Early Stage Research Articles

Association Between Laboratory Coagulation Parameters and Postpartum Hemorrhage in Preterm and Term Caesarean Section: A Retrospective Analysis.

Background: Deranged antepartum laboratory parameters may be risk factors for postpartum hemorrhage (PPH). However, whether this is also valid in women who give birth prematurely is currently unknown. Methods: We performed a retrospective single-center study to assess the role of antepartum hemoglobin, platelet count, fibrinogen, activated partial thromboplastin time, and prothrombin time as risk factors for PPH following caesarean section. We defined PPH as documented blood loss of at least 1 L and/or transfusion of red blood cell concentrates. We stratified the included patients according to gestational age: extremely preterm (gestational age < 28 weeks), very preterm (gestational age between 28 and 32 weeks), late and moderate preterm (gestational age between 32 and 37 weeks), and term (gestational age ≥ 37 weeks). Results: We included 1734 patients, 112 (6%) of whom had PPH. In total, 19 patients (10%) were in the extremely preterm group, 13 patients (10%) were in the very preterm group, 44 patients (9%) were in the late and moderate preterm group, and 36 patients (4%) were in the term group. Hemoglobin predicted PPH in all gestational age groups. Platelet count was associated with PPH in term, but not in preterm patients. Fibrinogen was associated with PPH in late prematurity but not in term patients and not in patients with early or extreme prematurity. Conclusions: Antepartum hemoglobin was the only factor predicting PPH in preterm and term caesarean sections. Platelet count and fibrinogen concentration were associated with PPH in term and late prematurity, respectively, but not in earlier stages of prematurity.

Application of systems safety principles for O&M of floating offshore wind

Abstract The offshore wind industry is growing rapidly and is also a high risk industry with unique safety challenges. As the industry grows, more research is needed to make sure it operates safely and provides a workplace in which all involved can go home free of injury. The adoption of floating wind turbines brings new hazards and increased complexity to offshore wind operations and maintenance. Floating wind operations will involve the development of new deepwater sites and require the adoption of new strategies such as floating to floating transfers and towing operations. As the complexity of offshore operations increases it is important that the understanding of the hazards involved are developed. Floating wind is a new branch of the offshore wind industry and as technologies and systems have yet to become established there is the opportunity to do things differently and embed safety improvements in the industry from the outset. This study has looked at the potential application of systems safety theories to floating wind operations and maintenance. The application of systems engineering to improve safety performance has been growing across many industries in recent years. Systems safety considers that safety is an emergent property of a complex system that is a result of many interacting factors. This study looks at how systems safety could be applied to the emerging floating wind industry to build safety into the industry at the earliest stages. This study reviewed the applications of systems safety across similar industries and the offshore wind industry. It then looks at existing hazards of floating wind that have already been identified in the literature and completed a systems theory hazard analysis of floating wind O&amp;M activities. This involved the mapping of the safety control structure for floating wind operations and the identification of potential gaps between the safety controls and safety requirements. It then explores how systems safety processes could be applied to floating wind and makes recommendations for how these could be implemented to the emergent industry. The study found existing research of systems safety applied to the offshore wind industry is currently very limited. Its application has been successful in similar industries and there is potential for a systems safety approach to be used in the development of floating wind operations and maintenance. The systems theory hazard analysis can help identify potential systemic risks arising as a result of the interaction of multiple systems. It can be used to develop appropriate control structures to manage safety and could also be used for the identification of leading indicators to manage safety performance.

Metabolomics: A Tool to Envisage Biomarkers in Clinical Interpretation of Cancer.

