BLM helicase unwinds lagging strand substrates to assemble the ALT telomere damage response.

The Bloom syndrome (BLM) helicase is critical for alternative lengthening of telomeres (ALT), a homology-directed repair (HDR)-mediated telomere maintenance mechanism that is prevalent in cancers of mesenchymal origin. The DNA substrates that BLM engages to direct telomere recombination during ALT remain unknown. Here, we determine that BLM helicase acts on lagging strand telomere intermediates that occur specifically in ALT-positive cells to assemble a replication-associated DNA damage response. Loss of ATRX was permissive for BLM localization to ALT telomeres in S and G2, commensurate with the appearance of telomere C-strand-specific single-stranded DNA (ssDNA). DNA2 nuclease deficiency increased 5'-flap formation in a BLM-dependent manner, while telomere C-strand, but not G-strand, nicks promoted ALT. These findings define the seminal events in the ALT DNA damage response, linking aberrant telomeric lagging strand DNA replication with a BLM-directed HDR mechanism that sustains telomere length in a subset of human cancers.

Supramolecular Interactions-Assisted Polymorphism and Unique Mechanofluorochromism in 9,10-Bis((E)-4-(trifluoromethyl)styryl)anthracene.

A fluorinated distyrylanthracene (DSA) derivative, 9, 10-bis((E)-4-(trifluoromethyl)styryl)anthracene abbreviated as 4FDSA with two crystalline polymorphs (4FDSA-G (green emission) and 4FDSA-O (orange emission)), showing remarkable aggregation-induced enhanced emission and mechanofluorochromic characteristics, was developed. One of the polymorphs in its crystalline arrangement exhibits the hardly seen F…F interactions. It questions the conventional belief of the non-polarisable nature of fluorine atoms in forming the halogen bond. The twisted molecular conformation facilitated by the various supramolecular interactions resulted in the formation of another intensely emissive bluer nanocrystal (4FDSA-NC) at aggregating conditions. Even though, the both polymorphs show distinct tricolor luminescence switching on the action of mechanical force, fumigation of ground crystals with solvent vapor resulted in the formation of a more thermodynamically favorable 4FDSA-NC form. The work demonstrates the effect of supramolecular interactions assisted conformational changes in tuning the unique mechanofluorochromic characteristics of the polymorphic crystals.

A novel benzothiophene incorporated Schiff base acting as a "turn-on" sensor for the selective detection of Serine in organic medium.

A novel fluorogenic sensor N-benzo[b]thiophen-2-yl-methylene-4,5-dimethyl-benzene-1,2-diamine (BTMPD) was synthesized and characterized by using spectroscopic methods including UV-visible, FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The designed fluorescent probe, owing to its remarkable properties, behaves as an efficient turn-on sensor for the sensing of amino acid Serine (Ser). Also, the strength of the probe enhances upon the addition of Ser via charge transfer, and the renowned properties of the fluorophore were duly found. The sensor BTMPD shows incredible execution potential with respect to key performance indicators such as high selectivity, sensitivity, and low detection limit. The concentration change was linear ranging from 5 × 10-8 M to 3 × 10-7 M, which is an indication of the low detection limit of 1.74 ± 0.02 nM under optimal reaction conditions. Interestingly, the Ser addition leads to an increased intensity of the probe at λ = 393 nm which other co-existing species did not. The information about the arrangement and the features of the system and the HOMO-LUMO energy levels was found out theoretically using DFT calculations which is fairly in good agreement with the experimental cyclic voltammetry results. The fluorescence sensing using the synthesized compound BTMPD reveals the practical applicability and its application in real sample analysis.

Analyzing the Scholarly Impact of Cardiothoracic Surgery Research Using the Relative Citation Ratio.

INTRODUCTION: The National Institutes of Health (NIH) recently developed the relative citation ratio (RCR), calculated as article citations benchmarked to NIH-funded publications in the same field. Here, we characterized the scholarly impact of academic cardiothoracic (CT) surgeons and their research using the RCR. MATERIALS AND METHODS: Using a database of 992 CT surgeons, we calculated the RCR for all articles published by each surgeon since 1980 using the NIH iCite database. All data were collected from publicly available online sources. Data are presented as median (interquartile range) or as odds ratios (ORs) for multivariable logistic regression analysis. RESULTS: Where RCR 1.00 indicates equal impact as an NIH-funded publication, the RCR among all 37,402 CT surgery articles was 0.84 (0.33-1.83) and the RCR among NIH-funded CT surgery articles was 1.07 (0.53-2.17). CT surgeons exhibited a career median RCR of 0.82 (0.54-1.13) and maximum RCR of 6.20 (3.04-13.57). Predictors of career median RCR >1.00 included female gender (OR 2.23, P = 0.001), thoracic subspecialization (OR 2.50, P < 0.001), full professor rank (OR 1.89, P = 0.001), and NIH funding (OR 1.75, P = 0.001). Predictors of career maximum RCR >50th percentile among CT surgeons included male gender (OR 1.87, P = 0.030), thoracic subspecialization (OR 2.05, P < 0.001), full professor rank (OR 4.89, P < 0.001), NIH funding (OR 3.17, P < 0.001), and career duration (OR 1.03, P = 0.002). CONCLUSIONS: We present the first assessment of the NIH-validated RCR for academic CT surgery. CT surgery research is highly impactful, although gender disparities persist with respect to the highest-impact research of our specialty.

