Miracle-dz/UniFAR-FTUs huggingface dataset:
Breast Cancer and HIV in Sub-Saharan Africa: A Complex Relationship

Introduction The number and lifespan of individuals living with HIV have increased significantly with the scale-up of antiretroviral therapy. Furthermore, the incidence of breast cancer in women with HIV is growing, especially in sub-Saharan Africa (SSA). However, the association between HIV infection and breast cancer is not well understood. Methods A literature search was performed to identify articles published in journals pertaining to breast cancer and HIV, with an emphasis on SSA. Selected US-based studies were also identified for comparison. Results Among the 56 studies reviewed, the largest study examined 314 patients with breast cancer and HIV in the United States. There is no consensus on whether HIV infection acts as a pro-oncogenic or antioncogenic factor in breast cancer, and it may have no relation to breast cancer. A higher incidence of breast cancer is reported in high-income countries than in SSA, although breast cancer in SSA presents at a younger age and at a more advanced stage. Some studies show that patients with breast cancer and HIV experience worse chemotherapy toxicity than do patients without HIV. Data on treatment outcomes are limited. The largest study showed worse treatment outcomes in patients with HIV, compared with their counterparts without HIV. Conclusion HIV infection has not been associated with different clinical presentation of breast cancer. However, some evidence suggests that concurrent diagnosis of HIV with breast cancer is associated with increased therapy-related toxicity and worse outcomes. Systematic prospective studies are needed to establish whether there is a specific association between breast cancer and HIV.
Characterization of Precursor-Dependent Steroidogenesis in Human Prostate Cancer Models

Castration-resistant prostate tumors acquire the independent capacity to generate androgens by upregulating steroidogenic enzymes or using steroid precursors produced by the adrenal glands for continued growth and sustainability. The formation of steroids was measured by liquid chromatography-mass spectrometry in LNCaP and 22Rv1 prostate cancer cells, and in human prostate tissues, following incubation with steroid precursors (22-OH-cholesterol, pregnenolone, 17-OH-pregnenolone, progesterone, 17-OH-progesterone). Pregnenolone, progesterone, 17-OH-pregnenolone, and 17-OH-progesterone increased C21 steroid (5-pregnan-3,20-dione, 5-pregnan-3,17-diol-20-one, 5-pregnan-3-ol-20-one) formation in the backdoor pathway, and demonstrated a trend of stimulating dihydroepiandrosterone or its precursors in the backdoor pathway in LNCaP and 22Rv1 cells. The precursors differentially affected steroidogenic enzyme messenger RNA (mRNA) expressions in the cell lines. The steroidogenesis following incubation of human prostate tissue with 17-OH-pregnenolone and progesterone produced trends similar to those observed in cell lines. Interestingly, the formation of C21 steroids from classical pathway was not stimulated but backdoor pathway steroids (e.g., 5-pregnan-3,20-dione, 5-pregnan-3-ol-20-one) were elevated following incubations with prostate tissues. Overall, C21 steroids were predominantly formed in the classical as well as backdoor pathways, and steroid precursors induced a diversion of steroidogenesis to the backdoor pathway in both cell lines and human prostate tissue, and influenced adaptive steroidogenesis to form C21 steroids.
The geography of multinational production

