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Introduction: Multiple sclerosis (MS) is a persistent condition characterized by immune-mediated processes in the central nervous system, affecting around 2.8 million individuals globally. While historically less prevalent in the Middle East and North Africa (MENA) region, recent trends mirror the global rise in MS. Area covered: The impact of MS is substantial, particularly in the MENA region, with costs per patient surpassing nominal GDP per capita in certain countries. Disease-modifying therapies aim to alleviate MS effects, but challenges persist, especially in managing progressive MS as it shifts from inflammatory to neurodegenerative phases. Limited resources in the MENA region hinder care delivery, though awareness initiatives and multidisciplinary centers are emerging. Contrary to global projections of a decline in the MS market, the MENA region is poised for growth due to increased prevalence, healthcare expenditures, and infrastructure investments. Expert opinion: This review underscores the urgent necessity for effective treatments, robust disease management, and early diagnosis in tackling MS's repercussions in the MENA region. Bolstering resources tailored to MS patients and elevating the quality of care stand as pivotal strategies for enhancing health outcomes in this context. Taking decisive action holds the key to enhancing the overall well-being of individuals grappling with MS. [ABSTRACT FROM AUTHOR]

Coupled microring lattices are versatile photonic systems that can be used to realize various topological phases of matter. In two‐dimensional (2D) microring lattices, the periodic and unidirectional circulation of light in each microring gives rise to a time‐like dimension, so that the lattice emulates a (2 + 1)D system with much richer topological behaviors than static 2D lattices. Accurate treatment of these systems requires a departure from the static tight‐binding model of coupled resonators and take into account the periodic coupling sequence of light in the lattice network. This article provides an overview of the theory and design of (2 + 1)D microring lattices for realizing Floquet topological photonic insulators (TPIs). Particular focus is placed on the microring Lieb lattice with perfect couplings, which emulates an anomalous Floquet insulator with all flat bands. Such a system exhibits some unique properties, including wide edge mode continuum exceeding a Floquet–Brillouin zone, super‐robustness to lattice disorder, Aharonov–Bohm (AB) caging and compact localized flat‐band states that can be used to realize high‐quality factor topological resonators. All‐bands‐flat Floquet–Lieb microring lattices provide a versatile platform for investigating topological physics as well as potential applications in realizing topologically‐protected photonic devices. [ABSTRACT FROM AUTHOR]

Postoperative pain affects most patients after major surgery and can transition to chronic pain. The considerable side effects and limited efficacy of current treatments underline the need for new therapeutic options. We observed increased amounts of the metabolites BH4 and serotonin after skin injury. Mast cells were primary postoperative sources of Gch1, the rate-limiting enzyme in BH4 synthesis, itself an obligate cofactor in serotonin production by tryptophan hydroxylase (Tph1). Mice deficient in mast cells or in mast cell–specific Gch1 or Tph1 showed drastically decreased postoperative pain. We found that injury induced the nociceptive neuropeptide substance P, mast cell degranulation, and granule nerve colocalization. Substance P triggered serotonin release in mouse and human mast cells, and substance P receptor blockade substantially ameliorated pain hypersensitivity. Our findings highlight the importance of mast cells at the neuroimmune interface and substance P–driven mast cell BH4 and serotonin production as a therapeutic target for postoperative pain treatment. Editor's summary: Inflammation caused by surgical tissue injury can evolve into chronic pain. Starkl et al. used a mouse model of surgical tissue injury to decipher a role for mast cell–derived metabolites in postoperative pain. Tetrahydrobiopterin (BH4) has been previously detected in injured nerves and correlates with pain intensity and is required for serotonin production by tryptophan hydroxylase (Tph1). Nerve-proximal mast cells were identified as a source of GTP cyclohydrolase 1 (Gch1), a rate-limiting enzyme for BH4 synthesis. Deletion of Gch1 or Tph1 from mast cells or mast cell depletion reduced tissue injury pain. The nociceptive neuropeptide substance P was detected at tissue injury sites and triggered BH4-dependent serotonin release from mast cells, thus defining how neuropeptides can act on mast cells and propagate pain responses. —Christiana Fogg [ABSTRACT FROM AUTHOR]

π modes are unique topological edge states appearing in Floquet systems with periodic modulations of the underlying lattice structure in the evolution variable, such as dynamically modulated Su–Schrieffer–Heeger (SSH) lattices. These edge states are anomalous states usually appearing between Floquet replicas of the same band, even if the standard topological index remains zero for this band. While linear and nonlinear π modes were observed in conservative systems, they have never been studied in the nonlinear regime in the non-Hermitian systems with structured gain and losses. Here, we show that the SSH waveguide array with periodically oscillating waveguide positions in the propagation direction and with the parity-time symmetric refractive index landscape can support π modes that are damped or amplified at different ends of the array. By including nonlinearity and nonlinear absorption into our continuous system, we achieve stable lasing in the π mode at one end of the array. The representative feature of this system is that lasing in it is thresholdless and occurs even at low gain–loss amplitudes. The degree of localization of lasing π modes can be flexibly controlled by the amplitude of transverse waveguide oscillations. This work therefore introduces a new type of topological Floquet laser and a route to manipulate π modes by structured gain and losses. [ABSTRACT FROM AUTHOR]

Background: Magnolia kobus belongs to the Magnoliaceae family and the genus Magnolia. The flowers are widely used in herbal tea and dietary supplements. It is effectively used in traditional medicines and its chemical constituents have various biological activities, such as anti-obesity, antioxidant, anticancer, anti-inflammatory, and anti-hyperlipidaemic activities. The flower developmental process of M. kobus involves a complex regulatory network and is intensively related to the quality and relative composition of primary and secondary metabolites of the flower. Hence, the identification of metabolic changes during different developmental stages of the flower was important for enhancing organoleptic and nutritional characteristics. To our knowledge, to date, none of the studies has investigated the relationship between metabolic changes (primary and secondary metabolites) during different developmental stages of the M. kobus flower. Results: This study investigated metabolic changes in 47 hydrophilic and 13 lipophilic compounds and biological activities in Magnolia kobus flowers during four developmental stages. Metabolites were identified using HPLC, GC–qMS, and GC–TOFMS. Throughout flower development, metabolite accumulation showed significant differences based on metabolomics approaches. The dynamic changes of 21 differential metabolites occurred between the young and mature stages. Flower buds exhibited high levels of phenylpropanoids and phytosterols. The total phenolic and flavonoid contents were most abundant in the buds and decreased from the bud to the old stages. Flower bud extracts showed the most powerful effects in three antioxidant assays and antibacterial effects against 10 pathogenic bacterial strains. Conclusions: These findings emphasise the value of M. kobus flower buds as an edible natural source and provide valuable insight into the metabolic changes that occur in M. kobus flowers during development. [ABSTRACT FROM AUTHOR]

