Search

Almost all accreting black hole and neutron star (NS) X-ray binary systems (XRBs) exhibit prominent brightness variations on a few characteristic time-scales and their harmonics. These quasi-periodic oscillations (QPOs) are thought to be associated with the precession of a warped accretion disc, but the physical mechanism that generates the precessing warp remains uncertain. Relativistic frame dragging (Lense–Thirring precession) is one promising candidate, but a misaligned magnetic field is an alternative, especially for NS XRBs. Here, we report the discovery of five accreting white dwarf systems (AWDs) that display strong optical QPOs with characteristic frequencies and harmonic structures that suggest they are the counterpart of the QPOs seen in XRBs. Since AWDs are firmly in the classical (non-relativistic) regime, Lense–Thirring precession cannot account for these QPOs. By contrast, a weak magnetic field associated with the white dwarf can drive disc warping and precession in these systems, similar to what has been proposed for NS XRBs. Our observations confirm that magnetically driven warping is a viable mechanism for generating QPOs in disc-accreting astrophysical systems, certainly in AWDs and possibly also in NS XRBs. Additionally, they establish a new way to estimate magnetic field strengths, even in relatively weak-field systems where other methods are not available. [ABSTRACT FROM AUTHOR]

CXOU J110926.4−650224 is a candidate transitional millisecond pulsar (tMSP) with X-ray and radio emission properties reminiscent of those observed in confirmed tMSPs in their X-ray 'subluminous' disc state. We present the results of observing campaigns that, for the first time, characterise the optical and near-infrared variability of this source and establish a connection with the mode-switching phenomenon observed in X-rays. The optical emission exhibited flickering activity, frequent dipping episodes where it appeared redder, and a multi-peaked flare where it was bluer. The variability pattern was strongly correlated with that of the X-ray emission. Each dip matched an X-ray low-mode episode, indicating that a significant portion of the optical emission originates from nearly the same region as the X-ray emission. The near-infrared emission also displayed remarkable variability, including a dip of 20 min in length during which it nearly vanished. Time-resolved optical spectroscopic observations reveal significant changes in the properties of emission lines from the disc and help infer the spectral type of the companion star to be between K0 and K5. We compare the properties of CXOU J110926.4−650224 with those of other tMSPs in the X-ray subluminous disc state and discuss our findings within the context of a recently proposed scenario that explains the phenomenology exhibited by the prototypical tMSP PSR J1023+0038. [ABSTRACT FROM AUTHOR]

The classical nova CP Puppis has been observed to have particularly puzzling and peculiar properties. In particular, this classical nova displays occasional bursts in its long-term ASAS-SN light curve. Here, we report on five sectors of TESS data displaying two of these rapid bursts, lasting ∼1 d. Based on the estimated lower energy limits of the bursts, we discuss whether the bursts may be examples of micronovae resulting from localized thermonuclear explosion. Furthermore, its orbital period remains uncertain, with several inconsistent periodic signals appearing in spectroscopic and photometric observations at various wavelengths. Although we cannot unambiguously unravel the physical origin of the signals, the previously suggested nature of CP Puppis as a long orbital period system may be a viable explanation. The recurrence time of the bursts in CP Puppis, together with the unexplained variable modulations make it a prime candidate for intense monitoring. [ABSTRACT FROM AUTHOR]

The urgency to decarbonize the transportation sector covers all kinds of vehicles, here included high-performance competition vehicles. Among the technologies able to guarantee zero emissions during the use phase, fuel cells (FCs) and energy storage systems (ESS), e.g. batteries, offer a great and still largely underexplored potential for complementary and synergic use in hybrid powertrains. Vehicles based on such technologies are cells-battery hybrid electric vehicles (FCHEV), and a niche of these are electric supercars (FCHES). In this context, the degrees of freedom of hybrid powertrains design and the different requirements of FCs and batteries frame the highly complex task of defining a clear and objective methodology to identify an optimal ratio among FC-battery power sources, whose lack jeopardizes a rigorous decision process as well as a general consensus and leads to the acceptance of sub-optimal solutions.In this study an energy/power-based methodology is developed in MATLAB environment considering the longitudinal vehicle dynamics of a typical high-performance parallel FCHES, using telemetry data from a real racetrack as common target for all the evaluated powertrain candidates and using realistic mass values. Under the constraint of equal performance (i.e., equal lap time), several FC-battery parallel hybrid powertrains are numerically evaluated with varying relative energy, power, weight, and under different regenerative braking levels. The set of obtained results allows to draw an objective rightsizing on the FC-battery power share and on the required energy capacity for a parallel FCHEV, as well as mass, hydrogen consumption, etc. The presented methodology offers a general use workflow applicable to any category of vehicles, supporting the engineering of hybrid FC-battery high-performance propulsion systems. The developed code will be made available upon request under the FAIR (Findable, Accessible, Interoperable, Reusable) guidelines.

