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Background: Team communication remains a challenge in hospital settings. Hospital-based teams are diverse, team composition changes daily, and team members are frequently not co-located. Novice nurses and medical residents entering the workforce during the coronavirus 2019 pandemic experienced higher communication challenges than before and lacked adequate opportunities for interprofessional learning and communication., Method: We evaluated perceptions of safety and communication among novice nurses and medical residents after a 1-hour focused team engagement consisting of an interprofessional virtual simulation and debrief. We conducted a retrospective pre/post survey to measure perceptions of interprofessional collaboration using the Interprofessional Socialization and Valuing Scale., Results: Sixty-eight pediatric nurse residents and medical residents participated in the survey. Overall, the focused team engagements significantly improve participants' perceptions of interprofessional collaboration, with participants showing statistically significant improvement in seven of nine retrospective pre/post survey questions. When analyzing by discipline, nurse residents show stronger gains than medical residents., Conclusions: The interprofessional structured debriefings encourage nurses and medical residents to collaborate and discuss important safety topics away from bedside stressors. After completing the virtual simulation, the outcomes show improved perceptions of interprofessional collaboration and enhanced knowledge of safety techniques., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: The Pediatric Cardiac Critical Care Consortium (PC4) cardiac arrest prevention (CAP) quality improvement (QI) project facilitated a decreased in-hospital cardiac arrest (IHCA) incidence rate across multiple hospitals. The sustainability of this outcome has not been determined., Objective: To examine the IHCA incidence rate at participating hospitals after the QI project ended and discern which factors best aligned with sustained improvement., Design, Setting, and Participants: This observational cohort study compared IHCA data from the CAP era (July 1, 2018, to December 31, 2019) with data from the 2-year follow-up era (March 1, 2020, to February 28, 2022). Data were obtained from pediatric cardiac intensive care units (CICUs) from 17 PC4 CAP-participating hospitals., Intervention: The CAP practice bundle was designed to facilitate local practice integration, with the intention to implement, adapt, and continue CAP processes beyond the CAP era. A web-based survey was administered 2 years after the end of the project to estimate CAP-specific QI work., Main Outcomes and Measures: Risk-adjusted IHCA incidence rates across all admissions were compared between study eras. The survey generated a novel hospital-specific QI sustainability score, which is generally reflective of the sum of local CAP work performed., Results: There were no clinically important differences in demographic and admission characteristics between the 13 082 CAP era admissions and 16 284 follow-up admissions (total mean [SD] age, 5.1 [8.4] years; 56.1% male). Risk-adjusted IHCA incidences were not different between the CAP vs follow-up eras (2.8% vs 2.8%; odds ratio, 1.03; 95% CI, 0.89-1.19), suggesting sustained prevention improvement. There was also no difference between eras in risk-adjusted IHCA incidence within medical, surgical, or high-risk subgroups. A lower hospital QI sustainability score was correlated with higher odds for IHCA in the follow-up vs CAP era (correlation coefficient, -0.58; P = .02). Five hospitals had increases of 1% or greater in risk-adjusted IHCA rates in the follow-up era; these hospitals had significantly lower QI sustainability scores and were less likely to have adopted sustainability elements during the CAP era or report persistent engagement for CAP-related QI processes during follow-up., Conclusions and Relevance: In this cohort study of all CICU admissions across 17 hospitals, IHCA prevention was feasible and sustainable; the established reduction in risk-adjusted IHCA rate was maintained for at least 2 years after the end of the CAP project. Both implementation strategies and continued engagement in CAP processes during the follow-up era were associated with sustained improvement.

The Centers for Disease Control and Prevention (CDC) continues to promote the utilization of electronic health records (EHRs) to support population health management and reduce disparities. However, access to EHRs with capabilities to disaggregate data or generate digital dashboards is not always readily available in rural areas. With funding from CDC's DP-18-1815, the Division of Diabetes and Heart Disease Management (Division) at the South Carolina Department of Health and Environmental Control designed a quality improvement initiative to reduce health disparities for people with hypertension and high blood cholesterol in rural areas. With support from a nonprofit partner, the Division used qualitative evaluation methods to evaluate the extent to which practices were able to disaggregate data and report quality measures., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression., Methods: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression., Results: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (β - 7.5 × 10 -6 , CI - 1.2 × 10 -5 , - 3 × 10 -6 , p = 0.001) and incident cases of NS (vs. prevalent) (β - 1.1, CI - 2.22, - 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (β 0.16, CI 0.04, 0.29, p = 0.01) over time., Conclusion: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

5-Aminolevulinic acid (ALA) is an intraoperative imaging agent approved for protoporphyrin IX (PpIX) fluorescence-guided resection of glioblastoma (GBM). It is currently under clinical evaluation for photodynamic therapy (PDT) after the completion of GBM surgery. We previously showed that lapatinib, a clinical kinase inhibitor of epidermal growth factor receptor 1 & 2 (EGFR and HER2), enhanced PpIX fluorescence in a panel of GBM cell lines by blocking ABCG2 (ATP-binding cassette super-family G member 2)-mediated PpIX efflux, which suggests its potential for improving ALA for GBM surgery and PDT. Here we show that lapatinib enhanced PDT-induced cytotoxicity by promoting GBM cell death with the induction of apoptosis followed by necrosis. While the induction of tumor cell apoptosis was massive and rapid in the H4 cell line with no detectable Bcl-2 and a low level of Bcl-xL, it was delayed and much less in extent in A172, U-87 and U-118 cell lines with higher levels of pro-survival Bcl-2 family proteins. Lapatinib treatment alone neither reduced GBM cell viability nor had any significant effect on EGFR downstream signaling. Its enhancement of ALA-PDT was largely due to the increase of intracellular PpIX particularly in the mitochondria, resulting in the activation of mitochondria-mediated apoptosis in H4 cells. Our present study demonstrates that lapatinib inhibits ABCG2-mediated PpIX efflux and sensitizes GBM cells to ALA-PDT by inducing tumor cell death., (© 2024. The Author(s).)

Energy-based displacement tracking of ultrasound images can be implemented by optimizing a cost function consisting of a data term, a mechanical congruency term, and first- and second-order continuity terms. This approach recently provided a promising solution to two-dimensional axial and lateral displacement tracking in ultrasound strain elastography. However, the associated second-order regularizer only considers the unmixed second derivatives and disregards the mixed derivatives, thereby providing suboptimal noise suppression and limiting possibilities for total strain tensor imaging. We propose to improve axial, lateral, axial shear, and lateral shear strain estimation quality by formulating and optimizing a novel L1-norm-based second-order regularizer that penalizes both mixed and unmixed displacement derivatives. We name the proposed technique L1-MixTURE, which stands for L1-norm Mixed derivative for Total UltRasound Elastography. When compared to simulated ground truth results, the mean structural similarity (MSSIM) obtained with L1-MixTURE ranged 0.53 to 0.86 and the mean absolute error (MAE) ranged 0.00053 to 0.005. In addition, the mean elastographic signal-to-noise ratio (SNR) achieved with simulated, experimental phantom, and in vivo breast datasets, ranged 1.87 to 52.98, and the mean elastographic contrast-to-noise ratio (CNR) ranged 7.40 to 24.53. When compared to a closely related existing technique that does not consider the mixed derivatives, L1-MixTURE generally outperformed the MSSIM, MAE, SNR, and CNR by up to 37.96%, 67.82%, and 25.53% in the simulated, experimental phantom, and in vivo datasets, respectively. These results collectively highlight the ability of L1-MixTURE to deliver highly accurate axial, lateral, axial shear, and lateral shear strain estimates and advance the state-of-the-art in elastography-guided diagnostic and interventional decisions.