Cancer is amongst the most dreadful ailments of modern times, and its impact continuously worsens global health systems. Early diagnosis and suitable therapeutic agents are the prime keys to managing this disease. Metabolomics deals with the complete profiling of cells and physiological phenomena in their organelles, thus helping in keen knowledge of the pathological status of the disease. It has been proven to be one of the best strategies in the early screening of cancer. This review has covered the recent updates on the promising role of metabolomics in the identification of significant biochemical markers in cancer-prone individuals that could lead to the identification of cancer in the early stages. The literature was collected through various databases, like Scopus, PubMed, and Google Scholar, with stress laid on the last ten years' publications. It was assessed in this review that early recognition of cancerous growth could be achieved via complete metabolic profiling in association with transcriptomics and proteomics. The outcomes are rooted in various clinical studies that anticipated various biomarkers like tryptophan, phenylalanine, lactates, and different metabolic pathways associated with the Warburg effect. This metabolite imaging has been a fundamental step for the target acquisition, evaluation of predictive cancer biomarkers for early detection, and outlooks into cancer therapy along with critical evaluation. Significant efforts should be made to make this technique most reliable and easy.

LabEmbryoCam: An opensource phenotyping system for developing aquatic animals

Phenomics is the acquisition of high-dimensional data on an individual-wide scale and is proving transformational in areas of biological research related to human health including medicine and the crop sciences. However, more broadly, a lack of accessible transferrable technologies and research approaches is significantly hindering the uptake of phenomics, in contrast to molecular-omics for which transferrable technologies have been a significant enabler. Aquatic embryos are natural models for phenomics, due to their small size, taxonomic diversity, ecological relevance, and high levels of temporal, spatial and functional change. Here, we present LabEmbryoCam, an autonomous phenotyping platform for timelapse imaging of developing aquatic embryos cultured in a multiwell plate format, and while optimised for embryos, the instrument is extremely versatile. The LabEmbryoCam capitalises on 3D printing, single board computers, consumer electronics and stepper motor enabled motion. These provide autonomous X, Y and Z motion, a web application streamlined for rapid setup of experiments, user email notifications and a humidification chamber to reduce evaporation over prolonged acquisitions. Downstream analyses are provided, enabling automated embryo segmentation, heartbeat detection, motion tracking, and energy proxy trait (EPT) measurement. LabEmbryoCam is a scalable, and flexible laboratory instrument, that leverages embryonic and early life stage organisms to tackle key global challenges including biological sensitivity assessment, toxicological screening, but also to support broader engagement with the earliest stages of life.

Transmission of highly virulent CXCR4 tropic HIV-1 through the mucosal route in an individual with a wild-type CCR5 genotype

BackgroundNearly all transmitted/founder (T/F) HIV-1 are CCR5 (R5)-tropic. While previous evidence suggested that CXCR4 (X4)-tropic HIV-1 are transmissible, virus detection and characterization were not at the earliest stages of acute infection. MethodsWe identified an X4-tropic T/F HIV-1 in a participant (40700) in the RV217 acute infection cohort. Coreceptor usage was determined in TZM-bl cell line, NP-2 cell lines, and primary CD4+ T cells using pseudovirus and infectious molecular clones. CD4 subset dynamics were analyzed using flow cytometry. Viral load in each CD4 subset was quantified using cell-associated HIV RNA assay and total and integrated HIV DNA assay. FindingsParticipant 40700 was infected by an X4 tropic HIV-1 without CCR5 using ability. This participant experienced significantly faster CD4 depletion compared to R5 virus infected individuals in the same cohort. Naïve and central memory (CM) CD4 subsets declined faster than effector memory (EM) and transitional memory (TM) subsets. All CD4 subsets, including the naïve, were productively infected. Increased CD4+ T cell activation was observed over time. This X4-tropic T/F virus is resistant to broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 regions, while most of the R5 T/F viruses in the same cohort are sensitive to the same panel of bNAbs. InterpretationsX4-tropic HIV-1 is transmissible through mucosal route in people with wild-type CCR5 genotype. The CD4 subset tropism of HIV-1 may be an important determinant for transmissibility and virulence. FundingInstitute of Human Virology, National Institutes of Health, Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.

