Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of Vancomycin Dosing Guidance During Transition of Care

Vancomycin is an antibiotic commonly used to treat serious gram‐positive infections. Patients requiring prolonged therapy in Singapore routinely receive intermittent vancomycin infusion in the hospital and are switched to continuous infusion for outpatient parenteral antibiotic therapy. During this transition of care, there may be a risk of not achieving therapeutic targets. We evaluated the performance of a model‐based dosing algorithm in achieving a therapeutic target within 7 days of care transition. A published population pharmacokinetic model was used as the foundation to guide vancomycin dosing when discharging inpatients on intermittent infusion to outpatient care on continuous infusion. Selected demographic variables (age, weight, and creatinine clearance) were used to devise initial dosing. Patients with guided dosing were compared with historic controls (dosing by clinicians alone). The primary outcome of the study was to achieve vancomycin steady‐state concentration of 20‐25 mg/L. Compared with historic controls, the proportion of patients attaining a therapeutic target by day 7 was significantly improved (6 of 19 [31.6%] vs 12 of 17 [70.6%], P = .04). Our model‐based approach could guide customized dosing to facilitate switching patients from intermittent to continuous infusion during transition of care. Further validation in a larger patient cohort is warranted.
Dreaming during the Covid-19 pandemic: Computational assessment of dream reports reveals mental suffering related to fear of contagion

The current global threat brought on by the Covid-19 pandemic has led to widespread social isolation, posing new challenges in dealing with metal suffering related to social distancing, and in quickly learning new social habits intended to prevent contagion. Neuroscience and psychology agree that dreaming helps people to cope with negative emotions and to learn from experience, but can dreaming effectively reveal mental suffering and changes in social behavior? To address this question, we applied natural language processing tools to study 239 dream reports by 67 individuals, made either before the Covid-19 outbreak or during the months of March and April, 2020, when lockdown was imposed in Brazil following the WHO’s declaration of the pandemic. Pandemic dreams showed a higher proportion of anger and sadness words, and higher average semantic similarities to the terms “contamination” and “cleanness”. These features seem to be associated with mental suffering linked to social isolation, as they explained 40% of the variance in the PANSS negative subscale related to socialization (p = 0.0088). These results corroborate the hypothesis that pandemic dreams reflect mental suffering, fear of contagion, and important changes in daily habits that directly impact socialization.
Cloning, expression and purification of recombinant dermatopontin in Escherichia coli

Dermatopontin (DPT) is an extracellular matrix (ECM) protein with diversified pharmaceutical applications. It plays important role in cell adhesion/migration, angiogenesis and ECM maintenance. The recombinant production of this protein will enable further exploration of its multifaceted functions. In this study, DPT protein has been expressed in Escherichia coli (E.coli) aiming at cost effective recombinant production. The E.coli GJ1158 expression system was transformed with constructed recombinant vector (pRSETA-DPT) and protein was expressed as inclusion bodies on induction with NaCl. The inclusion bodies were solubilised in urea and renaturation of protein was done by on-column refolding procedure in Nickel activated Sepharose column. The refolded Histidine-tagged DPT protein was purified and eluted from column using imidazole and its purity was confirmed by analytical techniques. The biological activity of the protein was confirmed by collagen fibril assay, wound healing assay and Chorioallantoic Membrane (CAM) angiogenesis assay on comparison with standard DPT. The purified DPT was found to enhance the collagen fibrillogenesis process and improved the migration of human endothelial cells. About 73% enhanced wound closure was observed in purified DPT treated endothelial cells as compared to control. The purified DPT also could induce neovascularisation in the CAM model. At this stage, scaling up the production process for DPT with appropriate purity and reproducibility will have a promising commercial edge.
Antiproliferative, Antimicrobial and Antiviral Activity of β-Aryl-δ-iodo-γ-lactones, Their Effect on Cellular Oxidative Stress Markers and Biological Membranes

The aim of this work was the examination of biological activity of three selected racemic cis-β-aryl-δ-iodo-γ-lactones. Tested iodolactones differed in the structure of the aromatic fragment of molecule, bearing isopropyl (1), methyl (2), or no substituent (3) on the para position of the benzene ring. A broad spectrum of biological activity as antimicrobial, antiviral, antitumor, cytotoxic, antioxidant, and hemolytic activity was examined. All iodolactones showed bactericidal activity against Proteus mirabilis, and lactones 1,2 were active against Bacillus cereus. The highest cytotoxic activity towards HeLa and MCF7 cancer cell lines and NHDF normal cell line was found for lactone 1. All assessed lactones significantly disrupted antioxidative/oxidative balance of the NHDF, and the most harmful effect was determined by lactone 1. Contrary to lactone 1, lactones 2 and 3 did not induce the hemolysis of erythrocytes after 48 h of incubation. The differences in activity of iodolactones 1–3 in biological tests may be explained by their different impact on physicochemical properties of membrane as the packing order in the hydrophilic area and fluidity of hydrocarbon chains. This was dependent on the presence and type of alkyl substituent. The highest effect on the membrane organization was observed for lactone 1 due to the presence of bulky isopropyl group on the benzene ring.
Detection of Methanobrevobacter smithii and Methanobrevibacter oralis in Lower Respiratory Tract Microbiota

