Search

Increasing preclinical and clinical results have demonstrated that mRNA vaccines efficiently prevent infectious diseases and are safe in animal models and humans. In this study, we fabricated a multivalent influenza mRNA lipid nanoparticle (LNP) vaccine with mRNAs of hemagglutinins from influenza H1N1 and H3N2 viruses, matrix protein 1, and nucleoprotein. We found that cutaneous immunization with mRNA LNPs induced strong Th1 and Th2 cellular immunity with robust antigen-specific antibody titers and increased cytokine-secreting splenocytes and antibody-secreting cells. The supplement of cGAMP improved the immunogenicity of mRNA LNPs. Compared with αGC or cGAMP/αGC adjuvanted mRNA LNP formulations in our study, cGAMP mRNA LNPs induced more robust antibody responses. Enhanced cellular immunity with more IL-4 and IFN-γ secreting cells and effector memory T cell populations in spleens, as well as increased CD4+ resident memory (T

Background The presence of active or inactive (i.e., postproduction) oil and gas wells in neighborhoods may contribute to ongoing pollution. Racially discriminatory neighborhood security maps developed by the Home-Owners Loan Corporation (HOLC) in the 1930s may contribute to environmental exposure disparities. Objective To determine whether receiving worse HOLC grades was associated with exposure to more oil and gas wells. Methods We assessed exposure to oil and gas wells among HOLC-graded neighborhoods in 33 cities from 13 states where urban oil and gas wells were drilled and operated. Among the 17 cities for which 1940 census data were available, we used propensity score restriction and matching to compare well exposure neighborhoods that were similar on observed 1940 sociodemographic characteristics but that received different grades. Results Across all included cities, redlined D-graded neighborhoods had 12.2 ± 27.2 wells km−2, nearly twice the density in neighborhoods graded A (6.8 ± 8.9 wells km−2). In propensity score restricted and matched analyses, redlined neighborhoods had 2.0 (1.3, 2.7) more wells than comparable neighborhoods with a better grade. Significance Our study adds to the evidence that structural racism in federal policy is associated with the disproportionate siting of oil and gas wells in marginalized neighborhoods.

Purpose of Review Climate change is causing warming over most parts of the USA and more extreme weather events. The health impacts of these changes are not experienced equally. We synthesize the recent evidence that climatic changes linked to global warming are having a disparate impact on the health of people of color, including children. Recent Findings Multiple studies of heat, extreme cold, hurricanes, flooding, and wildfires find evidence that people of color, including Black, Latinx, Native American, Pacific Islander, and Asian communities are at higher risk of climate-related health impacts than Whites, although this is not always the case. Studies of adults have found evidence of racial disparities related to climatic changes with respect to mortality, respiratory and cardiovascular disease, mental health, and heat-related illness. Children are particularly vulnerable to the health impacts of climate change, and infants and children of color have experienced adverse perinatal outcomes, occupational heat stress, and increases in emergency department visits associated with extreme weather. Summary The evidence strongly suggests climate change is an environmental injustice that is likely to exacerbate existing racial disparities across a broad range of health outcomes.

