Independent Analysis Research Articles

Immune gene features and prognosis in colorectal cancer: insights from ssGSEA typing

BackgroundColorectal cancer (CRC) is a molecularly heterogeneous disease, and its treatment and prognosis vary greatly among subgroups. Therefore, it is necessary to identify prognostic factors associated with the biological heterogeneity of CRC in order to improve patients' survival expectations.MethodsWe obtained and merged RNA-Seq data along with clinical details for colorectal cancer (CRC) from The Cancer Genome Atlas (TCGA) repository, and then performed immunocluster typing on all CRC specimens. We conducted differential expression gene (DEG) analysis, gene set enrichment analysis (GSEA), and tumor microenvironment (TME) analysis on CRC samples that were divided into high and low Immunity categories. Moreover, we pinpointed prognostic genes from immune-related gene (IRGs) sets, developed a prognostic risk model, and executed survival analysis, receiver operating characteristic (ROC) curve analysis, and independent prognostic analysis. Additionally, we assessed the risk for patients categorized into high- and low-risk groups based on the model. Lastly, we created a Nomogram to customize the prediction of survival outcomes in CRC patients.ResultsCRC samples were divided into high and low Immunity groups based on the median value of the immunity score. Between the two groups, a total of 1550 DEGs were identified and 395 differentially expressed immune-related genes (DE-IRGs) were identified by intersection with 2483 IRGs. The DE-IRGs of the high Immunity group were dominated by Cytokine receptor interactions, chemokine signaling pathways and immune cell-mediated cytotoxicity, and molecule function of immune effector process. TME analysis showed that most of the 27 immune cells and functions were highly enriched in high Immunity group, whose Immune Score, Stromal Score and ESTIMATE Score were significantly higher. Subsequently, a prognostic risk model of CRC was constructed based on 12 prognostic genes, and the accuracy and reliability of the model prediction were verified. Finally, Nomogram enabled accurate individual prediction of the survival prognosis of CRC patients.ConclusionsOur study develops an immune-related prognostic model and Nomogram that reliably predicts survival outcomes in CRC patients and enhances understanding of the tumor immunity and molecular mechanisms of CRC.

Multivariate Cox regression analysis of prognostic genes and therapeutic mechanisms of gastric cancer

Gastric cancer (GC) is a common malignant tumor, which originated from the epithelial cells of the stomach. It has the characteristics of high incidence and poor prognosis. Therefore, it is urgent to find new prognostic markers for the diagnosis and treatment of GC. Download gene expression matrix and clinical data from TCGA database and GSE84437 dataset. Through independent prognostic analysis and clinical correlation analysis, 74 prognostic related genes (PRG) were screened out. A PPI network was established for PRG to identify four key genes (KG), namely LMOD1, CRYAB, VCL and MYL9. Survival analysis showed that patients with high expression of KG had poor prognosis. Multivariate Cox regression analysis showed that KG was an independent prognostic factor. TCGA database verifies the importance and significance of KG as a prognostic indicator. Functional enrichment analysis showed that KG was mainly involved in cell adhesion molecules, adhesion spots and PI3K/AKT signaling pathway. KG may be a potential therapeutic target for gastric cancer.

A hybrid [18F]fluoropivalate PET-multiparametric MRI to detect and characterise brain tumour metastases based on a permissive environment for monocarboxylate transport.

