked to join the study and fill out the Delphi questionnaire. After they agreed, the Delphi questionnaires were sent. All data were acquired anonymously., (© 2025. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Neonatal seizures require urgent treatment, but often go undetected without expert EEG monitoring. We have developed and validated a seizure detection model using retrospective EEG data from 332 neonates. A convolutional neural network was trained and tested on over 50,000 hours (n = 202) of annotated single-channel EEG containing 12,402 seizure events. This model was then validated on two independent multi-reviewer datasets (n = 51 and n = 79). Increasing data and model size improved performance: Matthews correlation coefficient (MCC) and Pearson's correlation (r) increased by up to 50% (15%) with data (model) scaling. The largest model (21m parameters) achieved state-of-the-art on an open-access dataset (MCC = 0.764, r = 0.824, and AUC = 0.982). This model also attained expert-level performance on both validation sets, a first in this field, with no significant difference in inter-rater agreement when the model replaces an expert (∣Δκ∣ < 0.094, p > 0.05)., Competing Interests: Competing interests: All authors are affiliated with CergenX Ltd, a company developing neuromonitoring technologies for newborns: G.B. and S.G. are co-founders; R.H., A.L., and J.O.T. are employees; and S.M. and S.V. were paid contractors., (© 2025. The Author(s).)

Fatigue is prevalent in immune-mediated inflammatory and neurodegenerative diseases, yet its assessment relies largely on patient-reported outcomes, which capture perception but not fluctuations over time. Wearable sensors, like inertial measurement units (IMUs), offer a way to monitor daily activities and evaluate functional capacity. This study investigates the relationship between sit-to-stand and stand-to-sit transitions and self-reported physical and mental fatigue in participants with Parkinson's, Huntington's, rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren's syndrome and inflammatory bowel disease. Over 4 weeks, participants wore an IMU and reported fatigue levels four times daily. Using mixed-effects models, associations were identified between fatigue and specific kinematic features, such as 5th and 95th percentiles of sit-to-stand performance, suggesting that fatigue alters the control and effort of movement. These kinematic features show promise as indicators for fatigue in these patient populations., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

We are often confronted with a simple question, "which gene editing technique is the best?"; the simple answer is "there isn't one". In 2021, a year after prime editing first made its mark, we evaluated the landscape of this potentially transformative advance in genome engineering towards getting treatments to the clinic [1]. Nearly 20% of the papers we cited were still in pre-print at the time which serves to indicate how early-stage the knowledge base was at that time. Now, three years later, we take a look at the landscape and ask what has been learnt to ensure this tech is broadly accessible, highlighting some key advances, especially those that push this towards the clinic. A big part of the appeal of prime editing is its ability to precisely edit DNA without double stranded breaks, and to install any of the 12 possible single-nucleotide conversion events as well as small insertions and/or deletions, or essentially any combination thereof. Over the last few decades, other transformative and Nobel prize-winning technologies that rely on Watson-Crick base-pairing such as PCR, site-directed mutagenesis, RNA interference, and one might say, "classic" CRISPR, were swiftly adopted across labs around the world because of the speed with which mechanistic rules governing their efficiency were determined. Whilst this perspective focuses on the context of gene therapy applications of prime editing, we also further look at the recent studies which have increased our understanding of the mechanism of PEs and simultaneously improved the efficiency and diversity of the PE toolbox., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In recent years, as river-borne sediment transport has decreased, land loss in estuarine areas has become increasingly severe. Particularly from 2009 to 2022, due to the reduced sediment load from the upper reaches of the Yangtze River, significant changes in the erosion-deposition conditions at the Yangtze River Estuary have become a critical concern. The suspended sediment concentration (SSC) in the estuary is closely linked to sediment content, and against this backdrop, this study aims to thoroughly explore the response mechanisms of the Yangtze River Estuary's SSC to changes in erosion-deposition conditions, with the goal of providing scientific bases and strategic recommendations for erosion-deposition management. To this end, this research collected historical water depth data for the Yangtze River Estuary, measured vertical distribution of SSC in September 2022, surface suspended sediment concentration (SSSC) data from 2021 to 2023, and 25 factors influencing SSSC, to analyze in detail the changes in the erosion-deposition conditions at the Yangtze River Estuary and the response mechanisms of SSC to these changes. The analysis showed that between 2009 and 2022, the mouth bar area of the Yangtze River Estuary experienced net erosion for the first time since 1958, with an annual erosion rate reaching 63.2 × 10^6 m 3 /yr, and the highest erosion rate occurring in the North Passage area, reaching 83.3 mm/yr. This phenomenon is likely caused by human-induced changes in underwater topography, with the Yangtze River Estuary shifting from deposition to erosion. Between 2021 and 2023, the turbidity maximum zone (TMZ) of the Yangtze River Estuary did not show regular changes in SSSC, which may be related to the frequent occurrence of typhoons and changes in sediment supply in the submerged delta of the Yangtze River Estuary., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The performance gains achieved by deep learning models nowadays are mainly attributed to the usage of ever larger datasets. In this study, we present and contrast the performance gains that can be achieved via accessing larger high-quality datasets versus the gains that can be achieved from harnessing the latest deep learning architectural and training advances. Modelling neonatal EEG is particularly affected by the lack of publicly available large datasets. It is shown that greater performance gains can be achieved from harnessing the latest deep learning advances than using a larger training dataset when adopting AUC as a metric, whereas using AUC90 or AUC-PR as metrics greater performance gains are achieved from using a larger dataset than harnessing the latest deep learning advances. In all scenarios the best performance is obtained by combining both deep learning advances and larger datasets. A novel developed architecture is presented that outperforms the current state-of-the-art model for the task of neonatal seizure detection. A novel method to fine-tune the presented model towards site-specific settings based on pseudo labelling is also outlined. The code and the weights of the model are made publicly available for benchmarking future model performances for neonatal seizure detection., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethics Statement This study has the full ethical approval from the Clinical Ethics Committee of the Cork Teaching Hospitals., (© 2024. The Author(s).)

