Association between fine particulate matter (PM) and infant mortality in a North Carolina birth cohort (2003-2015).

Background: While the association between fine particulate matter (PM) and adult mortality is well established, few studies have examined the association between long-term PM exposure and infant mortality.

Methods: We conducted an unmatched case-control study of 5992 infant mortality cases and 60,000 randomly selected controls from a North Carolina birth cohort (2003-2015). PM during critical exposure periods (trimesters, pregnancy, first month alive) was estimated using residential address and a national spatiotemporal model at census block centroid.

Regulatory elements in (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits.

Purpose: The etiopathogenesis of coronal nonsyndromic craniosynostosis (cNCS), a congenital condition defined by premature fusion of 1 or both coronal sutures, remains largely unknown.

Methods: We conducted the largest genome-wide association study of cNCS followed by replication, fine mapping, and functional validation of the most significant region using zebrafish animal model.

Results: Genome-wide association study identified 6 independent genome-wide-significant risk alleles, 4 on chromosome 7q21.

Long-term ambient sulfur dioxide exposure during gestation and preterm birth in North Carolina, 2003-2015.

Background: Coal-fired power plants are major contributors of ambient sulfur dioxide (SO) air pollution. Epidemiological literature suggests an adverse association between SO exposure during gestation and preterm birth (PTB; <37 weeks completed gestation). PTB is strongly associated with infant mortality and increased risk for later life morbidities.

SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.

While it is widely thought that de novo mutations (DNMs) occur randomly, we previously showed that some DNMs are enriched because they are positively selected in the testes of aging men. These "selfish" mutations cause disorders with a shared presentation of features, including exclusive paternal origin, significant increase of the father's age, and high apparent germline mutation rate. To date, all known selfish mutations cluster within the components of the RTK-RAS-MAPK signaling pathway, a critical modulator of testicular homeostasis.

A Comparison of Structural Variant Calling from Short-Read and Nanopore-Based Whole-Genome Sequencing Using Optical Genome Mapping as a Benchmark.

The identification of structural variants (SVs) in genomic data represents an ongoing challenge because of difficulties in reliable SV calling leading to reduced sensitivity and specificity. We prepared high-quality DNA from 9 parent-child trios, who had previously undergone short-read whole-genome sequencing (Illumina platform) as part of the Genomics England 100,000 Genomes Project. We reanalysed the genomes using both Bionano optical genome mapping (OGM; 8 probands and one trio) and Nanopore long-read sequencing (Oxford Nanopore Technologies [ONT] platform; all samples).

Cell cycle-dependent centrosome clustering precedes proplatelet formation.

Platelet-producing megakaryocytes (MKs) primarily reside in the bone marrow, where they duplicate their DNA content with each cell cycle resulting in polyploid cells with an intricate demarcation membrane system. While key elements of the cytoskeletal reorganizations during proplatelet formation have been identified, what initiates the release of platelets into vessel sinusoids remains largely elusive. Using a cell cycle indicator, we observed a unique phenomenon, during which amplified centrosomes in MKs underwent clustering following mitosis, closely followed by proplatelet formation, which exclusively occurred in G of interphase.

Reassessing the association: Evaluation of a polyalanine deletion variant of RUNX2 in non-syndromic sagittal and metopic craniosynostosis.

The RUNT-related transcription factor RUNX2 plays a critical role in osteoblast differentiation, and alterations to gene dosage cause distinct craniofacial anomalies. Uniquely amongst the RUNT-related family, vertebrate RUNX2 encodes a polyglutamine/polyalanine repeat (Gln-Glu-Ala in humans), with the length of the polyalanine component completely conserved in great apes. Surprisingly, a frequent 6-amino acid deletion polymorphism, p.

The phenotype of MEGF8-related Carpenter syndrome (CRPT2) is refined through the identification of eight new patients.

Carpenter syndrome (CRPTS) is a rare autosomal recessive condition caused by biallelic variants in genes that encode negative regulators of hedgehog signalling (RAB23 [CRPT1] or, more rarely, MEGF8 [CRPT2]), and is characterised by craniosynostosis, polysyndactyly, and other congenital abnormalities. We describe a further six families comprising eight individuals with MEGF8-associated CRPT2, increasing the total number of reported cases to fifteen, and refine the phenotype of CRPT2 compared to CRPT1. The core features of craniosynostosis, polysyndactyly and (in males) cryptorchidism are almost universal in both CRPT1 and CRPT2.

BTB domain mutations perturbing KCTD15 oligomerisation cause a distinctive frontonasal dysplasia syndrome.

Introduction: encodes an oligomeric BTB domain protein reported to inhibit neural crest formation through repression of Wnt/beta-catenin signalling, as well as transactivation by TFAP2. Heterozygous missense variants in the closely related paralogue KCTD1 cause scalp-ear-nipple syndrome.

