Accessible Target Research Articles

Geospatial intelligence framework for BTS infrastructure planning toward universal internet access target in Indonesia

Equitable internet coverage has emerged as a key global priority, which is essential for promoting inclusive and sustainable development. The Indonesian government aims to provide universal internet access by 2024, particularly in remote regions. This study introduces a novel machine-learning-based approach to identify the priority areas for deploying Base Transceiver Station (BTS) towers, which are crucial for achieving the internet access targets of the government. A BTS Network Priority Index was developed by integrating the internet demand estimates with a BTS suitability index derived from key predictors: proximity to fiber optic stations, physical–environmental suitability, and infrastructure–economic readiness. The model identified areas with high internet demand and high BTS suitability as the most critical for immediate development, covering 20 km2. Additionally, future BTS development should target areas with high demand but medium suitability (900 km2) and medium demand but high suitability (280 km2). To validate the methodology, the Random Forest model was employed, which achieved an area under the curve value of 0.7315, indicating strong predictive performance. For the BTS Deployment Suitability parameter, the median was 0.65, with the lower and upper quartiles at 0.44 and 0.85, respectively, confirming that most proposed locations are highly suitable for development. This systematic approach provides data-driven insights for the equitable distribution of BTS towers to ensure efficient internet infrastructure expansion across Indonesia. Furthermore, the study offers a framework that can be adapted by other countries aiming to improve their digital infrastructure and achieve comprehensive, equitable internet access.

A resurrected ancestor of Cas12a expands target access and substrate recognition for nucleic acid editing and detection.

The properties of Cas12a nucleases constrict the range of accessible targets and their applications. In this study, we applied ancestral sequence reconstruction (ASR) to a set of Cas12a orthologs from hydrobacteria to reconstruct a common ancestor, ReChb, characterized by near-PAMless targeting and the recognition of diverse nucleic acid activators and collateral substrates. ReChb shares 53% sequence identity with the closest Cas12a ortholog but no longer requires a T-rich PAM and can achieve genome editing in human cells at sites inaccessible to the natural FnCas12a or the engineered and PAM-flexible enAsCas12a. Furthermore, ReChb can be triggered not only by double-stranded DNA but also by single-stranded RNA and DNA targets, leading to non-specific collateral cleavage of all three nucleic acid substrates with similar efficiencies. Finally, tertiary and quaternary structures of ReChb obtained by cryogenic electron microscopy reveal the molecular details underlying its expanded biophysical activities. Overall, ReChb expands the application space of Cas12a nucleases and underscores the potential of ASR for enhancing CRISPR technologies.

Tumor-Derived Extracellular Vesicles Enable Tumor Tropism Chemo-Genetherapy for Local Immune Activation in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is highly heterogeneous, lacks accessible therapeutic targets, and features an immunosuppressive tumor microenvironment (TME). Anthracycline-based chemotherapy remains the primary treatment method for TNBC, while the current popular immune checkpoint inhibitors persistently encounter therapeutic resistance. Therefore, there is an urgent need to explore combined therapeutic strategies to remodel the TME and improve the treatment response. Considering the highly specific homing ability of tumor cell-derived vesicles and the key role of the signal transduction and activation of the transcription factor 3 (STAT3) pathway in TNBC, we propose a synergistic therapeutic strategy that integrates gene therapy, chemotherapy, and immunotherapy based on STAT3 short interfering RNA (siSTAT3) and doxorubicin (DOX)-functionalized tumor-derived extracellular vesicles (TEVs) (siSTAT3-DOX@TEV). The in vitro and in vivo results demonstrate that siSTAT3-DOX@TEV target tumor tissues precisely, downregulate STAT3 expression, and synergistically and efficiently induce immunogenic death, thereby reversing the immunosuppressive TME. Moreover, mass cytometry and immunohistochemistry reveal the local immune activation effect of siSTAT3-DOX@TEV, with a significant increase in M1 macrophages, CD4+ T cells, and CD8+ T cells in tumor tissues. These results provide strong hints for the development of TEV-based chemo-gene therapeutic agents for TNBC treatment at the clinical level.

