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Abstract Familial hypercholesterolemia (FH) is an inherited metabolic disease affecting cholesterol metabolism, with 90% of cases caused by mutations in the LDL receptor gene (LDLR), primarily missense mutations. This study aims to integrate six commonly used predictive software to create a new model for predicting LDLR mutation pathogenicity and mapping hot spot residues. Six predictive‐software are selected: Polyphen‐2, SIFT, MutationTaster, REVEL, VARITY, and MLb‐LDLr. Software accuracy is tested with the characterized variants annotated in ClinVar and, by bioinformatic and machine learning techniques all models are integrated into a more accurate one. The resulting optimized model presents a specificity of 96.71% and a sensitivity of 98.36%. Hot spot residues with high potential of pathogenicity appear across all domains except for the signal peptide and the O‐linked domain. In addition, translating this information into 3D structure of the LDLr highlights potentially pathogenic clusters within the different domains, which may be related to specific biological function. The results of this work provide a powerful tool to classify LDLR pathogenic variants. Moreover, an open‐access guide user interface (OptiMo‐LDLr) is provided to the scientific community. This study shows that combination of several predictive software results in a more accurate prediction to help clinicians in FH diagnosis.

O-glycosylation is an abundant post-translational modification but its relevance for bioactive peptides is unclear. Here, the authors detect O-glycans on almost one third of the classified peptide hormones and show that O-glycosylation can modulate peptide half-lives and receptor activation properties.

Background: Mesenchymal stem cells (MSCs) are stem cells present in adult tissues. They can be cultured, have great growth capacity, and can differentiate into several cell types. The isolation of urine-derived mesenchymal stem cells (hUSCs) was recently described. hUSCs present additional benefits in the fact that they can be easily obtained noninvasively. Regarding gene delivery, nonviral vectors based on cationic niosomes have been used and are more stable and have lower immunogenicity than viral vectors. However, their transfection efficiency is low and in need of improvement. Methods: We isolated hUSCs from urine, and the cell culture was tested and characterized. Different cationic niosomes were elaborated using reverse-phase evaporation, and they were physicochemically characterized. Then, they were screened into hUSCs for transfection efficiency, and their internalization was evaluated. Results: GPxT-CQ at a lipid/DNA ratio of 5:1 (w/w) had the best transfection efficiency. Intracellular localization studies confirmed that nioplexes entered mainly via caveolae-mediated endocytosis. Conclusions: In conclusion, we established a protocol for hUSC isolation and their transfection with cationic niosomes, which could have relevant clinical applications such as in gene therapy. This methodology could also be used for creating cellular models for studying and validating pathogenic genetic variants, and even for performing functional studies. Our study increases knowledge about the internalization of tested cationic niosomes in these previously unexplored cells.

Cardiovascular disease (CVD), the leading cause of mortality worldwide is primarily caused by atherosclerosis, which is promoted by the accumulation of low-density lipoproteins into the intima of large arteries. Multiple nanoparticles mimicking natural HDL (rHDL) have been designed to remove cholesterol excess in CVD therapy. The goal of this investigation was to assess the cholesterol efflux efficiency of rHDLs with different lipid compositions, mimicking different maturation stages of high-density lipoproteins (HDLs) occurring in vivo. Methods: the cholesterol efflux activity of soybean PC (Soy-PC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), DPPC:Chol:1-palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine (LysoPC) and DPPC:18:2 cholesteryl ester (CE):LysoPC rHDLs was determined in several cell models to investigate the contribution of lipid composition to the effectiveness of cholesterol removal. Results: DPPC rHDLs are the most efficient particles, inducing cholesterol efflux in all cellular models and in all conditions the effect was potentiated when the ABCA1 transporter was upregulated. Conclusions: DPPC rHDLs, which resemble nascent HDL, are the most effective particles in inducing cholesterol efflux due to the higher physical binding affinity of cholesterol to the saturated long-chain-length phospholipids and the favored cholesterol transfer from a highly positively curved bilayer, to an accepting planar bilayer such as DPPC rHDLs. The physicochemical characteristics of rHDLs should be taken into consideration to design more efficient nanoparticles to promote cholesterol efflux.