Study question Does the microRNA expression profile in blastocysts change with different embryonic quality parameters? Summary answer MicroRNA expression showed significant changes when aneuploidy was present, in day-6 compared to day-5 blastocysts and with different trophectoderm (TE) morphology grades. What is known already MicroRNA (miRNA) is a gene expression regulatory mechanism used as a diagnostic marker for some conditions. Despite the great magnitude of studies investigating the miRNA role in implantation and pregnancy complications, limited work has been done to evaluate it as a potential marker for preimplantation embryo quality. With the accelerated changes in gene expression at early embryos, the miRNA profile is a potential indicator of embryo quality. This study investigates the blastocyst miRNA profile in relation to three quality parameters: aneuploidy, the day of blastocyst formation and morphology. Study design, size, duration We collected 122 surplus embryos donated for research by 46 consenting couples from Centre for Reproductive and Genetic Health, London. All samples were ICSI derived blastocysts (day5/6) with PGT-A results. For aneuploidy status comparison, samples were categorized according to the number of chromosomes affected (single/multiple) and type of aneuploidy (gain/loss/partial), compared to euploid. The day of blastocyst development has (day5/day6) groups, and finally samples were compared based on TE morphology (excellent/good/fair). Participants/materials, setting, methods Frozen human embryos were individually thawed and transferred to a lysis buffer. The miRNAs were extracted from each sample then sequenced by next generation sequencing (NGS) using miRNA Library Kit (QIAGEN) with NextSeqTM 500 (illumina). The differential expression analysis was conducted using DESeq2 via GeneGlobe (QIAGEN). We set the significance cut-offs to (-2> foldchange >2) and ( Main results and the role of chance Compared to the euploid blastocysts, all aneuploid categories, except the single chromosome aneuploidy, had significant differences in miRNA expression. Nine miRNAs were altered in the group with multiple aneuploidies, and one was highly upregulated in embryos with partial losses or gains. The majority of differentially expressed (DE) miRNAs in samples with whole chromosomal gain or loss were downregulated. Conversely, four miRNAs showed a significant increase in day-6 blastocysts compared to day-5. Morphology grade comparisons showed no differences between excellent and good TE; however, six miRNAs were significantly changed in fair TE compared to good. The frequently altered miRNAs in these comparisons were ( hsa-let-7c-5p, hsa-miR-206, hsa-miR-184 and hsa-miR-203a-3p ). Unsurprisingly, pathway annotation of the DE miRNAs showed an involvement of key biological processes, like apoptosis, cell-cycle and differentiation, signalling and gene expression regulation, in all groups. The pathways of note in aneuploid blastocysts included DNA damage response, intrinsic and extrinsic apoptotic signalling, and regulation of cell-cycle G1/S associated events. In blastocyst day5/day6 comparison, embryonic and organ development were the most involved pathways, while in TE morphology, kinase activity and phosphorylation along with apoptosis and DNA damage response were significant. Limitations, reasons for caution Differential expression analysis based on inner cell mass (ICM) morphology and blastocyst expansion were not applicable due to the inadequate number of embryos per group; as all the samples collected were in excellent or good quality. Wider implications of the findings Gene expression profiling of miRNAs in human blastocysts will potentially identify biomarkers predictive of implantation success. Trial registration number not applicable

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic. The virus is rapidly evolving, characterized by the emergence of several major variants. Stable prefusion spike protein (Pre) is the immunogen in current vaccines but is limited in protecting against different variants. Here, the immune responses induced by the relatively conserved stem subunit (S2) of spike protein versus Pre are investigated. Pre generates the most robust neutralization responses against SARS-CoV-2 variants in vesicular stomatitis virus pseudovirus-based assessment but elicits less antibody-dependent cellular cytotoxicity (ADCC) activity than S2. By contrast, S2 induces the most balanced immunoglobulin G (IgG) antibodies with potent and broad ADCC activity although produces weaker neutralization. The immunogenicity of S2 and Pre improves by incorporating the two proteins into double-layered protein nanoparticles. The resulting protein nanoparticles Pre/S2 elicit higher neutralizing antibodies than Pre alone, and stronger ADCC than S2 alone. Moreover, nanoparticles produce more potent and balanced serum IgG antibodies than the corresponding soluble protein mixture, and the immune responses are sustained for at least four months after the immunization. Thus, the double-layered protein nanoparticles have the potential to be developed into broader SARS-CoV-2 vaccines with excellent safety profiles.

The influenza epidemics pose a significant threat to public health. Of them, type B influenza coincided with several severe flu outbreaks. The efficacy of the current seasonal flu vaccine is limited due to the antigenicity changes of circulating strains. In this study, we generated structure-stabilized HA stalk antigens from influenza B and fabricated double-layered protein nanoparticles as universal influenza B vaccine candidates. In vitro studies found that the resulting protein nanoparticles were effectively taken up to activate dendritic cells. Nanoparticle immunization induced broadly reactive immune responses conferring robust and sustained cross-immune protection against influenza B virus strains of both lineages. The results reveal the potential of layered protein nanoparticles incorporated with structure-stabilized constant antigens as a universal influenza vaccine with improved immune protective potency and breadth.