The production of cementitious formulations involves the addition of chemical additives essential for the optimization of many properties. Superplasticizers are considered additives of great interest but when mixed with concrete they lead to an undesirable increase of air content, with the consequent development of foam. This can adversely affect both mechanical properties and workability, therefore, the use of an antifoam agent is also necessary which should be able to prevent or destroy the foam. This work aims to synthesize esters derived from the reaction of glycine betaine with saturated and unsaturated fatty alcohols of different chain lengths. The reaction products were analyzed by 1H NMR analysis, and the stability of antifoam agents in a superplasticizer solution was studied through foaming tests according to the Ross-Miles method. At the same time, their effectiveness in the cementitious systems was evaluated through flow Table tests. Finally, the effectiveness of the antifoam agents was quantified through an image analysis software, Image J, which allowed the investigation of the contents of the bubble in concrete samples. All synthesized antifoams showed properties superior to the commercial product, especially defoamers containing saturated fatty alcohols. It has been found that alcohols with too small or too long carbon chains were not effective. In particular, it was verified the optimal range of carbon atoms number contained in the antifoam chain which included between 12 and 14.

In this work we investigate the ultrabroadband dynamics of transverse coupled cavity VCSELs. This study is based on a multimode rate equation model, whose parameters are directly provided by a full-wave vectorial electromagnetic solver. This approach sets a step towards the comprehensive physics-based modeling of transverse-coupled cavity VCSELs, providing a relation between the features of the optical supermodes and the enhancements of the intensity modulation response. The approach emphasizes how the bandwidth enhancement, ascribable to a photon-photon resonance picture, can be triggered by forcing asymmetries in the bias and modulation contacting scheme of the device, and the importance of collecting the fields from each single cavity, providing an interpretation of recent experimental observations and paving the way towards more systematic design strategies.

This work reports a multiscale physics-based approach aimed at investigating the benefits of introducing a single tunnel junction (TJ) within conventional AlGaAs Vertical-Cavity Surface-Emitting Lasers (VCSELs). Our comprehensive VCSEL solver VENUS is augmented with a non-equilibrium Green's function (NEGF) approach to extract the band-to-band tunneling rate across the TJ. To showcase the NEGF-VENUS features, we apply it to the commercial pin oxide confined AlGaAs VCSEL previously investigated by VENUS, by inserting a TJ with minimal variations to the optical resonator. Besides finding the optimal position of TJ and oxide aperture, we can also compare the different hole injection schemes in the active region. Our results show the potential of doubling the maximum output power with the same threshold current, with perspectives of further enhancement by stacking more tunnel junctions.

On-chip spectrometers are increasingly becoming tools that might help in everyday life needs. The possibility offered by several available integration technologies and materials to be used to miniaturize spectrometers has led to a plethora of very different devices, that in principle can be compared according to their metrics. Having access to a reference database can help in selecting the best-performing on-chip spectrometers and being up to date in terms of standards and developments. In this paper, an overview of the most relevant publications available in the literature on miniaturized spectrometers is reported and a database is provided as an open-source project to which researchers can have access and participate in order to improve the share of knowledge in the interested scientific community.

Ketoprofen is a non-biodegradable drug and is not removed by conventional treatments. The need to remove pharmaceutical compounds from water and wastewater has aroused considerable interest in advanced oxidation processes (AOP), whose effectiveness depends on the generation of reactive free radicals capable of oxidizing and decomposing numerous compounds. Heterogeneous photocatalysis is an efficient method if an active semiconductor is used. In this work, the photodegradation reaction of ketoprofen promoted by TiO2 was studied, analyzing the kinetics obtained by changing variables such as temperature, initial concentration, and quantity of photocatalyst. It was determined that the mechanism is of the Langmuir–Hinshelwood type and that the system is operating in the kinetic regime, while tests at different temperatures have shown that the adsorption of ketoprofen and byproducts are both exothermic. Experimental data were interpreted with reliable models that allow to retrieve quantitatively the kinetic and thermodynamic parameters.