Abstract C019: A novel SDC1-targeted therapeutic antibody inhibits macropinocytosis and induces anti-tumor immunity in pancreatic cancer

Abstract Given that the mutated KRAS oncogene (KRAS*) dominates the genetic landscape of pancreatic ductal adenocarcinoma (PDAC), the development of KRAS* inhibitors represents a significant breakthrough in PDAC therapy. However, emerging evidence suggests that PDAC may eventually overcome its dependency on KRAS* and develop resistance to KRAS* inhibitor treatment. Our laboratory is dedicated to uncovering novel, accessible therapeutic targets that govern the mechanisms essential for KRAS*- driven PDAC cell survival. Our recent work has identified Syndecan1 (SDC1), a major heparan sulfate proteoglycan, as a critical mediator of KRAS* activity, promoting nutrient salvaging and fueling cancer cell growth, even in cases where PDAC cells have evaded KRAS* targeted therapy. Our finding positions SDC1 as a promising new therapeutic target for PDAC therapy. In our pursuit of new therapeutic approaches that can directly and specifically target SDC1 activity, we have successfully developed a monoclonal antibody against SDC1 (22B mAb), which exhibits remarkable sensitivity and specificity for human SDC1. Our results indicate that 22B mAb exerts substantial inhibition of PDAC cell growth in vitro and desirable tumor inhibitory effects in vivo in murine PDAC tumors and human PDAC cell-derived xenograft tumors. Interrogation of mechanism of actions further demonstrates that 22B elicits both direct effect in inhibiting macropinocytosis to block nutrient salvage of PDAC cells and indirect effect in inducing antibody-dependent cellular cytotoxicity (ADCC) to eliminate tumor cells. Notably, our 22B mAb synergizes with KRAS* inhibitors, chemotherapy, or immunotherapy, resulting in significantly enhanced therapeutic effects. In summary, our 22B mAb represents the first in class of anti-SDC1 antibody that not only directly targets the PDAC cells but also elicits immune cell-mediated killing. Additionally, our antibody holds the potential for developing new anti-PDAC therapeutic strategies, including antibody drug conjugates with cytotoxic or radionuclides payloads, for SDC1 targeted therapy/theranostics in PDAC. Thus, our newly developed 22B therapeutic antibody provides an alternate strategy for PDAC treatment and opens up new research horizons in therapeutic targeting of SDC1 in other malignancies characterized by aberrant SDC1 expression. Citation Format: Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Xiaofei Wang, Jun Yao, Jennifer Li, Jangho Park, Yangxi Zheng, Long T Vien, Laura Bover, Haoqiang Ying, Wantong Yao. A novel SDC1-targeted therapeutic antibody inhibits macropinocytosis and induces anti-tumor immunity in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr C019.

A novel super-resolution microscopy platform for cutaneous alpha-synuclein detection in Parkinson's disease.

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson's disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, we imaged total and phosphorylated-aSyn at the single molecule level in sweat glands and nerve bundles of skin biopsies from healthy controls (HCs) and PD patients. We developed a user-friendly analysis platform that offers a comprehensive toolkit for researchers that combines analysis algorithms and applies a series of cluster analysis algorithms (i.e., DBSCAN and FOCAL) onto dSTORM images. Using this platform, we found a significant decrease in the ratio of the numbers of neuronal marker molecules to phosphorylated-aSyn molecules, suggesting the existence of damaged nerve cells in fibers highly enriched with phosphorylated-aSyn molecules. Furthermore, our analysis found a higher number of aSyn aggregates in PD subjects than in HC subjects, with differences in aggregate size, density, and number of molecules per aggregate. On average, aSyn aggregate radii ranged between 40 and 200 nm and presented an average density of 0.001-0.1 molecules/nm2. Our dSTORM analysis thus highlights the potential of our platform for identifying quantitative characteristics of aSyn distribution in skin biopsies not previously described for PD patients while offering valuable insight into PD pathology by elucidating patient aSyn aggregation status.