Influenza viral infection causes acute upper respiratory diseases in humans, posing severe risks to global public health. However, current vaccines provide limited protection against mismatched circulating influenza A viruses. Here, the immune responses induced in mice by novel double-layered protein nanoparticles were investigated. The nanoparticles were composed of influenza nucleoprotein (NP) cores and hemagglutinin (HA) or matrix 2 protein ectodomain (M2e) shells. Vaccination with the nanoparticles significantly enhanced M2e-specific serum antibody titers and concomitant ADCC responses. Robust NP-specific T cell responses and robust HA neutralization were also detected. Moreover, vaccination with a trivalent nanoparticle combination containing two routinely circulated HA, conserved M2e, and NP reduced lung virus titers, pulmonary pathologies, and weight loss after homologous virus challenge. This combination also improved survival rates against heterologous and heterosubtypic influenza virus challenges. Our results demonstrate that the trivalent combination elicited potent and long-lasting immune responses conferring influenza viral cross-protection.

A generalisation of the Susceptible-Infectious model is made to include a time-dependent transmission rate, which leads to a close analytical expression in terms of a logistic function. The solution can be applied to any continuous function chosen to describe the evolution of the transmission rate with time. Taking inspiration from real data of the Covid-19, for the case of cumulative confirmed positives and deaths, we propose an exponentially decaying transmission rate with two free parameters, one for its initial amplitude and another one for its decaying rate. The resultant time-dependent SI model, which under extra conditions recovers the standard Gompertz functional form, is then compared with data from selected countries and its parameters fit using Bayesian inference. We make predictions about the asymptotic number of confirmed positives and deaths, and discuss the possible evolution of the disease in each country in terms of our parametrisation of the transmission rate.

The original version of this article unfortunately contained a mistake. Three values in Table 1 were incorrect. In “months of recurrence”, range row, the intervals should be in numbers. They should read as 3–83 instead of Mar-83, 9–83 instead of Sep-83 and 3–36 instead of Mar-36. The corrected Table 1 is given below. The original article has been corrected.

Beckwith-Wiedemann syndrome (BWS) is the most common epigenetic overgrowth and cancer predisposition disorder. Due to both varying molecular defects involving chromosome 11p15 and tissue mosaicism, patients can present with a variety of clinical features, leading to the newly defined Beckwith-Wiedemann spectrum (BWSp). The BWSp can be further divided into three subsets of patients: those presenting with classic features, those presenting with isolated lateralized overgrowth (ILO) and those not fitting into the previous two categories, termed atypical BWSp. Previous reports of patients with BWS have focused on those with the more recognizable, classic features, and limited information is available on those who fit into the atypical and ILO categories. Here, we present the first cohort of patients recruited across the entire BWSp, describe clinical features and molecular diagnostic characteristics, and provide insight into practical diagnosis and management recommendations that we have gained from this cohort.

Significance A noninvasive intranasal (i.n.) influenza vaccine can induce mucosal immune responses in respiratory tracts, preventing infection at the portal of virus entry. However, the absence of appropriate mucosal adjuvants at present hinders the development of such a vaccine. Here, we developed polyethyleneimine-functionalized two-dimensional graphene oxide nanoparticles (GP) that showed high antigen-loading capacities and superior immunoenhancing properties. Robust and broadly reactive immune responses were induced with i.n. immunization with GP-HA nanoparticles, conferring protection against homologous and heterologous viruses. With versatility and flexibility, GP nanoparticles can be easily adapted for constructing mucosal vaccines of different respiratory pathogens., Intranasal (i.n.) immunization is a promising vaccination route for infectious respiratory diseases such as influenza. Recombinant protein vaccines can overcome the safety concerns and long production phase of virus-based influenza vaccines. However, soluble protein vaccines are poorly immunogenic if administered by an i.n. route. Here, we report that polyethyleneimine-functionalized graphene oxide nanoparticles (GP nanoparticles) showed high antigen-loading capacities and superior immunoenhancing properties. Via a facile electrostatic adsorption approach, influenza hemagglutinin (HA) was incorporated into GP nanoparticles and maintained structural integrity and antigenicity. The resulting GP nanoparticles enhanced antigen internalization and promoted inflammatory cytokine production and JAWS II dendritic cell maturation. Compared with soluble HA, GP nanoparticle formulations induced significantly enhanced and cross-reactive immune responses at both systemic sites and mucosal surfaces in mice after i.n. immunization. In the absence of any additional adjuvant, the GP nanoparticle significantly boosted antigen-specific humoral and cellular immune responses, comparable to the acknowledged potent mucosal immunomodulator CpG. The robust immune responses conferred immune protection against challenges by homologous and heterologous viruses. Additionally, the solid self-adjuvant effect of GP nanoparticles may mask the role of CpG when coincorporated. In the absence of currently approved mucosal adjuvants, GP nanoparticles can be developed into potent i.n. influenza vaccines, providing broad protection. With versatility and flexibility, the GP nanoplatform can be easily adapted for constructing mucosal vaccines for different respiratory pathogens.

