Disruption Rate Research Articles

Efficient gene editing with an Arg-tRNA promoter-driven CRISPR/Cas9 in the rice blast fungus Pyricularia oryzae

CRISPR/Cas9 technology has been widely adopted for genome editing in a wide range of organisms, including many fungi. Pyricularia oryzae is a filamentous fungal pathogen that causes the devastating rice blast disease. However, an efficient and cost-effective CRISPR/Cas9 system for the rice blast fungus has yet to be established. Here, we report an 84-bp arginyl (Arg)-tRNA promoter-driven CRISPR/Cas9 system, which enables efficient and cost-effective gene editing in P. oryzae. Preliminary screening of three tRNAs from the 179 predicted tRNAs in P. oryzae showed that two Arg-tRNA CRISPR/Cas9 cassettes reproducibly generated MoB56 disruption efficiently. Further, five genes located on distinct chromosomes, including two previously uncharacterized genes, were randomly picked up to test the efficiency of the Mo_tRNAArg24-gRNA-Cas9 cassette. Ppg1 is a gene essential to the pathogenicity and important for mycelial growth and conidiation of P. oryzae, which is located at chromosome 2 and exhibited a relatively low gene replacement rate (< 1/500) by the traditional gene replacement approach. By using the Mo_tRNAArg24-gRNA-Cas9 cassette, Ppg1 gene disruption rate was increased up to 75.9%. In addition, Bip2, an uncharacterized genes located close to the centromere of chromosome 4, was disrupted at 66.7%. For all the five tested genes, our Mo_tRNAArg24-gRNA-Cas9 cassette showed high gene disruption efficiency in P. oryzae, ranging from 66.7% to 100%. Importantly, it rarely induces Cas9 toxicity to P. oryzae. The Mo_tRNAArg24-gRNA-Cas9 cassette described in this study can be adopted as an alternative for functional genomics study in P. oryzae.

Smart β-cyclodextrin-dominated helical supramolecular dendritic assemblies improve the foliar affinity and biofilm disruption for treating alarming bacterial diseases

Recent outbreaks of alarming bacterial diseases have significantly impacted global agricultural productivity. Conventional bactericides exhibit certain limitations in efficiently impeding biofilm formation and annihilating biofilm-dispersed pathogens, and often expose to high off-target movement during foliar spraying. Here, we produce an innovative helical dendrimer-like supramolecular material (PhA28@β-CD) assembled by a bioactive small-molecule 2-chlorophenylisopropanolamine (PhA28) and β-cyclodextrin (β-CD) through host-guest recognition principle. In this system, the advisable optimization by a macrocyclic oligosaccharide—β-CD significantly enhances the water-solubility, biocompatibility, and bioavailability of PhA28. At a low-dose of 6.8 μg/mL, PhA28@β-CD discloses an outstanding biofilm disruption rate of 82.4 %, notably exceeding that of PhA28 (60.6 %), which thereby reduces the biofilm-associated virulence. Meanwhile, the self-assembled PhA28@β-CD possesses superior wetting and dispersing properties on hydrophobic leaves, leading to effective foliar deposition and prolong retention of active components. In vivo studies reveal that PhA28@β-CD exhibits superior curative (66.0 %) and protective (72.6 %) activities against citrus canker at 200 μg/mL, markedly surpassing those of the existing bactericide thiodiazole‑copper (46.8 % and 52.2 %) and single PhA28. This material also has broad-spectrum control efficiency (53.0 % ~ 59.5 %) against rice bacterial blight. This research lays the groundwork for developing carbohydrate-optimized multifunctional dendrimer-like assemblies aimed at disrupting biofilms and improving sustained bioavailability to combat bacterial diseases.