Computational design and validation of siRNA molecules to silence oncogenic CTNNB1 mRNA as a potential therapeutic strategy against hepatitis B/C virus-associated hepatocellular carcinoma

The majority of hepatocellular carcinoma cases are caused by infection with hepatitis B (HBV) or C (HCV) viruses. CTNNB1 is the most mutated oncogene in HBV- and HCV-associated tumors. CTNNB1 mutations can lead to β-catenin accumulation, resulting in tumor progression. Small interfering RNAs (siRNAs) can be used to silence CTNNB1 mRNA. After prediction and evaluation, four siRNAs were found to have the highest silencing potential. All four siRNAs had an acceptable GC content, no palindromic sequences, no off-targets, were thermostable, and had accessible target sites. Molecular docking of the siRNAs to Argonaute 2 demonstrated favorable docking scores within the binding pocket for three siRNAs. Molecular dynamics simulations and binding energy calculations demonstrated that the siRNAs steadily remained in the binding pocket. In this study, three siRNAs were successfully designed to silence oncogenic CTNNB1 mRNA as a therapeutic strategy against hepatocellular carcinoma and warrant further in vitro and in vivo validation.

Genome-wide chromatin accessibility reveals transcriptional regulation of heterosis in inter-subspecific hybrid rice.

The utilization of rice heterosis is essential for ensuring global food security; however, its molecular mechanism remains unclear. In this study, comprehensive analyses of accessible chromatin regions (ACRs), DNA methylation, and gene expression in inter-subspecific hybrid and its parents were performed to determine the potential role of chromatin accessibility in rice heterosis. The hybrid exhibited abundant ACRs, in which the gene ACRs and proximal ACRs were directly related to transcriptional activation rather than the distal ACRs. Regarding the dynamic accessibility contribution of the parents, paternal ZHF1015 transmitted a greater number of ACRs to the hybrid. Accessible genotype-specific target genes were enriched with overrepresented transcription factors, indicating a unique regulatory network of genes in the hybrid. Compared with its parents, the differentially accessible chromatin regions with upregulated chromatin accessibility were much greater than those with downregulated chromatin accessibility, reflecting a stronger regulation in the hybrid. Furthermore, DNA methylation levels were negatively correlated with ACR intensity, and genes were strongly affected by CHH methylation in the hybrid. Chromatin accessibility positively regulated the overall expression level of each genotype. ACR-related genes with maternal Z04A-bias allele-specific expression tended to be enriched during carotenoid biosynthesis, whereas paternal ZHF1015-bias genes were more active in carbohydrate metabolism. Our findings provide a new perspective on the mechanism of heterosis based on chromatin accessibility in inter-subspecific hybrid rice.

The brain microvasculature is a primary mediator of interferon-α neurotoxicity in human cerebral interferonopathies

Aicardi-Goutières syndrome (AGS) is an autoinflammatory disease characterized by aberrant interferon (IFN)-α production. The major cause of morbidity in AGS is brain disease, yet the primary source and target of neurotoxic IFN-α remain unclear. Here, we demonstrated that the brain was the primary source of neurotoxic IFN-α in AGS and confirmed the neurotoxicity of intracerebral IFN-α using astrocyte-driven Ifna1 misexpression in mice. Using single-cell RNA sequencing, we demonstrated that intracerebral IFN-α-activated receptor (IFNAR) signaling within cerebral endothelial cells caused a distinctive cerebral small vessel disease similar to that observed in individuals with AGS. Magnetic resonance imaging (MRI) and single-molecule ELISA revealed that central and not peripheral IFN-α was the primary determinant of microvascular disease in humans. Ablation of endothelial Ifnar1 in mice rescued microvascular disease, stopped the development of diffuse brain disease, and prolonged lifespan. These results identify the cerebral microvasculature as a primary mediator of IFN-α neurotoxicity in AGS, representing an accessible target for therapeutic intervention.

