Miracle-dz/UniFAR-FTUs huggingface dataset:
A precision approach to breast cancer treatment based on cell lineage-specific vulnerabilities

Breast cancers display significant intra-tumoral heterogeneity posing a major barrier to effective breast cancer treatments [1, 2]. This heterogeneity can be manifested in terms of genetic abnormalities or the presence of distinct cell types bearing similarities to the different epithelial lineages in the normal adult mammary gland including: luminal cells, basal cells, their respective progenitors, and stem cells [3]. The cell lineages present within a given tumor may determine the likelihood of progression. This is best exemplified by sub-populations of tumor-initiating cells present in aggressive breast cancers, some of which resemble adult mammary stem cells [4-9] and thus are termed stem-like. These stem-like cells are enriched in residual tumors after chemotherapy [10] as well as early metastatic lesions [11], suggesting they play a critical role in breast cancer progression. While attempts to treat breast cancers based on genetic mutations have largely been unsuccessful, therapies targeting particular cell lineages, including stem-like cells, are gaining renewed appreciation. Toward this goal, studies have uncovered distinct dependencies among different breast cancer cell types for particular cell death/survival pathways. These recent advances may open the door for new highly personalized approaches to breast cancer therapy. Our previous studies found that stem-like cells were highly sensitive to cell death induced by p53-upregulated mediator of apoptosis (PUMA) [12], a pro-apoptotic BH3-only member of the Bcl-2 family. These effects were specific to PUMA [12] as the related family member NOXA had no effect on stem-like cells consistent with its role in targeting basal-like breast cancer cells [13]. We further found that driving PUMA expression was sufficient to deplete stem-like cells and reduce metastasis in vivo, revealing its role as an important metastasis suppressor. Our results are consistent with published findings that PUMA-mediated cell death is the preferred response in some normal adult stem cell populations [14]. In an effort Research Perspective
Trends of Antibacterial Resistance at the National Reference Laboratory in Cameroon: Comparison of the Situation between 2010 and 2017

Introduction Antimicrobial resistance represents a growing public health threat. One of the World Health Organization's strategic objectives is “strengthening knowledge through surveillance and research. ” Sub-Saharan African countries are still far from achieving this objective. We aimed to estimate and compare the prevalence of antibacterial resistance in 2010 and 2017 in Cameroon. Methods We conducted a retrospective study on all clinical specimens cultured in Centre Pasteur du Cameroun (CPC) in 2010 and 2017. Data were extracted from the CPC's laboratory data information system software and then managed and analyzed using R. Bacterial resistance rates were calculated in each year and compared using chi-square or Fisher's tests, and relative changes were calculated. Outcomes included acquired resistance (AR), WHO priority resistant pathogens, some specific resistances of clinical interest, and resistance patterns (multi, extensively, and pan drug resistances) for five selected pathogens. Results A total of 10,218 isolates were analyzed. The overall AR rate was 96.0% (95% CI: 95.4–96.6). Most of WHO priority bacterial resistance rates increased from 2010 to 2017. The most marked increases expressed as relative changes concerned imipenem-resistant Acinetobacter (6.2% vs. 21.6%, +248.4%, p = 0.02), imipenem-resistant Pseudomonas aeruginosa (13.5% vs. 23.5%, +74.1%, p < 0.01), 3rd generation-resistant Enterobacteriaceae (23.8% vs. 40.4%, +65.8%, p < 10−15), methicillin-resistant Staphylococcus aureus (27.3% vs. 46.0%, +68.6%, p < 0.002), fluoroquinolone-resistant Salmonella (3.9% vs. 9.5%, +142.9%, p = 0.03), and fluoroquinolone-resistant Enterobacteriaceae (32.6% vs. 54.0%, +65.8%, p < 10−15). For selected pathogens, global multidrug resistance was high in 2010 and 2017 (74.9% vs. 78.0% +4.1%, p = 0.01), intensively drug resistance rate was 5.8% (7.0% vs. 4.7%; p = 0.07), and no pan drug resistance has been identified. Conclusion Bacterial resistance to antibiotics of clinical relevance in Cameroon was high and appeared to increase between 2010 and 2017. There is a need for regular surveillance of antibacterial resistance to inform public health strategies and empirically inform prescription practices.
Seroprevalence and Associated Factors of Human Immunodeficiency Virus, Treponema pallidum, Hepatitis B Virus, and Hepatitis C Virus among Female Sex Workers in Dessie City, Northeast Ethiopia