To assess the potential of a paper diary for strengthening accountability in public agricultural extension services. Therefore a paper diary called 'Diary for Agricultural Extension Officers' was developed and tested in Uganda. A qualitative case study research approach was applied for the development and assessment of the diary. Data were collected using focus group discussions and individual face-to-face interviews. Data analysis was conducted using the content analysis method. Paper diaries can strengthen accountability in public agricultural extension services by enabling alignment of the extension activities of the field agents to the goals of the extension service and to the needs of the beneficiaries, in addition to mitigating information asymmetry about the extension activities. However, the implementation of paper diaries requires sensitization of the beneficiaries on the need for verification and feedback. This study is centred around addressing a practical problem of field agents' accountability and results have the potential to improve management of public services such as agricultural extension. Moreover, the findings could also be relevant for all types of organizations and service delivery methods. This study expanded the boundaries of the principal-agent theory by applying it to the accountability of agricultural extension services using paper diaries, which have hitherto not been widely applied. This study advances the debates of accountability and coordination of agricultural extension services by assessing the potential of a paper diary as the literature has to date assessed the potential of electronic diaries. [ABSTRACT FROM AUTHOR]

The construction of a small molecule library that includes compounds with medium-sized rings is increasingly essential in drug discovery. These compounds are essential for identifying novel therapeutic agents capable of targeting "undruggable" targets through high-throughput and high-content screening, given their structural complexity and diversity. However, synthesizing medium-sized rings presents notable challenges, particularly with direct cyclization methods, due to issues such as transannular strain and reduced degrees of freedom. This review presents an overview of current strategies in synthesizing medium-sized rings, emphasizing innovative approaches like ring-expansion reactions. It highlights the challenges of synthesis and the potential of these compounds to diversify the chemical space for drug discovery, underscoring the importance of medium-sized rings in developing new bioactive compounds. [ABSTRACT FROM AUTHOR]

Internal tides are known to be an important source of mixing in the oceans, especially in the bottom boundary layer. The depth of internal-tide generation therefore seems important for benthic life and the formation of cold-water coral mounds, but internal-tide conversion is generally investigated in a depth-integrated sense. Using both idealized and realistic simulations on continental slopes, we found that the depth of internal-tide generation increases with increasing slope steepness and decreases with intensified shallow stratification. The depth of internal-tide generation also shows a typical latitudinal dependency related to Coriolis effects. Using a global database of cold-water corals, we found that, especially in Northern Hemisphere autumn and winter, the global depth pattern of internal-tide generation correlates (rautumn = 0.70, rwinter = 0.65, p < 0.01) with that of cold-water corals: shallowest near the poles and deepest around the Equator, with a decrease in depth around 25° S and N, and shallower north of the Equator than south. We further found that cold-water corals are situated significantly more often on topography that is steeper than the internal-tide beam (i.e. where supercritical reflection of internal tides occurs) than would be expected from a random distribution: in our study, in 66.9 % of all cases, cold-water corals occurred on a topography that is supercritical to the M2 tide whereas globally only 9.4 % of all topography is supercritical. Our findings underline internal-tide generation and the occurrence of supercritical reflection of internal tides as globally important for cold-water coral growth. The energetic dynamics associated with internal-tide generation and the supercritical reflection of internal tides likely increase the food supply towards the reefs in food-limited winter months. With climate change, stratification is expected to increase. Based on our results, this would decrease the depth of internal-tide generation, possibly creating new suitable habitat for cold-water corals shallower on continental slopes. [ABSTRACT FROM AUTHOR]

Framework-forming cold-water corals (CWCs) are ecosystem engineers that build mounds in the deep sea that can be up to several hundred metres high. The effect of the presence of cold-water coral mounds on their surroundings is typically difficult to separate from environmental factors that are not affected by the mounds. We investigated the environmental control on and the importance of ecosystem engineering for cold-water coral reefs using annotated video transect data, spatial variables (MEMs), and hydrodynamic model outputs in a redundancy analysis and with variance partitioning. Using available hydrodynamic simulations with cold-water coral mounds and simulations where the mounds were artificially removed, we investigated the effect of coral mound ecosystem engineering on the spatial configuration of reef habitat and discriminated which environmental factors are and which are not affected by the mounds. We find that downward velocities in winter, related to non-engineered environmental factors, e.g. deep winter mixing and dense-water cascading, cause substantial differences in reef cover at the broadest spatial scale (20–30 km). Such hydrodynamic processes that stimulate the food supply towards the corals in winter seem more important for the reefs than cold-water coral mound engineering or similar hydrodynamic processes in summer. While the ecosystem-engineering effect of cold-water corals is frequently discussed, our results also highlight the importance of non-engineered environmental processes. We further find that, due to the interaction between the coral mound and the water flow, different hydrodynamic zones are found on coral mounds that likely determine the typical benthic zonations of coral rubble at the mound foot, the dead coral framework on the mound flanks, and the living corals near the summit. Moreover, we suggest that a so-called Massenerhebung effect (well known for terrestrial mountains) exists, meaning that benthic zonation depends on the location of the mound rather than on the height above the seafloor or water depth. Our finding that ecosystem engineering determines the configuration of benthic habitats on cold-water coral mounds implies that cold-water corals cannot grow at deeper depths on the mounds to avoid the adverse effects of climate change. [ABSTRACT FROM AUTHOR]

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. [ABSTRACT FROM AUTHOR]

Topological photonics is a rapidly developing field that leverages geometric and topological concepts to engineer and control the characteristics of light. Currently, the research on topological photonics has expanded from traditional one-dimensional (1D) and two-dimensional (2D) to three-dimensional (3D) and higher-dimensional spaces. However, most reviews on topological photonics focus on 1D and 2D systems, and a review that provides a detailed classification and introduction of 3D and higher-dimensional systems is still missing. Here, we review the photonic topological states in 3D and higher-dimensional systems on different platforms. Moreover, we discuss internal connections between different photonic topological phases and look forward to the future development direction and potential applications of 3D and higher-dimensional systems. [ABSTRACT FROM AUTHOR]