The purpose of this thesis is to contribute to the development of a theoretical model which captures the main firm, sector and location characteristics of multinational firm activity. The knowledge capital model (Markusen and Venables, 1995, 1996) is extended by intra and inter-industry supply linkages to allow multinational firms to be attracted to a country to exploit the agglomeration externalities created by pooling of national or other multinational firms. The main finding through computational general equilibrium (CGE) simulations is that firms show a preference to locate their affiliates in countries with strong supply linkages, as long as the competition among sectors for limited endowments do not increase the factor prices to a level that makes the country disadvantageous. Multinational firms (MNFs) particularly in sectors with high total scale economies, low trade costs and high plant versus firm level scale economies prefer to locate in close proximity to industrial clusters. The propositions obtained from CGE simulations are also tested empirically for manufacturing sector affiliates. The empirical findings provides evidence on the importance of supply linkages in a host economy for attracting MNFs in technology-intensive sectors and that the sub-sectors may vary on the importance they set on finding locations with industrial clusters. In addition to these, the determinants of location decisions of MNFs in Europe and the impact of the European integration policies on multinational production are investigated. The empirical analysis for the potential effects of a regional integration policy reveals that central and peripheral countries may benefit from different aspects of an integration process. Moreover, the intra-region and extra-region foreign direct investment may display different motives for choosing a location for their affiliates. The findings provide support on the hypothesis that intra-EU FDI has become more efficiency seeking, hence, leading to a redistribution of multinational activity within the region.
Rapid eruption of the Columbia River flood basalt and correlation with the mid-Miocene climate optimum

U-Pb ages show Earth’s youngest flood basalt province erupted in 750 ka starting ~16.65 Ma during Miocene global warming. Flood basalts, the largest volcanic events in Earth history, are thought to drive global environmental change because they can emit large volumes of CO2 and SO2 over short geologic time scales. Eruption of the Columbia River Basalt Group (CRBG) has been linked to elevated atmospheric CO2 and global warming during the mid-Miocene climate optimum (MMCO) ~16 million years (Ma) ago. However, a causative relationship between volcanism and warming remains speculative, as the timing and tempo of CRBG eruptions is not well known. We use U-Pb geochronology on zircon-bearing volcanic ash beds intercalated within the basalt stratigraphy to build a high-resolution CRBG eruption record. Our data set shows that more than 95% of the CRBG erupted between 16.7 and 15.9 Ma, twice as fast as previous estimates. By suggesting a recalibration of the geomagnetic polarity time scale, these data indicate that the onset of flood volcanism is nearly contemporaneous with that of the MMCO.
A framework for distinguishing benign from malignant breast histopathological images using deep residual networks

Studies have shown that there are discrepancies among pathologists in the classification of breast histopathological slides. In this study we propose a framework for categorizing hematoxylin-eosin stained breast images either as benign or malignant at four magnification factors, and then aggregating the classification results of a patient’s images from different magnification factors to make the ultimate diagnosis for each patient. We used a publicly available database, containing 7786 images from 81 patients. The images were acquired in four visual magnification factors, namely x40, x100, x200, and x400, with an effective pixel size of 0.49 μm, 0.20 μm, 0.10 μm, and 0.05 μm respectively. In order to mitigate the inconsistencies in the color of the images, stain normalization was performed. Next, for each magnification factor, a deep residual network (ResNet) with 152 layers has been trained for classifying patches from the images as benign or malignant. Then, a meta-decision tree was used to combine classification results of a patient’s images from different magnification factors to provide a patient-level diagnosis. The ResNets achieved correct classification rates (CCR) of 98.52%, 97.90%, 98.33%, and 97.66% at x40, x100, x200, and x400 magnification factors, respectively. For classification of patients either as benign or malignant, a CCR of 98.77% was obtained. In conclusion, our study showed that the proposed framework can be helpful in the categorization of breast digital slides.
Outcomes of Low-Intensity Treatment of Acute Lymphoblastic Leukemia at Butaro Cancer Center of Excellence in Rwanda