Lipidomics and Metabolomics in Infant Atopic Dermatitis: What's the Correlation with Early Nutrition?

To date, the complex picture of atopic dermatitis (AD) has not yet been fully clarified, despite the important prevalence of this disease in the pediatric population (20%) and the possibility of persistence into adulthood, with important implications for the quality of life of those affected, as well as significant social and financial costs. The most recent scientific evidence suggests a new interpretation of AD, highlighting the important role of the environment, particularly that of nutrition in the early stages of development. In fact, the new indications seem to point out the harmful effect of elimination diets, except in rare cases, the uselessness of chrono-insertions during complementary feeding and some benefits, albeit weak, of breastfeeding in those at greater risk. In this context, metabolomics and lipidomics can be necessary for a more in-depth knowledge of the complex metabolic network underlying this pathology. In fact, an alteration of the metabolic contents in children with AD has been highlighted, especially in correlation to the intestinal microbiota. While preliminary lipidomic studies showed the usefulness of a more in-depth knowledge of the alterations of the skin barrier to improve the development of baby skin care products. Therefore, investigating the response of different allergic phenotypes could be useful for better patient management and understanding, thus providing an early intervention on dysbiosis necessary to regulate the immune response from the earliest stages of development.

The Drosophila adult midgut progenitor cells arise from asymmetric divisions of neuroblast-like cells.

The Drosophila adult midgut progenitor cells (AMPs) give rise to all cells in the adult midgut epithelium, including the intestinal stem cells (ISCs). While they share many characteristics with the ISCs, it remains unclear how they are generated in the early embryo. Here, we show that they arise from a population of endoderm cells, which exhibit multiple similarities with Drosophila neuroblasts. These cells, which we have termed endoblasts, are patterned by homothorax (Hth) and undergo asymmetric divisions using the same molecular machinery as neuroblasts. We also show that the conservation of this molecular machinery extends to the generation of the enteroendocrine lineages. Parallels have previously been drawn between the pupal ISCs and larval neuroblasts. Our results suggest that these commonalities exist from the earliest stages of specification of progenitor cells of the intestinal and nervous systems and may represent an ancestral pathway for multipotent progenitor cell specification.

Clustering classifier of FRP strengthened concrete beams using superpixels and principal component analysis

Nowadays, the application of Fiber Reinforced Polymer (FRP) materials in concrete structures is more and more extended because of their advantages. However, premature and brittle failure caused by debonding of FRP materials from the concrete surface may be critical and needs to be detected at its earliest stages to avoid possible catastrophic events. Digital image correlation (DIC) has been used in the past for the detection of abnormalities from surface digital images. In this work, an efficient computer-aided diagnosis (CAD) system for damage identification for this type of FRP strengthening is developed. It is based on the combination of cells of strain maps built with a DIC system and an automated clustering classifier optimized with the use of superpixels and principal component analysis. Additionally, preprocessing of the images is also done with some filters to enhance the accuracy of the methodology. The procedure has been validated with experimental results on a progressively damaged FRP externally strengthened beam. Results show that the proposed detection scheme achieves an effective automated classification method for the damage detection of this kind of strengthened specimens. Furthermore, the optimal choice of the subset size, number of superpixels and principal components contributed to the success of the method. Simultaneously, an attempt to quantify damage from the proposed method and its validation with electromechanical impedance method has been developed.

