The genetic landscape of chromosomal aberrations in 3776 Vietnamese fetuses with clinical anomalies during pregnancy.

Background: Copy number variation sequencing (CNV-seq) is a powerful tool to discover structural genomic variation, but limitations associated with its retrospective study design and inadequate diversity of participants can be impractical for clinical application. Aim: This study aims to use CNV-seq to assess chromosomal aberrations in pregnant Vietnamese women. Materials & methods: A large-scale study was conducted on 3776 pregnant Vietnamese women with abnormal ultrasound findings. Results: Chromosomal aberrations were found in 448 (11.86%) women. Of these, 274 (7.26%) had chromosomal aneuploidies and 174 (4.61%) carried pathogenic/likely pathogenic CNVs. Correlations were established between chromosomal aberrations and various phenotypic markers. Conclusion: This comprehensive clinical study illuminates the pivotal role of CNV-seq in prenatal diagnosis for pregnancies featuring fetal ultrasound anomalies.

The fasciola cinereum of the hippocampal tail as an interventional target in epilepsy.

Targeted tissue ablation involving the anterior hippocampus is the standard of care for patients with drug-resistant mesial temporal lobe epilepsy. However, a substantial proportion continues to suffer from seizures even after surgery. We identified the fasciola cinereum (FC) neurons of the posterior hippocampal tail as an important seizure node in both mice and humans with epilepsy. Genetically defined FC neurons were highly active during spontaneous seizures in epileptic mice, and closed-loop optogenetic inhibition of these neurons potently reduced seizure duration. Furthermore, we specifically targeted and found the prominent involvement of FC during seizures in a cohort of six patients with epilepsy. In particular, targeted lesioning of the FC in a patient reduced the seizure burden present after ablation of anterior mesial temporal structures. Thus, the FC may be a promising interventional target in epilepsy.

Early-life house dust mite aeroallergen exposure augments cigarette smoke-induced myeloid inflammation and emphysema in mice.

BACKGROUND: Longitudinal studies have identified childhood asthma as a risk factor for obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) where persistent airflow limitation can develop more aggressively. However, a causal link between childhood asthma and COPD/ACO remains to be established. Our study aimed to model the natural history of childhood asthma and COPD and to investigate the cellular/molecular mechanisms that drive disease progression. METHODS: Allergic airways disease was established in three-week-old young C57BL/6 mice using house dust mite (HDM) extract. Mice were subsequently exposed to cigarette smoke (CS) and HDM for 8 weeks. Airspace enlargement (emphysema) was measured by the mean linear intercept method. Flow cytometry was utilised to phenotype lung immune cells. Bulk RNA-sequencing was performed on lung tissue. Volatile organic compounds (VOCs) in bronchoalveolar lavage-fluid were analysed to screen for disease-specific biomarkers. RESULTS: Chronic CS exposure induced emphysema that was significantly augmented by HDM challenge. Increased emphysematous changes were associated with more abundant immune cell lung infiltration consisting of neutrophils, interstitial macrophages, eosinophils and lymphocytes. Transcriptomic analyses identified a gene signature where disease-specific changes induced by HDM or CS alone were conserved in the HDM-CS group, and further revealed an enrichment of Mmp12, Il33 and Il13, and gene expression consistent with greater expansion of alternatively activated macrophages. VOC analysis also identified four compounds increased by CS exposure that were paradoxically reduced in the HDM-CS group. CONCLUSIONS: Early-life allergic airways disease worsened emphysematous lung pathology in CS-exposed mice and markedly alters the lung transcriptome.

Type 2 vomeronasal receptor-A4 subfamily: Potential predator sensors in mice.

Sensory signals detected by olfactory sensory organs are critical regulators of animal behavior. An accessory olfactory organ, the vomeronasal organ, detects cues from other animals and plays a pivotal role in intra- and inter-species interactions in mice. However, how ethologically relevant cues control mouse behavior through approximately 350 vomeronasal sensory receptor proteins largely remains elusive. The type 2 vomeronasal receptor-A4 (V2R-A4) subfamily members have been repeatedly detected from vomeronasal sensory neurons responsive to predator cues, suggesting a potential role of this receptor subfamily as a sensor for predators. This review focuses on this intriguing subfamily, delving into its receptor functions and genetic characteristics.