Robotic Technologies and Automation in Construction: A Systematic Review

The global construction industry is experiencing a high rate of disruption arising from the deployment of emerging robotic technologies and process automation. This study investigates research trends in robotic technologies and automation in the construction industry. Using topic-specific keywords to organise and summarise pertinent studies, the study undertook a systematic literature review and meta-analysis of robotic technologies and automation in construction. A systematic search of the databases of Scopus, Web of Science, and Dimensions was conducted, with a total of 9,515 journal articles retrieved from them. Based on inclusion and exclusion criteria, a total of 51 research papers met the parameters for meta analysis and systematic review. Data relating to the research papers' demography and to robotic technologies as well as automation in construction were mined, with a quantitative meta-analysis performed on them. The results show a spread of research efforts across Europe, Asia and America, with an increase in research output between 2019 and 2023. The results further show that construction gantry systems, bricklaying robots and 3D concrete printers are the most studied robotic technologies and automation processes in the sector. The study concludes that there is still a paucity of research on robotic technologies and automation in construction. The study therefore recommends further research on robotic technologies and automation in construction, especially with regard to their appropriate application and deployment in construction projects across Africa.

Enhancing supply chain resilience under disruption: analysis of the farmed data by Monte Carlo simulation

Motivated by the critical need for supply chains to withstand disruptions, this paper investigates the application of three core resilience strategies and their combinations at the network design level. We propose an investigation framework that utilises Monte Carlo simulation to generate disruption rates of varying severity. This allows for the mathematical optimisation of eight different models, each representing a combination of the three core resilience strategies, based on the simulated disruptions. The framework also incorporates farmed structured data analysis to examine the performance and features of each model. Considering disruptions that can affect both suppliers and factories, a detailed comparison is performed between the strategies. Numerical comparisons reveal that the model incorporating all resilience strategies (Multiple Allocation Network with Backup Suppliers and Factories, or MANBSF) outperforms others, potentially achieving zero shortages even under significant disruptions. This comprehensive model allows for multiple allocations of facilities and incorporates backup suppliers and factories. The analysis further suggests that network resilience increases with size, density, and the number of complete paths.

Posterior Cartilage Endplate Disruption on T1-weighted Magnetic Resonance Imaging as a Predictor for Postoperative Recurrence of Lumbar Disk Herniation.

A retrospective cohort study. This study aimed to investigate the relationship between disruption of cartilage endplates and postoperative recurrence of lumber disk herniation (LDH) using preoperative T1-weighted magnetic resonance imaging (MRI-T1WI). Recurrence of LDH is a relatively common complication after discectomy. Although several risk factors have been identified, their predictive capability remains limited. Previous histologic studies reported that cartilage endplates were present in 85% of patients with recurrent LDH. Patients with a single level of LDH who underwent open or microendoscopic discectomy were retrospectively reviewed. On the basis of preoperative sagittal MRI-T1WI, cartilage endplates were divided into anterior and posterior portions at the center of the disk and evaluated for discontinuity. Patient background characteristics, spinopelvic sagittal parameters, degrees of disk degeneration, and recurrence level were also evaluated. A total of 100 patients were included in this study (mean age, 50.5 years old; 41% female). Symptomatic recurrence of LDH occurred in 15 patients (15%). There were no significant differences in patient background characteristics (age, 46.9 vs. 51.2 years old; %female, 60% vs. 38%; smoking, 33% vs. 41%; diabetes mellitus, 27% vs. 29%) or spinopelvic parameters (PI, 44.1 vs. 47.0 degrees; PT, 16.8 vs. 19.4 degrees; SS, 27.3 vs. 27.6 degrees; LL, 37.7 vs. 33.7 degrees). In the recurrence group, MRI-T1WI showed a higher rate of cartilage endplate disruption in the posterior portion than in the no-recurrence group (73% vs. 34%, P=0.01). A multivariate analysis demonstrated that the disruption of the posterior cartilage endplate remained an independent predictor of recurrence. Disruption in the posterior cartilage endplate on preoperative MRI-T1WI was closely associated with recurrence after LDH surgery. These results suggest that this MRI finding is a practical and useful predictor of LDH recurrence. Level III.

Acid-degradable lipid nanoparticles enhance the delivery of mRNA.

