Miracle-dz/UniFAR-FTUs huggingface dataset:
COVID-19 and Antimicrobial Resistance: A Review

As the world continues to respond to the coronavirus pandemic (COVID-19), there is a larger hidden threat of antimicrobial resistance (AMR) lurking behind. AMR remains worrisome in that the pathogens causing resistant infections to thrive in hospitals and medical facilities, putting all patients at risk, irrespective of the severity of their medical conditions, further compounding the management of COVID-19. This study aims to provide overview of early findings on COVID-19 and AMR as well as to provide recommendations and lesson learned toward improving antimicrobial stewardship. We conducted a rapid narrative review of published articles by searching PubMed and Google Scholar on COVID-19 and Antimicrobial Resistance with predetermined keywords. Secondary bacterial infections play crucial roles in mortality and morbidity associated with COVID-19. Research has shown that a minority of COVID-19 patients need antibiotics to treat secondary bacterial infections. Current evidence reiterates the need not to give antibiotic therapy or prophylaxis to patients with mild COVID-19 or to patients with suspected or confirmed moderate COVID-19 illness unless it is indicated. The pandemic has also brought to the fore the deficiencies in health systems around the world. This comes with a lot of lessons, one of which is that despite the advances in medicine; we remain incredibly vulnerable to infections with limited or no standard therapies. This is worth thinking in the context of AMR, as the resistant pathogens are evolving and leading us to the era of untreatable infections. There is a necessity for continuous research into understanding and controlling infectious agents, as well as the development of newer functional antimicrobials and the need to strengthen the antimicrobial stewardship programs.
DTYMK Expression Predicts Prognosis and Chemotherapeutic Response and Correlates with Immune Infiltration in Hepatocellular Carcinoma

Introduction Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Identifying specific molecular markers that can predict HCC prognosis is extremely important. The protein deoxythymidylate kinase (DTYMK) has been reported to contribute to unfavorable prognosis in non-small cell lung cancer patients, but its role in the prediction of HCC patient prognosis has not been clarified. Methods Samples from the TCGA and GEO databases were consecutively enrolled for gene expression analysis, clinicopathology analysis, immune microenvironment analysis and chemotherapeutic response prediction. The results were validated using 86 samples from the First Affiliated Hospital of Sun Yat-sen University. Cox regression analysis was used to analyze the effect of DTYMK on progression-free survival (PFS) and overall survival (OS). Functional enrichment analysis was used to describe the marker pathways that were significantly related to DTYMK. TIMER (Tumor Immune Estimation Resource), TISIDB (Tumor and Immune System Interaction DataBase) and CIBERSORT (Cell type Identification By Estimating Relative Subsets Of RNA Transcripts) were used to explore the immune microenvironment. Results We found that DTYMK expression upregulation is associated with poor prognosis in HCC patients and tightly related to the pathways regulating the cell cycle and acid metabolism. Our findings revealed that hepatocellular carcinoma cell lines with high DTYMK expression were more sensitive to sorafenib and many other chemotherapeutic drugs. We also found an inhibiting effect of DTYMK on the immune microenvironment in the process of tumorigenesis. Discussion We found that DTYMK has potential as a new prognostic and chemotherapeutic response biomarker for HCC patients and correlates with the immune microenvironment in HCC. However, there are some deficiencies in our study. First, this is a retrospective study that may lead to selection bias. Second, the protein expression of DTYMK was investigated via immunohistochemical analysis. Finally, we did not explore the exact underlying molecular mechanisms of DTYMK in tumorigenesis in this study, which is needed to be clarified in future research.
Evidence and Current Use of Levosimendan in the Treatment of Heart Failure: Filling the Gap

Abstract Levosimendan is a distinctive inodilator combing calcium sensitization, phosphodiesterase inhibition and vasodilating properties through the opening of adenosine triphosphate-dependent potassium channels. It was first approved in Sweden in 2000 for the short-term treatment of acutely decompensated severe chronic heart failure when conventional therapy is not sufficient, and in cases where inotropic support is considered appropriate. After more than 20 years, clinical applications have considerably expanded across critical care and emergency medicine, and levosimendan is now under investigation in different cardiac settings (eg, septic shock, pulmonary hypertension) and for non-cardiac applications (eg, amyotrophic lateral sclerosis). This narrative review outlines key milestones in levosimendan history, by addressing regulatory issues, pharmacological peculiarities and clinical aspects (efficacy and safety) of a drug that did not receive great attention in the heart failure guidelines. A brief outlook to the ongoing clinical trials is also offered.
Investigating the Mechanism of Scutellariae barbata Herba in the Treatment of Colorectal Cancer by Network Pharmacology and Molecular Docking

