The Role of and Ultra-Rare Variants in Hirschsprung Disease (HSCR): Extended Gene Discovery for Risk Profiling of Patients.

Background: Hirschsprung disease (HSCR) is a rare neurodevelopmental disorder caused by disrupted migration and proliferation of enteric neural crest cells during enteric nervous system development. Genetic studies suggest a complex etiology involving both rare and common variants, but the contribution of ultra-rare pathogenic variants (PAs) remains poorly understood.

Methods: We perform whole-exome sequencing (WES) on 301 HSCR probands and 109 family trios, employing advanced statistical methods and gene prioritization strategies to identify genes carrying and ultra-rare coding pathogenic variants.

Friends and foes: symbiotic and algicidal bacterial influence on blooms.

Harmful Algal Blooms (HABs) of the toxigenic dinoflagellate (KB) are pivotal in structuring the ecosystem of the Gulf of Mexico (GoM), decimating coastal ecology, local economies, and human health. Bacterial communities associated with toxigenic phytoplankton species play an important role in influencing toxin production in the laboratory, supplying essential factors to phytoplankton and even killing blooming species. However, our knowledge of the prevalence of these mechanisms during HAB events is limited, especially for KB blooms.

Intrahemispheric White Matter Asymmetries and Interhemispheric Connections Underlying the Lateralization of Language Production and Spatial Attention in Left-Handers.

Leftward language production and rightward spatial attention are salient features of functional organization in most humans, but their anatomical basis remains unclear. Interhemispheric connections and intrahemispheric white matter asymmetries have been proposed as important factors underlying functional lateralization. To investigate the role of white matter connectivity in functional lateralization, we first identified 96 left-handers using visual half field naming tasks.

Predictive acoustical processing in human cortical layers.

In our dynamic environments, predictive processing is vital for auditory perception and its associated behaviors. Predictive coding formalizes inferential processes by implementing them as information exchange across cortical layers and areas. With laminar-specific blood oxygenation level dependent we measured responses to a cascading oddball paradigm, to ground predictive auditory processes on the mesoscopic human cortical architecture.

Temporal and Notch identity determine layer targeting and synapse location of medulla neurons.

How specification mechanisms that generate neural diversity translate into specific neuronal targeting, connectivity, and function in the adult brain is not understood. In the medulla region of the optic lobe, neural progenitors generate different neurons in a fixed order by sequentially expressing a series of temporal transcription factors as they age. Then, Notch signaling in intermediate progenitors further diversifies neuronal progeny.

Culturally Congruent Latino-Adapted Telemonitoring of Underrepresented Adults With Type 2 Diabetes: The CULTURA-DM2 Trial.

This study reports on the development and testing of a comprehensive diabetes telemonitoring program tailored to meet the needs of underserved Hispanic/Latino patients with diabetes. Individuals participating in the culturally tailored program had significantly better 6-month outcomes than those receiving comprehensive outpatient management for A1C, blood pressure, and diabetes self-efficacy, with no differences between groups in quality of life, medication adherence, emotional functioning, patient activation, or unscheduled physician visits. These findings suggest that culturally congruent diabetes telemonitoring may be effective for this underserved population.

Associations between social behaviour and proinflammatory immune activation are modulated by age in a free-ranging primate population.

The effect of the social environment on the proinflammatory immune response may mediate the relationship between social environment and fitness but remains understudied outside captive animals and human populations. Age can also influence both immune function and social behaviour, and hence may modulate their relationships. This study investigates the role of social interactions in driving the concentrations of two urinary markers of proinflammatory immune activation, neopterin and soluble urokinase plasminogen activator receptor (suPAR), in a free-ranging population of rhesus macaques, .

Low-concentration atropine (0.01%) on quantitative contrast sensitivity function in Chinese children with myopia.

Aim: To investigate the effect of 0.01% low-concentration atropine (LA) on quantitative contrast sensitivity function (qCSF) in children with myopia.

Methods: This paired case-control study included 90 eyes of 58 children who were sex-, age-, and refraction-matched and equally divided into two groups: the 0.

The Relationship Between School Connectedness and Bullying in U.S. High School Students.

The relationship between school connectedness and bullying among a cohort of American high school students in the COVID and post-COVID eras has yet to be studied. Data from the 2021 Youth Risk Behavior Survey were analyzed to gain insight into this association. Weighted percentages were calculated, and multivariable logistic regression was conducted.

Impact of Pediatric Palliative Care on Goal Concordant Care in the Neonatal Intensive Care Unit.

Context: Little is known about the prevalence of goal-concordant care (GCC) in the NICU and whether it can be measured from chart data.

Objectives: To determine if GCC can be evaluated using chart data, to identify factors associated with GCC, and to evaluate the impact of pediatric palliative care (PPC) consultation on GCC.

Methods: Retrospective review of infants who died in a level IV NICU over a 10-year period (2014-2024).

Metabolic dysfunction in mice with adipocyte specific ablation of the adenosine A2A receptor.

It has been well established that adenosine plays a key role in the control of inflammation through G protein coupled receptors and recently shown that it can regulate thermogenesis. Here we investigated the specific requirements of the adenosine A2A receptor (A2AR) in mature adipocytes for thermogenic functionality and metabolic homeostasis. We generated fat tissue specific adenosine A2A receptor knock-out mice to assess the influence of signaling through this receptor on brown and beige fat functionality, obesity, insulin sensitivity, inflammation and liver function.

Characterization and Targeting of the Main Drivers of Elective Imaging Utilization: A Cross-sectional Study Applying Conjoint Analysis.

