Early Stage Research Articles

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.

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.

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.

Patient journey from the appearance of red flags to the diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) in Japan: a nationwide retrospective study using a medical claims database

Abstract Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of common cardiovascular conditions in the elderly, with relatively high rates among patients diagnosed with heart failure (HF) with preserved ejection fraction. In addition to cardiac symptoms such as HF, extracardiac symptoms such as carpal tunnel syndrome (CTS) and lumbar spinal stenosis (LSS) are also red flags for ATTR-CM. Tafamidis is currently the only disease-modifying therapy approved for the treatment of patients with ATTR-CM and is likely to be more effective in the earlier stage. Patients with ATTR-CM often undergo a long and difficult diagnostic journey because of the nonspecificity of clinical manifestations, resulting in delays in establishing the correct diagnosis. Purpose To identify the timing of appearance of comorbidities in patients with ATTR-CM during diagnosis. Methods In this retrospective, non-interventional, observational study using a claims database (dataset period: April 1, 2014–August 31, 2021), adult patients with a diagnosis of ATTR-CM or prescription for tafamidis 80 mg were included. The index date was defined as the first date of recording ATTR-CM diagnosis or the prescription of tafamidis 80 mg, whichever was earlier. The baseline period was defined as the period between the index date and 6 months before the index date. The onset date was defined as the first date of recording diagnosis of the first red-flags that was suspicious for ATTR-CM. Results Of 11,101,578 patients in the database, 246 patients with ATTR-CM met the inclusion criteria. A total of 239 patients were included, of whom 139 had received tafamidis 80 mg. The median (range) age at the index date was 79.0 (46.0–95.0) years, and 79.9% (191/239) were male. The most frequently reported comorbidity defined as onset of ATTR-CM was conduction disorders (88.7%) followed by atrial fibrillation/atrial flutter (50.6%), hypertensive heart disease (19.7%), aortic stenosis (15.9%), and hypertrophic cardiomyopathy (11.7%), with the median (interquartile range [IQR]) time to the index date being 15.5 (5.0–24.5), 14.0 (5.0–22.0), 9.0 (2.0–18.0), 5.0 (2.0–16.0), and 12.0 (6.5–21.5) months, respectively (Fig. 1). LSS (23.9%), neuropathy (13.0%), and CTS (7.5%) were frequently observed as extracardiac symptoms at baseline, and the median (IQR) time from appearance to the index date was 19 (9.0–28.0), 5.0 (1.0–16.0), and 18.0 (14.0–25.0) months, respectively (Fig. 2). Conclusions This study elucidated the time lag between the appearance of cardiac and extracardiac complications of ATTR-CM and its diagnosis in real-world clinical settings. These novel findings highlight the potential for earlier detection of ATTR-CM.

Ensuring sustainable impact of the national report on climate change and health in Germany 2023

Abstract Issue/problem The Robert Koch Institute recently coordinated a status report on climate change and health for Germany, detailing the current and future impact of climate change on health through 14 chapters. Description of the problem A central aim was to ensure the report’s long-term impact and public health value. Essential areas of focus have therefore been stakeholder-specific communication and establishing a network of experts for continued scientific exchange. Results The publication of the report as peer-reviewed articles has served to reach the scientific community. Another target group are public health practitioners and decision makers at subnational levels, who can contribute towards climate change mitigation and adaptation measures relevant to health, as recommended in the report. This latter group was reached through various methods and formats of science communication, including conferences aimed at the public health sector, through target-group oriented podcasts, social media engagement and digital town hall discussions. Following publication, the experts involved in writing, reviewing and using the report were invited to establish a network in order to support long-term scientific exchange and collaborations and in turn ensure the report’s sustainable impact and value. Lessons Through follow-up evaluations, the reception of the report and the further communication needs of this target group were analysed. A major lesson was to include the insights of public health practitioners more systematically and at an earlier stage in any future reports. As for the establishment of a network, a survey amongst the authors and other experts showed what this group considers the goals of this network: creating synergies and connections with existing initiatives and providing a platform for further exchange, especially amongst researchers addressing similar questions, such as the efficacy of mitigation and adaptation measures, from different angles. Key messages • Local public health practitioners are important stakeholders for climate change and health for ensuring public health impact. • The expertise in the network will support continued scientific exchange on climate change and health and thus ensure the national report’s sustainability.