Vascular Ehlers-Danlos, Marfan and Loeys-Dietz syndromes have increased risk of aortic dilation and dissection. Previous early studies showed hypermobile Ehlers-Danlos syndrome (hEDS) may also have increased risk, with echocardiography screening recommended; subsequent studies have not confirmed the risk or recommended echocardiography. This pediatric-based study assessed aortic dilation prevalence in those with hEDS by serial echocardiographic examinations and assessed family history for aortic dissections. We retrospectively identified individuals with hEDS who had echocardiography studies from the electronic medical records at one pediatric center. Aortic root Z-scores >2.0 were found in 15/225 subjects (average age 12.9 years) on initial echocardiograms, with no Z-score >3.0. Subsequent studies (n = 68) found statistically significant decline in aortic root Z-scores. Repeat echocardiography in those with initial aortic root Z-score >2.0 (n = 10) demonstrated a decline in Z score <2.0 in seven. On final examination, 9/225 (4.0%) had a Z-score >2.0, not statistically different from the general population. No aortic dissection occurred in first- or second-degree relatives. In conclusion, aortic root dilation rate in hEDS is likely not different from the general population. We propose that in the absence of other cardiac findings or suspicion for another disorder, echocardiography is not required in hEDS., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Objective: To update state-specific estimates of diabetes-attributable costs in the U.S. and assess changes in spending from 2013 to 2021., Research Design and Methods: We used an attributable fraction approach to estimate direct medical costs of diagnosed diabetes using the 2021 State Health Expenditure Accounts, the 2021 Behavioral Risk Factor Surveillance System, and the Centers for Medicare and Medicaid Services 2018-2019 Minimum Data Set. We estimated diabetes-attributable productivity losses from morbidity and mortality using the 2016-2021 National Health Interview Survey and the 2021 mortality data from the Centers for Disease Control and Prevention. Costs were adjusted to 2021 U.S. dollars., Results: Total diabetes-attributable cost in 2021 was $640 billion ($335 billion in direct medical costs and $305 billion in indirect costs). The median state-level total diabetes-attributable cost was $8.2 billion (range $842 million to $81 billion). The median state-level per-person cost was $21,082, ranging from $17,452 to $37,090. Total diabetes-attributable cost increased by a median of 33% between 2013 and 2021, ranging from 16 to 68% across states. Medical costs increased by 50% overall (range 33-79%) and by 27% (range 15-41%) for per person with diabetes. Costs paid by Medicaid experienced the highest increase between 2013 and 2021 (median 153%; range 41-483%)., Conclusions: State economic costs of diagnosed diabetes are substantial and increased over the last decade. These costs and their growth vary considerably across states. These findings may help state policy makers in developing evidenced-based public health interventions in their respective states to prevent and control the prevalence of diabetes., (© 2024 by the American Diabetes Association.)

Severe aplastic anemia (SAA) is a rare potentially fatal hematologic disorder. Although overall outcomes with treatment are excellent, there are variations in management approach, including differences in treatment between adult and pediatric patients. Certain aspects of treatment are under active investigation in clinical trials. Because of the rarity of the disease, some pediatric hematologists may have relatively limited experience with the complex management of SAA. The following recommendations reflect an up-to-date evidence-based approach to the treatment of children with relapsed or refractory SAA., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Severe aplastic anemia (SAA) is a rare potentially fatal hematologic disorder. Although overall outcomes with treatment are excellent, there are variations in management approach, including differences in treatment between adult and pediatric patients. Certain aspects of treatment are under active investigation in clinical trials. Because of the rarity of the disease, some pediatric hematologists may have relatively limited experience with the complex management of SAA. The following recommendations reflect an up-to-date evidence-based approach to the treatment of children with newly diagnosed SAA., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

This randomized controlled study assessed the feasibility, acceptability, and preliminary impact of the PrEP iT! mHealth intervention designed to improve PrEP adherence among young men who have sex with men (YMSM). A national sample of 80 YMSM in the U.S. (M age  = 25 years; 54% racial/ethnic minority), recruited through social media ads, were randomized to either the PrEP iT! or usual PrEP care conditions. Participants completed online surveys and submitted self-collected dried blood sample (DBS) data as measures of PrEP adherence. Differences in PrEP adherence across treatment arms and between participants with high versus low engagement in PrEP iT! were assessed. Retention was high at the three (94%) and six (93%) month assessment, and participants in PrEP iT! reported satisfactory acceptability of the intervention. There were no significant differences in self-reported or DBS-derived PrEP adherence between randomized groups. However, YMSM in the PrEP iT! group with high PrEP adherence (the equivalent of four or more doses/week through self-report and DBS-derived measures) demonstrated significantly higher engagement in the intervention than those with low PrEP adherence (the equivalent of 3 or fewer doses/week). Overall, the PrEP iT! intervention demonstrated strong feasibility and acceptability. The finding that high PrEP iT! intervention engagement was associated with protective levels of PrEP adherence suggests it is a viable adherence support tool that should be further evaluated in definitive trial among YMSM who need basic support, or as part of a more comprehensive adherence support package for those who need greater assistance.Trial registration Clinical Trials # NCT04509076 (registered August 10, 2020)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Disparities in cardiovascular disease prevalence and death exist among South Carolina's rural residents. Blood pressure self-monitoring (BPSM), where individuals measure their own blood pressure outside of the clinical environment, coupled with additional support, is an evidence-based, cost-effective strategy that is underutilized at large., Program: The YMCA's BPSM program is an evidence-based, 4-month program that includes 2 individualized office hours with a Healthy Heart Ambassador and 4 nutrition education sessions per month. Participants are provided with a blood pressure cuff and notebook to track their blood pressure at home in between sessions., Implementation: The SC Department of Health and Environmental Control partnered with the SC Alliance of YMCAs to expand the YMCA's BPSM program virtually. The traditional program was adapted to allow for virtual participant encounters. To target rural communities, partnerships were leveraged or established with rural health centers, federally qualified health centers, free medical clinics, and other state health department regions for participant referrals into the program., Evaluation: A developmental evaluation design was utilized to monitor the virtual adaptation of the YMCA's BPSM program from April 2021 to May 2023. At the end of the project, 10 referral sources were identified to refer participants to the program. In total, 253 participants were referred to the program, 126 participants enrolled into the program, and 52 participants completed the program. Completers of the virtual program were successful in improving their blood pressure., Discussion: Successes of the virtual program were not without challenges. Lessons learned from the virtual expansion of this program included ensuring participants' readiness to engage in a 4-month program, assessing participants' digital literacy, and considering broadband access in rural areas. Improvements in blood pressure and the program's reach demonstrate merit in continuing to scale the virtual adaptation of this program; however, contextual and structural factors should be considered., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

During vaginal delivery, the delivery requires the fetal head to mold to accommodate the geometric constraints of the birth canal. Excessive molding can produce brain injuries and long-term sequelae. Understanding the loading of the fetal brain during the second stage of labor (fully dilated cervix, active pushing, and expulsion of fetus) could thus help predict the safety of the newborn during vaginal delivery. To this end, this study proposes a finite element model of the fetal head and maternal canal environment that is capable of predicting the stresses experienced by the fetal brain at the onset of the second phase of labor. Both fetal and maternal models were adapted from existing studies to represent the geometry of full-term pregnancy. Two fetal positions were compared: left-occiput-anterior and left-occiput-posterior. The results demonstrate that left-occiput-anterior position reduces the maternal tissue deformation, at the cost of higher stress in the fetal brain. In both cases, stress is concentrated underneath the sutures, though the location varies depending on the presentation. In summary, this study provides a patient-specific simulation platform for the study of vaginal delivery and its effect on both the fetal brain and maternal anatomy. Finally, it is suggested that such an approach has the potential to be used by obstetricians to support their decision-making processes through the simulation of various delivery scenarios., (Copyright © 2024 by ASME.)