Introduction Sexually transmitted infections (STIs) are prevalent in Ethiopia and elsewhere among different population groups particularly among female sex workers (FSWs). Because of their work and their behavior, FSWs are at high risk to acquire STIs. The aim of the study was to assess the seroprevalence and associated factors of HIV, HBV, HCV, and T. pallidum among FSWs in Dessie City, Northeast Ethiopia. Methods This cross-sectional study was conducted in Dessie City, Amhara Region, Northeastern Ethiopia, from November 2017 to April 2018. A total of 360 FSWs whose age is greater than or equal to 18 years and who are willing to participate were recruited by simple random sampling technique. Interview-based questionnaire was administered, and 5 ml of venous blood from each participant was drawn under aseptic conditions. The rapid test was performed to obtain the result of the four STIs (HIV, T. pallidum, HBV, and HCV). The collected data were entered and analyzed by SPSS version 20.0. From the bivariable analysis, variables having P value < 0.2 were retained into multivariable analysis. From the multivariable analysis, variables with P value < 0.05 were affirmed as statistically associated factors. Adjusted odds ratios and their 95% confidence intervals were used as indicators of the strength of association. Results Majority of study participants were urban dwellers, 10 (2.8%) respondents were married, 61 (16.9%) have more than two children, and more than half of them were at the age range between 18 and 27 years. Any infection with STIs was 84 (23.3%), whereas 27 (7.5%), 47 (13.1%), 2 (0.6%), and 45 (12.5%) study participants were positive for laboratory test of HIV, HBV, HCV, and T. pallidum, respectively. Marital status, sharing of sharp materials, breakage of condom, number of customers per week, genital discharge, and pain had significant association with any STI. Conclusions In comparison with different research works in Ethiopia and abroad, the prevalence of any STI, HIV, HBV, and T. pallidum was found to be relatively high. Preventive approach and appropriate treatment of STIs should be developed. Concerned body should work together to alleviate the problem by counseling and recruiting them on other productive job sectors in the country.
Association of mammographic density with blood DNA methylation

ABSTRACT Background: Altered DNA methylation may be an intermediate phenotype between breast cancer risk factors and disease. Mammographic density is a strong risk factor for breast cancer. However, no studies to date have identified an epigenetic signature of mammographic density. We performed an epigenome-wide association study of mammographic density. Methods: White blood cell DNA methylation was measured for 385 postmenopausal women using the Illumina Infinium MethylationEPIC BeadChip array. Differential methylation was assessed using genome-wide, probe-level, and regional analyses. We implemented a resampling-based approach to improve the stability of our findings. Results: On average, women with elevated mammographic density exhibited DNA hypermethylation within CpG islands and gene promoters compared to women with lower mammographic density. We identified 250 CpG sites for which DNA methylation was significantly associated with mammographic density. The top sites were located within genes associated with cancer, including HDLBP, TGFB2, CCT4, and PAX8, and were more likely to be located in regulatory regions of the genome. We also identified differential DNA methylation in 37 regions, including within the promoters of PAX8 and PF4, a gene involved in the regulation of angiogenesis. Overall, our results paint a picture of epigenetic dysregulation associated with mammographic density. Conclusion: Mammographic density is associated with differential DNA methylation throughout the genome, including within genes associated with cancer. Our results suggest the potential involvement of several genes in the biological mechanisms behind differences in breast density between women. Further studies are warranted to explore these potential mechanisms and potential links to breast cancer risk.
Sugar-sweetened beverage consumption and overweight and obesity in adolescents in Ho Chi Minh City, Vietnam: a population-based analysis.