Characterization of Cardiothoracic Surgeons Actively Leading Basic Science Research.

BACKGROUND: There is increasing concern regarding the attrition of surgeon-scientists in cardiothoracic (CT) surgery. However, the characteristics of CT surgeons who are actively leading basic science research (BSR) have not been examined. We hypothesized that early exposure to BSR during training and active grant funding are important factors that facilitate the pursuit of BSR among practicing CT surgeons. MATERIALS AND METHODS: We created a database of 992 CT surgeons listed as faculty at accredited United States CT surgery teaching hospitals in 2018. Data regarding each surgeon's training/professional history, publication record, and National Institutes of Health funding were acquired from publicly available online sources. Surgeons who published at least one first- or last-author paper in 2017-2018 were considered to be active, lead researchers. RESULTS: Of the 992 CT surgeons, 73 (7.4%) were actively leading BSR, and 599 (60.4%) were actively leading only non-BSR. Only 2 women were actively leading BSR. Surgeons actively leading BSR were more likely to have earned a PhD degree (20.5% versus 9.7%, P = 0.0049), and more likely to have published a first-author BSR paper during training (76.7% versus 40.9%, P< 0.0001). Surgeons actively leading BSR were also more likely to have an active National Institutes of Health grant (34.2% versus 5.8%, P< 0.0001), especially an R01 grant (21.9% versus 2.5%, P< 0.0001). CONCLUSIONS: A small minority of CT surgeons at academic training hospitals are actively leading BSR. In order to facilitate the development of surgeon-scientists, additional support must be given to trainees and junior faculty, especially women, to enable early engagement in BSR.

Decreased Nutritional Risk Index is associated with mortality after heart transplantation.

INTRODUCTION: Validated scoring tools, such as the Nutritional Risk Index (NRI), can aid clinicians in quantifying the degree of malnourishment in patients prior to an operation. We evaluated the association between NRI and outcomes after heart transplantation. METHODS: The United Network for Organ Sharing (UNOS) database was used to identify adult patients (age > 18) undergoing heart transplantation between 1987 and 2016. NRI was calculated and categorized into previously established groupings representing severity of malnutrition. Multivariate Cox proportional hazards modeling were used to assess the primary outcome of all-cause mortality. RESULTS: A total of 25,236 patients were included in the analysis. Most patients (75.4%) were male. Malnourishment was absent (NRI ≥ 100) in 11,022 (44%) patients, while 2,898 (12%) were mildly malnourished (97.5 ≤ NRI < 100), 8,685 (34%) were moderately malnourished (83.5 ≤ NRI < 97.5), and 2,631 (10%) were severely malnourished (NRI < 83.5). Moderate-to-severe malnutrition was associated with increased mortality (HR = 1.18, p < .001, 95%CI: 1.13-1.24), and post-transplant renal failure requiring dialysis (OR: 1.13, p < .001, 95%CI: 1.03-1.23). CONCLUSION: Malnourishment determined by NRI is independently associated with mortality and post-transplant dialysis after heart transplant. This is the largest study of NRI in heart transplant recipients.

Photonic crystal lightsail with nonlinear reflectivity for increased stability.

Recent research has studied the feasibility of using laser radiation pressure to propel lightweight spacecraft, such as sails, at relativistic speeds. One major challenge is the effect of laser beam distortion on sail stability. We propose and investigate the use of lightsails based on Kerr nonlinear photonic crystals as a passive method for increasing sail stability. The key concept is to flatten the dependence of reflected intensity on incident intensity at the laser wavelength, using a specially designed, guided-resonance mode of the nonlinear photonic crystal. We use coupled-mode theory to analyze the resonance characteristics that yield the flattest curve. We then design a silicon nitride photonic crystal that supports a resonance with the desired properties. We show that our design simultaneously provides both high stability and high thrust on the sail, unlike designs based on linear materials.

