Genomic sequencing in diverse and underserved pediatric populations: parent perspectives on understanding, uncertainty, psychosocial impact, and personal utility of results.

Purpose: Limited evidence evaluates parents' perceptions of their child's clinical genomic sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research (CSER) consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap.

Methods: Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure.

Newborn screening for common genetic variants associated with permanent hearing loss: Implementation in Ontario and a review of the first 3 years.

Purpose: Universal newborn hearing screening (UNHS) programs using audiometric techniques alone are limited in ability to detect non-congenital childhood permanent hearing loss (PHL). In 2019, Ontario launched universal newborn screening (NBS) for PHL risk factors: congenital cytomegalovirus (cCMV) and 22 common variants in GJB2 and SLC26A4. Here we describe our experience with genetic risk factor screening.

Pyridine polymer tubular structures connected with polyoxometalates as bifunctional electrocatalysts for water splitting.

In this work, we successfully prepared four POM-based organic-inorganic hybrids, namely, [(CHN)(CHN)][PMoO] (1), [(CHN)(CHN)][PMoO] (2), [(CHN)][PMoO]·4HO (3), and [(CHN)][PMoO] (4) (where CHN = pyridine, CHN = pyrazine, CHN = 2,7-diamino-1,3,4,6,8,9-hexaazaspiro[4.4] nonane, and CHN = 3-amino-1,2,4-triazole), using a hydrothermal method. Compounds 1 and 2 exhibited a lamellar three-dimensional structure.

BaNDyT: Bayesian Network Modeling of Molecular Dynamics Trajectories.

Bayesian network modeling (BN modeling, or BNM) is an interpretable machine learning method for constructing probabilistic graphical models from the data. In recent years, it has been extensively applied to diverse types of biomedical data sets. Concurrently, our ability to perform long-time scale molecular dynamics (MD) simulations on proteins and other materials has increased exponentially.

Effects of the Transcutaneous Electrical Stimulation System on Heartburn, Regurgitation and Esophageal Acid Exposure in GERD Patients-An Uncontrolled Feasibility Study.

Background: Proton pump inhibitors (PPI) for gastroesophageal reflux disease (GERD) are associated with a high failure rate. Our uncontrolled feasibility study aimed determining the effect of a transcutaneous electrical stimulation system (TESS) on GERD symptoms and acid exposure time (AET).

Methods: Recruited patients with heartburn and regurgitation.

Discovery of New Benzohydrazide Derivatives Containing 4-Aminoquinazoline as Effective Agricultural Fungicides, the Related Mechanistic Study, and Safety Assessment.

A total of 38 new benzohydrazide derivatives bearing the 4-aminoquinazoline moiety were designed and synthesized based on the active subunit combination approach and tested in detail for their inhibition activities against eight agricultural phytopathogenic fungi. The bioassay results indicated that many of the synthesized compounds exhibited extraordinary fungicidal activities in vitro against the tested fungi. For example, compounds , , , and had EC (half-maximal effective concentration) values of 0.

Pegloticase and Methotrexate Cotherapy in Patients With Uncontrolled Gout With Prior Pegloticase Monotherapy Failure: Findings of an Open-Label Trial.

Objective: Patients with uncontrolled gout have few treatment options. Pegloticase lowers serum urate (SU) levels, but antidrug antibodies limit SU-lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) cotherapy increases pegloticase response rates and lowers IR risk in pegloticase-naïve patients.

Characteristics of Resection Parameters in Robot-Assisted Total Knee Arthroplasty With the Ligament Balancing Workflow.

Objective: Robotic-assisted total knee arthroplasty (TKA) is a novel orthopedic technique. The workflow of robotic-assisted TKA is quite different from that of traditional manual TKA and may result incompletely different resection parameters. Understanding these parameters may help surgeons better perform robotic-assisted TKA.

Assessing spatial sequencing and imaging approaches to capture the molecular and pathological heterogeneity of archived cancer tissues.

