Plant reproduction is a very important process on Earth from the perspective of biodiversity, biomass gain and crop productivity. It is therefore important to understand sex determination process and many researchers are investigating the molecular basis of this phenomenon. However, information on the influence of transcription factors (TFs) on this process is limited, although cucumber is a model plant in this regard. In the present study, based on RNA-seq data for differential gene expression (DEG) analyses, we aimed to investigate the regulatory TFs that may influence the metabolomic processes in the shoot apex containing the forming flower buds. Therefore, a robust TF database was established for the B10v3 cucumber genome. Sex-specific interactome network maps were generated, indicating the regulatory TFs by their effects on DEGs and further on processes leading to the formation of different sex flowers. The network analysis identified major families of regulatory TFs. The most abundant families were: MYB, AP2/ERF, NAC and bZIP, and those with the greatest impact on developmental processes were identified, namely the AP/ERF family, followed by DOF, MYB, MADS and others. Thus, the central nodes and key regulators in the networks were identified with respect to male, female and hermaphrodite. Here, we proposed the first model of the regulatory network of TFs that influences the metabolism of sex development in cucumber. These findings may help to understand the molecular genetics and functional mechanisms underlying sex determination processes.

Pregnancy associated plasma protein-A (PAPP-A) plays an integral role in breast cancer (BC), especially triple negative breast cancer (TNBC). This subtype accounts for the most aggressive BC, possesses high tumor heterogeneity, is least responsive to standard treatments and has the poorest clinical outcomes. There is a critical need to address the lack of effective targeted therapeutic options available. PAPP-A is a protein that is highly elevated during pregnancy. Frequently, higher PAPP-A expression is detected in tumors than in healthy tissues. The increase in expression coincides with increased rates of aggressive cancers. In BC, PAPP-A has been demonstrated to play a role in tumor initiation, progression, metastasis including epithelial-mesenchymal transition (EMT), as well as acting as a biomarker for predicting patient outcomes. In this review, we present the role of PAPP-A, with specific focus on TNBC. The structure and function of PAPP-A, belonging to the pappalysin subfamily, and its proteolytic activity are assessed. We highlight the link of BC and PAPP-A with respect to the IGFBP/IGF axis, EMT, the window of susceptibility and the impact of pregnancy. Importantly, the relevance of PAPP-A as a TNBC clinical marker is reviewed and its influence on immune-related pathways are explored. The relationship and mechanisms involving PAPP-A reveal the potential for more treatment options that can lead to successful immunotherapeutic targets and the ability to assist with better predicting clinical outcomes in TNBC.

This research examines the impact of social equity on energy consumption. We constructed a digital twin for residential energy consumption by enriching the synthetic population with real-world surveys and feeding them with other environmental and appliance data to the energy modeling framework. We analyzed household hourly energy consumption data from Albemarle County and Charlottesville City in Virginia, USA, for the year 2019. We used clustering analysis to identify patterns in social equity and energy consumption. The results demonstrated the impact of different residential attributes on energy poverty. Statistical analyses, including ANOVA and Chi-Squared tests, were conducted to test for significant differences between racial groups in quantitative and categorical variables. The study found that race is significant in determining the location and quality of housing. People of color often live in areas with higher pollution and less access to green spaces. Additionally, income levels and the age of the house are influential factors in determining energy efficiency. Future work should focus on collecting and analyzing data at the country level and using qualitative data collection methods to gain a more comprehensive understanding of social equity issues concerning energy consumption. Overall, this study provides valuable insights into the relationship between different residential attributes and energy consumption, which can inform policy development to promote more equitable and sustainable communities.

Circulating tumor DNA (ctDNA), the tumor-derived cell-free DNA fragments in the bloodstream carrying tumor-specific genetic and epigenetic alterations, represents an emerging novel tool for minimal residual disease (MRD) assessment in patients with resected colorectal cancer (CRC). For many decades, precise risk-stratification following curative-intent colorectal surgery has remained an enduring challenge. The current risk stratification strategy relies on clinicopathologic characteristics of the tumors that lacks precision and results in over-and undertreatment in a significant proportion of patients. Consequently, a biomarker that can reliably identify patients harboring MRD would be of critical importance in refining patient selection for adjuvant therapy. Several prospective cohort studies have provided compelling data suggesting that ctDNA could be a robust biomarker for MRD that outperforms all existing clinicopathologic criteria. Numerous clinical trials are currently underway to validate the ctDNA-guided MRD assessment and adjuvant treatment strategies. Once validated, the ctDNA technology will likely transform the adjuvant therapy paradigm of colorectal cancer, supporting ctDNA-guided treatment escalation and de-escalation. The current article presents a comprehensive overview of the published studies supporting the utility of ctDNA for MRD assessment in patients with CRC. We also discuss ongoing ctDNA-guided adjuvant clinical trials that will likely shape future adjuvant therapy strategies for patients with CRC.

