Lorenzo D. Botto

Background: Population‐based data on healthcare utilization in adults with congenital heart disease (CHD) are limited. We examined utilization patterns in a multi‐site, population‐based U.S. cohort of adults with CHD. Methods: This retrospective cohort linked health and administrative records from five regions (Colorado, North Carolina, Utah, metropolitan Atlanta, and New York). Adults aged 19–64 years with at least one CHD‐related ICD‐9‐CM code recorded during 2011–2013 were included. We evaluated inpatient, emergency department (ED), outpatient, and cardiology outpatient encounters, as well as cardiac diagnostic/imaging, therapeutic/interventional, and vascular procedures. Multivariable mixed‐effects logistic regression models compared utilization by CHD severity (severe vs. non‐severe), adjusting for sex, race/ethnicity, insurance, comorbidity, and site, and including age group as an effect modifier. Results: Over 3 years, this cohort of 18,877 adults (20.7% severe CHD), 45.9% had at least one hospitalization, 35.1% had an ED visit, 92.1% had an outpatient encounter, and 43.8% had a cardiology outpatient visit. Cardiac diagnostic/imaging procedures occurred in 67.8%, cardiac interventions in 20.3%, and vascular procedures in 10.5%. Severe CHD was associated with higher odds of cardiac procedures but lower odds of ED use than non‐severe CHD. Age modified these associations, and site‐level variation was marked, with cardiology visit rates ranging from 21% to 59%. Conclusions: Adults with CHD had high healthcare utilization, including frequent ED use, yet fewer than half saw a cardiology specialist, particularly at older ages. These findings highlight persistent gaps in lifelong care and substantial geographic variation, underscoring the need to improve access to specialized care for adults with CHD.

The 51st Annual Meeting of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) was held from 2 to 5 November 2025 in Magaliesburg, South Africa. The meeting brought together clinicians, epidemiologists, public health practitioners and researchers from 24 countries to discuss advances in the surveillance, prevention, and management of birth defects. Hosting the meeting in South Africa reflected a strategic effort to strengthen engagement with low- and middle-income countries and to expand African participation in global birth defects surveillance initiatives. Scientific sessions addressed methodological developments in surveillance systems, etiological research, and approaches to improving the interpretation and communication of surveillance data for policy and public health action. Emphasis was placed on strengthening data quality, harmonising case definitions and reporting practices across registries, and building technical capacity in emerging surveillance programmes. Contributions from African researchers highlighted both the challenges and opportunities associated with implementing surveillance in resource-constrained settings. The meeting underscored the importance of international collaboration, inclusive surveillance networks, and effective translation of data into prevention strategies and health system planning. Strengthening global surveillance remains essential for informing prevention efforts and improving outcomes for children and families affected by birth defects.

Background: Total anomalous pulmonary venous return (TAPVR) is a rare heart defect in which the pulmonary veins do not connect to the left atrium, instead draining into the right atrium or directly into other venous systems. We explored factors associated with TAPVR using the National Birth Defects Prevention Study (NBDPS; 1997–2011) and Birth Defects Study To Evaluate Pregnancy exposureS (BD‐STEPS; 2014–2021) data. Methods: We identified potential risk or protective factors from the literature and used logistic regression to calculate crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between 22 factors encompassing maternal demographics, health history, and medication use and TAPVR. In an exploratory analysis among the subset of NBDPS cases and controls, we examined 163 potential factors using random forest. Results: In the primary analysis including 393 cases with TAPVR and 13,914 non‐malformed controls, we observed positive associations between TAPVR and maternal age at delivery < 20 (OR 2.00; 95% CI 1.30–3.06) and 20–24 (1.62; 1.19–2.22) vs. 25–29 years, having one (1.40; 1.07–1.82) and two or more previous live births (1.69; 1.25–2.27) vs. none, and multiple gestation (1.85; 1.11–2.92). Non‐Hispanic Black mothers had the lowest risk (0.55; 0.35–0.85) while mothers of other races/ethnicities had the highest risk (1.72; 1.19–2.44) compared to non‐Hispanic White mothers. The random forest identified an inverse effect of maternal fish consumption. Conclusions: Our findings confirmed previously observed associations of younger maternal age and having previous live births with TAPVR. Maternal fish consumption may confer a protective effect and deserves further investigation.