The assessment of volatile breath biomarkers has been targeted with a lot of interest by the scientific and medical communities during the past decades due to their suitability for an accurate, painless, non-invasive, and rapid diagnosis of health states and pathological conditions. This paper reviews the most relevant bibliographic sources aiming to gather the most pertinent volatile organic compounds (VOCs) already identified as putative cancer biomarkers. Here, a total of 265 VOCs and the respective bibliographic sources are addressed regarding their scientifically proven suitability to diagnose a total of six carcinogenic diseases, namely lung, breast, gastric, colorectal, prostate, and squamous cell (oesophageal and laryngeal) cancers. In addition, future trends in the identification of five other forms of cancer, such as bladder, liver, ovarian, pancreatic, and thyroid cancer, through perspective volatile breath biomarkers are equally presented and discussed. All the results already achieved in the detection, identification, and quantification of endogenous metabolites produced by all kinds of normal and abnormal processes in the human body denote a promising and auspicious future for this alternative diagnostic tool, whose future passes by the development and employment of newer and more accurate collection and analysis techniques, and the certification for utilisation in real clinical scenarios. [ABSTRACT FROM AUTHOR]

The rapid development of additive manufacturing has fueled a revolution in various research fields and industrial applications. Among the myriad of advanced 3D printing techniques, two‐photon polymerization lithography (TPL) uniquely offers a significant advantage in nanoscale print resolution, and has been widely employed in diverse fields, for example, life sciences, materials sciences, mechanics, and microfluidics. More recently, by virtue of the optical transparency of most of the resins used, TPL is finding new applications in optics and photonics, with nanometer to millimeter feature dimensions. It enables the minimization of optical elements and systems, and exploration of light‐matter interactions with new degrees of freedom, never possible before. To review the recent progress in the TPL related optical research, it starts with the fundamentals of TPL and material formulation, then discusses novel fabrication methods, and a wide range of optical applications. These applications notably include diffractive, topological, quantum, and color optics. With a panoramic view of the development, it is concluded with insights and perspectives of the future development of TPL and related potential optical applications. [ABSTRACT FROM AUTHOR]

Twelve novel neo-tanshinlactone-chalcone hybrid molecules were constructed through a versatile methodology involving the Horner-Wadsworth-Emmons (HWE) olefination of 4-formyl-2H-benzo [h]chromen-2-ones and phosphonic acid diethyl esters, as the key step, and evaluated for anticancer activity against a series of four breast cancers and their related cell lines, viz. MCF-7 (ER + ve), MDAMB-231 (ER-ve), HeLa (cervical cancer), and Ishikawa (endometrial cancer). The title compounds showed excellent to moderate in vitro anti-cancer activity in a range of 6.8-19.2 μM (IC50). Compounds 30 (IC50 = 6.8 μM and MCF-7; IC50 = 8.5 μM and MDA-MB-231) and 31 (IC50 = 14.4 μM and MCF-7; IC50 = 15.7 μM and MDA-MB-231) exhibited the best activity with compound 30 showing more potent activity than the standard drug tamoxifen. Compound 30 demonstrated a strong binding affinity with tumor necrosis factor α (TNF-α) in molecular docking studies. This is significant because TNFα is linked to MCF-7 cancer cell lines, and it enhances luminal breast cancer cell proliferation by upregulating aromatase. Additionally, virtual ADMET studies confirmed that hybrid compounds 30 and 31 met Lipinski's rule; displayed high bioavailability, excellent oral absorption, favorable albumin interactions, and strong penetration capabilities; and improved blood-brain barrier crossing. Based on the aforementioned results, compound 30 has been identified as a potential anti-breast cancer lead molecule. [ABSTRACT FROM AUTHOR]

Topological and non‐Hermitian physics provide powerful tools for manipulating light in different ways. Recently, intense studies have converged on the interplay between topology and non‐Hermiticity, and have produced fruitful results in various photonic settings. Currently, the realization of this interplay falls under the paradigm of enabling energy exchange between topological systems and the environment. Beyond this paradigm, it is revealed that a non‐Hermitian phenomenon, i.e., the anti‐parity‐time phase transition, naturally emerges from a Hermitian system realized by coupled topological valley waveguides. Such phase transition gives two exotic topological superstates in the spectral domain. By further combining the two phases with topological robustness, a photonic topological bi‐functional device is realized on a silicon‐on‐insulator platform at telecommunications frequencies. The results provide a new perspective on light manipulation and integrated device applications. [ABSTRACT FROM AUTHOR]

The non‐trivial polarization topology of bound states in the continuum (BICs) provides new strategies in nanophotonics. The polarization topology depends on the geometric parameters and energy‐momentum dispersion of the system and can be engineered to add specific functionalities for light molding. Herein, such a possibility is investigated by studying the topology of the polarization states associated with the optical field radiated by BICs when Dirac‐cone‐degeneracy is lifted. The opening of a pseudogap in the Dirac cone dispersion of square‐lattice dielectric photonic crystal slabs is achieved by tuning the slab thickness. First, the emergence of half‐integer topological charges without the requirement of BIC annihilation is theoretically shown, which instead occurs when in‐plane inversion symmetry is broken. Then, using spin‐to‐orbital angular momentum conversion, the theory of half‐integer topological charges mediated by BICs is demonstrated and experimentally proved. The same device is able to give rise to vortices with different orbital angular momentum depending on the way it is illuminated, thus improving the potential of optical multiplexing. In addition, the additive character of the topology‐induced phase‐vortex generation is finally demonstrated for both integer and half‐integer charges using also vortex states as input beams, which is of relevance for information delivery. [ABSTRACT FROM AUTHOR]