Infants requiring admission to the neonatal intensive care unit (NICU) are particularly vulnerable to developing brain injury. The severity of the underlying clinical conditions and the complexity of care call for continuous, cot-side, non-invasive monitoring tools. Near-infrared spectroscopy (NIRS) measures the regional tissue oxygen saturation of hemoglobin (rStO 2 ) and provides continuous information on the net-result of several factors. Cerebral rStO 2 correlates with echocardiography-derived measures of blood flow. Cerebral fractional tissue oxygen extraction provides information on the balance between oxygen supply and demand and can be continuously derived from the combined use of cerebral rStO 2 and arterial oxygen saturation. Information on cerebral blood flow autoregulatory capacity can be obtained from combining cerebral rStO 2 and invasive blood pressure monitoring by appropriate software. Cerebral rStO 2 provides real-time, end-organ information on perfusion-oxygenation, and when interpreted in the clinical context based on pathophysiological principles may be used as a help to guide interventions in the NICU. In this review we will discuss how to optimize NIRS monitoring for application in the NICU, with a particular focus on the preterm infant. IMPACT: Near-infrared spectroscopy (NIRS) provides cot-side, real-time information on blood and oxygen supply to the brain. Therefore, it is a valuable tool to better understand the pathophysiology underlaying disease processes. Current evidence suggests that NIRS-guided treatment in extremely preterm infants during transitional circulation does not improve clinical outcomes. Specific training is needed to maximize potential performance. Pathophysiological interpretation of cerebral NIRS data in the given clinical context may help in decision-making. Appropriate use of this monitoring technique, interpreted concurrently with other routine parameters, is a potential clinical tool to guide interventions in the NICU setting., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Stress in sea urchins leads to high mortality and economic losses in both the environment and aquaculture. The green sea urchin Strongylocentrotus droebachiensis has been documented emitting complex biofluorescence, yet how this responds to external stressors is unknown. Adult sea urchins (n = 210) were divided between control (n = 30) and experimental groups (n = 180), using three transport variables: out of water, in water at elevated temperatures, (warm-water) and in water at seawater temperature (cold-water). Hyperspectral imaging of external fluorescence and fluorospectrometric analysis on coelomic fluid was measured at five intervals (hour 0,3,6,9,12). External green emissions (∼580 nm) responded to all treatments, peaking at h9. External red emissions (∼680-730 nm) in the cold-water remained low until an h9 peak. The warm water increased emissions at each interval, peaking at h9. The out of water gradually increased, with the highest at h12. The coelomic fluid fluorescence (∼680 nm) was low to nonexistent except in warm-water, whose elevated levels suggest that fluorescent emissions are a measurable byproduct of internal adaptation(s) to stress. Early detection of fluorescent emissions (broken spines, lesions) may prevent economic losses. The observed link between fluorescence and the applied stressors provides a baseline for developing non-invasive technology for improving echinoderm welfare., (© 2024. The Author(s).)

There is insufficient research on bioaerosols in hospital waste decontamination stations. This study aimed to investigate the effect of three-layer and N95 masks in reducing the inhalation risk of bacterial bioaerosols in a waste decontamination station at a teaching hospital. Active sampling was conducted on five different days at three locations: the yard, resting room, and autoclave room in three different modes: without a mask, with a three-layer mask, and with an N95 mask. Bacterial bioaerosols passing through the masks were identified using biochemical tests and polymerase chain reaction (PCR). The median concentration and interquartile range (IQR) of bacterial bioaerosols was 217.093 (230.174) colony-forming units per cubic meter (CFU/m 3 ), which is higher than the recommended amount by Pan American Health Organization (PAHO). The resting room had high contamination levels, with a median (IQR) of 321.9 (793.529) CFU/m 3 of bacterial bioaerosols. The maximum concentration of bioaerosols was also recorded in the same room (2443.282 CFU/m 3 ). The concentration of bacterial bioaerosols differed significantly between using a three-layer or N95 mask and not using a mask (p-value < 0.001). The non-carcinogenic risk level was acceptable in all cases, except in the resting room without a mask (Hazard Quotient (HQ) = 2.07). The predominant bacteria were Gram-positive cocci (33.98%). Micrococci (three-layer mask = 51.28%, N95 mask = 50%) and Coagulase-negative Staphylococci (three-layer mask = 30.77%, N95 mask = 31.82%) were the most abundant bioaerosols passing through the masks. The results obtained are useful for managerial decisions in hospital waste decontamination stations to reduce exposure to bioaerosols and develop useful guidelines., (© 2024. The Author(s).)

Endometriosis is a chronic systemic disease, which results in endometrial-type tissue growing outside the uterus, and affects approximately 10% of reproductive-aged women worldwide. Its aetiology is poorly understood, and there is currently no long-term cure. Development and persistence of the disease depend on several coexisting factors including the vaginal microbiome. However, the role played by this important entity in endometriosis and its systemic involvement is not fully understood. Here, we investigated the vaginal microbiota, the serum and urine glycome, and antibody glycosylation in endometriosis patients. We reveal an endometriosis-specific vaginal microbiota in patients, being distinct from that present in a control group. Endometriosis patients were typified by a loss of the dominant Lactobacillus species, i.e. Lactobacillus iners, increased bacterial diversity and the presence of species such as Anaerococcus senegalensis, Prevotella jejuni, Porphyromonas bennonis and Anaerococcus octavius. The presence of trigalactosylated and triantennary serum glycans and urine core fucosylated mono-antennary glycans from IgG correlated with the vaginal presence of the bacterium A. senegalensis in endometriosis patients. Urine glycans did not differ in endometriosis, but urine IgG identified four novel sulfated glycans differing from serum IgG indicating functional relevance. Our findings contribute to understanding the relationships between the vaginal microbiota and the serum and urine glycome on the one hand, and endometriosis on the other. Further functional studies are warranted., (© 2024. The Author(s).)