Low density lipoprotein cholesterol and cardiovascular disease risk in patients with absence of coronary artery calcification: a multicenter cohort study

Abstract Background Low-density lipoprotein cholesterol (LDL-C) plays a central role in the development of coronary heart disease (CHD). Absence of coronary artery calcification (CAC 0), as assessed by coronary computed tomography angiography (CCTA), is associated with a favorable outcome as it indicates a low burden of atherosclerosis. However, questions remain regarding the risk of non-calcified plaque and CHD in younger patients with CAC zero, as atherosclerosis tends to be non-calcified in earlier stages. Purpose To assess if LDL-C is associated with presence of non-calcified plaque and future cardiovascular events in patients with CAC zero across the age spectrum. Methods This observational multicenter cohort study included patients aged 18 years or more who underwent CCTA between January 2008 and May 2021 with CAC zero. LDL-C was measured prior to CCTA. Patients were followed from date of CCTA to occurrence of cardiovascular event, death, or 1st of October 2022. No patients were lost to follow-up. We assessed the association between LDL-C and presence of non-calcified plaque on CCTA as adjusted odds ratios, and risk for myocardial infarction and CHD (myocardial infarction or coronary revascularization) as adjusted hazard ratios using Cox regression analyses, across different age groups. Results A total of 23,776 patients with CAC zero were included in the study. Median age was 54 years (IQR 47-61) and 14,605 (61%) were women. During median follow-up of 5.5 years, 165 (0.7%) and 427 (1.8%) experienced myocardial infarction and CHD, respectively. Overall, the prevalence of non-calcified plaque was 11.1% (n=2,650). Higher LDL-C was associated with presence of non-calcified plaque with an odds ratio of 1.21 (95% CI 1.16-1.27) per 1 mmol/L higher LDL-C. Individuals aged ≤45 years had a higher odds ratio for non-calcified plaque per 1 mmol/L higher LDL-C compared to individuals aged 46-60 and >60 years; 1.36 (95% CI 1.22-1.52), 1.22 (95% CI 1.15-1.30) and 1.13 (95% CI 1.04-1.22), respectively, p value for interaction between the youngest and oldest age group was <0.05. Overall, LDL-C was associated with higher risk for myocardial infarction and CHD with hazard ratios of 1.29 (95% CI 1.10-1.52) and 1.26 (95% CI 1.14-1.39) per 1 mmol/L higher LDL-C, despite CAC zero. Conclusions Particularly in younger patients with absence of CAC, elevated LDL-C is associated with presence of non-calcified plaque and increased risk for future cardiovascular events. These data are important for clinical practice, as they demonstrate the importance of managing LDL-C in younger individuals over the long-time horizon despite CAC zero.

ADGRU: Adaptive DenseNet with gated recurrent unit for automatic diagnosis of periodontal bone loss and stage periodontitis with tooth segmentation mechanism.

Periodontics and gingivitis are two of the most widely prevalent illnesses that affect people nowadays. The sixth most common disease in the world is periodontitis, and detecting periodontal bone loss is essential in the earlier condition and is crucial for the development of the proper diagnosis. Early bone loss detection can be assisted by using computer-assisted radiography examination. Understanding disease progression helps to select the most effective treatment action. An effective deep model is suggested to detect periodontal bone loss at an earlier stage for preventing the progression of Periodontics bone loss. This work is intimated by collecting images from online resources. Further, the images gathered from the dataset are preceded by the tooth segmentation which is done using DenseUNet + + . Further, the segmented images are given to the Adaptive DenseNet with Gated Recurrent Unit (AD-GRU) for detecting periodontal bone loss and this diagnosis is used for the periodontitis stage, where the ADGRU performance is augmented by optimizing the attributes using the Refined Red Kite Optimization Algorithm (RRKOA). The offered approach attained an accuracy of 94.45% which is higher than the88.63%, 90.58%, 89.54%, and 92.96% attained by the LSTM, DenseNet, GRU, DenseNet-GRU. The findings of the simulation proved the designed framework outperformed the traditional model with high accuracy. The developed effectual deep model-based periodontal bone loss and stage periodontitis diagnosis structure is used in healthcare applications.