New impulse-based test method for early-age elastic modulus measurement in cementitious materials

Accurate monitoring of the elastic modulus evolution during the early-age fluid-solid transition in cementitious materials is crucial for understanding their mechanical behavior under early stresses. While existing methods, such as EMM-ARM, have proven effective, they are often associated with high costs or complex setups. This study presents the development of a low-cost, easy-to-implement system that employs impulse excitation applied to a composite beam, introducing the EMM-IRM method for the effective assessment of the elastic modulus of cement paste from the earliest stages of hydration. The use of impulse excitation is particularly advantageous in low-cost systems with accelerometers of lower sensitivity, as it enhances signal clarity and reduces interference from background noise, thereby improving measurement reliability. The system was validated through experimental comparisons with conventional EMM-ARM, cyclic compression, and traditional impulse excitation techniques, using Portland cement paste as the test material. The results show that EMM-IRM consistently estimates the elastic modulus, with a maximum deviation of 6.33% from other methods. Moreover, despite its cost-effectiveness, EMM-IRM demonstrates a higher signal-to-noise ratio compared to conventional EMM-ARM. This approach offers a practical solution for early-age characterization of cementitious materials, balancing cost, simplicity, and measurement accuracy.

Numerical Modelling of Carrier Transport in Organic Field Effect Transistors

Background: Organic field effect transistors (OFETs), used in the fabrication of nanosensors, are one of the most promising devices in organic electronics because of their lightweight, flexibility, and low fabrication cost. However, the optimization of such OFETs is still in an early stage due to the minimal analytical and numerical models presented in the literature. Objective: This research presses to demonstrate a numerical carrier transport model based on the finite element method (FEM) to investigate the I-V characteristic of OFETs. Methods: Two various organic semiconductor materials have been included in the study, polyaniline and pentacene, where micro-scale, as well as nano-scale models have been presented. OFETs regarding channel length, dielectric thickness, and doping level impact have been studied. We nominated the threshold voltage, the on/off current ratio, the sub-threshold swing, and the field effect mobilities as the primary output evaluating parameters. Results: The numerical model has shown the criticality of the doping effect on tuning the device flowing drain current to exceed 300 μA saturation current, along with a threshold voltage of -0.1 V under a channel length of 30 nm. Conclusion: The study highlights the effectiveness of polyaniline over pentacene as nano-channel length OFET due to the boosted conductivity of polyaniline concerning pentacene.

Comparing tooth development timing between ethnic groups, excluding nutritional and environmental influences.

The timing of dental development in ethnic Finns and Somalis, who were born and living in Finland, was compared, with efforts to minimize environmental bias. The developmental status of seven lower left permanent teeth were staged according to Demirjian et al., using panoramic radiographs from 2,100 Finnish and 808 Somali females and males, aged 2 to 23 years. For each tooth, a continuation-ratio model was constructed to analyze the allocated stages as a function of sex and ethnic origin. Several statistically significant differences in mean age of certain tooth developmental stage transitions were revealed. While Somalis generally displayed stage transitions at younger age, none of the seven teeth consistently showed earlier stage transitions in Somalis compared to Finns. Within each tooth, the lowest (or highest) mean age of stage transition varied without any discernible pattern between the two ethnic groups. Overall, the observed differences in mean age of stage transition between the groups was minimal, suggesting a low impact on clinical and forensic age assessment practice. In conclusion, the studied ethnic Finn and Somali groups with equal nutritional and /or environmental conditions exhibit similar timing in the development of all lower left permanent teeth.

The Role of Neuropeptide Y in the Pathogenesis of Alzheimer’s Disease: Diagnostic Significance and Neuroprotective Functions

Background. Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases. It has been suggested that the factors that cause pathologic changes and lead to the development of AD may also include changes in certain neuropeptides. The implication of the neuropeptide (NPY) in the pathogenesis of AD and its potential therapeutic role is possible due to the following properties: involvement in adult neurogenesis, regulatory effects on the immune system, the inhibition of potential-dependent Ca2+ channels, and the reduction in glutamate excitotoxicity. The aim of our review was to summarize recent data on the role of NPY in AD development and to explore its potential as a biomarker and a possible therapeutic target. Materials and methods. We performed a systematic review of studies, for which we search using the keywords “Alzheimer’s disease and neuropeptide Y”, “Alzheimer’s disease and NPY”, “AD and NPY”, “Neuropeptide Y and Neurodegenerative disease”. Nineteen articles were included in the review. Results. The NPY levels in cerebrospinal fluid and plasma have been found to be reduced or unchanged in AD patients; however, these findings need to be confirmed in more recent studies. Data obtained in transgenic animal models support the role of NPY in AD pathogenesis. The neuroprotective effects of NPY have been demonstrated in vitro and in vivo in AD models. Conclusion. The findings may open new possibilities for using NPY as a diagnostic marker to detect AD at earlier stages of the disease or as a potential therapeutic target due to its neuroprotective properties.

