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Objectives: Limited data on performing bilateral pulmonary artery banding (BPAB) before stage 1 Norwood procedure suggest that some patients may benefit through the postponement of the major cardiopulmonary bypass procedure. The objective of this study was to evaluate the effectiveness of BPAB in the surgical management of high-risk patients with hypoplastic left heart syndrome (HLHS). Methods: A retrospective review of all high-risk neonates with HLHS who underwent BPAB at our institution was performed. No patients, including those with intact or highly restrictive atrial septum (IAS), were excluded. Results: Between October 2015 and April 2021, 49 neonates with HLHS (including 6 with IAS) underwent BPAB, 40 of whom progressed to the Norwood procedure. Risk factors for not progressing to the Norwood procedure after BPAP include low birth weight (P = .043), the presence of multiple extracardiac anomalies (P = .005), and the presence of genetic disorders (P = .028). Operative mortality was 7.5% (3/40). IAS was associated with operative mortality (P = .022). Conclusions: The strategy of BPAB prestage 1 Norwood procedure was successful in identifying at-risk patients and improving Norwood survival. Although not all patients will need this hybrid approach, a significant number can be expected to benefit from this tactic. These results support the need for a substantial hybrid strategy, in addition to a primary stage 1 Norwood surgical strategy, in the management of HLHS.

Values of undercatch-corrected liquid-equivalent snowfall rate (S) at a ground site and microwave reflectivity (Z) retrieved using an airborne W-band radar were acquired during overflights. The temperature at the ground site was between −6 and −15 ∘C. At flight level, within clouds containing ice and supercooled liquid water, the temperature was approximately 7 ∘C colder. Additionally, airborne measurements of snow particle imagery were acquired. The images demonstrate that most of the snow particles were rimed, at least at flight level. A relatively small set of S–Z pairs (four) is available from the overflights. Important distinctions between these measurements and those of Pokharel and Vali (2011), who reported S–Z pairs and an S–Z relationship for rimed snow particles, are (1) the fewer S–Z pairs, (2) the method used to acquire S, and (3) the altitude, relative to ground, of the W-band Z retrievals. This analysis corroborates the fact that the S–Z relationship reported in Pokharel and Vali (2011) yields an S – in scenarios with snowfall produced by riming – substantially larger than that derived using an S–Z relationship developed for unrimed snow particles.

Abstract Introduction In recent years, there has been a significant increase in the development of artificial intelligence (AI) algorithms aimed at reviewing radiographs after total joint arthroplasty (TJA). This disruptive technology is particularly promising in the context of preoperative planning for revision TJA. Yet, the efficacy of AI algorithms regarding TJA implant analysis has not been examined comprehensively. Methods PubMed, EBSCO, and Google Scholar electronic databases were utilized to identify all studies evaluating AI algorithms related to TJA implant analysis between 1 January 2000, and 27 February 2023 (PROSPERO study protocol registration: CRD42023403497). The mean methodological index for non-randomized studies score was 20.4 ± 0.6. We reported the accuracy, sensitivity, specificity, positive predictive value, and area under the curve (AUC) for the performance of each outcome measure. Results Our initial search yielded 374 articles, and a total of 20 studies with three main use cases were included. Sixteen studies analyzed implant identification, two addressed implant failure, and two addressed implant measurements. Each use case had a median AUC and accuracy above 0.90 and 90%, respectively, indicative of a well-performing AI algorithm. Most studies failed to include explainability methods and conduct external validity testing. Conclusion These findings highlight the promising role of AI in recognizing implants in TJA. Preliminary studies have shown strong performance in implant identification, implant failure, and accurately measuring implant dimensions. Future research should follow a standardized guideline to develop and train models and place a strong emphasis on transparency and clarity in reporting results. Level of Evidence Level III.