Purpose Children with acute lymphoblastic leukemia (ALL) in low-income countries have disproportionately lower cure rates than those in high-income countries. At Butaro Cancer Center of Excellence (BCCOE), physicians treated patients with ALL with the first arm of the Hunger Protocol, a graduated-intensity method tailored for resource-limited settings. This article provides the first published outcomes, to our knowledge, of patients with ALL treated with this protocol. Methods This is a retrospective descriptive study of patients with ALL enrolled at BCCOE from July 1, 2012 to June 30, 2014; data were collected through December 31, 2015. Descriptive statistics were used to calculate patient demographics, disease characteristics, and outcomes; event-free survival was assessed at 2 years using the Kaplan-Meier method. Results Forty-two consecutive patients with ALL were included. At the end of the study period, 19% (eight) were alive without evidence of relapse: three completed treatment and five were continuing treatment. Among the remaining patients, 71% (30) had died and 10% (four) were lost to follow-up. A total of 83% (25) of the deaths were disease related, 3% (one) treatment-related, and 13% (four) unclear. Event-free survival was 22% (95% CI, 11% to 36%), considering lost to follow-up as an event, and 26% (95% CI, 13% to 41%) if lost to follow-up is censored. Conclusion As expected, relapse was the major cause of failure with this low-intensity regimen. However, toxicity was acceptably low, and BCCOE has decided to advance to intensity level 2. These results reflect the necessity of a data-driven approach and a continual improvement process to care for complex patients in resource-constrained settings.
Improved Socio-Emotional and Behavioral Functioning in Students with Autism Following School-Based Smartglasses Intervention: Multi-Stage Feasibility and Controlled Efficacy Study

Background: Students with Autism Spectrum Disorder (ASD) commonly demonstrate prominent social communication deficits, symptoms of attention-deficit/hyperactivity disorder, and chronic irritability. These challenges hinder academic progress and frequently persist despite educational, behavioral, and medical interventions. An assistive smartglasses technology may aid these individuals, especially if the technology is efficacious in ecologically-valid school settings. This study explored the feasibility and efficacy of Empowered Brain, a computerized smartglasses intervention designed as a socio-emotional behavioral aid for students with ASD. Methods: This two-part six-week study involved four school children with ASD from a public elementary school. The study incorporated an initial three-week feasibility stage followed by a three-week controlled longitudinal efficacy stage. Both stages involved the use of a twice-daily socio-emotional intervention with the smartglasses. Educators completed pre-intervention and post-intervention Aberrant Behavioral Checklist (ABC) ratings at the start of the feasibility stage, and weekly during the efficacy stage. Primary outcome measures were improvements in the ABC subscales of irritability, hyperactivity, and social withdrawal. Results: Students in both feasibility and efficacy stages demonstrated improvements (decreases) in irritability, hyperactivity, and social withdrawal compared to a baseline period and control periods, respectively. Participants in the controlled efficacy stage demonstrated decreased ABC subscale scores of 90% for irritability, 41.6% for hyperactivity, and 45.6% for social withdrawal. An intervention exposure-response improvement in irritability and hyperactivity was found during the efficacy stage. Educators rated the technology as superior or vastly superior compared to other assistive technologies. Conclusion: A substantial number of school children with ASD demonstrate chronic and impairing cognitive and behavioral challenges. This study provides evidence that Empowered Brain, a smartglasses-based socio-emotional aid for autism, is both feasible and efficacious in improving symptoms of social withdrawal, irritability, and hyperactivity in students with autism. The improvement is demonstrated as part of a longitudinal school-based intervention. Further studies involving larger samples and incorporation of randomized controlled trial methodology are underway to further elucidate the impact of this technology.
Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes: A soft clustering analysis

