Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of Trachoma in 47 Administrative Districts of Zambia: Results of 32 Population-Based Prevalence Surveys

ABSTRACT Purpose: A number of previous administrative-district-level baseline trachoma prevalence estimates in Zambia required verification. We used methodologies and systems for trachoma surveys considered to represent international best practice in order to generate reliable estimates of the prevalence of trachoma. Methods: Between March 2016 and July 2017, we undertook 32 population-based prevalence surveys covering 47 administrative districts. In each of the 32 evaluation units (EUs), we selected 31 households in each of 24 clusters. In selected households, trained, certified graders examined all residents aged 1 year and above for evidence of trachomatous inflammation—follicular (TF) and trichiasis. In eyes that had trichiasis, the presence or absence of trachomatous scarring (TS) was recorded, and the subject was asked about previous trichiasis management recommendations from health workers. Results: Five EUs (encompassing seven administrative districts) had prevalence estimates of trichiasis+TS unknown to the health system in ≥15-year-olds of ≥0.2%, and require public-health-level implementation of trichiasis surgery services. Eleven EUs (encompassing 16 administrative districts) had TF prevalence estimates in 1–9-year-olds of ≥5%. Intervention with the A, F and E components of the SAFE strategy for trachoma elimination is required for nearly 1.5 million people. Conclusion: Trachoma is a public health problem in some parts of Zambia. The Ministry of Health will continue to partner with other stakeholders to implement the multi-sectoral SAFE strategy. Consideration should be given to re-surveying other suspected-endemic administrative districts in which surveys using older methodologies returned TF prevalence estimates ≥5%.
The immunomodulatory effects of measles‐mumps‐rubella vaccination on persistence of heterologous vaccine responses

It is proposed that measles‐containing vaccines have immunomodulatory effects which include a reduction in all‐cause childhood mortality. The antibody response to heterologous vaccines provides a means to explore these immunomodulatory effects. This is the first study to investigate the influence of measles‐mumps‐rubella (MMR) vaccine on the persistence of antibodies to a broad range of heterologous infant vaccinations given in the first year of life. In total, 319 children were included in the study. All infants received routine vaccinations at 6 weeks, 4 and 6 months of age. At 12 months of age, 212 children were vaccinated with MMR and Haemophilus influenzae type b‐meningococcus C (Hib‐MenC) vaccines while the remaining 99 children had not yet received these vaccines. In the MMR/Hib‐MenC‐vaccinated group, blood was taken 28 ± 14 days after receiving these vaccines. Antibodies against diphtheria, tetanus, pertussis [pertussis toxin (PT), filamentous hemagglutinin, pertactin], poliomyelitis (type 1, 2, 3) and 13 pneumococcal serotypes were measured. Seroprotection rates and geometric mean antibody concentrations were compared between MMR/MenC‐Hib‐vaccinated and MMR/MenC‐Hib‐naïve participants. In the final analysis, 311 children were included. Seroprotection rates were lower in MMR/Hib‐MenC‐vaccinated children against PT and pneumococcal serotype 19A. After adjustment for prespecified factors, MMR/Hib‐MenC‐vaccinated infants had significantly higher antibody concentrations against tetanus (likely explained by a boosting effect of the carrier protein, a tetanus toxoid), while for the other vaccine antigens there was no difference in antibody concentrations between the two groups. MMR vaccination given at 12 months of age in a developed country does not significantly influence antibody concentrations to heterologous vaccines received in the first year of life.
Deep Learning for Image Quality Assessment of Fundus Images in Retinopathy of Prematurity