Abstract: Here we describe a case in which an ultrasound-guided supraorbital nerve block was used for the purposes of confirming the diagnosis of trigeminal neuralgia associated with Herpes Zoster and determining which trigeminal nerve branch is the pain generator in a patient with clinically suggestive findings. We discuss how performing a nerve block at the site of where the affected nerve exits the skull may identify which nerve is mediating the patient's symptoms and therefore guide possible further treatment options which could potentially provide a more lasting duration of relief., Competing Interests: Disclosures: The authors have no conflict of interest to disclose, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This phenomenological qualitative study examined the lived experience of pediatric nurse residents' transition to practice during the COVID-19 pandemic. The purposive sample included nine pediatric nurses, participating in a nurse residency program, who entered the nursing profession during the first year of the pandemic. The setting was a free-standing, Magnet-recognized, pediatric academic medical center in the Northeastern U.S. Individual interviews were audio recorded and transcribed. Narratives were analyzed using a hermeneutic phenomenological approach. Five themes emerged from the data: Our New Normal; The Rules Keep Changing; I'm Not Ready for This (transition to practice); The Toll of COVID; and Shattered Family-Centered Care. Sub-themes emerged in The Toll of COVID theme: COVID and the Nursing Care Environment, Emotional Toll of COVID, Burnout: A Universal Truth, and The Pandemic within the Pandemic. The nurse residents' narratives uncovered the essence of their uncertainty, sorrow, growth, and resilience. Through the eyes of pediatric nurse residents, this study illuminated the experiences of these novices as they entered the nursing profession amid a pandemic.

Aim: Patient preferences for the features of targeted chronic lymphocytic leukemia (CLL) therapies may differ. Materials & methods: A discrete-choice experiment (DCE) survey was administered to 229 respondents recruited through the CLL Society. Results: Respondents placed most importance on increasing the chance of progression-free survival (PFS) at 2 years from 70 to 90% and confirming results with measurable residual disease (MRD) testing instead of routine testing. Respondents also preferred daily oral administration over intravenous infusion every 4 weeks, fixed-duration treatments over treat-to-progression treatments and treatments with lower side effect risks. Reducing risk of tumor lysis syndrome was least important relative to changes in other attributes. Conclusion: The combination of improving PFS combined with confirming results using MRD testing was more important than changes in all other study attributes included in the DCE. Results from this study can help inform shared decision-making when selecting therapies for CLL.

Background: The importance of offering on-site cardiac troponin (cTn) testing at pediatric hospitals may be underappreciated. We developed a rapid rule-in process for myocardial injury at a pediatric hospital experiencing delays in off-site high-sensitivity cardiac troponin T (hs-cTnT) testing., Methods: Collect-to-verify turnaround times (TATs) for off-site testing were reviewed. Pre-analytic changes to improve TATs were devised, implemented and evaluated, after which a new analyzer was selected and evaluated for on-site cTn testing. Performance of the new analyzer's assay was compared to the off-site hs-cTnT assay, and post go-live TATs for on-site testing were assessed., Results: Median collect-to-verify TAT for short turnaround-time (STAT) priority off-site plasma hs-cTnT testing was 104 min, with 35% of orders having a TAT >120 min. Eliminating serum separator tubes and requiring a separate plasma separator tube did not significantly reduce TATs. A QuidelOrtho Triage® MeterPro whole blood cardiac troponin I (cTnI) assay was implemented to "triage" time-critical and STAT priority specimens collected for off-site hs-cTnT testing. Elevated cTnI (≥0.02 µg/L) had a sensitivity of 91% for clear elevations in hs-cTnT (≥53 ng/L) but a 0% sensitivity for modest elevations (5 to 13 ng/L, 14 to 52 ng/L). An interpretive comment was auto-appended to cTnI results indicating that clinicians should wait for the hs-cTnT result if cTnI was normal. Median collect-to-verify TAT for on-site cTnI testing was <50% the TAT for off-site hs-cTnT testing., Conclusions: On-site point-of-care whole blood cTn testing can rapidly confirm significant or late-presenting myocardial injury. Combined with simultaneous off-site high-sensitivity cardiac troponin (hs-cTn) testing, this workflow is a viable interim solution for pediatric hospitals without on-site hs-cTn testing., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: One in four South Carolinians lives in a county along a nearly 200-mile stretch of Interstate 95 (I-95). Stretching from North Carolina to Georgia, this region is among the most rural, economically depressed, and racially/ethnically diverse in the state. Research is needed to identify social factors contributing to adverse health outcomes along the I-95 corridor, guide interventions, and establish a baseline for measuring progress. This study assessed social determinants of health in counties in South Carolina's I-95 corridor relative to the rest of the state., Method: Data for South Carolina's 46 counties were extracted from the Centers for Disease Control and Prevention Minority Health Social Vulnerability Index (SVI), which grouped 34 census variables into six themes: socioeconomic status, household composition and disability, minority status and language, housing type and transportation, health care infrastructure, and medical vulnerability. Each theme was ranked from 0 (least vulnerable) to 1 (most vulnerable). Measures between regions were compared using the Wilcoxon-Mann-Whitney test., Results: Compared with counties outside the I-95 corridor (n = 29 ), counties in the corridor (n = 17 ) scored higher on socioeconomic status vulnerability (.67 and .82, respectively) and medical vulnerability (.65 and .79, respectively). No statistically significant differences were found across other themes., Conclusion: Identifying social determinants of health in South Carolina's I-95 corridor is a crucial first step toward alleviating health disparities in this region. Interventions and policies should be developed in collaboration with local stakeholders to address distal social factors that create and reinforce health disparities.