Neonatology is a pediatric sub-discipline focused on providing care for newborn infants, including healthy newborns, those born prematurely, and those who present with illnesses or malformations requiring medical care. The European Training Requirements (ETR) in Neonatology provide a framework for standardized quality and recognition of equality of training throughout Europe. The latest ETR version was approved by the Union of European Medical Specialists (UEMS) in April 2021. Here, we present the curriculum of the European School of Neonatology Master of Advanced Studies (ESN MAS), which is based on the ETR in Neonatology and aims to provide a model for effective and standardized training and education in neonatal medicine. We review the history and theory that form the foundation of contemporary medical education and training, provide a literature review on best practices for medical training, pediatric training, and neonatology training specifically, including educational frameworks and evidence-based systems of evaluation. The ESN MAS Curriculum is then evaluated in light of these best practices to define its role in meeting the need for a standardized empirically supported neonatology training curriculum for physicians, and in the future for nurses, to improve the quality of neonatal care for all infants. IMPACT STATEMENT: A review of the neonatology training literature was conducted, which concluded that there is a need for standardized neonatology training across international contexts to keep pace with growth in the field and rapidly advancing technology. This article presents the European School of Neonatology Master of Advanced Studies in Neonatology, which is intended to provide a standardized training curriculum for pediatricians and nurses seeking sub-specialization in neonatology. The curriculum is evaluated in light of best practices in medical education, neonatology training, and adult learning theory., (© 2024. The Author(s).)

Early induced therapeutic hypothermia represents the cornerstone treatment in neonates with probable hypoxic-ischemic encephalopathy. The selection of patients for treatment usually involves meeting criteria indicating evidence of perinatal hypoxia-ischemia and the presence of moderate or severe encephalopathy. In this review, we highlight the variability that exists between some of the different regional and national eligibility guidelines. Determining the potential presence of perinatal hypoxia-ischemia may require either one, two or three signs amongst history of acute perinatal event, prolonged resuscitation at delivery, abnormal blood gases and low Apgar score, with a range of cutoff values. Clinical neurological exams often define the severity of encephalopathy differently, with varying number of domains required for determining eligibility and blurred interpretation of findings assigned to different severity grades in different systems. The role of early electrophysiological assessment is weighted differently. A clinical implication is that infants may receive different care depending on the location in which they are born. This could also impact epidemiological data, as inference of rates of moderate-severe encephalopathy based on therapeutic hypothermia rates are misleading and influenced by different eligibility methods used. We would advocate that a universally endorsed single severity staging of encephalopathy is vital for standardizing management and neonatal outcome. IMPACT: Variability exists between regional and national therapeutic hypothermia eligibility guidelines for neonates with probable hypoxic-ischemic encephalopathy. Differences are common in both criteria indicating perinatal hypoxia-ischemia and criteria defining moderate or severe encephalopathy. The role of early electrophysiological assessment is also weighted unequally. This reflects in different individual care and impacts research data. A universally endorsed single severity staging of encephalopathy would be crucial for standardizing management., (© 2024. The Author(s).)

Seasonal rhythms are gaining attention given their impact on metabolic disorders development such as obesity gut microbiota is emerging as a key factor in mediating this link. However, the underlying mechanisms are still poorly understood. In this regard, corticosterone may play a role as it has been shown to be affected by gut bacteria and seasonal rhythms, and has been linked to obesity. Thus, this study aimed to investigate if seasonal rhythms effects on corticosterone are influenced by gut microbiota in obese rats and whether this may be related to seasonal and clock genes expression in the pituitary gland and colon. Fischer 344 male rats fed with cafeteria diet (CAF) were housed under different photoperiods for 9 weeks and treated with an antibiotic cocktail (ABX) in drinking water during the last 4 weeks. Rats fed with standard chow and CAF-fed rats without ABX were included as controls. ABX altered gut microbiota, corticosterone levels and seasonal clock expression in the pituitary depending on photoperiod conditions. These results suggest a link between gut bacteria, seasonal rhythms and corticosterone and a novel nutrigenomic target for obesity., (© 2024. The Author(s).)