Lipid nanoparticle (LNP)-mRNA complexes are transforming medicine. However, the medical applications of LNPs are limited by their low endosomal disruption rates, high toxicity and long tissue persistence times. LNPs that rapidly hydrolyse in endosomes (RD-LNPs) could solve the problems limiting LNP-based therapeutics and dramatically expand their applications but have been challenging to synthesize. Here we present an acid-degradable linker termed 'azido-acetal' that hydrolyses in endosomes within minutes and enables the production of RD-LNPs. Acid-degradable lipids composed of polyethylene glycol lipids, anionic lipids and cationic lipids were synthesized with the azido-acetal linker and used to generate RD-LNPs, which significantly improved the performance of LNP-mRNA complexes in vitro and in vivo. Collectively, RD-LNPs delivered mRNA more efficiently to the liver, lung, spleen and brains of mice and to haematopoietic stem and progenitor cells in vitro than conventional LNPs. These experiments demonstrate that engineering LNP hydrolysis rates in vivo has great potential for expanding the medical applications of LNPs.

Dynamic deadline constrained multi-objective workflow scheduling in multi-cloud environments

Workflow scheduling becomes difficult and demanding in multi-cloud systems because of the variety of billing models and resource kinds, as well as the susceptibility of processes to time limitations. In which the execution duration of the workflow needs to be flexibly adjusted according to the urgency or otherwise of the real situation, in this work, we model the workflow scheduling problem with deadline constraints as a dynamically constrained multi-objective optimization problem (DCMOP), where the disruption rate of the special cloud resources and the failure probability in different cloud environments are expressed as the disruption probability of the workflow in a comprehensive manner while considering the execution time and cost. Dynamics arise from price changes for specialized cloud resources and changes in the execution duration of workflows. In addition, an algorithm for dynamically constrained multi-objective optimization (DC-MOEA-DPDS) is proposed in this paper. The algorithm based on two-population synergy as well as diversity selection. The auxiliary population ignores constraint limitations to help the main population speed up convergence, and diversity selection enables the auxiliary population to have better diversity to assist the general public in looking for more viable areas. Through dynamic constrained workflow simulation experiments in a multi-cloud environment, our algorithm reduces the execution time by an average of 13.29%, the cost by an average of 32.26%, and the interruption probability by 56.75%. In addition, our algorithm outperforms other algorithms in experiments on a dynamically constrained benchmark set.

Robotic-Assisted and Laparoscopic Bariatric Surgeries Still Have Clinically Comparable Outcomes

PurposeBariatric surgery is considered the main treatment option for patients with severe obesity. The objective of our study is to compare intra- and postoperative outcomes between the robotic and laparoscopic approaches within the sleeve gastrectomy (SG), duodenal switch (DS), and Roux-en-Y gastric bypass (RYGB).Materials and MethodsThe data from the MBSAQIP were collected for patients who underwent SG, DS, and RYGB between 2015 and 2021. The postoperative and procedural outcomes including 30-day morbidity and mortality as well as operation length were analyzed using regression models.ResultsOur analysis included 1,178,886 surgeries with SG comprising the majority (70%) followed by RYGB (28%) and DS (1%). Other than a higher adjusted risk of unplanned reoperation for robotic RYGB (relative risk (RR) 1.07) and a statistically significant higher rate of postoperative wound disruption in robotic SG for robotic surgery (RR 1.56), there were no statistically significant between-approach differences including infection, wound disruption, death, or reoperation for DS, RYGB, or SG. Our data showed no significant difference in anastomotic leak rate between laparoscopic and robotic approaches in either the DS (p = 0.521) or RYGB (p = 0.800) procedures. Across our study period, the median operation lengths decreased significantly per year for both the robotic SG and DS.ConclusionsRobotic and laparoscopic bariatric surgical procedures have statistically similar 30-day patient outcomes. Robotic bariatric procedures do have significantly longer median operative times than laparoscopic procedures. The decision to use a robotic approach or laparoscopic approach should be made based upon surgeon experience and possibly cost.Graphical