Accurate image-based medical diagnosis relies upon adequate image quality and clarity. This has important implications for clinical diagnosis, and for emerging methods such as telemedicine and computer-based image analysis. In this study, we trained a convolutional neural network (CNN) to automatically assess the quality of retinal fundus images in a representative ophthalmic disease, retinopathy of prematurity (ROP). 6,043 wide-angle fundus images were collected from preterm infants during routine ROP screening examinations. Images were assessed by clinical experts for quality regarding ability to diagnose ROP accurately, and were labeled "acceptable" or "not acceptable. " The CNN training, validation and test sets consisted of 2,770 images, 200 images, and 3,073 images, respectively. Test set accuracy was 89.1%, with area under the receiver operating curve equal to 0.964, and area under the precision-recall curve equal to 0.966. Taken together, our CNN shows promise as a useful prescreening method for telemedicine and computer-based image analysis applications. We feel this methodology is generalizable to all clinical domains involving image-based diagnosis.
Hormone therapy use and breast tissue DNA methylation: analysis of epigenome wide data from the normal breast study

ABSTRACT Hormone therapy (HT) is associated with increased risk of breast cancer, strongly dependent on type, duration, and recency of use. HT use could affect cancer risk by changing breast tissue transcriptional programs. We hypothesize that these changes are preceded by changes in DNA methylation. To explore this hypothesis we used histologically normal-appearing breast tissue from the Normal Breast Study (NBS). DNA methylation β-values were obtained using the Illumina HumanMethylation 450 BeadChips for 90 samples including all NBS-participants who used HT within 5 y before surgery. Data were analyzed using the reference-free cell mixture method. Cancer Genome Atlas (TCGA) mRNA-Seq data were used to assess correlation between DNA methylation and gene expression. We identified 527 CpG sites in 403 genes that were associated with ever using HT at genome wide significance (FDR q < 0.05), of these, 68 sites were also significantly associated with duration of use or recency of use. Twelve sites reached significance in all analyses one of which was cg01382688 in ARHGEF4 (p < 1.2x10−7). Mutations in ARHGEF4 have been reported in breast tumors, but this is the first report of possible breast cancer-related DNA methylation changes. In addition, 22 genes included more than one significant CpG site and a majority of these sites were significantly correlated with gene expression. Although based on small numbers, these findings support the hypothesis that HT is associated with epigenetic alterations in breast tissue, and identifies genes with altered DNA methylation states which could be linked to breast cancer development.
Pre-clinical assessment of a water-in-fluorocarbon emulsion for the treatment of pulmonary vascular diseases

Abstract Hypoxic pulmonary vasoconstriction (HPV) is a well-characterized vascular response to low oxygen pressures and is involved in life-threatening conditions such as high-altitude pulmonary edema (HAPE) and pulmonary arterial hypertension (PAH). While the efficacy of oral therapies can be affected by drug metabolism, or dose-limiting systemic toxicity, inhaled treatment via pressured metered dose inhalers (pMDI) may be an effective, nontoxic, practical alternative. We hypothesized that a stable water-in-perfluorooctyl bromide (PFOB) emulsion that provides solubility in common pMDI propellants, engineered for intrapulmonary delivery of pulmonary vasodilators, reverses HPV during acute hypoxia (HX). Male Sprague Dawley rats received two 10-min bouts of HX (13% O2) with 20 min of room air and drug application between exposures. Treatment groups: intrapulmonary delivery (PUL) of (1) saline; (2) ambrisentan in saline (0.1 mg/kg); (3) empty emulsion; (4) emulsion encapsulating ambrisentan or sodium nitrite (NaNO2) (0.1 and 0.5 mg/kg each); and intravenous (5) ambrisentan (0.1 mg/kg) or (6) NaNO2 (0.5 mg/kg). Neither PUL of saline or empty emulsion, nor infusions of drugs prevented pulmonary artery pressure (PAP) elevation (32.6 ± 3.2, 31.5 ± 1.2, 29.3 ± 1.8, and 30.2 ± 2.5 mmHg, respectively). In contrast, PUL of aqueous ambrisentan and both drug emulsions reduced PAP by 20–30% during HX, compared to controls. IL6 expression in bronchoalveolar lavage fluid and whole lung 24 h post-PUL did not differ among cohorts. We demonstrate proof-of-concept for delivering pulmonary vasodilators via aerosolized water-in-PFOB emulsion. This concept opens a potentially feasible and effective route of treating pulmonary vascular pathologies via pMDI.
Toward a consensual taxonomy of emotions