The valorization of industrial byproducts is an emerging practice that aims to transform waste materials generated during production processes into valuable resources. In this work, a preliminary study was carried out on the thermal conversion of an industrial solid byproduct resulting from the pickling of metal surfaces, mainly containing iron (II) oxalate. In a fixed-bed reactor, the thermal conversion was investigated as a function of the operating temperature and overall time. The starting material and the products obtained after heat treatment were characterized in detail, using numerous qualitative and semi-quantitative techniques. The aim of this research was to determine the optimal operating conditions for the transformation of the industrial byproduct into a high-quality product. By varying the operating conditions, it was found that complete conversion of iron (II) oxalate to magnetite was achieved at high temperatures (i.e., 773 K and 873 K) after one hour of treatment. The resulting product had a low degree of crystallization, which increased slightly with an increasing reaction time at a temperature of 873 K, reaching a maximum of about 11%. The magnetite obtained can be used in the future as a starting material for chemical looping processes as a chemical/energy carrier for the production of hydrogen.

Amidation of lactobionic acid with N,N-dimethylaminopropyltriamine was conducted to obtain N-(3′-dimethylaminopropyl)-lactamido-3-aminopropane (DDLPD), which was quaternized with bromoalkanes of different carbon chain lengths to synthesize double-stranded lactosylamide quaternary ammonium salt N-[N′[3-(lactosylamide)]propyl-N′-alkyl] propyl-N,N-dimethyl-N-alkylammonium bromide (CnDDLPB, n = 8, 10, 12, 14, 16). The surface activity and the adsorption and aggregation behaviors of the surfactants were investigated via equilibrium surface tension, dynamic light scattering, and cryo-electron microscopy measurements in an aqueous solution. The application properties of the products in terms of wettability, emulsification, foam properties, antistatic, salt resistance, and bacteriostatic properties were tested. CnDDLPB exhibited a low equilibrium surface tension of 27.82 mN/m. With an increase in the carbon chain length, the critical micellar concentration of CnDDLPBD decreased. Cryo-electron microscopy revealed that all products except C8DDLPB formed stable monolayer, multi-layer, and multi-compartmental vesicle structures in an aqueous solution. C14DDLPB has the best emulsification performance on soybean oil, with a time of 16.6 min; C14DDLPB has good wetting and spreading properties on polytetrafluoroethylene (PTFE) when the length of carbon chain is from 8 to 14, and the contact angle can be lowered to 33°~40°; CnDDLPB has low foam, which is typical of low-foaming products; C8DDLPB and C10DDLPB both show good antistatic properties. C8DDLPB and C14DDLPB have good salt resistance, and C12DDLPB has the best antimicrobial property, with the inhibition rate of 99.29% and 95.28% for E. coli and Gluconococcus aureus, respectively, at a concentration of 350 ppm.

Every year, new compounds contained in consumer products, such as detergents, paints, products for personal hygiene, and drugs for human and veterinary use, are identified in wastewater and are added to the list of molecules that need monitoring. These compounds are indicated with the term emerging contaminants (or Contaminants of Emerging Concern, CECs) since they are potentially dangerous for the environment and human health. To date, among the most widely used methodologies for the removal of CECs from the aquatic environment, adsorption processes play a role of primary importance, as they have proven to be characterized by high removal efficiency, low operating and management costs, and an absence of undesirable by-products. In this paper, the adsorption of ibuprofen (IBU), a nonsteroidal anti-inflammatory drug widely used for treating inflammation or pain, was performed for the first time using two different types of geopolymer-based materials, i.e., a metakaolin-based (GMK) and an organic–inorganic hybrid (GMK-S) geopolymer. The proposed adsorbing matrices are characterized by a low environmental footprint and have been easily obtained as powders or as highly porous filters by direct foaming operated directly into the adsorption column. Preliminary results demonstrated that these materials can be effectively used for the removal of ibuprofen from contaminated water (showing a concentration decrease of IBU up to about 29% in batch, while an IBU removal percentage of about 90% has been reached in continuous), thus suggesting their potential practical application.

Serum biomarkers represent a reproducible, sensitive, minimally invasive and inexpensive method to explore possible adverse cardiovascular effects of antineoplastic treatments. They are useful tools in risk stratification, the early detection of cardiotoxicity and the follow-up and prognostic assessment of cancer patients. In this literature review, we aim at describing the current state of knowledge on the meaning and the usefulness of cardiovascular biomarkers in patients with cancer; analyzing the intricate relationship between cancer and cardiovascular disease (especially HF) and how this affects cardiovascular and tumor biomarkers; exploring the role of cardiovascular biomarkers in the risk stratification and in the identification of chemotherapy-induced cardiotoxicity; and providing a summary of the novel potential biomarkers in this clinical setting.