Background Colorectal cancer (CRC) is one of the most common gastrointestinal tumors, which accounts for approximately 10% of all diagnosed cancers and cancer deaths worldwide per year. Scutellariae barbatae Herba (SBH) is one of the most frequently used traditional Chinese medicine (TCM) in the treatment of CRC. Although many experiments have been carried out to explain the mechanisms of SBH, the mechanisms of SBH have not been illuminated fully. Thus, we constructed a network pharmacology and molecular docking to investigate the mechanisms of SBH. Methods We adopted active constituent prescreening, target predicting, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, differentially expressed gene analysis, and molecular docking to establish a system pharmacology database of SBH against CRC. Results A total of 64 active constituents of SBH were obtained and 377 targets were predicted, and the result indicated that quercetin, luteolin, wogonin, and apigenin were the main active constituents of SBH. Glucocorticoid receptor (NR3C1), pPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA), cellular tumor antigen p53 (TP53), transcription factor AP-1 (JUN), mitogen-activated protein kinase 1 (MAPK1), Myc protooncogene protein (MYC), cyclin-dependent kinase 1 (CDK1), and broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) were the major targets of SBH in the treatment of CRC. GO analysis illustrated that the core biological process regulated by SBH was the regulation of the cell cycle. Thirty pathways were presented and 8 pathways related to CRC were involved. Molecular docking presented the binding details of 3 key targets with 6 active constituents. Conclusions The mechanisms of SBH against CRC depend on the synergistic effect of multiple active constituents, multiple targets, and multiple pathways.
Analyzing COVID‐19 Using Multisource Data: An Integrated Approach of Visualization, Spatial Regression, and Machine Learning

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2, was first identified in Wuhan, China, in December 2019. As the number of COVID‐19 infections and deaths worldwide continues to increase rapidly, the prevention and control of COVID‐19 remains urgent. This article aims to analyze COVID‐19 from a geographical perspective, and this information can provide useful insights for rapid visualization of spatial‐temporal epidemic information and identification of the factors important to the spread of COVID‐19. A new type of vitalization method, called the point grid map, is integrated with calendar‐based visualization to show the spatial‐temporal variations in COVID‐19. The combination of mixed geographically weighted regression (mixed GWR) and extreme gradient boosting (XGBoost) is used to identify the potential factors and the corresponding importance. The visualization results clearly reflect the spatial‐temporal patterns of COVID‐19. The quantified results reveal that the impact of population outflow from Wuhan is the most important factor and indicate statistically significant spatial heterogeneity. Our results provide insights into how multisource big geodata can be employed within the framework of integrating visualization and analytical methods to characterize COVID‐19 trends. In addition, this work can help understand the influential factors for controlling and preventing epidemics, which is important for policy design and effective decision‐making for controlling COVID‐19. The results reveal that one of the most effective ways to control COVID‐19 include controlling the source of infection, cutting off the transmission route, and protecting vulnerable groups.
A Defect Detection Method for Rail Surface and Fasteners Based on Deep Convolutional Neural Network

As a result of long-term pressure from train operations and direct exposure to the natural environment, rails, fasteners, and other components of railway track lines inevitably produce defects, which have a direct impact on the safety of train operations. In this study, a multiobject detection method based on deep convolutional neural network that can achieve nondestructive detection of rail surface and fastener defects is proposed. First, rails and fasteners on the railway track image are localized by the improved YOLOv5 framework. Then, the defect detection model based on Mask R-CNN is utilized to detect the surface defects of the rail and segment the defect area. Finally, the model based on ResNet framework is used to classify the state of the fasteners. To verify the robustness and effectiveness of our proposed method, we conduct experimental tests using the ballast and ballastless railway track images collected from Shijiazhuang-Taiyuan high-speed railway line. Through a variety of evaluation indexes to compare with other methods using deep learning algorithms, experimental results show that our method outperforms others in all stages and enables effective detection of rail surface and fasteners.
Patient and treatment characteristics and safety outcomes of patients with relapsing-remitting multiple sclerosis treated with natalizumab in Greece: Results from the multicenter, 5-year prospective observational study ‘TOPICS greece’