Objective: To characterize patient and referring physician preferences when selecting where to have elective imaging performed METHODS: In this Institutional Research Board approved survey-based study, online surveys were completed by 393 patients who had recently had a non-contrast MRI of the shoulder, lumbar spine, or knee within the past 2 years and 168 physicians who had ordered at least 12 such MRIs in the past year. The survey data included explicit questions about preferences as well as a set of conjoint choice screens. Conjoint analysis utilized a logistic model estimated using maximum likelihood estimation.

A multicenter Phase II randomized, placebo-controlled single-blind trial with the SV2A ligand seletracetam in photosensitive epilepsy patients.

The objective of this study was to evaluate the effect of seletracetam (SEL), a potent modulator of synaptic vesicle glycoprotein 2A (SV2A), in patients with photoparoxysmal EEG response (PPR) to intermittent photic stimulation (IPS) as proof-of-principle of efficacy in patients with epilepsy. In this multicenter, single-blind Phase II study, adults with photosensitive epilepsy, with/without concomitant antiseizure medication therapy, underwent IPS under 3 eye conditions (at eye closure, eyes closed and eyes open) after a single oral dose of placebo (day - 1) or SEL (day 1; 0.5, 1, 2, 4, 10, or 20 mg).

Novel bilayered zirconia systems using recycled 3Y-TZP for dental applications.

Objective: To synthesize bilayer zirconia systems based on commercial or recycled 3Y-TZP obtained from non-milled remnants and to compare their optical and mechanical properties before and after aging.

Methods: Bilayer zirconia samples were fabricated using either recycled 3Y-TZP (3Y-R/4Y and 3Y-R/5Y) or commercial powders (3Y/4Y and 3Y/5Y). Microstructure and phase composition were analyzed using ScanningElectronMicroscopy (SEM) and X-Ray Diffraction (XRD).

What substance use services are advertised by local governments? An analysis of data from county websites in New York state.

Objective: To assess the substance use disorder (SUD) prevention and response activities that county governments in New York advertise.

Study Design: Cross-sectional study.

Methods: We coded websites of county public health, mental health, emergency, and social service departments to identify whether any government agency provided information about ten evidence-based SUD services.

Reciprocal relationships between adolescent mental health difficulties and alcohol consumption.

The directionality of the relationship between adolescent alcohol consumption and mental health difficulties remains poorly understood. This study investigates the longitudinal relationship between alcohol use frequency, internalizing and externalizing symptoms from the ages of 11 to 17. We conducted a random-intercept cross-lagged panel model across three timepoints (ages: 11yrs, 14yrs, 17yrs; 50.

Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer's disease, and late-onset Alzheimer's disease.

Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.

Acoustic features of instrumental movie soundtracks elicit distinct and mostly non-overlapping extra-musical meanings in the mind of the listener.

Music can evoke powerful emotions in listeners. However, the role that instrumental music (music without any vocal part) plays in conveying extra-musical meaning, above and beyond emotions, is still a debated question. We conducted a study wherein participants (N = 121) listened to twenty 15-second-long excerpts of polyphonic instrumental soundtrack music and reported (i) perceived emotions (e.

Microfluidic mixing probe: generating multiple concentration-varying flow dipoles.

This study advances microfluidic probe (MFP) technology through the development of a 3D-printed Microfluidic Mixing Probe (MMP), which integrates a built-in pre-mixer network of channels and features a lined array of paired injection and aspiration apertures. By combining the concepts of hydrodynamic flow confinements (HFCs) and "Christmas-tree" concentration gradient generation, the MMP can produce multiple concentration-varying flow dipoles, ranging from 0 to 100%, within an open microfluidic environment. This innovation overcomes previous limitations of MFPs, which only produced homogeneous bioreagents, by utilizing the pre-mixer to create distinct concentration of injected biochemicals.

Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

Racial disparities in lung transplantation for cystic fibrosis in the era of highly effective modulator therapy.

Background: Highly effective modulator therapies (HEMT) including ivacaftor (IVA) and elexacaftor/tezacaftor/ivacaftor (ETI) have transformed treatment for people with cystic fibrosis (pwCF). However, non-HEMT-responsive mutations are more common in pwCF of non-White race/ethnicity; introduction of HEMT might have exacerbated racial/ethnic disparities in CF care.

Methods: Using the Scientific Registry of Transplant Recipients, we identified all lung transplant candidates and recipients 05/2005-12/2022 and categorized them by diagnosis (CF/non-CF), race/ethnicity (non-Hispanic White/Black/Hispanic) and era [Pre-HEMT (2005-1/30/2012), IVA (1/31/2012-10/30/2019), ETI (10/31/2019-12/31/2022)].

Attention rhythmically shapes sensory tuning.

Attention is key to perception and human behavior, and evidence shows that it periodically samples sensory information (<20Hz). However, this view has been recently challenged due to methodological concerns and gaps in our understanding of the function and mechanism of rhythmic attention. Here we used an intensive ∼22-hour psychophysical protocol combined with reverse correlation analyses to infer the neural representation underlying these rhythms.

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies.

Estimating the impacts of calorie labels in fast-food settings using a novel comparison: Comparing California drive-through and in-store purchases.

Prior studies assessing the impact of calorie labels in fast-food settings have relied on comparisons across local and state jurisdictions with and without labeling mandates; several well-designed studies indicate a small reduction of calories purchased as a result of the labels. This study exploits a staggered roll-out of calorie labels in California to study the same issue using a novel comparison of in-store purchases with calorie information and drive-through purchases without calorie information at the same locations. With this design, consumers in both the treatment and comparison groups have been subject to the same social signals associated with the policy change and may have been exposed to calorie information during prior purchases, narrowing the intervention under study to the impact of posted menu labels at the point of purchase.