Background Type 2 diabetes (T2D) is a heterogeneous disease for which (1) disease-causing pathways are incompletely understood and (2) subclassification may improve patient management. Unlike other biomarkers, germline genetic markers do not change with disease progression or treatment. In this paper, we test whether a germline genetic approach informed by physiology can be used to deconstruct T2D heterogeneity. First, we aimed to categorize genetic loci into groups representing likely disease mechanistic pathways. Second, we asked whether the novel clusters of genetic loci we identified have any broad clinical consequence, as assessed in four separate subsets of individuals with T2D. Methods and findings In an effort to identify mechanistic pathways driven by established T2D genetic loci, we applied Bayesian nonnegative matrix factorization (bNMF) clustering to genome-wide association study (GWAS) results for 94 independent T2D genetic variants and 47 diabetes-related traits. We identified five robust clusters of T2D loci and traits, each with distinct tissue-specific enhancer enrichment based on analysis of epigenomic data from 28 cell types. Two clusters contained variant-trait associations indicative of reduced beta cell function, differing from each other by high versus low proinsulin levels. The three other clusters displayed features of insulin resistance: obesity mediated (high body mass index [BMI] and waist circumference [WC]), “lipodystrophy-like” fat distribution (low BMI, adiponectin, and high-density lipoprotein [HDL] cholesterol, and high triglycerides), and disrupted liver lipid metabolism (low triglycerides). Increased cluster genetic risk scores were associated with distinct clinical outcomes, including increased blood pressure, coronary artery disease (CAD), and stroke. We evaluated the potential for clinical impact of these clusters in four studies containing individuals with T2D (Metabolic Syndrome in Men Study [METSIM], N = 487; Ashkenazi, N = 509; Partners Biobank, N = 2,065; UK Biobank [UKBB], N = 14,813). Individuals with T2D in the top genetic risk score decile for each cluster reproducibly exhibited the predicted cluster-associated phenotypes, with approximately 30% of all individuals assigned to just one cluster top decile. Limitations of this study include that the genetic variants used in the cluster analysis were restricted to those associated with T2D in populations of European ancestry. Conclusion Our approach identifies salient T2D genetically anchored and physiologically informed pathways, and supports the use of genetics to deconstruct T2D heterogeneity. Classification of patients by these genetic pathways may offer a step toward genetically informed T2D patient management.
Evidence of a distinct group of Black African patients with systemic lupus erythematosus

Background The autoimmune disease systemic lupus erythematosus (SLE) occurs more frequently in patients of African descent with high morbidity and mortality. Current SLE diagnostic criteria including antinuclear antibody (ANA) reactivity are derived largely from non-African populations. This study characterises ANA reactivity patterns and relates them to SLE clinical presentation in Black African patients. Methods Sera from Black participants (61 patients with SLE and 100 controls) aged 1–81 years were analysed for reactivity against the antigens: uridine 1-ribonuclear protein, Smith uridine-1-5 ribonuclear protein antigen, soluble substance-A, recombinant Ro-52, soluble substance-B, Scl-70, cytoplasmic histidyl-tRNA synthetase antigen, proliferating cell nuclear antigen (PCNA), nucleosomes, ribonuclear P-protein, antimitochondrial antibody M2 (AMA-M2), histones, double-stranded DNA (dsDNA), centromere protein B and polymyositis–sclerosis overlap antigen. Findings A significantly higher proportion (97%) of the 61 patients with SLE had detectable autoantibody reactivity compared with 15% of the 100 controls (p<0.001). The highest frequencies of autoantibody reactivity in patients with SLE were against the dsDNA antigen (41%) and PCNA (54%). Anti-PCNA and anti-dsDNA reactivity were mutually exclusive (p<0.001) giving rise to two distinct groups of Black African patients with SLE. The first group (n=25) had reactivity profiles consistent with international standard SLE definitions, including anti-dsDNA reactivity, and was 13 times more likely to present with joint symptoms. The larger, second group (n=34), characterised by anti-PCNA and anti-AMA-M2 reactivity, was nine times more likely to present with only cutaneous symptoms. Interpretation Our study demonstrates a need to extend autoantibody panels to include anti-PCNA in the diagnostic process of Black African patients and further refine the predictive values of the reactivity to different antigens to differentiate SLE syndromes in African populations.
The ABC Clinical Guide to Herbs