Escherichia coli exopolysaccharides disrupt Pseudomonas aeruginosa biofilm and increase its antibiotic susceptibility

Pseudomonas aeruginosa (P. aeruginosa) is a major pathogen that causes infectious diseases. It has high tendency to form biofilms, resulting in the failure of traditional antibiotic therapies. Inspired by the phenomenon that co-culture of Escherichia coli (E. coli) and P. aeruginosa leads to a biofilm reduction, we reveal that E. coli exopolysaccharides (EPS) can disrupt P. aeruginosa biofilm and increase its antibiotic susceptibility. The results show that E. coli EPS effectively inhibit biofilm formation and disrupt mature biofilms in P. aeruginosa, Staphylococcus aureus, and E. coli itself. The maximal inhibition and disruption rates against P. aeruginosa biofilm are 40 % and 47 %, respectively. Based on the biofilm-disrupting ability of E. coli EPS, we develop an E. coli EPS/antibiotic combining strategy for the treatment of P. aeruginosa biofilms. The combination with E. coli EPS increases the antibacterial efficiency of tobramycin against P. aeruginosa biofilms in vitro and in vivo. This study provides a promising strategy for treating biofilm infections. Statement of significanceBiofilm formation is a leading cause of chronic infections. It blocks antibiotics, increases antibiotic-tolerance, and aids in immune evasion, thus representing a great challenge in clinic. This study proposes a promising approach to combat pathogenic Pseudomonas aeruginosa (P. aeruginosa) biofilms by combining Escherichia coli exopolysaccharides with antibiotics. This strategy shows high efficiency in different P. aeruginosa stains, including two laboratory strains, PAO1 and ATCC 10145, as well as a clinically acquired carbapenem-resistant strain. In addition, in vivo experiments have shown that this approach is effective against implanted P. aeruginosa biofilms and can prevent systemic inflammation in mice. This strategy offers new possibilities to address the clinical failure of conventional antibiotic therapies for microbial biofilms.

The impact of prior ACL reconstruction on total knee arthroplasty outcomes: a retrospective matched cohort study.

Discrepant data exists regarding the outcomes following total knee arthroplasty (TKA) with a prior anterior cruciate reconstruction (ACLR). The purpose of our study was to compare surgical and medical outcomes in the patients with prior ACLR undergoing TKAs compared to a matched control group of the patients who had undergone TKAs without prior ACLR. We hypothesized that the patients with prior ACLR would have inferior clinical outcomes. We retrospectively queried the PearlDiver-database for patients who underwent TKA following ACLR from 2011 to 2020. We used propensity-score matching to create two cohorts. The two-sided independent t-test and Chi-Squared test were used. We identified 2,174 patients who had prior ACLR before the TKAs. There were another 1,348,870 patients who did not have ACLR before the TKAs. After matching, each group had 2,171 patients. The ACLR-TKA group had significantly lower rates of aseptic revision at 2 years (1.2% vs. 4.0%, OR 0.3, p < 0.01), PJI requiring antibiotic spacer at 2 years (0.3% vs. 0.8%, OR 0.35, p = 0.02), and MUA at 90 days (0.4% vs. 7.5%, OR 0.05, p < 0.01). The rate of wound disruption was lower for the ACLR-TKA group at 90 days (p = 0.03) as were several medical complications including AKI at 90 days (p < 0.01), DVT at 90 days (p < 0.01), pneumonia at 90 days (0.04), and required blood transfusion at 90 days (p < 0.01). These results differed from our expectations. Within the limitations of the study, we are unable to determine the factors for the lower complications in the ACLR-TKA group. The data from this study are different from what had been reported in the previous studies.

Lived experiences of caregivers with infants treated at home with continuous invasive or noninvasive ventilation.

