Circulating High Mobility Group Box-1 Does Not Predict Pulmonary Arterial Hypertension in Children with Congenital Heart Disease: A Prospective Cohort Study.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a devastating complication of pediatric congenital heart disease (CHD). A recent study has identified the protein high mobility group box-1 (HMGB1) as a diagnostic tool in adults with CHD-associated PAH. HMGB1 levels in adults with CHD-associated PAH correlated with mean pulmonary artery pressure and pulmonary vascular resistance, and HGMB1 levels fell in response to sildenafil therapy. We wanted to assess if HGMB1 was a biomarker of pediatric CHD-PAH. DESIGN: Prospective cohort study. SETTING: Quaternary pediatric academic hospital PARTICIPANTS: Children ≤18 years with CHD with and without known pulmonary hypertension. Controls were children undergoing dental or urologic surgery with no known heart disease. INTERVENTIONS: Pulmonary hemodynamics, echocardiographic assessment, and biomarker measurement. Controls had biomarker measurement only. MEASUREMENTS AND MAIN RESULTS: Patients with CHD-PAH had mean pulmonary vascular resistance index of 10 Wood units/m2. Neither HGMB1 nor N-terminal pro-brain-type natriuretic peptide levels were significantly different between the groups. Neither marker correlated with pulmonary hypertension. CONCLUSIONS: Unlike in adults, HGMB1 is not a biomarker of PAH in pediatric CHD. Further work will continue to explore for biomarkers for this high-risk population.

The Relationship Between Body Mass Index and Long-Term Outcomes Following Traumatic Injury.

INTRODUCTION: Little is known about the relationship between body mass index (BMI), a function of mass and height (masskg/height2m) and long-term outcomes among traumatic injury survivors. In this prospective cohort study, we investigate the relationship between BMI and long-term health outcomes in the trauma population. METHODS: Adult trauma survivors with an injury severity score ≥9 admitted to one of three level 1 trauma centers, from January 1, 2015 to December 31, 2022, were surveyed via telephone between 6 and 12 mo postinjury. Participants were stratified into one of five groups by BMI at the time of trauma: L-BMI (BMI <18.5), N-BMI (BMI 18.5-24.9), H1-BMI (BMI 25-29.9), H2-BMI (BMI 30-34.9), and H3-BMI (BMI ≥35); N-BMI was used as the referent. Mental and physical health-related quality of life scores, pain, new functional limitations, and hospital readmissions were evaluated. Univariate and multivariate analyses were used to compare outcomes between study groups. RESULTS: 3830 patients were included. Of those, 124 were L-BMI (3.2%), 1495 N-BMI (39%), 1318 H1-BMI (34.4%), 541 H2-BMI (14.1%), and 352 H3-BMI (9.2%). L-BMI was associated with adverse physical (b = -3.13, CI = -5.71 to -0.55, P = 0.017) and mental health (b = -3.17, CI = -5.87 to -0.46, P = 0.022) outcomes 6-12 mo postinjury compared to the referent. H1-BMI and H2-BMI had higher odds of wo`rse physical outcomes (b = -1.47, CI = -2.42 to -0.52, P = 0.002; b = -3.11, CI = - 4.33 to -1.88, P ≤ 0.001, respectively) and chronic pain (adjusted odds ratio (aOR) = 1.24, CI = 1.04-1.47, P = 0.016; aOR = 1.52, CI = 1.21-1.90, P ≤ 0.001, respectively). Patients with H3-BMI had higher odds of worse physical outcomes compared to N-BMI (b = -4.82, CI = -6.28 to -3.37, P ≤ 0.001), chronic pain (aOR = 2.11, CI = 1.61-2.78, P ≤ 0.001), all-cause hospital readmissions (aOR = 1.62, CI = 1.10-2.34, P = 0.013), and new functional limitations (aOR = 1.39, CI = 1.08-1.79, P = 0.01). CONCLUSIONS: BMI variance above or below N-BMI is associated with worse long-term outcomes following traumatic injury.