Elucidating how cell populations promote onset and progression of intervertebral disc degeneration (IDD) has the potential to enable more precise therapeutic targeting of cells and mechanisms. Single-cell RNA-sequencing (scRNA-seq) is performed on surgically separated annulus fibrosus (AF) (19,978; 26,983 cells) and nucleus pulposus (NP) (20,884; 24,489 cells) from healthy and diseased human intervertebral discs (IVD). In both tissue types, depletion of cell subsets involved in maintenance of healthy IVD is observed, specifically the immature cell subsets - fibroblast progenitors and stem cells - indicative of an impairment of normal tissue self-renewal. Tissue-specific changes are also identified. In NP, several fibrotic populations are increased in degenerated IVD, indicating tissue-remodeling. In degenerated AF, a novel disease-associated subset is identified, which expresses disease-promoting genes. It is associated with pathogenic biological processes and the main gene regulatory networks include thrombospondin signaling and FOXO1 transcription factor. In NP and AF cells thrombospondin protein promoted expression of genes associated with TGFβ/fibrosis signaling, angiogenesis, and nervous system development. The data reveal new insights of both shared and tissue-specific changes in specific cell populations in AF and NP during IVD degeneration. These identified mechanisms and molecules are novel and more precise targets for IDD prevention and treatment., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The use of reduced-intensity conditioning (RIC) regimens has increased in an effort to minimize hematopoietic stem cell transplantation (HCT) end-organ toxicity, including gonadal toxicity. We aimed to describe the incidence of fertility potential and gonadal function impairment in adolescent and young adult survivors of HCT and to identify risk factors (including conditioning intensity) for impairment. We performed a multi-institutional, international retrospective cohort study of patients age 10 to 40 years who underwent first allogeneic HCT before December 1, 2019, and who were alive, in remission, and available for follow-up at 1 to 2 years post-HCT. For females, an AMH level of ≥.5 ng/mL defined preserved fertility potential; an AMH level of ≥.03 ng/mL was considered detectable. Gonadal failure was defined for females as an elevated follicle-stimulating hormone (FSH) level >30 mIU/mL with an estradiol (E2) level <17 pg/mL or current use of hormone replacement therapy (regardless of specific indication or intent). For males, gonadal failure was defined as an FSH level >10.4 mIU/mL or current use of hormone replacement therapy. A total of 326 patients (147 females) were available for analysis from 17 programs (13 pediatric, 4 adult). At 1 to 2 years post-HCT, 114 females (77.6%) had available FSH and E2 levels and 71 (48.3%) had available AMH levels. FSH levels were reported for 125 males (69.8%). Nearly all female HCT recipients had very low levels of AMH. One of 45 (2.2%) recipients of myeloablative conditioning (MAC) and four of 26 (15.4%) recipients of reduced-intensity conditioning (RIC) (P = .06) had an AMH ≥.5 ng/m, and 8 of 45 MAC recipients (17.8%) and 12 of 26 RIC recipients (46.2%) (P = .015) had a detectable AMH level. Total body irradiation (TBI) dose and cyclophosphamide equivalent dose (CED) were not associated with detectable AMH. The incidence of female gonadal hormone failure was 55.3%. In univariate analysis, older age at HCT was associated with greater likelihood of gonadal failure (median age, 17.6 versus 13.9; P < .0001), whereas conditioning intensity (RIC versus MAC), TBI, chronic graft-versus-host disease requiring systemic therapy, and CED were not significantly associated with gonadal function. In multivariable analysis, age remained statistically significant (odds ratio [OR]. 1.11; 95% confidence interval [CI], 1.03 to 1.22) for each year increase; P = .012), Forty-four percent of the males had gonadal failure. In univariate analysis, older age (median, 16.2 years versus 14.4 years; P = .0005) and TBI dose (P = .002) were both associated with gonadal failure, whereas conditioning intensity (RIC versus MAC; P = .06) and CED (P = .07) were not statistically significant. In multivariable analysis, age (OR, 1.16; 95% CI, 1.06-1.27 for each year increase; P = .0016) and TBI ≥600 cGy (OR, 6.23; 95% CI, 2.21 to 19.15; P = .0008) remained significantly associated with gonadal failure. Our data indicate that RIC does not significantly mitigate the risk for gonadal failure in females or males. Age at HCT and (specifically in males) TBI use seem to be independent predictors of post-transplantation gonadal function and fertility status. All patients should receive pre-HCT infertility counseling and be offered appropriate fertility preservation options and be screened post-HCT for gonadal failure., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Biallelic loss-of-function variants in TBC1D2B have been reported in five subjects with cognitive impairment and seizures with or without gingival overgrowth. TBC1D2B belongs to the family of Tre2-Bub2-Cdc16 (TBC)-domain containing RAB-specific GTPase activating proteins (TBC/RABGAPs). Here, we report five new subjects with biallelic TBC1D2B variants, including two siblings, and delineate the molecular and clinical features in the ten subjects known to date. One of the newly reported subjects was compound heterozygous for the TBC1D2B variants c.2584C>T; p.(Arg862Cys) and c.2758C>T; p.(Arg920*). In subject-derived fibroblasts, TBC1D2B mRNA level was similar to control cells, while the TBC1D2B protein amount was reduced by about half. In one of two siblings with a novel c.360+1G>T splice site variant, TBC1D2B transcript analysis revealed aberrantly spliced mRNAs and a drastically reduced TBC1D2B mRNA level in leukocytes. The molecular spectrum included 12 different TBC1D2B variants: seven nonsense, three frameshifts, one splice site, and one missense variant. Out of ten subjects, three had fibrous dysplasia of the mandible, two of which were diagnosed as cherubism. Most subjects developed gingival overgrowth. Half of the subjects had developmental delay. Seizures occurred in 80% of the subjects. Six subjects showed a progressive disease with mental deterioration. Brain imaging revealed cerebral and/or cerebellar atrophy with or without lateral ventricle dilatation. The TBC1D2B disorder is a progressive neurological disease with gingival overgrowth and abnormal mandible morphology. As TBC1D2B has been shown to positively regulate autophagy, defects in autophagy and the endolysosomal system could be associated with neuronal dysfunction and the neurodegenerative disease in the affected individuals., (© 2024. The Author(s).)

Introduction: Reaching, enrolling, and retaining participants in lengthy lifestyle change interventions for weight loss is a major challenge. The objective of our meta-analysis was to investigate whether lifestyle interventions addressing nutrition and physical activity lasting 6 months or less are effective for weight loss., Methods: We searched for peer-reviewed studies on lifestyle change interventions of 6 months or less published from 2012 through 2023. Studies were screened based on inclusion criteria, including randomized controlled trials (RCTs) for adults with overweight or obesity. We used a random-effects model to pool the mean difference in weight loss between intervention and control groups. We also performed subgroup analyses by intervention length and control type., Results: Fourteen RCTs were identified and included in our review. Half had interventions lasting less than 13 weeks, and half lasted from 13 to 26 weeks. Seven were delivered remotely, 4 were delivered in person, and 3 used combined methods. The pooled mean difference in weight change was -2.59 kg (95% CI, -3.47 to -1.72). The pooled mean difference measured at the end of the intervention was -2.70 kg (95% CI, -3.69 to -1.71) among interventions lasting less than 13 weeks and -2.40 kg (95% CI, -4.44 to -0.37) among interventions of 13 to 26 weeks., Conclusion: Short-term multicomponent interventions involving physical activity and nutrition can achieve weight loss for adults with overweight or obesity. Offering short-term interventions as alternatives to long-term ones may reach people who otherwise would be unwilling or unable to enroll in or complete longer programs.