Spontaneous immunological activities in the target tissue of vitiligo-prone Smyth and vitiligo-susceptible Brown lines of chicken.

Vitiligo is an acquired de-pigmentation disorder characterized by the post-natal loss of epidermal melanocytes (pigment-producing cells) resulting in the appearance of white patches in the skin. The Smyth chicken is the only model for vitiligo that shares all the characteristics of the human condition including: spontaneous post-natal loss of epidermal melanocytes, interactions between genetic, environmental and immunological factors, and associations with other autoimmune diseases. In addition, an avian model for vitiligo has the added benefit of an easily accessible target tissue (a growing feather) that allows for the repeated sampling of an individual and thus the continuous monitoring of local immune responses over time. Using a combination of flow cytometry and gene expression analyses, we sought to gain a comprehensive understanding of the initiating events leading to expression of vitiligo in growing feathers by monitoring the infiltration of leukocytes and concurrent immunological activities in the target tissue beginning prior to visual onset and continuing throughout disease development. Here, we document a sequence of immunologically significant events, including characteristic rises in infiltrating B and αβ T cells as well as evidence of active leukocyte recruitment and cell-mediated immune activities (CCL19, IFNG, GZMA) leading up to visual vitiligo onset. Examination of growing feathers from vitiligo-susceptible Brown line chickens revealed anti-inflammatory immune activities which may be responsible for preventing vitiligo (IL10, CTLA4, FOXP3). Furthermore, we detected positive correlations between infiltrating T cells and changes in their T cell receptor diversity supporting a T cell-specific immune response. Collectively, these results further support the notion of cell-mediated immune destruction of epidermal melanocytes in the pulp of growing feathers and open new avenues of study in the vitiligo-prone Smyth and vitiligo-susceptible Brown line chickens.

EVALUATION OF DIFFERENCES IN MATERNAL AND NEWBORN HEALTH COVERAGE ACROSS URBAN AND RURAL AREAS

Objective: This study aims to examine whether the variables that reveal the maternal and newborn health coverage of countries differ in rural and urban areas. Understanding the coverage of maternal and newborn health across rural and urban populations is important for assessing the health needs of populations and addressing health disparities. Methods: The data of the study were obtained from the "Maternal and Newborn Health Coverage Database 2022" published by UNICEF. Data were analyzed using IBM SPSS Statistics (IBM SPSS Statistics for Windows, Version 26.0. Armonk, United States). Results: As a result of the research, it was found that all variables of antenatal care, c-section rate, percentage of deliveries in a health facility, percentage of deliveries attended by skilled health personnel, and postnatal care for newborns and mothers differ statistically between rural and urban areas. Conclusion: This research reveals that women and newborns living in rural areas are disadvantaged compared to urban areas in antenatal, delivery and postnatal cares. It is recommended to make interventions for health workforce retention in rural, take steps to reduce socio-economic inequalities in rural areas, to set minimum targets for access to antenatal and postnatal care, subsidize maternity services in hospitals, and to develop a referral system among health institutions in rural areas.