The incidence of Intracranial Metastatic Disease (IMD) continues to increase in part due to improvements in systemic therapy resulting in durable control of extra-cranial disease (ECD). Contrast-enhanced Magnetic Resonance Imaging (CE-MRI) is the preferred method for imaging IMD, but has limitations particularly in follow-up surveillance scans to optimise patient care. We investigate a new diagnostic approach of hybrid ([18]F]fluoropivalate (FPIA) Positron Emission Tomography-multiparametric MRI (PET-mpMRI), in 12 treatment-naïve and 10 stereotactic radiosurgery (SRS)-treated patients (± combination therapy within 4-8 weeks). High FPIA uptake was seen in all IMD compared to contralateral white matter, regardless of ECD tumour-of-origin (p = 0.0001) and FPIA-PET volumes extended beyond CE-MRI volumes in treatment-naïve but not SRS-treated tumours. Patients with maximum PET Standardised Uptake Value, (SUVmax) ≥ 2.0 showed particularly short overall-survival (median 4 v 15 months, p = 0.0136), while CE-MRI was uninformative regarding outcome; a PET-mpMRI grade-measure also provided non-invasive prediction of overall-survival, warranting larger studies of PET-mpMRI. Independent metabolomics analyses were consistent with shared adaptation of IMD to utilise or accumulate monocarboxylates and acylcarnitines, respectively, providing a common phenotypic basis to FPIA-PET. Reprogrammed monocarboxylate metabolism-related FPIA-PET provides new insights into annotating IMD, to be expounded in future opportunities for therapy decisions for the growing number of cancer patients with IMD [Trial registration reference: Clinicaltrials.gov NCT04807582; 3rd November 2021, retrospectively registered].

The Challenges of Using Large Language Models: Balancing Traditional Learning Methods with New Technologies in the Pedagogy of Sociology

The increasing use of artificial intelligence (hereafter AI) in education, particularly through large-scale language models such as ChatGPT and Bing, offers both challenges and opportunities. These models facilitate interaction in conversations and can perform tasks that require natural language processing, from answering questions to solving problems. However, their integration into education raises concerns about the credibility and reliability of the information they provide and about the role of the teacher, emphasizing the need for guided use in educational environments. This article contributes to the discourse from the perspective of the pedagogy of sociology, focusing on the role of chatbots in analyzing texts within the social sciences and humanities fields. Our pilot study, conducted with 17 first-year master’s students studying sociology, reveals that while chatbots can optimize the creation of summaries and the provision of basic information, their reliance on sources such as Wikipedia calls into question the depth and impartiality of the content. In addition, students have criticized chatbots for providing biased or inaccurate outputs. A significant part of our research has compared the epistemological and methodological approaches of chatbots with a traditional, independent literature analysis (deep reading), and we found notable differences in learning outcomes. However, a hybrid approach that combines AI tools with conventional methods offers a promising way to improve learning and teaching strategies and can enhance the critical analytical skills that are crucial for future pedagogies.

Examining the Digital Literacy Levels of Syrian Refugee University Students

The aim of this study is to examine the digital literacy levels of Syrian refugee students studying at universities in Turkey across different variables. A descriptive survey model was used in the research. The sample of the study consisted of 184 Syrian university students studying at Selçuk University in Konya. The "Student Information Form" and the "Digital Literacy Scale" were used as data collection tools. In the analysis of the data, independent sample t-tests and ANOVA analysis were conducted using the SPSS software package. According to the findings, the digital literacy levels of Syrian university students were found to be above average. The study concluded that there was no significant difference in digital literacy scores between male and female students. Additionally, the digital literacy scores of 4th-year students were found to be significantly higher than those of 1st-year students. An analysis of age groups revealed that the digital literacy scores of students aged 19-21 were significantly higher than those of students aged 25-27.

Exploring the equivalence of causality-based and quantum mechanics-based sum rules for harmonic generation in nonlinear optical materials

The Kramers-Kronig relations and various oscillator strength sum rules represent strong constraints on the physical response of materials. In this work, taking inspiration from the well-established equivalence between f-sum rules and Thomas-Reiche-Kuhn sum rules in linear optics, we explore the connection between causality-based and quantum-mechanics-based sum rules in the context of nonlinear optical processes. Specifically, by considering the sum-over-states expression for the second harmonic generation susceptibility, we deduce a new representation basis for the imaginary part of this susceptibility and we use it to derive, from causality-based integral sum rules, a new set of discrete sum rules that the transition dipole moments must satisfy. As in the case of the Thomas-Reiche-Kuhn sum rules, we also show that these results can alternatively be derived through an independent quantum mechanical analysis. Finally, we consider the implications of the derived sum rules for the second-harmonic-generation susceptibility of two- and three-level systems and, more broadly, we discuss the possible significance and challenges of using these results for the goal of identifying fundamental limits to the response of nonlinear optical materials.