Caring for children dependent upon continuous invasive ventilation in the home setting requires extensive expertise, coordination, and can result in impaired caregiver quality of life. Less is known regarding the experiences of caregivers with children requiring continuous noninvasive ventilation. To evaluate caregiver experiences with invasive and noninvasive home mechanical ventilation, and to compare parental quality of life based on the child's mode of ventilation. Caregivers of infants who were discharged home with continuous ventilatory support were recruited to complete semi-structured qualitative interviews. Interviews explored their decision-making process, the transition to home, and health related quality of life. Caregivers of 16 children were interviewed, of whom eight were treated with continuous invasive ventilation, and eight with continuous noninvasive ventilation. The decision to pursue home ventilation in both groups was greatly influenced by the desire to be discharged and reunite the family at home. Following the transition to home, caregivers from both groups described high rates of insomnia, emotional distress, work disruption and familial hardship. Despite this, parents were overwhelmingly pleased with the decision to proceed with home ventilation and perceived their children to be living enriched lives outside of the hospital. Factors associated with easing the transition to home were in-hospital training and the presence of a robust support system. Lives of families with children dependent on continuous mechanical ventilation are characterized by isolation, lifestyle disruption, adverse mental and physical health consequences, and impaired interpersonal relationships, irrespective of the mode of ventilation.

Sleep Disruption Persists and Relates to Memory Disability After Traumatic Brain Injury: A Cross-Sectional Study of Adults in the Chronic Phase of Injury.

To examine sleep disruption in chronic traumatic brain injury (TBI) across 3 aims: (1) to examine differences in self-reported sleep disruption between adults with and without a chronic history of TBI; (2) to query reported changes in sleep after TBI; and (3) to explore the relationship between self-reported sleep disruption and memory failures in daily life. Community-dwelling participants completed self-report sleep and memory surveys as part of their participation in a larger patient registry. This study included 258 participants, and half (n=129) of them have a chronic history of moderate-severe TBI (mean time since injury is 5.1 [SD 6.5] years). We report descriptive statistics from this matched cross-sectional study on sleep in the chronic phase of injury. We also used planned Wilcoxon ranked-sum tests and exploratory correlations to examine the relationships of sleep disruption with TBI diagnosis, injury chronicity, and memory. We used the Pittsburgh Sleep Quality Index to measure sleep disruption and the Epworth Sleepiness Scale to measure daytime sleepiness. Participants answered questions about postinjury sleep and responded to the Everyday Memory Questionnaire as a measure of memory failures in daily life. Individuals with TBI had significantly higher rates of sleep disruption than those without TBI, as measured by the Pittsburgh Sleep Quality Index but not on the Epworth Sleepiness Scale. Sleep disruption in TBI manifested more in sleep quality than quantity. Half of the participants with TBI reported a negative change in sleep postinjury. In an exploratory analysis, sleep disruption was related to memory failure in daily life in the TBI sample. Sleep disruption persists long after TBI but may be under-recognized in people with chronic TBI. Given that sleep is critical for memory and rehabilitation outcomes well into the chronic phase of injury, steps to improve the identification and management of sleep disruption are needed. Key words:chronic, memory, sleep, traumatic brain injury.

Tidal Disruption of Planetesimals from an Eccentric Debris Disk Following a White Dwarf Natal Kick

The surfaces of many white dwarfs are polluted by metals, implying a recent accretion event. The tidal disruption of planetesimals is a viable source of white dwarf pollution and offers a unique window into the composition of exoplanet systems. The question of how planetary material enters the tidal disruption radius of the white dwarf is currently unresolved. Using a series of N-body simulations, we explore the response of the surrounding planetesimal debris disk as the white dwarf receives a natal kick caused by anisotropic mass loss on the asymptotic giant branch. We find that the kick can form an apse-aligned, eccentric debris disk in the range 30–240 au, which corresponds to the orbits of Neptune, the Kuiper Belt, and the scattered disk in our solar system. In addition, many planetesimals beyond 240 au flip to counterrotating orbits. Assuming an isotropic distribution of kicks, we predict that approximately 80% of white dwarf debris disks should exhibit significant apsidal alignment and a fraction of counterrotating orbits. The eccentric disk is able to efficiently and continuously torque planetesimals onto radial, star-grazing orbits. We show that the kick causes both an initial burst in tidal disruption events as well as an extended period of 100 Myr where tidal disruption rates are consistent with observed mass accretion rates on polluted white dwarfs.