Systematic multi-trait AAV capsid engineering for efficient gene delivery.

Broadening gene therapy applications requires manufacturable vectors that efficiently transduce target cells in humans and preclinical models. Conventional selections of adeno-associated virus (AAV) capsid libraries are inefficient at searching the vast sequence space for the small fraction of vectors possessing multiple traits essential for clinical translation. Here, we present Fit4Function, a generalizable machine learning (ML) approach for systematically engineering multi-trait AAV capsids. By leveraging a capsid library that uniformly samples the manufacturable sequence space, reproducible screening data are generated to train accurate sequence-to-function models. Combining six models, we designed a multi-trait (liver-targeted, manufacturable) capsid library and validated 88% of library variants on all six predetermined criteria. Furthermore, the models, trained only on mouse in vivo and human in vitro Fit4Function data, accurately predicted AAV capsid variant biodistribution in macaque. Top candidates exhibited production yields comparable to AAV9, efficient murine liver transduction, up to 1000-fold greater human hepatocyte transduction, and increased enrichment relative to AAV9 in a screen for liver transduction in macaques. The Fit4Function strategy ultimately makes it possible to predict cross-species traits of peptide-modified AAV capsids and is a critical step toward assembling an ML atlas that predicts AAV capsid performance across dozens of traits.

Complementary Nanoparticle Characterization by Resistive-Pulse Sensing, Electron Microscopy, and Charge Detection Mass Spectrometry.

Nanotechnology has provided novel modalities for the delivery of therapeutic and diagnostic agents. In particular, nanoparticles (NPs) can be engineered at a low cost for drug loading and delivery. For example, silica NPs have proven useful as a controlled release platform for anti-inflammatory drugs. Despite the wide-ranging potential applications for NPs, robust characterization across all size ranges remains elusive. Electron microscopy (EM) is the conventional tool for measuring NP diameters. However, imitations in throughput and the inability to provide comprehensive information on physical properties, such as mass and density, without underlying assumptions, hinder a complete analysis. In addition, assessing sample heterogeneity, aggregation, or coalescence in solution by traditional EM analysis is not possible. Resistive-pulse sensing (RPS) provides a high throughput, solution-phase method for characterizing particle heterogeneity based on volume. Complementing these methods, charge detection mass spectrometry (CD-MS), a single particle technique, provides accurate mass information for heterogeneous samples including NPs. By combining EM, RPS and CD-MS, accurate volume, mass, and densities were obtained for silica NPs of various sizes. The results show that the density for 20 nm silica NPs is close to the density of fused silica (2.2 g/cm3). Larger silica NPs were found to have densities that were either smaller or larger, while also falling outside the range of densities usually found for silica colloids and NPs (1.9-2.3 g/cm3). Lower densities are attributed to pores (i.e., porous particles). For one sample, the mass distribution showed two components attributed to two populations of particles in the sample with different densities. The synergistic combination of EM, RPS, and CD-MS measurements outlined here for NP samples, allows much more extensive information to be obtained than from any of the techniques alone.

Advancements in treatment strategies for periprosthetic joint infections: A comprehensive review.

