bluuebunny/crossref_metadata_2025_split huggingface dataset:
Field comparison of STANDARD™ Q Filariasis Antigen Test (QFAT) with Bioline Filariasis Test Strip (FTS) for the detection of Lymphatic Filariasis in Samoa, 2023
Authors: Scott Jessica L , Mayfield Helen J , Sinclair Jane , Martin Beatris Mario , Howlett Maddison , Muttucumaru Ramona , Won Kimberly Y , Thomsen Robert , Viali Satupaitea , Tofaeono-Pifeleti Rossana , Graves Patricia M , Lau Colleen L 
Published: April 2024

AbstractBackgroundTo monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag ofWuchereria bancrofti, the causative agent of LF, under field conditions.Methodology/Principal FindingsDuring an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from Ag-positive samples. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29% and 30% by QFAT. Concordance between the two tests was 94% (Kappa=0.85). Of the 105 Mf slides available, 38.1% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability.Conclusion/SignificanceQFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field conditions.Author SummaryLymphatic filariasis (LF) is a debilitating tropical disease caused by an infection with parasitic filarial worms that are transmitted by mosquitoes. Long-term infection can lead to stigmatising chronic conditions like lymphoedema and elephantiasis. The World Health Organization initiated the global programme to eliminate lymphatic filariasis (GPELF) in 2000, which focuses on the mass administration of anti-LF drugs to stop transmission in endemic countries. However, to monitor the success of this programme and to make informed decisions to stop costly mass drug administrations, it is crucial to have access to accurate and reliable rapid diagnostics. Here, we evaluated the performance of a new rapid antigen test called the Q Filariasis antigen test and compared it to the currently recommended filariasis test strip under field conditions in Samoa. This study showed that the new rapid test could be a suitable alternative to the currently recommended test for use in GPELF-related activities with more user-friendly features.
Distal Protein-Protein Interactions Contribute to SARS-CoV-2 Main Protease Substrate Binding and Nirmatrelvir Resistance
Authors: Lewandowski Eric M. , Zhang Xiujun , Tan Haozhou , Jaskolka-Brown Aiden , Kohaal Navita , Frazier Aliaksandra , Madsen Jesper J. , Jacobs Lian M.C. , Wang Jun , Chen Yu 
Published: April 2024

AbstractSARS-CoV-2 main protease, Mpro, is responsible for the processing of the viral polyproteins into individual proteins, including the protease itself. Mprois a key target of anti-COVID-19 therapeutics such as nirmatrelvir (the active component of Paxlovid). Resistance mutants identified clinically and in viral passage assays contain a combination of active site mutations (e.g. E166V, E166A, L167F), which reduce inhibitor binding and enzymatic activity, and non-active site mutations (e.g. P252L, T21I, L50F), which restore the fitness of viral replication. Although the mechanism of resistance for the active site mutations is apparent, the role of the non-active site mutations in fitness rescue remains elusive. In this study, we use the model system of a Mprotriple mutant (L50F/E166A/L167F) that confers not only nirmatrelvir drug resistance but also a similar fitness of replication compared to the wild-type both in vitro and in vivo. By comparing peptide and full-length Mproprotein as substrates, we demonstrate that the binding of Mprosubstrate involves more than residues in the active site. In particular, L50F and other non-active site mutations can enhance the Mprodimer-dimer interactions and help place the nsp5-6 substrate at the enzyme catalytic center. The structural and enzymatic activity data of MproL50F, L50F/E166A/L167F, and others underscore the importance of considering the whole substrate protein in studying Mproand substrate interactions, and offers important insights into Mprofunction, resistance development, and inhibitor design.
An exploratory study on becoming a traditional spiritual healer among Baganda in Central Uganda
Authors: Sekagya Yahaya H. K. , Muchunguzi Charles , Unnikrishnan Payyappallimana , Mulogo Edgar M. 
Published: April 2024

AbstractTraditional medicinal knowledge and healing practices of indigenous spiritual healers play important roles in health care, and contribute towards achieving Universal Health Care. Traditional spiritual healers (TSHs) are grouped into three categories. One category of Baganda TSHs,Balubaale, engage ancestral spirits during health management.Balubaaleare socially significant but not legally accepted. Their initiation and training practices have not been documented in Uganda. The study purpose was to understand and establish the training of traditional spiritual healers. Twelve (10M, 2F); practicing TSHs in Central Uganda were purposively selected and recruited between 15thJuly 2019 and 29thApril 2020, and were prospectively interacted with for 24 months. Transcribed data was coded and thematically analyzed using ATLAS ti. 22 computer software and presented based on an inductive approach. Findings show key areas of TSHs training include connecting with ancestral spirits and the spiritual powers of non-materials and materials such as living and non-living things through rituals. Spiritual healers train in diagnosis and health management based on ancestral spirits and they finally pass out in a communal ceremony witnessed by family and community members. We conclude that TSHs undergo training and are supervised and supported by experienced spiritualists, family and the community. We recommend similar studies among other ethnic groups to contextualize the process of becoming a TSH, compare and harmonize findings to facilitate inter-medical systems communication and policy considerations.
By the numbers and in their own words: A mixed methods study of unmet needs and humanitarian inclusion of older Syrian refugees in Lebanon
Authors: Al Omari Sarah , Honein-AbouHaidar Gladys , Mehio Sibai Abla 
Published: April 2024