Lime is an essential raw material for iron and steel production, in construction and agriculture, in civil engineering, in environmental protection, and in manifold chemical manufacturing processes. To address the problem of unavoidable process CO2 emissions associated with the production of lime, efficient capture technologies need to be developed and implemented. The indirectly heated carbonate looping (IHCaL) process is an efficient candidate for this application because it utilizes lime as the sorbent for the CO2 capture. In this work, a retrofit configuration of this process is presented and analyzed for net negative CO2 emissions. This is done considering different fuels that provide the heat required for the regeneration of the sorbent. The different scenarios were simulated with an AspenPlus® model, key performance indicators were calculated, and the process was compared with other post-combustion capture methods. The results show that net negative CO2 emissions as high as −1805 kgCO2/tCaO, calculated with a state-of-the-art coal power plant energy scenario (ηe = 44.2 %; eref,el = 770 kgCO2/MWhel), can be obtained. This represents an equivalent CO2 avoidance of more than 230% with respect to the reference plant without capture (1368 kgCO2/tCaO). A specific primary energy consumption for CO2 avoided (SPECCA) lower than 1.5 MJLHV/kgCO2,av was achieved for the same energy scenario. Particularly promising results can be accomplished when applying fuels with high biogenic fraction and low specific CO2 emissions, such as solid recovered fuels (SRFs) with a high calorific value. [ABSTRACT FROM AUTHOR]

Topological photonic devices with dynamically tunable functions are highly on demand in practice, but the majority of previously proposed photonic systems have been limited to fixed performances, once fabricated. Although several approaches have been proposed for obtaining the tunability in topological photonic systems, they are limited to first‐order topological states and require rather complicated structures. Herein, second‐order topological properties of rhombic photonic crystals (PCs) are revealed, for the first time, enabling to realize tunable photonic devices. For this purpose, the conventional square lattice PCs composed of four rigid dielectric rods are reshaped to rhomboid ones with preserved inversion symmetry, which exhibit well‐quantized bulk polarizations. Since the eigenfrequencies of topological edge and corner states depend on the angle between the neighboring sides of unit cells, the second‐order topological systems exhibit dynamic tunability, being useful for diverse applications such as optical switching and flexible beam control. Unlike the previous results for reconfigurable routing limited to special angles, this lattice‐reshaping mechanism has the ability to realize dynamically tunable routing, extending the realm of applications of topological photonics. For its simplicity and feasibility, this mechanical lattice‐reshaping approach paves the way toward higher‐order topological photonic devices with dynamically controlled functions. [ABSTRACT FROM AUTHOR]

High-risk behaviours, such as smoking, alcohol consumption, substance use, and pre/extramarital sex are considered major public health issues. The present study aimed to estimate the prevalence rate of high-risk behaviours among medical students in the North-West of Iran. This study recruited 500 medical students of the Tabriz University of Medical Science. Data collection was performed by using the self-administered tool of the Youth Risk Behaviour Surveillance System (YRBSS). Data analysis was done with the SPSS software version 16 by using the chi-squared test and logistic regression. The mean (standard deviation) of age for participants was 23.85 (2.36) years. The prevalence rates of cigarette smoking, alcohol consumption, and pre/extramarital sexual contact were 18.88%, 11.62%, and 14.43%, respectively. The prevalence rates for use of substances and non-prescribed Ritalin were 9.22% and 16.03%, respectively. The current use was documented in 3.22% for substances and 4.02% for Ritalin. The prevalence rate of at least one of the five high-risk behaviours in the previous month was 25.00%. Males and students living alone were significantly more likely to conduct high-risk behaviours. Peer pressure was the most common motivator for these risky practices. About one-fourth of the students engaged in at least one of the high-risk behaviours in the previous 30 days, which is relatively high for medical students. Therefore, the student counselling centers should implement screening programs especially for males and students who live alone, to provide appropriate behavioural interventional programs for harm reduction. Timely attitude improvement programs are highly recommended from a younger age. [ABSTRACT FROM AUTHOR]

Purpose of Review: Patients with different types of choreic syndromes, specially those with Huntington's (HD) and Wilson's (WD) diseases, report frequent sleep complaints. This review focuses on the main findings of studies addressing the sleep features in these diseases, and other less frequent causes of chorea associated with sleep disorders, including a new syndrome described in the last decade associated with IgLON5 antibodies. Recent Findings: Patients with HD and WD showed a bad quality of sleep and high frequency of insomnia and excessive daytime somnolence. WD patients also showed high scores on a specific scale for rapid eye movement sleep behavior disorders. HD and WD share decreased sleep efficiency and increased REM sleep latencies, percentage of sleep stage N1, and wake after sleep onset (WASO) among their polysomnographic features. Summary: Patients with HD and WD showed a high prevalence of different sleep disorders. Patients with other causes of chorea, including neuroacanthocytosis, parasomnia with sleep breathing disorder associated with antibodies to IgLON5, Sydenham's chorea, and choreic syndromes associated to certain genetic mutations show sleep disorders as well. [ABSTRACT FROM AUTHOR]

Immunotoxins (ITXs) are chimeric molecules that combine the specificity of a targeting domain, usually derived from an antibody, and the cytotoxic potency of a toxin, leading to the selective death of tumor cells. However, several issues must be addressed and optimized in order to use ITXs as therapeutic tools, such as the selection of a suitable tumor-associated antigen (TAA), high tumor penetration and retention, low kidney elimination, or low immunogenicity of foreign proteins. To this end, we produced and characterized several ITX designs, using a nanobody against EGFR (VHH 7D12) as the targeting domain. First, we generated a nanoITX, combining VHH 7D12 and the fungal ribotoxin α-sarcin (αS) as the toxic moiety (VHHEGFRαS). Then, we incorporated a trimerization domain (TIEXVIII) into the construct, obtaining a trimeric nanoITX (TriVHHEGFRαS). Finally, we designed and characterized a bispecific ITX, combining the VHH 7D12 and the scFv against GPA33 as targeting domains, and a deimmunized (DI) variant of α-sarcin (BsITXαSDI). The results confirm the therapeutic potential of α-sarcin-based nanoITXs. The incorporation of nanobodies as target domains improves their therapeutic use due to their lower molecular size and binding features. The enhanced avidity and toxic load in the trimeric nanoITX and the combination of two different target domains in the bispecific nanoITX allow for increased antitumor effectiveness. [ABSTRACT FROM AUTHOR]

Perpetuating the discipline of philosophy is not the main educational responsibility of philosophers. Instead, it is to equip students with those distinctively philosophical intellectual resources that will serve students in serving the public good through participation in the economy (broadly conceived) and democratic life. Given this responsibility philosophers, individually and collectively, have a duty to take teaching and learning more seriously than they do. The paper offers some confident ideas about what this means when it comes to approaching training and professional development and some more tentative ideas about what it means, specifically, for the Philosophy curriculum and the pedagogical strategies philosophers should adopt in the classroom. [ABSTRACT FROM AUTHOR]