Experiences of racism in the U.S. - A perspective from Asian & Pacific Islander, Black, Latina, and Middle Eastern women.

Introduction: Racism is a critical social determinant of health because it can have a direct impact on health and well-being, as well as infiltrate systems, policies, and practices. Few studies have explored the similarities and differences of experiences with racism and health between different minoritized groups. The objective of this paper is to examine how racism influences life experiences from the perspectives of Asian & Pacific Islander, Black, Latina, and Middle Eastern women. Methods: Eleven online racially/ethnically homogeneous focus groups with a total of 52 participants were conducted in the U.S., with representation from the North, South, and West coast. The online focus groups were recorded, transcribed, and two were translated into English (from Vietnamese and Spanish). The data was coded through NVivo and analyzed through a series of team meetings to establish themes. Results: Participants reported experiences of racism and discrimination, including physical and verbal personal attacks. They shared the role of microaggressions in their daily life, along with the ubiquitous anti-Black sentiment discussed in every group. Our participants discussed the complexities of intersectionality in their experience of discrimination, specifically regarding immigration status, language spoken, and gender. Participants also reported the role of direct racism and vicarious racism (e.g., the experiences with racism of friends or family, awareness of racist incidents via the news) in affecting their mental health. Some effects were fear, stress, anxiety, depression, and self-censoring. For participants in the Black and Latina focus groups, mental health stressors often manifested into physical issues. Discussion: Understanding the nuances in experiences across racial/ethnic groups is beneficial in identifying potential interventions to prevent and address racism and its negative health impacts.

Road Traffic Injuries and the Built Environment in Bogotá, Colombia, 2015-2019: A Cross-Sectional Analysis.

Nine in 10 road traffic deaths occur in low- and middle-income countries (LMICs). Despite this disproportionate burden, few studies have examined built environment correlates of road traffic injury in these settings, including in Latin America. We examined road traffic collisions in Bogotá, Colombia, occurring between 2015 and 2019, and assessed the association between neighborhood-level built environment features and pedestrian injury and death. We used descriptive statistics to characterize all police-reported road traffic collisions that occurred in Bogotá between 2015 and 2019. Cluster detection was used to identify spatial clustering of pedestrian collisions. Adjusted multivariate Poisson regression models were fit to examine associations between several neighborhood-built environment features and rate of pedestrian road traffic injury and death. A total of 173,443 police-reported traffic collisions occurred in Bogotá between 2015 and 2019. Pedestrians made up about 25% of road traffic injuries and 50% of road traffic deaths in Bogotá between 2015 and 2019. Pedestrian collisions were spatially clustered in the southwestern region of Bogotá. Neighborhoods with more street trees (RR, 0.90; 95% CI, 0.82-0.98), traffic signals (0.89, 0.81-0.99), and bus stops (0.89, 0.82-0.97) were associated with lower pedestrian road traffic deaths. Neighborhoods with greater density of large roads were associated with higher pedestrian injury. Our findings highlight the potential for pedestrian-friendly infrastructure to promote safer interactions between pedestrians and motorists in Bogotá and in similar urban contexts globally.

Conductive Glassy Nonconjugated Open-Shell Radical Polymer with Organosulfur Backbone for Macroscopic Conductivity.

Nonconjugated organic radicals with an open-shell radical active group exhibit unique functionality due to their radical pendant site. Compared with the previously studied doped conjugated polymers, radical polymers reveal superior processability, stability, and optical properties. Despite the success of organic radical polymer conductors based on the TEMPO radicals, it still requires potential design substitutions to meet the fundamental limits of charge transport in the radical polymer. To do so, we demonstrate that the amorphous, nonconjugated radical polymer with backbone-pendant group interaction and low glass transition temperature enables the macromolecules to have rapid charge transport in the solid state, resulting in conductivity higher than 32 S m-1. This charge transport is due to the formation of the local ordered regime with an energetically favored orientation caused by the strong coupling between the backbone and pendant group, which can significantly modulate the polymer packing with active electronic communications. The nonconjugate nature of the radical polymer maintains an optical transparency up to 98% at a 1.5 µm thick film. Thus, this effort will be a dramatically advanced model in the organic radical community for the creation of next-generation polymer conductors.