Perioperative applications of near-infrared spectroscopy (NIRS) to monitor regional tissue oxygenation and perfusion in cardiac and noncardiac surgery are of increasing interest in neonatal care. Complex neonatal surgery can impair adequate oxygen delivery and tissue oxygen consumption and increase the risk of neurodevelopmental delay. Coupled with conventional techniques, NIRS monitoring may enable targeted hemodynamic management of the circulation in both cardiac and noncardiac surgical procedures. In this narrative review, we discuss the application of perioperative NIRS in specific neonatal interventions, including surgical intervention for congenital heart defects, definitive closure of the patent ductus arteriosus, neurological and gastrointestinal disorders, and use of extracorporeal membrane oxygenation. We identified areas for future research within disease-specific indications and offer a roadmap to aid in developing evidence-based targeted diagnostic and management strategies in neonates. IMPACT: There is growing recognition that perioperative NIRS monitoring, used in conjunction with conventional monitoring, may provide critical hemodynamic information that either complements clinical impressions or delivers novel physiologic insight into the neonatal circulatory and perfusion pathways., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: The aim of this systematic qualitative review was to give an overview of reference ranges defined as normal values or centile charts of regional tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) in term and preterm neonates., Methods: A systematic search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed. Additional articles were identified by manual search of cited references. Only human studies in neonates were included., Results: Nineteen studies were identified. Eight described regional tissue oxygen saturation during fetal-to-neonatal transition, six during the first 3 days after birth, four during the first 7 days after birth, and one during the first 8 weeks after birth. Nine described regional tissue oxygen saturation in term, nine in preterm neonates, and one in both. Eight studies published centile charts for cerebral regional tissue oxygen saturation, and only five included large cohorts of infants. Eleven studies described normal values for cerebral, muscle, renal, and abdominal regional tissue oxygen saturation, the majority with small sample sizes. Four studies of good methodological quality were identified describing centile charts of cerebral regional tissue oxygen saturation., Conclusions: In clinical settings, quality centile charts are available and should be the preferred method when using NIRS monitoring., Impact: Near-infrared spectroscopy (NIRS) enables a bed-side non-invasive continuous monitoring of tissue oxygenation. When using NIRS monitoring in a clinical setting, centile charts with good quality are available and should be preferred to normal values. High-quality reference ranges of regional tissue oxygenation in term and preterm born neonates are an important step toward routine clinical application of NIRS., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Neonatal neurocritical intensive care is dedicated to safeguarding the newborn brain by prioritising clinical practices that promote early identification, diagnosis and treatment of brain injuries. The most common newborn neurological emergency is neonatal seizures, which may also be the initial clinical indication of neurological disease. A high seizure burden in the newborn period independently contributes to increased mortality and morbidity. The majority of seizures in newborns are subclinical (without clinical presentation), and hence identification may be difficult. Neuromonitoring techniques most frequently used to monitor brain wave activity include conventional electroencephalography (cEEG) or amplitude-integrated EEG (aEEG). cEEG with video is the gold standard for diagnosing and treating seizures. Many neonatal units do not have access to cEEG, and frequently those that do, have little access to real-time interpretation of monitoring. IMPACT: EEG monitoring is of no benefit to an infant without expert interpretation. Whilst EEG is a reliable cot-side tool and of diagnostic and prognostic use, both conventional EEG and amplitude-integrated EEG have strengths and limitations, including sensitivity to seizure activity and ease of interpretation. Automated seizure detection requires a sensitive and specific algorithm that can interpret EEG in real-time and identify seizures, including their intensity and duration., (© 2024. The Author(s).)

Amyloid-β (Aβ) is thought to be neuronally derived in Alzheimer's disease (AD). However, transcripts of amyloid precursor protein (APP) and amyloidogenic enzymes are equally abundant in oligodendrocytes (OLs). By cell-type-specific deletion of Bace1 in a humanized knock-in AD model, APP NLGF , we demonstrate that OLs and neurons contribute to Aβ plaque burden. For rapid plaque seeding, excitatory projection neurons must provide a threshold level of Aβ. Ultimately, our findings are relevant for AD prevention and therapeutic strategies., (© 2024. The Author(s).)

Cerebrovascular reactivity defines the ability of the cerebral vasculature to regulate its resistance in response to both local and systemic factors to ensure an adequate cerebral blood flow to meet the metabolic demands of the brain. The increasing adoption of near-infrared spectroscopy (NIRS) for non-invasive monitoring of cerebral oxygenation and perfusion allowed investigation of the mechanisms underlying cerebrovascular reactivity in the neonatal population, confirming important associations with pathological conditions including the development of brain injury and adverse neurodevelopmental outcomes. However, the current literature on neonatal cerebrovascular reactivity is mainly still based on small, observational studies and is characterised by methodological heterogeneity; this has hindered the routine application of NIRS-based monitoring of cerebrovascular reactivity to identify infants most at risk of brain injury. This review aims (1) to provide an updated review on neonatal cerebrovascular reactivity, assessed using NIRS; (2) to identify critical points that need to be addressed with targeted research; and (3) to propose feasibility trials in order to fill the current knowledge gaps and to possibly develop a preventive or curative approach for preterm brain injury. IMPACT: NIRS monitoring has been largely applied in neonatal research to assess cerebrovascular reactivity in response to blood pressure, PaCO 2 and other biochemical or metabolic factors, providing novel insights into the pathophysiological mechanisms underlying cerebral blood flow regulation. Despite these insights, the current literature shows important pitfalls that would benefit to be addressed in a series of targeted trials, proposed in the present review, in order to translate the assessment of cerebrovascular reactivity into routine monitoring in neonatal clinical practice., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

The resident microbiome in food industries may impact on food quality and safety. In particular, microbes residing on surfaces in dairy industries may actively participate in cheese fermentation and ripening and contribute to the typical flavor and texture. In this work, we carried out an extensive microbiome mapping in 73 cheese-making industries producing different types of cheeses (fresh, medium and long ripened) and located in 4 European countries. We sequenced and analyzed metagenomes from cheese samples, raw materials and environmental swabs collected from both food contact and non-food contact surfaces, as well as operators' hands and aprons. Dairy plants were shown to harbor a very complex microbiome, characterized by high prevalence of genes potentially involved in flavor development, probiotic activities, and resistance to gastro-intestinal transit, suggesting that these microbes may potentially be transferred to the human gut microbiome. More than 6100 high-quality Metagenome Assembled Genomes (MAGs) were reconstructed, including MAGs from several Lactic Acid Bacteria species and putative new species. Although microbial pathogens were not prevalent, we found several MAGs harboring genes related to antibiotic resistance, highlighting that dairy industry surfaces represent a potential hotspot for antimicrobial resistance (AR) spreading along the food chain. Finally, we identified facility-specific strains that can represent clear microbial signatures of different cheesemaking facilities, suggesting an interesting potential of microbiome tracking for the traceability of cheese origin., (© 2024. The Author(s).)