Shadab, Alam et al., We present the cosmological implications from final measurements of clustering using galaxies, quasars, and Lyα forests from the completed Sloan Digital Sky Survey (SDSS) lineage of experiments in large-scale structure. These experiments, composed of data from SDSS, SDSS-II, BOSS, and eBOSS, offer independent measurements of baryon acoustic oscillation (BAO) measurements of angular-diameter distances and Hubble distances relative to the sound horizon, rd, from eight different samples and six measurements of the growth rate parameter, fσ8, from redshift-space distortions (RSD). This composite sample is the most constraining of its kind and allows us to perform a comprehensive assessment of the cosmological model after two decades of dedicated spectroscopic observation. We show that the BAO data alone are able to rule out dark-energy-free models at more than eight standard deviations in an extension to the flat, ΛCDM model that allows for curvature. When combined with Planck Cosmic Microwave Background (CMB) measurements of temperature and polarization, under the same model, the BAO data provide nearly an order of magnitude improvement on curvature constraints relative to primary CMB constraints alone. Independent of distance measurements, the SDSS RSD data complement weak lensing measurements from the Dark Energy Survey (DES) in demonstrating a preference for a flat ΛCDM cosmological model when combined with Planck measurements. The combined BAO and RSD measurements indicate σ8=0.85±0.03, implying a growth rate that is consistent with predictions from Planck temperature and polarization data and with General Relativity. When combining the results of SDSS BAO and RSD, Planck, Pantheon Type Ia supernovae (SNe Ia), and DES weak lensing and clustering measurements, all multiple-parameter extensions remain consistent with a ΛCDM model. Regardless of cosmological model, the precision on each of the three parameters, ωΛ, H0, and σ8, remains at roughly 1%, showing changes of less than 0.6% in the central values between models. In a model that allows for free curvature and a time-evolving equation of state for dark energy, the combined samples produce a constraint ωk=-0.0022±0.0022. The dark energy constraints lead to w0=-0.909±0.081 and wa=-0.49-0.30+0.35, corresponding to an equation of state of wp=-1.018±0.032 at a pivot redshift zp=0.29 and a Dark Energy Task Force Figure of Merit of 94. The inverse distance ladder measurement under this model yields H0=68.18±0.79 km s-1 Mpc-1, remaining in tension with several direct determination methods; the BAO data allow Hubble constant estimates that are robust against the assumption of the cosmological model. In addition, the BAO data allow estimates of H0 that are independent of the CMB data, with similar central values and precision under a ΛCDM model. Our most constraining combination of data gives the upper limit on the sum of neutrino masses at mν, This paper represents an effort by both the SDSS-III and SDSS-IV collaborations. Funding for SDSS-III was provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the U.S. Department of Energy Office of Science. Funding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutions. SDSS-IV acknowledges support and resources from the Center for High-Performance Computing at the University of Utah. The SDSS website is www.sdss.org. SDSS-IV is managed by the Astrophysical Research Consortium for the Participating Institutions of the SDSS Collaboration including the Brazilian Participation Group, the Carnegie Institution for Science, Carnegie Mellon University, the Chilean Participation Group, the French Participation Group, Harvard-Smithsonian Center for Astrophysics, Instituto de Astrofísica de Canarias, the Johns Hopkins University, Kavli Institute for the Physics and Mathematics of the Universe (IPMU)/University of Tokyo, Lawrence Berkeley National Laboratory, Leibniz Institut für Astrophysik Potsdam (AIP), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Max-Planck-Institut für Astrophysik (MPA Garching), Max-Planck-Institut für Extraterrestrische Physik (MPE), National Astronomical Observatory of China, New Mexico State University, New York University, University of Notre Dame, Observatário Nacional/MCTI, The Ohio State University, Pennsylvania State University, Shanghai Astronomical Observatory, United Kingdom Participation Group, Universidad Nacional Autónoma de México, University of Arizona, University of Colorado Boulder, University of Portsmouth, University of Utah, University of Virginia, University of Washington, University of Wisconsin, Vanderbilt University, and Yale University.