TMEM106B coding variant is protective and deletion detrimental in a mouse model of tauopathy.

TMEM106B is a risk modifier of multiple neurological conditions, where a single coding variant and multiple non-coding SNPs influence the balance between susceptibility and resilience. Two key questions that emerge from past work are whether the lone T185S coding variant contributes to protection, and if the presence of TMEM106B is helpful or harmful in the context of disease. Here, we address both questions while expanding the scope of TMEM106B study from TDP-43 to models of tauopathy. We generated knockout mice with constitutive deletion of TMEM106B, alongside knock-in mice encoding the T186S knock-in mutation (equivalent to the human T185S variant), and crossed both with a P301S transgenic tau model to study how these manipulations impacted disease phenotypes. We found that TMEM106B deletion accelerated cognitive decline, hind limb paralysis, tau pathology, and neurodegeneration. TMEM106B deletion also increased transcriptional correlation with human AD and the functional pathways enriched in KO:tau mice aligned with those of AD. In contrast, the coding variant protected against tau-associated cognitive decline, synaptic impairment, neurodegeneration, and paralysis without affecting tau pathology. Our findings reveal that TMEM106B is a critical safeguard against tau aggregation, and that loss of this protein has a profound effect on sequelae of tauopathy. Our study further demonstrates that the coding variant is functionally relevant and contributes to neuroprotection downstream of tau pathology to preserve cognitive function.

Novel films of pectin extracted from ambarella fruit peel and jackfruit seed slimy sheath: Effect of ionic crosslinking on the properties of pectin film.

Here, we prepared ionically crosslinked films using pectin extracted from agro-wastes, specifically ambarella peels (AFP) and jackfruit seed slimy sheath (JFS). Physiochemical properties of pectins, including moisture content, molecular weight (Mw), degree of esterification (DE), and galacturonic acid (GA), were analyzed. Optimal extraction was determined, i.e., citric acid concentration 0.3 M, time 60 min, solid/liquid ratio 1:25, and temperature 90 °C for AFP or 85 °C for JFS. Pectin yields under these conditions were 29.67 % ± 0.35 % and 29.93 ± 0.49 %, respectively. AFP pectin revealed Mw, DE, and GA values of 533.20 kDa, 67.08 % ± 0.68 %, and 75.39 ± 0.82 %, while JFS pectin exhibited values of 859.94 kDa, 63.04 % ± 0.47 %, and 78.63 % ± 0.71 %, respectively. The pectin films crosslinked with Ca2+, Cu2+, Fe3+, or Zn2+ exhibited enhanced tensile strength and Young's modulus, along with reduced elongation at break, moisture content, water solubility, water vapor permeability, and oxygen permeability. Structural analyses indicated metal ions were effectively crosslinked with carboxyl groups of pectin. Notably, the Cu2+-crosslinked film demonstrated superior water resistance, mechanical properties, and exhibited the highest antioxidant and antibacterial activities among all tested films. Therefore, the pectin films represent a promising avenue to produce eco-friendly food packaging materials with excellent properties.

GLP-1 Receptor Agonists Promote Weight Loss Among People with HIV.

BACKGROUND: Weight gain and associated metabolic complications are increasingly prevalent among people with HIV (PWH). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin-based therapies for diabetes and weight management that have been shown to result in substantial weight loss; however, studies of their effects in PWH are limited. METHODS: A retrospective single-center cohort study was conducted among PWH who were taking GLP-1RAs at UC San Diego Owen Clinic between 2/1/2021 to 2/1/2023. Baseline clinical data were collected and changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before starting GLP-1RAs compared to the most recent clinic visit were calculated (with a minimum of 3 months follow-up time required). Logistic regression was performed to identify variables associated with >5% of total body weight loss. RESULTS: A total of 225 patients received on average 13 months of GLP-1RA therapy, with 85 (37.8%) achieving the maximum GLP-1RA dose. GLP-1RA therapy resulted, on average, in a loss of 5.4 kg, decrease in BMI by 1.8 kg/m2, and decrease in A1C by 0.6%. In the multivariable analysis, higher baseline BMI [OR 1.10 (1.03-1.16)], treatment duration of GLP-1RA therapy greater than 6 months [OR 3.12 (1.49-6.49], and use of tirzepatide [OR 5.46 (1.44-20.76)] were significantly more likely to be associated with >5% weight loss. CONCLUSIONS: Use of GLP-1RAs led to declines in weight, BMI, and hemoglobin A1C among PWH and offers an additional strategy to address weight gain and diabetes.