Optimizing launch window opportunities for ESA's comet Interceptor mission using primer vector theory

Comet Interceptor (Comet-I) was selected in June 2019 as the first ESA F-Class mission and aims to explore a pristine comet, which will visit the inner Solar System for the first time. Comet-I will hitch a ride to a Sun-Earth L2 quasi-halo orbit, as a co-passenger in ESA's M4 ARIEL's launch. At the time of writing, this is scheduled for 2029. It will then remain there awaiting the right departure conditions to leave definitively and intercept a newly discovered comet. Comet-I will be the first mission to be designed and launched without an already identified target. Given the latter, the Comet-I Target Identification Working Group is tasked with the continuous follow-up of newly discovered comets, to analyse their characteristics as virtual targets for Comet-I. The goal of the paper is to inform the decision-making process that will eventually be necessary to commit Comet-I spacecraft to its final target.Within this context, this paper presents a trajectory optimization process based on Primer Vector theory that considers intercept trajectories with multiple revolutions and multiple deep space manoeuvres (DSM). The process is applied to 21 long period comets, which were discovered since July 1, 2020 and whose characteristics are of interest for the Comet-I mission. In fact, one of the latest of these recently discovered comets, C/2023H2, is the most accessible virtual target discovered at the time of writing, with delta-V intercept costs well within Comet-I capabilities. A complete launch window analysis is thus presented for C/2023H2, which accounts not only for the most optimal delta-V intercept transfer, but also considers all launch options that satisfy all Comet-I's current boundary conditions and flyby constraints. A systematic launch window analysis is made possible by a grid search approach on which departure and fly-by dates are fixed and the remaining design variables, including the times for manoeuvres and their Δv impulse vector, are optimized via Primer Vector theory. This allows to understand the latest possible departure date, but also the sensitivity to departure and arrival dates of key encounter characteristics such as relative fly-by speed, the solar aspect angle and the Earth distance.

TINJAUAN IMPLEMENTASI TEORI PERENCANAAN DALAM PENYUSUNAN DOKUMEN STRATEGI SANITASI KABUPATEN BENER MERIAH

The Regency Sanitation Strategy (RSS) document represents the government's initiative to address the consequences of market failure resulting from insufficient sanitation services, that lead to environmental pollution and a decline in public health. This failure has hindered the attainment of the universal access target (100-0-100), characterized by shortcomings in environmental quality, health, and community welfare in Bener Meriah Regency. This study aims to assess the application of planning theory in formulating RSS documents in Bener Meriah Regency. The research employed methods such as document review, interviews, stakeholder mapping, and qualitative descriptive analysis of interview findings. The outcomes include identifying stakeholders, planning approaches, the role of planners, and uncovering weaknesses and ethical issues in the planning process. Conclusions drawn from the discussion are: 1) Six key actors are involved in preparing the RSS document; 2) Various approaches, including mixed scanning, comprehensive rationale, advocacy planning, and collaborative planning, are employed in the RSS preparation process in Bener Meriah; 3) All planning roles play a part in the RSS preparation process; and 4) Weaknesses in the document preparation process encompass inadequate data quality, unrealistic aspects of funding and human resources, and limited engagement of external stakeholders.

Prevalence and factors associated with contraceptive use among sexually active adolescent girls in 25 sub-Saharan African countries.

Various countries in sub-Saharan Africa have taken divergent steps toward achieving the Sustainable Development Goal's target of universal access to sexual and reproductive health-care services by 2030, particularly among sexually active adolescent girls who are at risk of unplanned pregnancies and sexually transmitted infections. However, because contraceptive use among sexually active adolescents remains unexplored in sub-Saharan Africa, the researchers intended to examine the prevalence and factors associated with contraceptive use among adolescent girls who had been sexually active in the previous four weeks. Cross-sectional data from the most recent demographic and health surveys of 25 sub-Saharan African countries on 16,442 sexually active adolescent girls were analyzed. In the analyses, descriptive statistics and multivariate binary logistic regression were used. Analyses were statistically significant at p<0.05. The overall prevalence of contraceptive use was 25.4%. Chad had the lowest prevalence (4%), while Namibia had the highest (60.5%). Over 90% of the countries studied had less than 50% contraceptive use among sexually active adolescent girls. Adolescent girls withhigher education were eight times more likely than those with no formal education to use contraception (aOR = 7.97, 95% Cl = 6.26-9.45). When compared to single adolescent girls, married adolescent girls were 66% less likely to use contraceptives (aOR = 0.34, 95% Cl = 0.31-0.36). Adolescent girls with two or more children were seven times more likely than those without a child to use contraceptives (aOR = 6.91, 95% Cl = 5.58-8.56). It is established that there exists a low prevalence of contraceptive use among adolescent girls in sub-Saharan Africa. As countries in the sub-region strive for universal access to reproductive health services, it is critical for the governments and civil societies in countries with low contraceptive use to strengthen mass education on the use of contraception among sexually active adolescents, with special emphasis on the less educated, married, and adolescent girls from poor households.