Abstract: Liver disease has not been well described in patients with Fanconi anemia (FA). Improvements in outcomes of transplant mean that more individuals with FA are reaching adulthood and new features of the FA phenotype are being discovered. We performed a retrospective review of liver function in a cohort of 97 patients with FA followed-up for at least 10 years at a single center. We identified a high frequency of transaminitis (n = 31, 32%) without elevation of bilirubin and with no evidence of structural hepatic abnormality in patients with FA. Transaminitis was persistent in many cases, sometimes lasting more than a decade without clinical manifestation, although 2 patients with prolonged transaminitis are deceased from liver failure, indicating important long-term clinical consequences. Transaminitis was found in patients who had and had not received transplant but was more frequent in recipients of transplant. Exposure to total body irradiation increased risk (odds ratio, 15.5 [95% confidence interval, 2.44-304.54]; P = .01), whereas treatment with androgens did not. Review of limited numbers of liver biopsies and autopsy material showed a cholestatic pattern of liver injury, with progressive fibrosis, in the majority of patients. Occurrence in cases without transplant as well as cases with transplant argues against a potential diagnosis of atypical liver graft-versus-host disease. Limited data regarding therapy suggest no benefit from treatment with steroids or other immune suppressive medications or ursodeoxycholic acid. Our data show that liver disease is common in patients with FA, and because most children with FA now reach adulthood, end-stage liver disease in young adulthood means systematic testing of potential therapies is urgently needed., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Pathogenic variants in TTN cause a spectrum of autosomal dominant and recessive cardiovascular, skeletal muscle and cardioskeletal disease with symptom onset across the lifespan. The aim of this study was to characterise the genotypes and phenotypes in a cohort of TTN +paediatric patients., Methods: Retrospective chart review was performed at four academic medical centres. Patients with pathogenic or truncating variant(s) in TTN and paediatric-onset cardiovascular and/or neuromuscular disease were eligible., Results: 31 patients from 29 families were included. Seventeen patients had skeletal muscle disease, often with proximal weakness and joint contractures, with average symptom onset of 2.2 years. Creatine kinase levels were normal or mildly elevated; electrodiagnostic studies (9/11) and muscle biopsies (11/11) were myopathic. Variants were most commonly identified in the A-band (14/32) or I-band (13/32). Most variants were predicted to be frameshift truncating, nonsense or splice-site (25/32). Seventeen patients had cardiovascular disease (14 isolated cardiovascular, three cardioskeletal) with average symptom onset of 12.9 years. Twelve had dilated cardiomyopathy (four undergoing heart transplant), two presented with ventricular fibrillation arrest, one had restrictive cardiomyopathy and two had other types of arrhythmias. Variants commonly localised to the A-band (8/15) or I-band (6/15) and were predominately frameshift truncating, nonsense or splice-site (14/15)., Conclusion: Our cohort demonstrates the genotype-phenotype spectrum of paediatric-onset titinopathies identified in clinical practice and highlights the risk of life-threatening cardiovascular complications. We show the difficulties of obtaining a molecular diagnosis, particularly in neuromuscular patients, and bring awareness to the complexities of genetic counselling in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Food insecurity is a major public health issue. Millions of households worldwide have intermittent and unpredictable access to food and this experience is associated with greater risk for a host of negative health outcomes. While food insecurity is a contemporary concern, we can understand its effects better if we acknowledge that there are ancient biological programs that evolved to respond to the experience of food scarcity and uncertainty, and they may be particularly sensitive to food insecurity during development. Support for this conjecture comes from common findings in several recent animal studies that have modeled insecurity by manipulating predictability of food access in various ways. Using different experimental paradigms in different species, these studies have shown that experience of insecure access to food can lead to changes in weight, motivation and cognition. Some of these studies account for changes in weight through changes in metabolism, while others observe increases in feeding and motivation to work for food. It has been proposed that weight gain is an adaptive response to the experience of food insecurity as 'insurance' in an uncertain future, while changes in motivation and cognition may reflect strategic adjustments in foraging behavior. Animal studies also offer the opportunity to make in-depth controlled studies of mechanisms and behavior. So far, there is evidence that the experience of food insecurity can impact metabolic efficiency, reproductive capacity and dopamine neuron synapses. Further work on behavior, the central and peripheral nervous system, the gut and liver, along with variation in age of exposure, will be needed to better understand the full body impacts of food insecurity at different stages of development., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Congenital heart disease (CHD) is one of the most common congenital birth defects. As surgical and interventional techniques have improved, the mortality has been greatly reduced and the focus has shifted to quality of life and long-term outcomes. The impact of CHD on development and cognition is becoming increasingly recognized. However, more research is needed to understand how children with CHD perform across various cognitive and intellectual domains. This study explored the performance of children with CHD on the newest version of the Wechsler Intelligence Scale for Children compared to normative controls. Children with CHD performed more poorly than normal controls across all indices and most subtests with large effect sizes. Additionally, we explored the patterns of impairment across indices and subtests, as well as the relationships between heard disease variables and WISC-V performance. Block design, Digit Span, and Similarities were the most commonly impaired scores in children with CHD, while Symbol Search, Picture Span, Figure Weights, and Vocabulary were least likely to be impaired., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancers exploit coinhibitory receptors on T cells to escape tumor immunity, and targeting such mechanisms has shown remarkable clinical benefit, but in a limited subset of patients. We hypothesized that cancer cells mimic noncanonical mechanisms of early development such as axon guidance pathways to evade T cell immunity. Using gain-of-function genetic screens, we profiled axon guidance proteins on human T cells and their cognate ligands and identified fibronectin leucine-rich transmembrane protein 3 (FLRT3) as a ligand that inhibits T cell activity. We demonstrated that FLRT3 inhibits T cells through UNC5B, an axon guidance receptor that is up-regulated on activated human T cells. FLRT3 expressed in human cancers favored tumor growth and inhibited CAR-T and BiTE + T cell killing and infiltration in humanized cancer models. An FLRT3 monoclonal antibody that blocked FLRT3-UNC5B interactions reversed these effects in an immune-dependent manner. This study supports the concept that axon guidance proteins mimic T cell checkpoints and can be targeted for cancer immunotherapy.

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an embryonic role of CELSR3 in CNS and urinary tract formation., (© 2024. The Author(s).)

Abstract: Allogeneic hematopoietic cell transplantation (HCT) can be complicated by life-threatening organ toxicity and infection necessitating intensive care. Epidemiologic data have been limited by single-center studies, poor database granularity, and a lack of long-term survivors. To identify contemporary trends in intensive care unit (ICU) use and long-term outcomes, we merged data from the Center for International Blood and Marrow Transplant Research and the Virtual Pediatric Systems databases. We identified 6995 pediatric patients with HCT aged ≤21 years who underwent first allogeneic HCT between 2008 and 2014 across 69 centers in the United States or Canada and followed patients until the year 2020. ICU admission was required for 1067 patients (8.3% by day +100, 12.8% by 1 year, and 15.3% by 5 years after HCT), and was linked to demographic background, pretransplant organ toxicity, allograft type and HLA-match, and the development of graft-versus-host disease or malignancy relapse. Survival to ICU discharge was 85.7%, but more than half of ICU survivors required ICU readmission, leading to 52.5% and 42.6% survival at 1- and 5-years post-ICU transfer, respectively. ICU survival was worse among patients with malignant disease, poor pretransplant organ function, and alloreactivity risk factors. Among 1-year HCT survivors, those who required ICU in the first year had 10% lower survival at 5 years and developed new dialysis-dependent renal failure at a greater rate (P<.001). Thus, although ICU management is common and survival to ICU discharge is high, ongoing complications necessitate recurrent ICU admission and lead to a poor 1-year outcome in select patients who are at high risk., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Several lung diseases lead to alterations in regional lung mechanics, including ventilator- and radiation-induced lung injuries. Such alterations can lead to localized underventilation of the affected areas, resulting in the overdistension of the surrounding healthy regions. Thus, there has been growing interest in quantifying the dynamics of the lung parenchyma using regional biomechanical markers. Image registration through dynamic imaging has emerged as a powerful tool to assess lung parenchyma's kinematic and deformation behaviors during respiration. However, the difficulty in validating the image registration estimation of lung deformation, primarily due to the lack of ground-truth deformation data, has limited its use in clinical settings. To address this barrier, we developed a method to convert a finite-element (FE) mesh of the lung into a phantom computed tomography (CT) image, advantageously possessing ground-truth information included in the FE model. The phantom CT images generated from the FE mesh replicated the geometry of the lung and large airways that were included in the FE model. Using spatial frequency response, we investigated the effect of " imaging parameters" such as voxel size (resolution) and proximity threshold values on image quality. A series of high-quality phantom images generated from the FE model simulating the respiratory cycle will allow for the validation and evaluation of image registration-based estimations of lung deformation. In addition, the present method could be used to generate synthetic data needed to train machine-learning models to estimate kinematic biomarkers from medical images that could serve as important diagnostic tools to assess heterogeneous lung injuries.