Effect of the COVID-19 pandemic on the well-being of middle-aged and older Europeans

The COVID-19 pandemic has been associated with a general decline in well-being. However, there is limited evidence on the effect of the pandemic on the general population, and especially among the ageing population. We assessed the overall impact of the pandemic on the well-being of middle-aged and older adults residing in 27 European countries, focusing on the time-period before summer 2021. We used a sample of 46,209 respondents from the two population-based longitudinal Corona Surveys collected during summer 2020 and summer 2021. To test our hypotheses, we used latent change score models. All analyses were stratified by sex. The COVID-19 pandemic affected middle-aged and older Europeans’ well-being irrespective of their sex. Being infected by the COVID-19 virus at the start of the pandemic had a negative impact on well-being. As expected, adults with Long COVID experienced the most pronounced decline in well-being. A novel finding was the decline in the level of well-being among adults not infected by the COVID-19 virus. Support should be provided at community levels with specific attention towards individuals with Long COVID symptoms and those infected with COVID-19 at earlier stages of the pandemic.

Strengthening ecosystems

Abstract The mission of THCS activities with respect to strengthening ecosystems is based on the understanding that the actual transformation of health and care systems is dependent on the ability of numerous actors to align their goals and actions so that they are complementary. At the same time, it is also true that the transformation takes place at national, regional and local levels, making activities and support at these levels essential for the success of THCS. Therefore, the focus lies on connecting and supporting the broad community and other stakeholders in developing ecosystem-wide approaches and creating awareness and urgency among ecosystem layers and components, thus serving as a platform for transformation. One strand of activities for strengthening ecosystems aims at identifying, analysing, describing and disseminating key learnings from successful transformative ecosystems (TE’s). TE’s are broad constellations of interacting organisations and people who are committed, and through aligned actions, able to reach joint, explicitly defined goals in long-term. Making not only the most successful TE’s but also the dynamics explaining their achievements visible, value is being added through three main routes. Firstly, the experiences are distributed widely on European arenas and platforms as well as through national, regional and local channels to inspire ecosystem building processes in earlier stages of maturity. Secondly, collaboration between identified forerunner ecosystems is supported to enable mutual peer-learning. Thirdly, the examples are used to give guidance and inspiration to consortia that are applying for or receiving THCS project funding. As strategic partners of the ecosystem strengthening activities, other work packages of the THCS programme as well as the THCS National Mirror Groups are of great importance.

Future of Uremic Toxin Management

During the progression of chronic kidney disease (CKD), the retention of uremic toxins plays a key role in the development of uremic syndrome. Knowledge about the nature and biological impact of uremic toxins has grown exponentially over the past decades. However, the science on reducing the concentration and effects of uremic toxins has not advanced in parallel. Additionally, the focus has remained for too long on dialysis strategies, which only benefit the small fraction of people with CKD who suffer from advanced kidney disease, whereas uremic toxicity effects are only partially prevented. This article reviews recent research on alternative methods to counteract uremic toxicity, emphasizing options that are also beneficial in the earlier stages of CKD, with a focus on both established methods and approaches which are still under investigation or at the experimental stage. We will consequently discuss the preservation of kidney function, the prevention of cardiovascular damage, gastro-intestinal interventions, including diet and biotics, and pharmacologic interventions. In the final part, we also review alternative options for extracorporeal uremic toxin removal. The future will reveal which of these options are valid for further development and evidence-based assessment, hopefully leading to a more sustainable treatment model for CKD than the current one.

Inter-brain synchrony is associated with greater shared identity within naturalistic conversational pairs.

