Miracle-dz/UniFAR-FTUs huggingface dataset:
Applying Topical Anesthetic on Pediatric Lacerations in the Emergency Department: A Quality Improvement Project

Background Caring for pediatric lacerations in the Emergency Department (ED) is typically painful because of irrigation and suturing. To improve this painful experience, we aimed to increase the use of a topical anesthetic, Eutectic Mixture of Local Anesthetics (EMLA) on eligible pediatric lacerations with an attainable, sustainable, and measurable goal of 60%. Local Problem The baseline rate of applying topical anesthetic to eligible lacerations was 23% in our ED. We aimed to increase the use of topical anesthetics on eligible pediatric lacerations to a measurable goal of 60% within 3 months of implementing our intervention. Methods We conducted a prospective, single center, interrupted time series, ED quality improvement project from November 2019 to July 2020. A multidisciplinary team of physicians and nurses performed a cause-and-effect analysis identifying two key drivers: early placement of EMLA and physician buy-in on which we built our Plan, Do, Study, and Act (PDSA) cycles. We collected data on number of eligible patients receiving EMLA, as well as patient and physician feedback via phone calls within 2 days post encounter. Balancing measures included ED length of stay (LOS), patient and physician satisfaction with EMLA, and side effects of EMLA. Results We needed 3 PDSA cycles to reach our goal of 60% in 3 months, which was also maintained for 5 months. PDSA cycles used educational interventions, direct provider feedback about non-compliance and patient satisfaction results obtained via phone calls. Balancing measures were minimally impacted: 75% good patient satisfaction, No adverse events but an increase in LOS of patients who received EMLA compared to those who did not (1.79 +/- 0.66 VS 1.41 +/- 0.83 hours, p<0.001). The main reasons for dissatisfaction for physicians were the increased LOS and the preference for procedural sedation or intranasal medications. Conclusion With a few simple interventions, our aim of applying EMLA to 60% of eligible pediatric lacerations was attained and maintained.
A microbial consortium‐based product promotes potato yield by recruiting rhizosphere bacteria involved in nitrogen and carbon metabolisms

The effect of a microbial consortium‐based (MCB) biocontrol product, composed of Bacillus subtilis, Trichoderma harzianum strain and diatomaceous earth as a carrier, on potato yield, and potential modes of action for its effect were investigated. The MCB product (300 kg ha−1) was added to furrows in which the potato seed tubers each year for 3 years (2016, 2017 and 2018), while potato planting without the MCB product treatment served as the control. A metagenomic analysis indicated that bacterial phylotypes dominated the microbial community, with a relatively small contribution of archaea and fungal taxa. The relative abundance of beneficial bacterial taxa increased significantly in response to the MCB product treatment. Notably, a higher relative abundance of bacterial taxa with carbon fixation, carbon‐degrading and nitrogen metabolism properties were observed in the MCB product‐treated potato rhizosphere. This was also reflected in the identification of a greater abundance of genes encoding enzymes involved in nitrogen metabolism, carbon fixation and carbon degradation pathways in the conducted metagenomic analysis. The greater relative abundance of these beneficial bacterial taxa in the rhizosphere of MCB product‐treated plots, as well as the higher abundance of genes associated with the indicated cellular processes, were associated with an increase in tuber yield. The observed changes in microbial community structure at an early stage of tuber development appears to have a beneficial impact on tuber yield.
Assessment of Mortality-Related Risk Factors and Effective Antimicrobial Regimens for Treatment of Bloodstream Infections Caused by Carbapenem-Resistant Enterobacterales

