Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Kidney Disease and Associated Risk Factors Assessment among Diabetes Mellitus Patients at A Tertiary Hospital, Northwest Ethiopia

Background The prevalence of chronic kidney disease, particularly in diabetic patients, is increasing rapidly throughout the world. Nowadays, many individuals in developing nations are suffering from diabetes which is one of the primary risk factors of chronic kidney disease. Methods Institution based cross-sectional study was conducted at the University of Gondar Hospital from February to April 2016. A total of 229 study participants were selected using systematic random sampling technique. Urine sample was collected for albumin determination by dipstick. The Simplified Modification of Diet in Renal Disease study equation was used to estimate glomerular filtration rate. Binary logistic regression model was used to identify risk factors. Results Of the total 229 study participants, 50.2% were females and the mean age was 47±15.7 years. Among study participants, the prevalence of chronic kidney disease (CKD) was found to be 21.8% (95% CI: 16% – 27%). Of all study participants, 9(3.9%) had renal impairment (eGFR < 60 ml/min/ 1.73 m2) and 46 (20.1%) had albuminuria. Older age (AOR: 5.239, 95% CI: 2.255–12.175), systolic blood pressure ≥140mmHg (AOR: 3.633, 95% CI: 1.597–8.265), type 2 diabetes mellitus (AOR: 3.751, 95% CI: 1.507–9.336) and longer duration of diabetes (AOR: 3.380, 95% CI: 1.393–8.197) were independent risk factors of CKD. Conclusions The study identified high prevalence (21.8%) of CKD among diabetic adults. CKD was significantly associated with older age, systolic blood pressure, type 2 DM and longer duration of DM. Thus, DM patients should be diagnosed for chronic kidney disease and then managed accordingly.
Dental approach of orofacial pain in head and neck cancer patients

Background Orofacial pain (OFP) is an undesirable sensation frequently associated with head and neck cancer (HNC) and its treatment. OFP negatively impacts the quality of life of oncological patients. The approach to OFP diagnosis and management can differ if the patient visits a dentist or physician. The aim of this study was to present a case series of HNC with OFP managed by a dentist team and to discuss its role in the management of OFP. Material and Methods We recruited twenty-two adult patients with OFP and previous diagnosis of HNC referred to an academic dental clinic from 2015 to 2017. Results Nociceptive was more frequent than mixed and neuropathic pain, however 54,4% of the cases showed a neurological component. All types of pain were managed by dentist through removal of pain’s cause and appropriated local and systemic treatment. The intensity of pain was reduced in 86,3% of patients, and 45,4% of them reported absence of pain at the end of treatment. Conclusions Dentist’s assessment plays a distinct and crucial role in the diagnosis and management of OFP in HNC patients throughout the oncological treatment. Key words:Pain, orofacial, neoplasm, head and neck, dentist.
Metabolomic Analysis of Defense-Related Reprogramming in Sorghum bicolor in Response to Colletotrichum sublineolum Infection Reveals a Functional Metabolic Web of Phenylpropanoid and Flavonoid Pathways

The metabolome of a biological system provides a functional readout of the cellular state, thus serving as direct signatures of biochemical events that define the dynamic equilibrium of metabolism and the correlated phenotype. Hence, to elucidate biochemical processes involved in sorghum responses to fungal infection, a liquid chromatography-mass spectrometry-based untargeted metabolomic study was designed. Metabolic alterations of three sorghum cultivars responding to Colletotrichum sublineolum, were investigated. At the 4-leaf growth stage, the plants were inoculated with fungal spore suspensions and the infection monitored over time: 0, 3, 5, 7, and 9 days post inoculation. Non-infected plants were used as negative controls. The metabolite composition of aqueous-methanol extracts were analyzed on an ultra-high performance liquid chromatography system coupled to high-definition mass spectrometry. The acquired multidimensional data were processed to create data matrices for multivariate statistical analysis and chemometric modeling. The computed chemometric models indicated time- and cultivar-related metabolic changes that reflect sorghum responses to the fungal infection. Metabolic pathway and correlation-based network analyses revealed that this multi-component defense response is characterized by a functional metabolic web, containing defense-related molecular cues to counterattack the pathogen invasion. Components of this network are metabolites from a range of interconnected metabolic pathways with the phenylpropanoid and flavonoid pathways being the central hub of the web. One of the key features of this altered metabolism was the accumulation of an array of phenolic compounds, particularly de novo biosynthesis of the antifungal 3-deoxyanthocynidin phytoalexins, apigeninidin, luteolinidin, and related conjugates. The metabolic results were complemented by qRT-PCR gene expression analyses that showed upregulation of defense-related marker genes. Unraveling key characteristics of the biochemical mechanism underlying sorghum—C. sublineolum interactions, provided valuable insights with potential applications in breeding crop plants with enhanced disease resistance. Furthermore, the study contributes to ongoing efforts toward a comprehensive understanding of the regulation and reprogramming of plant metabolism under biotic stress.
Qualitative Analysis of Emotional Distress in Cardiac Patients From the Perspectives of Cognitive Behavioral and Metacognitive Theories: Why Might Cognitive Behavioral Therapy Have Limited Benefit, and Might Metacognitive Therapy Be More Effective?