Characteristics and Challenges of AI Education in the Liberal Arts Curriculum of Domestic Universities : With Emphasis on the Linkage between the Primary and Secondary Education Curriculum and the Liberal Arts Curriculum of University in the Digital Trans

This paper aims to explore the characteristics and challenges of Artificial Intelligence (AI) education in the liberal arts curriculum of domestic universities. The revision of the curriculum to strengthen digital literacy has been in the field of the liberal arts in major universities. However, universities haven’t been aligning their curriculum with the core competencies developed in earlier stages. This has resulted in a disconnect occurring between AI education at the primary/secondary level and the university level. This gap can lead to students struggling to advance in AI-related topics as they transition to higher education. The liberal arts education of universities does not consider or reflect any linkage with the coherent system of the national curriculum, such as the 2022 revised national curriculum, of primary and secondary schools, which prevents the progress of students’ learning agency. For example, universities should take steps to open and run AI-related courses, regardless of government-supported projects, such as software (SW)-centered university projects. In fact, these project-based courses have not successfully addressed the need for a comprehensive AI and digital literacy education within the liberal arts. This paper, therefore, makes the following suggestions. Firstly, the liberal arts curriculum for AI education should restore its essence of humanity, preparing students to critically assess both the benefits and risks of AI in experiencing the digital transition. Secondly, universities should open and support AI-related courses in the liberal arts, ensuring that lecturers and professors receive the necessary resources to teach comprehensive AI education effectively.

Analysis Of The Result Of DNA (Deoxyribonucleic Acid) Electrophoresis On Vaginal Mucosal Swabs With Cervical Cancer Patients

Background: Cervical cancer is one of the second-highest sexually transmitted diseases in the world, accounting for 13% of the total 22% of deaths caused by non-communicable diseases. Today there have been many developments about cervical cancer diagnosis methods especially in early detection aimed at recognizing cervical cancer at an earlier stage, including molecular biology detection using PCR tools and electrophoresis. Objective: To identify the results of DNA electrophoresis in vaginal mucosal swabs with cervical cancer. Method : The research method used is experimental. Results: Based on the results of a study using a documentary gel, 2 samples of HPV DNA tape were detected, it was tested positive because there was 450 bp DNA tape and 4 samples of negative results were obtained. Conclusion: The frequency distribution of respondents from 6 samples by using electrophoresis and focumerary gel as readers detected 2 positive samples. A positive result is expressed if a result in the documentary gel is found to be a DNA band. The size of the DNA ribbon produced with the DNA marker markers is at 450 bp, according to the sample target. This shows that the DNA bands in the sample are about 450 bp in size.

Narratives of growth of formative technological innovation systems based on a knowledge perspective: the case of medical devices