Methods: Exome sequencing was performed on a two-generation family affected by a distinctive phenotype comprising a lipomatous frontonasal malformation, anosmia, cutis aplasia of the scalp and/or sparse hair, and congenital heart disease.

Homozygous variants in two unrelated patients with craniosynostosis and radioulnar synostosis.

Background: encodes an intracellular inhibitor of the bone morphogenetic protein (BMP) signalling pathway. Until now, rare heterozygous loss-of-function variants in were demonstrated to increase the risk of disparate clinical disorders including cardiovascular disease, craniosynostosis and radioulnar synostosis. Only two unrelated patients harbouring biallelic variants presenting a complex cardiovascular phenotype and facial dysmorphism have been described.

Dynamic actin/septin network in megakaryocytes coordinates proplatelet elaboration.

Megakaryocytes (MK) undergo extensive cytoskeletal rearrangements as they give rise to platelets. While cortical microtubule sliding has been implicated in proplatelet formation, the role of the actin cytoskeleton in proplatelet elongation is less understood. It is assumed that actin filament reorganization is important for platelet generation given that mouse models with mutations in actin-associated proteins exhibit thrombocytopenia.

Factors associated with per- and polyfluoroalkyl substances (PFAS) serum concentrations in residents of New Hanover County, North Carolina: The GenX exposure study.

In 2017, people living in New Hanover County, North Carolina, learned that for ∼40 years they were unknowingly exposed to per- and polyfluoroalkyl substances (PFAS) through drinking water sourced by the Cape Fear River. Using data from the GenX Exposure Study, which measured serum PFAS levels in county residents, we aimed to understand questionnaire-measured factors associated with serum PFAS levels. Because most residents were served by the same municipal water source, we focused on surrogate factors of drinking water exposure that may contribute to variability in PFAS levels.

Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project.

Background: Current clinical testing methods used to uncover the genetic basis of rare disease have inherent limitations, which can lead to causative pathogenic variants being missed. Within the rare disease arm of the 100 000 Genomes Project (100kGP), families were recruited under the clinical indication 'single autosomal recessive mutation in rare disease'. These participants presented with strong clinical suspicion for a specific autosomal recessive disorder, but only one suspected pathogenic variant had been identified through standard-of-care testing.

Affordable method for measuring fluorescence using Gaussian distributions and bounded MESE.

We present an accurate and low-cost method for measuring fluorescence in materials. Our method outputs an estimate of the material's Donaldson matrix, which is a commonly used two-dimensional spectral characterization of its fluorescence and reflectance properties. To find the estimate, only a few measurements of the material's reflectance under a few illuminants are needed, which we demonstrate using low-cost optical components.

Short-term exposure to air pollution and infant mortality: A systematic review and meta-analysis.

Background And Aim: Infant mortality is a widely reported indicator of population health and a leading public health concern. In this systematic review and meta-analysis, we review the available literature for epidemiologic evidence of the association between short-term air pollution exposure and infant mortality.

Methods: Relevant publications were identified through PubMed and Web of Science databases using comprehensive search terms and screened using predefined inclusion/exclusion criteria.

Delivery of acute ischaemic stroke treatments in the European region in 2019 and 2020.

Introduction: We assessed best available data on access and delivery of acute stroke unit (SU) care, intravenous thrombolysis (IVT) and endovascular treatment (EVT) in the European region in 2019 and 2020.

Patients And Methods: We compared national data per number of inhabitants and per 100 annual incident first-ever ischaemic strokes (AIIS) in 46 countries. Population estimates and ischaemic stroke incidence were based on United Nations data and the Global Burden of Disease Report 2019, respectively.

Development of Erf-Mediated Craniosynostosis and Pharmacological Amelioration.

ETS2 repressor factor () insufficiency causes craniosynostosis (CRS4) in humans and mice. ERF is an ETS domain transcriptional repressor regulated by Erk1/2 phosphorylation via nucleo-cytoplasmic shuttling. Here, we analyze the onset and development of the craniosynostosis phenotype in an Erf-insufficient mouse model and evaluate the potential of the residual Erf activity augmented by pharmacological compounds to ameliorate the disease.

Sulfur dioxide reduction at coal-fired power plants in North Carolina and associations with preterm birth among surrounding residents.

Unlabelled: Coal-fired power plants (CFPP) are major contributors of air pollution, including the majority of anthropogenic sulfur dioxide (SO) emissions, which have been associated with preterm birth (PTB). To address a 2002 North Carolina (NC) policy, 14 of the largest NC CFPPs either installed desulfurization equipment (scrubbers) or retired coal units, resulting in substantial reductions of SO air emissions. We investigated whether SO air emission reduction strategies at CFPPs in NC were associated with changes in prevalence of PTB in nearby communities.