Spatial transcriptomics (ST) offers enormous potential to decipher the biological and pathological heterogeneity in precious archival cancer tissues. Traditionally, these tissues have rarely been used and only examined at a low throughput, most commonly by histopathological staining. ST adds thousands of times as many molecular features to histopathological images, but critical technical issues and limitations require more assessment of how ST performs on fixed archival tissues.

Regulation of Zinc Hydroxide Sulfate Growth Environment for Stable Zinc Anode/Electrolyte Interfaces.

Metallic Zn is a promising anode for high-safety, low-cost, and large-scale energy storage systems. However, it is strongly hindered by unstable electrode/electrolyte interface issues, including zinc dendrite, corrosion, passivation, and hydrogen evolution reactions. In this work, an in situ interface protection strategy is established by turning the corrosion/passivation byproducts (zinc hydroxide sulfates, ZHSs) into a stable hybrid protection layer.

MRI detects tubulointerstitial changes in mouse models of radiation-induced nephropathy.

Purpose: We hypothesized that radiation-induced tubulointerstitial changes in the kidney can be assessed using MRI-based T relaxation time measurements.

Methods: We performed MRI, histology, and serum biochemistry in two mouse models of radiation nephropathy: one involving external beam radiotherapy and the other using internal irradiation with an α-particle-emitting actinium-225 radiolabeled antibody. We compared the mean T values of different renal compartments between control and external beam radiotherapy or α-particle-emitting actinium-225 radiolabeled antibody-treated groups and between the two radiation-treated groups using a Wilcoxon rank-sum test.

Structural insights into the role of the prosegment binding loop in a papain-superfamily cysteine protease from Treponema denticola.

Periodontal diseases afflict 20-50% of the global population and carry serious health and economic burdens. Chronic periodontitis is characterized by inflammation of the periodontal pocket caused by dysbiosis. This dysbiosis is coupled with an increase in the population of Treponema denticola, a spirochete bacterium with high mobility and invasivity mediated by a number of virulence factors.

Vertical Graphene Growth on LDH Nanosheets and Carbon Cloth Nanofibers with NiCo Nanoparticles as a Freestanding Host for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur batteries have been recognized as one of the excellent candidates for next-generation energy storage batteries because of their high energy density and low cost and low pollution. However, lithium-sulfur batteries have been challenged by low conductivity, low sulfur utilization, poor cycle life, and the shuttle effect of polysulfides. To address these problems, we report here an independent mixed sulfur host.

Maternal Incarceration and Health Risk Behaviors Among Adolescents: A Latent Class Analysis.

Most studies on the impact of maternal incarceration on adolescent health risk behaviors have focused on singular, separated behaviors, even though these behaviors often cluster and co-occur. This study used the FFCWS dataset to examine the association between maternal incarceration and the aggregation of health risk behaviors among adolescents. Latent class analysis suggested the four-class model had the optimal model fit.

Anti-arthritic potential of crude sulfated polysaccharide from marine macroalgae (Turner) C. Agardh: Regulation of cytokine cascade.

Seaweeds have been utilized as food, fodder, fertilizer, and medicine since ancient times; nevertheless, they have received only a little attention. In the current work, we extracted the sulfated polysaccharide from a marine source and investigated its anti-arthritic potential . The isolated and freeze-dried polysaccharide was tested for acute oral toxicity based on OECD 423.

Adaptive functioning in children and young adults with monogenic neurodevelopmental disorders.

Aim: To examine the adaptive behaviour profiles of children with monogenic neurodevelopmental disorders (NDDs) to determine whether syndrome-specific or transdiagnostic approaches provide a better understanding of the adaptive behavioural phenotypes of these NDDs.

Method: This cross-sectional study included parents and caregivers of 243 (48% female) individuals (age range = 1-25 years; mean = 8 years 10 months, SD = 5 years 8 months) with genetically confirmed monogenic NDDs (CDK13, DYRK1A, FOXP2, KAT6A, KANSL1, SETBP1, BRPF1, and DDX3X). Parents and caregivers completed the Vineland Adaptive Behavior Scales, Third Edition to assess communication, daily living, socialization, and motor skills.

Multifaceted Links Between Microbial Carbon Use Efficiency and Soil Organic Carbon Sequestration.