In utero, the developing brain is highly susceptible to the environment. For example, adverse maternal experiences during the prenatal period are associated with outcomes such as altered neurodevelopment and emotion dysregulation. Yet, the underlying biological mechanisms remain unclear. Here, we investigate whether the function of a network of genes co-expressed with the serotonin transporter in the amygdala moderates the impact of prenatal maternal adversity on the structure of the orbitofrontal cortex (OFC) in middle childhood and/or the degree of temperamental inhibition exhibited in toddlerhood. T1-weighted structural MRI scans were acquired from children aged 6–12 years. A cumulative maternal adversity score was used to conceptualize prenatal adversity and a co-expression based polygenic risk score (ePRS) was generated. Behavioural inhibition at 18 months was assessed using the Early Childhood Behaviour Questionnaire (ECBQ). Our results indicate that in the presence of a low functioning serotonin transporter gene network in the amygdala, higher levels of prenatal adversity are associated with greater right OFC thickness at 6–12 years old. The interaction also predicts temperamental inhibition at 18 months. Ultimately, we identified important biological processes and structural modifications that may underlie the link between early adversity and future deviations in cognitive, behavioural, and emotional development. [ABSTRACT FROM AUTHOR]

Non–small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths. Immune checkpoint blockade has improved survival for many patients with NSCLC, but most fail to obtain long-term benefit. Understanding the factors leading to reduced immune surveillance in NSCLC is critical in improving patient outcomes. Here, we show that human NSCLC harbors large amounts of fibrosis that correlates with reduced T cell infiltration. In murine NSCLC models, the induction of fibrosis led to increased lung cancer progression, impaired T cell immune surveillance, and failure of immune checkpoint blockade efficacy. Associated with these changes, we observed that fibrosis leads to numerically and functionally impaired dendritic cells and altered macrophage phenotypes that likely contribute to immunosuppression. Within cancer-associated fibroblasts, distinct changes within the Col13a1-expressing population suggest that these cells produce chemokines to recruit macrophages and regulatory T cells while limiting recruitment of dendritic cells and T cells. Targeting fibrosis through transforming growth factor–β receptor signaling overcame the effects of fibrosis to enhance T cell responses and improved the efficacy of immune checkpoint blockade but only in the context of chemotherapy. Together, these data suggest that fibrosis in NSCLC leads to reduced immune surveillance and poor responsiveness to checkpoint blockade and highlight antifibrotic therapies as a candidate strategy to overcome immunotherapeutic resistance. Editor's summary: Treatment for non–small cell lung cancer (NSCLC) has improved considerably since the development of immune checkpoint blockade therapies, but a number of patients' tumors still fail to respond. Here, Herzog et al. found that tumor-associated fibrosis, which is common in patients but not found in murine models, impaired antitumor immune responses. The authors modeled fibrosis in murine models of NSCLC and found that targeting fibrosis through inhibition of transforming growth factor β signaling could sensitize tumors to immune checkpoint blockade when used in combination with chemotherapy. Together, these results highlight a potential path forward to increase the sensitivity of NSCLC tumors to immunotherapy. —Courtney Malo [ABSTRACT FROM AUTHOR]

Cystic fibrosis-related diabetes (CFRD) is a complication associated with a negative prognosis in patients with cystic fibrosis (CF). Although the oral glucose tolerance test (OGTT) is the widely recommended screening test for CFRD diagnosis, continuous glucose monitoring (CGM) is increasingly considered a useful and easy-to-perform test for diagnosis and follow-up in clinical practice. Regarding CFRD treatment, although insulin is the classic approved pharmacological option, incretins could also be a helpful alternative in early stages. CGM could be also a useful tool to measure the early response to this therapy. METHODS: We studied 25 CF patients with abnormal OGTT results and compared glucose and insulin levels during the OGTTs with CGM results as a tool for early CFRD diagnosis. In addition, we evaluated glycaemic control with CGM before and after treatment with sitagliptin. RESULTS: A correlation was found between lower plasma insulin levels during the OGTTs and higher average sensor glucose (p = 0.009) and hyperglycaemic excursions (p = 0.017). The CGM data on sitagliptin treatment (n = 25) showed an average glycaemic improvement from 124.2 to 117.2 mg/dL (p = 0.002) with a 5.6-point standard deviation of glucose decrease (p < 0.001). Hyperglycaemic excursions ≥200 mg/dL diminished 57.1% (p = 0.021). Both time in range and time above 180 mg/dL improved during treatment (p = 0.036 and p = 0.006, respectively). CONCLUSION: CGM is a useful tool that offers valuable information for both the diagnosis and the management of CFRD. Lower plasma insulin levels during OGTTs are associated with a poor ambulatory glucose profile in CGM. Sitagliptin could play an important role in the treatment of the early stages of CFRD. [ABSTRACT FROM AUTHOR]

Framework-forming cold-water corals are ecosystem engineers that build mounds in the deep-sea that can be several hundred meters high. The effect of the presence of cold-water coral mounds on their surrounding is typically difficult to separate from environmental factors that are not affected by the mounds. We investigated the environmental control on cold-water coral reefs at multiple spatial scales, using annotated video transects data, spatial variables (MEMs) and hydrodynamic model output in a redundancy analysis and with variance partitioning. Using available hydrodynamic simulations with cold-water coral mounds and simulations where the mounds were artificially removed, we investigated the effect of coral mound ecosystem engineering on the spatial configuration of reef habitat and discriminated which environmental factors are and which are not affected by the mounds. We find that, due to the interaction between the coral mound and the water flow, different hydrodynamic zones are created on a coral mound that likely determine the typical benthic zonation of coral rubble at the mound foot, dead coral framework on the mound flank, and living corals near the summit. Moreover, we observed a so-called massenerhebung effect (well-known for terrestrial mountains) meaning that benthic zonation depends on the location on the mound rather than on the height above the seafloor or water depth. Our finding that ecosystem engineering determines the configuration of benthic habitats on cold-water coral mounds has many implications, such as that cold-water corals cannot simply move towards deeper water depths to avoid the adverse effects of climate change. We further find that downward velocities in winter, related to non-engineered environmental factors, e.g., deep winter mixing and dense water cascading, correlated to substantial differences in reef cover at the broadest spatial scale (20–30 km). Such hydrodynamic processes that stimulate the food supply towards the corals in winter are more important for the reefs than similar hydrodynamic processes in summer. There is much research on the ecosystem engineering effects of cold-water corals, but our results highlight that the influence of non-engineered environmental processes that accelerate the food supply towards the cold-water corals should not be underestimated. [ABSTRACT FROM AUTHOR]