ABSTRACT In this article, I chart certain origins of the science of emotion back to the cognitive revolution. I then highlight new developments in the field – the influences of emotion upon cognition, the focus on over 20 emotions, the expanding emphasis on positive emotion, and an abiding interest in the functions emotions serve. I close by arguing for the need for the field to move toward a conceptual taxonomy of emotions, to move beyond decades of terminological debates about what emotions are to a convergent effort to understand what emotions do for people.
Maternal hair cortisol levels affect neonatal development among women conceiving with assisted reproductive technology

ABSTRACT Objective: To compare stress levels throughout pregnancy in women who had conceived using assisted reproductive technology (ART) and women who had conceived naturally and somatometric values for infants. Background: Pregnant women who have received ART are exposed to high levels of stress. Methods: Ninety-one women attending a prenatal appointment at a Health Centre (Granada, Spain), and their 91 newborns participated in this study: 69 women conceiving naturally and 22 conceiving using ART. Assessment consisted of measuring hair cortisol levels, the Prenatal Distress Questionnaire, the Perceived Stress Scale and the Symptom Checklist-90-Revised. Results: Women conceiving using ART had higher cortisol levels in the first trimester than women who conceived naturally. In the third trimester, women who used ART reported higher levels of perceived stress than those who had conceived naturally. Maternal cortisol levels in the first trimester explained 32% of the variance in neonatal head circumference in the group of women who had conceived using ART. Conclusions: Women who had conceived using ART showed higher levels of cortisol in the first trimester and higher levels of perceived stress in the third trimester than women who had conceived naturally, rendering them more vulnerable to adverse outcomes. Maternal cortisol predicted the infants’ development.
Bias‐reduced and separation‐proof GEE with small or sparse longitudinal binary data

Generalized estimating equation (GEE) is a popular approach for analyzing correlated binary data. However, the problems of separation in GEE are still unknown. The separation created by a covariate often occurs in small correlated binary data and even in large data with rare outcome and/or high intra‐cluster correlation and a number of influential covariates. This paper investigated the consequences of separation in GEE and addressed them by introducing a penalized GEE, termed as PGEE. The PGEE is obtained by adding Firth‐type penalty term, which was originally proposed for generalized linear model score equation, to standard GEE and shown to achieve convergence and provide finite estimate of the regression coefficient in the presence of separation, which are not often possible in GEE. Further, a small‐sample bias correction to the sandwich covariance estimator of the PGEE estimator is suggested. Simulations also showed that the GEE failed to achieve convergence and/or provided infinitely large estimate of the regression coefficient in the presence of complete or quasi‐complete separation, whereas the PGEE showed significant improvement by achieving convergence and providing finite estimate. Even in the presence of near‐to‐separation, the PGEE also showed superior properties over the GEE. Furthermore, the bias‐corrected sandwich estimator for the PGEE estimator showed substantial improvement over the standard sandwich estimator by reducing bias in estimating type I error rate. An illustration using real data also supported the findings of simulation. The PGEE with bias‐corrected sandwich covariance estimator is recommended to use for small‐to‐moderate size sample (N ≤ 50) and even can be used for large sample if there is any evidence of separation or near‐to‐separation.
Development of rule-based eye-hand-decoupling in children and adolescents