Exploring Psychosocial and Structural Syndemic Effects as Predictors of HIV Risk Behaviors Among Black Women (HPTN 064).

Background: Syndemic models have been used in previous studies exploring HIV-related outcomes; however, these models do not fully consider intersecting psychosocial (e.g., substance use, depressive symptoms) and structural factors (unstable housing, concentrated housing vacancy) that influence the lived experiences of women. Therefore, there is a need to explore the syndemic effects of psychosocial and structural factors on HIV risk behaviors to better explain the multilevel factors shaping HIV disparities among black women. Methods: This analysis uses baseline data (May 2009-August 2010) from non-Hispanic black women enrolled in the HIV Prevention Trials Network 064 Women's Seroincidence Study (HPTN 064) and the American Community Survey 5-year estimates from 2007 to 2011. Three parameterizations of syndemic factors were applied in this analysis a cumulative syndemic index, three syndemic groups reflecting the level of influence (psychosocial syndemic group, participant-level structural syndemic group, and a neighborhood-level structural syndemic group), and syndemic factor groups. Clustered mixed effects log-binomial analyses measured the relationship of each syndemic parameterization on HIV risk behaviors in 1,347 black women enrolled in HPTN 064. Results: A higher syndemic score was significantly associated with increased prevalence of unknown HIV status of the last male sex partner (adjusted prevalence ratio (aPR) = 1.07, 95% confidence interval or CI 1.04-1.10), involvement in exchange sex (aPR = 1.17, 95% CI: 1.14-1.20), and multiple sex partners (aPR = 1.07, 95% CI: 1.06-1.09) in the last 6 months. A dose-response relationship was observed between the number of syndemic groups and HIV risk behaviors, therefore, being in multiple syndemic groups was significantly associated with increased prevalence of reporting HIV risk behaviors compared with being in one syndemic group. In addition, being in all three syndemic groups was associated with increased prevalence of unknown HIV status of the last male sex partner (aPR = 1.67, 95% CI: 1.43-1.95) and multiple sex partners (aPR = 1.53, 95% CI: 1.36-1.72). Conclusions: Findings highlight syndemic factors influence the lived experiences of black women.

Elucidating the Role of Reduction Kinetics in the Phase-Controlled Growth on Preformed Nanocrystal Seeds: A Case Study of Ru.

This study demonstrates the crucial role of reduction kinetics in phase-controlled synthesis of noble-metal nanocrystals using Ru nanocrystals as a case study. We found that the reduction kinetics played a more important role than the templating effect from the preformed seed in dictating the crystal structure of the deposited overlayers despite their intertwined effects on successful epitaxial growth. By employing two different polyols, a series of Ru nanocrystals with tunable sizes of 3-7 nm and distinct patterns of crystal phase were synthesized by incorporating different types of Ru seeds. Notably, the use of ethylene glycol and triethylene glycol consistently resulted in the formation of Ru shell in natural hexagonal close-packed (hcp) and metastable face-centered cubic (fcc) phases, respectively, regardless of the size and phase of the seed. Quantitative measurements and theoretical calculations suggested that this trend was a manifestation of the different reduction kinetics associated with the precursor and the chosen polyol, which, in turn, affected the reduction pathway (solution versus surface) and packing sequence of the deposited Ru atoms. This work not only underscores the essential role of reduction kinetics in controlling the packing of atoms and thus the phase taken by Ru nanocrystals but also suggests a potential extension to other noble-metal systems.

The late effects of haematopoietic stem cell transplants in paediatric patients: a 25 year review.