Background: The validated CT-based autonomous finite element system Simfini (Yosibash et al., 2020) is used in clinical practice to assist orthopedic oncologists in determining the risk of pathological femoral fractures due to metastatic tumors. The finite element models are created automatically from CT-scans, assigning to lytic tumors a relatively low stiffness as if these were a low-density bone tissue because the tumors could not be automatically identified., Methods: The newly developed automatic deep learning algorithm which segments lytic tumors in femurs, presented in (Rachmil et al., 2023), was integrated into Simfini. Finite element models of twenty femurs from ten CT-scans of patients with femoral lytic tumors were analyzed three times using: the original methodology without tumor segmentation, manual segmentation of the lytic tumors, and the new automatic segmentation deep learning algorithm to identify lytic tumors. The influence of explicitly incorporating tumors in the autonomous finite element analysis on computed principal strains is quantified. These serve as an indicator of femoral fracture and are therefore of clinical significance., Findings: Autonomous finite element models with segmented lytic tumors had generally larger strains in regions affected by the tumor. The deep learning and manual segmentation of tumors resulted in similar average principal strains in 19 regions out of the 23 regions within 15 femurs with lytic tumors. A high dice similarity score of the automatic deep learning tumor segmentation did not necessarily correspond to minor differences compared to manual segmentation., Interpretation: Automatic tumor segmentation by deep learning allows their incorporation into an autonomous finite element system, resulting generally in elevated averaged principal strains that may better predict pathological femoral fractures., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Pathogenic GATA6 variants have been associated with congenital heart disease (CHD) and a spectrum of extracardiac abnormalities, including pancreatic agenesis, congenital diaphragmatic hernia, and developmental delay. However, the comprehensive genotype-phenotype correlation of pathogenic GATA6 variation in humans remains to be fully understood., Methods: Exome sequencing was performed in a family where four members had CHD. In vitro functional analysis of the GATA6 variant was performed using immunofluorescence, western blot, and dual-luciferase reporter assay., Results: A novel, heterozygous missense variant in GATA6 (c.1403 G > A; p.Cys468Tyr) segregated with affected members in a family with CHD, including three with persistent truncus arteriosus. In addition, one member had childhood onset diabetes mellitus (DM), and another had necrotizing enterocolitis (NEC) with intestinal perforation. The p.Cys468Tyr variant was located in the c-terminal zinc finger domain encoded by exon 4. The mutant protein demonstrated an abnormal nuclear localization pattern with protein aggregation and decreased transcriptional activity., Conclusions: We report a novel, familial GATA6 likely pathogenic variant associated with CHD, DM, and NEC with intestinal perforation. These findings expand the phenotypic spectrum of pathologic GATA6 variation to include intestinal abnormalities., Impact: Exome sequencing identified a novel heterozygous GATA6 variant (p.Cys468Tyr) that segregated in a family with CHD including persistent truncus arteriosus, atrial septal defects and bicuspid aortic valve. Additionally, affected members displayed extracardiac findings including childhood-onset diabetes mellitus, and uniquely, necrotizing enterocolitis with intestinal perforation in the first four days of life. In vitro functional assays demonstrated that GATA6 p.Cys468Tyr variant leads to cellular localization defects and decreased transactivation activity. This work supports the importance of GATA6 as a causative gene for CHD and expands the phenotypic spectrum of pathogenic GATA6 variation, highlighting neonatal intestinal perforation as a novel extracardiac phenotype., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

When compared to fundamental B-mode imaging, coherence-based beamforming, and harmonic imaging are independently known to reduce acoustic clutter, distinguish solid from fluid content in indeterminate breast masses, and thereby reduce unnecessary biopsies during a breast cancer diagnosis. However, a systematic investigation of independent and combined coherence beamforming and harmonic imaging approaches is necessary for the clinical deployment of the most optimal approach. Therefore, we compare the performance of fundamental and harmonic images created with short-lag spatial coherence (SLSC), M-weighted SLSC (M-SLSC), SLSC combined with robust principal component analysis with no M-weighting (r-SLSC), and r-SLSC with M-weighting (R-SLSC), relative to traditional fundamental and harmonic B-mode images, when distinguishing solid from fluid breast masses. Raw channel data acquired from 40 total breast masses (28 solid, 7 fluid, 5 mixed) were beamformed and analyzed. The contrast of fluid masses was better with fundamental rather than harmonic coherence imaging, due to the lower spatial coherence within the fluid masses in the fundamental coherence images. Relative to SLSC imaging, M-SLSC, r-SLSC, and R-SLSC imaging provided similar contrast across multiple masses (with the exception of clinically challenging complicated cysts) and minimized the range of generalized contrast-to-noise ratios (gCNRs) of fluid masses, yet required additional computational resources. Among the eight coherence imaging modes compared, fundamental SLSC imaging best identified fluid versus solid breast mass contents, outperforming fundamental and harmonic B-mode imaging. With fundamental SLSC images, the specificity and sensitivity to identify fluid masses using the reader-independent metrics of contrast difference, mean lag one coherence (LOC), and gCNR were 0.86 and 1, 1 and 0.89, and 1 and 1, respectively. Results demonstrate that fundamental SLSC imaging and gCNR (or LOC if no coherence image or background region of interest is introduced) have the greatest potential to impact clinical decisions and improve the diagnostic certainty of breast mass contents. These observations are additionally anticipated to extend to masses in other organs.

Background: Pre-exposure prophylaxis (PrEP) and HIV treatment as prevention, which underlies the Undetectable = Untransmittable (U = U) campaign, are two effective biomedical approaches for HIV prevention among sexual minority men (SMM). Attitudes toward PrEP and U = U may differ between SMM emerging adults (EA: 18-24 years old) and young adults (YA: 25-29 years old) to drive differences in sexual behavior. However, to date, few studies assessed the degree to which YAs and EAs differ in their beliefs in the effectiveness of PrEP and U = U., Method: A national sample of 80 SMM in the USA (M age  = 25.1 years; 53.7% racial/ethnic minority; 38.8% EA; 61.3% YA) participated in a 6-month mHealth intervention for PrEP adherence. Non-parametric tests assessed differences in sexual behaviors and attitudes toward the effectiveness of PrEP and U = U between EAs and YAs using baseline data., Results: Compared to EAs, higher proportions of YAs trusted PrEP's effectiveness and considered condom use unnecessary after taking PrEP. More YAs than EAs were willing to engage in sexual behaviors that they felt too risky before learning about U = U and were more comfortable having condomless sex with HIV-positive partners. Conversely, a greater proportion of EAs than YAs preferred to use condoms even when their partners are on anti-HIV medications., Conclusion: Overall, YAs trusted the effectiveness of U = U and PrEP more than EAs, underscoring developmental differences in SMM's perspectives on biomedical HIV prevention tools. Our findings underscore the importance of tailoring messages on biomedical HIV prevention options differently for EAs and YAs to optimize uptake., (© 2023. International Society of Behavioral Medicine.)

Study purpose: New treatments for atopic dermatitis (AD) are emerging; however, little is known about the treatment preferences of patients with mild-to-moderate AD. To measure patients' preferences, a cross-sectional, web-based discrete choice experiment (DCE) survey was developed and administered to 300 adults in the United States with a self-reported physician diagnosis of mild-to-moderate AD. Materials and methods: In the DCE, respondents evaluated pairs of hypothetical AD treatment profiles defined by efficacy, risk, and mode and frequency of administration attributes. The DCE data were analyzed using a random parameters logit model. Subgroup analysis was used to investigate preference heterogeneity. Results: The results revealed achieving clear or almost clear skin within 3-4 months of treatment was the most important attribute relative to all other study attributes. The results indicated that a topical cream applied twice daily was preferred to systemic treatments. Subgroup analysis revealed that respondents with lower self-assessed disease burden were more likely to choose topical over systemic treatments and less averse to the risk of pain, burning, and/or stinging from the medicine (all other treatment features remaining equal) than respondents with higher self-assessed disease burden. Conclusion: The results of this study can help inform shared decision-making to manage mild-to-moderate AD.