AbstractOlder people constitute an overlooked vulnerable population in humanitarian crises. Lebanon is a small country that hosts the largest number of refugees per capita in the world. With exacerbating socioeconomic conditions, exclusionary policies against refugees, and a fragmented humanitarian system, the status of older Syrian refugees (OSRs) requires special attention. This study aimed to explore OSRs’ unmet needs, coping strategies, available humanitarian services, and some indicators of the humanitarian inclusion standards focusing on the shelter, health, nutrition and food security, and water, sanitation and hygiene sectors. We conducted a convergent mixed-methods study between December 2021 and March 2022 in the North and Bekaa, including a cross-sectional survey with 461 participants and 14 semi-structured interviews. Results show that OSRs lived in inappropriate shelters (cold, leaking rainwater), especially in informal tented settlements. High rent prices pushed refugee households with elderly to prioritize paying rent at the expense of other needs such as food and medication, particularly when food cash transfer is the sole source of income, jeopardizing food security and intake. Access to dignifying and accessible bathing facilities was compromised in ITSs with shared facilities. Substantial medical costs hindered OSRs access to healthcare such as surgeries. Due to the crisis, chronic medications are not always available in dispensaries for subsidized cost, pushing OSRs to non-compliance and selling food assistance to buy medications. Soaring fuel prices hindered OSRs access to heating and transportation to receive healthcare. No efforts were reported in collecting data on OSRs’ needs, targeting them with information on services, or soliciting feedback for programming, especially in the absence of any age-tailored interventions. Findings shed light on the precarious living conditions of OSRs in Lebanon and add to the body of evidence documenting their invisibility to the humanitarian response. An age-inclusive response is needed through holistic, tailored, and sustainable interventions.
Shared genetic etiology between hypothyroidism and complex diseases: a large-scale genome-wide cross-trait analysis
Authors: Li Shifang , Gong Meijiao 
Published: April 2024

AbstractHypothyroidism is a common condition of thyroid hormone insufficiency, and there is growing evidence of its link with additional diseases. It remains unclear whether these associations share a common genetic architecture. To address this gap, by leveraging summary-level genetic data from the UK Biobank of hypothyroidism and the FinnGen study of three complex diseases (sarcoidosis, chronic sinusitis, and interstitial lung disease (ILD) endpoints), we evaluated their shared genetic etiology. A significant genetic correlation was found between hypothyroidism and the three diseases. Cross-trait analyses utilizing the MTAG and CPASSOC models revealed 12, 2, and 12 shared loci between hypothyroidism and chronic sinusitis, ILD endpoints, and sarcoidosis, respectively. The SNP heritability enrichment analysis across 37 tissues and 136 cell types at the single-cell level identified candidate tissues and cell types that were shared by the diseases. Interestingly, we found a positive genetic relationship between these four diseases and central memory CD4+ T cells in the blood, supported by strong colocalization evidence (posterior probability >0.9). Mendelian randomization and colocalization analysis showed a link between hypothyroidism and sarcoidosis with two genes (DOCK6 and CD226) in the blood. Furthermore, among the hypothyroidism-driven plasma proteins, RIPK2 was identified as a potentially actionable mediator of hypothyroidism’s effect on ILD endpoints. Overall, our findings contribute to improving our understanding of the molecular basis of these diseases’ intricate relationships, as well as providing insights toward disease prevention and comorbidity management.
Generative Modeling of the Circle of Willis Using 3D-StyleGAN
Authors: Aydin Orhun Utku , Hilbert Adam , Koch Alexander , Lohrke Felix , Rieger Jana , Tanioka Satoru , Frey Dietmar 
Published: April 2024