Bloodstream infections (BSIs) attributable to carbapenem-resistant Enterobacterales (CRE-BSIs) are dangerous and a major cause of mortality in clinical settings. This study was therefore designed to define risk factors linked to 30-day mortality in CRE-BSI patients and to examine the relative efficacies of different antimicrobial treatment regimens in affected individuals. ABSTRACT Bloodstream infections (BSIs) attributable to carbapenem-resistant Enterobacterales (CRE-BSIs) are dangerous and a major cause of mortality in clinical settings. This study was therefore designed to define risk factors linked to 30-day mortality in CRE-BSI patients and to examine the relative efficacies of different antimicrobial treatment regimens in affected individuals. Data pertaining to 187 CRE-BSI cases from four teaching hospitals in China collected between January 2018 and December 2020 were retrospectively analyzed. For the 187 patients analyzed in this study, the 30-day mortality of CRE-BSI was 41.7% (78/187). Multivariate logistic regression analyses revealed that Pitt bacteremia score, immunocompromised status, meropenem MIC of ≥8 mg/liter,absence of source control of infection, and appropriate empirical therapy were independent predictors of CRE-BSI patient 30-day mortality. After controlling for potential confounding factors relative to ceftazidime-avibactam (CAZ-AVI) treatment, combination therapies including CAZ-AVI (odds ratio [OR], 1.287; 95% confidence interval [CI], 0.124 to 13.403; P = 0.833) were not related to any significant change in patient mortality risk, whereas the 30-day mortality risk was higher for patients administered other antimicrobial regimens (OR, 12.407; 95% CI, 1.684 to 31.430; P = 0.011). When patients were treated with antimicrobial regimens not containing CAZ-AVI, combination therapy (OR, 0.239; 95% CI, 0.077 to 0.741; P = 0.013) was related to a decreased 30-day mortality risk relative to monotherapy treatment. The mortality-related risk factors and relative antimicrobial regimen efficacy data demonstrated in this study may guide the management of CRE-BSI patients.
Bioactive components, ABTS radical scavenging capacity and physical stability of orange, yellow and purple sweet potato (Ipomoea batatas) powder processed by convection‐ or vacuum‐drying methods

Summary This study aims to investigate the antioxidant properties and physical stability of convection- or vacuum-dried orange, yellow and purple sweet potato (Ipomoea batatas) powder upon room temperature storage at different relative humidity (RH) of 33%, 43%, 54% and 75% for 25 days. Both convection and vacuum-dried samples had lower total phenolic content (TPC), anthocyanin content and antioxidant activity compared to the fresh samples. Vacuum-dried powder retained higher antioxidant activity than convection-dried powder. Storage of the powder at high RH of 75% resulted in apparent clump formation, which was likely attributed to the decrease of glass transition temperature (Tg). In general, purple sweet potato powder contained the highest TPC (255.0 mg GAE 100 g DW−1) and antioxidant activity (1924.0 μmol TEAC 100 g DW−1), while orange powder had the highest beta-carotene content (127.2 mg 100 g DW−1). Vacuum-dried sweet potato powder, which has relatively higher antioxidant activity, could be a potential functional ingredient or natural colourant for the food industry.
Real-World Analysis of Therapeutic Outcome in Type 1 Diabetes Mellitus at a Tertiary Care Center

Insulin replacement in type 1 diabetes mellitus (T1DM) needs intensified treatment, which can either be performed by multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). This retrospective analysis of a real-world scenario aimed to evaluate whether glycaemic and cardiovascular risk factors could be controlled with CSII outclass MDI as suggested by recent evidence. Data from patients with either insulin pump (n=68) or injection (n=224) therapy at an Austrian tertiary care centre were analysed between January 2016 and December 2017. There were no significant differences with regard to the latest glycosylated hemoglobin, cardiovascular risk factor control or diabetes-associated late complications. Hypoglycaemia was less frequent (P<0.001), sensor-augmented therapy was more common (P=0.003) and mean body mass index (BMI) was higher (P=0.002) with CSII treatment. This retrospective analysis of real-world data in T1DM did not demonstrate the superiority of insulin pump treatment with regard to glycaemic control or cardiovascular risk factor control.
In Silico Pharmacokinetics Studies for Quinazolines Proposed as EGFR Inhibitors

In silico pharmacokinetics studies can aid the search for molecules with potential ability to be drug candidates. In this paper, a number of quinazoline candidates for epidermal growth factor receptor inhibitors—EGFR, important targets for the treatment of cancer, are computationally analyzed. The literature described that 69 quinazoline molecules were synthesized and the respective half maximum inhibitory concentrations (IC50) were obtained. A bilinear parabolic model was built to investigate the druglikeness by correlating the corresponding lipophilicities, which can be represented by the ideal Log P , with the optimal biological activity in terms of pIC50 values. Structural characteristics leading to improved pharmacokinetics parameters were then analyzed. Compound 56 exhibited the lowest IC50 and, therefore, it had the highest ability to inhibit the EGFR. In the present work, the most potent inhibitor 56 is not calculated to be the most promising drug candidate, since it’s out of the parabolic model obtained due to a Log P above 5, which is not within the expected optimum range. Finally, this work is an example of computational prediction that an experimentally, highly active EGFR inhibitor can be unsuccessful as drug candidate because of pitfalls in pharmacokinetics parameters.
Low-level laser therapy for oral mucositis in children with cancer