CONTEXT: A rare, large single centre study covering all long-term health outcomes of paediatric allogeneic HSCT survivors, to provide comprehensive local data, and identify gaps and future directions for improved care. OBJECTIVE: To document endocrine sequelae and other late effects of all HSCT recipients. DESIGN: Retrospective review. SETTING: Royal Children's Hospital Melbourne. PATIENTS: 384 children and adolescents received HSCT. 228 formed the study cohort; 212 were alive at commencement of data accrual. INTERVENTION: None. MAIN OUTCOME MEASURES: Incidence of endocrinopathies; fertility, growth, bone and metabolic status; subsequent malignant neoplasms (SMNs). RESULTS: Gonadotoxicity was more common in females (p<0.001). Total body irradiation (TBI) conditioning was more toxic than chemotherapy alone. All females receiving TBI or higher cyclophosphamide equivalent doses (CED) developed premature ovarian insufficiency (POI) . In males, impaired spermatogenesis +/- testicular endocrine dysfunction was associated with increasing testicular radiation exposure. Preservation of gonadal function was associated with younger age at HSCT. Of sexually active females, 22% reported spontaneous pregnancies. Short stature was common, with growth hormone axis disruption in 30% of these. Of patients exposed to thyroid radiation 51% developed nodules, 30% malignant. Metabolic disturbances included hypertension, dyslipidemias, with both excess and underweight reported. Fragility fractures occurred in 6%; avascular necrosis in 6%. 13% developed SMNs, risk continuing to rise throughout follow-up. CONCLUSIONS: We confirm gonadal dysfunction, multiple endocrine and metabolic abnormalities, thyroid cancer and SMNs, as common sequelae of HSCT, and identify gaps in management - particularly the need for informed fertility counselling and pretreatment fertility preservation, evaluation and management of bone health, and underline need for early lifestyle modification, long-term surveillance, and prospective planned studies aimed at reducing complication risk.

Regulatory Issues of Platform Trials: Learnings from EU-PEARL.

Although platform trials have many benefits, the complexity of these designs may result not only in increased methodological but also regulatory and ethical challenges. These aspects were addressed as part of the IMI project EU Patient-Centric Clinical Trial Platforms (EU-PEARL). We reviewed the available guidelines on platform trials in the European Union and the United States. This is supported and complemented by feedback received from regulatory interactions with the European Medicines Agency and the US Food and Drug Administration. Throughout the project we collected the needs of all relevant stakeholders including ethics committees, regulators, and health technology assessment bodies through active dialog and dedicated stakeholder workshops. Furthermore, we focused on methodological aspects and where applicable identified the corresponding guidance. Learnings from the guideline review, regulatory interactions, and workshops are provided. Based on these, a master protocol template was developed. Issues that still need harmonization or clarification in guidelines or where further methodological research is needed are also presented. These include questions around clinical trial submissions in Europe, the need for multiplicity control across the whole master protocol, the use of non-concurrent controls, and the impact of different randomization schemes. Master protocols are an efficient and patient-centered clinical trial design that can expedite drug development. However, they can also introduce additional operational and regulatory complexities. It is important to understand the different requirements of stakeholders upfront and address them in the trial. While relevant guidance is increasing, early dialog with relevant stakeholders can help to further support such designs.

Evaluation of the safety and immune stimulatory effects of multi-strain Lab Mix product on laboratory animals.

Background & aims: Probiotics are alive and beneficial bacteria used as food complements with sufficient amounts to improve and balance the intestinal flora in the human gastrointestinal tract and inhibit harmful microorganisms. In this study, we conducted experiments to evaluate he safety and the effect of one of our probiotics on selected biochemical parameters in animal models. Methods: LabMix is a probiotic product containing three bacterial strains, including Lactobacillus acidophilus LA 304.17, Lactobacillus casei LC 304.08, and Bifidobacterium bifidum BF 304.98, with a density of 9 × 109 CFU/g and being mixed with suitable excipients. In this study, we conducted experiments to evaluate LabMix's acute ttoxicity in mice as well as subchronic toxicity in rats. Results: The LD50 dose in mice of this product could not be determined since no death or disorder was recorded. In rats receiving LabMix with doses of 2.52 × 109 CFU/kg and 12.6 × 109 CFU/kg continuously for 28 days, this product caused no significant changes in the amount of red and white blood cells and platelets. Similarly, no significant changes were recorded in serum concentrations of hemoglobin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, protein, cholesterol, bilirubin, and creatinine. Besides, LabMix products also did not cause any changes in the histology of the liver, kidney, and spleen in rats. Moreover, LabMix was well tolerated without affecting the normal growth and feeding of rats. Furthermore, LabMix also decreased serum cytokines and increased serum and gut mucosal IgA antibodies. Conclusions: LabMix product is possibly considered safe for human., and this sproduct reduced the release of pro-inflammatory cytokines (IL-6 and TNF-α), but increased IgA levels. However, it is necessary to further evaluate the product's effectiveness in the preclinical phase as well as in further phases before mass production and commercialization.