Tunable, polarization-sensitive, dual guided-resonance modes in photonic crystals.

We present a photonic-crystal design which supports multiple guided-resonance modes in a narrow spectral range. Introduction of mutually-orthogonal slots within a conventional lattice allows us to create polarization-sensitive guided modes with distinct near-field periodicities and tunable resonance wavelengths. The device can potentially be used as a reconfigurable optical trap, multiband tunable filter, or differential sensor.

Delayed Surgical Management of Type A Intramural Hematoma Is Not Associated with Worse Outcomes Than Emergent Operation.

OBJECTIVES: Management of acute aortic intramural hematomas (IMHs) involving the ascending aorta and root remains controversial. Some series have suggested that delaying operative intervention beyond the first 24-hours may be beneficial. METHODS: A retrospective single-institution analysis was performed to identify patients presenting with type A IMH. These patients were classified by whether they underwent surgery within 24 hours or delayed operative intervention. Patients with additional indications for emergent operation, such as acute aortic regurgitation or malperfusion syndromes, were excluded. Outcomes were assessed with logistic regression, and the Kaplan-Meier method was used to analyze long-term survival. RESULTS: Of the 129 patients with acute type A aortic pathology, 36 (27.9%) presented with isolated IMH. IMH patients were less likely to present with acute aortic regurgitation (8.6% versus 27.9%, P = .020) or limb ischemia (0% versus 12.6%, P = .027). Of the IMH patients without other emergent operative indications, 23 (67.6%) underwent surgery within 24 hours. Delayed operative repair was not associated with increased risk of mortality, stroke, or renal failure (all P >.05). Survival analysis showed no difference in survival at 1 year. CONCLUSIONS: In well-selected patients, delayed operation for type An intramural hematoma is not associated with adverse outcomes.

Tunable size selectivity and nanoparticle immobilization on a photonic crystal optical trap.

We harness residual thermal effects in a low-absorptivity system to manipulate parallel optical trapping of particles on the nanoscale. A photonic crystal is used to generate a 2D array of optical traps. We show that the size selectivity of the trap can be tuned by adding a non-ionic surfactant to the solution, altering the thermophoretic effect that delivers nanoparticles to trapping sites. We further show that particles can be permanently immobilized on the photonic crystal via photopolymerization of the trapping medium.

Framed, Interactive Theory-Driven Texting: Effects of Message Framing on Health Behavior Change for Weight Loss.

More approaches to support weight control are needed, especially among racial minorities who shoulder a disproportionate obesity burden. Using an approach influenced by regulatory fit theory, we conducted a 28-day, 4-arm experimental trial with 89 obese adults recruited from urban, predominantly African American churches to ascertain the efficacy of framed text messages to motivate behaviors conducive to weight loss. Participants were assigned to receive message framing that was matched versus mismatched to their motivational orientation. Results were mixed overall; however, matched texts elicited greater motivation to change eating and exercise behavior, suggesting promise in using motivational approaches to tailor messages.

Enhanced and selective optical trapping in a slot-graphite photonic crystal.

Applicability of optical trapping tools for nanomanipulation is limited by the available laser power and trap efficiency. We utilized the strong confinement of light in a slot-graphite photonic crystal to develop high-efficiency parallel trapping over a large area. The stiffness is 35 times higher than our previously demonstrated on-chip, near field traps. We demonstrate the ability to trap both dielectric and metallic particles of sub-micron size. We find that the growth kinetics of nanoparticle arrays on the slot-graphite template depends on particle size. This difference is exploited to selectively trap one type of particle out of a binary colloidal mixture, creating an efficient optical sieve. This technique has rich potential for analysis, diagnostics, and enrichment and sorting of microscopic entities.

Clinical Relevance of Left Atrial Strain to Predict Recurrence of Atrial Fibrillation after Catheter Ablation: A Meta-Analysis.

BACKGROUND: The purpose of this meta-analysis was to analyze the clinical relevance of left atrial (LA) strain to predict recurrence of atrial fibrillation (AF) after catheter ablation (CA). METHODS AND RESULTS: We searched in different databases (Medline, EMBASE, and Cochrane) prospective studies that analyzed LA strain before CA. Eight studies (2 with only paroxysmal AF and 6 with mixed population of paroxysmal and persistent AF) were included in the final analysis (total patient number = 686). Patients with recurrence of AF were principally characterized by lower LA strain in comparison with those without AF recurrence (mean 18.4% [range 8.8-24.5%] versus 25.3% [13.6-32.7%], weighted mean difference -4.89% [95% CI -5.83% to -3.95%], P < 0.001). In addition, receiver operating curves shown that LA strain was strongly associated with recurrence of AF after CA (weighted mean: AUC 0.798 [95% CI 0.700-0.943], cutoff 22.8% [18.8-30%], sensitivity 78% [65-86%], and specificity 75% [66-100%]). In line, these results were similar using LA strain with QRS-analysis and P-analysis as well as using different software package such as Echo-Pac, QLab, TomTec, and VVI. CONCLUSION: In patients with AF candidate for CA, the analysis of the LA using LA strain could be of great usefulness to identify patients with high risk of AF recurrence. Nonetheless, further studies are needed to establish the clinical relevance of LA strain in patients with persistent AF.