Periprosthetic joint infection (PJI) presents a critical challenge in orthopedic care, contributing to significant patient morbidity and healthcare costs. This burden is expected to increase secondary to growing demand for total joint arthroplasty (TJA). Despite the profound significance of PJI, there is currently no universally accepted "gold standard" diagnostic criteria using serum biomarker thresholds; latest criteria fail to differentiate acute infections from chronic or consider time since initial surgery. Furthermore, contemporary PJI treatment, which conventionally requires 2-stage revision surgery in conjunction with rigorous antibiotic treatment, can be particularly taxing on patients. Fortunately, recent years have seen marked evolution in both PJI diagnosis and treatment methods. Contemporary research supports time-dependent serum biomarker thresholds with greater sensitivity and specificity than previously reported, as well as alternative surgical options which may be more suitable for certain patients. The following narrative review aims to describe the significance and pathogenesis of PJI before characterizing current challenges, novel innovations, and the future landscape of PJI diagnosis and management. Here, we spotlight the emerging utility of novel biomarkers and metagenomic next-generation sequencing for diagnosis, advancements in patient-centered surgical outcome prediction tools for PJI risk assessment and prevention, and evolving surgical techniques including 1-stage and a "hybrid" 1.5-stage revision surgeries. Additionally, we explore cutting-edge therapeutic modalities including peptide and bacteriophage-based treatments, intraoperative anti-biofilm gel, the VT-X7 antibiotic pump, and promising immune-based interventions. Ultimately, these advancements hold the potential to revolutionize PJI management, offering hope for improved outcomes and reduced burdens on healthcare systems.

Prognostic utility of exercise cardiovascular magnetic resonance in patients with systemic sclerosis-associated pulmonary arterial hypertension.

AIMS: Systemic sclerosis complicated by pulmonary arterial hypertension (SSc-PAH) is a rare condition with poor prognosis. The majority of patients are categorized as intermediate risk of mortality. Cardiovascular magnetic resonance (CMR) is well placed to reproducibly assess right heart size and function, but most patients with SSc-PAH have less overtly abnormal right ventricles than other forms of PAH. The aim of this study was to assess if exercise CMR measures of cardiac size and function could better predict outcome in patients with intermediate risk SSc-PAH compared with resting CMR. METHODS AND RESULTS: Fifty patients with SSc-PAH categorized as intermediate risk underwent CMR-augmented cardiopulmonary exercise testing. Most patients had normal CMR-defined resting measures of right ventricular (RV) size and function. Nine (18%) patients died during a median follow-up period of 2.1 years (range 0.1-4.6). Peak exercise RV indexed end-systolic volume (ESVi) was the only CMR metric to predict prognosis on stepwise Cox regression analysis, with an optimal threshold < 39 mL/m2 to predict favourable outcome. Intermediate-low risk patients with peak RVESVi < 39 mL/m2 had significantly better survival than all other combinations of intermediate-low/-high risk status and peak RVESVi< or ≥39 mL/m2. In our cohort, ventilatory efficiency and resting oxygen consumption (VO2) were predictive of mortality, but not peak VO2, peak cardiac output, or peak tissue oxygen extraction. CONCLUSION: Exercise CMR assessment of RV size and function may help identify SSc-PAH patients with poorer prognosis amongst intermediate risk cohorts, even when resting CMR appears reassuring, and could offer added value to clinical PH risk stratification.

Charge Detection Mass Spectrometry Enables Molecular Characterization of Nucleic Acid Nanoparticles.

Nucleic acid nanoparticles (NANPs) are increasingly used in preclinical investigations as delivery vectors. Tools that can characterize assembly and assess quality will accelerate their development and clinical translation. Standard techniques used to characterize NANPs, like gel electrophoresis, lack the resolution for precise characterization. Here, we introduce the use of charge detection mass spectrometry (CD-MS) to characterize these materials. Using this technique, we determined the mass of NANPs varying in size, shape, and molecular mass, NANPs varying in production quality due to formulations lacking component oligonucleotides, and NANPs functionalized with protein and nucleic acid-based secondary molecules. Based on these demonstrations, CD-MS is a promising tool to precisely characterize NANPs, enabling more precise assessments of the manufacturing and processing of these materials.

A Finite Element Analysis Model for Magnetomotive Ultrasound Elastometry Magnet Design with Experimental Validation.