Zero-dose children, or children who have not received any routine vaccination, are a priority population for global health policy makers as these children are at high risk of mortality from vaccine-preventable illnesses. We conducted a narrative review to identify potential interventions, both within and outside of the health sector, to reach zero-dose children. We reviewed peer-reviewed and grey literature and identified 59 relevant resources. Additionally, we interviewed six key informants to enhance synthesis of our findings. Data were organized into three priority settings: (1) urban slums, (2) remote or rural communities, and (3) conflict settings. We found that zero-dose children in the three-priority settings face differing barriers to vaccina-tion and, therefore, require context-specific interventions, such as leveraging slum health commit-tees for urban slums or integrating with existing humanitarian response services for conflict set-tings. Three predominant themes emerged for grouping the various interventions: (1) community engagement, (2) health systems strengthening and integration, and (3) technological innovations. The barriers to reaching zero-dose children are multifaceted and nuanced to each setting, there-fore, no one intervention is enough. Technological interventions especially must be coupled with community engagement and health systems strengthening efforts. Evaluations of the suggested interventions are needed to guide scale up, as the evidence-base around these interventions is rel-atively small.

The concept of omics-based technological approaches has promoted translational research by integrating knowledge from diverse areas to understand their dynamics by exploring the molecular mechanisms underlying various processes paving the way for further improvements in the crops quality by providing sound knowledge on controlling plant diseases. This area is not profoundly investigated a decade back and hence this knowledge has become exceedingly important in modern times as it has got potential for being utilized in crop improvement programs. In this review, the contributions of different omics technologies including genomics, transcriptomics, proteomics, and metabolomics in understanding and materializing the ways involved in the plant pathogen interaction (PPI) is discussed. Furthermore, opportunities, challenges, and perspectives of omics linked to signaling mechanisms have also been highlighted that are significantly linked to plant-microbe interactions.

The soil-borne pathogens, particularly Fusarium oxysporum f. sp. niveum (FON) and southern root-knot nematode (RKN, Meloidogyne incognita) are the major threat to watermelon production in the south-eastern United States. The role of soil micronutrients on induced resistance (IR) to plant diseases is well-documented in soil-based mediums. However, soil-based mediums limit the determination of the role(s) of individual micronutrients in IR. In this manuscript, we utilized hydroponics to assess the effect of controlled application of micronutrient, including iron (Fe), manganese (Mn), and zinc (Zn) on the expression of some IR genes (PR1, PR5, and NPR1 from salicylic acid (SA) pathway, and VSP, PDF, and LOX genes from jasmonic acid (JA) pathway) in watermelon seedlings upon inoculation with either FON or RKN or both. Plants were treated with higher (3X) or lower (0.5X) concentrations of micronutrients in Steiner solution (X= standard dose of micronutrient) for 7 days in a hydroponics system under greenhouse conditions. A subset of micronutrient-treated plants was inoculated (on the 8th day of micronutrient application) with FON and RKN (single and mixed). The expression of the IR genes in treated and control samples were evaluated using qRT-PCR. Although, significant phenotypic differences were not observed with respect to the severity of wilt symptoms or RKN galling with any of the micro-nutrient treatments within the 30 day-experimental-period, differences in the induction of IR genes were observed. However, the level of gene expression varied with sampling period, type and concentration of micro-nutrients ap-plied, and pathogen-inoculation. In the absence of pathogens, no significant changes were observed in the expression level of IR genes on 7th day of micronutrient treatment. However, pathogen inoculation affected the expression levels of the IR genes at 3-day post-inoculation. In FON inoculated plants, PDF was upregulated in high Fe treatment, whereas in RKN inoculated plants, low Mn treatment resulted in up-regulation of VSP. In the case of mixed inoculation with FON and RKN, the plants with low Zn treatment resulted in the upregulation of PR1. These observations suggest that the type and concentration of micronutrients in watermelon may potentially induce systemic resistance against FON and RKN through SA and JA pathways.

