Targeting Mycobacterium tuberculosis Biotin Protein Ligase (MtBPL) with Nucleoside-Based Bisubstrate Adenylation Inhibitors

Mycobacterium tuberculosis (Mtb), responsible for both latent and symptomatic tuberculosis (TB), remains the second leading cause of mortality among infectious diseases worldwide. Mycobacterial biotin protein ligase (MtBPL) is an essential enzyme in Mtb and regulates lipid metabolism through the post-translational biotinylation of acyl coenzyme A carboxylases. We report the synthesis and evaluation of a systematic series of potent nucleoside-based inhibitors of MtBPL that contain modifications to the ribofuranosyl ring of the nucleoside. All compounds were characterized by isothermal titration calorimetry (ITC) and shown to bind potently with KDs ≤ 2 nM. Additionally, we obtained high-resolution cocrystal structures for a majority of the compounds. Despite fairly uniform biochemical potency, the whole-cell Mtb activity varied greatly with minimum inhibitory concentrations (MIC) ranging from 0.78 to >100 μM. Cellular accumulation studies showed a nearly 10-fold enhancement in accumulation of a C-2'-α analogue over the corresponding C-2'-β analogue, consistent with their differential whole-cell activity

Parental Loss During Childhood: Increases the Likelihood of Anxiety and Depression in Adulthood

Loss is a normal part of life. However, it is important to understand the different types of loss that can occur. These include death, divorce, loss of parental rights, and incarceration. While all of these can be traumatic, experiencing the loss of a parent can make it even more difficult, especially if you lose the parent during childhood. This thesis paper focuses on highlighting the findings from a meta-analysis of studies examining different types of loss. The effects of the loss will be discussed as well as how they overlap. I completed this meta-analysis to bring to attention, the effects of losing a parent, regardless of how the loss occurred. I also wanted to provide evidence of how important it is to intervene in a child’s life as early as possible following the occurrence of a loss. Findings reveal that by intervening early, the likelihood of later anxiety and depression in adulthood can be lessened

Cervical cancer diagnosis and treatment delays in the developing world: Evidence from a hospital-based study in Zambia

The dataset presented in this article is secondary data obtained from the registry unit of the only cancer treatment Centre in Zambia, the Cancer Diseases Hospital (CDH) in Lusaka. Information relating to patients with a maiden diagnosis of cervical cancer presenting to CDH is outlined in the data. The data is a set of patient demographics, relevant clinical information and the clinical referral channel obtained from patient case files stored at CDH

Dataset on diagnostic errors of Ear, Nose and Throat (ENT) diseases

This data assessed the diagnosis outcomes that were made by the patient’s non-ENT clinicians at the referral health facilities and those that were made by ENT specialists at the hospital patients were referred to. The ENT specialist's diagnoses were made after further investigation and this diagnosis was the definitive or final diagnosis. Furthermore, where there was an agreement between the diagnosis made by the non-ENT clinicians and the ENT specialists, it was referred to as a ‘match’ and differences in diagnosis were classified as a 'mismatch'.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Spatial and spatio-temporal methods for mapping malaria risk: a systematic review

BACKGROUND:Approaches in malaria risk mapping continue to advance in scope with the advent of geostatistical techniques spanning both the spatial and temporal domains. A substantive review of the merits of the methods and covariates used to map malaria risk has not been undertaken. Therefore, this review aimed to systematically retrieve, summarise methods and examine covariates that have been used for mapping malaria risk in sub-Saharan Africa (SSA). METHODS:A systematic search of malaria risk mapping studies was conducted using PubMed, EBSCOhost, Web of Science and Scopus databases. The search was restricted to refereed studies published in English from January 1968 to April 2020. To ensure completeness, a manual search through the reference lists of selected studies was also undertaken. Two independent reviewers completed each of the review phases namely: identification of relevant studies based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, data extraction and methodological quality assessment using a validated scoring criterion. RESULTS:One hundred and seven studies met the inclusion criteria. The median quality score across studies was 12/16 (range: 7-16). Approximately half (44%) of the studies employed variable selection techniques prior to mapping with rainfall and temperature selected in over 50% of the studies. Malaria incidence (47%) and prevalence (35%) were the most commonly mapped outcomes, with Bayesian geostatistical models often (31%) the preferred approach to risk mapping. Additionally, 29% of the studies employed various spatial clustering methods to explore the geographical variation of malaria patterns, with Kulldorf scan statistic being the most common. Model validation was specified in 53 (50%) studies, with partitioning data into training and validation sets being the common approach. CONCLUSIONS:Our review highlights the methodological diversity prominent in malaria risk mapping across SSA. To ensure reproducibility and quality science, best practices and transparent approaches should be adopted when selecting the statistical framework and covariates for malaria risk mapping. Findings underscore the need to periodically assess methods and covariates used in malaria risk mapping; to accommodate changes in data availability, data quality and innovation in statistical methodology

Dataset evaluating the treatment timeliness of cervical cancer in Zambia

Cervical cancer is the fourth most common cancer diagnosed among women globally. Effective screening routines and early detection are vital in reducing its disease burden and mortality. Several factors can influence the timely detection and treatment of cervical cancer, especially in low middle-income countries where the burden of this disease is highest. The data presented in this paper relates to the research article “Cervical cancer diagnosis and treatment delays in the developing world: Evidence from a hospital-based study in Zambia”. The raw and analysed data include the studied patients’ social demographic factors, clinical data concerning the stage and histological subtype of cancer, dates at which the various activities within the cancer treatment pathway occurred and delays to definitive treatment of cervical cancer at Zambia's only cancer treatment facility. Detailing delays to the treatment of cervical cancer allows recognition of specific points in the cancer treatment pathway requiring intervention to effectively improve cancer care and reduce the morbidity and mortality associated with the disease