Objectives: Acute kidney injury has been described after Fontan surgery, but the duration and outcomes are unknown. We sought to describe the incidence of and risk factors for acute kidney injury and the phenotype of renal recovery, and evaluate the impact of renal recovery phenotype on outcomes., Methods: All children who underwent a Fontan operation at a single center between 2009 and 2022 were included. Data collected included Fontan characteristics, vasopressor use, all measures of creatinine, and postoperative outcomes. Logistic regression models were used to assess predictors of acute kidney injury and the association between acute kidney injury and outcomes., Results: We enrolled 141 children (45% female). Acute kidney injury occurred in 100 patients (71%). Acute kidney injury duration was transient (<48 hours) in 77 patients (55%), persistent (2-7 days) in 15 patients (11%), more than 7 days in 4 patients (3%), and unknown in 4 patients (3%). Risk factors for acute kidney injury included higher preoperative indexed pulmonary vascular resistance (odds ratio, 3.90; P  = .004) and higher postoperative inotrope score on day 0 (odds ratio, 1.13, P  = .047). Risk factors for acute kidney injury duration more than 48 hours included absence of a fenestration (odds ratio, 3.43, P  = .03) and longer duration of cardiopulmonary bypass (odds ratio, 1.22 per 15-minute interval, P  = .01). Acute kidney injury duration more than 48 hours was associated with longer length of stay compared with transient acute kidney injury (median 18 days [interquartile range, 9-62] vs 10 days [interquartile range, 8-16], P  = .006) and more sternal wound infections (17% vs 4%, P  = .049)., Conclusions: Acute kidney injury after the Fontan operation is common. The occurrence and duration of acute kidney injury have significant implications for postoperative outcomes., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2023 The Author(s).)

Objective: To document the experience of 14 academic child and adolescent psychiatry programs in transitioning to and managing telehealth services during the COVID-19 pandemic. The goal was to understand how programs adopted and sustained telehealth during the pandemic. Telehealth was defined as services delivered via videoconferencing and telephony., Method: In this descriptive study, faculty from 14 programs completed online surveys about the use of both telehealth and in-person services from February 2020 to June 2021. Survey questions addressed telehealth practices (e.g., policies, support resources), monthly service utilization, telehealth modality (videoconferencing vs. telephony), and missed appointments., Results: Programs varied in the proportion of appointments delivered by telehealth prior to the pandemic (February 2020; 0-27%). By May 2020 all programs were providing a majority of visits via telehealth (64-100%). In June 2021, all programs continued to provide services via telehealth (41% to 100%) and reported that they would continue to do so moving forward. Programs addressed many challenges to telehealth provision during the study period, including adding interpreter services, technological support for providers and patients, and formalizing safety and training requirements., Conclusion: Academic child and adolescent psychiatry programs provided outpatient services primarily via telehealth throughout the COVID-19 pandemic and reported that they planned to continue utilizing telehealth in combination with in-person services moving forward. Academic programs should therefore address logistical, technological, and financial barriers to the sustained use of telehealth.

Purpose: To recognize and address various sources of bias essential for algorithmic fairness and trustworthiness and to contribute to a just and equitable deployment of AI in medical imaging, there is an increasing interest in developing medical imaging-based machine learning methods, also known as medical imaging artificial intelligence (AI), for the detection, diagnosis, prognosis, and risk assessment of disease with the goal of clinical implementation. These tools are intended to help improve traditional human decision-making in medical imaging. However, biases introduced in the steps toward clinical deployment may impede their intended function, potentially exacerbating inequities. Specifically, medical imaging AI can propagate or amplify biases introduced in the many steps from model inception to deployment, resulting in a systematic difference in the treatment of different groups., Approach: Our multi-institutional team included medical physicists, medical imaging artificial intelligence/machine learning (AI/ML) researchers, experts in AI/ML bias, statisticians, physicians, and scientists from regulatory bodies. We identified sources of bias in AI/ML, mitigation strategies for these biases, and developed recommendations for best practices in medical imaging AI/ML development., Results: Five main steps along the roadmap of medical imaging AI/ML were identified: (1) data collection, (2) data preparation and annotation, (3) model development, (4) model evaluation, and (5) model deployment. Within these steps, or bias categories, we identified 29 sources of potential bias, many of which can impact multiple steps, as well as mitigation strategies., Conclusions: Our findings provide a valuable resource to researchers, clinicians, and the public at large., (© 2023 The Authors.)

Emotional intelligence includes an assortment of factors related to emotion function. Such factors involve emotion recognition (in this case via facial expression), emotion trait, reactivity, and regulation. We aimed to investigate how the subjective appraisals of emotional intelligence (i.e. trait, reactivity, and regulation) are associated with objective emotion recognition accuracy, and how these associations differ between young and older adults. Data were extracted from the CamCAN dataset (189 adults: 57 young/118 older) from assessments measuring these emotion constructs. Using linear regression models, we found that greater negative reactivity was associated with better emotion recognition accuracy among older adults, though the pattern was opposite for young adults with the greatest difference in disgust and surprise recognition. Positive reactivity and depression level predicted surprise recognition, with the associations significantly differing between the age groups. The present findings suggest the level to which older and young adults react to emotional stimuli differentially predicts their ability to correctly identify facial emotion expressions. Older adults with higher negative reactivity may be able to integrate their negative emotions effectively in order to recognize other's negative emotions more accurately. Alternatively, young adults may experience interference from negative reactivity, lowering their ability to recognize other's negative emotions.

In this case study, we aim to understand how health departments in 5 US jurisdictions addressed health inequities and implemented strategies to reach populations disproportionately affected by COVID-19 during the initial Omicron variant period. We used qualitative methods to examine health department experiences during the initial Omicron surge, from November 2021 to April 2022, assessing successful interventions, barriers, and lessons learned from efforts to promote health equity. Our findings indicate that government leadership supported prioritizing health equity from the beginning of the pandemic, seeing it as a need and vital part of the response framework. All jurisdictions acknowledged the historical trauma and distrust of the government. Health departments found that collaborating and communicating with trusted community leaders helped mitigate public distrust. Having partnerships, resources, and infrastructure in place before the pandemic facilitated the establishment of equity-focused COVID-19 response activities. Finally, misinformation about COVID-19 was a challenge for all jurisdictions. Addressing the needs of diverse populations involves community-informed decisionmaking, diversity of thought, and delivery measures that are tailored to the community. It is imperative to expand efforts to reduce and eliminate health inequities to ensure that individuals and communities recover equitably from the effects of COVID-19.