There is a growing emphasis worldwide on the use of knowledge mobilization (KMb) to improve policies and practices with the latest research evidence. This emphasis calls upon knowledge producers (e.g., university researchers) to produce more relevant evidence, and knowledge users (e.g., practitioners) to access and apply evidence. However, doing KMb can be challenging for these groups without effective support and training. Therefore, individuals and organizations are undertaking capacity development interventions to facilitate the KMb process with more effective support structures, skills, and incentives. Despite its recognized importance, theoretical evidence and practical guidance on capacity development for KMb are scattered across disciplines and practices. To address this, we conducted a scoping review study to review the current practices and concepts and identify significant gaps. One-thousand six-hundred thirty records were gathered, and 105 peer-reviewed and gray literature documents from 2010 to 2020 were reviewed. Two reviewers worked independently in screening the records, and one researcher analyzed the retained documents. The analysis reveals that capacity development for KMb is a multidimensional and multiscalar concept and practice with a diverse range of initiators, initiatives, and beneficiaries. This study also reports on three thematic areas of significance emerging from the literature, namely: (a) individuals' and organizations' challenges in doing and supporting KMb, (b) the capacities and supports deemed needed for effective KMb, and (c) the strategies being used for delivering capacity development. Furthermore, this study identifies evidence gaps related to the process aspects of capacity development for KMb (i.e., planning), capacity development initiatives being undertaken in developing country contexts, and results from more formal evaluations of KMb capacity-building effectiveness. [ABSTRACT FROM AUTHOR]

Surface-Enhanced Raman Scattering (SERS) technology, as a powerful tool to identify molecular species by collecting molecular spectral signals at the single-molecule level, has achieved substantial progresses in the fields of environmental science, medical diagnosis, food safety, and biological analysis. As deepening research is delved into SERS sensing, more and more high-performance or multifunctional SERS substrate materials emerge, which are expected to push Raman sensing into more application fields. Especially in the field of biological analysis, intrinsic and extrinsic SERS sensing schemes have been widely used and explored due to their fast, sensitive and reliable advantages. Herein, recent developments of SERS substrates and their applications in biomolecular detection (SARS-CoV-2 virus, tumor etc.), biological imaging and pesticide detection are summarized. The SERS concepts (including its basic theory and sensing mechanism) and the important strategies (extending from nanomaterials with tunable shapes and nanostructures to surface bio-functionalization by modifying affinity groups or specific biomolecules) for improving SERS biosensing performance are comprehensively discussed. For data analysis and identification, the applications of machine learning methods and software acquisition sources in SERS biosensing and diagnosing are discussed in detail. In conclusion, the challenges and perspectives of SERS biosensing in the future are presented. [ABSTRACT FROM AUTHOR]

Many have suggested different ways of conceptualizing mental health conditions in mental health services. However, eliciting the unicity of the individual experience of mental health conditions in the diagnostic process remains challenging. In this position paper, we describe the diagnostic process in psychiatry and outline three challenges for which insights from the design research paradigm, in particular so-called generative sessions, may represent an opportunity for innovation. We suggest that by implementing generative sessions, conversations about individual experience can be initiated, the focus on diagnostic categories can be shifted towards personal variation, and the integration of empirical evidence of recovery can be facilitated. Therefore, we argue that exploring generative sessions in the diagnostic process can stimulate incremental and iterative advancements in diagnostic systems. To test its hypothesized impact on clinical practice, we recommend several directions for further research in co-creation with traditional mental health professionals, people with mental health conditions, and people with lived experience. [ABSTRACT FROM AUTHOR]

In this study, the sorption capacity of limestone samples for CO2 was investigated to determine the conditions under which they can be used in the high-temperature carbonate loop process. For the work, limestone samples from the Czech Republic were used, which contained a high proportion of CaO (more than 97 wt.%). A total of 20 cycles of calcination (950 °C) and subsequent CO2 sorption–carbonation (650 °C) were performed for each limestone sample tested. The sorption capacity towards CO2 in the 20th cycle was less than 10% of the value determined in the first carbonation cycle of the samples and the most significant decrease was observed between the first and second cycles. The highest sorption capacity was determined for the Branžovy sample, which captured 268 mL of CO2/per 1 g of sorbent by chemisorption. Only 15 mL of carbon dioxide per 1 g of sorbent was bound by physisorption. However, in repeated use, the Vitošov limestone had the highest sorption capacity for CO2. For all samples, the amount of carbon dioxide bound by physisorption was in the range of 4 to 10% of the amount bound by chemisorption. Due to sintering of the material, the BET specific surface area decreased by 95 to 96%. [ABSTRACT FROM AUTHOR]

We analyze long-term impacts of the 1967–1970 Nigerian Civil War, providing the first evidence of intergenerational impacts. War exposure among women results in reduced adult stature, an increased likelihood of being overweight, earlier age at first birth, and lower educational attainment. War exposure of mothers has adverse impacts on next-generation child survival, growth, and education. Impacts vary with age of exposure. For the mother and child health outcomes, the largest impacts stem from adolescent exposure. Exposure to a primary education program mitigates impacts of war exposure. War exposure leads to men marrying later and having fewer children. [ABSTRACT FROM AUTHOR]

Quantum entanglement plays a key role in both understanding the fundamental aspects of quantum physics and realizing various quantum devices for practical applications. Here we propose how to achieve a coherent switch of optomechanical entanglement in an optical whispering-gallery-mode resonator, by tuning the phase difference of the driving lasers. We find that the optomechanical entanglement and the associated two-mode quantum squeezing can be well tuned in a highly asymmetric way, providing an efficient way to protect and enhance quantum entanglement against optical backscattering, in comparison with conventional symmetric devices. Our findings shed a new light on improving the performance of various quantum devices in the practical noisy environment, which is crucial in such a wide range of applications as noise-tolerant quantum processing and the backscattering-immune quantum metrology. [ABSTRACT FROM AUTHOR]