Background: In response to the increasing need for mental health services in Canadian children and youth, the Canadian Institutes of Health Research launched funding towards developing pan-Canadian standards for children and youth mental health services. Objective: The objective of this rapid review is to synthesize current evidence-based recommendations on assessment and treatment for children and youth with anxiety, depression, obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). Methods: This rapid review was developed and conducted using the STARR decision tool and the Cochrane organization's minimum standards. We included evidence-based guidelines providing recommendations for and comparative studies evaluating the effectiveness of implementation of evidence-based guideline recommendations on assessment and/or treatment of anxiety, depression, OCD, or TS in children and youth compared to usual care. Results: Twenty guidelines and one study of the effectiveness of treatment approximating guideline standards were included in this review. There was reasonable consistency in recommendations between guidelines, especially for the management of anxiety disorders and TS, where psychological therapies were recommended as first line. For depression, some minor differences were noted in recommendations for the management of moderate to severe depression, with psychological therapies or SSRIs recommended as first-line in the some guidelines, whereas other guidelines prioritized psychological therapies. Conclusion: Current evidence-based guidelines prioritize psychological therapies for children and adolescents with anxiety, depression, OCD, or TS. If adequate and equitable service provision is a priority for decision makers, it is essential for the healthcare system to fund appropriately trained mental health therapists to deliver these interventions. [ABSTRACT FROM AUTHOR]

The frequency of forest disturbances has increased in recent years, provoking widespread defoliation, crown dieback and tree mortality. The ICP Forests monitoring network offers a unique platform for observing the impacts on forests of heatwaves, droughts and other extreme climatic events, as well as the trends of defoliation and mortality. The Italian ICP Forests Level I network consists of 261 permanent plots where tree crown defoliation and damage symptoms are assessed visually each year by well-trained crews of the Corpo Forestale dello Stato (2001-2016) and the Carabinieri Forestale from 2017 onward. This paper aims to assess the main tree species’ responses, in terms of defoliation and mortality, to severe climatic events. The results are discussed in relation to species-specific physiological behaviour and bioclimatic regions. A significant trend toward increasing defoliation and mortality has been observed since 2010 in both conifers and broadleaves. Conifers (especially Picea abies), which are largely diffuse in the Alpine regions, have suffered from bark beetle outbreaks due to severe windstorms (such as Vaia in 2018) and recurrent dry years. In the temperate regions, characterised by deciduous broadleaved trees, the most relevant defoliation events coincided with the driest and hottest years, with low relative humidity (2012, 2017 and 2021-2022), only partially recovering in the subsequent years. Among them, Fagus sylvatica and Quercus cerris, along with increased defoliation, showed symptoms caused by fungi of the genus Biscogniauxia, causal agents of “charcoal canker”, in less favourable site conditions. Quercus pubescens was the most resilient species, able to restore its crown after defoliation. The Mediterranean forests, with evergreen broadleaved species, showed no significant trends but were impacted at the most drought-prone coastal sites. The findings evidenced that the current ICP Forests network in Italy represents a fundamental infrastructure for monitoring impacts and trends connected to climate change and species-specific responses. A local intensification of the grid would help to capture under-represented species or ecological conditions.