Assessment of the association between health problems and cooking fuel type, and barriers towards clean cooking among rural household people in Bangladesh

BackgroundIn low- and middle-income countries, households mainly use solid fuels like wood, charcoal, dung, agricultural residues, and coal for cooking. This poses significant public health concerns due to the emission of harmful particles and gases. To address these issues and support Sustainable Development Goals (SDGs), adopting cleaner cooking fuels like electricity and gas are acknowledged as a viable solution. However, access to these cleaner fuels is limited, especially in rural areas.MethodsThis study conducted a face-to-face survey with 1240 individuals in rural Bangladesh to explore the link between health issues and cooking fuel type, as well as barriers to transitioning to clean cooking. Using a convenient sampling technique across four divisions/regions, the survey gathered socio-demographic and health data, along with information on clean cooking barriers through a semi-structured questionnaire. Binary and multivariable logistic regression analyses were then employed to identify significant associations between cooking fuel type and health problems.ResultsThe study revealed that a majority of participants (73.3%) relied on solid fuel for cooking. The use of solid fuel was significantly correlated with factors such as lower education levels, reduced family income, location of residence, and the experience of health issues such as cough, chest pressure while breathing, eye discomfort, diabetes, asthma, and allergies. Economic challenges emerged as the foremost obstacle to the adoption of clean cooking, accompanied by other contributing factors.ConclusionThe use of solid fuel in rural Bangladeshi households poses substantial health risks, correlating with respiratory, eye, cardiovascular, and metabolic issues. Lower education and income levels, along with specific residential locations, were associated with higher solid fuel usage. Economic challenges emerged as the primary obstacle to adopting clean cooking practices. These findings emphasize the need for implementing strategies to promote clean cooking, address barriers, and contribute to achieving Sustainable Development Goal targets for health and sustainable energy access in Bangladesh.

Experiences of delivering and receiving mental healthcare in the acute hospital setting: a qualitative study

BackgroundRecent investment in UK liaison psychiatry services has focused on expanding provision for acute and emergency referrals. Little is known about the experiences of users and providers of these services. The aim of this study was to explore the experiences of users of acute liaison mental health services (LMHS) and those of NHS staff working within LMHS or referring to LMHS. A secondary aim was to explore the potential impact of a one-hour service access target on service delivery.MethodsCross-sectional qualitative study. Individual interviews were audio-recorded, transcribed verbatim and interpreted using framework analysis.ResultsService users reported mixed experiences of LMHS, with some reporting positive experiences and some reporting poor care. Most service users described the emergency department (ED) environment as extremely stressful and wished to be seen as quickly as possible. Staff described positive benefits of the one-hour access target but identified unintended consequences and trade-offs that affected other parts of the liaison service.ConclusionsThe assessment and treatment of people who attend ED with mental health problems needs to improve and particular attention should be given to the stressful nature of the ED environment for those who are extremely agitated or distressed.