Background Natalizumab is a highly efficacious treatment for relapsing-remitting multiple sclerosis (RRMS). Objective To assess the real-world long-term safety of natalizumab in RRMS. Methods This multicenter, 5-year prospective observational study, included adults with RRMS newly initiated on natalizumab as per the approved product label in the routine care in Greece. Safety was evaluated by collecting serious adverse events (SAEs) following study enrollment. Results Between 19-Apr-2012 and 18-Dec-2014, 304 eligible patients (median age at natalizumab initiation: 38.0 years; median disease duration: 6.2 years) were enrolled by 20 hospital-based neurologists. Over a median treatment duration period of 58.7 months, 50.7% of the patients discontinued natalizumab, mainly due to anti-JCV antibody detection (59.1%). The adverse event treatment discontinuation rate was 5.2%. The SAE incidence rate during the safety data collection period (median: 48.7 months) was 4.6%. The most common SAEs were infections (1.0%), including 2 cases (0.7%) of progressive multifocal leukoencephalopathy (PML), and no other opportunistic infections. PML diagnoses occurred 6.2-6.7 years after natalizumab initiation, and approximately 2 years after first detection of anti-JCV antibody for both patients. The incidence rate of malignancies was 0.7%. Conclusion In real-world settings in Greece, natalizumab displayed an acceptable safety profile, with no new safety signals emerging.
The effect of mouthwashes on fluoride dentifrices in preventing dental abrasion or erosion

Erosive tooth wear (ETW) refers to the chemical dissolution of mineralized tissues by acids of non-bacterial origin. It occurs in the primary as well as the permanent dentition. In this study, our objectives were to investigate and compare the impact of chlorhexidine gluconate (CHX), essential oils (EO), and cetylpyridinium chloride (CPC) on ETW protection produced by conventional fluoride kinds of toothpaste. A clinically relevant in-vitro erosion/abrasion pH cycling model was employed to test the effect of the aforementioned mouthwashes on modulating the ability of NaF and SnF2 types of toothpaste. The mean dentin surface loss associated with NaF toothpaste was significantly lower than for the SnF2 toothpaste. On the other hand, enamel surface loss with SnF2 toothpaste was significantly lower than for the NaF toothpaste. Also, the surface loss of erosion was significantly higher when associated with abrasion than without brushing and for both enamel and dentin. There was no significant difference in the surface loss among all types of mouthwash. Commonly used types of mouthwash containing antimicrobial agents or additional fluoride do not impact fluoride toothpaste action on erosion/abrasion. Also, considering erosion only, the tested SnF2 dentifrice provided better protection against surface loss of enamel than the other.
The inverse relation between risks and benefits: The impact of individual differences in information processing style

Existing research shows that evaluations of the risks and benefits of various hazards (i.e., technologies and activities) are inversely related. The affect heuristic explains the negative relation between risks and benefits, as based on the strength of positive or negative affect associated with a hazard. Research on the affect heuristic previously investigated under which conditions people judge risk and benefits independently, focusing on expertise as a factor that might exempt from inversely related judgements of risk and benefits. Measurements within Dual Process Theories have been found to be associated with rational, analytical decision making and accurate judgments. In this paper we investigated the extent to which rational information processing styles can predict the risk-benefit relation of technologies in a medical and food applications and whether the attitudes influence the strength or direction of the relationship. Using the Need for Cognition Scale (NFC), a psychometric-based risk scale and an explicit measure of attitude, in a representative sample of 3228 Swedes, we found that the high NFC group judged the risks and benefits of technologies to be inversely related. In contrast, the low NFC group judged the risks and benefits to be positively related. These results were confirmed across all studied technologies by applying moderation analysis. We discuss the results in light of recent research on cognitive processing and polarization over technologies’ risks.
Radiocesium concentrations in great cormorants (Phalacrocorax carbo) between 2011 and 2012 after the Fukushima Dai-ichi Nuclear Power Plant accident

Radiocesium concentrations were measured in the pectoralis muscles of great cormorant (n = 36) collected from Gunma Prefecture between November 2011 and July 2012. The 137Cs contamination levels in great cormorant were consistent with the 137Cs deposition levels on ground soil and 137Cs concentrations in freshwater fishes. The Tag of great cormorants were comparable with those of other birds except for copper pheasant.
Are advanced clinical practice roles in England’s National Health Service a remedy for workforce problems? A qualitative study of senior staff perspectives