AbstractThe circle of Willis (CoW) is a network of cerebral arteries with significant inter-individual anatomical variations. Deep learning has been used to characterize and quantify the status of the CoW in various applications for the diagnosis and treatment of cerebrovascular disease. In medical imaging, the performance of deep learning models is limited by the diversity and size of training datasets. To address medical data scarcity, generative adversarial networks (GANs) have been applied to generate synthetic vessel neuroimaging data. However, the proposed methods produce synthetic data with limited anatomical fidelity or downstream utility in tasks concerning vessel characteristics.We adapted the StyleGANv2 architecture to 3D to synthesize Time-of-Flight Magnetic Resonance Angiography (TOF MRA) volumes of the CoW. For generative modeling, we used 1782 individual TOF MRA scans from 6 open source datasets. To train the adapted 3D StyleGAN model with limited data we employed differentiable data augmentations and used mixed precision and a cropped region of interest of size 32×128×128 to tackle computational constraints. The performance was evaluated quantitatively using the Fréchet Inception Distance (FID), MedicalNet distance (MD) and Area Under the Curve of the Precision and Recall Curve for Distributions (AUC-PRD). Qualitative analysis was performed via a visual Turing test. We demonstrated the utility of generated data in a downstream task of multiclass semantic segmentation of CoW arteries. Vessel segmentation performance was assessed quantitatively using the Dice coefficient and the Hausdorff distance.The best-performing 3D StyleGANv2 architecture generated high-quality and diverse synthetic TOF MRA volumes (FID: 12.17, MD: 0.00078, AUC-PRD: 0.9610). Multiclass vessel segmentation models trained on synthetic data alone achieved comparable performance to models trained using real data in most arteries.In conclusion, generative modeling of the Circle of Willis via synthesis of 3D TOF MRA data paves the way for generalizable deep learning applications in cerebrovascular disease. In the future, the extensions of the provided methodology to other medical imaging problems or modalities with the inclusion of pathological datasets has the potential to advance the development of more robust models for clinical applications.
Comparing microbiological and molecular diagnostic tools for the surveillance of anthrax
Authors: Ochai Sunday O. , Hassim Ayesha , Dekker Edgar H. , Magome Thuto , Lekota Kgaugelo E. , Makgabo S. Marcus , de Klerk-Loris Lin-Mari , van Schalkwyk O. Louis , Kamath Pauline L. , Turner Wendy C. , van Heerden Henriette 
Published: April 2024

AbstractThe diagnosis of anthrax, a zoonotic disease caused byBacillus anthraciscan be complicated by detection of closely related species. Conventional diagnosis of anthrax involves microscopy, culture identification of bacterial colonies and molecular detection. Genetic markers used are often virulence gene targets such asBacillus anthracisprotective antigen (pagA,as also called BAPA, occurring on plasmid pXO1), lethal factor (lef,on pXO1), as well as chromosomal (Ba-1) and plasmid (capsule-encodingcapB/C, located on pXO2). Combinations of genetic markers using real-time/quantitative polymerase chain reaction (qPCR) are used to confirmB. anthracisfrom culture but can also be used directly on diagnostic samples to avoid propagation and its associated biorisks and for faster identification. We investigated how the presence of closely related species could complicate anthrax diagnoses with and without culture to standardise the use of genetic markers using qPCR for accurate anthrax diagnosis. Using blood smears from 2012-2020 from wildlife mortalities (n=1708) in Kruger National Park in South Africa where anthrax is endemic, we contrasted anthrax diagnostic results based on qPCR, microscopy, and culture. From smears, 113/1708 grew bacteria in culture, from which 506 isolates were obtained. Of these isolates, only 24.7% (125 isolates) were positive forB. anthracisbased on genetic markers or microscopy. However, among these, merely 4/125 (3.2%) were confirmedB. anthracisisolates (based on morphology, microscopy, and sensitivity testing to penicillin and gamma-phage) from the blood smear, likely due to poor survival of spores on stored smears. This study identifiedB. cereus sensu lato, which includedB. cereusandB. anthracis, Peribacillus spp., andPriestia spp.clusters usinggyrB gene in selected bacterial isolates positive for BAPA. Using qPCR on blood smears, 52.1% (890 samples) tested positive forB. anthracisbased on one or a combination of genetic markers which included the 25 positive controls. Notably, the standardlefprimer set displayed the lowest specificity and accuracy. Interestingly, various marker combinations, such as Ba-1+capB, BAPA+capB, Ba-1+BAPA+capB+lef, and BAPA+lef+capB, all demonstrated 100.0% specificity and 98.7% accuracy, while maintaining a sensitivity of 96.6%. The BAPA+lef+Ba-1 combination showed 100% specificity, sensitivity, and accuracy. Using Ba-1+BAPA+lef+capB, as well as Ba-1+BAPA+lefwith molecular diagnosis accurately detectsB. anthracisin the absence of bacterial culture. Systematically combining microscopy and molecular markers holds promise for notably reducing false positives, thereby significantly enhancing the detection and surveillance of diseases like anthrax in southern Africa and beyond and reducing the need for propagation of the bacteria in culture.
VIRAL LOAD SUPPRESSION AND ASSOCIATED FACTORS AMONG HIV-INFECTED PATIENTS ON SECOND-LINE ANTIRETROVIRAL THERAPY AT PUBLIC HEALTH FACILITIES OF WEST GUJI, GUJI AND BORENA ZONES, SOUTHERN ETHIOPIA: FACILITY BASED CROSS-SECTIONAL STUDY
Authors: Hailu Digafe , Jara Dube , Edin Alo , Awol Abdurazak , Ayele Angefa , Fekadu Yohannes , Endale Dereje , Gelchu Miesa , Lemma Kebebew 
Published: April 2024