Validation of N-Methylpyridinium as a Feasible Biomarker for Roasted Coffee Intake

Health-related nutritional human studies rely on the validity of dietary data provided by study participants. Reliable biomarkers for food intake help objectify data collected by food frequency questionnaires. They facilitate the monitoring of compliance with the study requirements, e.g., abstinence from food, help clean biased data, and remove non-compliant individuals. Biomarker candidates are often revealed by sophisticated metabolomics analyses of body fluids, e.g., urine or plasma, collected from case and control study populations. However, validation for using a biomarker candidate in real-life scenarios is seldomly executed. Coffee is a food item of high interest because of the abundance of bioactive compounds and the regularity of life-time consumption by a large part of the population. Coffee has been found to positively impact cardiovascular risk, type 2 diabetes, and cognitive decline. Coffee and its health implications, therefore, are of high interest. A suitable dietary biomarker for coffee consumption is desirable for the clear classification of study participants as coffee drinkers or non-coffee drinkers to enable correlation of physiological response to dietary habits, e.g., coffee consumption. Here, we propose the roast coffee compound N-methylpyridinium (NMP) as a promising biomarker of pragmatic use to distinguish a coffee drinker from a non-coffee drinker. NMP is an easily accessible analytical target from the plasma and urine matrix that can help determine precedent exposure to roasted coffee products. We review the published information on the coffee compound N-methylpyridinium in foods, coffee, and plasma/urine after coffee consumption, and evaluate the data in the context of the proposed food biomarker criteria “plausibility”, “time- and dose–response”, “robustness”, “reliability”, “stability”, “analytical performance”, and “reproducibility”. An additional data set is acquired to fill the gaps in the literature. In summary, we conclude that the abundance of NMP can serve as a reliable analytical tool to verify recent consumption of roasted coffee. The use of NMP appears limited to being qualitative, as NMP abundance in coffee and human biosamples is affected by several parameters, e.g., the roasting conditions and the volume and time of coffee consumed.

Personal care product use patterns in association with phthalate and replacement biomarkers across pregnancy

BackgroundHumans are exposed to phthalates, a class of non-persistent chemicals, through multiple products, including personal care and cosmetics. Associations between specific phthalates and product use have been inconsistent. However, determining these connections could provide avenues for exposure reduction.ObjectiveExamine the association between patterns of personal care product use and associations with phthalate and replacement biomarkers.MethodsIn the Human Placenta and Phthalates Study, 303 women were enrolled in early pregnancy and followed for up to 8 visits across gestation. At each visit, women completed a questionnaire about product use in the prior 24 hours and contributed urine samples, subsequently analyzed for 18 phthalate and replacement metabolites. At early, mid-, and late pregnancy, questionnaire responses were condensed and repeated metabolite concentrations were averaged. Latent class analysis (LCA) was used to determine groups of women with similar use patterns, and weighted associations between group membership and biomarker concentrations were assessed.ResultsLCA sorted women into groups which largely corresponded to: (1) low fragranced product use (16-23% of women); (2) fragranced product and low body wash use (22–26%); 3) fragranced product and low bar soap use (26–51%); and (4) low product use (7–34%). Monoethyl phthalate (MEP) urinary concentrations were 7–10% lower and concentrations of summed di(2-ethylhexyl) terephthalate metabolites were 15–21% lower among women in the “low fragranced product use” group compared to the population mean. Few other consistent associations between group and biomarker concentrations were noted.Impact statementPersonal care products and cosmetics are a known exposure source for phthalates and potentially represent one of the most accessible intervention targets for exposure reduction. However, in this analysis accounting for concurrent use and fragranced status of products, we did not find any use patterns that corresponded to universally lower levels.