Introduction: Cognitive behavioral therapy (CBT) alleviates emotional distress in mental health settings, but has only modest effects in cardiac patients. Metacognitive therapy (MCT) also alleviates depression and anxiety in mental health settings and is in its initial stages of evaluation for cardiac patients. Aim: Our objective is to compare how CBT and MCT models conceptualize cardiac patients' distress, and to explore why CBT has had limited benefit for cardiac patients and whether MCT has the potential to be more efficacious. Method: Forty-nine cardiac rehabilitation patients, who screened positively for anxiety and/or depression, provided semi-structured interviews. We analyzed transcripts qualitatively to explore the “fit” of patients' accounts of their distress with the main elements of cognitive behavioral and metacognitive theories. Four illustrative cases, representative of the diverse presentations in the broader sample, were analyzed in detail and are presented here. Results: Conceptualizing patients' distress from the perspective of CBT involved applying many distinct categories to describe specific details of patients' talk, particularly the diversity of their concerns and the multiple types of cognitive distortion. It also required distinction between realistic and unrealistic thoughts, which was difficult when thoughts were associated with the risk or consequences of cardiac events. From the perspective of MCT a single category—perseverative negative thinking—was sufficient to understand all this talk, regardless of whether it indicated realistic or unrealistic thoughts, and could also be applied to some talk that did not seem relevant from a CBT perspective. Discussion: Conceptualizing distress from the perspective of CBT presents multiple, diverse therapeutic targets, not all of which a time-limited therapy would be able to address. Given the difficulty of identifying them as unrealistic or not, thoughts about disease, death or disability may not be amenable to classic CBT techniques such as reality testing. MCT proved more parsimonious and, because it did not distinguish between realistic and unrealistic thoughts, might prove a better fit to emotional distress in cardiac patients.
Repurposing Screen Identifies Unconventional Drugs With Activity Against Multidrug Resistant Acinetobacter baumannii

Antibiotic-resistant nosocomial infections are an emerging public health issue; carbapenem-resistant gram-negative bacteria such as Acinetobacter baumannii are among the pathogens against which new therapeutic agents are desperately needed. Drug repurposing has recently emerged as an alternative approach to rapidly identifying effective drugs and drug combinations to combat drug resistant bacteria. We performed a drug repurposing screen against a highly virulent, multidrug resistant, Acinetobacter baumannii strain AB5075. This strain, isolated from a patient, is resistant to 25 first-line antibiotics for gram-negative bacteria. A compound screen using a bacterial growth assay led to identification and confirmation of 43 active compounds. Among these confirmed compounds, seven are approved drugs or pharmacologically active compounds for non-antimicrobial indications. Three of these drugs, 5-fluorouracil, fluspirilene, and Bay 11-7082 resensitized strain AB5075 to azithromycin and colistin in a two-drug combination format. The approach using a drug repurposing screen with a pathogen sample isolated from a patient and a high throughput bacterial growth assay led to the successful identification of new drug combinations to overcome a multidrug resistant bacterial infection.
Potential Role of Accessory Domains in Polyproteins Encoded by Retrotransposons in Anti-viral Defense of Host Cells