This study was conducted to examine whether online information regarding male infertility on Swedish fertility clinics' websites was readable, suitable, and of appropriate quality. A cross-sectional design was used to evaluate 22 fertility clinics' websites focusing on male infertility by using the Suitability Assessment of Materials (SAM), and the DISCERN instrument. Results showed that information focusing on male infertility was scanty but had an "adequate" readability and was easy to comprehend. The conclusion was that the information on the websites must be reliable, so that men can base their choices concerning their fertility issues on reliable facts. It is important that health care professionals develop high quality sources of information regarding male infertility. [ABSTRACT FROM AUTHOR]

Although second‐order topological photonic systems have been extensively investigated in the last several years, topological edge and corner states have been considered mainly in the systems with single topology. Herein, multiple topological photonic systems consisting of two different types of topologically nontrivial unit cells and their trivial counterparts which are related to each other under a relevant continuous transformation are presented. The dispersing characteristics of edge states are diverse at different topological interfaces of the system and can be controlled with relevant structural parameters, resulting in novel mechanism for multichannel topological beam splitting. Interestingly enough, second‐order topological corner states exist even in the structure of nontrivial photonic crystals surrounded by another nontrivial one unlike the previous cases with trivial surroundings, which can be confirmed from the spectral charge distributions. This enables us to obtain both spatially and spectrally separated multiband‐like corner states as well as edge ones in a multiple topological photonic system, which can be used for wavelength demultiplexer. The results in this work will trigger extensive studies on multiple topology for wide photonic applications. [ABSTRACT FROM AUTHOR]

The article presents the discussion on people with cystic fibrosis (CF). Topics include lives of persons with CF (PwCF) being profoundly changed by the advent of highly effective CF transmembrane conductance regulator (CFTR) modulator therapy (HEMT); and emerging technologies for the management of diabetes including advanced insulin pumps and continuous glucose monitoring (CGM).

This paper investigates the effectiveness of a school-based management policy in Sri Lanka, the Programme for School Improvement (PSI). The PSI established new management structures and provided training and support services to: (a) devolve decisions for a range of activities to the school level; (b) increase participation of parents and the local community; and (c) focus schools' efforts on student learning. A randomized controlled trial show some evidence of behaviour changes in both principals and teachers in PSI schools, but most observed behaviours did not change. There are no statistically significant effects on student learning as measured by test scores. [ABSTRACT FROM AUTHOR]

Carbon dioxide and combustion products are among the main waste streams deriving from the energy sector. Efficient and cost-effective methods of solid waste valorization and carbon capture, storage and utilization are needed in the transition period towards carbon neutrality in light of the recent scenarios forecasting energy demand and energy supply mix under dynamic social, economic and political circumstances. Within this paper, the current advances in carbon dioxide mineralization, combining carbon dioxide utilization and combustion products valorization, are presented in terms of the recognized methodological options of carbonation methods, process efficiency and effects on the process product properties. Special attention is given to the studies on the valorization of fluidized bed boilers fly ash, differing in a range of parameters from the conventional boilers fly ash, as well as the effects of the carbonation process on the stabilization and improvement of its properties and the resulting extended range of applicability. The relevant research fields needing further investigations, as well as the desired decision makers' supporting actions, are also specified. [ABSTRACT FROM AUTHOR]

Greek-letter student social groups, better known as fraternities and sororities, are a ubiquitous feature on many American higher education campuses. These organizations, especially fraternities, have a reputation for encouraging unruly and improper behaviour among both members and non-members. This paper investigates the effect of the degree of prevalence of these Greek organizations at a campus, as measured by the percentage of students who are members of fraternities and sororities, on the instances of liquor and drug law violations on campuses, as measured by the number of arrests for liquor and drug laws violations. Using a unique dataset, which combines data from three sources, we address any potential selection bias by including several controls associated with party culture and through the inclusion of institution-level fixed effects. We find that a larger percentage of students in fraternities (but not sororities) is associated with an increase in the number of arrests for drug law violations. A larger percentage of students in sororities (but not the percentage of students in fraternities) is associated with a larger number of arrests for liquor law violations. This result is highly significant and is robust across various specifications. [ABSTRACT FROM AUTHOR]

As an emerging field, nonlinear topological photonics attracts great attention nowadays, where pioneering works show interesting phenomena including topological edge solitons and nonlinearity‐induced coupling of light into topological edge states. In this work, the nonlinear effects in a photonic topological insulator in the synthetic space including the frequency axis of light, in a ring resonant array under dynamic modulations are studied, where the four‐wave mixing nonlinear process is included. Such nonlinear process not only induces local interactions, but also creates long‐range interactions in the frequency dimension. These results show destruction on topologically protected edge states when the nonlinear effects are increasing. Moreover, it also breaks the symmetry in the synthetic space as well as the band structure, which reflects different propagation behaviors for the different input sources with positive and negative frequency shifts and exhibits short‐time robustness in weak nonlinear cases. This work hence explores the role of nonlinear effects in affecting the edge modes in the synthetic space, which may be useful in quantum many‐body simulations and find possible applications in information processing. [ABSTRACT FROM AUTHOR]

Bringing evidence into policy and practice discussions is political; more so when evidence from health studies or programme data are deemed controversial or unexpected, or when results are manipulated and misrepresented. Furthermore, opinion and misinformation in recent years has challenged our notions about how to achieve evidence-informed decision-making (EIDM). Health policy and systems (HPS) researchers and practitioners are battling misrepresentation that only serves to detract from important health issues or, worse, benefit powerful interests. This paper describes cases of politically and socially controversial evidence presented by researchers, practitioners and journalists during the Health Systems Research Symposium 2020. These cases cut across global contexts and range from public debates on vaccination, comprehensive sexual education, and tobacco to more inward debates around performance-based financing and EIDM in refugee policy. The consequences of engaging in controversial research include threats to commercial profit, perceived assaults on moral beliefs, censorship, fear of reprisal, and infodemics. Consequences for public health include research(er) hesitancy, contribution to corruption and leakage, researcher reflexivity, and ethical concerns within the HPS research and EIDM fields. Recommendations for supporting researchers, practitioners and advocates include better training and support structures for responding to controversy, safe spaces for sharing experiences, and modifying incentive structures. [ABSTRACT FROM AUTHOR]