OBJECTIVE: Magnetomotive ultrasound (MMUS) using magnetic nanoparticle contrast agents has shown promise for thrombosis imaging and quantitative elastometry via magnetomotive resonant acoustic spectroscopy (MRAS). Young's modulus measurements of smaller, stiffer thrombi require an MRAS system capable of generating forces at higher temporal frequencies. Solenoids with fewer turns, and thus less inductance, could improve high frequency performance, but the reduced force may compromise results. In this work, a computational model capable of predicting improved MRAS magnet configurations optimized for elastometry is presented and validated. APPROACH: Finite element analysis (FEA) was used to model the force and inductance of MRAS systems. The simulations incorporated both solenoid electromagnets and permanent magnets in three-dimensional steady-state, frequency domain, and time domain studies. MAIN RESULTS: The model successfully predicted a configuration in which permanent magnets could be used to increase the force supplied by an existing MRAS system. Accordingly, the displacement measured in a magnetically labeled validation phantom increased by a factor of $2.2 \pm 0.3$ when the force was predicted to increase by a factor of $2.2 \pm 0.2$. The model additionally identified a new solenoid configuration consisting of four smaller coils capable of providing sufficient force at higher driving frequencies. SIGNIFICANCE: These results indicate two methods by which MRAS systems could be designed to deliver higher frequency magnetic forces without the need for experimental trial and error. Either the number of turns within each solenoid could be reduced while permanent magnets are added at precise locations, or a larger number of smaller solenoids could be used. These findings overcome a key challenge toward the goal of thrombosis elastometry via MMUS.

Inhibition of autophagy as a novel treatment for neurofibromatosis type 1 tumors.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutation of the NF1 gene that is associated with various symptoms, including the formation of benign tumors, called neurofibromas, within nerves. Drug treatments are currently limited. The mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib is used for a subset of plexiform neurofibromas (PNs) but is not always effective and can cause side effects. Therefore, there is a clear need to discover new drugs to target NF1-deficient tumor cells. Using a Drosophila cell model of NF1, we performed synthetic lethal screens to identify novel drug targets. We identified 54 gene candidates, which were validated with variable dose analysis as a secondary screen. Pathways associated with five candidates could be targeted using existing drugs. Among these, chloroquine (CQ) and bafilomycin A1, known to target the autophagy pathway, showed the greatest potential for selectively killing NF1-deficient Drosophila cells. When further investigating autophagy-related genes, we found that 14 out of 30 genes tested had a synthetic lethal interaction with NF1. These 14 genes are involved in multiple aspects of the autophagy pathway and can be targeted with additional drugs that mediate the autophagy pathway, although CQ was the most effective. The lethal effect of autophagy inhibitors was conserved in a panel of human NF1-deficient Schwann cell lines, highlighting their translational potential. The effect of CQ was also conserved in a Drosophila NF1 in vivo model and in a xenografted NF1-deficient tumor cell line grown in mice, with CQ treatment resulting in a more significant reduction in tumor growth than selumetinib treatment. Furthermore, combined treatment with CQ and selumetinib resulted in a further reduction in NF1-deficient cell viability. In conclusion, NF1-deficient cells are vulnerable to disruption of the autophagy pathway. This pathway represents a promising target for the treatment of NF1-associated tumors, and we identified CQ as a candidate drug for the treatment of NF1 tumors.

Simultaneous removal of endotoxins, inflammatory mediators and uremic toxins in ICU patients with septic shock: a retrospective cohort study.

Sepsis, one of the leading causes of death, is still lacking specific treatment. OXIRIS (BAXTER, Deerfield, IL, USA) is the first device allowing combined removal of endotoxins, inflammatory mediators and uremic toxins, alongside fluid balance control. Available data is very limited. This retrospective propensity score-matched cohort study of adult patients with septic shock aimed to evaluate septic shock duration and mortality in patients treated with either standard of care renal replacement therapy (RRT) or RRT with combined hemoadsorption, who were admitted to the interdisciplinary surgical intensive care unit at Heidelberg University Hospital during the years 2018 through 2021. Main outcomes were duration of shock, thirty-day mortality and plasma interleukin-6 levels before and after initiation of hemoadsorption. Included were 117 patients (female, 33%; male 67%); median age: 67 (16) years. After matching: 42 patients (female, 33%; male, 67%); mean age: 59.1 ± 13.8 years. There was no statistically significant difference in septic shock duration (p = 0.94; hazard ratio (HR) 0.97 (95% CI, 0.48-1.97)). Thirty-day survival analysis showed a non-statistically significant survival difference. (p = 0.063; HR 0.43 (95% CI, 0.17-1.09)). A post-hoc 90-day survival analysis revealed statistically significant longer survival and lower death hazard ratio in patients treated with RRT + HA (p = 0.037; HR = 0.42 (95% CI, 0.18-0.99). In conclusion, RRT with combined hemoadsorption of endotoxins, inflammatory mediators and uremic toxins is a modality worth further investigation.