Inter-brain synchrony occurs between individuals who feel connected socially, but how synchrony relates to felt connectedness under naturalistic social interaction has remained enigmatic. We hypothesized that inter-brain synchrony between naturally interacting individuals might be associated with the internalization of a social identity, a link between an individual's personal identity and the social group to which the individual belongs. A convenience sample of sixty participants were split into dyads and interacted naturalistically on a social task. Through mapping EEG oscillatory waveforms onto a conceptual model categorizing the formation of a social identity within a naturalistic conversation, greater inter-brain synchrony was observed in the emergent stage within the formation of a social identity compared to earlier stages, where a social identity was not present. We provide evidence for greater neural synchrony related to higher socio-psychological connectedness during the development of social identity under naturalistic social interaction.

The Pattern of Gene Expression (Igf Family, Muscle Growth Regulatory Factors, and Osteogenesis-Related Genes) Involved in the Growth of Skeletal Muscle in Pikeperch (Sander lucioperca) During Ontogenesis

The pikeperch (Sander lucioperca) is an economically important freshwater fish and a valuable food with high market acceptance. It is undergoing important changes in growth and regulatory metabolism during the ontogeny. Hence, the current study aims to investigate the mRNA expression of the growth hormone (gh)/insulin-like growth factor (igf) axis (ghr, igfI, igfbp, igfr), muscle regulatory factors (pax7, myf5, myod, myogenin, mrf, mymk, mstn), and osteogenesis-related genes (colla1a, fib1a, on, op, ostn) from hatching through day 40th post-hatching (DPH). The average total length (TL) of larvae measured at hatching was 3.6 ± 0.4 mm (67 degree days), and at the end of the experiment (40 DPH, 777 degree days), it was 27.1 ± 1.1 mm. The results showed three phases of gene expression in day 0 (egg), larval, and juvenile stages of pikeperch, which can be a progression or transition from the initial state toward the juvenile state. The expression pattern of myf5, mymk, and fib1a genes showed the highest value at day 0. The growth hormone receptor gene (ghr) and igfbp5 were raised to 1 DPH, whereas increased expression of igfI, igfII, igf1bp4, igf1rb, myod2, and mrf4 was detected at 14 DPH. The myod1, pax7, op, ostc, on, igf1ra, and col1a1a genes were highly expressed at 21 DPH and juvenile stages. According to the PLS-DA model, the most relevant VIPs are myf5 and mymk as best markers of earlier stages and igf1ra, ostc, pax7, and ghr as markers of later stages of ontogeny. Results from this study suggest that basal metabolism, growth of body cells and muscles, and bone proliferation and development can be regulated by the dynamic changes in gene expression patterns in this species. The identified genes will help to understand the basic biological process of pikeperch larvae and development, which is very important in pikeperch farming

Changes in Clinical Competence of Novice Physical Therapists During Their First Year of Employment: A Single Center Retrospective Observational Study in Japan

Background and Objectives: This study aimed to examine the development of clinical competence of novice physical therapists (PTs) during their first year of employment, following the implementation of an original in-house educational program. The educational program was designed to offer diverse training opportunities at an early stage, during the first year of employment. Methods: Thirty-eight novice PTs (21 males and 17 females, mean age 23.4 ± 3.2 years) participated in this study. All participants underwent educational programs and a self-assessment using the Clinical Competence Evaluation Scale in Physical Therapy (CEPT) on the first day of employment (entry-level) and after 1, 3, 6, and 12 months of employment. The total score and CEPT component-wise scores—“knowledge,” “clinical reasoning,” “skill,” “communication,” “attitude,” “self-education,” and “self-management”—at the 4 assessment points (1, 3, 6, and 12 months) were compared with values on the first day. Results: The total scores at 3, 6, and 12 months of employment were significantly higher than those on the first day of employment (P < .05). Among the total scores on the 7 components, those for “knowledge,” “clinical reasoning,” “skill,” and “communication” at 3, 6, and 12 months after employment were also significantly higher than those on the first day of employment (P < .05). The scores for “attitude” and “self-education” 12 months after employment were significantly higher than those on the first day of employment. However, the “self-management” scores at 1, 3, 6, and 12 months after employment did not significantly change compared with those on the first day of employment. Conclusions: The total score was significantly higher after 3 months. The participant’s clinical competence may have improved because they participated in an educational program related to “knowledge,” “clinical reasoning,” “skills,” and “communication” at an earlier stage in the first year. However, their progress was comparatively slower in other areas, suggesting that the content might not have been sufficient. This study revealed the effectiveness of the educational program on novice PTs’ clinical competence at a single institution in Japan. Positive outcomes were obtained for several parameters. Furthermore, the results reveal the need for content modifications within the educational program to improve PTs’ performance across all evaluated items.