Purpose This study aims to analyze the narratives of growth during the initial stages of development of the medical device technological innovation system (TIS). This paper used micro/nanofluidic-based point-of-care testing (mnPOCT), a breakthrough technology in the health-care sector. Design/methodology/approach This study presents a framework that includes measures of knowledge breadth and sharing mechanisms based on cognitive and actor-based networks. The framework integrates bibliometric, network and statistics-based approaches with a focus on the first decade of mnPOCT development. Findings In addition to the typical patterns of technological emergence, the mnPOCT sector exhibits distinctive characteristics. This paper observed significant scientific content and a high geographic concentration. Although small- and medium-sized enterprises, particularly startups, detonate knowledge development, large companies play a subtle yet impactful role as innovation mediators. Interfirm alliances are sparse, reflecting the complementarities between startups and large firms throughout the innovation value chain. These alliances show a significant correlation with SME knowledge creation. Research limitations/implications This study provides researchers and practitioners with guidelines for assessing the dynamics of the growth of technologies in the earliest stages of growth through knowledge and implications for research strategy toward the development and deployment of effective system interventions. Originality/value The study of formative TISs presents challenges because of the nascent characteristics and uncertainties surrounding emerging technologies. Current discussions on the narratives of growth of emerging TISs are limited to broad descriptions, which hinder understanding of these formative stages. This study offers a unique approach to assessing the initial stages of technological evolution. Moreover, it contributes to the existing literature by providing guidelines for managing new technologies for R&amp;D researchers and practitioners.

Chimeric Antigen Receptor T Cells for the Treatment of Multiple Myeloma.

Multiple myeloma (MM), characterized by abnormal proliferation of clonal plasma cells, is an incurable hematological malignancy. Various immunotherapy strategies have emerged as an efficacious approach for the treatment of MM, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T (CAR-T) cells. Anti-B-cell maturation antigen (BCMA) CAR-T cells have revolutionized the treatment of MM patients with relapsed/refractory disease and their clinical use was approved for the treatment of these patients. Despite this progress, the efficacy of CAR-T cells in MM is limited by the responsiveness of only a part of the treated patients, the relapse of other patients, the cost of the treatment and the diminished response in patients with prior exposure to anti-BCMA targeting agents. Ongoing clinical trials are evaluating the use of CAR-T cells at an earlier stage of MM disease and the use of CAR-T cells targeting other membrane antigens expressed on malignant plasma cells.

Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy.

Myocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown. We aimed at establishing a relevant role of cardiac inflammation in the impairment of mitochondrial energy production in advanced ischaemic and non-ischaemic HF. We included 81 patients with stage D HF (ICM, n=44; DCM, n=37) undergoing left ventricular assist device implantation (n=59) or heart transplantation (n=22) and obtained left ventricular tissue samples during open heart surgery. We quantified mitochondrial oxidative capacity, citrate synthase activity (CSA) and fibrosis and lymphocytic infiltration. We considered infiltration of >14 CD3+ cells/mm2 relevant inflammation. Patients with ICM or DCM did not differ regarding age (61.5±5.7 vs. 56.5±12.7years, P=0.164), sex (86% vs. 84% male, P=0.725), type 2 diabetes mellitus (34% vs. 18%, P=0.126) or chronic kidney disease (8% vs. 11%, P=0.994). ICM exhibited oxidative capacity reduced by 23% compared to DCM (108.6±41.4 vs. 141.9±59.9pmol/(s*mg), P=0.006). Maximum production of reactive oxygen species was not significantly different between ICM and DCM (0.59±0.28 vs. 0.69±0.36pmol/(s*ml), P=0.196). Mitochondrial content, detected by CSA, was lower in ICM (359.6±164.1 vs. 503.0±198.5nmol/min/mg protein, P=0.002). Notably, relevant inflammation was more common in ICM (27% vs. 6%, P=0.024), and the absolute number of infiltrating leucocytes correlated with lower oxidative capacity (r=-0.296, P=0.019). Fibrosis was more prevalent in ICM (20.9±21.2 vs. 7.2±5.6% of area, P=0.002), but not associated with oxidative capacity (r=-0.13, P=0.327). More than every fourth ICM patient with advanced HF displays myocardial inflammation in the range of inflammatory cardiomyopathy associated with reduced mitochondrial oxidative capacity. Future studies may evaluate inflammation in ICM at earlier stages in standardised fashion to explore the therapeutic potential of immunosuppression to influence trajectories of HF in ICM.

The causal relationship of DTI phenotypes and epilepsy: A two sample mendelian randomization study.