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Objectives: The current study was designed to monitor the relationship between Lipid Profile and calcyphosin a level by studying the correlation of calcyphosin a concentration in blood serum with T. Cho and TG in women with PCOS in Anbar Governorate. Methods: This study included 100 Iraqi women (age: 18-45 years) who were divided into two groups, polycystic ovary syndrome women group (60 women) and healthy women group (40 women). Body mass index was measured for all participating women. CAPS levels were evaluated using ELISA technology, while levels of (Total Cholesterol) were assessed using a spectrophotometer. Results: The mean CAPS was significantly higher in the group of women with PCOS than in the group of healthy women. This study also showed that there are no statistically significant changes in the level of In comparison to a control group of healthy women, PCOS women had higher levels of total cholesterol, triglycerides, good cholesterol (HDL), and low-density lipoprotein (VLDL). However, the study's findings and statistical analysis revealed that PCOS patients also had significantly higher levels of VLDL. Conclusion: Serum CAPS levels can be used as a novel biomarker in the detection of PCOS and may be an effective biomarker in the diagnostic test of PCOS. [ABSTRACT FROM AUTHOR]

With the growth of online mental healthcare platforms, health professionals have been providing online consultation services during their spare time. However, little is known about the prosocial behaviors of health professionals on these platforms and their effect on professionals' economic performance. In this research, we aim to identify and quantify the main effect of prosocial behaviors (i.e., offering free services) on future economic performance and the potential mediation effects of relationship capital and reputation capital in an online mental healthcare platform. Based on signaling and commitment theories, we use a panel dataset from a Chinese online mental healthcare platform to test our hypotheses. Our findings show that a mental health professional's previous prosocial behavior has a positive impact on economic performance and that this effect may manifest through the relationship capital pathway. However, reputation capital generated from prosocial behaviors does not significantly mediate the impact of prosocial behavior on economic performance. Our research provides important implications for healthcare operations concerning service offerings and healthcare providers' performance on online mental healthcare platforms. [ABSTRACT FROM AUTHOR]

Basal Cell Carcinoma (BCC) is the most commonly diagnosed cancer worldwide. While the survivability of BCC is high, many patients are excluded from clinically available treatments due to health risks or personal choice. Further, patients with advanced or metastatic disease have severely limited treatment options. The dysregulation of the Hedgehog (Hh) signaling cascade drives onset and progression of BCC. As such, the modulation of this pathway has driven advancements in BCC research. In this review, we focus firstly on inhibitors that target the Hh pathway as chemotherapeutics against BCC. Two therapies targeting Hh signaling have been made clinically available for BCC patients, but these treatments suffer from limited initial efficacy and a high rate of chemoresistant tumor recurrence. Herein, we describe more recent developments of chemical scaffolds that have been designed to hopefully improve upon the available therapeutics. We secondly discuss the history and recent efforts involving modulation of the Hh genome as a method of producing in vivo models of BCC for preclinical research. While there are many advancements left to be made towards improving patient outcomes with BCC, it is clear that targeting the Hh pathway will remain at the forefront of research efforts in designing more effective chemotherapeutics as well as relevant preclinical models. [ABSTRACT FROM AUTHOR]

Seabed sedimentary bedforms (SSBs) are strong indicators of current flow (direction and velocity) and can be mapped in high resolution using multibeam echosounders. Many approaches have been designed to automate the classification of such SSBs imaged in multibeam echosounder data. However, these classification systems only apply a geomorphological contextualisation to the data without making direct assertions on the velocities of benthic currents that form these SSBs. Here, we apply an object-based image analysis (OBIA) workflow to derive a geomorphological classification of SSBs in the Moira Mounds area of the Belgica Mound Province, NE Atlantic through k-means clustering. Cold-water coral reefs as sessile filter-feeders benefit from strong currents are often found in close association with sediment wave fields. This OBIA provided the framework to derive SSB wavelength and wave height, these SSB attributes were used as predictor variables for a multiple linear regression to estimate current velocities. Results show a bimodal distribution of current flow directions and current speed. Furthermore, a 5 k-means classification of the SSB geomorphology exhibited an imprinting of current flow consistency which altered throughout the study site due to the interaction of regional, local, and micro scale topographic steering forces. This study is proof-of-concept for an assessment tool applied to vulnerable marine ecosystems but has wider applications for applied seabed appraisals and can inform management and monitoring practice across a variety of spatial and temporal scales. Deriving spatial patterns of hydrodynamic processes from widely available multibeam echosounder maps is pertinent to many avenues of research including scour predictions for offshore structures such as wind turbines, sediment transport modelling, benthic fisheries, e.g., scallops, cable route and pipeline risk assessment and habitat mapping. [ABSTRACT FROM AUTHOR]

Group 1 innate lymphoid cells (ILCs) comprising circulating natural killer (cNK) cells and tissue-resident ILC1s are critical for host defense against pathogens and tumors. Despite a growing understanding of their role in homeostasis and disease, the ontogeny of group 1 ILCs remains largely unknown. Here, we used fate mapping and single-cell transcriptomics to comprehensively investigate the origin and turnover of murine group 1 ILCs. Whereas cNK cells are continuously replaced throughout life, we uncovered tissue-dependent development and turnover of ILC1s. A first wave of ILC1s emerges during embryogenesis in the liver and transiently colonizes fetal tissues. After birth, a second wave quickly replaces ILC1s in most tissues apart from the liver, where they layer with embryonic ILC1s, persist until adulthood, and undergo a specific developmental program. Whereas embryonically derived ILC1s give rise to a cytotoxic subset, the neonatal wave establishes the full spectrum of ILC1s. Our findings uncover key ontogenic features of murine group 1 ILCs and their association with cellular identities and functions. Innate cell waves: Group 1 innate lymphoid cells (ILCs), classified as either circulating natural killer (cNK) cells or tissue-resident ILC1s, are critical to innate immune responses against pathogens and tumors. Sparano et al. examined the origin and turnover of murine ILC1s to better understand how their development influences their biology. Through genetic fate mapping and single-cell RNA sequencing studies, they observed that cNK cells emerge shortly after birth and continuously turn over throughout life. In contrast, a first wave of ILC1s develops during the fetal stage, persists in the liver, and gives rise to cytotoxic ILC1s, whereas ILC1s that arise during the neonatal wave seed tissues as helper-like ILC1s. These observations were complemented by analysis of human adult and fetal liver NK cells and together illustrate ontogenic characteristics of ILC1s that influence their phenotype and function. [ABSTRACT FROM AUTHOR]