Methanogens, the sole microbes producing methane, are archaea commonly found in human anaerobic microbiota. Methanogens are emerging as opportunistic pathogens associated with dysbiosis and are also detected and cultured in anaerobic abscesses. Their presence in the respiratory tract is yet unknown. As a preliminary answer, prospective investigation of 908 respiratory tract samples using polyphasic approach combining PCR-sequencing, real-time PCR, fluorescent in situ hybridization (FISH), and methanogens culture was carried out. Methanobrevibacter smithii and Methanobrevibacter oralis DNA sequences, were detected in 21/527 (3.9%) sputum samples, 2/188 (1.06%) bronchoalveolar lavages, and none of 193 tracheo-bronchial aspirations. Further, fluorescence in situ hybridization detected methanogens in three sputum investigated specimens with stick morphology suggesting M. oralis and in another one bronchoalveolar lavage sample investigated, diplococal morphology suggesting M. smithii. These observations extend the known territory of methanogens to the respiratory tract and lay the foundations for further interpretation of their detection as pathogens in any future cases of isolation from bronchoalveolar lavages and the lungs.
Evasion of the Cell-Mediated Immune Response by Alphaherpesviruses

Alphaherpesviruses cause various diseases and establish life-long latent infections in humans and animals. These viruses encode multiple viral proteins and miRNAs to evade the host immune response, including both innate and adaptive immunity. Alphaherpesviruses evolved highly advanced immune evasion strategies to be able to replicate efficiently in vivo and produce latent infections with recurrent outbreaks. This review describes the immune evasion strategies of alphaherpesviruses, especially against cytotoxic host immune responses. Considering these strategies, it is important to evaluate whether the immune evasion mechanisms in cell cultures are applicable to viral propagation and pathogenicity in vivo. This review focuses on cytotoxic T lymphocytes (CTLs), natural killer cells (NK cells), and natural killer T cells (NKT cells), which are representative immune cells that directly damage virus-infected cells. Since these immune cells recognize the ligands expressed on their target cells via specific activating and/or inhibitory receptors, alphaherpesviruses make several ligands that may be targets for immune evasion. In addition, alphaherpesviruses suppress the infiltration of CTLs by downregulating the expression of chemokines at infection sites in vivo. Elucidation of the alphaherpesvirus immune evasion mechanisms is essential for the development of new antiviral therapies and vaccines.
Low education is associated with poor periodontal status in patients with type 2 diabetes mellitus: A cross‐sectional study

Cardiovascular disease remains the most common cause of death in patients with type 2 diabetes mellitus. Because periodontitis is a risk factor of cardiovascular disease, identification of risk factors of periodontitis is valuable to control periodontitis effectively. The purpose of this study was to examine the association of education and household income with periodontal status in patients with type 2 diabetes mellitus.
Characterization of humic‐like substances in Arctic aerosols

Humic‐like substances (HULIS) are a complex group of relatively high molecular weight organic compounds which contribute considerably to the mass of organic carbon (OC) and influence the light‐absorbing properties of aerosols. In this work, HULIS were investigated for the first time in the high‐Arctic atmosphere, focusing on the chemical characterization and mass contribution of HULIS to the total suspended particle (TSP) mass using weekly aerosol samples collected at Station Nord, northeast Greenland every fourth week during 2010. Average HULIS‐C concentration was 11 ng C m−3 during the darker months (November–April) and 4 ng C m−3 during the other months (May–October) with an annual mass concentration of 0.02 ± 0.01 µg m−3. HULIS‐C contributed to 3–16% of water‐soluble organic carbon (WSOC), whereas HULIS accounted for 0.7–4.1% of TSP mass, with TSP typically below 1.0 µg m−3. Concentrations of OC, WSOC, HULIS, selected HULIS functional groups (carboxylic acids, aromatic carboxylic acids, and organosulfates) and levoglucosan overlapped with the typical Arctic haze pattern with elevated concentrations during winter to early spring. The aromatic carboxylic acid portion accounted for a larger share of total carboxylic acid of HULIS during the darker months (7%) compared to the brighter months (3%). The more abundant aromatic carboxylic acid functional groups and the moderate correlation between HULIS and levoglucosan concentrations during the darker months both indicate that biomass burning aerosols and thereby emissions of aromatic compounds could contribute to HULIS in the Arctic, especially during late winter. During the brighter months, relatively higher average molecular weight of HULIS was observed.
Inference of mutability landscapes of tumors from single cell sequencing data