The statistical power of Lyman-${\alpha}$ forest Baryon Acoustic Oscillation (BAO) measurements is set to increase significantly in the coming years as new instruments such as the Dark Energy Spectroscopic Instrument deliver progressively more constraining data. Generating mock datasets for such measurements will be important for validating analysis pipelines and evaluating the effects of systematics. With such studies in mind, we present LyaCoLoRe: a package for producing synthetic Lyman-${\alpha}$ forest survey datasets for BAO analyses. LyaCoLoRe transforms initial Gaussian random field skewers into skewers of transmitted flux fraction via a number of fast approximations. In this work we explain the methods of producing mock datasets used in LyaCoLoRe, and then measure correlation functions on a suite of realisations of such data. We demonstrate that we are able to recover the correct BAO signal, as well as large-scale bias parameters similar to literature values. Finally, we briefly describe methods to add further astrophysical effects to our skewers - high column density systems and metal absorbers - which act as potential complications for BAO analyses., Comment: 29 pages, 7 figures

Ultra-light bosons as dark matter has become a model of major interest in Cosmology, due to the possible imprint of a distinct signature in the cosmic structure both at the linear and non-linear scales. In this work we show that the equations of motion for density perturbations for this kind of models can be written in terms of a modified gravitational potential. Taking advantage of this parallelism, we use the MG-PICOLA code originally developed for modified gravity models to evolve the density field of axion models with and without self-interaction. Our results indicate that the quantum potential adds extra suppression of power at the non-linear level, and it is even capable of smoothing any bumpy features initially present in the mass power spectrum., Comment: 11 pages, 4 figures

We present a measurement of baryonic acoustic oscillations (BAO) from Lyman-$\alpha$ (Ly$\alpha$) absorption and quasars at an effective redshift $z=2.33$ using the complete extended Baryonic Oscillation Spectroscopic Survey (eBOSS). The sixteenth and final eBOSS data release (SDSS DR16) contains all data from eBOSS and its predecessor, the Baryonic Oscillation Spectroscopic Survey (BOSS), providing $210,005$ quasars with $z_{q}>2.10$ that are used to measure Ly$\alpha$ absorption. We measure the BAO scale both in the auto-correlation of Ly$\alpha$ absorption and in its cross correlation with $341,468$ quasars with redshift $z_{q}>1.77$. Apart from the statistical gain from new quasars and deeper observations, the main improvements over previous work come from more accurate modeling of physical and instrumental correlations and the use of new sets of mock data. Combining the BAO measurement from the auto- and cross-correlation yields the constraints of the two ratios $D_{H}(z=2.33)/r_{d} = 8.99 \pm 0.19$ and $D_{M}(z=2.33)/r_{d} = 37.5 \pm 1.1$, where the error bars are statistical. These results are within $1.5\sigma$ of the prediction of the flat-$\Lambda$CDM cosmology of Planck~(2016). The analysis code, \texttt{picca}, the catalog of the flux-transmission field measurements, and the $\Delta \chi^{2}$ surfaces are publicly available., Comment: 37 pages, 23 figures, Matches the published version by ApJ