Abstract Cell engineering strategies typically rely on energy‐consuming overexpression of genes or radical gene‐knock out. Both strategies are not particularly convenient for the generation of slightly modulated phenotypes, as needed in biosimilar development of for example differentially fucosylated monoclonal antibodies (mAbs). Recently, transiently transfected small noncoding microRNAs (miRNAs), known to be regulators of entire gene networks, have emerged as potent fucosylation modulators in Chinese hamster ovary (CHO) production cells. Here, we demonstrate the applicability of stable miRNA overexpression in CHO production cells to adjust the fucosylation pattern of mAbs as a model phenotype. For this purpose, we applied a miRNA chaining strategy to achieve adjustability of fucosylation in stable cell pools. In addition, we were able to implement recently developed artificial miRNAs (amiRNAs) based on native miRNA sequences into a stable CHO expression system to even further fine‐tune fucosylation regulation. Our results demonstrate the potential of miRNAs as a versatile tool to control mAb fucosylation in CHO production cells without adverse side effects on important process parameters.

Advances in high-throughput technologies have enhanced our ability to describe microbial communities as they relate to human health and disease. Alongside the growth in sequencing data has come an influx of resources that synthesize knowledge surrounding microbial traits, functions, and metabolic potential with knowledge of how they may impact host pathways to influence disease phenotypes. These knowledge bases can enable the development of mechanistic explanations that may underlie correlations detected between microbial communities and disease. In this review, we survey existing resources and methodologies for the computational integration of broad classes of microbial and host knowledge. We evaluate these knowledge bases in their access methods, content, and source characteristics. We discuss challenges of the creation and utilization of knowledge bases including inconsistency of nomenclature assignment of taxa and metabolites across sources, whether the biological entities represented are rooted in ontologies or taxonomies, and how the structure and accessibility limit the diversity of applications and user types. We make this information available in a code and data repository at: https://github.com/lozuponelab/knowledge-source-mappings. Addressing these challenges will allow for the development of more effective tools for drawing from abundant knowledge to find new insights into microbial mechanisms in disease by fostering a systematic and unbiased exploration of existing information.

BackgroundHealth care organizations strive to improve patient care experiences. Some use one-on-one provider counseling (shadow coaching) to identify and target modifiable provider behaviors.ObjectiveWe examined whether shadow coaching improves patient experience across 44 primary care practices in a large urban Federally Qualified Health Center.Research designSeventy-four providers with "medium" (ie, slightly below average) overall provider ratings received coaching and were compared with 246 uncoached providers. We fit mixed-effects regression models with random effects for provider (level of treatment assignment) and fixed effects for time (linear spline with a knot and "jump" at coaching date), patient characteristics and site indicators. By design, coached providers performed worse at selection; models account for the very small (0.2 point) regression-to-the-mean effects. We assessed differential effects by coach.SubjectsA total of 46,452 patients (from 320 providers) who completed the Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) Visit Survey 2.0.MeasuresCAHPS overall provider rating and provider communication composite (scaled 0-100).ResultsProviders not chosen for coaching had a nonsignificant change in performance during the period when selected providers were coached. We observed a statistically significant 2-point (small-to-medium) jump among coached providers after coaching on the CAHPS overall provider rating and provider communication score. However, these gains disappeared after 2.5 years; effects differed by coach.ConclusionsShadow coaching improved providers' overall performance and communication immediately after being coached. Regularly planned shadow coaching "booster" sessions might maintain or even increase the improvement gained in patient experience scores, but research examining additional coaching and optimal implementation is needed.

Approximately 1.6 million patients in the United States are affected by tricuspid valve regurgitation, which occurs when the tricuspid valve does not close properly to prevent backward blood flow into the right atrium. Despite its critical role in proper cardiac function, the tricuspid valve has received limited research attention compared to the mitral and aortic valves on the left side of the heart. As a result, proper valvular function and the pathologies that may cause dysfunction remain poorly understood. To promote further investigations of the biomechanical behavior and response of the tricuspid valve, this work establishes a parameter-based approach that provides a template for tricuspid valve modeling and simulation. The proposed tricuspid valve parameterization presents a comprehensive description of the leaflets and the complex chordae tendineae for capturing the typical three-cusp structural deformation observed from medical data. This simulation framework develops a practical procedure for modeling tricuspid valves and offers a robust, flexible approach to analyze the performance and effectiveness of various valve configurations using isogeometric analysis. The proposed methods also establish a baseline to examine the tricuspid valves structural deformation, perform future investigations of native valve configurations under healthy and disease conditions, and optimize prosthetic valve designs.