Background: Neonatal sepsis is a deadly disease with non-specific clinical signs, delaying diagnosis and treatment. There remains a need for early biomarkers to facilitate timely intervention. Our objective was to identify neonatal sepsis gene expression biomarkers that could predict sepsis at birth, prior to clinical presentation., Methods: Among 720 initially healthy full-term neonates in two hospitals (The Gambia, West Africa), we identified 21 newborns who were later hospitalized for sepsis in the first 28 days of life, split into early-onset sepsis (EOS, onset ≤7 days of life) and late-onset sepsis (LOS, onset 8-28 days of life), 12 neonates later hospitalized for localized infection without evidence of systemic involvement, and 33 matched control neonates who remained healthy. RNA-seq was performed on peripheral blood collected at birth when all neonates were healthy and also within the first week of life to identify differentially expressed genes (DEGs). Machine learning methods (sPLS-DA, LASSO) identified genes expressed at birth that predicted onset of neonatal sepsis at a later time., Findings: Neonates who later developed EOS already had ∼1000 DEGs at birth when compared to control neonates or those who later developed a localized infection or LOS. Based on these DEGs, a 4-gene signature (HSPH1, BORA, NCAPG2, PRIM1) for predicting EOS at birth was developed (training AUC = 0.94, sensitivity = 0.93, specificity = 0.92) and validated in an external cohort (validation AUC = 0.72, sensitivity = 0.83, and specificity = 0.83). Additionally, during the first week of life, EOS disrupted expression of >1800 genes including those influencing immune and metabolic transitions observed in healthy controls., Interpretation: Despite appearing healthy at birth, neonates who later developed EOS already had distinct whole blood gene expression changes at birth, which enabled the development of a 4-gene predictive signature for EOS. This could facilitate early recognition and treatment of neonatal sepsis, potentially mitigating its long-term sequelae., Funding: CIHR and NIH/NIAID., Competing Interests: Declaration of interests AA provided legal consultation for MCIC Vermont Inc and received honorarium for lecture on neonatal sepsis from the University of Rome. BK participated in a Data Safety Monitoring Board for Johnson & Johnson. JDA received travel funding from the American Society for Histocompatibility and Immunogenetics, World Vaccine Congress, and International Network of Special Immunization Services. OAO received travel funding from the American Academy of Pediatrics. OL is a named inventor on patents held by Boston Children's Hospital relating to small molecule adjuvants (e.g., Novel imidazopyrimidine compounds and uses thereof; EP3709998A1) and to human in vitro systems that model responses to immunomodulators and vaccines (e.g., Tissue constructs and uses thereof; US20150152385A1), has served as a consultant to Glaxo Smith Kline and Hillevax, and is co-founder of and advisor to Ovax, Inc. REWH has a contract from Sepset Biosciences for development of diagnostic assays for adult sepsis (indirect relationship to this work) and is CEO of Asep Medical and Sepset BioSciences that are commercially developing adult sepsis diagnostics, although the signatures described here have not been filed for patent protection. All other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Little is known about factors modulating pain and pain-related functional impairment in isolated cervical dystonia (CD)., Objective: The aim was to assess the prevalence and interrelationship between pain-modulating factors and pain-related determinants of functional impairment and quality of life in CD., Methods: We analyzed pain-aggravating and pain-relieving external factors, the degree of pain-related functional impact on routine activities, and the relationship between these and pain severity, using cross-sectional data collected using the Pain in Dystonia Scale (PIDS) from 85 participants with CD. Pairwise correlation analyses and age- and sex-adjusted linear regression models estimated the relationship between pain-modulating factors and pain severity, and the impact of pain severity, dystonia severity, and psychiatric symptoms on pain-related functional impairment and disease-specific quality of life (measured using the Craniocervical Dystonia Questionnaire-24)., Results: Stress and prolonged fixed position were the most frequent and impacting pain triggers, with women reporting larger impact. The average impact of pain-relieving factors was lower than that of pain triggers. Physical exercise and social gatherings were the most impacted activities by pain in CD. The intensity of external modulating factors was a predictor of pain severity. Severity of pain, CD, and psychiatric symptoms independently predicted pain-related functional impairment, whereas quality of life was predicted by pain severity, pain-related functional impairment, and psychiatric symptom severity, but not dystonia severity., Conclusion: The PIDS provides insight into external modulation and functional impact of pain in CD. The pattern of external modulation of pain in CD is in line with a multifactorial modulation and complex physiology., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Pain is a common non-motor symptom in patients with cervical dystonia (CD), severely impacting their quality of life. The pathophysiology of CD is incompletely understood but it involves altered processing of proprioceptive and pain signals., Objectives: The purpose of this proof-of-concept study was to determine if vibro-tactile stimulation (VTS)-a non-invasive form of neuromodulation targeting the somatosensory system-can modulate neck pain in people with CD., Methods: In a multi-center study, 44 CD patients received VTS to sternocleidomastoid and/or trapezius muscles for up to 45 min under 9 different stimulation conditions that either targeted a single or a pair of muscles. The primary outcome measure was a perceived pain score (PPS) rated by participants on a 100-point analogue scale., Results: During VTS, 29/44 (66%) of participants experienced a reduction in PPS of at least 10% with 17/44 (39%) reporting a reduction in pain of 50% or higher. After VTS cessation, 57% of participants still reported a 10% or higher reduction in PPS. Effects were significant at the group level and persisted for up to 20 min post-treatment. No distinct optimal stimulation profiles were identified for specific CD phenotypes. Clinical markers of disease severity or duration did not predict the degree of VTS-induced pain reduction., Conclusion: This proof-of-concept study demonstrates the potential of VTS as a new non-invasive therapeutic option for treating neck pain associated with CD. Further research needs to delineate optimal dosage and long-term effects., (© 2024. The Author(s).)