Introduction: Although the provision of clinical education (CE) experiences affords many benefits to clinical stakeholders, little published literature exists regarding the factors influencing decisions of site coordinators of CE (SCCE), clinical administrators, and clinical instructors (CI) to provide CE., Review of Literature: Site coordinators of CE and CIs navigate workplace expectations while making decisions about their engagement in CE experiences. The purpose of this study was to determine clinical stakeholders' perceptions of facilitators and barriers to the provision of CE experiences for entry-level Doctor of Physical Therapy students., Subjects: This study used survey data from a previous study on perspectives related to payment for CE experiences. The survey questions analyzed included responses provided by 501 clinical administrators, 445 SCCEs, and 657 CIs., Methods: Retrospective analysis of survey data included frequencies and percentages of responses for nominal and categorical data. Open-ended survey questions underwent content analysis to identify overarching concepts and subordinate categories., Results: Clinicians are most motivated to serve as CIs by "enjoyment of teaching" (274, 49.4%) and a sense of "professional responsibility" (147, 26.5%). Site coordinators of CEs indicated that the top challenges faced in soliciting CIs were the ability to manage challenging students (347, 69.0%), lack of experience serving as a CI (227, 63.4%), ability to maintain productivity standards (220, 61.5%), and clinician burnout (219, 61.2%). Although all participants agreed that their organization promotes a culture of teaching, clinical administrators agreed at a higher percentage than SCCEs (97.8% vs 94.3%, respectively)., Discussion and Conclusion: Clinical instructors identified values and benefits that were, at times, in contrast to the organizational culture. The discrepancies in perceptions among stakeholders that were uncovered by this research provide a unique lens that has not been addressed in the literature to date. To provide meaningful support for CIs, it is imperative that directors of CEs, clinical administrators, and SCCEs clearly understand the perceptions of the CI., (Copyright © 2023 Academy of Physical Therapy Education, APTA.)

Background: The pediatric palliative care literature provides little evidence regarding the lived experiences of adolescents and young adults (AYAs). Objectives: We sought to evaluate the aspects of a palliative care peer support program, which were most helpful to patients, and identify areas for improvement to better address their psychosocial needs. Design: This was a retrospective, cross-sectional study, which described self-reported Streetlight program evaluation using thematic analysis of interviews with AYAs. A total of 10 interviews was completed. Setting/Subjects: Thirty-three current and former Streetlight participants (13-30), enrolled in the Streetlight program for at least six months, were recruited during hospital admissions and clinic visits at UF Health Shands Hospital in the United States. Of the 33, 2 participants died before interviews could be conducted. A total of 10 interviews were conducted. Results: Thematic analysis of the 10 individuals identified 5 themes. They were (1) normalization of life in hospital, (2) mental health and instillation of hope, (3) companionship and connection, (4) diversity of volunteers, and (5) gratitude. Conclusions: Results suggest that AYAs who participated in a peer support, palliative care program benefitted from their exposure to volunteer social support. Addressing the need for continued study of this population provides opportunities to expand peer support, pediatric palliative care programs to other hospitals and care facilities.

Background: Sexual minority men (SMM) who engage in condomless anal sex and injection drug use are at increased risk for viral Hepatitis C (HCV) infection. Additionally, studies have found racial disparities in HCV cases across the United States. However, very few epidemiological studies have examined factors associated with HCV infection in HIV-negative Black and Latino SMM. This paper describes the rationale, design, and methodology of a prospective epidemiological study to quantify the HCV prevalence and incidence and investigate the individual and environmental-level predictors of HCV infection among HIV-negative, Black and Latino SMM in the Southern U.S., Methods: Beginning in September 2021, 400 Black and Latino SMM, aged 18 years and above, will be identified, recruited and retained over 12-months of follow-up from two study sites: greater Washington, DC and Dallas, TX areas. After written informed consent, participants will undergo integrated HIV/STI testing, including HCV, HIV, syphilis, gonorrhea, and chlamydia. Subsequently, participants will complete a quantitative survey-including a social and sexual network inventory-and an exit interview to review test results and confirm participants' contact information. Individual, interpersonal, and environmental factors will be assessed at baseline and follow-up visits (6 and 12 months). The primary outcomes are HCV prevalence and incidence. Secondary outcomes are sexual behavior, substance use, and psychosocial health., Results: To date (March 2023) a total of 162 participants have completed baseline visits at the DC study site and 161 participants have completed baseline visits at the Texas study site., Conclusion: This study has several implications that will directly affect the health and wellness of Black and Latino SMM. Specifically, our results will inform more-focused HCV clinical guidelines (i.e., effective strategies for HCV screening among Black/Latino SMM), intervention development and other prevention and treatment activities and development of patient assistance programs for the treatment of HCV among uninsured persons, especially in Deep South, that have yet to expand Medicaid., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ogunbajo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The cervix is a soft tissue exhibiting time-dependent behavior under mechanical loads. The cervix is a vital mechanical barrier to protect the growing fetus. The remodeling of the cervical tissue, characterized by an increase in time-dependent material properties, is necessary for a safe parturition. The failure of its mechanical function and accelerated tissue remodeling is hypothesized to lead to preterm birth, which is birth before 37 weeks of gestation. To understand the mechanism of the time-dependent behavior of the cervix under compressive states, we employ a porous-viscoelastic material model to describe a set of spherical indentation tests performed on nonpregnant and term pregnant tissue. A genetic algorithm-based inverse finite element analysis is used to fit the force-relaxation data by optimizing the material parameters, and the statistical analysis of the optimized material parameters is conducted on different sample groups. The force response is captured well using the porous-viscoelastic model. The indentation force-relaxation of the cervix is explained by the porous effects and the intrinsic viscoelastic properties of the extracellular matrix (ECM) microstructure. The hydraulic permeability obtained from the inverse finite element analysis agrees with the trend of the value directly measured previously by our group. The nonpregnant samples are found significantly more permeable than the pregnant samples. Within nonpregnant samples, the posterior internal os is found significantly less permeable than the anterior and posterior external os. The proposed model exhibits the superior capability to capture the force-relaxation response of the cervix under indentation, as compared to the conventional quasi-linear viscoelastic framework (range of r 2 of the porous-viscoelastic model 0.88-0.98 vs. quasi-linear model: 0.67-0.89). As a constitutive model with a relatively simple form, the porous-viscoelastic framework has the potential to be used to understand disease mechanisms of premature cervical remodeling, model contact of the cervix with biomedical devices, and interpret force readings from novel in-vivo measurement tools such as an aspiration device., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Community-based participatory research (CBPR) and community engaged research (CEnR) are key to promoting community and patient engagement in actionable evidence-based strategies to improve research for health equity. Rapid growth of CBPR/CEnR research projects have led to the broad adoption of partnering principles in community-academic partnerships and among some health and academic organizations. Yet, transformation of principles into best practices that foster trust, shared power, and equity outcomes still remain fragmented, are dependent on individuals with long term projects, or are non-existent. This paper describes how we designed our Engage for Equity PLUS intervention that leverages the leadership and membership of champion teams (including community-engaged faculty, community partners and patient advocates) to improve organizational policies and practices to support equity based CBPR/CEnR. This article describes the feasibility and preliminary findings from engaging champion teams from three very different academic health centers. We reflect on the learnings from Engage for Equity PLUS; the adaptation of the intervention design and implementation, including the development of a new institutional assessment using mixed research methods; and our organizational theory of change. In summary, our design and preliminary data from the three academic health centers provide support for new attention to the role of institutional practices and processes needed to sustain equity-based patient and community-engaged research and CBPR and transform the field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sanchez-Youngman, Adsul, Gonzales, Dickson, Myers, Alaniz and Wallerstein.)

In congregate living settings when active coronavirus disease 2019 (COVID-19) transmission is present, limiting the scope of dental care to urgent and emergent treatment minimizes exposure risk for patients and staff. Engineering controls to mitigate aerosol production during dental procedures, including enhanced high-volume evacuation, high-efficiency particulate absorbing air filtration, and the use of a dental dam provide additional protection for dental providers and staff. Properly fitted N-95 respirators are of particular importance to limit COVID-19 transmission when SARS-CoV-2 containing aerosols may be present. When patients are known to be COVID-19 positive, the use of powered air-purifying respirators is appropriate. Further protection against the spread of disease among patients and staff may be provided by point-of-care testing for patients prior to dental procedures during outbreaks.