One of the hallmarks of cancer is the extremely high mutability and genetic instability of tumor cells. Inherent heterogeneity of intra-tumor populations manifests itself in high variability of clone instability rates. Analogously to fitness landscapes, the instability rates of clonal populations form their mutability landscapes. Here, we present MULAN (MUtability LANdscape inference), a maximum-likelihood computational framework for inference of mutation rates of individual cancer subclones using single-cell sequencing data. It utilizes the partial information about the orders of mutation events provided by cancer mutation trees and extends it by inferring full evolutionary history and mutability landscape of a tumor. Evaluation of mutation rates on the level of subclones rather than individual genes allows to capture the effects of genomic interactions and epistasis. We estimate the accuracy of our approach and demonstrate that it can be used to study the evolution of genetic instability and infer tumor evolutionary history from experimental data. MULAN is available at https://github.com/compbel/MULAN.
A proteomic approach to understand the clinical significance of acute myeloid leukemia-derived extracellular vesicles reflecting essential characteristics of leukemia.

Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. Enzyme-linked immunosorbent assay results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML-derived EVs could reflect essential leukemia biology.
Real-Time Locating System in Production Management

Real-time monitoring and optimization of production and logistics processes significantly improve the efficiency of production systems. Advanced production management solutions require real-time information about the status of products, production, and resources. As real-time locating systems (also referred to as indoor positioning systems) can enrich the available information, these systems started to gain attention in industrial environments in recent years. This paper provides a review of the possible technologies and applications related to production control and logistics, quality management, safety, and efficiency monitoring. This work also provides a workflow to clarify the steps of a typical real-time locating system project, including the cleaning, pre-processing, and analysis of the data to provide a guideline and reference for research and development of indoor positioning-based manufacturing solutions.
Antimicrobial Resistance in Typhoidal Salmonella: Surveillance for Enteric Fever in Asia Project, 2016–2019

Abstract Background Clinicians have limited therapeutic options for enteric as a result of increasing antimicrobial resistance, and therefore typhoid vaccination is recommended as a preventive measure. As a part of the Surveillance for Enteric Fever in Asia Project (SEAP), we investigated the extent measured the burden of antimicrobial resistance (AMR) among confirmed enteric fever cases in Bangladesh, Nepal, and Pakistan. Methods From September 2016–September 2019, SEAP recruited study participants of all age groups from its outpatient, inpatient, hospital laboratory, laboratory network, and surgical sites who had a diagnosis of febrile illness that was either suspected or blood culture confirmed for enteric fever. Antimicrobial resistance of isolates was determined by disc diffusion using Clinical and Laboratory Standard Institute cut-off points. We reported the frequency of multidrug resistance (MDR)(resistance to ampicillin, cotrimoxazole, and chloramphenicol), extensive drug resistance (XDR) (MDR plus non-susceptible to fluoroquinolone and any 3rd generation cephalosporins), and fluoroquinolone (FQ) and azithromycin non-susceptibility. Results We enrolled 8,705 blood culture confirmed enteric fever cases: 4,873 (56%) from Bangladesh, 1,602 (18%) from Nepal and 2,230 (26%) from Pakistan. Of these, 7,591 (87%) were Salmonella Typhi and 1114 (13%) were S. Paratyphi. MDR S. Typhi was identified in 17% (701/4065) of isolates in Bangladesh, and 1% (19/1342) in Nepal. In Pakistan, 16 % (331/2084) of S. Typhi isolates were MDR, and 64% (1319/2074) were XDR. FQ nonsusceptibility among S. Typhi isolates was 98% in Bangladesh, 87% in Nepal, and 95% in Pakistan. Azithromycin non-susceptibility was detected in 77 (2%) in Bangladesh, 9 (.67%) in Nepal and 9 (.59%) isolates in Pakistan. In Pakistan, three (2%) S. Paratyphi isolates were MDR; no MDR S. Paratyphi was reported from Bangladesh or Nepal. Conclusions Although AMR against S. Paratyphi was low across the three countries, there was widespread drug resistance among S. Typhi, including FQ non-susceptibility and the emergence of XDR S. Typhi in Pakistan, limiting treatment options. As typhoid conjugate vaccine (TCV) is rolled out, surveillance should continue to monitor changes in AMR to inform policies and to monitor drug resistance in S. Paratyphi, for which there is no vaccine.
Assessing the Diversity and Population Substructure of Sarda Breed Bucks by Using Mtdna and Y-Chromosome Markers