Research on Water-Entry Hydrodynamics for a Cross-Wing Underwater Vehicle

The optimization of the water-entry strategy for cross-wing underwater vehicles has become a research hotspot in the field of engineering, and its water-entry process is quite different from that of wedges and cylinders. In order to address this problem, a water-entry numerical model for the cross-wing underwater vehicle was first established based on the CFD method. The governing equations and boundary conditions of the dynamic model were defined, along with the basic principles of discretization and turbulent flow of the governing equations. The overset mesh and the VOF multiphase flow model were introduced, and a mesh size independence analysis of the numerical model was conducted. Furthermore, the numerical results were compared with the experimental results to ensure the accuracy of the numerical model. The research focused on the cross-wing underwater vehicle’s impact with calm water and regular waves, respectively. The results show that: (1) the numerical simulations are in good agreement with the experimental results (the maximum predictive error is less than 10%), which verifies the accuracy of the numerical model in this paper; (2) when the cross-wing underwater vehicle impacts calm water, the slamming pressure curve firstly shows a trend of increasing, reaching a peak, and then decreasing sharply, and finally stabilizes. As the water-entry velocity increases, the peak slamming pressure exhibits a gradual increase; (3) during the water entry of the cross-wing underwater vehicle into calm water, the acceleration profile demonstrates a trend of initial increase, followed by a decrease, another increase, and then a subsequent decrease as the entry velocity continues to rise. It should be noted that there are two peaks in the acceleration, with the first peak being significantly smaller than that of the second; (4) when the cross-wing underwater vehicle impacts a regular wave, the slamming pressure is lowest when impacting the crest and highest when impacting the trough.

Caring Readiness Among Parents of Children Who Have Undergone Liver Transplantation and Are Transitioning From the Intensive Care Unit: A Cross-Sectional Study.

To investigate the status and influencing factors of caring readiness among parents of children undergoing liver transplantation transitioning from the intensive care unit, and to explore the associations between caring readiness and other variables. A cross-sectional study. A total of 126 parents of children who underwent liver transplantation at a tertiary hospital in China took a questionnaire survey via convenience sampling. Independent t-test, ANOVA and correlation analysis were conducted to analyse the data. Multivariable stepwise linear regression was used to analyse the influencing factors of caring readiness. The PROCESS macro (Model 4) was used to verify the mediating effect of caregiver burden between social support and caring readiness. The STROBE checklist was used as a guideline in this study. The mean score of caring readiness among parents of children who had undergone liver transplantation and were transitioning from the intensive care unit was 23.62 ± 5.34. Multivariable stepwise linear regression analysis indicated that experience with caregiving, intensive care unit length of stay, social support and caregiver burden were the factors associated with caring readiness, explaining 18.6% of the variance in caring readiness among parents. Caregiver burden partially moderated the relationship between social support and caring readiness (20.93%). The study shows caring readiness was moderate among parents of children who have undergone liver transplantation and are transitioning from the intensive care unit. It reveals that lack of caregiving experience and children's short intensive care unit length of stay should be emphasised, preventing inadequate readiness of parents. Furthermore, enhancing social support interventions and burden-reduction strategies are important for improving parents' caring readiness. The findings demonstrate that health care professionals should provide timely and appropriate intervention strategies to enhance parents' caring readiness, which could potentially be achieved by increasing social support and reducing caregiver burden. Parents of children who underwent liver transplantation participated in this study via a questionnaire survey.

Outcome of patients with Fabry disease: An independent analysis from a single clinic in Calgary

Outcome of patients with Fabry disease: An independent analysis from a single clinic in Calgary

Factors Influencing Knowledge and Attitudes towards Second-Hand Smoking Exposure Among University Students: An Exploratory Study.