BACKGROUND To describe the patterns of consumption of multiple sugary sweetened beverages (including modern and traditional) among adolescents in Ho Chi Minh City and to identify a possible relationship between this consumption and overweight and obesity and with other main factors. METHOD A secondary analysis from a cross-sectional study of 11 to 15-year-old students from 31 junior high schools across Ho Chi Minh City. We measured the students' anthropometric status and assessed beverage consumption using a validated FFQ. Multivariate logistic regression models were used to identify the association between the consumption of sugar-sweetened beverages and obesity and other factors. RESULTS The sugar-sweetened beverages (SSB) ranged widely from modern soft drinks and powdered drinks to traditional sugar-added fruit, leaf juices and milk-based. These beverages were very popular among 2,660 participants with 36% consuming at least one variety daily. Factors positively associated with the sugar-sweetened beverage consumption included a higher level of physical activeness, higher consumption of fast foods, and daily fruit and vegetable consumption. We found a negative association between milk-based SSBs with overweight & obesity status of the students, with every kcal more of fresh milk with sugar and condensed milk can reduce an odd of 0.005 (95%CI [0.002-0.008], p<0.001) and 0.004 (95%CI [0.002-0.010], p=0.044) consecutively. None of other SSBs was significantly related to adolescent overweight and obesity. CONCLUSION Milk based drinks potentially protect adolescents against overweight and obesity and further research to assess this protection is needed.
Mass spectrometry and machine learning for the accurate diagnosis of benzylpenicillin and multidrug resistance of Staphylococcus aureus in bovine mastitis

Staphylococcus aureus is a serious human and animal pathogen threat exhibiting extraordinary capacity for acquiring new antibiotic resistance traits in the pathogen population worldwide. The development of fast, affordable and effective diagnostic solutions capable of discriminating between antibiotic-resistant and susceptible S. aureus strains would be of huge benefit for effective disease detection and treatment. Here we develop a diagnostics solution that uses Matrix-Assisted Laser Desorption/Ionisation–Time of Flight Mass Spectrometry (MALDI-TOF) and machine learning, to identify signature profiles of antibiotic resistance to either multidrug or benzylpenicillin in S. aureus isolates. Using ten different supervised learning techniques, we have analysed a set of 82 S. aureus isolates collected from 67 cows diagnosed with bovine mastitis across 24 farms. For the multidrug phenotyping analysis, LDA, linear SVM, RBF SVM, logistic regression, naïve Bayes, MLP neural network and QDA had Cohen’s kappa values over 85.00%. For the benzylpenicillin phenotyping analysis, RBF SVM, MLP neural network, naïve Bayes, logistic regression, linear SVM, QDA, LDA, and random forests had Cohen’s kappa values over 85.00%. For the benzylpenicillin the diagnostic systems achieved up to (mean result ± standard deviation over 30 runs on the test set): accuracy = 97.54% ± 1.91%, sensitivity = 99.93% ± 0.25%, specificity = 95.04% ± 3.83%, and Cohen’s kappa = 95.04% ± 3.83%. Moreover, the diagnostic platform complemented by a protein-protein network and 3D structural protein information framework allowed the identification of five molecular determinants underlying the susceptible and resistant profiles. Four proteins were able to classify multidrug-resistant and susceptible strains with 96.81% ± 0.43% accuracy. Five proteins, including the previous four, were able to classify benzylpenicillin resistant and susceptible strains with 97.54% ± 1.91% accuracy. Our approach may open up new avenues for the development of a fast, affordable and effective day-to-day diagnostic solution, which would offer new opportunities for targeting resistant bacteria.
How does onchocerciasis-related skin and eye disease in Africa depend on cumulative exposure to infection and mass treatment?