Objectives: This study aimed to identify the individual- and community-level determinants of mothers' healthcare-seeking behaviour for children under the age of 5 years with acute respiratory infection (ARI) symptoms in low-and middle-income countries (LMICs)., Study Design: Nationally representative Demographic and Health Survey datasets from 29 LMICs were used., Methods: The study included 16,893 children aged under 5 years with ARI symptoms in the 2 weeks prior to the survey. A multilevel logistic regression model was used to examine associations between individual- and community-level factors with health-seeking behaviour for ARIs. The adjusted odds ratio (AOR) along with 95% confidence intervals (CIs) were reported as a measure of association., Results: The overall prevalence of healthcare-seeking behaviour for ARIs among children under 5 years in LMICs was 58.83% (95% CI: 58.08, 59.57). Findings showed that mothers with primary or higher education (AOR = 1.20; 95% CI: 1.08, 1.33), and those residing in rich households (AOR = 1.32; 95% CI: 1.18, 1.48), attending antenatal care (ANC) visits (AOR = 1.53; 95% CI: 1.31, 1.79) and delivering at a healthcare facility (AOR = 1.28; 95% CI: 1.16, 1.41) were more likely to seek healthcare for ARIs. A higher level of community maternal education (AOR = 1.44; 95% CI: 1.24, 1.68) was positively associated with seeking healthcare for ARIs, while a higher level of community poverty (AOR = 0.83; 95% CI: 0.72, 0.96) was negatively associated with healthcare seeking for ARIs., Conclusions: This study revealed that mothers' healthcare-seeking behaviour for ARIs was closely linked to modifiable risk factors, including maternal education, household wealth, use of maternal health services (e.g., ANC), as well as community poverty and literacy levels. Future interventions should consider these modifiable risk factors when developing strategies to improve child health outcomes in LMICs., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Although Ethiopia has substantial improvements in various health indicators such as maternal and child mortality, the burden of neonatal mortality remains high. Between 2016 and 2019, neonatal mortality increased from 29 deaths per 1,000 live births to 33 deaths per 1,000 live births. This study aimed to explore the spatial patterns and factors contributing to neonatal mortality in Ethiopia., Methods: Data from the Ethiopian Demographic and Health Surveys (EDHS) for the years 2000, 2005, 2011, 2016, and 2019 were analyzed. The EDHS sampling design uses a two-stage cluster sampling technique, considering census enumeration areas as primary sampling units and households as secondary sampling units. We used the Spatial Scan analysis in SaTScan and Getis-Ord Gi* statistic in Geographic Information System (GIS), to analyse the spatiotemporal patterns of neonatal mortality. Maternal, newborn and health service-related factors contributing to neonatal mortality were also analyzed using a multilevel logistic regression model. Adjusted Odds Rios (AOR) with corresponding 95% CI were presented as a measure of association and a P-value of 0.05 was used to declare statistical significance., Results: During the initial three consecutive surveys, there was a consistent pattern of hot spot clusters in the Amhara and Benshangul Gumuz regions, along with certain parts of the Oromia region. However, in later surveys, these clusters shifted to the eastern parts of the country, notably including the Somali region. Early initiation of breast feeding was associated with reduced chances of neonatal death (Adjusted Odds Ratio [AOR]) = 0.27; 95% Confidence Interval [CI]: 0.23, 0.32). Neonates born at home (AOR = 1.46; 95% CI: 1.16, 1.82) and male babies had a higher likelihood of mortality during the neonatal period compared to their counterparts (AOR = 1.36; 95% CI: 1.24, 1.51). The odds of neonatal mortality increased with the number of children a mother had ever given birth to (AOR = 1.36; 95% CI: 1.24, 1.51). In contrast, longer birth intervals were associated with a reduced risk of neonatal mortality (AOR = 0.76; 95% CI: 0.68, 0.83)., Conclusion: The central southern, central-western, north-western, and northern parts of Ethiopia had most of the neonatal death clusters in the first three rounds of DHS while eastern Ethiopia had the highest neonatal mortality clusters in the latest two surveys. Our results underscore the importance for policymakers and health administrators to reassess intervention approaches and reallocate resources to regions identified as hot spots for neonatal mortality. Enhancing the initiation of breastfeeding within the first hour of birth would improve newborn survival rates. Special attention and