Fatigue life prediction of composite materials using strain distribution images and a deep convolution neural network

The damage process of composite materials, such as short fiber-reinforced plastics (SFRP), is complex. Therefore, it is necessary to accurately represent the damage process in fatigue life prediction. Herein, fatigue life prediction was conducted by combining the digital image correlation method, which is a non-destructive testing technique, with a convolutional neural network (CNN), using Xception as the network architecture. High prediction accuracy was obtained when training and testing were performed on the same SFRP specimens. In contrast, using different specimens for training and testing resulted in lower accuracy. This issue may be improved by increasing the number of specimens. The regions of interest in the model were visualized by Gradient-weighted Class Activation Mapping. Notably, the model indicated the breaking point as the region of interest from the early stages of the test. The breaking point was identified at an earlier stage by the CNN than by visual inspection, demonstrating the potential for a new method of damage observation.

Syntax and the brain: language evolution as the missing link(ing theory)?

IntroductionThis paper provides proof of concept that neurolinguistic research on human language syntax would benefit greatly by expanding its scope to include evolutionary considerations, as well as non-propositional functions of language, including naming/nicknaming and verbal aggression. In particular, an evolutionary approach can help circumvent the so-called granularity problem in studying the processing of syntax in the brain, that is, the apparent mismatch between the abstract postulates of syntax (e.g. Tense Phrase (TP), Determiner Phrase (DP), etc.) and the concrete units of neurobiology (neurons, axons, etc.).MethodsFirst, we decompose syntax into its evolutionary primitives, identifying one of the earliest stages as a simple, flat combination of just one verb and one noun. Next, we identify proxies (“living fossils”) of such a stage in present-day languages, including compounds and small clauses, lacking at least some layers of structure, e.g. TPs and DPs. These proxies of ancestral language have been subjected to fMRI neuroimaging experiments.ResultsWe discuss the finding that less hierarchical small clauses, in contrast to full sentences with TPs and DPs, show reduced activation in the left Broca’s area (BA) 44 and the right basal ganglia, consistent with the hypothesis that more recent, more elaborate syntax requires more connectivity in the Broca’s-basal ganglia network, whose neuronal density has been significantly enhanced in recent evolution, implicating mutations in FOXP2 and other genes. We also discuss the finding that the processing of ancestral verb-noun compounds, which are typically used for (derogatory) naming and nicknaming, shows enhanced activation in the right fusiform gyrus area (BA 37), the area that is implicated in the processing of metaphoricity and imageability, but also in naming and face recognition, opening up an intriguing possibility that the enhanced face recognition in humans was facilitated by the early emergence of a simple syntactic strategy for naming.DiscussionThe considerations in this paper are consistent with the hypothesis of a gradual gene-culture co-evolution of syntax and the brain, targeting cortico-striatal brain networks. It is also of note that a sound grounding in neurobiology of language should in turn inform syntactic theories themselves.

Identification of Potential Predictive Transcript Isoform-Biomarkers for the Early Diagnosis of Breast Cancer Using Bioinformatics Tools