Objective A major issue facing all health systems is improving population health while at the same time responding to both growing patient numbers and needs and developing and retaining the health care workforce. One policy response to workforce shortages has been the development of advanced clinical practice roles. In the context of an English national policy promoting such roles in the health service, we explored senior managers’ and senior clinicians’ perceptions of factors at the organization level that support or inhibit the introduction of advanced clinical practice roles. The investigation was framed by theories of the diffusion of innovation and the system of professions. Methods We conducted a qualitative interview study of 39 senior manager and clinicians in 19 National Health Service acute, community, mental health and ambulance organizations across a metropolitan area in 2019. Results Small numbers of advanced clinical practice roles were reported, often in single services. Four main influences were identified in the development of advanced clinical practice roles: staff shortages (particularly of doctors in training grades) combined with rising patient demand, the desire to retain individual experienced staff, external commissioners or purchasers of services looking to shape services in line with national policy, and commissioner-funded new roles in new ambulatory care services and primary care. Three factors were reported as enabling the roles: finance for substantive posts, evidence of value of the posts, and structural support within the organization. Three factors were perceived as inhibiting developing the roles: confusion and lack of knowledge amongst clinicians and managers, the availability of finance for the roles, and a nervousness (sometimes resistance) to introducing the new roles. Conclusions While the national policy was to promote advanced clinical practice roles, the evidence suggested there was and would continue to be limited implementation at the operational level. Development scenarios that introduced new monies for such roles reduced some of the inhibiting factors. However, where the introduction of roles required funding to move from one part of a service to another, and potentially from one staff group to another, the growth of these roles was and is likely to be contested. In such scenarios, research and business evidence of relative advantage will be important, as too will be supporters in powerful positions. The paucity of publicly available evidence on the effectiveness of advanced clinical practice roles across the specialties and professions in different contexts requires urgent attention.
Volumetric growth analysis of maxillary sinus using computed tomography scan segmentation: a pilot study of Indonesian population

The aim of this study is to investigate the volumetric measurements of the maxillary sinus among Indonesian population through computed tomography (CT) scan semi-automated segmentation. This project collected 802 retrospective head CT scan archives from Department of Radiology, Hasan Sadikin Hospital, Bandung, Indonesia between 2019–2020. Patients with craniofacial anomalies/pathology fracture in proximity of the maxillary sinuses, and mediocre image quality were excluded from this study resulting only 97 CT scan archives (194 maxillary sinuses; 52 males; 45 females; age range 0–25 years old). Three-dimensional craniofacial structures were reconstructed and volumetric measurements of the maxillary sinus were computed through semi-automated segmentation using ITK-SNAP. This study recorded the initial phase of maxillary sinus pneumatization during infancy. The maxillary sinus developed until reaching the maximum of average maxillary sinus volume at 13,278.73 mm3 in 16 to 20 years old group in which afterwards fell to 12,325.21 mm3. There was no difference found between right and left maxillary sinus volume. This study revealed that the pneumatization of maxillary sinus begin during infancy and climb until reaching the second decade of life, in which after that slowly decrease. Moreover, no difference between right and left maxillary sinus volume was detected. The volumetric dimension of maxillary sinus presented in this study may serve as the basis knowledge surgical intervention of maxillary sinus and its related structures.
Out‐of‐hospital cardiac arrest and differential risk of cardiac and non‐cardiac QT‐prolonging drugs in 37 000 cases

Drugs that prolong the QT interval, either by design (cardiac QT‐prolonging drugs: anti‐arrhythmics) or as off‐target effect (non‐cardiac QT‐prolonging drugs), may increase the risk of ventricular arrhythmias and out‐of‐hospital cardiac arrest (OHCA). Risk mitigation measures were instituted, in particular, surrounding prescription of cardiac QT‐prolonging drugs. We studied OHCA risk of both drug types in current clinical practice.
The aminoshikimic acid pathway in bacteria as source of precursors for the synthesis of antibacterial and antiviral compounds

Abstract The aminoshikimic acid (ASA) pathway comprises a series of reactions resulting in the synthesis of 3-amino-5-hydroxybenzoic acid (AHBA), present in bacteria such as Amycolatopsis mediterranei and Streptomyces. AHBA is the precursor for synthesizing the mC7N units, the characteristic structural component of ansamycins and mitomycins antibiotics, compounds with important antimicrobial and anticancer activities. Furthermore, aminoshikimic acid, another relevant intermediate of the ASA pathway, is an attractive candidate for a precursor for oseltamivir phosphate synthesis, the most potent anti-influenza neuraminidase inhibitor treatment of both seasonal and pandemic influenza. This review discusses the relevance of the key intermediate AHBA as a scaffold molecule to synthesize diverse ansamycins and mitomycins. We describe the structure and control of the expression of the model biosynthetic cluster rif in A. mediterranei to synthesize ansamycins and review several current pharmaceutical applications of these molecules. Additionally, we discuss some relevant strategies developed for overproducing these chemicals, focusing on the relevance of the ASA pathway intermediates kanosamine, AHAB, and ASA.