Despite extensive global research on second-hand smoking (SHS) exposure, there is a noticeable lack of studies focusing on the knowledge and attitudes of university students in Bangladesh. This cross-sectional study aimed to address this gap by assessing the levels of knowledge and attitudes towards SHS exposure among university students in Bangladesh. Utilizing a convenience sampling technique, data were collected from 383 university students, encompassing socio-demographic information, as well as knowledge and attitude-related inquiries. Statistical analyses were conducted using SPSS software, including independent t-tests and analysis of variance (ANOVA) and multiple linear regression. The findings revealed that participants exhibited a moderate level of knowledge and attitude towards SHS exposure. Multiple linear regression identified age, gender, mother's education, and self-rated health status as significant predictors of knowledge, explaining 12.9% of its variance (R2 = 0.129, F = 6.117, P < .001). Furthermore, age, gender, and living with parents emerged as significant predictors of attitude, explaining 14.7% of its variance (R2 = 0.147, F = 7.165, P < .001). The study highlights the need for interventions aimed at enhancing awareness and fostering positive attitudes towards SHS exposure among university students in Bangladesh. It is recommended that university authorities organize seminars and implement health education initiatives targeting vulnerable populations to address the findings and promote a smoke-free environment on campus.

APOKASC-3: The Third Joint Spectroscopic and Asteroseismic Catalog for Evolved Stars in the Kepler Fields

Abstract In the third APOKASC catalog, we present data for the complete sample of 15,808 evolved stars with APOGEE spectroscopic parameters and Kepler asteroseismology. We used 10 independent asteroseismic analysis techniques and anchor our system on fundamental radii derived from Gaia L and spectroscopic T eff. We provide evolutionary state, asteroseismic surface gravity, mass, radius, age, and the data used to derive them for 12,418 stars. This includes 10,036 exceptionally precise measurements, with median fractional uncertainties in ν max , Δν, mass, radius, and age of 0.6%, 0.6%, 3.8%, 1.8%, and 11.1%, respectively. We provide more limited data for 1624 additional stars that either have lower-quality data or are outside of our primary calibration domain. Using lower red giant branch (RGB) stars, we find a median age for the chemical thick disk of 9.14 ± 0.05(ran) ± 0.9(sys) Gyr with an age dispersion of 1.1 Gyr, consistent with our error model. We calibrate our red clump (RC) mass loss to derive an age consistent with the lower RGB and provide asymptotic GB and RGB ages for luminous stars. We also find a sharp upper-age boundary in the chemical thin disk. We find that scaling relations are precise and accurate on the lower RGB and RC, but they become more model dependent for more luminous giants and break down at the tip of the RGB. We recommend the use of multiple methods, calibration to a fundamental scale, and the use of stellar models to interpret frequency spacings.

Conquering future worries: How positive thinking training helps students overcome anxiety

Anxiety is a common occurrence among individuals facing transitions in life phases, including students who have certain hopes, goals, and standards of living related to their future. As they near the end of their studies, in addition to their final assignments, envisioning the future also becomes a source of anxiety for students. Anxiety is influenced by cognitive performance, especially the perception of things not yet experienced. Anxiety about the future is influenced by negative perceptions of things not yet experienced. One effective therapy in reducing this anxiety is positive thinking therapy. This study aims to prove the effect of positive thinking therapy on 17 male and female students aged between 20 – 24 years old. The participants were selected by purposive sampling method and obtained 17 participants. The 17 participants were randomly divided into two groups, as control and experimental groups. The experiments conducted with repeated measure control group design. The result of repeated measure from the experimental group showed F = 28.2, p &lt; 0.01 and control group showed F = 46,1 and p &lt; 0.01. Meanwhile, the results of independent sample t-test analysis showed a score of F = 2.25 with P &lt; 0.05. The result showed that positive thinking therapy is capable to decrease the symptoms of future anxiety.

Optimization of Flight Mode and Independent Impact Analysis of Operational Parameters on Droplet Deposition and Drift of Unmanned Aerial Spraying Systems (UASS)

In recent years, extensive research has been conducted on pesticide application technology using unmanned aerial spraying systems (UASS) due to their efficiency and ability to overcome terrain obstacles. However, the coupling effect between the operational parameters of UASS and their influence on droplet deposition has not been sufficiently studied. A thorough and methodical analysis is essential to assess the deposition performance and drift risk of UASS. This study evaluated the spraying performance of an electric six-rotor UASS in wheat fields in Zibo between 2021 and 2022, focusing on three operational modes determined by flight speed and flow rate. Furthermore, the individual effects of these two parameters on droplet deposition quality and drift risk were explored. Based on the deposition quality of in-swath droplets and the drift degree after application, the results demonstrate that the optimal comprehensive characteristics of droplet deposition occur at a flight speed of 4.5 m/s, a flow rate of 2.025 L/min, and a spray amount of 1 L/ha. The increase in spray flow rate (2.475 L/min) results in a 3.92-fold enhancement in the deposition rate within the spray area compared with that of group of the minimum spray flow rate (1.575 L/min). A higher flight speed (5.5 m/s) improves the uniformity of droplet deposition, with the coefficient of variation decreases by 25.2% compared with that of the minimum flight speed (3.5 m/s), and this higher flight speed leads to a drift distance of 28.8 m.