Background: Several studies have demonstrated that the expression status of isoforms is more informative as a biomarker than overall gene expression. This study aimed to determine highly but significantly expressed transcript isoforms and evaluate their prognostic and diagnostic impact in breast invasive carcinoma (BRCA) stage I patients. Methods: The differentially expressed genes and their transcript isoforms in BRCA stage I were determined using the Cancer Differentially Expressed Isoform and gene (Cancer DEIso) platform based on The Cancer Genome Atlas (TCGA) data. The prognostic and diagnostic impact of significantly upregulated top 10 genes and their transcripts were revealed using the Cancer DEIso tool, the Kaplan-Meier (KM) method, and the Receiver Operating Characteristic Curve (ROC) approach, respectively. Isoform-level protein-protein interactions (PPI) were constructed using the Domain Interaction Graph Guided ExploreR (DIGGER) database. ConsensusPathDB was used to perform pathway enrichment analysis based on the constructed interactions. Results: This study revealed that NM_024037, NM_001143782, and NM_021619 transcript isoforms have significant diagnostic ability with AUC values 93.2%, 77.1% and 75.3%, respectively to distinguish stage I BRCA patients from normal. KM-plot analysis showed that these three isoforms have no prognostic significance in stage I patients, but their upregulation was correlated with decreased survival in BRCA patients regardless of stage. Isoform-based pathway enrichment analyses indicated that these three isoforms involved in chromatin organization, senescense, DNA damage and several signalling pathways which promotes cancer when there is misregulation. . Conclusion: NM_024037, NM_001143782, and NM_021619 transcript isoforms are potential biomarkers for detecting early-stage BRCA. Thus, it is essential to find out how these three isoforms contribute to the development of breast carcinogenesis and evolve a new approach for capturing breast tumors at an earlier stage of the clinical landscape.

Impacts of black soldier fly, Hermetia illucens, larval frass on the emergence and seedling vigor of three vegetable crop species

Abstract The waste material from rearing black soldier fly, Hermetia illucens (L.), (Diptera: Stratiomyidae), larvae (BSFL), frass, could serve as a partial replacement for fertilizer or growing media, such as peat. Studies have shown that depending on the crop life cycle, long or short, the incorporation of frass can have positive impacts on vegetable growth. Investigating the earlier stages of growth, such as emergence, can provide more information on the acute impacts of insect frass on plant production. Two greenhouse studies were designed to investigate the use of frass in vegetable production at the seedling stage: BSFL frass as a partial replacement for peat in a growth germination medium and BSFL frass as a fertility replacement in a growth germination medium. Tomato, lettuce, and arugula seeds were grown in a standard control growing media, a growing media amended with frass to partially replace peat, and a growing media with frass applications to substitute the fertility source. In all treatments and varieties, the control growing media produced better or comparable results to the treatments. As a peat replacement, the two tomato varieties, lettuce, and arugula seedlings grown in frass had comparable seedling vigour and days to emergence to those grown in the control. As a fertility replacement, seedlings grown in frass had significantly lower percent emergence in all four cultivars when compared to the control. The tomato varieties also had significantly lower seedling vigour in the BSFL fertility treatments than the control. Depending on crop and growing media composition, the impacts of frass on early plant development vary. The adoption of frass into growing practices should include preliminary tests for nutrient composition and microbial contamination.

The oncogenic axis YAP/MYC/EZH2 impairs PTEN tumor suppression activity enhancing lung tumorigenicity

The tumor suppressor PTEN (phosphatase and tensin homolog deleted in chromosome 10) is genetically deleted or downregulated in many cancer types. Loss of PTEN protein expression is frequently found in lung cancer while genetic alterations are less abundant. PTEN expression is regulated at multiple genetic and epigenetic levels and even partial reduction of its expression increases cancer occurrence. We show that YAP and TAZ cooperate with EZH2, and MYC to transcriptionally repress onco-suppressor genes, including PTEN, in non-small cell lung cancer (NSCLC) cells. YAP/TAZ-EZH2-MYC transcriptional regulators form a nuclear complex that represses PTEN transcription, while their combinatorial targeting restores PTEN expression, attenuates NSCLC cell growth, and prevents compensatory responses induced by single treatments. Datasets analysis of NSCLC patients revealed that PTEN expression is negatively correlated to YAP/TAZ, EZH2 and MYC and that low expression of PTEN is predictive of poor prognosis, especially at earlier stages of the disease. These findings highlight the repressive role of the YAP/TAZ-EZH2-MYC axis on tumor-suppressor genes and offer a potential therapeutic strategy for lung cancer patients with low PTEN levels.