Juggling access vs retention and academic performance: The experience of a lecturer teaching in an open, distance e-learning institution

In response to the growing number of people requiring access to higher education, the student numbers at distance education institutions grew significantly over the last decade (Unisa 2013; 2020). Unfortunately, many students who enrol at open distance learning institutions are not ready for the demands of distance e-learning. More than half of students enrolled at the open distance learning institution where this study was done drop out and the reasons have been well researched (Joubert and Snyman 2018; Mashile, Fynn, and Matoane 2020). It seems that universities’ responses to Sustainable Development Goal 4 (SDG 4.3 ‒ equal access to technical, vocational and higher education) (Unesco 2021) may unintentionally have created new vulnerabilities for the very group of people they have targeted for progress to end poverty, hunger and discrimination. As nearly a third of all students in South Africa are enrolled at Africa’s largest open distance learning institution (Unisa 2018), it becomes crucial not only to increase access, but simultaneously to prioritise student retention and academic performance. This raises the question: How can and should lecturers teaching at distance-education institutions optimise the online teaching and learning environment in order to bridge the gap between access targets and academic performance targets? Following an autoethnographic research design, I share my own experiences of teaching two year-modules of the Bachelor of Education (B.Ed) Foundation Phase programme offered via a continuous assessment (CA) approach. Two theoretical frameworks, namely the socio-critical model of Subotzky and Prinsloo (2011, 184), and Luna’s (2018) theory of layers of vulnerability guided my understanding of the challenges associated with distance learning as well as my research design. My study reveals that the promise of CA does not always convert to optimal performance, and that contextual factors in distance education have a powerful impact on academic achievement despite the effort made by lecturers.

Exercise, memory, and the hippocampus: Uncovering modifiable lifestyle reserve factors in refractory epilepsy

Physical exercise is an emerging target for improving cognition in aging and neurological disease. Due to the beneficial impact of exercise on hippocampal health and the vulnerability of the hippocampus in medication-resistant temporal lobe epilepsy (TLE), exercise could present a promising intervention in TLE. We investigated whether exercise engagement is associated with verbal memory function and hippocampal integrity in 29 young to middle-aged adults with refractory TLE and 21 demographically matched controls. Participants completed a self-reported questionnaire of weekly exercise, three tests of verbal memory, and a subset (n = 44) underwent structural MRI. Individuals with TLE self-reported lower exercise scores than controls across all levels of exercise intensity (p < 0.001). In TLE, greater exercise engagement was associated with better verbal memory (word-list recall and associative learning; rho = 0.46–0.47; ps FDR < 0.05), and with larger contralateral hippocampal volumes (rho = 0.61; p < 0.01). These effects remained significant when controlling for epilepsy-related and demographic factors. Within the limitations of a cross-sectional observational study, these findings suggest that exercise may be a cognitive reserve factor in TLE, potentially mitigating memory decline by enhancing contralateral hippocampal integrity. With future replication and longitudinal studies to clarify the causal pathways of these relationships, exercise holds promise as a low-cost, accessible, and modifiable lifestyle target for improving cognitive health in individuals with refractory TLE.

A Novel Target Biomarker could be Galectin-3 for the Diagnosis and Treatment of Intervertebral Disc Degeneration?

The process of disc degeneration represents an abnormal, cell-mediated response leading to progressive structural failure. A degenerated disc is one with structural breakdown accelerated or accompanied by signs of advanced aging. It tends to exhibit degenerative and aging changes earlier than other connective tissues in the body. Given the relationship between back pain and disc degeneration, it\'s considered clinically significant. The roles of Galectin-3 in brain development, within glial cells, and their interaction with other neural and invading cells in pathological conditions have been observed. Successful nerve regeneration via functional repair involves both internal and external factors such as neurons\' ability to rebuild axons, support for axonal growth, and accessible target tissues for re-innervation. The study evaluated the role of Galectin protein in tissue regeneration and its potential as a diagnostic marker in Lumbar Herniated Disc degeneration. It was conducted on a total of 50 individuals, including 29 LD trauma cases and 21 healthy subjects, at the Brain Surgery Clinic. Assessing the expression of two molecules in Lumbar disc degeneration, no significant difference was found in resistin levels between groups (p=0.853), whereas Galectin levels were significantly different between the Control and LD (Lumbar disc) groups (p&lt;0.001). Galectin protein secretion was found to be higher in the LD group compared to the control group. Early assessment of Galectin protein could p