1 A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia, Department of Virology, Biological Faculty, Moscow State University, Moscow, Russia, 3 Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia, 4 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia, 5 Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, Russia
The Genetic Structures of an Extensively Drug Resistant (XDR) Klebsiella pneumoniae and Its Plasmids

Multi-, extensively-, and pan-drug resistant bacteria are a threat to our health today, because their wide resistance spectra make their infections difficult to cure. In this work, we isolated an extensively drug resistant (XDR) Klebsiella pneumoniae 2-1 strain from the stool sample of a patient diagnosed of colorectal cancer. K. pneumoniae 2-1 was found to be resistant to all the antibiotics tested except for cefepime, tigecycline, and ceftazidime-avibactam. By sequencing the complete genome of K. pneumoniae 2-1, we found it contains a chromosome of 5.23 Mb and two circular plasmids with the size of 246 and 90 kb. The larger plasmid, pKP21HI1 was found to be a new conjugation-defective plasmid belonging to incompatibility group HI1B and a new sequence type. Further comparative genomics analysis and antimicrobial resistance gene analysis showed that although a great deal of changes took place on the chromosome of K. pneumoniae 2-1 in comparison with the reference genome, the extensively drug resistance phenotype of K. pneumoniae 2-1 is primarily due to the two multidrug resistant plasmids it contains. This work explains the genetic and mechanistic basis of the extensive drug resistance of K. pneumoniae 2-1, and found that plasmids play key roles in the strong antibiotic resistance of bacteria.
Embedding of Genes Using Cancer Gene Expression Data: Biological Relevance and Potential Application on Biomarker Discovery

Artificial neural networks (ANNs) have been utilized for classification and prediction task with remarkable accuracy. However, its implications for unsupervised data mining using molecular data is under-explored. We found that embedding can extract biologically relevant information from The Cancer Genome Atlas (TCGA) gene expression dataset by learning a vector representation through gene co-occurrence. Ground truth relationship, such as cancer types of the input sample and semantic meaning of genes, were showed to retain in the resulting entity matrices. We also demonstrated the interpretability and usage of these matrices in shortlisting candidates from a long gene list as in the case of immunotherapy response. 73 related genes are singled out while the relatedness of 55 genes with immune checkpoint proteins (PD-1, PD-L1, and CTLA-4) are supported by literature. 16 novel genes (ACAP1, C11orf45, CD79B, CFP, CLIC2, CMPK2, CXCR2P1, CYTIP, FER, MCTO1, MMP25, RASGEF1B, SLFN12, TBC1D10C, TRAF3IP3, TTC39B) related to immune checkpoint proteins were identified. Thus, this method is feasible to mine big volume of biological data, and embedding would be a valuable tool to discover novel knowledge from omics data. The resulting embedding matrices mined from TCGA gene expression data are interactively explorable online (http://bit.ly/tcga-embedding-cancer) and could serve as an informative reference for gene relatedness in the context of cancer and is readily applicable to biomarker discovery of any molecular targeted therapy.
Interactive Effects of Genotype and Molybdenum Supply on Yield and Overall Fruit Quality of Tomato

Molybdenum (Mo) is an essential trace element for plant growth, development, and production. However, there is little known about the function and effects of molybdenum in tomato plants. The present study assessed the influences of different Mo concentrations on four tomato F1 hybrids (“Bybal” F1, “Tyty” F1, “Paride” F1, and “Ornela” F1) grown using a soilless system with different Mo levels [0.0, 0.5 (standard NS), 2.0, and 4.0 μmol L−1, respectively]. The crop yield, plant vigor, fruit skin color, TA, fruit water content as well as the accumulation of SSC, and some antioxidant compounds such as lycopene, polyphenols and ascorbic acid were evaluated. The minerals concentration, including nitrogen (N), Mo, iron (Fe), and copper (Cu), were measured in tomato fruits. Results revealed that tomato plants grown with 2.0 μmol Mo L−1 compared to plants grown with 0.5 μmol Mo L−1 incurred a significant increase of total yield by 21.7%, marketable yield by 9.1%, aboveground biomass by 16.7%, plant height at 50 DAT by 6.5%, polyphenol content by 3.5%, ascorbic acid by 1.0%, SSC by 3.5%, N fruit content by 24.8%, Mo fruit content by 20.0%, and Fe fruit content by 60.5%. However, the Mo concentration did not significantly influence the average fruit weight, b* fruit skin color coordinate and TA. Furthermore, tomato fruits from plants grown with 2.0 μmol Mo L−1 showed a lower Cu fruit content (16.1%) than fruits from plants grown with 0.5 μmol Mo L−1 (standard NS). Consequently, our study highlights the different behavior of the tomato genotypes tested when subjected to different levels of Mo concentration in the nutrient solution. Nevertheless, taking all in consideration our results clearly suggest that a Mo fertilization of 2.0 μmol Mo L−1 effectively enhance crop performance and overall fruit quality of tomato.
Source of Circulating Pentraxin 3 in Septic Shock Patients