care need to be given to babies born of smaller sizes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kibret et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Iron deficiency is a widespread micronutrient deficiency, impacting over 30% of the global population. Iron Folic Acid supplement is recommended for pregnant women to counter iron deficiency anemia and neural tube anomalies. Although Iron Folic Acid supplementation is integral to Ethiopian antenatal care, one in four women in Ethiopia experiences anemia during pregnancy suggesting poor compliance. This study aimed to investigate compliance level and associated factors of Iron Folic Acid supplementation among pregnant women attending antenatal care in Wuchale Woreda of North Shoa Zone, Ethiopia. An institutional-based cross-sectional study was conducted among 302 pregnant women from March 20 to April 5, 2021, who were selected using a systematic random sampling technique. Data were collected through face-to-face interview, entered epi-data, and exported to Statistical Package for the Social Sciences for analysis. A multivariable logistic regression was used to identify factors associated with compliance level. All the results were presented with 95% confidence intervals. The compliance with Iron Folic Acid supplementation was 47.0%. Residing nearest to the health facility (AOR = 2.46; 95% CI 1.32, 4.57), initiating antenatal care at health center (AOR = 2.23; 95% CI 1.17, 4.51), having a family size of 4 and above (AOR = 4.99; 95% CI 2.43, 10.24), and receiving information from health extension workers (AOR = 5.52; 95% CI 1.30, 23.54) increased compliance with Iron Folic Acid supplementation. Less than half of the pregnant women were compliant with Iron Folic Acid utilization. There is a need to prioritize promoting the importance of Iron Folic Acid supplementation through health education particularly by targeting pregnant women with identified factors., (© 2024. The Author(s).)

Globally women face inequality in cancer outcomes; for example, smaller improvements in life expectancy due to decreased cancer-related deaths than men (0.5 vs 0.8 years, 1981-2010). However, comprehensive global evidence on the burden of cancer among women (including by reproductive age spectrum) as well as disparities by region, remains limited. This study aimed to address these evidence gaps by considering 34 cancer types in 2020 and their projections for 2040. The cancer burden among women in 2020 was estimated using population-based data from 185 countries/territories sourced from GLOBOCAN. Mortality to Incidence Ratios (MIR), a proxy for survival, were estimated by dividing the age-standardised mortality rates by the age-standardised incidence rates. Demographic projections were performed to 2040. In 2020, there were an estimated 9.3 million cancer cases and 4.4 million cancer deaths globally. Projections showed an increase to 13.3 million (↑44%) and 7.1 million (↑60%) in 2040, respectively, with larger proportional increases in low- and middle-income countries. MIR among women was higher (poorer survival) in rare cancers and with increasing age. Countries with low Human Development Indexes (HDIs) had higher MIRs (69%) than countries with very high HDIs (30%). There was inequality in cancer incidence and mortality worldwide among women in 2020, which will further widen by 2040. Implementing cancer prevention efforts and providing basic cancer treatments by expanding universal health coverage through a human rights approach, expanding early screening opportunities and strengthening medical infrastructure are key to improving and ensuring equity in cancer control and outcomes., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Introduction: Supportive cancer care is vital to reducing the current disparities in cancer outcomes in Sub-Saharan Africa (SSA), including poor survival and low quality of life, and ultimately achieving equity in cancer care. This is the first review aimed to evaluate the extent of unmet supportive care needs and identify their contributing factors among patients with cancer in SSA., Methods: Six electronic databases (CINAHL, Embase, Medline [Ovid], PsycINFO, PubMed, and Cochrane Library of Databases] were systematically searched. Studies that addressed one or more domains of unmet supportive cancer care needs were included. Findings were analyzed using narrative analysis and meta-analysis, as appropriate., Result: Eleven articles out of 2732 were retained in the review. The pooled prevalence of perceived unmet need for cancer care in SSA was 63% (95% CI: 45, 81) for physical, 59% (95% CI: 45, 72) for health information and system, 58% (95% CI: 42, 74) for psychological, 44% (95% CI: 29, 59) for patient