The Tourette OCD Alberta Network (TOAN) supports mental health therapists to improve the delivery of care to patients with Tourette syndrome (TS) and OCD in Alberta. We evaluated the professional development needs of health care workers to develop a continuing professional development (CPD) webinar series. Health care workers demonstrated an urgent need to access a CPD program grounded in evidenced based knowledge about TS and OCD. While 80% of health care workers treated children with TS and OCD, 50% had no formal training. A curriculum consisting of a series of twelve live, online webinars was developed and delivered between September 2020 and June 2021, covering a range of clinical topics. The webinars were attended on average by 63 attendees, with the outcome of a positive knowledge gain. In future, the educational program will need to reflect the ongoing developing clinical understanding of TS and OCD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Parkinson's disease (PD) has been consistently linked to alterations within the gut microbiome., Objective: Our goal was to identify microbial features associated with PD incidence and progression., Methods: Metagenomic sequencing was used to characterize taxonomic and functional changes to the PD microbiome and to explore their relation to bacterial metabolites and disease progression. Motor and non-motor symptoms were tracked using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and levodopa equivalent dose across ≤5 yearly study visits. Stool samples were collected at baseline for metagenomic sequencing (176 PD, 100 controls)., Results: PD-derived stool samples had reduced intermicrobial connectivity and seven differentially abundant species compared to controls. A suite of bacterial functions differed between PD and controls, including depletion of carbohydrate degradation pathways and enrichment of ribosomal genes. Faecalibacterium prausnitzii-specific reads contributed significantly to more than half of all differentially abundant functional terms. A subset of disease-associated functional terms correlated with faster progression of MDS-UPDRS part IV and separated those with slow and fast progression with moderate accuracy within a random forest model (area under curve = 0.70). Most PD-associated microbial trends were stronger in those with symmetric motor symptoms., Conclusion: We provide further evidence that the PD microbiome is characterized by reduced intermicrobial communication and a shift to proteolytic metabolism in lieu of short-chain fatty acid production, and suggest that these microbial alterations may be relevant to disease progression. We also describe how our results support the existence of gut-first versus brain-first PD subtypes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Psychiatric symptoms are common in neurodevelopmental movement disorders, including some types of dystonia. However, research has mainly focused on motor manifestations and underlying circuits. Myoclonus-dystonia is a rare and homogeneous neurodevelopmental condition serving as an illustrative paradigm of childhood-onset dystonias, associated with psychiatric symptoms. Here, we assessed the prevalence of psychiatric disorders and the severity of depressive symptoms in patients with myoclonus-dystonia and healthy volunteers (HV). Using resting-state functional neuroimaging, we compared the effective connectivity within and among non-motor and motor brain networks between patients and HV. We further explored the hierarchical organization of these networks and examined the relationship between their connectivity and the depressive symptoms. Comparing 19 patients to 25 HV, we found a higher prevalence of anxiety disorders and more depressive symptoms in the patient group. Patients exhibited abnormal modulation of the cerebellum on the cerebral cortex in the sensorimotor, dorsal attention, salience, and default mode networks. Moreover, the salience network activity was directed by the cerebellum in patients and was related to depressive symptoms. Altogether, our findings highlight the role of the cerebellar drive on both motor and non-motor cortical areas in this disorder, suggesting cerebellar involvement in the complex phenotype of such neurodevelopmental movement disorders., (© 2024. The Author(s).)

Understanding of newborn immune ontogeny in the first week of life will enable age-appropriate strategies for safeguarding vulnerable newborns against infectious diseases. Here we conducted an observational study exploring the immunological profile of infants longitudinally throughout their first week of life. Our Expanded Program on Immunization - Human Immunology Project Consortium (EPIC-HIPC) studies the epigenetic regulation of systemic immunity using small volumes of peripheral blood samples collected from West African neonates on days of life (DOL) 0, 1, 3, and 7. Genome-wide DNA methylation and single nucleotide polymorphism markers are examined alongside matched transcriptomic and flow cytometric data. Integrative analysis reveals that a core network of transcription factors mediates dynamic shifts in neutrophil-to-lymphocyte ratios (NLR), which are underpinned by cell-type specific methylation patterns in the two cell types. Genetic variants are associated with lower NLRs at birth, and healthy newborns with lower NLRs at birth are more likely to subsequently develop sepsis. These findings provide valuable insights into the early-life determinants of immune system development., (© 2024. The Author(s).)