Extreme Weather Disruptions and Emergency Preparedness Among Older Adults in Ohio: An Eight-County Assessment

The disproportionate risks and impacts of climate change and extreme weather on older adults are increasingly evident. While especially true in disaster-prone areas, human-caused climate change introduces an element of uncertainty even in previously identified “safe” regions such as the Midwestern United States. Using a cumulative disadvantage and vulnerability-informed framework and descriptive statistics from multiple data sources, this article provides an overview of climate impacts, vulnerabilities, and county-level characteristics, focusing on older adults living in Central Ohio. A comparative multiple-case study methodology was used to triangulate regionally representative primary and secondary data sources to examine state and county-level measures of vulnerability, emergency preparedness, and disruptions caused by extreme weather among older adults across eight counties in Central Ohio. Seventy-eight percent of older adults in the sample reported being prepared for emergencies per Federal Emergency Management Agency guidelines. Older adults in Union County reported the highest rates of preparedness, while those in Fayette County reported the lowest. County-level rates of disruption of life activities by extreme weather ranged widely. Among the most rural in the region, Fayette County emerged as uniquely disadvantaged, with the lowest median income, the most vulnerable across multiple social vulnerability dimensions, and the most reported disruptions to life activities from extreme weather. County profiles offer a snapshot of existing vulnerabilities, socioeconomic conditions, special needs, preparedness, and current disruptions among older adults in the region and can inform resource mobilization across community and policy contexts.

Saponin rich Gypsophila eriocalyx Boiss methanolic extract (GEME) exhibit anticancerogenic effect against neuroblastoma cancer cell line (SH-SY5Y)

Purpose: Herein, we sought to determine whether of saponin rich Gypsophila eriocalyx methanol extract (GEME) would exhibit any anti-carcinogenic activity on neuroblastoma cancer cell line (SH-SY5Y). &#x0D; Materials and Methods: We therefore determined GEME’s saponin composition using LC-MS analysis, its impact on cell viability using MTT analysis, flow cytometry, and to find out its impact on apoptosis using qRT-PCR analysis. &#x0D; Results: In the LC-MS analysis we determined that GEME contained high amounts of saponin (0.05-0.48 µg/g). We determined that GEME had an IC50 dose of 100 μg/mL at 48 hours. GEME had the effect of substantially increasing the percentage of apoptotic cells (5.19% and 65.21%) and disruption of mitochondria (46.18%). We also demonstrated that BCL2 gene expression (2.76 fold) was significantly reduced than that of the control while BAX (2.21 fold), CASP3 (2.43 fold), CASP7 (2.98 fold), CASP8 (2.23 fold), CASP9 (2.78 fold), and CYCS (2.12 fold) genes were expressed significantly higher than those of the control.&#x0D; Conclusion: Considering the findings, it becomes clear that saponin-rich GEME stands out as a significant anticarcinogenic agent. Its remarkable efficacy is demonstrated through its capabilities to notably reduce cell viability, effectively trigger apoptosis, and significantly increase the rate of mitochondrial disruption in cancer cells.

‘’Comparative outcome study between simple closure and flap technique in Pilonidal sinus disease’’

I have read the interesting article ‘’Comparative outcome study between simple closure and flap technique in Pilonidal sinus disease’’ by Dr. Ram Magar and Dr. Rupali Magar published in your journal on 15th March 2022. According to this valuable study; Limberg flap method has has been found to have better outcome with less wound infection, wound disruption, postoperative discharge and recurrence rate compared to simple closure group. And as stated, it is safe and easy procedure. So it is recommended that Limberg flap method should be used in the treatment of pilonidal sinus disease over other modalities.[1]&#x0D; In our 767 patients study group results, we had recommended Limberg Flap Repair Technique for surgical treatment of pilonidal sinus disease. This technique had an acceptable “short” ‘Return to Work Outcome’ when compared with open techniques. Also had the smallest postoperative infection rate and low recurrence rate.&#x0D; Still in our daily surgical practice, earlier healing, shorter return to work, lower rates of infection and recurrence are the major factors that make us to use Limberg Flap Repair Technique mostly. Moreover, it is easy, fast, and practical to apply.[2]

Association of Smokeless Tobacco and Complications Following Ankle and Hindfoot Arthrodesis.