We present the characteristics of the damped Lyα (DLA) systems found in data release DR16 of the extended Baryon Oscillation Spectroscopic Survey of the Sloan Digital Sky Survey. The DLAs were identified using the convolutional neural network of Parks et al. (2018). A total of 117,458 absorber candidates were found with 2 ≤ z DLA ≤ 5.5 and 19.7 ≤ log ( N ( H I ) / cm − 2 ) ≤ 22 , including 57,136 DLA candidates with log ( N ( H I ) / cm − 2 ) ≥ 20.3 . Mock quasar spectra were used to estimate the DLA detection efficiency and the purity of the resulting catalog. Restricting the quasar sample to bright forests, i.e., those with mean forest fluxes f λ ¯ > 2 × 10 − 19 W m − 2 nm − 1 , the efficiency and purity are greater than 90% for DLAs with column densities in the range 20.1 ≤ log ( N ( H I ) / cm − 2 ) ≤ 22 .

In a recent paper, Erik Verlinde has developed the interesting possibility that spacetime and gravity may emerge from the entangled structure of an underlying microscopic theory. In this picture, dark matter arises as a response to the standard model of particle physics from the delocalized degrees of freedom that build up the dark energy component of the Universe. Dark matter physics is then regulated by a characteristic acceleration scale $a_0$, identified with the radius of the (quasi)-de Sitter universe we inhabit. For a point particle matter source, or outside an extended spherically symmetric object, MOND's empirical fitting formula is recovered. However, Verlinde's theory critically departs from MOND when considering the inner structure of galaxies, differing by a factor of 2 at the centre of a regular massive body. For illustration, we use the eight classical dwarf spheroidal satellites of the Milky Way. These objects are perfect testbeds for the model given their approximate spherical symmetry, measured kinematics, and identified missing mass. We show that, without the assumption of a maximal deformation, Verlinde's theory can fit the velocity dispersion profile in dwarf spheroidals with no further need of an extra dark particle component. If a maximal deformation is considered, the theory leads to mass-to-light ratios that are marginally larger than expected from stellar population and formation history studies. We also compare our results with the recent phenomenological interpolating MOND function of McGaugh {\it et al}, and find a departure that, for these galaxies, is consistent with the scatter in current observations., Comment: 12 pages, 5 figures, 1 table. To appear in MNRAS

The biodegradable microneedle patch (MNP) is a novel technology for vaccine delivery that could improve the immunogenicity of vaccines. To broaden the protective efficiency of conventional influenza vaccines, a new 4M2e-tFliC fusion protein construct containing M2e sequences from different subtypes was generated. Purified fusion protein was encapsulate into MNPs with a biocompatible polymer for use as a boosting vaccine. The results demonstrated that mice receiving a conventional inactivated vaccine followed by a skin-applied dissolving 4M2e-tFliC MNP boost could better maintain the humoral antibody response than that by the conventional vaccine-prime alone. Compared with an intramuscular injection boost, mice receiving the MNP boost showed significantly enhanced cellular immune responses, hemagglutination-inhibition (HAI) titers, and neutralization titers. Increased frequency of antigen-specific plasma cells and long-lived bone marrow plasma cells was detected in the MNP boosted group as well, indicating that skin vaccination with 4M2e-tFliC facilitated a long-term antibody-mediated immunity. The 4M2e-tFliC MNP-boosted group also possessed enhanced protection against high lethal dose challenges against homologous A/PR/8/34 and A/Aichi/2/68 viruses and protection for a majority of immunized mice against a heterologous A/California/07/2009 H1N1 virus. High levels of M2e specific immune responses were observed in the 4M2e-tFliC MNP-boosted group as well. These results demonstrate that a skin-applied 4M2e-tFliC MNP boosting immunization to seasonal vaccine recipients may be a rapid approach for increasing the protective efficacy of seasonal vaccines in response to a significant drift seen in circulating viruses. The results also provide a new perspective for future exploration of universal influenza vaccines.