Antibodies targeting the PD-1, PD-L1, and CTLA-4 immune checkpoint axis have been used in a variety of tumor types. They achieve anti-tumor activity through activating the patient's own immune system to target immune response evading cancer cells. However, this unique mechanism of action may cause immune-related adverse events, irAEs. One of these irAEs is myocarditis which is associated with an alarming mortality rate. In this study we presented clinical cases of myocarditis from safety trial datasets submitted to the U.S. Food and Drug Administration, FDA. Additionally, we analyzed over fourteen million FDA Adverse Event Reporting System, FAERS, submissions. The statistical analysis of the FAERS data provided evidence of significantly increased reporting of myocarditis in patients administered immune checkpoint inhibitors alone, in combination with another immune checkpoint inhibitor, the kinase inhibitor axitinib, or chemotherapy, for all cancer types, when compared to patients administered chemotherapy. All combination therapies led to further increased reporting odds ratios of myocarditis. We further analyzed the occurrence of myocarditis by stratifying the reports into sub-cohorts based on specific cancer types and treatment/control groups in major cancer immunotherapy efficacy trials and confirmed the observed trend for each cohort.

We assess the association between survey layout and response rates (RRs) in the 2017 Medicare Advantage Consumer Assessment of Healthcare Providers and Systems mail survey. Among 438 Medicare Advantage plans surveyed by six vendors, there was latitude in survey layout, and plans could add up to 12 supplemental items. Regression models predicted survey response from survey characteristics (page count, number of supplemental items, and survey attractiveness), and beneficiary sociodemographics. Beneficiary-age-by-survey-characteristic interactions assessed whether survey characteristics were more strongly related to RRs among older beneficiaries. We found that surveys with more supplemental items and less attractive layouts had lower adjusted odds of response. RRs were more sensitive to format among older beneficiaries. The difference in adjusted RRs for the most favorable versus the least favorable survey design was 14.5%. For a 65-year-old, this difference was 13.6%; for an 80-year-old, it was 21.0%. These findings suggest that even within a relatively standardized survey, formatting can substantially influence RRs.

BackgroundSturge-Weber syndrome (SWS) is a sporadic, neurocutaneous syndrome involving the skin, brain, and eyes. Because of the variability of the clinical manifestations and the lack of prospective studies, consensus recommendations for management and treatment of SWS have not been published.ObjectiveThis article consolidates the current literature with expert opinion to make recommendations to guide the neuroimaging evaluation and the management of the neurological and ophthalmologic features of SWS.MethodsThirteen national peer-recognized experts in neurology, radiology, and ophthalmology with experience treating patients with SWS were assembled. Key topics and questions were formulated for each group and included (1) risk stratification, (2) indications for referral, and (3) optimum treatment strategies. An extensive PubMed search was performed of English language articles published in 2008 to 2018, as well as recent studies identified by the expert panel. The panel made clinical practice recommendations.ConclusionsChildren with a high-risk facial port-wine birthmark (PWB) should be referred to a pediatric neurologist and a pediatric ophthalmologist for baseline evaluation and periodic follow-up. In newborns and infants with a high-risk PWB and no history of seizures or neurological symptoms, routine screening for brain involvement is not recommended, but brain imaging can be performed in select cases. Routine follow-up neuroimaging is not recommended in children with SWS and stable neurocognitive symptoms. The treatment of ophthalmologic complications, such as glaucoma, differs based on the age and clinical presentation of the patient. These recommendations will help facilitate coordinated care for patients with SWS and may improve patient outcomes.