The effectiveness of “Boteli” and Fed on exercises to court tennis backhand groundstroke rally skills

Introduction and objective. Study aims to determine the effectiveness of Boteli exercises and fed on the groundstroke rally skills of backhand tennis in sports students. Methodology. 110 sports students participated in a pseudo-experimental study with a two group pretest-posttest design over 12 meetings. Test the instrument using Hewwit's Tennis Achievement. Paired t-test and independent t-test at significance α = 0.05 were used for data analysis with the help of SPSS 25 software. Results. Analysis of the paired t-test results showed that the Boteli and Passed exercises obtained Sig. (2-tailed) values of 0.000 and 0.024. Based on the results of the independent t-test analysis, it is known that the value of Sig. (2-tailed) of the post-test data of the second exercise is 0.001. This means that there is a difference between the average score of the Boteli and fed on exercise post-test. The average score of the Boteli exercise post-test was 11.209 and the Feeder exercise was 9.091. Conclusions. Based on the results of data analysis, the two exercises influence improving the groundstroke backhand rally skills of sports students. From the results of the independent t-test analysis, it is known that the average score of the post-test of the Boteli exercise is greater than that of the fed on exercise. This means that Boteli exercises are better than Fed exercises in improving the backhand groundstroke rally skills of sports students. This study concluded that backhand groundstroke rally skills in court tennis can be improved with varied practice.

Pemanfaatan Model Pembelajaran Project Based Learning Berbantu Geospatial Technology Terhadap Berpikir Kreatif Siswa Kelas XI Fase F di SMA Negeri 1 Batang Kapas

This study aims to determine the effect of the project based learning model assisted by geospatial technology on the creative thinking skills of class XI Phase F students at SMA Negeri 1 Batang Kapas. This study is a quasi-experimental design study with a pretest posttest control group design. The population of the subjects of this study were 64 students of class XI Phase F who were divided into two classes. Class XI F/8 as the experimental group and class XI F/10 as the control group with the number of students in each class. The data collection technique in this study used a test in the form of 20 multiple-choice questions and 5 essay questions that had been tested for validity and reliability. Hypothesis testing in this study used the Independent T-Test analysis to test the difference in scores obtained by students in the control class and the experimental class after learning (post-test). The results showed that there was an effect of the project based learning model assisted by geospatial technology on the creative thinking skills of class XI Phase F students at SMA Negeri 1 Batang Kapas

Fluorescence-Guided Surgery to Detect Microscopic Disease in Ovarian Cancer: A Systematic Review with Meta-Analysis