The density of individual particles is commonly assessed experimentally by quantifying the settling velocity of a collection of particles transferred into a settling column and allowed to settle under the action of gravity. The individual settling velocities of the particles are recorded close to the bottom of the settling column, in a region where it is assumed that the particles have reached their Stokes terminal velocity after the particle cloud has broken up. In the present study we use numerical particle-based simulations in the Stokes regime to demonstrate that this fundamental assumption might not be fulfilled in practice. Even at low volume fraction of monodisperse spheres, a large deviation from the Stokes settling velocity was found. In the case of a collection of polydisperse spheres, a distinction could be made between particles belonging to a cloud, and particles trailing the cloud. It was found that the velocity of the largest trail particles is reasonably close to their Stokes settling velocity. However, the particles close to the core of the cloud can have velocities more than ten times their Stokes velocities, making the use of the single-particle Stokes velocity based on the core particle not suitable to extract the particle density without corrections. An expression based on the local volume fraction, the cloud radius and the particle settling velocity in the cloud is proposed to estimate the single-particle Stokes settling velocity, and therefrom the particle density.

The viscosity of nanoparticle suspensions is always expected to increase with particle concentration. However, a growing body of experiments on suspensions of atomically thin nanomaterials such as graphene contradicts this expectation. Some experiments indicate effective suspension viscosities below that of pure solvent at high shear rates and low solid concentrations, i.e., the intrinsic viscosity is negative. Using molecular dynamics simulations, we investigate the shear viscosity of few-nanometer graphene sheets in water at high Péclet numbers (Pe ≥ 100), for aspect ratios from 4.5 to 12.0. These simulations robustly confirm that the intrinsic viscosity decreases with increasing aspect ratio and becomes negative beyond a threshold ≈5.5, providing a molecular-level confirmation of this behavior in a realistic graphene-water system. Comparison with continuum boundary integral modeling shows quantitative agreement in the dilute regime, confirming the effect is hydrodynamic in origin. We demonstrate that this anomalous behavior originates from hydrodynamic slip at the liquid-solid interface, which suppresses particle rotation and promotes stable alignment with the flow direction, thereby reducing viscous dissipation relative to dissipation in pure solvent. This slip mechanism holds for both fully 3D disc-like and quasi-2D particle geometries explored in the molecular simulations. As the concentration of graphene particles increases in the dilute regime, the viscosity initially decreases, falling below that of pure water. At higher concentrations, however, particle aggregation becomes significant, leading to a rise in viscosity after a minimum is reached. Our work has important implications for the design of lubricants, inks, and nanocomposites with tunable viscosity.

Background: Survival of individuals with congenital heart disease (CHD) has improved, leading to a growing and aging population of adults living with these conditions. Over their lifetime, they often face an array of comorbidities that affect outcomes and complicate medical management. However, population‐based information on such comorbidities is scarce, reducing opportunities for prevention. Methods: This population‐based, cross‐sectional study assessed comorbid conditions in adults with CHD residing in five geographic areas in the United States (in Colorado, Georgia, New York, North Carolina, and Utah). The study included 18,672 adults aged 19 to 64 years who had a healthcare encounter between 2011 and 2013 associated with ≥ 1 CHD‐related diagnosis code. Data were derived from linked clinical and administrative sources, reflecting inpatient, outpatient, and emergency department encounters. Results: Most adults with CHD experienced at least one (88.5%) and usually multiple (76%) comorbidities. Overall, noncardiac comorbidities exceeded cardiac comorbidities. The most frequent noncardiac comorbidities were endocrine/metabolic conditions (e.g., diabetes, hyperlipidemia, hypothyroidism), hypertension, and neuropsychiatric conditions (e.g., anxiety, depression). The presence and number of comorbidities varied in different sociodemographic groups. Men and older individuals experienced higher rates of many comorbidities, cardiac and noncardiac, regardless of CHD type. Conclusions: Preventable and treatable comorbidity and multimorbidity are common in adults with CHD, with patterns shaped by sociodemographic factors and CHD type. Reducing preventable mortality in this growing population will require sustained tracking of health metrics and coordinated, data‐driven, and lifelong care.