care and support, and 43% (95% CI: 23, 63) for sexual. Older age, female sex, rural residence, advanced cancer stage, and low access to health information were related to high rates of multiple unmet needs within supportive care domains., Conclusion: In SSA, optimal cancer care provision was low, up to two-thirds of patients reported unmet needs for one or more domains. Strengthening efforts to develop comprehensive and integrated systems for supportive care services are keys to improving the clinical outcome, survival, and quality of life of cancer patients in SSA., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background: Identifying the critical modifiable risk factors for acute respiratory tract infections (ARIs) and diarrhoea is crucial to reduce the burden of disease and mortality among children under 5 years of age in sub-Saharan Africa (SSA) and ultimately achieving the Sustainable Development Goals (SDGs). We investigated the modifiable risk factors of ARI and diarrhoea among children under five using nationally representative surveys., Methods: We used the most recent demographic and health survey (DHS) data (2014-2021) from 25 SSA countries, encompassing a total of 253,167 children. Countries were selected based on the availability of recent datasets (e.g., DHS-VII or DHS-VIII) that represent the current socioeconomic situations. Generalised linear latent mixed models were used to compute odds ratios (ORs). Population attributable fractions (PAFs) were calculated using adjusted ORs and prevalence estimates for key modifiable risk factors among ARI and diarrhoeal cases., Findings: This study involved 253,167 children, with a mean age of 28.7 (±17.3) months, and 50.5% were male. The highest PAFs for ARI were attributed to unclean cooking fuel (PAF = 15.7%; 95% CI: 8.1, 23.1), poor maternal education (PAF = 13.4%; 95% CI: 8.7, 18.5), delayed initiation of breastfeeding (PAF = 12.4%; 95% CI: 9.0, 15.3), and poor toilets (PAF = 8.5%; 95% CI: 4.7, 11.9). These four modifiable risk factors contributed to 41.5% (95% CI: 27.2, 52.9) of ARI cases in SSA. The largest PAFs of diarrhoea were observed for unclean cooking fuel (PAF = 17.3%; 95% CI: 13.5, 22.3), delayed initiation of breastfeeding (PAF = 9.2%; 95% CI: 7.5, 10.5), household poverty (PAF = 7.0%; 95% CI: 5.0, 9.1) and poor maternal education (PAF = 5.6%; 95% CI: 2.9, 8.8). These four modifiable risk factors contributed to 34.0% (95% CI: 26.2, 42.3) of cases of diarrhoea in SSA., Interpretation: This cross-sectional study identified four modifiable risk factors for ARI and diarrhoea that should be a priority for policymakers in SSA. Enhancing home-based care and leveraging female community health workers is crucial for accelerating the reduction in under-5 mortality linked to ARI and diarrhoea in SSA., Funding: None., Competing Interests: All other authors declare no competing interests., (© 2024 The Author(s).)

Objectives: Although tuberculosis (TB) related stigma has a significant impact on the diagnosis, patient adherence with treatment, and recovery from the disease, there is limited evidence from Ethiopia regarding perceived stigma among patient with pulmonary tuberculosis (PTB).The purpose of this study was to assess perceived stigma and associated factors among patient with PTB on treatment in southwest Ethiopia., Methods: Institution-based cross-sectional study was conducted from April to May 2019 among 410 patient with PTB. Data were collected by using the perceived tuberculosis stigma scale. Epi data v3.1 and SPSSv23 were used for data entry and analysis. Multivariable logistic regression models were fitted to identify factors associated with perceived stigma. Results are presented as adjusted odds ratios (AORs) with 95% confidence intervals (CIs)., Result: Prevalence of perceived stigma among patient with Pulmonary tuberculosis was 57.1% (95% CI: 52.2, 61.7). Poor social support (AOR = 2.41; 95% CI: 1.06, 5.48), above a month duration of illness (AOR = 2.48; 95% CI: 1.33, 4.64), high perceived stress (AOR = 1.95; 95% CI:1.09, 3.49), current khat use (AOR = 1.88; 95% CI:1.05, 3.37), and presence of depression (AOR = 8.18; 95% CI:4.40, 15.22) were significantly associated with perceived stigma. Patient with HIV co-infection were 5.67 times (AOR = 5.67; 95% CI: 2.32, 13.87) more likely to have Perceived stigma than their counterparts., Conclusion: TB related stigma was reported by more than half of the study participant. Stigma reduction measures are needed to lower TB related stigma perceived by the patient, the level of distress associated with it, and to promote the psychological wellbeing of patient with TB., Competing Interests: The authors have declared that no competing interests exist.