Clinical studies indicated a link between DTI imaging characteristics and epilepsy, but the causality of this connection had not been established. Therefore, we employed the Mendelian randomization analysis method to determine the causal relationship between DTI imaging characteristics and epilepsy. We used Mendelian randomization analysis to identify the causal relationship between brain structure and the risk of epilepsy. GWAS data of DTI phenotypes, focal epilepsy, and genetic generalized epilepsy (GGE) were utilized in the analysis. Our study found that DTI imaging phenotypes had a causal risk relationship with epilepsy. These phenotypes had a statistical impact on the risk of epilepsy seizures. There were differences in DTI phenotype causality between GGE and focal epilepsy, which were associated with the clinical phenotype differences of the two types of epilepsy. Our study demonstrated that the diagnosis of subtypes could be assisted by comparing the differences in DTI phenotypes of specific brain regions. This meant that by studying the changes in brain regions before the onset of epilepsy, we might be able to intervene in epilepsy at an earlier stage. Our study used Mendelian randomization to explore the causal relationship between brain structure, as seen in DTI imaging, and epilepsy. We found that specific DTI phenotypes are linked to an increased risk of epilepsy seizures, with notable differences between genetic generalized epilepsy and focal epilepsy. This suggested that analyzing DTI phenotypes could help in diagnosing and potentially intervening in epilepsy earlier by finding brain changes before seizures begin.

Polyclonal-to-monoclonal transition in colorectal precancerous evolution.

Unravelling the origin and evolution of precancerous lesions is crucial for effectively preventing malignant transformation, yet our current knowledge remains limited1-3. Here we used a base editor-enabled DNA barcoding system4 to comprehensively map single-cell phylogenies in mouse models of intestinal tumorigenesis induced by inflammation or loss of the Apc gene. Through quantitative analysis of high-resolution phylogenies including 260,922 single cells from normal, inflamed and neoplastic intestinal tissues, we identified tens of independent celllineages undergoing parallel clonal expansions within each lesion. We also found polyclonal origins of human sporadic colorectal polyps through bulk whole-exome sequencing and single-gland whole-genome sequencing. Genomic and clinical data support a model of polyclonal-to-monoclonal transition, with monoclonal lesions representing a more advanced stage. Single-cell RNA sequencing revealed extensive intercellular interactions in early polyclonal lesions, but there was significant loss of interactions during monoclonal transition. Therefore, our data suggest that colorectal precancer is often founded by many different lineages and highlight their cooperative interactions in the earliest stages of cancer formation. These findings provide insights into opportunities for earlier intervention in colorectal cancer.

Prevalence and Clinical Significance of Skin Manifestations in Parkinson Disease Patients

Background: Parkinson's disease (PD) is primarily characterized by motor symptoms, but non-motor symptoms, including skin manifestations, are increasingly recognized. These remain underexplored despite their potential impact on quality of life. Objectives: This study aimed to evaluate the prevalence and clinical features of skin findings in PD patients, with a focus on identifying potential pathogenetic links between dermatological conditions and PD. Methods: A total of 215 PD patients were included. Comprehensive dermatological examinations were performed, and demographic and clinical data were collected. Statistical analysis was conducted using SPSS 23.0, with significance set at P &lt; 0.05. Results: Skin conditions were found in 92.1% of PD patients. Xerosis, seborrheic dermatitis, and hyperhidrosis were the most common findings. Pre-PD xerosis was associated with an earlier stage of PD (P = 0.001). Use of PD medications, such as levodopa/carbidopa/entacapone, was linked to a lower incidence of seborrheic dermatitis (P = 0.040). A significant correlation was also noted between rosacea and cherry angioma (P = 0.01). Conclusion: Dermatological conditions are prevalent in PD and may precede its motor symptoms. Skin assessments could aid early diagnosis and management of PD, highlighting the need for further research on their pathogenetic mechanisms.