Abstract: Background: The objective in epithelial ovarian cancer is to reach maximal cytoreduction with no visible residual tumor. Tumor detection during cytoreductive surgery depends on visual inspection, palpation, or blind biopsy, methods that lack reliability for identifying microscopic disease. Although the importance of microscopic disease in epithelial ovarian cancer is controversial, it may harbor chemoresistant cells and explain the high recurrence rates. Fluorescence-guided surgery (FGS) is an emerging approach. However, the potential in ovarian cancer remains underexplored; the majority of the existing evidence pertains to gastrointestinal tumors and a limited group of ovarian cancer patients. Their comparative effectiveness is still uncertain. Objective: To systematically review and evaluate the role of fluorescence-guided surgical techniques in detecting microscopic disease in ovarian cancer and compare their efficacy to total peritonectomy. Data Sources: A systematic search was made in three databases (PubMed, Web of Science, and Embase). The search was conducted from 1975 to 2024, including randomized controlled trials, observational studies, and conference abstracts in the last 25 years. Study Selection: Clinical studies published in English involving ovarian cancer patients undergoing FGS or total peritonectomy were included. Case reports, reviews, animal studies, and studies involving mixed cancer populations without ovarian cancer-specific data were excluded. Two independent reviewers screened 631 studies, yielding 12 eligible studies for final analysis. Data Extraction and Synthesis: Data were extracted and synthesized in accordance with PRISMA and MOOSE guidelines, using random-effects models for independent analysis. Sensitivity, specificity, positive predictive value (PPV), and odds ratios (ORs) were grouped, accompanied by subgroup analyses based on the fluorescence agent employed. For quality assessment, we utilized the NIH quality tool. Main Outcome(s) and Measure(s): The primary outcome was the rate of change in surgical management due to fluorescence guidance or total peritonectomy. Secondary outcomes comprised lesion-level sensitivity, specificity, and PPV. Safety outcomes included adverse events associated with fluorescence agents. Results: There were 12 studies involving 429 ovarian cancer patients. FGS improved the detection of microscopic disease compared to standard visualization methods, with a pooled sensitivity of 0.77. Folate receptor-targeted agents had high sensitivity (84%) but low specificity (26%). Aminolevulinic acid (5-ALA) showed superior diagnostic accuracy with a sensitivity of 84% and a specificity of 96%. Total peritonectomy showed no significant advantage over FGS for detecting microscopic disease. The adverse events were mild, with no serious events reported. We observed a high heterogeneity across studies and methodologies. Conclusions and Relevance: Fluorescence-guided surgery utilizing fluorescence tracers demonstrates potential in improving the detection of microscopic disease and may change surgical management in epithelial ovarian cancer, particularly with 5-ALA. Variability in performance and limited data on survival outcomes necessitates additional research. Total peritonectomy does not offer further advantage in the detection of microscopic disease. Future trials should focus on standardizing methodology and evaluating the effects of microscopic disease removal on survival outcomes. Registration: The study was registered to PROSPERO as CRD42024578274.

Druggable genome CRISPRi screen in 3D hydrogels reveals regulators of cortactin-driven actin remodeling in invading glioblastoma cells.

To identify new therapeutic targets that limit glioblastoma (GBM) invasion, we applied druggable-genome CRISPR screens to patient-derived GBM cells in micro-dissectible biomimetic 3D hydrogel platforms that permit separation and independent analysis of core vs. invasive fractions. We identified 12 targets whose suppression limited invasion, of which ACP1 (LMW-PTP) and Aurora Kinase B (AURKB) were validated in neurosphere assays. Proximity labeling analysis identified cortactin as an ACP1- AURKB link, as cortactin undergoes serine phosphorylation by AURKB and tyrosine dephosphorylation by ACP1. Suppression of ACP1 or AURKB in culture and in vivo shifted the balance of cortactin phosphorylation in GBM and reduced actin polymerization and actin-cortactin co-localization. Additional biophysical analysis implicated AURKB in GBM cell adhesion and cortical stiffness, and ACP1 in resistance to mechanical stress and shape plasticity needed for 3D migration. These findings reveal a novel targetable axis that balances kinase and phosphatase activities to regulate actin polymerization during GBM invasion.

The application of multidisciplinary team combined flipped classroom teaching model in oral general course for clinical undergraduates

BackgroundOral general course (OGC) is a basic subject of medical education. The implementation of multidisciplinary team (MDT) meets the individual needs of patients. Based on the concept of MDT, this study combined the theory and practice of flipped classroom teaching method to evaluate the teaching effect, so as to provide a basis and reference for the thinking transformation of medical students to clinicians.MethodsThe participants of the study were 760 clinical undergraduates in OGC training in Hainan Medical University from 2021 to 2023. A total of 760 students were divided into a control group and an observation group of 380 cases, each using the random number table method. The control group used traditional teaching methods, the observation group adopted the MDT combined with flipped classroom teaching model and organized dental postgraduates team to participate in the teaching task. A unified assessment of the teaching outcomes was conducted after 1 semester study duration.ResultsThe basic theory, independent learning ability and case analysis scores of the observation group were higher than those in the control group, and the differences were statistically significant (P < 0.05). Except there was no statistically significant difference in literature searching ability between the two groups (P > 0.05), the other indicators of teaching satisfaction in the observation group were higher than those in the control group, and the difference was statistically significant (P < 0.05). The postgraduates team gave relatively good feedback to the MDT combined flipped classroom teaching model.ConclusionMDT combined flipped classroom teaching model had outstanding effect in OGC, this student-centered teaching method was a beneficial supplement to their clinical thinking and practical ability, and worth further promotion.Trial registrationNot applicable.