Necrotizing enterocolitis (NEC) involves intestinal epithelial damage and inflammatory response and is associated with high morbidity and mortality in infants. To improve therapeutic prospects, elucidating underlying molecular mechanisms of intestinal epithelial damage during NEC is of the essence. Poly (ADP-ribose) polymerase 1 (PARP1)-dependent parthanatos is a programmed inflammatory cell death. In the present study, the presence of parthanatos-associated proteins PARP1 and poly (ADP-ribose) (PAR), along with high expression of DNA damage-associated biomarkers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and phosphorylation of histone H2AX (γH2AX), were discovered in the intestinal tissues of NEC infants. Additionally, the upregulated expression of PARP1 and PAR in NEC intestinal tissues correlated distinctly with clinical indices indicative of NEC incidence and severity. Furthermore, we demonstrated that inhibiting the expression of parthanatos-associated proteins, by either pharmacological blockage using 3-aminobenzamide (3-AB), an inhibitor of PARP1, or genetic knockout using Parp1-deficient mice, resulted in substantial improvements in both histopathological severity scores associated with intestinal injury and inflammatory reactions. Moreover, in an in vitro NEC model, reactive oxygen species (ROS)-induced DNA damage promoted the formation of PAR and nuclear translocation of apoptosis-inducing factor (AIF), thus activating PARP1-dependent parthanatos in Caco-2 cells and human intestinal organoids. Our work verifies a previously unexplored role for parthanatos in intestinal epithelial damage during NEC and suggests that inhibition of parthanatos may serve as a potential therapeutic strategy for intervention of NEC., (© 2024. The Author(s).)

Immunological adaptions during pregnancy play a crucial role in healthy fetal development. Aberrant immune modifications however contribute to adverse pregnancy outcomes, which may be driven by maternal factors such as previous pregnancies and BMI. This secondary analysis of the MicrobeMom2 RCT investigates the changes to maternal inflammatory biomarkers derived from serum and stimulated peripheral blood mononuclear cells (PBMCs) during pregnancy, and the effects of previous pregnancies (parity) and BMI on maternal immune responses. Changes in immune and metabolic biomarkers from early (11-15 weeks' gestation) to late (28-32 weeks' gestation) pregnancy were compared using paired t-tests. Participants were then split by parity (nulliparous, parous) and BMI (BMI < 25, BMI > = 25), and the relationship between parity and BMI with immune biomarker levels was examined using independent t-tests, paired t-tests, ANCOVA, and linear regression. Equivalent non-parametric tests were used for skewed data. Recruited women (n = 72) were on average 31.17 (SD ± 4.53) years of age and 25.11 (SD ± 3.82) BMI (kg/m 2 ). Of these, 51 (70.8%) had a previous term pregnancy. Throughout gestation, PBMC cytokines displayed contrasting trends to serum, with a dampening of immune responses noted in PBMCs, and enhanced production of cytokines observed in the serum. Significant decreases in PBMC derived TNF-α, IL-10 and IFN-γ were seen from early to late pregnancy. Serum C3, IL-17A, IL-6, TNF-α, CD163, GDF-15 and leptin increased throughout gestation. First pregnancy was associated with higher levels of leptin in late pregnancy, while parous women showed significant decreases in PBMC derived TNF-α, IL10, and IFN-γ with gestation. Differences in levels of C3, IL-17A, TNF-α, GDF-15 and leptin were observed across BMI groups. Overall, serum-derived cytokines exhibit contrasting levels to those derived from stimulated PBMCs. Maternal immune responses undergo significant changes from early to late pregnancy, which are influenced by parity and BMI. These differences aid our understanding as to why first-time mothers are at greater risk of placental disease such as pre-eclampsia and fetal growth restriction., (© 2024. The Author(s).)

Non-invasive cardiac output monitoring, via electrical biosensing technology (EBT), provides continuous, multi-parameter hemodynamic variable monitoring which may allow for timely identification of hemodynamic instability in some neonates, providing an opportunity for early intervention that may improve neonatal outcomes. EBT encompasses thoracic (TEBT) and whole body (WBEBT) methods. Despite the lack of relative accuracy of these technologies, as compared to transthoracic echocardiography, the use of these technologies in neonatology, both in the research and clinical arena, have increased dramatically over the last 30 years. The European Society of Pediatric Research Special Interest Group in Non-Invasive Cardiac Output Monitoring, a group of experienced neonatologists in the field of EBT, deemed it appropriate to provide recommendations for the use of TEBT and WBEBT in the field of neonatology. Although TEBT is not an accurate determinant of cardiac output or stroke volume, it may be useful for monitoring longitudinal changes of hemodynamic parameters. Few recommendations can be made for the use of TEBT in common neonatal clinical conditions. It is recommended not to use WBEBT to monitor cardiac output. The differences in technologies, study methodologies and data reporting should be addressed in ongoing research prior to introducing EBT into routine practice. IMPACT STATEMENT: TEBT is not recommended as an accurate determinant of cardiac output (CO) (or stroke volume (SV)). TEBT may be useful for monitoring longitudinal changes from baseline of hemodynamic parameters on an individual patient basis. TEBT-derived thoracic fluid content (TFC) longitudinal changes from baseline may be useful in monitoring progress in respiratory disorders and circulatory conditions affecting intrathoracic fluid volume. Currently there is insufficient evidence to make any recommendations regarding the use of WBEBT for CO monitoring in neonates. Further research is required in all areas prior to the implementation of these monitors into routine clinical practice., (© 2024. The Author(s).)

The process of implementation of the UN Sustainable Development Goals (SDGs) which were approved by the UN General Assembly in 2015 has not been simple, being influenced by variety of social, economic, and logistical problems. It has also been negatively affected by the COVID-19 pandemic. There are to date no specific studies aimed at assessing the extent to which higher universities institutions in Europe are active in the SDGs implementation process. Departing from this research need, this paper reports on a study aimed at examining the current degree of engagement of European universities in the implementing the SDGs. By using a multi-methods approach, which entails a review of existing documents, a survey involving participants from 22 countries and case studies, the paper maps, documents and disseminates examples of what European universities are doing to implement the SDGs, the challenges they face, and the solutions being deployed to overcome them., (© 2024. The Author(s).)