Rothmund–Thomson syndrome (RTS) is an ultra‐rare, genetically heterogeneous autosomal recessive genodermatosis characterized by poikiloderma, sparse hair and eyebrows, photosensitivity, and short stature. The recently described RTS type 4 (RTS‐4), caused by biallelic variants in the DNA2 gene, is associated with additional distinctive features such as microphthalmia, corneal opacity, congenital cataracts (rather than juvenile), and hypothyroidism. To date, eight individuals with RTS‐4 have been reported, all carrying a deep intronic variant in DNA2 (ENST00000358410.8:c.588‐2214A>G) and originating from Brazilian or Portuguese ethnic backgrounds. We present the first patient with RTS‐4 outside these ethnic backgrounds, harboring the same deep intronic DNA2 variant (ENST00000358410.8:c.588‐2214A>G) in combination with a novel pathogenic variant (ENST00000358410.8:c.2519 T>C, Leu840Pro). This patient expands the molecular spectrum of RTS‐4 and underscores the critical role of genome sequencing in identifying pathogenic deep intronic variants. Additionally, the patient's response to recombinant human growth hormone treatment is described. Finally, this patient, undiagnosed for several years, was solved through an international effort at the 2024 Undiagnosed Hackathon, highlighting the value of international cooperation and resource sharing toward ensuring that no patient remains undiagnosed.

Diamond-Blackfan anemia syndrome (DBAS) is a rare congenital disorder with variable penetrance and expressivity and is characterized by pure red cell aplasia that typically manifests as early-onset chronic macrocytic or normocytic anemia and is often associated with other congenital anomalies. DBAS is etiologically heterogeneous with >20 known DBAS-associated genes that encode small and large ribosomal protein subunits and an inheritance pattern that is largely autosomal dominant or sporadic. We report 2 DBAS cases with previous negative genetic testing, which included targeted gene panels, karyotype analysis, chromosome breakage analysis, and whole exome sequencing. Although clinical whole genome sequencing (WGS) was initially negative, in-depth reanalysis identified 2 novel noncoding variants in the RPS gene family, namely a maternally inherited splicing variant at the end of the first noncoding exon in RPS7 (NM_001011.4, c.-19G>C) in family 1 and a deep intronic de novo variant in RPS19 (NM_001022.4, c.172+350C>T) in family 2. In family 1, several maternal relatives were identified who shared the same variant through cascade testing; clinically, they exhibited variable degrees of anemia and elevated erythrocyte adenosine deaminase activity, a marker for DBAS. RNA sequencing analysis demonstrated deleterious functional consequences for both noncoding variants. In case 1, hematopoietic stem cell transplant with an unaffected matched sibling donor who did not carry the variant successfully cured the congenital anemia. This study identified novel noncoding variants and underscores the clinical utility of WGS in accelerating diagnosis and improving care for rare genetic disorders, particularly when timely treatment decisions are critically important.

Gorlin‐Goltz Syndrome (GGS) is a rare autosomal dominant genetic disorder encompassing a diverse range of clinical manifestations, including congenital anomalies and predisposition to cancer. Pathogenic variants in PTCH1 and SUFU account for up to 79% and 6% of cases, respectively. Currently, an estimated 15%–27% of individuals with a clinical diagnosis of GGS do not have a pathogenic variant identified in either gene. We report on a 17‐year‐old female referred to the Undiagnosed Disease Network with a clinical diagnosis of GGS that manifested as both classic and unusual findings, including isolated hypogonadotropic hypogonadism and anosmia (Kallmann syndrome), orofacial cleft, and abnormal semicircular canals (SCC). Prior genetic testing, including a targeted gene panel, genomic microarray, exome sequencing, and genome sequencing, was non‐diagnostic, although these studies identified a variant of uncertain significance in CHD7, which may have contributed to elements of the phenotype (e.g., abnormal SCC). Reanalysis of genome sequencing data using research analytic methods, together with karyotyping, FISH, and Sanger sequencing, identified a novel de novo paracentric inversion that truncated PTCH1. These findings underscore the value of in‐depth phenotype‐guided genomic analysis, including chromosomal structural variants, as well as the occurrence of possible dual genetic diagnoses in the same individuals. Moreover, the definitive diagnosis provided the patient and family with a firmer basis for management and counseling.

Faster evaporation leads to higher buckling modes in dried graphene oxide capsules.