Rationale: Chronic obstructive pulmonary disease (COPD) results from gene-environment interactions over the lifetime. These interactions are captured by epigenetic changes, such as DNA methylation. Objectives: To systematically review the evidence form epigenome-wide association studies related to COPD and lung function. Methods: A systematic literature search performed on PubMed, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases identified 1,947 articles that investigated epigenetic changes associated with COPD and/or lung function; 17 of them met our eligibility criteria, from which data were manually extracted. Differentially methylated positions (DMPs) and/or annotated genes were considered replicated if identified by two or more studies with a P  < 1 × 10 -4 . Measurements and Main Results: Ten studies profiled DNA methylation changes in blood and seven in respiratory samples, including surgically resected lung tissue ( n  = 3), small airway epithelial brushings ( n  = 2), BAL ( n  = 1), and sputum ( n  = 1). Main results showed: 1 ) high variability in study design, covariates, and effect sizes, which prevented a formal meta-analysis; 2 ) in blood samples, 51 DMPs were replicated in relation to lung function and 12 related to COPD; 3 ) in respiratory samples, 42 DMPs were replicated in relation to COPD but none in relation to lung function; and 4 ) in COPD versus control studies, 123 genes (2.6% of total) were shared between one or more blood and one or more respiratory samples and associated with chronic inflammation, ion transport, and coagulation. Conclusions: There is high heterogeneity across published COPD and/or lung function epigenome-wide association studies. A few genes ( n  = 123; 2.6%) were replicated in blood and respiratory samples, suggesting that blood can recapitulate some changes in respiratory tissues. These findings have implications for future research. Systematic Review [protocol] registered with Open Science Framework (OSF).

Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in newborn pups without altering behavioural outcomes in adult littermates. Whole-genome bisulfite sequencing of neonatal brain and liver revealed stochastic influence on DNA methylation that was mostly tissue-specific, with some perturbations likely originating as early as gastrulation. DNA methylation differences were enriched in non-coding genomic regions with regulatory potential indicative of broad effects of alcohol on genome regulation. Replication studies in human cohorts with fetal alcohol spectrum disorder suggested some effects were metastable at genes linked to disease-relevant traits including facial morphology, intelligence, educational attainment, autism, and schizophrenia. In our murine model, a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation. Our studies demonstrate that early moderate exposure is sufficient to affect fetal genome regulation even in the absence of overt phenotypic changes and highlight a role for preventative maternal dietary interventions., Competing Interests: MB, AL, NK, EC, CB, JF, EE, JC, EM, JH, DH, SB, RL, MS, DM No competing interests declared, (© 2023, Bestry et al.)

Background and Purpose: The quality of resting-state functional MRI (rs-fMRI) under anesthesia is variable and there are no guidelines on optimal image acquisition or anesthesia protocol. We aim to identify the factors that may lead to compromised clinical rs-fMRI under anesthesia., Materials and Methods: In this cross-sectional study, we analyzed clinical rs-fMRI data acquired under anesthesia from 2009-2023 at Massachusetts General Hospital. Independent component analysis driven resting state networks (RSN) of each patient were evaluated qualitatively and quantitatively and grouped as robust or weak. Overall networks were evaluated using the qualitative method, and motor and language networks were evaluated using the quantitative method. RSN robustness was analyzed in 4 outcome categories: overall, combined Motor-Language, individual motor, and language networks. Predictor variables included rs-fMRI acquisition parameters, anesthesia medications, underlying brain structural abnormalities, age, and sex. Logistic regression was used to examine the effect of the study variables on RSN robustness., Results: Sixty-nine patients were identified. With qualitative assessment, 40 had robust and 29 had weak overall RSN. Quantitatively, 45 patients had robust, while 24 had weak Motor-Language networks. Among all the predictor variables, only sevoflurane significantly contributed to the outcomes, with sevoflurane administration reducing the odds of having robust RSN in overall (Odds Radio (OR)= 0.2, 95% Confidence Interval (CI) = [0.05;0.79], p = .02), Motor-Language (OR = 0.18, 95% CI = [0.04;0.80], p = .02) and individual motor (OR= 0.1, 95% CI = [0.02;0.64], p= .02) categories. Individual language network robustness was not associated with the tested predictor variables., Conclusions: Sevoflurane anesthesia may compromise the visibility of fMRI resting state networks, particularly impacting motor networks. This finding suggests that the type of anesthesia is a critical factor in rs-fMRI quality. We did not observe the association of the MR acquisition technique or underlying structural abnormality with the RSN robustness., Abbreviations: BOLD = Blood Oxygen Level-Dependent; ICA = Independent Component Analysis; Rs-fMRI = Resting-State Functional Magnetic Resonance Imaging; RSN = Resting-State Networks; SNR = Signal-to-Noise Ratio., (© 2024 by American Journal of Neuroradiology.)