Mark Blumenthal is one of the best known scholars interested in medicinal plants and ethnobotany. This beautifully written and . well organized 480 page guide is intended primarily for health professionals, but its main points are understandable by non-herbal professionals or laypersons. This book is considered an excellent reference in the field of herbal medicine from clincial perspective. It is accredited as a continous education course for physicians, pharmacists, nurses, dietitians, researchers, herbalists, consumers, and people engaged in phyto-pharmaceutical based industries. The book is organized into four main sections as follow: Introduction, Herb chapters, where each chapter is specified for a herb, Proprietary Herbal Product Monographs, and Appendix. Section one, constsis of two parts. Part one gives an introduction about herbal medicine, its history, safety, legal and regulatory status, rational phytotherapy, and evidence-base medicine. The information contained is compiled by a team of professionals including MDs and is the result of an extensive research of the available literature. The consumer section (called patient information sheet) contains a short and easy to read description of most commonly used herbals alongwith an overview, uses, dosage, duration of administration, chemistry, pharmacological actions, mechanisms of action, containdications adverse effects, drug ineractions, and AHPA Safety Rating of each herb. While part two gives an idea about the book, its purpose, and why the herbs in this book were selected. Section two gives clinical reviews, patients sheets, and single herb monograph for the following 29 herbs: Bilberry, Black Cohosh, Cats Claw, Cayenne, Chamomile, Chaste Tree, Cranberry, Echinacea, Eleuthero, Ephedra, Evening Primrose Oil, Feverfew, Flax, Garlic, Ginger, Ginkgo, Ginseng (American and Asian), Goldenseal, Hawthorn, Horse Chestnut, Kava, Licorice, Milk Thistle, Peppermint, Saw Palmetto, St. Johns Wort, Tea (black and green), Valerian, respectively. The clinical overviews are written for physicians, who would be better served to read this book, and other health care professionals. In addition, a table of clinical studies, if any, is listed at the end of the herb monograph. Section three, has propietary herb product monograph for the following: pycnogenol (French Marin Pine Bark extract), Alluna, Esberitox, Euvegal, Hochuekki-to, Hova, Liv.52, Mastodynon, Nutrilite, Padma, Phytodolor, Prostagutt, and Sinupert. Finally, section four, has an appendix which contains, a list of reviewers, general reference, tabels of commercial products used in clinical studies, and proprietary herbal product monograph, a list of company contact information for commercial products used in the clinical studies, and top-selling herbal supplements in food, drug, and mass market retail outlets, a list of recent studies, abbreviation and symbols, and glossary. The book contains a wealth of information and is scientifically based. This book should be on every clinic and pharmacy reference shelves. I hope that this book also receive attention of producers of herbal based remedies.
Nocturnal supervision and SUDEP risk at different epilepsy care settings

Objective To estimate the incidence of sudden unexpected death in epilepsy (SUDEP) in people with intellectual disabilities in residential care settings and to ascertain the effects of nocturnal seizures and nocturnal supervision on SUDEP risk. Methods We conducted a nested case-control study reviewing records of all people who died at 2 residential care settings over 25 years. Four controls per case were selected from the same population, matched on age (±5 years) and residential unit. Nocturnal supervision was graded in 3 categories: (1) no supervision; (2) a listening device or a roommate or physical checks at least every 15 minutes; and (3) 2 of the following: a listening device, roommate, additional device (bed motion sensor/video monitoring), or physical checks every 15 minutes. Outcome measures were compared using Mann-Whitney U tests and Fisher exact tests. Results We identified 60 SUDEP cases and 198 matched controls. People who died of SUDEP were more likely to have nocturnal convulsive seizures in general (77% of cases vs 33% of controls, p < 0.001) and a higher frequency of nocturnal convulsive seizures. Total SUDEP incidence was 3.53/1,000 patient-years (95% confidence interval [CI] 2.73–4.53). The incidence differed among centers: 2.21/1,000 patient-years (95% CI 1.49–3.27) vs 6.12/1,000 patient-years (95% CI 4.40–8.52). There was no significant difference in nocturnal supervision among cases and controls, but there was a difference among centers: the center with a lowest grade of supervision had the highest incidence of SUDEP. Conclusions Having nocturnal seizures, in particular convulsions, may increase SUDEP risk. Different levels of nocturnal supervision may account for some of the difference in incidence.
Update on corneal neurotisation

Corneal neurotisation describes surgical restoration of nerve growth into the cornea to restore corneal sensation and trophic function. It represents an exciting and effective emerging treatment for neurotrophic keratopathy. Techniques described to date involve either direct nerve transfer or an interpositional nerve graft coapted to a healthy donor nerve. We review the experience to date with particular emphasis on a detailed review of techniques, outcomes and current thoughts.