Electroencephalogram (EEG) is an important biomarker for neonatal encephalopathy (NE) and has significant predictive value for brain injury and neurodevelopmental outcomes. Quantitative analysis of EEG involves the representation of complex EEG data in an objective, reproducible and scalable manner. Quantitative EEG (qEEG) can be derived from both a limited channel EEG (as available during amplitude integrated EEG) and multi-channel conventional EEG. It has the potential to enable bedside clinicians to monitor and evaluate details of cortical function without the necessity of continuous expert input. This is particularly useful in NE, a dynamic and evolving condition. In these infants, continuous, detailed evaluation of cortical function at the bedside is a valuable aide to management especially in the current era of therapeutic hypothermia and possible upcoming neuroprotective therapies. This review discusses the role of qEEG in newborns with NE and its use in informing monitoring and therapy, along with its ability to predict imaging changes and short and long-term neurodevelopmental outcomes. IMPACT: Quantitative representation of EEG data brings the evaluation of continuous brain function, from the neurophysiology lab to the NICU bedside and has a potential role as a biomarker for neonatal encephalopathy. Clinical and research applications of quantitative EEG in the newborn are rapidly evolving and a wider understanding of its utility is valuable. This overview summarizes the role of quantitative EEG at different timepoints, its relevance to management and its predictive value for short- and long-term outcomes in neonatal encephalopathy., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: 'Neonatal encephalopathy' (NE) describes a group of conditions in term infants presenting in the earliest days after birth with disturbed neurological function of cerebral origin. NE is aetiologically heterogenous; one cause is peripartum hypoxic ischaemia. Lack of uniformity in the terminology used to describe NE and its diagnostic criteria creates difficulty in the design and interpretation of research and complicates communication with families. The DEFINE study aims to use a modified Delphi approach to form a consensus definition for NE, and diagnostic criteria., Methods: Directed by an international steering group, we will conduct a systematic review of the literature to assess the terminology used in trials of NE, and with their guidance perform an online Real-time Delphi survey to develop a consensus diagnosis and criteria for NE. A consensus meeting will be held to agree on the final terminology and criteria, and the outcome disseminated widely., Discussion: A clear and consistent consensus-based definition of NE and criteria for its diagnosis, achieved by use of a modified Delphi technique, will enable more comparability of research results and improved communication among professionals and with families., Impact: The terms Neonatal Encephalopathy and Hypoxic Ischaemic Encephalopathy tend to be used interchangeably in the literature to describe a term newborn with signs of encephalopathy at birth. This creates difficulty in communication with families and carers, and between medical professionals and researchers, as well as creating difficulty with performance of research. The DEFINE project will use a Real-time Delphi approach to create a consensus definition for the term 'Neonatal Encephalopathy'. A definition formed by this consensus approach will be accepted and utilised by the neonatal community to improve research, outcomes, and parental experience., (© 2024. The Author(s).)

We report the results of 24 women, 50% (N = 12) with hormone receptor-positive breast cancer and 50% (N = 12) with advanced triple-negative breast cancer, treated with entinostat + nivolumab + ipilimumab from the dose escalation (N = 6) and expansion cohort (N = 18) of ETCTN-9844 ( NCT02453620 ). The primary endpoint was safety. Secondary endpoints were overall response rate, clinical benefit rate, progression-free survival and change in tumor CD8:FoxP3 ratio. There were no dose-limiting toxicities. Among evaluable participants (N = 20), the overall response rate was 25% (N = 5), with 40% (N = 4) in triple-negative breast cancer and 10% (N = 1) in hormone receptor-positive breast cancer. The clinical benefit rate was 40% (N = 8), and progression-free survival at 6 months was 50%. Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Assessment of current and future growth in the global rooftop area is important for understanding and planning for a robust and sustainable decentralised energy system. These estimates are also important for urban planning studies and designing sustainable cities thereby forwarding the ethos of the Sustainable Development Goals 7 (clean energy), 11 (sustainable cities), 13 (climate action) and 15 (life on land). Here, we develop a machine learning framework that trains on big data containing ~700 million open-source building footprints, global land cover, road, and population datasets to generate globally harmonised estimates of growth in rooftop area for five different future growth narratives covered by Shared Socioeconomic Pathways. The dataset provides estimates for ~3.5 million fishnet tiles of 1/8 degree spatial resolution with data on gross rooftop area for five growth narratives covering years 2020-2050 in decadal time steps. This single harmonised global dataset can be used for climate change, energy transition, biodiversity, urban planning, and disaster risk management studies covering continental to conurbation geospatial levels., (© 2024. The Author(s).)

Persistent post-surgical pain (PPSP) is defined as pain which continues after a surgical operation in a significant form for at least three months (and is not related to pre-existing painful conditions). PPSP is a common, under-recognised, and important clinical problem which affects millions of patients worldwide. Preventative measures which are currently available include the selection of a minimally invasive surgical technique and an aggressive multimodal perioperative analgesic regimen. More recently, a role for the gut microbiota in pain modulation has become increasingly apparent. This study aims to investigate any relationship between the gut microbiota and PPSP. A prospective observational study of 68 female adult patients undergoing surgery for management of breast cancer was carried out. Stool samples from 45 of these patients were obtained to analyse the composition of the gut microbiota. Measures of pain and state-trait anxiety were also taken to investigate further dimensions in any relationship between the gut microbiota and PPSP. At 12 weeks postoperatively, 21 patients (51.2%) did not have any pain and 20 patients (48.8%) reported feeling pain that persisted at that time. Analysis of the gut microbiota revealed significantly lower alpha diversity (using three measures) in those patients reporting severe pain at the 60 min post-operative and the 12 weeks post-operative timepoints. A cluster of taxa represented by Bifidobacterium longum, and Faecalibacterium prausnitzii was closely associated with those individuals reporting no pain at 12 weeks postoperatively, while Megamonas hypermegale, Bacteroides pectinophilus, Ruminococcus bromii, and Roseburia hominis clustered relatively closely in the group of patients fulfilling the criteria for persistent post-operative pain. We report for the first time specific associations between the gut microbiota composition and the presence or absence of PPSP. This may provide further insights into mechanisms behind the role of the gut microbiota in the development of PPSP and could inform future treatment strategies., (© 2024. The Author(s).)