ABSTRACT In the present study, we characterize how the ability to decouple guiding visual information from a motor action emerges during childhood and adolescence. Sixty-two participants (age range 8–15 yrs.) completed two eye-hand coordination tasks. In a direct interaction task, vision and motor action were in alignment, and participants slid their finger along a vertical touch screen to move a cursor from a central target to one of four peripheral targets. In an eye-hand-decoupled task, eye and hand movements were made in different planes and cursor feedback was 180° reversed. We analyzed whether movement planning, timing and trajectory variables differed across age in both task conditions. There were no significant relationships between age and any movement planning, timing, or execution variables in the direct interaction task. In contrast, in the eye-hand-decoupled task, we found a relationship between age and several movement planning and timing variables. In adolescents (13–15 yrs.), movement planning and timing was significantly shorter than that of young children (8–10 yrs.). Eye-hand-decoupled maturation emerged mainly during late childhood (11–12 yrs.). Notably, we detected performance differences between young children and adolescents exclusively during the eye-hand decoupling task which required the integration of rule-based cognitive information into the motor action. Differences were not observed during the direct interaction task. Our results quantify an important milestone for eye-hand-decoupling development in late childhood, leading to improved rule-based motor performance in early adolescence. This eye-hand-decoupling development may be due to frontal lobe development linked to rule-based behavior and the strengthening of fronto-parietal networks.
Quantitative and thematic analysis of complaints by clients against clinical veterinary practitioners in New Zealand

ABSTRACT Aims: To provide a descriptive analysis of all notifications and complaints received by the Veterinary Council of New Zealand (VCNZ) during 1992–2016 and to use a thematic analysis of complaints made by clients to the VCNZ during 2013–2015 to determine the underlying reasons for their complaints. Methods: A mixed methods approach was used. Notifications and complaints against veterinarians between 1992–2016 (n=1218) were summarised based on complaint categories and by gender of the veterinarian respondents, the number of years registered with the VCNZ and the animal species to which the complaint related. In-depth thematic analysis was made of the content of clients’ complaints between 2013–2015 (n=141) to identify details of the key themes and subthemes underlying the complaints. Results: The VCNZ categorised 595/959 (62.0%) of the complaints made between 1992–2016 as related to technical competency, and 308/959 (32%) to professional behaviour. Of the 1,218 complaints, 818 (67.2%) were not investigated or were dismissed, and 18 (1.5%) cases were upheld due to technical competency concerns. Of the complaints in which animal species was identified, 623/738 (84.4%) involved companion animals and 104/738 (14.1%) involved large animals. Male veterinarians were the subject of 855/1,218 (70.2%) complaints. Of the complaints that recorded the number of years the respondent had been registered, 488/1,121 (43.5%) involved veterinarians who had been registered ≥21 years. Thematic analysis identified client expectations as the one overarching theme, within which were four subthemes; a veterinarian would be trustworthy and honest, provide good quality care, communicate in a way that the client finds acceptable, and charge fairly. Conclusions and clinical relevance: Notifications and complaints against male practitioners outnumbered those against female practitioners, and companion animal practitioners were over-represented. Many complaints that were ostensibly related to technical failures, were shown by thematic analysis to also represent underlying failures of professional behaviour. Key issues included lack of trustworthiness, honesty, good quality care and acceptable communication with the client. These data should not be interpreted as an accurate indicator of the prevalence of misconduct in practice, as the proportion of dissatisfied clients who did not raise a notification or complaint is unknown. Accurate classification of complaints will enable veterinary regulators and educators to identify competencies that could be developed or improved through training and experience.
Correlative Super-resolution and Electron Microscopy to Resolve Protein Localization in Zebrafish Retina

We present a method to investigate the subcellular protein localization in the larval zebrafish retina by combining super-resolution light microscopy and scanning electron microscopy. The sub-diffraction limit resolution capabilities of super-resolution light microscopes allow improving the accuracy of the correlated data. Briefly, 110 nanometer thick cryo-sections are transferred to a silicon wafer and, after immunofluorescence staining, are imaged by super-resolution light microscopy. Subsequently, the sections are preserved in methylcellulose and platinum shadowed prior to imaging in a scanning electron microscope (SEM). The images from these two microscopy modalities are easily merged using tissue landmarks with open source software. Here we describe the adapted method for the larval zebrafish retina. However, this method is also applicable to other types of tissues and organisms. We demonstrate that the complementary information obtained by this correlation is able to resolve the expression of mitochondrial proteins in relation with the membranes and cristae of mitochondria as well as to other compartments of the cell.
Field and Laboratory Performance of False Codling Moth, Thaumatotibia Leucotreta (Lepidoptera: Troticidae) on Orange and Selected Vegetables