Abstract Advancing global sustainable development hinges on strengthening the connections between science, society, and policy, as well as addressing existing science inequalities. Research funding programmes play a pivotal role in this context, but little is known about how they can actively nurture required transformations of the science systems. In this paper, we investigate how science funders can actively promote science-society-policy interactions through transdisciplinary research (TDR) as a means to advance sustainable development in the Global South. Our primary focus is on the research funding programme “LIRA 2030 Africa”. Our research has revealed three closely intertwined pathways for cultivating TDR in this context: (1) Enabling African scientists to lead high-quality TDR projects, (2) empowering African scientists to pursue a career as TDR researchers, and 3) enhancing the context conditions for doing TDR in Africa. By scrutinising the advantages and challenges associated with these pathways and their associated activities, we conclude that fostering TDR in Africa necessitates a multifaceted approach. This approach entails a combination of measures, such as providing research grants, offering TDR and leadership training, fostering networks, developing institutions, and facilitating collaboration across various funders.

Abstract Opioid use disorders (OUD) and opioid-related fatal overdoses are a public health concern in the United States. Approximately 100,000 fatal opioid-related overdoses occurred annually from mid-2020 to the present, the majority of which involved fentanyl or fentanyl analogs. Vaccines have been proposed as a therapeutic and prophylactic strategy to offer selective and long-lasting protection against accidental or deliberate exposure to fentanyl and closely related analogs. To support the development of a clinically viable anti-opioid vaccine suitable for human use, the incorporation of adjuvants will be required to elicit high titers of high-affinity circulating antibodies specific to the target opioid. Here we demonstrate that the addition of a synthetic TLR7/8 agonist, INI-4001, but not a synthetic TLR4 agonist, INI-2002, to a candidate conjugate vaccine consisting of a fentanyl-based hapten, F1, conjugated to the diphtheria cross-reactive material (CRM), significantly increased generation of high-affinity F1-specific antibody concentrations, and reduced drug distribution to the brain after fentanyl administration in mice.

The complex interplay of magnetohydrodynamics, gravity, and supersonic turbulence in the interstellar medium (ISM) introduces a non-Gaussian structure that can complicate a comparison between theory and observation. In this paper, we show that the wavelet scattering transform (WST), in combination with linear discriminant analysis (LDA), is sensitive to non-Gaussian structure in 2D ISM dust maps. WST-LDA classifies magnetohydrodynamic (MHD) turbulence simulations with up to a 97% true positive rate in our testbed of 8 simulations with varying sonic and Alfvénic Mach numbers. We present a side-by-side comparison with two other methods for non-Gaussian characterization, the reduced wavelet scattering transform (RWST) and the three-point correlation function (3PCF). We also demonstrate the 3D-WST-LDA, and apply it to the classification of density fields in position-position-velocity (PPV) space, where density correlations can be studied using velocity coherence as a proxy. WST-LDA is robust to common observational artifacts, such as striping and missing data, while also being sensitive enough to extract the net magnetic field direction for sub-Alfvénic turbulent density fields. We include a brief analysis of the effect of point-spread functions and image pixelization on 2D-WST-LDA applied to density fields, which informs the future goal of applying WST-LDA to 2D or 3D all-sky dust maps to extract hydrodynamic parameters of interest.

The James Webb Space Telescope (JWST) is capable of probing extremely early eras of our Universe, when the supersonic relative motions between dark matter and baryonic overdensities modulate structure formation ( z ≳ 10). We study low-mass galaxy formation, including this “stream velocity,” using high-resolution AREPO hydrodynamics simulations and present theoretical predictions of the UV luminosity function (UVLF) and galaxy stellar mass function down to extremely faint and low-mass galaxies ( M _UV ≳ −15, 10 ^4 M _⊙ ≤ M _* ≤ 10 ^8 M _⊙ ). We show that, although the stream velocity suppresses early star formation overall, it induces a short period of rapid star formation in some larger dwarfs, leading to an enhancement in the faint end of the UVLF at z = 12. We demonstrate that JWST observations are close to this enhanced regime and propose that the UVLF may constitute an important probe of the stream velocity at high redshift for JWST and future observatories.