A novel programmable implantable neurostimulation platform based on photonic power transfer has been developed for various clinical applications with the main focus of being safe to use with MRI scanners. The wires usually conveying electrical current from the neurostimulator to the electrodes are replaced by optical fibers. Photovoltaic cells at the tip of the fibers convert laser light to biphasic electrical impulses together with feedback signals with 54% efficiency. Furthermore, a biocompatible, implantable and ultra-flexible optical lead was developed including custom optical fibers. The neurostimulator platform incorporates advanced signal processing and optical physiological sensing capabilities thanks to a hermetically sealed transparent nonmetallic casing. Skin transparency also allowed the development of a high-speed optical transcutaneous communication channel. This implantable neurostimulation platform was first adapted to a vagus nerve stimulator for the treatment of epilepsy. This neurostimulator has been designed to fulfill the requirements of a class III long-term implantable medical device. It has been proven compliant with standard ISO/TS10974 for 1.5 T and 3 T MRI scanners. The device poses no related threat and patients can safely undergo MRI without specific or additional precautions. Especially, the RF induced heating near the implant remains below 2 °C whatever the MRI settings used. The main features of this unique advanced neurostimulator and its architecture are presented. Its functional performance is evaluated, and results are described with a focus on optoelectronics aspects and MRI safety., (© 2024. The Author(s).)

Phocaeicola dorei and Phocaeicola vulgatus are very common and abundant members of the human gut microbiome and play an important role in the infant gut microbiome. These species are closely related and often confused for one another; yet, their genome comparison, interspecific diversity, and evolutionary relationships have not been studied in detail so far. Here, we perform phylogenetic analysis and comparative genomic analyses of these two Phocaeicola species. We report that P. dorei has a larger genome yet a smaller pan-genome than P. vulgatus. We found that this is likely because P. vulgatus is more plastic than P. dorei, with a larger repertoire of genetic mobile elements and fewer anti-phage defense systems. We also found that P. dorei directly descends from a clade of P. vulgatus¸ and experienced genome expansion through genetic drift and horizontal gene transfer. Overall, P. dorei and P. vulgatus have very different functional and carbohydrate utilisation profiles, hinting at different ecological strategies, yet they present similar antimicrobial resistance profiles., (© 2024. The Author(s).)

Background: There are no early, accurate, scalable methods for identifying infants at high risk of poor cognitive outcomes in childhood. We aim to develop an explainable predictive model, using machine learning and population-based cohort data, for this purpose., Methods: Data were from 8858 participants in the Growing Up in Ireland cohort, a nationally representative study of infants and their primary caregivers (PCGs). Maternal, infant, and socioeconomic characteristics were collected at 9-months and cognitive ability measured at age 5 years. Data preprocessing, synthetic minority oversampling, and feature selection were performed prior to training a variety of machine learning models using ten-fold cross validated grid search to tune hyperparameters. Final models were tested on an unseen test set., Results: A random forest (RF) model containing 15 participant-reported features in the first year of infant life, achieved an area under the receiver operating characteristic curve (AUROC) of 0.77 for predicting low cognitive ability at age 5. This model could detect 72% of infants with low cognitive ability, with a specificity of 66%., Conclusions: Model performance would need to be improved before consideration as a population-level screening tool. However, this is a first step towards early, individual, risk stratification to allow targeted childhood screening., Impact: This study is among the first to investigate whether machine learning methods can be used at a population-level to predict which infants are at high risk of low cognitive ability in childhood. A random forest model using 15 features which could be easily collected in the perinatal period achieved an AUROC of 0.77 for predicting low cognitive ability. Improved predictive performance would be required to implement this model at a population level but this may be a first step towards early, individual, risk stratification., (© 2024. The Author(s).)

Wearable sensors have recently been extensively used in sports science, physical rehabilitation, and industry providing feedback on physical fatigue. Information obtained from wearable sensors can be analyzed by predictive analytics methods, such as machine learning algorithms, to determine fatigue during shoulder joint movements, which have complex biomechanics. The presented dataset aims to provide data collected via wearable sensors during a fatigue protocol involving dynamic shoulder internal rotation (IR) and external rotation (ER) movements. Thirty-four healthy subjects performed shoulder IR and ER movements with different percentages of maximal voluntary isometric contraction (MVIC) force until they reached the maximal exertion. The dataset includes demographic information, anthropometric measurements, MVIC force measurements, and digital data captured via surface electromyography, inertial measurement unit, and photoplethysmography, as well as self-reported assessments using the Borg rating scale of perceived exertion and the Karolinska sleepiness scale. This comprehensive dataset provides valuable insights into physical fatigue assessment, allowing the development of fatigue detection/prediction algorithms and the study of human biomechanical characteristics during shoulder movements within a fatigue protocol., (© 2024. The Author(s).)