NASC 2023: Showcasing Diversity in North American Supramolecular Chemistry.

Diversity in supramolecular chemistry can showcase itself in many ways. This includes the diversity of thought and topics covered in research (from fundamental science to applications in biology and materials), as well as the diversity of people (e.g., diversity in race, gender, sexual orientation, country of origin, type of higher education institute, career stage,…). At the North American Supramolecular Chemistry (NASC) meetings, we aim to bring together the best that supramolecular chemistry has to offer in North America, create a sense of community and provide a platform for researchers at any stage of their career to present their work. NASC 2023 was the successful second edition of the NASC meeting series, and this proceedings article highlights the research and impressions of some of the speakers at NASC 2023.

Long term outcomes after lobar versus sublobar resection for patients with Non-Small cell lung Cancer: Systematic review and individual patient data Meta-Analysis.

OBJECTIVES: Surgical resection remains the primary treatment for early-stage non-small cell lung cancer (NSCLC), with lobectomy considered the standard approach. However, recent evidence suggests that sublobar resection may be an alternative option for select patients. MATERIALS AND METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Randomized controlled trials (RCTs) and propensity-score matched (PSM) cohort studies comparing lobectomy and sublobar resection in NSCLC patients were included. The primary outcome was overall survival (OS), and secondary outcomes included disease-free survival (DFS), 30-day mortality, and cancer recurrence rates. Individual patient data (IPD) were reconstructed from Kaplan-Meier curves, and one-stage and two-stage meta-analyses were performed. RESULTS: A total of 18 studies involving 6,075 NSCLC patients (3,119 undergoing lobectomy, 2,956 undergoing sublobar resection) were included. Lobectomy was associated with significantly better OS compared to sublobar resection (hazard ratio [HR]: 0.78, 95 % confidence interval [CI]: 0.68-0.89, p < 0.001). However, when sublobar resection was further divided into segmentectomy and wedge resection, no significant difference in OS was observed between lobectomy and segmentectomy (HR:0.92, 95 %CI: 0.75-1.14, p = 0.464) whereas lobar resection was associated with better OS compared to wedge resection (HR:0.52, 95 %CI: 0.41-0.67, p < 0.001). DFS outcomes were similar between lobectomy and sublobar resection (HR:0.98, 95 %CI: 0.84-1.14, p = 0.778). CONCLUSION: Lobectomy is associated with better overall survival compared to sublobar resection in NSCLC patients. However, when sublobar resection is subdivided, segmentectomy shows comparable outcomes to lobectomy, while wedge resection is inferior. These findings support the consideration of segmentectomy as the surgical option of choice for Stage IA NSCLC patients.

Stable isotopes reveal trophic ontogeny in Cisco (Coregonus artedi).

Cisco (Coregonus artedi) are a widespread, cold-water zooplanktivore native to North America. Although Cisco are generally referred to as an "obligate zooplanktivore," there is some evidence that the species exhibits considerable variability in trophic niche. Here, we assessed how Cisco body size relates to trophic position, that is, trophic ontogeny. We analysed 13C and 15N isotopes from Cisco ranging from 127 to 271 mm in body length (n = 66) from Trout Lake, Vilas County, Wisconsin, USA. 15N isotopes showed smaller Cisco had a trophic position of ~3, which steadily increased to ~3.5 for larger Cisco. Further, 13C isotope signatures showed Cisco transitioned to be more pelagically reliant (lower 13C signatures). Using gillnet catch data, we found that larger Cisco were using deeper habitats than smaller Cisco. Our results support that Cisco have significant variability in trophic niche even though they are traditionally thought of as an obligate planktivore. Overall, we emphasize that researchers should be cautious when generalizing Cisco trophic function, particularly when considering the broader food web.