Multilayer nanoparticle arrays for broad spectrum absorption enhancement in thin film solar cells.

In this paper, we present a theoretical study on the absorption efficiency enhancement of a thin film amorphous Silicon (a-Si) photovoltaic cell over a broad spectrum of wavelengths using multiple nanoparticle arrays. The light absorption efficiency is enhanced in the lower wavelengths by a nanoparticle array on the surface and in the higher wavelengths by another nanoparticle array embedded in the active region. The efficiency at intermediate wavelengths is enhanced by the simultaneous resonance from both nanoparticle layers. We optimize this design by tuning the radius of particles in both arrays, the period of the array and the distance between the two arrays. The optimization results in a total quantum efficiency of 62.35% for a 0.3 µm thick a-Si substrate.

Beating Heart Transplantation: How to Do It.

Heart transplantation utilizing deceased after circulatory death (DCD) donors has expanded the donor pool through the use of ex vivo normothermic perfusion. Compared with brain death donation, the conventional method of performing DCD heart transplantation includes an additional period of warm and cold ischemia. We have developed a beating heart implantation technique that obliviates the need for a second cardioplegic arrest and the associated reperfusion injury. We hypothesize this reproducible method may improve short-term and long-term outcomes to mirror results seen in brain death donors and provide details on how to perform beating heart transplantation.

Lung CT harmonization of paired reconstruction kernel images using generative adversarial networks.

BACKGROUND: The kernel used in CT image reconstruction is an important factor that determines the texture of the CT image. Consistency of reconstruction kernel choice is important for quantitative CT-based assessment as kernel differences can lead to substantial shifts in measurements unrelated to underlying anatomical structures. PURPOSE: In this study, we investigate kernel harmonization in a multi-vendor low-dose CT lung cancer screening cohort and evaluate our approach's validity in quantitative CT-based assessments. METHODS: Using the National Lung Screening Trial, we identified CT scan pairs of the same sessions with one reconstructed from a soft tissue kernel and one from a hard kernel. In total, 1000 pairs of five different paired kernel types (200 each) were identified. We adopt the pix2pix architecture to train models for kernel conversion. Each model was trained on 100 pairs and evaluated on 100 withheld pairs. A total of 10 models were implemented. We evaluated the efficacy of kernel conversion based on image similarity metrics including root mean squared error (RMSE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM) as well as the capability of the models to reduce measurement shifts in quantitative emphysema and body composition measurements. Additionally, we study the reproducibility of standard radiomic features for all kernel pairs before and after harmonization. RESULTS: Our approach effectively converts CT images from one kernel to another in all paired kernel types, as indicated by the reduction in RMSE (p < 0.05) and an increase in the PSNR (p < 0.05) and SSIM (p < 0.05) for both directions of conversion for all pair types. In addition, there is an increase in the agreement for percent emphysema, skeletal muscle area, and subcutaneous adipose tissue (SAT) area for both directions of conversion. Furthermore, radiomic features were reproducible when compared with the ground truth features. CONCLUSIONS: Kernel conversion using deep learning reduces measurement variation in percent emphysema, muscle area, and SAT area.

Beating Heart Transplant Procedures Using Organs From Donors With Circulatory Death.