Sepsis, which is the leading cause of death in intensive care units (ICU), has been acknowledged as a global health priority by the WHO in 2017. Identification of biomarkers allowing early stratification and recognition of patients at higher risk of death is crucial. One promising biomarker candidate is pentraxin-3 (PTX3); initially elevated and persistently increased plasma concentration in septic patients has been associated with increased mortality. PTX3 is an acute phase protein mainly stored in neutrophil granules. These cells are responsible for rapid and prompt release of PTX3 in inflammatory context, but the cellular origin responsible for successive days' elevation in sepsis remains unknown. Upon inflammatory stimulation, PTX3 can also be produced by other cell types, including endothelial and immune cells. As in septic patients immune alterations have been described, we therefore sought to investigate whether such cells participated in the elevation of PTX3 over the first days after septic shock onset. To address this point, PTX3 was measured in plasma from septic shock patients at day 3 after ICU admission as well as in healthy volunteers (HV), and the capacity of whole blood cells to secrete PTX3 after inflammatory stimulation was evaluated ex vivo. A significantly mean higher (100-fold) concentration of plasma PTX3 was found in patients compared to HV, which was likely due to the inflammation-induced initial release of the pre-existing PTX3 reservoir contained in neutrophils. Strikingly, when whole blood was stimulated ex vivo with LPS no significant difference between patients and HV in PTX3 release was found. This was in contrast with TNFα which decreased production was illustrative of the endotoxin tolerance phenomenon occurring in septic patients. Then, the release of PTX3 protein from a HV neutrophil-free PBMC endotoxin tolerance model was investigated. At the transcriptional level, PTX3 seems to be a weakly tolerizable gene similar to TNFα. Conversely, increased protein levels observed in anergy condition reflects a non-tolerizable phenotype, more likely to an anti-inflammatory marker. Hence, altered immune cells still have the ability to produce PTX3 in response to an inflammatory trigger, and therefore circulating white blood cell subset could be responsible of the sustained PTX3 plasma levels over the first days of sepsis setting.
Bright Dots and Smart Optical Microscopy to Probe Intracellular Events in Single Cells

Probing intracellular events is a key step in developing new biomedical methodologies. Optical microscopy has been one of the best options to observe biological samples at single cell and sub-cellular resolutions. Morphological changes are readily detectable in brightfield images. When stained with fluorescent molecules, distributions of intracellular organelles, and biological molecules are made visible using fluorescence microscopes. In addition to these morphological views of cells, optical microscopy can reveal the chemical and physical status of defined intracellular spaces. This review begins with a brief overview of genetically encoded fluorescent probes and small fluorescent chemical dyes. Although these are the most common approaches, probing is also made possible by using tiny materials that are incorporated into cells. When these tiny materials emit enough photons, it is possible to draw conclusions about the environment in which the tiny material resides. Recent advances in these tiny but sufficiently bright fluorescent materials are nextly reviewed to show their applications in tracking target molecules and in temperature imaging of intracellular spots. The last section of this review addresses purely optical methods for reading intracellular status without staining with probes. These non-labeling methods are especially essential when biospecimens are thereafter required for in vivo uses, such as in regenerative medicine.
Genome Sequencing and Comparative Transcriptomics Provide a Holistic View of 4-Nitrophenol Degradation and Concurrent Fatty Acid Catabolism by Rhodococcus sp. Strain BUPNP1

