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Background Child undernutrition is a severe health problem in the developing world, which affects children’s development in the long term. This study analyses the extent and patterns of under-five child undernutrition using Demographic and Health Surveys (DHS) for 73 low- and middle-income countries (LMICs). Methods First, we mapped the prevalence of undernutrition in the developing world. Second, using the LISA (a local indicator of spatial association) technique, we analyzed the geographical patterns in undernutrition to highlight the localized hotspots (regions with high undernutrition prevalence surrounded by similar other regions), cold spots (regions with low undernutrition prevalence surrounded by similar other regions), and outliers (regions with high undernutrition surrounded by low undernutrition and vice versa). Third, we used Moran’s I to find global patterns in child undernutrition. Results We find that South Asia has the highest under-five child undernutrition rates. The intra-country nutritional inequalities are highest in Burundi (stunting), Kenya (wasting), and Madagascar (underweight). The local indicator of spatial association (LISA) analysis suggests that South Asia, Middle East and North Africa (MENA) region, and Sub-Saharan Africa are undernutrition hotspots and Europe and Central Asia and Latin America, and the Caribbean are undernutrition cold spots (regions with low undernutrition surrounded by similar other regions). Getis Ord-Gi* estimates generally support LISA analysis. Moran’s I and Geary’s C gave similar results about the global patterns of undernutrition. Geographically weighted regressions suggest that several socioeconomic indicators significantly explain child undernutrition. Conclusions We found a significant within and across country variation in stunting, wasting and underweight rates among the under-five children’s population. The geospatial analysis also suggested that stunting, wasting, and underweight patterns exhibit clear regional patterns, underscoring the need for coordinated interventions at the regional level.

Incidence rate of cancer is estimated to increase by 40% in 2030. Furthermore, the development of resistance against currently available treatment strategies has contributed to the cancer-associated mortality. Scientists are now looking for the solutions that could help prevent the disease occurrence and could provide a pain-free treatment alternative for cancers. Therefore, efforts are now put to find a potent natural compound that could sever this purpose. Ursolic acid (UA), a triterpene acid, has potential to inhibit the tumor progression and induce sensitization to conventional treatment drugs has been documented. Though, UA is a hydrophobic compound therefore it is usually chemically modified to increase its bioavailability prior to administration. However, a thorough literature indicating its mechanism of action and limitations for its use at clinical level was not reviewed. Therefore, the current study was designed to highlight the potential mechanism of UA, its anti-cancer properties, and potential applications as therapeutic compound. This endeavour is a valuable contribution in understanding the hurdles preventing the translation of its potential at clinical level and provides foundations to design new studies that could help enhance its bioavailability and anti-cancer potential for various cancers.

Background Missense single-nucleotide polymorphisms (SNPs) in various genetic pathways can lead to the development of breast cancer. Protein kinase C delta ( PRKCD) is involved in various important cellular pathways, and its altered expression has been identified in different cancers. Genetic alteration in this gene can be involved in cancer onset and progression. To date, there are no studies performed to elucidate the role of PRKCD missense variants in the development of breast cancer. Therefore, this study aims to identify the association of pathogenic missense SNPs in PRKCD with breast cancer. Methods The missense variants of PRKCD were retrieved from the Ensembl and dbSNP databases. Missense variants were analysed through various computational tools, and four variants of PRKCD rs1703806197 (T/C) , rs782555227 (G/A) , rs1703449438 (T/C) , and rs1575535582 ( T/G ) were selected from the data. The genotype analysis for these variants was performed for 360 breast cancer patients and 363 healthy controls. Statistical association of variants with breast cancer clinical features was determined through chi-square/Fisher’s exact test with a significant P  value  ≤  0.05 using GraphPad Prism 8.0 software. Results Genotype analysis of PRKCD variants showed that missense SNPs rs782555227 ( G/A ), rs1703449438 ( T/C ), and rs1575535582 ( T/G ) were associated with breast cancer ( P  value < 0.05). Furthermore, genotypes in these SNPs were also found to be associated with various clinical features of breast cancer patients. Genotypes AG, TC, and TT in variants rs782555227, rs1703449438, and rs1575535582, respectively, were associated with breast cancer metastasis. While genotype AG of variant rs782555227 was also found to be associated with menopausal status and hereditary breast cancer. Moreover, genotype TT in variant rs1575535582 was associated with BRCA1 positive status among the breast cancer patients. Conclusion The present study identified for the first time the association of specific PRKCD missense variants with breast cancer. These variants could be developed into possible genetic markers for the diagnosis of breast cancer at an early stage; however, further validation studies with a multiethnic large cohort size are required. Furthermore, functional studies of these variants will also aid in attaining insight into the molecular mechanisms through which these missense variants are involved in breast cancer.