Rice pest dataset supports the construction of smart farming systems.

Rice holds a significant position in the global food supply chain, particularly in Asian, African, and Latin American countries. However, rice pests and diseases cause significant damage to the supply and growth of the rice cultivation industry. Therefore, this article provides a high-quality dataset that has been reviewed by agricultural experts. The dataset is well-suited to support the development of automation systems and smart farming practices. It plays a vital role in facilitating the automatic construction, detection, and classification of rice diseases. However, challenges arise due to the diversity of the dataset collected from various sources, varying in terms of disease types and sizes. This necessitates support for upgrading and enhancing the dataset through various operations in data processing, preprocessing, and statistical analysis. The dataset is provided completely free of charge and has been rigorously evaluated by agricultural experts, making it a reliable resource for system development, research, and communication needs.

Optimizing Outpatient Radiation Oncology Consult Workflow by Using Time-Driven Activity-Based Costing: Efficiency and Financial Impacts.

PURPOSE: Clinical efficiency is a key component of value-based health care. Our objective here was to identify workflow inefficiencies by using time-driven activity-based costing (TDABC) and evaluate the implementation of a new clinical workflow in high-volume outpatient radiation oncology clinics. METHODS: Our quality improvement study was conducted with the Departments of GI, Genitourinary (GU), and Thoracic Radiation Oncology at a large academic cancer center and four community network sites. TDABC was used to create process maps and optimize workflow for outpatient consults. Patient encounter metrics were captured with a real-time status function in the electronic medical record. Time metrics were compared using Mann-Whitney U tests. RESULTS: Individual patient encounter data for 1,328 consults before the intervention and 1,234 afterward across all sections were included. The median overall cycle time was reduced by 21% in GI (19 minutes), 18% in GU (16 minutes), and 12% at the community sites (9 minutes). The median financial savings per consult were $52 in US dollars (USD) for the GI, $33 USD for GU, $30 USD for thoracic, and $42 USD for the community sites. Patient satisfaction surveys (from 127 of 228 patients) showed that 99% of patients reported that their providers spent adequate time with them and 91% reported being seen by a care provider in a timely manner. CONCLUSION: TDABC can effectively identify opportunities to improve clinical efficiency. Implementing workflow changes on the basis of our findings led to substantial reductions in overall encounter cycle times across several departments, as well as high patient satisfaction and significant financial savings.

Survival outcomes and toxicity of adjuvant immunotherapy after definitive concurrent chemotherapy with proton beam radiation therapy for patients with inoperable locally advanced non-small cell lung carcinoma.

INTRODUCTION: Adjuvant immunotherapy (IO) following concurrent chemotherapy and photon radiation therapy confers an overall survival (OS) benefit for patients with inoperable locally advanced non-small cell lung carcinoma (LA-NSCLC); however, outcomes of adjuvant IO after concurrent chemotherapy with proton beam therapy (CPBT) are unknown. We investigated OS and toxicity after CPBT with adjuvant IO versus CPBT alone for inoperable LA-NSCLC. MATERIALS AND METHODS: We analyzed 354 patients with LA-NSCLC who were prospectively treated with CPBT with or without adjuvant IO from 2009 to 2021. Optimal variable ratio propensity score matching (PSM) matched CPBT with CPBT + IO patients. Survival was estimated with the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox proportional hazards regression evaluated the effect of IO on disease outcomes. RESULTS: Median age was 70 years; 71 (20%) received CPBT + IO and 283 (80%) received CPBT only. After PSM, 71 CPBT patients were matched with 71 CPBT + IO patients. Three-year survival rates for CPBT + IO vs CPBT were: OS 67% vs 30% (P < 0.001) and PFS 59% vs 35% (P = 0.017). Three-year LRFS (P = 0.137) and DMFS (P = 0.086) did not differ. Receipt of adjuvant IO was a strong predictor of OS (HR 0.40, P = 0.001) and PFS (HR 0.56, P = 0.030), but not LRFS (HR 0.61, P = 0.121) or DMFS (HR 0.61, P = 0.136). There was an increased incidence of grade ≥3 esophagitis in the CPBT-only group (6% CPBT + IO vs 17% CPBT, P = 0.037). CONCLUSION: This study, one of the first to investigate CPBT followed by IO for inoperable LA-NSCLC, showed that IO conferred survival benefits with no increased rates of toxicity.