Background Onchocerciasis (river-blindness) in Africa is targeted for elimination through mass drug administration (MDA) with ivermectin. Onchocerciasis may cause various types of skin and eye disease. Predicting the impact of MDA on onchocercal morbidity is useful for future policy development. Here, we introduce a new disease module within the established ONCHOSIM model to predict trends over time in prevalence of onchocercal morbidity. Methods We developed novel generic model concepts for development of symptoms due to cumulative exposure to dead microfilariae, accommodating both reversible (acute) and irreversible (chronic) symptoms. The model was calibrated to reproduce pre-control age patterns and associations between prevalences of infection, eye disease, and various types of skin disease as observed in a large set of population-based studies. We then used the new disease module to predict the impact of MDA on morbidity prevalence over a 30-year time frame for various scenarios. Results ONCHOSIM reproduced observed age-patterns in disease and community-level associations between infection and disease reasonably well. For highly endemic settings with 30 years of annual MDA at 60% coverage, the model predicted a 70% to 89% reduction in prevalence of chronic morbidity. This relative decline was similar with higher MDA coverage and only somewhat higher for settings with lower pre-control endemicity. The decline in prevalence was lowest for mild depigmentation and visual impairment. The prevalence of acute clinical manifestations (severe itch, reactive skin disease) declined by 95% to 100% after 30 years of annual MDA, regardless of pre-control endemicity. Conclusion We present generic model concepts for predicting trends in acute and chronic symptoms due to history of exposure to parasitic worm infections, and apply this to onchocerciasis. Our predictions suggest that onchocercal morbidity, in particular chronic manifestations, will remain a public health concern in many epidemiological settings in Africa, even after 30 years of MDA.
Reliability and Validity of the Patient Activation Measure in Kidney Disease: Results of Rasch Analysis

Visual Abstract Background and objectives Despite the increasing prioritization of the promotion of patient activation in nephrology, its applicability to people with CKD is not well established. Before the Patient Activation Measure is universally adopted for use in CKD, it is important to critically evaluate this measure. The aim of this study was to describe the psychometric properties of the Patient Activation Measure in CKD. Design, setting, participants, & measurements A survey containing the 13-item Patient Activation Measure was completed by 942 patients with CKD, not treated with dialysis. Data quality was assessed by mean, item response, missing values, floor and ceiling effects, internal consistency (Cronbach’s alpha and average interitem correlation), and item-rest correlations. Rasch modeling was used to assess item performance and scaling (item statistics, person and item reliability, rating scale diagnostics, factorial test of residuals, and differential item functioning). Results The item response was high, with a small number of missing values (<1%). Floor effect was small (range 1%–5%), but the ceiling effect was above 15% for nine items (range 15%–38%). The Patient Activation Measure demonstrated good internal consistency overall (Cronbach α=0.925, and average interitem correlation 0.502). The difficulty of the Patient Activation Measure items ranged from −0.90 to 0.86. Differential item functioning was found for disease type (item 3) and age (item 12). The person separation index was 9.48 and item separation index was 3.21. Conclusions The 13-item Patient Activation Measure appears to be a suitably reliable and valid instrument for assessing patient activation in CKD. In the absence of a kidney-specific instrument, our results support the 13-item Patient Activation Measure as a promising measure to assess activation in those with CKD, although consideration for several items is warranted. The high ceiling effect may be a problem when using the 13-item Patient Activation Measure to measure changes over time.
Complement Receptor 3 Forms a Compact High-Affinity Complex with iC3b

Key Points Complement receptor 3 forms a high-affinity complex with iC3b. In solution, iC3b appears to have a preferred location of the thioester domain. The CR3 headpiece molecule is valuable for analysis of receptor–ligand interactions. Complement receptor 3 (CR3, also known as Mac-1, integrin αMβ2, or CD11b/CD18) is expressed on a subset of myeloid and certain activated lymphoid cells. CR3 is essential for the phagocytosis of complement-opsonized particles such as pathogens and apoptotic or necrotic cells opsonized with the complement fragment iC3b and, to a lesser extent, C3dg. Although the interaction between the iC3b thioester domain and the ligand binding CR3 αM I-domain is structurally and functionally well characterized, the nature of additional CR3–iC3b interactions required for phagocytosis of complement-opsonized objects remains obscure. In this study, we analyzed the interaction between iC3b and the 150-kDa headpiece fragment of the CR3 ectodomain. Surface plasmon resonance experiments demonstrated a 30 nM affinity of the CR3 headpiece for iC3b compared with 515 nM for the iC3b thioester domain, whereas experiments monitoring binding of iC3b to CR3-expressing cells suggested an affinity of 50 nM for the CR3–iC3b interaction. Small angle x-ray scattering analysis revealed that iC3b adopts an extended but preferred conformation in solution. Upon interaction with CR3, iC3b rearranges to form a compact receptor–ligand complex. Overall, the data suggest that the iC3b–CR3 interaction is of high affinity and relies on minor contacts formed between CR3 and regions outside the iC3b thioester domain. Our results rationalize the more efficient phagocytosis elicited by iC3b than by C3dg and pave the way for the development of specific therapeutics for the treatment of inflammatory and neurodegenerative diseases that do not interfere with the recognition of noncomplement CR3 ligands.
Facile and simple fabrication of superhydrophobic and superoleophilic MS/PDA/DT sponge for efficient oil/water separation