The purpose of this study was to (1) evaluate the rates of postoperative complications following ankle or hindfoot arthrodesis among current smokeless tobacco users and people who smoke compared to matched controls, and (2) compare rates of postoperative complications in current smokeless tobacco users vs people who smoke tobacco cigarettes. A retrospective cohort study was conducted using a large national database. For patients who underwent ankle or hindfoot arthrodesis, smokeless tobacco users (n = 131) and people who smoke (n = 1948) were matched 1:4 with controls, and smokeless tobacco users (n = 131) were matched 1:4 with people who smoke tobacco cigarettes (n = 524). Orthopaedic complications within 90 days, 1 year, and 2 years were compared using multivariable logistic regressions. Within 90 days of ankle or hindfoot arthrodesis, smokeless tobacco users demonstrated significantly higher rates of hardware removal (odds ratio [OR] 5.01, 95% CI 1.65-15.20), wound disruption or dehiscence (OR 3.00, 95% CI 1.21-7.44), and pooled complications (16.0% vs 5.9%, OR 2.84, 95% CI 1.50-5.38) compared with tobacco-naïve controls. The rates of hardware removal, wound disruption and dehiscence, and pooled complications remained significant in the smokeless tobacco cohort at 1 and 2 years. At 2 years following ankle or hindfoot arthrodesis, smokeless tobacco users additionally demonstrated significantly higher rates of infection (OR 6.08, 95% CI 1.15-32.05) and nonunion (OR 2.35, 95% CI 1.31-4.20) compared with tobacco-naïve controls. Within 90 days of ankle or hindfoot arthrodesis, smokeless tobacco users demonstrated significantly lower rates of malunion or nonunion than patients who smoke tobacco cigarettes (OR 0.34, 95% CI 0.12-0.97), whereas all other complications were not significantly different. Smokeless tobacco use is associated with higher rates of complications following ankle or hindfoot arthrodesis compared with tobacco-naïve controls, and physicians should screen for smokeless tobacco use specifically and encourage cessation before operating electively. Level III, retrospective cohort study.

Abstract 6924: Structural variant dynamics in melanoma: Unraveling tumor heterogeneity and evolution

Abstract Melanoma is characterized by significant intratumoral heterogeneity and complex evolutionary dynamics. This diversity in genomic alterations leads to the emergence of various subclonal populations within a single tumor. In our research, we established a new model system composed of 24 single-cell-derived clonal sublines (C1-C24), originating from the M4 melanoma model. This model was developed using a genetically engineered hepatocyte growth factor (HGF)-transgenic mouse. We employed Trisicell (Triple-toolkit for single-cell intratumor heterogeneity inference), a cutting-edge computational tool for scalable analysis of intratumor heterogeneity and evaluation based on single-cell RNA mutations. This enabled us to construct a phylogeny tree, revealing melanoma’s intricate branching evolutionary patterns. These patterns show ancestral clones evolving into genetically distinct subclones, which demonstrate varied phenotypic traits such as drug sensitivity or resistance, cellular plasticity, and immunogenicity. In our study, we conducted long-read sequencing on these clonal sublines in the phylogeny and identified structural variants (SVs) using Severus, a tool optimized for phasing in long-read sequencing. The types of SVs we discovered include deletions, insertions, amplifications, translocations, and inversions. We explored their roles in subclonal evolution, particularly focusing on how they disrupt genes and accumulate during melanoma progression. Our initial data from eleven sublines indicated a higher prevalence of ancestral SVs, shared by all sublines, compared to subline-specific SVs, representing later events. Notably, the individual sublines showed a higher rate of gene disruption by SVs, hinting at potential functional selection. Our analysis further revealed that SVs common to all sublines are linked with genes in key cell growth pathways, such as Rap1, Hippo, and calcium signaling pathways. In contrast, subline-specific SVs primarily affect genes involved in neurophysiological pathways, such as glutamatergic synapse and morphine addiction pathways. These findings suggest that different genes, associated with various pathways, are disrupted at distinct stages of melanoma progression, providing insights into the genetic factors that may predispose individual melanocytes to melanomagenesis. This methodology presents a comprehensive tool for characterizing tumor genomes and understanding their relationship with disease progression and therapy resistance. We are continuing our analysis to map SVs across the entire mutation-based phylogeny of all sublines, which will further our understanding of melanoma’s genomic landscape. Citation Format: Xiwen Cui, Ayse G. Keskus, Farid R. Mehrabadi, Salem Malikic, Mikhail Kolmogorov, Chi-Ping Day, Glenn Merlino, S. Cenk Sahinalp. Structural variant dynamics in melanoma: Unraveling tumor heterogeneity and evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6924.