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features and intellectual disability caused by haploinsufficiency of the NSD1 gene. Genotype-phenotype correlations have been observed, with major anomalies seen more frequently in patients with 5q35 deletions than those with point mutations in NSD1. Though endocrine features have rarely been described, transient hyperinsulinemic hypoglycemia (HI) of the neonatal period has been reported as an uncommon presentation of Sotos syndrome. Eight cases of 5q35 deletions and one patient with an intragenic NSD1 mutation with transient HI have been reported. Here, we describe seven individuals with HI caused by NSD1 gene mutations with three having persistent hyperinsulinemic hypoglycemia. These patients with persistent HI and Sotos syndrome caused by NSD1 mutations, further dispel the hypothesis that HI is due to the deletion of other genes in the deleted 5q35 region. These patients emphasize that NSD1 haploinsufficiency is sufficient to cause HI, and suggest that Sotos syndrome should be considered in patients presenting with neonatal HI. Lastly, these patients help extend the phenotypic spectrum of Sotos syndrome to include HI as a significant feature.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with a heterogeneous phenotypic spectrum. There is an increased prevalence of monozygotic twinning in BWS. Given the epigenetic nature and phenotypic spectrum that defines BWS, twins are often discordant for clinical features, and clinicians are faced with the challenge of diagnosing and managing these twins. We present a cohort of multiple pregnancies in which one or more child from each pregnancy was diagnosed with BWS. We conducted a chart review of monochorionic and dichorionic gestations. Clinical scores for monochorionic twins demonstrated phenotypic discordance between the proband and twin. Based on linear regression analysis, a higher clinical score in the proband correlated with larger phenotypic discordance between twin siblings. Despite phenotypic discordance, however, we observed a consistent additive clinical score for a pregnancy (proband’s plus twin’s scores from a pregnancy). This idea of a finite degree of affectedness for a pregnancy implies a finite number of epigenetically affected cells. This further corroborates the idea that timing of monozygotic monochorionic twinning correlates with the disruption of establishment and/or maintenance of imprinting. The difference in clinical score between a proband and their twin may be due to diffused mosaicism, whereby there is an asymmetric distribution of affected cells among the multiple fetuses in a monozygotic monochorionic pregnancy, leading to a spectrum of variably affected phenotypes. Based on these findings, we recommend an algorithm for a conservative approach to clinically evaluate all children in a monozygotic multiple gestation affected by BWS.

We explore two possible scenarios to explain the observed gamma-ray emission associated with the atypical globular cluster Omega-Centauri: emission from millisecond pulsars (MSP) and dark matter (DM) annihilation. In the first case the total number of MSPs needed to produce the gamma-ray flux is compatible with the known (but not confirmed) MSP candidates observed in X-rays. A DM interpretation is motivated by the possibility of Omega-Centauri being the remnant core of an ancient dwarf galaxy hosting a surviving DM component. At least two annihilation channels, light quarks and muons, can plausibly produce the observed gama-ray spectrum. We outline constraints on the parameter space of DM mass versus the product of the pair-annihilation cross section and integrated squared DM density (the so-called J-factor). We translate upper limits on the dark matter content of Omega-Centauri into lower limits on the annihilation cross section. This shows s-wave annihilation into muons to be inconsistent with CMB observations, while a small window for annihilation into light quarks is allowed. Further analysis of Omega-Centauri's internal kinematics, and/or additional information on the resident MSP population will yield much stronger constraints and shed light about the origin of this otherwise mysterious gamma-ray source., Comment: 13 pages, 5 figures

A scalar field $\phi$ endowed with a trigonometric potential has been proposed to play the role of Dark Matter. A deep study of the cosmological evolution of linear perturbations, and its comparison to the Cold Dark Matter (CDM) and Fuzzy Dark Matter (FDM) cases (scalar field with quadratic potential), reveals an enhancement in the amplitude of the mass power spectrum for large wave numbers due to the non-linearity of the axion-like potential. For the first time, we study the scale-dependence on physical quantities such as the growth factor $D_k$, the velocity growth factor $f_k$, and $f_k \sigma_8$. We found that for $z, Comment: 43 pages, 17 figures. Updated data, new appendix. Matches version accepted in JCAP