PKCδ is a key isoform in the PKC subgroup of AGC-kinase proteins, known to be involved in various cellular processes. Dysregulation of its expression has been linked to multiple malignancies. Notably, PKCδ overexpression has been associated with breast cancer progression and poor prognosis. Previous research has shown that PKCδ phosphorylates specific serine residues on target proteins, leading to tumorigenesis and metastasis. However, the molecular mechanisms of PKCδ-driven breast cancer pathogenesis remain incompletely understood. Single-nucleotide polymorphisms (SNPs), the most common genetic variants, can contribute to cancer susceptibility by causing structural and functional changes in proteins. This study aimed to identify oncogenic non-synonymous variants in PKCδ and assess their impact on protein structure, stability, conservation, dynamics, and interactions. Analyzing a dataset of 613 non-synonymous variants with various computational and in silico tools based on sequence and structure approaches, four variants, including V114G, C189R, C189Y, W608R, were identified as highly oncogenic. Molecular dynamics simulations showed increased structural deviations and flexibility in these variants compared to the native protein, potentially leading to changes in structure, stability, and biophysical properties. These variants disrupted normal PKCδ function by causing surface distortion, changing net charge, and perturbing intramolecular interactions with STAT3, which may activate PKCδ in a non-canonical manner. The study also found an association between the oncogenic non-synonymous SNP W608R, located within the highly conserved AGC kinase domain, and breast cancer, with the TT genotype significantly linked to increased risk (OR = 2.7; RR = 1.6, p  < 0.0001). Although further functional validation in cellular models is necessary, this research provides a foundation for future studies on the impact of oncogenic PKCδ variants in breast cancer.

Background Viral hepatitis is the major contributor to liver cirrhosis and hepatocellular carcinoma (HCC). Studies indicated that the co-infection of hepatitis C and hepatitis B virus also prompts liver damage progression. Therefore, in the present study, the prevalence of HCV-HBV co-infection and the impact of HCV-HBV co-infection on the progression of liver damage was evaluated amongst the HCV-infected patients in Pakistan. Methods In this study 2500 HCV-positive patients were recruited from Pakistan. The presence and prevalence of HCV and HBV was confirmed through ELISA and nested PCR. To determine the liver damage due to viral infection levels of ALT, ALP, and total bilirubin were also determined. Diagnostic history of patients was thoroughly documented through serological tests and liver biopsy reports. Viral genotypes and viral loads were determined through multiplex polymerase chain reaction (PCR) and time PCR, respectively. Results The study outcomes showed that 12.5% of the HCV-infected patients were co-infected with HBV. Co-infection development was more common in females than in males, and females were at a higher risk of developing the infection ( p-value  = < 0.0001, OR = 2.437). Despite the variation among different age groups, there was no significant difference in co-infection prevalence. HCV genotype 3a was found to be most prevalent while in HBV genotype D was found to be prevalent among the patients. The HCV patients frequently developed co-infection with HBV genotype D. It was also determined that viral load for HBV genotype D was higher compared to non-D genotypes while for HCV viral load was higher in non-3a genotypes. Conclusions This study evaluated the prevalence of HCV and HBV co-infection among HCV-positive patients, revealing that 12.5% patients were co-infected with HBV. Co-infection was more common in females, who had a higher risk of developing it. The study also revealed that HBV genotype D was the most prevalent in co-infected patients, with no significant age-related differences in co-infection rates.

Floods destroy crop production; nevertheless, the extent of their impact on farmers' livelihoods in developing countries has been poorly investigated. This paper contributes to the growing evidence-based assessment of the impacts of shocks on communities. It assessed the post disaster livelihood of farmers affected by the 2012 flooding in the semi-arid zone of Benin. To this end, a survey was conducted on 228 farmers in two municipalities of the flood-prone part of the semi-arid zone of Benin (Malanville, Karimama). Information on the well-being of households was collected using semi-structured interviews. Data were analyzed using income and consumption approaches focusing on poverty and on subjective assessment using happiness approach. Additionally, a probit model was used for a poverty assessment. The survey revealed that flooded farmers were amongst the poorest in the study system. Seven variables determined poverty in this study: household size, location, the percentage of the farm size that was flooded, fishing, the farmer's gender, farm size, and 'holding a secondary activity'. Regarding happiness, 99% of the flooded farmers were unhappier after the flood in 2012. The results clearly show that being subjected to floods increases the incidence of poverty. The capacity of flood risk management and governance should be strengthened in the study system.