Interaction of sleep and emotion across the menstrual cycle.

Menstruating individuals experience an increased risk for sleep and affective disorders, attributed in part to monthly oscillations in sex hormones. Emotional functioning and sleep continuity worsens during the perimenstrual phase of the menstrual cycle. This study examined the interactive effects of sleep, menstrual phase, and emotion in healthy women. Participants (N = 51, 43% Caucasian) aged 18-35 (m = 24 years) completed actigraphy and daily sleep/emotion diaries over two menstrual cycles (m days = 51.29). Diary and actigraphic total wake time at night (TWT) and daily ratings of positive and negative affect were compared across four phases of the menstrual cycle: perimenstrual, mid-follicular, periovulatory, and mid-luteal. Relationships between phase, sleep, and emotion were estimated using multistep hierarchical linear modelling. Mean menstrual cycle length was 28.61 ± 2.69 days. Perimenstrual phase positively predicted anger (p < 0.001) but no other emotions. Additionally, the perimenstrual phase predicted higher rates of TWT, such that diary TWT was 8-16 min longer during the perimenstrual (m = 67.54, SE = 3.37) compared to other phases (p < 0.001). Actigraphic TWT was also increased by 4-7 min (m = 61.54, SE = 3.37) in the perimenstrual phase (p < 0.001). Positive emotions were 0.05-0.10 points lower (p = 0.006-0.02) when TWT was greater in the perimenstrual phase. Greater rates of anger and sleep disruption were seen during the perimenstrual phase compared with other phases. When poor sleep occurred during the perimenstrual phase individuals reported reduced positive emotions. Reducing perimenstrual sleep disruptions may be an important intervention target for those at risk for affective disorders.

Impact of non‐tariff measures on the survival of China's fresh fruit exports

Using data at the HS‐6 product level, this study presents evidence on the export survival of China's fresh fruit during the period 2002–2019, and identifies the impact of non‐tariff measures (NTMs) on the hazard rate of trade disruption. The results show that the average length of 2239 trade spells is 5.16 years. Notably, 67.04 per cent of these spells are no more than three years long, whereas only 7.95 per cent are more than 18 years long. Compared with major fruit‐exporting countries, the trade spell distribution of China's fresh fruit exports lacks advantages. The hazard rate can reach 0.41 in the first year of export and is negatively duration dependent. The implementation of NTMs by importing countries has significantly increased the hazard rate. The positive effect of NTMs on the hazard rate is primarily driven by non‐technical measures. Notably, technical barriers to trade measures decrease the export hazard rate of China's fresh fruits with comparative advantages, because these measures focus on product quality. Meanwhile, non‐technical measures increase the export hazard rate of such fruits; this may be because of the possible shock on the relevant fruit industry in the destination market.