Conceptual framework to unlock the mechanisms for microbial carbon use efficiency and SOC formation.

Increasing Contraception Documentation in an Academic Rheumatology Clinic: A Quality Improvement Approach.

Objective: This quality improvement initiative aimed to increase the rate of provider screening and documentation of contraception use for reproductive-aged women seen in an academic rheumatology fellows' clinic to >50% by 24 weeks, with sustained improvement at one year.

Methods: With a multidisciplinary team, we devised and implemented six interventional cycles over 24 weeks informed by key stakeholder survey responses. The primary outcome measure was the percentage of eligible visits with contraception information documented in the structured electronic health record field.

A Combination of Conventional Transconjunctival Lower Blepharoplasty and Percutaneous Nanofat Grafting in a Young Chinese Population With Eyelid Bags and Tear Trough Deformities.

Objective: A simple and minimally invasive combined procedure, including transconjunctival orbital fat removal and transcutaneous resected orbital fat injection, was performed based on the anatomical characteristics of the lower eyelids in our young Chinese patients. Our study aimed to investigate the efficacy and safety of this procedure in our study population.

Methods: In our retrospective study, a total of 183 consecutive patients underwent a combination of traditional transconjunctival blepharoplasty and nanofat grafting between February 2020 and June 2024.

Perspectives of Rehabilitation Professionals on Long COVID Interventions to Facilitate Return-to-Work.

The severe functional impact of long COVID presents a significant challenge for clients seeking to return to work. Despite emerging clinical management guidelines, long COVID remains a concern in the rehabilitation field. There is a need to establish optimal practices for sustainable rehabilitation paths that enhance the recovery of clients with long COVID, all while understanding the challenges faced by rehabilitation professionals working with this population.

Advances and applications of genome-edited animal models for severe combined immunodeficiency.

Severe combined immunodeficiency disease (SCID), characterized by profound immune system dysfunction, can lead to life-threatening infections and death. Animal models play a pivotal role in elucidating biological processes and advancing therapeutic strategies. Recent advances in gene-editing technologies, including zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), CRISPR/Cas9, and base editing, have significantly enhanced the generation of SCID models.

Functional evolution of thyrotropin-releasing hormone neuropeptides: Insights from an echinoderm.

Feeding behavior is regulated by a complex network of endogenous neuropeptides. In chordates, this role is suggested to be under the control of diverse factors including thyrotropin-releasing hormone (TRH). However, whether this regulatory activity of TRH is functionally conserved in non-chordate metazoans, and to what extent this process is underpinned by interactions of TRH with other neuropeptides such as cholecystokinin (CCK, known as a satiety signal), remain unclear.

Elevated CXCL1 triggers dopaminergic neuronal loss in the substantia nigra of C57BL/6J mice: Evaluation of a novel Parkinsonian mouse model.

Substantial evidence points to the early onset of peripheral inflammation in the development of Parkinson's disease (PD), supporting the "body-first" hypothesis. However, there remains a notable absence of PD-specific animal models induced by inflammatory cytokines. This study introduces a novel mouse model of PD driven by the proinflammatory cytokine CXCL1, identified in our previous research.

Intranasal iron administration induces iron deposition, immunoactivation, and cell-specific vulnerability in the olfactory bulb of C57BL/6 mice.

Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function; however, its abnormal accumulation is also implicated in various neurological disorders. The olfactory bulb (OB), an early target in neurodegenerative diseases, acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles. This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate (FAC).

Cross-species single-cell transcriptomics reveals neuronal similarities and heterogeneity in amniote pallium.

The amniote pallium, a vital component of the forebrain, exhibits considerable evolutionary divergence across species and mediates diverse functions, including sensory processing, memory formation, and learning. However, the relationships among pallial subregions in different species remain poorly characterized, particularly regarding the identification of homologous neurons and their transcriptional signatures. In this study, we utilized single-nucleus RNA sequencing to examine over 130 000 nuclei from the macaque ( ) neocortex, complemented by datasets from humans ( ), mice ( ), zebra finches ( ), turtles ( ), and lizards ( s), enabling comprehensive cross-species comparison.