Simple Summary Domestic goats show extraordinary adaptation to different environments. Sardinia (Italy), the second-largest island in the Mediterranean Sea, is the birthplace of Sarda goats which are raised to produce milk mainly devoted to cheesemaking. The aim of this research was to characterize genetic diversity of Sarda bucks, reared in eight subregions of the island, to gain information about the relationship between genetic variation and geography as well as to investigate the existence of population substructure. We performed genotyping of Y-chromosome markers, which trace the patrilineal diversity, and sequencing of a portion of mitochondrial DNA, which gives information about matrilineal diversity. Analysis of Y-chromosome markers revealed the occurrence of high levels of diversity in populations from Southwest Sardinia. Further analysis of both Y-chromosome and mitochondrial DNA data evidenced the lack of population substructure. These results suggest the occurrence of extensive gene flow between the different subregions of Sardinia. The introduction of goats from other geographical locations, outside Sardinia, and belonging to highly productive breeds probably contributed to enhance genetic variation. Abstract A sample of 146 Sarda bucks from eight subregions of Sardinia, Italy (Nuorese, Barbagia, Baronia, Ogliastra, Sarrabus, Guspinese, Iglesiente, Sulcis) were characterized for Y-chromosome and mtDNA markers to assess the levels of population substructure. Five polymorphic loci (SRY, AMELY, ZFY, and DDX3Y) on the Y-chromosome were genotyped. The control region of mtDNA was sequenced as a source of complementary information. Analysis of Y-chromosome data revealed the segregation of 5 haplotypes: Y1A (66.43%), Y2 (28.57%), Y1C (3.57%), Y1B1 (0.71%), and Y1B2 (0.71%). High levels of Y-chromosome diversity were observed in populations from Southwest Sardinia. The FST values based on Y-chromosome and mtDNA data were low, although a paternal genetic differentiation was observed when comparing the Nuorese and Barbagia populations (Central Sardinia) with the Sulcis, Iglesiente, and Sarrabus populations (Southern Sardinia). AMOVA analysis supported the lack of population substructure. These results suggest the occurrence of a historical and extensive gene flow between Sarda goat populations from different locations of Sardinia, despite the fact that this island is covered by several large mountain ranges. Introgression with foreign caprine breeds in order to improve milk production might have also contributed to avoiding the genetic differentiation amongst Sarda populations.
Monitoring Endothelin-A Receptor Expression during the Progression of Atherosclerosis

Cardiovascular disease remains the most frequent cause of death worldwide. Atherosclerosis, an underlying cause of cardiovascular disease, is an inflammatory disorder associated with endothelial dysfunction. The endothelin system plays a crucial role in the pathogenesis of endothelial dysfunction and is involved in the development of atherosclerosis. We aimed to reveal the expression levels of the endothelin-A receptor (ETAR) in the course of atherogenesis to reveal possible time frames for targeted imaging and interventions. We used the ApoE−/− mice model and human specimens and evaluated ETAR expression by quantitative rtPCR (qPCR), histology and fluorescence molecular imaging. We found a significant upregulation of ETAR after 22 weeks of high-fat diet in the aortae of ApoE−/− mice. With regard to translation to human disease, we applied the fluorescent probe to fresh explants of human carotid and femoral artery specimens. The findings were correlated with qPCR and histology. While ETAR is upregulated during the progression of early atherosclerosis in the ApoE−/− mouse model, we found that ETAR expression is substantially reduced in advanced human atherosclerotic plaques. Moreover, those expression changes were clearly depicted by fluorescence imaging using our in-house designed ETAR-Cy 5.5 probe confirming its specificity and potential use in future studies.
Gender moderates the relationship between media use and sleep quality

With high screen time and poor sleep commonly reported in adolescents, it is important to more fully understand how screen time impacts sleep. Despite similar overall screen times, male and female media preferences and usages differ, making it critical to determine if different domains of screen time differentially affect sleep quality. The present study examined whether differing amounts and domains of screen‐based media vary in impact on sleep quality of 16‐year‐old male and female adolescents over a 3‐month period. A total of 98 adolescents (mean [SD] age 16.27 [0.29] years; 51% female) completed two online surveys spaced 3 months apart and comprised of well‐validated self‐reported measures of sleep quality, media usage, and depressive symptoms. The various domains of media were categorised into screen‐based media with little‐to‐no peer‐to‐peer interaction involved (video‐only) and screen‐based media with interaction a predominant component to the usage (peer‐to‐peer interaction‐involved). Self‐reported sleep quality decreased across the 3‐month study period. Gender moderated the effect of interactive screen time on sleep quality 3 months later, with interactive screen time associated with better sleep quality in males, but remaining poorer in females. Screen time competes with sleep time and may do so differentially depending on the media domain. Compared to females, interactive components of screen time may lessen worsening sleep quality over time in males. Understanding the relationships among screen time, its content, age, and gender may inform guidelines for educators, parents, and adolescents to help improve sleep quality of adolescents.