Objective: To summarize the prevalence of PASC/Long COVID symptoms among the general population reported in published articles. This narrative review examined 21 PASC symptoms. Methods: A PubMed/manual search returned 114 articles on general PASC/Long COVID symptoms. Manuscripts were excluded if they were not research studies, didn’t report symptom prevalence, or used a pediatric population. Ninety-eight studies were selected for review and 59 met criteria for inclusion. Risk of bias was assessed with the Hoy critical appraisal tool. Results: After excluding studies with high risk of bias, meta-analysis of prevalence for 21 symptom categories ranged from 2.6-28.7% in studies based on surveys to 0.3%-7.1% in studies based on EHR data. Conclusions: PASC symptom studies are limited by variability in study design and representation of the general population. Further research is needed to effectively cluster symptoms in meaningful ways that enable focused treatment.

Background: Cytokines are multifunctional glycoproteins playing a vital role in the tumor microenvironment and in the progression of breast cancer. The immune responses in the tumors restrained by pro- and anti-inflammatory cytokine expressions could be influenced by genetic polymorphisms. Hence, the present study evaluated the contribution of IL6 (rs1800797, rs1800796, and rs1800795), and IL18 (rs1946518, rs187238, and rs549908) genotypes and its haplotypes with risk and progression of breast cancer in south Indian population. Methods: The polymorphisms of IL6 gene -597G>A, -572G>C, -174G>C and IL18 gene -607C>A, -137G>C, and 105A>T were genotyped through PCR-RFLP and As-PCR assays in blood DNA of 600 subjects. We have performed haplotype, LD, univariate, multivariate logistic regression and Kaplan-Meier analyses for the obtained data. Results: The frequency of AA genotype & A-allele of IL6 -597G>A, and CC genotype & C allele of IL6 -174G>C polymorphism was higher in breast cancer patients and was found to be significantly associated with TNM staging, late (advanced) stage, metastasis, etc. While, CG and GG genotypes of IL6 -572 C>G polymorphism had a protective role against breast cancer. Further, IL18 -607C>A, -137G>C & 105A>T polymorphisms were found to be associated with lobular carcinoma subtype, PR-ve and HER2+ve breast cancer patients. Perfect LD was observed between all SNPs of IL6 & IL18 genes under study; G-C-C, A-G-G and A-C-C haplotype combination of IL6 genes had conferred 2.09, 2.25 and 4.72 folds risk for breast cancer respectively. In survival analysis, we observed that the C allele of rs 1800795 was found to be significantly associated with 5years overall survival in breast cancer subjects. Conclusions: Overall, our results suggest the importance of genotypic and haplotype analysis of IL6, and IL18 gene variants in progression and risk identification of breast cancer.

Campylobacter is one of the major foodborne pathogens of concern in its growing trend of antimicrobial resistance. C. jejuni and C. coli are the major causative agents, with C. jejuni contributing to most of the cases in approximately 90% in the world. Infection is transmitted to humans due to consumption of contaminated food and water. Campylobacteriosis caused by C. jejuni is commonly presented with severe diarrhoea, abdominal pain, fever, headache, nausea, and vomiting with some extreme cases resulting in Guillain–Barré syndrome (GBS) and acute flaccid paralysis. Symptoms are severe in cases of children below 5 years, elderly and individuals who are immunocompromised. The infection is usually sporadic, and self-limiting and thus does not require antibiotics for treatment. Still, the antimicrobial resistance in Campylobacter is a major concern because of the transmission of resistance from animal sources to humans. This review highlights the recent epidemiology, geographical impact, resistance mechanisms, spread of Campylobacter spp. and the strategies to control the transmission of Campylobacter from veterinary sources and its antimicrobial resistance.

COVID-19 vaccination certificates (CVCs) have played a key role in safe reopening of borders for international travel and trade, so understanding key stakeholder perceptions of enablers and barriers for their effective use is critical. The COVID-19 Vaccination Policy Research and Deci-sion-Support Initiative in Asia (CORESIA) was established to address policy questions related to CVCs. We conducted two online surveys, i.e., one for the public and one for health and non-health sector experts, from June to October 2021 in nine Asian countries. Descriptive analysis identified participants, enablers, and barriers. Most participants (78% public, 89% experts) accepted the use of CVCs, primarily to resume international travel (76%). Most respondents in both surveys wanted the minimum vaccination coverage to be 60% before CVCs were implemented nation-wide. Most of the public (82%) agreed to maintain existing non-pharmaceutical interventions, while most experts wanted risk-based testing and quarantine policy for incoming travellers (51%) and both digital and paper format CVCs (64%). Support for CVCs for international travel remains high in Asia. Recognising key enablers and barriers for effective use of CVCs from COVID-19 pandemic may help policymakers draft effective border policies for future epidemics.