The Eocene Geiseltal Konservat-Lagerstätte (Germany) is famous for reports of three dimensionally preserved soft tissues with sub-cellular detail. The proposed mode of preservation, direct replication in silica, is not known in other fossils and has not been verified using modern approaches. Here, we investigated the taphonomy of the Geiseltal anurans using diverse microbeam imaging and chemical analytical techniques. Our analyses confirm the preservation of soft tissues in all body regions but fail to yield evidence for silicified soft tissues. Instead, the anuran soft tissues are preserved as two layers that differ in microstructure and composition. Layer 1 comprises sulfur-rich carbonaceous microbodies interpreted as melanosomes. Layer 2 comprises the mid-dermal Eberth-Katschenko layer, preserved in calcium phosphate. In addition, patches of original aragonite crystals define the former position of the endolymphatic sac. The primary modes of soft tissue preservation are therefore sulfurization of melanosomes and phosphatization of more labile soft tissues, i.e., skin. This is consistent with the taphonomy of vertebrates in many other Konservat-Lagerstätten. These findings emphasize an emerging model for pervasive preservation of vertebrate soft tissues via melanosome films, particularly in stagnation-type deposits, with phosphatization of more labile tissues where tissue biochemistry is favorable., (© 2024. The Author(s).)

Climate change is rapidly affecting species distributions across the globe, particularly in the North Atlantic. For highly mobile and elusive cetaceans, the genetic data needed to understand population dynamics are often scarce. Cold-water obligate species such as the white-beaked dolphin (Lagenorhynchus albirostris) face pressures from habitat shifts due to rising sea surface temperatures in addition to other direct anthropogenic threats. Unravelling the genetic connectivity between white-beaked dolphins across their range is needed to understand the extent to which climate change and anthropogenic pressures may impact species-wide genetic diversity and identify ways to protect remaining habitat. We address this by performing a population genomic assessment of white-beaked dolphins using samples from much of their contemporary range. We show that the species displays significant population structure across the North Atlantic at multiple scales. Analysis of contemporary migration rates suggests a remarkably high connectivity between populations in the western North Atlantic, Iceland and the Barents Sea, while two regional populations in the North Sea and adjacent UK and Irish waters are highly differentiated from all other clades. Our results have important implications for the conservation of white-beaked dolphins by providing guidance for the delineation of more appropriate management units and highlighting the risk that local extirpation may have on species-wide genetic diversity. In a broader context, this study highlights the importance of understanding genetic structure of all species threatened with climate change-driven range shifts to assess the risk of loss of species-wide genetic diversity., (© 2024. The Author(s).)

Compact and highly performing photonic devices are characterized by non-intuitive geometries, a large number of parameters, and multiple figures of merit. Optimization and machine learning techniques have been explored to handle these complex designs, but the existing approaches often overlook stochastic quantities. As an example, random fabrication uncertainties critically determines experimental device performance. Here, we present a novel approach for the stochastic multi-objective design of photonic devices combining unsupervised dimensionality reduction and Gaussian process regression. The proposed approach allows to efficiently identify promising alternative designs and model the statistic of their response. Incorporating both deterministic and stochastic quantities into the design process enables a comprehensive analysis of the device and of the possible trade-offs between different performance metrics. As a proof-of-concept, we investigate surface gratings for fiber coupling in a silicon-on-insulator platform, considering variability in structure sizes, silicon thickness, and multi-step etch alignment. We analyze 86 alternative designs presenting comparable performance when neglecting variability, discovering on the contrary marked differences in yield and worst-case figures for both fiber coupling efficiency and back-reflections. Pareto frontiers demonstrating optimized device robustness are identified as well, offering a powerful tool for the design and optimization of photonic devices with stochastic figures of merit., (© 2024. The Author(s).)

Modeling the functionality of the human brain is a major goal in neuroscience for which many powerful methodologies have been developed over the last decade. The impact of working memory and the associated brain regions on the brain dynamics is of particular interest due to their connection with many functions and malfunctions in the brain. In this context, the concept of brain flexibility has been developed for the characterization of brain functionality. We discuss emergence of brain flexibility that is commonly measured by the identification of changes in the cluster structure of co-active brain regions. We provide evidence that brain flexibility can be modeled by a system of coupled FitzHugh-Nagumo oscillators where the network structure is obtained from human brain Diffusion Tensor Imaging (DTI). Additionally, we propose a straightforward and computationally efficient alternative macroscopic measure, which is derived from the Pearson distance of functional brain matrices. This metric exhibits similarities to the established patterns of brain template flexibility that have been observed in prior investigations. Furthermore, we explore the significance of the brain's network structure and the strength of connections between network nodes or brain regions associated with working memory in the observation of patterns in networks flexibility. This work enriches our understanding of the interplay between the structure and function of dynamic brain networks and proposes a modeling strategy to study brain flexibility., (© 2024. The Author(s).)

Stellar chemical compositions can be altered by ingestion of planetary material 1,2 and/or planet formation, which removes refractory material from the protostellar disk 3,4 . These 'planet signatures' appear as correlations between elemental abundance differences and the dust condensation temperature 3,5,6 . Detecting these planet signatures, however, is challenging owing to unknown occurrence rates, small amplitudes and heterogeneous star samples with large differences in stellar ages 7,8 . Therefore, stars born together (that is, co-natal) with identical compositions can facilitate the detection of planet signatures. Although previous spectroscopic studies have been limited to a small number of binary stars 9-13 , the Gaia satellite 14 provides opportunities for detecting stellar chemical signatures of planets among co-moving pairs of stars confirmed to be co-natal 15,16 . Here we report high-precision chemical abundances for a homogeneous sample of ninety-one co-natal pairs of stars with a well defined selection function and identify at least seven instances of planetary ingestion, corresponding to an occurrence rate of eight per cent. An independent Bayesian indicator is deployed, which can effectively disentangle the planet signatures from other factors, such as random abundance variation and atomic diffusion 17 . Our study provides evidence of planet signatures and facilitates a deeper understanding of the star-planet-chemistry connection by providing observational constraints on the mechanisms of planet engulfment, formation and evolution., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)