The first few days of life are characterized by rapid external and internal changes that require substantial immune system adaptations. Despite growing evidence of the impact of this period on lifelong immune health, this period remains largely uncharted. To identify factors that may impact the trajectory of immune development, we conducted stringently standardized, high-throughput phenotyping of peripheral white blood cell (WBC) populations from 796 newborns across two distinct cohorts (The Gambia, West Africa; Papua New Guinea, Melanesia) in the framework of a Human Immunology Project Consortium (HIPC) study. Samples were collected twice from each newborn during the first week of life, first at Day of Life 0 (at birth) and then subsequently at Day of Life 1, 3, or 7 depending on the randomization group the newborn belongs to. The subsequent analysis was conducted at an unprecedented level of detail using flow cytometry and an unbiased automated gating algorithm. The results showed that WBC composition in peripheral blood changes along patterns highly conserved across populations and environments. Changes across days of life were most pronounced in the innate myeloid compartment. Breastfeeding, and at a smaller scale neonatal vaccination, were associated with changes in peripheral blood neutrophil and monocyte cell counts. Our results suggest a common trajectory of immune development in newborns and possible association with timing of breastfeeding initiation, which may contribute to immune-mediated protection from infection in early life. These data begin to outline a specific window of opportunity for interventions that could deliberately direct WBC composition, and with that, immune trajectory and thus ontogeny in early life. This trial is registered with NCT03246230., Competing Interests: Ofer Lefy declared the competing interest, he is a named inventor on patents held by Boston Children's Hospital relating to vaccine adjuvants (e.g., EP3709998A1) and human in vitro systems that model responses to immunomodulators and vaccines (e.g., US20150152385A1). He is an advisor to GlaxoSmithKline (GSK) and Hillevax and a cofounder of Ovax, Inc. The other authors declared no competing interest., (Copyright © 2024 Sebastiano Montante et al.)

Background: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year., Methods: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants., Results: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume., Conclusions: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Infants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunizations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation. Peripheral blood mononuclear cells from respiratory infection allergy/asthma-prone (IAP) infants and non-infection allergy/asthma prone (NIAP) were retrospectively selected for genome-wide DNA methylation and single nucleotide polymorphism analysis. The IAP infants were enriched for the low vaccine responsiveness (LVR) phenotype (Fisher's exact p-value = 0.02)., Results: An endotype signature of 813 differentially methylated regions (DMRs) comprising 238 lead CpG associations (FDR < 0.05) emerged, implicating pathways related to asthma, mucin production, antigen presentation and inflammasome activation. Allelic variation explained only a minor portion of this signature. Stimulation of mononuclear cells with monophosphoryl lipid A (MPL), a TLR agonist, partially reversed this signature at a subset of CpGs, suggesting the potential for epigenetic remodeling., Conclusions: This proof-of-concept study establishes a foundation for precision endotyping of IAP children and highlights the potential for immune modulation strategies using adjuvants for future investigation., (© 2024. The Author(s).)

Psoriatic arthritis (PsA) is a complex inflammatory disease that challenges diagnosis and complicates the rational selection of effective therapies. Although T cells are considered active effectors in psoriasis and PsA, the role of CD8+ T cells in pathogenesis is not well understood. We selected the humanized mouse model NSG-SGM3 transgenic strain to examine psoriasis and PsA endotypes. Injection of PBMCs and sera from patients with psoriasis and PsA generated parallel skin and joint phenotypes in the recipient mouse. The transfer of human circulating memory T cells was followed by migration and accumulation in the skin and synovia of these immunodeficient mice. Unexpectedly, immunoglobulins were required for recapitulation of the clinical phenotype of psoriasiform lesions and PsA domains (dactylitis, enthesitis, bone erosion). Human CD8+ T cells expressing T-bet, IL-32 and CXCL14 were detected by spatial transcriptomics in murine synovia and by immunofluorescence in the human PsA synovia. Importantly, depletion of human CD8+ T cells prevented skin and synovial inflammation in mice humanized with PsA peripheral blood cells. The humanized model of psoriasis and PsA represents a valid platform for accelerating the understanding of disease pathogenesis, improving the design of personalized therapies, and revealing psoriatic disease targets.