The Role of Immunotherapy in the Management of Esophageal Cancer in Patients Treated with Neoadjuvant Chemoradiation: An Analysis of the National Cancer Database.

BACKGROUND: The current National Comprehensive Cancer Network advises neoadjuvant chemoradiotherapy followed by surgery for locally advanced cases of esophageal cancer. The role of immunotherapy in this context is under heavy investigation. METHODS: Patients with esophageal adenocarcinoma were identified in the National Cancer Database (NCDB) from 2004 to 2019. Three groups were generated as follows: (a) no immunotherapy, (b) neoadjuvant immunotherapy, and (c) adjuvant immunotherapy. Overall survival was evaluated using the Kaplan-Meier method and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality. RESULTS: Of the total 14,244 patients diagnosed with esophageal adenocarcinoma who received neoadjuvant chemoradiation, 14,065 patients did not receive immunotherapy, 110 received neoadjuvant immunotherapy, and 69 received adjuvant immunotherapy. When adjusting for established risk factors, adjuvant immunotherapy was associated with significantly improved survival compared to no immunotherapy and neoadjuvant immunotherapy during a median follow-up period of 35.2 months. No difference was noted among patients who received no immunotherapy vs. neoadjuvant immunotherapy in the same model. CONCLUSIONS: In this retrospective analysis of the NCDB, receiving adjuvant immunotherapy offered a significant survival advantage compared to no immunotherapy and neoadjuvant immunotherapy in the treatment of esophageal adenocarcinoma. The addition of neoadjuvant immunotherapy to patients treated with neoadjuvant chemoradiation did not improve survival in this cohort. Further studies are warranted to investigate the long-term outcomes of immunotherapy in esophageal cancer.

Measurement invariance of the PROMIS emotional distress and subjective well-being domains among autistic and General Population adolescents.

PURPOSE: Quality of life (QoL) is identified as a clinical and research priority by the autistic community. Researchers have the responsibility to ensure that instruments used to measure QoL do so reliably and accurately among autistic participants. METHODS: Our study evaluated measurement invariance of Emotional Distress (Depression, Anxiety, Anger, Psychological Stress) and Subjective Well-Being (Life Satisfaction, Positive Affect, and Meaning & Purpose) scales of the Patient-Reported Outcomes Measurement Information System (PROMIS) among groups of autistic (N=140, n per scale=132-140) and general population (N=1,224, n per scale=406-411) teenagers (14-17 years). These scales were included in the PROMIS Autism Battery-Lifespan, which uses PROMIS scales to measure QoL domains most relevant for autistic people. RESULTS: Multi-group confirmatory factor analyses using permutation tests demonstrated that Depression and Positive Affect scales exhibited scalar invariance between groups, indicating that scores can be meaningfully compared across autistic and general population teens. Anger and Psychological Stress scales demonstrated metric invariance between groups, indicating that these scales measure the same latent trait in both groups, but group comparisons are not supported. CONCLUSION: We provide guidance as to how these scales can be used in psychometrically supported ways to capture constructs relevant for understanding QoL among autistic teens.

Quality of life is an important outcome for autistic people and their families. However, many quality of life scales have not been tested to make sure they accurately measure quality of life among autistic people. It is important to make sure that quality of life measures works similarly among the autistic population. The goal of our study is to test whether scales on a common quality of life measure ­ the Patient-Reported Outcomes Measurement Information System (PROMIS) ­ measures quality of life in the same way between autistic and general population adolescents. We found that some of the PROMIS scales worked the same way for autistic and general population adolescents and others did not. These results help researchers confidently use the PROMIS scales to measure different aspects of quality of life among autistic youth.