Pangenomics Links Boll Weevil Divergence With Ancient Mesoamerican Cotton Cultivation.

The boll weevil, Anthonomus grandis grandis Boheman, and thurberia weevil, Anthonomus grandis thurberiae Pierce, together comprise a species complex that ranges throughout Mexico, the southwestern regions of the United States and parts of South America. The boll weevil is a historically damaging and contemporaneously threatening pest to commercial upland cotton, Gossypium hirsutum L. (Malvales: Malvaceae), whereas the thurberia weevil is regarded as an innocuous non-pest subspecies that is mostly found on non-cultivated Thurber's or Arizona cotton, Gossypium thurberi L., throughout its native range in western Mexico and the southwestern United States. Recent independent analyses, using mitochondrial and whole-genome markers, have suggested the independent evolution of these lineages is more attributable to geographic isolation than biotic factors. We suggest a combination of drivers after employing comparative genomic, population genetic and pangenome methodologies to identify large and small polymorphisms. By leveraging genetic differences, we determined 39,310 diagnostic loci between the subspecies, find genes under selection, and model the subspecies' shared and unique evolutionary history. Interestingly, structural variations capture a large proportion of genes at the population level and demographic reconstruction suggests a split between approximately 3,320-16,300 before present (YBP), which coincides with cotton cultivation in Mesoamerica, approximately 3,000-5,000 YBP. Observed polymorphisms are enriched for reproductive, regulatory, and metabolic genes, which may be attributed to the subspecies split and coevolution with cultivated cotton. Our results demonstrate the utility of a holistic, comparative framework utilising small and large polymorphisms to reconstruct demography and identify genetic novelty via pangenomics.

Iron deposition is associated with motor and non-motor network breakdown in parkinsonism.

Iron deposition has been observed in Parkinsonism and is emerging as a diagnostic marker for movement disorders. Brain functional network disruption has also been detected in parkinsonism, and is believed to be accountable for specific symptoms in parkinsonism. However, how iron deposition influences brain network remains to be elucidated. We recruited 16 Parkinson's disease (PD), 8 multiple system atrophy (MSA) and 7 progressive supranuclear palsy (PSP) patients. T1-weighted, susceptibility weighted images and resting-state functional MRI (rs-fMRI) were acquired. Quantitative susceptibility mapping (QSM) analysis was performed to quantify iron deposition in substantia nigra, putamen and dentate nucleus. Cerebellar network, sensorimotor network, default mode network and language networks were segregated using independent analysis. Network and iron deposition status were evaluated in relation to diagnostic groups, motor and non-motor symptoms. The relationship between quantitative iron deposition and brain network status was further interrogated. To further validate the findings, 13 healthy controls and 37 PD patients who had available T1 and rs-fMRI scans were selected from Parkinson's progression markers initiative (PPMI) database, and network analysis was performed. In local cohort, compared to PD, MSA patients showed greater iron deposition in putamen, while PSP patients had greater iron deposition in caudate nucleus and thalamus. Cerebellar and language networks showed significant difference across diagnostic groups, while default mode network and sensorimotor network did not. MSA patients had significantly impaired cerebellar network and language networks compared to PD patients. Cerebellar network was positively associated with motor symptom scores while language network was positively associated with MoCA scores in the patients. Iron deposition was negatively associated with both networks' activity in the patients. In PPMI cohort, impairment was found in both cerebellar and language networks in PD. Cerebellar and language networks correlated with motor and cognitive impairment, respectively. Cerebellar network and language networks are differently influenced in MSA, PD and PSP, which can serve as potential diagnostic marker. Impairment of cerebellar network and language network are associated with motor symptoms and cognitive impairment, respectively. Moreover, dysfunction of the networks is associated with iron deposition in deep nuclei (SN, DN, Putamen).