False codling moth (FCM), Thaumatotibia leucotreta is a key pest of citrus orange and other plants causing fruit loss through larval feeding. Although this pest is native to sub-Saharan Africa little is known on its performance on orange and vegetables in Kenya and Tanzania. Our objective was to assess the incidence, oviposition preference and offspring performance of FCM on orange and vegetables, namely, okra, African eggplant, chili and sweet peppers. A higher percentage of orange with FCM damage symptoms was recorded from the ground than from the tree sampled fruit. However, FCM larval incidence was higher for the latter (tree sampled fruit). The highest FCM larval incidence amongst the vegetables was recorded on African eggplant (12%) while the lowest was on okra (3%). Orange was the most while African eggplant was the least preferred for oviposition by FCM. Among the vegetables tested, strong oviposition preference was found for sweet pepper; however, larval survival was lowest (62%) on this crop. Highest larval survival (77%) was recorded on orange. Most demographic parameters (i.e., intrinsic rate of increase, doubling time) were comparable among the studied host plants. The results are discussed in line of FCM management.
A stereological analysis on the calculation of the volume values of thoracic segments in ducks

Stereology is a method for examining two‐dimensional objects as three‐dimensional objects. The aim of this study was to offer volume values for thoracic segments in ducks by means of stereological methods. This study examined the data obtained from stereological analysis of the total volume and grey and white matter volume values of the thoracic segment, a part of the adult duck spinal cord with a weight of 3–4 kg. In the study, study samples consisted of 10 adult ducks (Anas) used without gender discrimination. To perfuse all of the animals, 10% formaldehyde was utilised. The perfused animals were kept in 10% formaldehyde for one week. The spinal cord was uncovered following the removal of arcus vertebrae parts of thoracic vertebrae in the thoracic part of dissected ducks. Tissue samples of thoracic segments were taken; 5‐µm‐thick cross sections from these tissue samples were taken via microtome. Attention was paid to obtaining samples at the ratio of 1/250 by taking 12 cross sections from each segment. The cross sections were subjected to haematoxylin‐eosin staining. Photographs of all cross sections were taken using a microscope. The volume values of all tissue and grey and white matter structures in each thoracic segment of the spinal cord were calculated. The total volume, grey and white matter volume densities in thoracic segments of ducks, as well as the data obtained as a result of proportioning volume values of one another are represented in the conclusion section of this study.
Alzheimer’s Amyloidopathy: An Alternative Aspect

The ‘amyloid hypothesis’ dominates Alzheimer’s disease (AD) research but has failed to deliver effective therapies. Amyloid precursor protein (APP) and presenilin-1 (PSEN1) genetic mutations are undoubtedly pathogenic, albeit by unclear mechanisms. Conversely, high dose B-vitamins convincingly slow brain atrophy in a pre-stage state of sporadic AD. Here we suggest a link between sporadic and genetic AD: 1) Increased serum homocysteine, a marker of B-vitamin deficiencies, is a significant risk factor for sporadic AD. It also correlates with elevated levels of antichymotrypsin, a serine protease inhibitor. 2) Family members with codon 717 APP mutations and dementia have low serum vitamin B12 values. Overexpression of the APP domain coding for a Kunitz type serine protease inhibitor might explain this. 3) PSEN1 mutations disrupt lysosomal function due to reduced proteolytic activity. They also trap cobalamin (B12) within lysosomes, leading to intracellular deficiency of the vitamin. In summary, APP and PSEN1 mutations both confer a risk for reduced protease activity and B12 bio-availability. Comparably, sporadic AD features a constellation of increased protease inhibition and B-vitamin deficiencies, the central part of which is believed to be B12. These concordant observations in three disparate AD etiologies suggest a common neuropathogenic pathway. This hypothesis is evaluable in laboratory and clinical trials.