Sex Differences in Sympathetic Transduction in Black and White Adults: Implications for Racial Disparities in Hypertension and Cardiovascular Disease Risk.

The prevalence of hypertension in non-Hispanic black (BL) individuals is the greatest of any racial/ethnic group. While women generally display lower rates of hypertension than men of the same background, BL women display a similar if not greater burden of hypertension compared to BL men. The risk for cardiovascular disease and related events is also highest in BL individuals. Given the importance of the sympathetic nervous system for the regulation of the cardiovascular system, a growing body of literature has investigated sympathetic function in BL and non-Hispanic white (WH) individuals. Herein, we are focused on emerging evidence indicating sympathetic function may be altered in BL individuals, with particular emphasis on the process by which bursts of muscle sympathetic nerve activity (MSNA) are transduced into vasoconstriction and increases in blood pressure (sympathetic vascular transduction). To synthesize this growing body of literature we discuss sex and race differences in 1) sympathetic outflow 2) sympathetic vascular transduction and 3) adrenergic receptor sensitivity. Sex differences are discussed foremost to set the stage for new data indicating a sex dimorphism in sympathetic regulation in BL individuals. Specifically, we highlight evidence for a potential neurogenic phenotype including greater adiposity-independent sympathetic outflow and enhanced sympathetic vascular transduction in BL men that is not observed in BL women. The implications of these findings for the greater hypertension and cardiovascular disease risk in BL adults are discussed along with areas that require further investigation.

Reporting Minority Race and Ethnicity in Cardiovascular and Thoracic Journals.

INTRODUCTION: Currently, there is no mandatory standard for reporting race and ethnicity in medical journals, presenting significant barriers to studying disparities in medical outcomes. We seek to investigate whether greater recent awareness of diversity and inclusion reflects in reporting of race and ethnicity by peer-reviewed cardiothoracic articles. METHODS: Pubmed was queried for clinical outcomes articles published from January 2017 to June 2023 in the Journal of Thoracic and Cardiovascular Surgery, Annals of Thoracic Surgery, Journal of Heart and Lung Transplantation, and CHEST Journal. Basic science, translational studies, and international studies were excluded. SAS Studio was used for statistical analysis. RESULTS: 817 papers were reviewed, 378 reported race/ethnicity with 354 (93%) reporting White, 267 (71%) reporting Black, 128 (34%) reporting Hispanic, and 119 (31%) reporting Asian. Over 8-y, there were no statistically significant changes in percent of articles that included White (odds ratio 0.808 95% confidence interval [0.624-1.047], P = 0.1068), Black (1.125 [0.984-1.288], P = 0.0857), or Asian (1.096 [0.960-1.250], P = 0.1751) groups. Hispanics were more likely to be reported in recent years (1.147 [1.006-1.307], P = 0.0397). Subset analysis was performed on cardiac (n = 157) and thoracic articles (n = 157) with no significant trends for race reporting in these subsets. CONCLUSIONS: Minorities remain underrepresented in reported patient populations in peer-reviewed cardiothoracic journals. Future efforts should prioritize accurately representing these populations in the literature. Inaccurate data and exclusion of minority populations can contribute to disparities observed in overall outcomes.

Tris-Silanide f-Block Complexes: Insights into Paramagnetic Influence on NMR Chemical Shifts.