Rhodococcus sp.strain BUPNP1 can utilize the priority environmental pollutant 4-nitrophenol (4-NP) as its sole source of carbon and energy. In this study, genome and transcriptome sequencing were used to gain mechanistic insights into 4-NP degradation. The draft BUPNP1 genome is 5.56 Mbp and encodes 4,963 proteins, which are significantly enriched in hypothetical proteins compared to other Rhodococcus sp. A novel 4-NP catabolic 43 gene cluster “nph” was identified that encodes all the genes required for the conversion of 4-NP into acetyl-CoA and succinate, via 4-nitrocatechol. The cluster also encodes pathways for the catabolism of other diverse aromatic compounds. Comparisons between BUPN1 growing on either 4-NP or glucose resulted in significant changes in the expression of many nph cluster genes, and, during 4-NP growth, a loss of lipid inclusions. Moreover, fatty acid degradation/synthesis genes were found within the nph cluster, suggesting fatty acids may be concurrently catabolised with 4-NP. A holistic model for the action of the nph gene cluster is proposed which incorporates genetic architecture, uptake and metabolism of aromatic compounds, enzymatic activities and transcriptional regulation. The model provides testable hypotheses for further biochemical investigations into the genes of the nph cluster, for potential exploitation in bioremediation.
γ-Secretase Studied by Atomistic Molecular Dynamics Simulations: Global Dynamics, Enzyme Activation, Water Distribution and Lipid Binding

γ-secretase, an intramembrane-cleaving aspartyl protease is involved in the cleavage of a large number of intramembrane proteins. The most prominent substrate is the amyloid precursor protein, whose proteolytic processing leads to the production of different amyloid Aβ peptides. These peptides are known to form toxic aggregates and may play a key role in Alzheimer's disease (AD). Recently, the three-dimensional structure of γ-secretase has been determined via Cryo-EM, elucidating the spatial geometry of this enzyme complex in different functional states. We have used molecular dynamics (MD) simulations to study the global dynamics and conformational transitions of γ-secretase, as well as the water and lipid distributions in and around the transmembrane domains in atomic detail. Simulations were performed on the full enzyme complex and on the membrane embedded parts alone. The simulations revealed global motions compatible with the experimental enzyme structures and indicated little dependence of the dynamics of the transmembrane domains on the soluble extracellular subunits. During the simulation on the membrane spanning part a transition between an inactive conformation (with catalytic residues far apart) toward a putatively active form (with catalytic residues in close proximity) has been observed. This conformational change is associated with a distinct rearrangement of transmembrane helices, a global compaction of the catalytically active presenilin subunit a change in the water structure near the active site and a rigidification of the protein fold. The observed conformational rearrangement allows the interpretation of the effect of several mutations on the activity of γ-secretase. A number of long-lived lipid binding sites could be identified on the membrane spanning surface of γ-secretase which may coincide with association regions of hydrophobic membrane helices to form putative substrate binding exosites.
IRE1α Activation in Bone Marrow-Derived Dendritic Cells Modulates Innate Recognition of Melanoma Cells and Favors CD8+ T Cell Priming

The IRE1α/XBP1s signaling pathway is an arm of the unfolded protein response (UPR) that safeguards the fidelity of the cellular proteome during endoplasmic reticulum (ER) stress, and that has also emerged as a key regulator of dendritic cell (DC) homeostasis. However, in the context of DC activation, the regulation of the IRE1α/XBP1s axis is not fully understood. In this work, we report that cell lysates generated from melanoma cell lines markedly induce XBP1s and certain members of the UPR such as the chaperone BiP in bone marrow derived DCs (BMDCs). Activation of IRE1α endonuclease upon innate recognition of melanoma cell lysates was required for amplification of proinflammatory cytokine production and was necessary for efficient cross-presentation of melanoma-associated antigens without modulating the MHC-II antigen presentation machinery. Altogether, this work provides evidence indicating that ex-vivo activation of the IRE1α/XBP1 pathway in BMDCs enhances CD8+ T cell specific responses against tumor antigens.