A Novel Polymer-Encapsulated Multi-Imaging Modality Fiducial Marker with Positive Signal Contrast for Image-Guided Radiation Therapy.

BACKGROUND: Current fiducial markers (FMs) in external-beam radiotherapy (EBRT) for prostate cancer (PCa) cannot be positively visualized on magnetic resonance imaging (MRI) and create dose perturbation and significant imaging artifacts on computed tomography (CT) and MRI. We report our initial experience with clinical imaging of a novel multimodality FM, NOVA. METHODS: We tested Gold Anchor [G-FM], BiomarC [carbon, C-FM], and NOVA FMs in phantoms imaged with kilovoltage (kV) X-rays, transrectal ultrasound (TRUS), CT, and MRI. Artifacts of the FMs on CT were quantified by the relative streak artifacts level (rSAL) metric. Proton dose perturbations (PDPs) were measured with Gafchromic EBT3 film, with FMs oriented either perpendicular to or parallel with the beam axis. We also tested the performance of NOVA-FMs in a patient. RESULTS: NOVA-FMs were positively visualized on all 4 imaging modalities tested. The rSAL on CT was 0.750 ± 0.335 for 2-mm reconstructed slices. In F-tests, PDP was associated with marker type and depth of measurement (p < 10-6); at 5-mm depth, PDP was significantly greater for the G-FM (12.9%, p = 10-6) and C-FM (6.0%, p = 0.011) than NOVA (4.5%). EBRT planning with MRI/CT image co-registration and daily alignments using NOVA-FMs in a patient was feasible and reproducible. CONCLUSIONS: NOVA-FMs were positively visible and produced less PDP than G-FMs or C-FMs. NOVA-FMs facilitated MRI/CT fusion and identification of regions of interest.

Morphological Changes of 3T3 Cells under Simulated Microgravity.

BACKGROUND: Cells are sensitive to changes in gravity, especially the cytoskeletal structures that determine cell morphology. The aim of this study was to assess the effects of simulated microgravity (SMG) on 3T3 cell morphology, as demonstrated by a characterization of the morphology of cells and nuclei, alterations of microfilaments and microtubules, and changes in cycle progression. METHODS: 3T3 cells underwent induced SMG for 72 h with Gravite®, while the control group was under 1G. Fluorescent staining was applied to estimate the morphology of cells and nuclei and the cytoskeleton distribution of 3T3 cells. Cell cycle progression was assessed by using the cell cycle app of the Cytell microscope, and Western blot was conducted to determine the expression of the major structural proteins and main cell cycle regulators. RESULTS: The results show that SMG led to decreased nuclear intensity, nuclear area, and nuclear shape and increased cell diameter in 3T3 cells. The 3T3 cells in the SMG group appeared to have a flat form and diminished microvillus formation, while cells in the control group displayed an apical shape and abundant microvilli. The 3T3 cells under SMG exhibited microtubule distribution surrounding the nucleus, compared to the perinuclear accumulation in control cells. Irregular forms of the contractile ring and polar spindle were observed in 3T3 cells under SMG. The changes in cytoskeleton structure were caused by alterations in the expression of major cytoskeletal proteins, including ß-actin and α-tubulin 3. Moreover, SMG induced 3T3 cells into the arrest phase by reducing main cell cycle related genes, which also affected the formation of cytoskeleton structures such as microfilaments and microtubules. CONCLUSIONS: These results reveal that SMG generated morphological changes in 3T3 cells by remodeling the cytoskeleton structure and downregulating major structural proteins and cell cycle regulators.