Importance: The use of ex vivo normothermic organ perfusion has enabled the use of deceased after circulatory death (DCD) donors for heart transplants. However, compared with conventional brain death donation, DCD heart transplantation performed with ex vivo organ perfusion involves an additional period of warm and cold ischemia, exposing the allograft to multiple bouts of ischemia reperfusion injury and may contribute to the high rates of extracorporeal membrane oxygenation usage after DCD heart transplantation. Objective: To assess whether the beating heart method of DCD heart transplantation is safe and whether it has an acceptable rate of extracorporeal membrane oxygenation use postoperatively. Design, Setting, and Participants: This case series includes 10 patients with end-stage heart failure undergoing DCD heart transplantation at a single academic medical center from October 1, 2022, to August 3, 2023. Data were analyzed from October 2022 to August 2023. Interventions: Using a beating heart method of implantation of the donor allograft. Main Outcomes and Measures: The main outcome was primary graft dysfunction necessitating postoperative initiation of mechanical circulatory support. Survival and initiation of mechanical circulatory support were secondary outcomes. Results: In this case series, 10 consecutive patients underwent DCD heart transplantation via the beating heart method. Ten of 10 recipients were male (100%), the mean (SD) age was 51.2 (13.8) years, and 7 (70%) had idiopathic dilated cardiomyopathy. Ten patients (100%) survived, and 0 patients had initiation of extracorporeal membrane oxygenation postoperatively. No other mechanical circulatory support, including intra-aortic balloon pump, was initiated postoperatively. Graft survival was 100% (10 of 10 patients), and, at the time of publication, no patients have been listed for retransplantation. Conclusions and Relevance: In this study of 10 patients undergoing heart transplantation, the beating heart implantation method for DCD heart transplantation was safe and may mitigate ischemia reperfusion injury, which may lead to lower rates of primary graft dysfunction necessitating extracorporeal membrane oxygenation. These results are relevant to institutions using DCD donors for heart transplantation.

Inter-vendor harmonization of CT reconstruction kernels using unpaired image translation.

The reconstruction kernel in computed tomography (CT) generation determines the texture of the image. Consistency in reconstruction kernels is important as the underlying CT texture can impact measurements during quantitative image analysis. Harmonization (i.e., kernel conversion) minimizes differences in measurements due to inconsistent reconstruction kernels. Existing methods investigate harmonization of CT scans in single or multiple manufacturers. However, these methods require paired scans of hard and soft reconstruction kernels that are spatially and anatomically aligned. Additionally, a large number of models need to be trained across different kernel pairs within manufacturers. In this study, we adopt an unpaired image translation approach to investigate harmonization between and across reconstruction kernels from different manufacturers by constructing a multipath cycle generative adversarial network (GAN). We use hard and soft reconstruction kernels from the Siemens and GE vendors from the National Lung Screening Trial dataset. We use 50 scans from each reconstruction kernel and train a multipath cycle GAN. To evaluate the effect of harmonization on the reconstruction kernels, we harmonize 50 scans each from Siemens hard kernel, GE soft kernel and GE hard kernel to a reference Siemens soft kernel (B30f) and evaluate percent emphysema. We fit a linear model by considering the age, smoking status, sex and vendor and perform an analysis of variance (ANOVA) on the emphysema scores. Our approach minimizes differences in emphysema measurement and highlights the impact of age, sex, smoking status and vendor on emphysema quantification.

Survival, function, and immune profiling after beating heart transplantation.

OBJECTIVE: Ex vivo normothermic perfusion of cardiac allografts has expanded the donor pool for heart transplant. Using a beating heart implantation method avoids the second cardioplegic arrest and subsequent ischemia-reperfusion injury typically associated with ex vivo heart perfusion. We sought to describe our institutional experience with beating heart transplantation. METHODS: This was a single-institution retrospective study of adult patients who underwent heart transplantation using ex vivo heart perfusion (EVHP) and a beating heart implantation technique between October 2022 and March 2024. Primary outcomes of interest included survival, initiation of mechanical circulatory support, and rejection. A subanalysis of our institutional series of nonbeating deceased after circulatory death (DCD) heart transplantations was performed as well. RESULTS: Twenty-four patients underwent isolated heart transplantation with the use of ex vivo heart perfusion and beating heart implantation between October 2022 and March 2024; 21 (87.5%) received hearts from DCD donors, and 3 (12.5%) received hearts from deceased after brain death (DBD) donors. The median duration of follow-up was 192 days (interquartile range [IQR], 124-253.5 days), and 23 out of 24 patients (95.8%) were alive at last follow-up. No patients required initiation of mechanical circulatory support. The majority of patients had pathologic grade 0 rejection at the time of biopsy (n = 16; 66.7%), and the median cell-free DNA percent was 0.04% (IQR, 0.04%-0.09%). The rate of mechanical circulatory support initiation in the 22-patient nonbeating DCD heart transplant cohort was significantly higher, at 36.4% (P < .005). CONCLUSIONS: A beating heart implantation technique can be used for transplantation of DCD and DBD hearts on EVHP and is associated with excellent survival and low levels of rejection.

Harmonized connectome resampling for variance in voxel sizes.

To date, there has been no comprehensive study characterizing the effect of diffusion-weighted magnetic resonance imaging voxel resolution on the resulting connectome for high resolution subject data. Similarity in results improved with higher resolution, even after initial down-sampling. To ensure robust tractography and connectomes, resample data to 1 mm isotropic resolution.