AbstractBackgroundEthiopia is one of the nation’s most severely impacted by HIV, with an estimated 700,000 people living with HIV/AIDS. Hence, many health facilities were providing second-line antiretroviral therapy, however little was known about viral load suppression among second-line users. This study aimed to assess the proportion of viral load suppression and associated factors among HIV-infected patients on second-line antiretroviral therapy at public health facilities of west Guji, Guji and Borena zones, Southern Ethiopia.MethodsA facility-based cross-sectional study was conducted among 256 HIV-infected patients on second-line antiretroviral therapy from January 1, 2019, to December 30, 2022, by using census after obtaining ethical clearance from Bule Hora University ethical review committee. Data were extracted using a structured, pre-tested checklist, entered into the EPI data version 3.1.0, and exported to SPSS version 25 for analysis. The proportion of viral load suppression was determined. A binary logistic regression model was fitted to identify factors associated with viral load suppression. Statistical significance was declared at a 95% confidence interval (CI) with a P-value <0.05.ResultsThis study revealed that the proportion of viral load suppression among HIV-infected patients on second-line antiretroviral therapy was 73.8% (95% CI, 68.0–79.1). Those who missed the second-line antiretroviral regimen [AOR = 0.315, 95% CI (0.162–0.612)], a baseline viral load count of <10,000 copies/mm3 [AOR = 2.291, 95% CI (1.216-4.316)], and a baseline body mass index of ≥18.5 kg/m2 [AOR = 2.438, 95% CI (1.098–5.414)] were significantly associated with viral load suppression.ConclusionsThe proportion of patients with viral load suppression fell below the WHO’s and national level. Viral load suppression was significantly influenced by missed second-line antiretroviral doses, a baseline viral load count of <10,000 copies/ml, and a baseline body mass index of ≥18.5 kg/m2. Hence interventions targeting counseling to patients that missed their antiretroviral therapy, keeping patient’s viral load to be less than 10,000 copies/ml through adequate adherence counseling among second-line antiretroviral therapy were recommended.
Factors influencing survival outcomes in patients with stroke in Zimbabwe: A 12-month longitudinal study
Authors: Kaseke Farayi , Gwanzura Lovemore , Musarurwa Cuthbert , Gori Elizabeth , Nyengerai Tawanda , Kaseke Timothy , Stewart Aimee 
Published: April 2024

AbstractBackgroundIn this longitudinal study, we aimed to determine factors influencing survival outcomes among patients with stroke over a 12-month period. The investigation sought to uncover influential determinants to enhance the precision of prognostic assessments and inform targeted interventions for individuals affected by strokes.MethodsEmploying a longitudinal study design, participants were observed for 12 months from baseline, censoring survivors at the endpoint. The dataset originated from a comprehensive study involving stroke patients treated at three referral hospitals in Zimbabwe: Parirenyatwa, Sally Mugabe, and Chitungwiza Central Hospital. The primary outcome variable, the duration of survival until death, was measured in days from the initiation of stroke treatment. Gompertz parametric regression analysis was utilized for data modeling following Accelerated Failure Time (AFT) model diagnostics.ResultsIn our study, 188 stroke patients were enrolled at baseline. However, 51 patients were excluded from the analysis due to either missing information or loss to follow-up. Among the remaining 137 patients who were tracked over a 12-month period, 42% were censored, and 58% were deceased. Individuals utilizing ’Free Service (older than 65/pensioners/retirees)’ hospital bill payment methods showed a decreased risk of death (HR: 0.4, 95% CI: 0.20, 0.80), suggesting a protective effect compared to cash paying patients. Those with a secondary school level education displayed a significantly lower risk of death (HR: 0.2, 95% CI: 0.04, 0.69) compared to those without formal education. Age was a significant factor, with individuals aged 45-65 and those over 65 years showing higher adjusted hazard ratios (HR: 4.9, 95% CI: 1.80, 13.25; HR: 5.5, 95% CI: 1.92, 15.95, respectively) relative to those below 45 years of age. Housing status revealed a protective effect for those residing with parents/relatives (adjusted HR: 0.4, 95% CI: 0.20, 0.66), while individuals with a ’Very severe’ functional outcome showed an increased hazard (adjusted HR: 4.9, 95% CI: 1.12, 21.33).ConclusionThe study findings demonstrate that hospital bill payment methods, housing status, educational attainment, functional outcome, and age significantly affect survival outcomes among stroke patients. This highlights the need to consider socio-demographic and clinical variables in the development of prognostic assessments and targeted interventions for individuals recovering from stroke.