The paramagnetism of f-block ions has been exploited in chiral shift reagents and magnetic resonance imaging, but these applications tend to focus on 1H NMR shifts as paramagnetic broadening makes less sensitive nuclei more difficult to study. Here we report a solution and solid-state (ss) 29Si NMR study of an isostructural series of locally D 3h -symmetric early f-block metal(III) tris-hypersilanide complexes, [M{Si(SiMe3)3}3(THF)2] (1-M; M = La, Ce, Pr, Nd, U); 1-M were also characterized by single crystal and powder X-ray diffraction, EPR, ATR-IR, and UV-vis-NIR spectroscopies, SQUID magnetometry, and elemental analysis. Only one SiMe3 signal was observed in the 29Si ssNMR spectra of 1-M, while two SiMe3 signals were seen in solution 29Si NMR spectra of 1-La and 1-Ce. This is attributed to dynamic averaging of the SiMe3 groups in 1-M in the solid state due to free rotation of the M-Si bonds and dissociation of THF from 1-M in solution to give the locally C 3v -symmetric complexes [M{Si(SiMe3)3}3(THF) n ] (n = 0 or 1), which show restricted rotation of M-Si bonds on the NMR time scale. Density functional theory and complete active space self-consistent field spin-orbit calculations were performed on 1-M and desolvated solution species to model paramagnetic NMR shifts. We find excellent agreement of experimental 29Si NMR data for diamagnetic 1-La, suggesting n = 1 in solution and reasonable agreement of calculated paramagnetic shifts of SiMe3 groups for 1-M (M = Pr and Nd); the NMR shifts for metal-bound 29Si nuclei could only be reproduced for diamagnetic 1-La, showing the current limitations of pNMR calculations for larger nuclei.

Effects of mineralization on the hierarchical organization of collagen-a synchrotron X-ray scattering and polarized second harmonic generation study.

The process of mineralization fundamentally alters collagenous tissue biomechanics. While the structure and organization of mineral particles have been widely studied, the impact of mineralization on collagen matrix structure, particularly at the molecular scale, requires further investigation. In this study, synchrotron X-ray scattering (XRD) and polarization-resolved second harmonic generation microscopy (pSHG) were used to study normally mineralizing turkey leg tendon in tissue zones representing different stages of mineralization. XRD data demonstrated statistically significant differences in collagen D-period, intermolecular spacing, fibril and molecular dispersion and relative supramolecular twists between non-mineralizing, early mineralizing and late mineralizing zones. pSHG analysis of the same tendon zones showed the degree of collagen fibril organization was significantly greater in early and late mineralizing zones compared to non-mineralizing zones. The combination of XRD and pSHG data provide new insights into hierarchical collagen-mineral interactions, notably concerning possible cleavage of intra- or interfibrillar bonds, occlusion and reorganization of collagen by mineral with time. The complementary application of XRD and fast, label-free and non-destructive pSHG optical measurements presents a pathway for future investigations into the dynamics of molecular scale changes in collagen in the presence of increasing mineral deposition.

Rotational spectroscopy of 2,4,6-cycloheptatriene-1-carbonitrile: facilitating the search for complex cyclic molecules in the ISM.

The recent astronomical observations of the simplest aromatic nitrile benzonitrile, c-C6H5CN, followed by a five-membered and a bicyclic CN-functionalized ring in TMC-1 have provided a significant impetus to the field for searches of cyclic complex organic molecules in space. One such example is 2,4,6-cycloheptatriene-1-carbonitrile, a seven-membered ring with a -CN group attached to the sp3-hybridized carbon atom. With a permanent electric dipole moment of 4.3 D, this molecule is an excellent candidate for laboratory rotational spectroscopy. In this study, experiments were performed in the 2-8 GHz, 18-26 GHz, and 75-110 GHz frequency ranges in a supersonic expansion setup and a room temperature flow cell setup. The measurements across the broad frequency range of 2-110 GHz have enabled the identification and assignment of the vibronic ground state, singly substituted rare-atom isotopologues, and vibrationally excited states. Here, we report the precise determination of the rotational constants, quartic centrifugal distortion constants, nitrogen nuclear quadrupole coupling constants, as well as molecular structure in its vibronic ground state. The comprehensive rotational spectroscopy study of this molecule, covering a large frequency range, forms the basis for its future astronomical detection and thus for extending the pool of detected complex cyclic molecules.