ABSTRACT To overcome the problems of frequent leakage accidents during oil exploitation, a superhydrophobic and superoleophilic porous MS/PDA/DT sponge was successfully prepared via mild solvent evaporation method, and a polydopamine assisted surface coating of 1-dodecanethiol (DT) on a melamine sponge (MS) substrate. Surface structure and performance of the MS/PDA/DT sponge were characterized by Scanning Electron Microscope (SEM), Fourier transform infrared spectrometer (FTIR), and Video Optical Contact Angle (CA) metre. The results showed that the as-prepared MS/PDA/DT sponge has a high-water contact angle (WCA) of 147.2°, which is probably attributed to both the rough surface derived from in situ growth and the low surface energy due to grafting of hydrophobic 1-dodecanethiol. The durability of the as-constructed MS/PDA/DT sponge was studied by repeated abrasion tests. After 50 abrasion cycles, the superhydrophobicity of the MS/PDA/DT sponge good mechanical durability. The MS/PDA/DT sponge can effectively absorb oil with an absorption capacity of up to 24 times its weight. The superhydrophobic and superoleophilic MS/PDA/DT sponge has the potential as a promising adsorbent for oil/water separation. Highlights The MS/PDA/DT sponge was prepared via the mild solvent evaporation method. The contact angle of the MS/PDA/DT sponge was 147.2o. The adsorption capacity of the MS/PDA/DT sponge was 24 times their weight. The cost-efficient, environmentally friendly porous materials show high oil/water separation efficiency. GRAPHICAL ABSTRACT
Molecular characterization of Cryptosporidium spp. from humans in Ethiopia

Data on the distribution and genotype of Cryptosporidium species is limited in Ethiopia. This study examined the presence and genetic diversity of Cryptosporidium species circulating in Ethiopian human population. Stool samples collected from patients who visited rural (n = 94) and urban (n = 93) health centers in Wurgissa and Hawassa district, respectively, were examined for the presence of Cryptosporidium spp. using microscopy, nested PCR and real-time PCR. To detect infection with PCR, analysis of 18S ribosomal RNA was performed. Subtyping was performed by sequencing a fragment of GP60 gene. The overall prevalence of infection was 46% (n = 86) by microscope and PCR. When 48 (out of 86) PCR positive samples were genotyped, two species were identified: C. parvum (n = 40) and C. hominis (n = 8). When 15 of the 40 C. parvum isolates were subtyped, zoonotic subtypes of IIaA14G1R1 (n = 1), IIaA15G2R1 (n = 1), IIaA16G1R1 (n = 2), IIaA16G3R1 (n = 2), IIaA17G1R1 (n = 1), IIaA19G1R1 (n = 1), IIaA20G1R1 (n = 3), IIaA22G1R1 (n = 1), IIaA22G2R1 (n = 1), IIdA23G1 (n = 1) and IIdA24G1 (n = 1) were identified. When 6 of the 8 C. hominis isolates were subtyped, subtypes IaA20 (n = 5), and IdA21(n = 1) were identified. This study suggests that C. parvum and C. hominis are causes of cryptosporidiosis in human in the Wurgissa district and Hawassa in Ethiopia. Zoonotic transmission might be the main route of transmission.