Background Chronic myeloid leukaemia (CML) is a type of blood cancer that begins in the hematopoietic stem cells. It is primarily characterized by a specific chromosomal aberration, the Philadelphia chromosome. While the fusion gene is a major contributor to CML, several other genes including ADGRE2, that are reported as highly expressed in hematopoietic stem cells and could be utilized as a therapeutic marker in leukemic patients are implicated in the disease’s progression. Until recently, little research had been conducted to identify single nucleotide polymorphisms (SNPs) associated with CML. Therefore, this study aims to investigate the influence of non-synonymous variants on the structure and function of the gene encoding adhesion G protein-coupled receptor E2, ADGRE2, and to evaluate their association with CML and its clinical and pathological characteristics. Methods Non-synonymous SNPs of ADGRE2 were retrieved from the ENSEMBL, COSMIC, and gnomAD genome browsers, and the pathogenicity of deleterious variants was assessed using several established computational tools, including SIFT, CADD, REVEL, PolyPhen, and MetaLR. Results Various in silico analyses explored the impact of damaging SNP on the function, stability, and structure of EGF-like modules containing mucin-like hormone receptor-like2 (EMR2) protein encoded by the ADGRE2 gene. Genotype analysis was performed on collected blood samples, revealing that altered genotype TT of variant rs765071211 (C/T) was associated significantly with CML patients compared to the control. Further in vitro and in vivo analyses suggest that this SNP holds potential for clinical translation.

In this brief, we draw attention to Pakistan with the purpose of diversifying research on brain drain of individuals who migrate from the country primarily in search of a better quality of life and institutions, particularly focusing on the healthcare sector. Brain drain in Pakistan has become a perpetually rising phenomenon with more and more highly skilled workers leaving the country, yet there is relatively less research on this group. Pakistan offers a unique insight into migration of skilled workers from developing states due to the recent economic turmoil, as well as the consequent effects on the country, the repercussions for those who remain behind, and policy instruments used to maximise benefits for all stakeholders. Brain drain in the country has led to a shortage of highly qualified medical professionals, and poor returns on investment by the government.INTRODUCTIONIn discussions about the flow of human capital, there is a common belief that developing countries are increasingly becoming a source of talented individuals who eventually end up in developed countries due to a lack of adequate institutions or environments in their home countries to support them. International migration benefits immigrants by allowing them to achieve a higher income and better quality of life.While origin countries experience an influx of remittances, increased trade and technological transfers, they also incur losses in human capital and subsequent brain drain. Despite increasing trends in brain drain, most studies on migrants’ demographics and sociology tend to neglect it.In this brief, we draw attention to Pakistan as a significant region to add to research and theory on studies of migration patterns in developing countries. Pakistan, we argue, exemplifies the global trend of brain drain as approximately 832,339 Pakistanis went abroad for employment in 2022, which is the highest number since 2016 and the third-highest ever recorded according to the Bureau of Emigration and Overseas Employment (BEOE). Additionally, official records indicate that among those who traveled overseas in 2022, over 92,000 were graduates and more than 350,000 were trained workers and labourers (BEOE, 2022). Therefore, Pakistan -a low income country- presents a distinctive prospect to analyse a rapidly growing and diverse brain drainphenomenon as it offers important insights for migration scholars in comprehending the various factors associated with high-skilled worker migration, its effects on the country, the repercussions for those who remain behind, and policy instruments used to maximise benefits for all stakeholders.

Background Protein Kinase C-epsilon (PKCε) is a member of the novel subfamily of PKCs (nPKCs) that plays a role in cancer development. Studies have revealed that its elevated expression levels are associated with cervical cancer. Previously, we identified pathogenic variations in its different domains through various bioinformatics tools and molecular dynamic simulation. In the present study, the aim was to find the association of its variants rs1553369874 and rs1345511001 with cervical cancer and to determine the influence of these variants on the protein-protein interactions of PKCε, which can lead towards cancer development and poor survival rates. Methods The association of the variants with cervical cancer and its clinicopathological features was determined through genotyping analysis. Odds ratio and relative risk along with Fisher exact test were calculated to evaluate variants significance and disease risk. Protein-protein docking was performed and docked complexes were subjected to molecular dynamics simulation to gauge the variants impact on PKCε’s molecular interactions. Results This study revealed that genetic variants rs1553369874 and rs1345511001 were associated with cervical cancer. Smad3 interacts with PKCε and this interaction promotes cervical cancer angiogenesis; therefore, Smad3 was selected for protein-protein docking. The analysis revealed PKCε variants promoted aberrant interactions with Smad3 that might lead to the activation of oncogenic pathways. The data obtained from this study suggested the prognostic significance of PRKCE gene variants rs1553369874 and rs1345511001. Conclusion Through further in vitro and in vivo validation, these variants can be used at the clinical level as novel prognostic markers and therapeutic targets against cervical cancer.