Objective To assess the efficacy of oral low-level laser therapy (LLLT) – also known as photobiomodulation – in the reduction of oral mucositis experienced by children and young people with cancer undergoing chemotherapy. Design A systematic review to evaluate the efficacy of oral LLLT for oral mucositis in children with cancer and the safety of oral LLLT in any age with cancer (International Prospective Register of Systematic Reviews/PROSPERO registration: CRD42018099772). Multiple databases and grey literature were screened. Randomised controlled trials were considered for assessing efficacy, and all studies were considered for assessing safety. Primary outcomes included severity of oral mucositis, oral pain and adverse events. Where results were compatible, meta-analysis was performed using a random-effects model. A narrative synthesis considered other outcome measures. Results 14 studies (n>416 children) were included in the narrative synthesis of LLLT efficacy. 5 studies (n=380 children and young people) were included in the meta-analyses. Results demonstrate that LLLT may reduce the severity of oral mucositis and the level of oral pain, but further randomised controlled trials are needed to confirm or deny this. There is vast variation in different trial protocols. Insufficient blinding between LLLT or sham therapy/control led to a strong risk of performance bias. 75 studies (encompassing 2712 patients of all ages who had undergone LLLT) demonstrated minor and infrequent adverse reactions, but most studies had significant areas of weakness in quality. Conclusion LLLT appears to be a safe therapy, but further evidence is needed to assess its efficacy as a prevention or treatment tool for oral mucositis in children with cancer. A meta-analysis and systematic review of safety and efficacy of using low-level laser therapy for oral mucositis in paediatric cancer patients - as the title says. Looks promising but more data are required regarding efficacy, and the availability and cost of such an approach.
Preclinical modeling in GBM PDX xenografts to guide clinical development of lisavanbulin - a novel tumor checkpoint controller targeting microtubules.

BACKGROUND Glioblastoma (GBM) is an incurable disease with few approved therapeutic interventions. Radiation therapy (RT) and temozolomide (TMZ) remain the standards of care. The efficacy and optimal deployment schedule of the orally bioavailable small-molecule tumor checkpoint controller lisavanbulin alone, and in combination with, standards of care were assessed using a panel of IDH-wildtype GBM patient-derived xenografts. METHODS Mice bearing intracranial tumors received lisavanbulin +/- RT +/- TMZ and followed for survival. Lisavanbulin concentrations in plasma and brain were determined by liquid chromatography with tandem mass spectrometry, while flow cytometry was used for cell cycle analysis. RESULTS Lisavanbulin monotherapy showed significant benefit (p<0.01) in 9 of 14 PDXs tested (median survival extension 9-84%) and brain-to-plasma ratios of 1.3 and 1.6 at 2- and 6-hours post-dose, respectively, validating previous data suggesting significant exposure in the brain. Prolonged lisavanbulin dosing from RT start until moribund was required for maximal benefit (GBM6: median survival lisavanbulin/RT 90 vs. RT alone 69 days, p=0.0001; GBM150: lisavanbulin/RT 143 days vs. RT alone 73 days, p=0.06). Similar observations were seen with RT/TMZ combinations (GBM39: RT/TMZ/lisavanbulin 502 days vs. RT/TMZ 249 days, p=0.0001; GBM26: RT/TMZ/lisavanbulin 172 days vs. RT/TMZ 121 days, p=0.04). Immunohistochemical analyses showed a significant increase in phospho-histone H3 with lisavanbulin treatment (p=0.01). CONCLUSIONS Lisavanbulin demonstrated excellent brain penetration, significant extension of survival alone or in RT or RT/TMZ combinations and was associated with mitotic arrest. These data provide a strong clinical rationale for testing lisavanbulin in combination with RT or RT/TMZ in GBM patients.
A study on echocardiographic findings in hospitalized patients with connective tissue diseases

Objective To determine the prevalence of echocardiographic findings and their change over time in patients with connective tissue diseases (CTDs) and to analyse which findings were associated with escalation of immunosuppressive therapy. Method We conducted a retrospective cohort study of consecutive hospitalized patients from a tertiary rheumatology referral centre who received transthoracic echocardiography between 1 January 2006 and 31 December 2015. We tested for associations between echocardiographic findings and treatment escalation via Fisher’s exact test; p < 0.05 was considered significant. Escalation of therapy was defined by dosage of glucocorticoids and type of disease-modifying anti-rheumatic drug. The clinical relevance of echocardiographic findings concerning change in immunosuppressive therapy was recorded. Results In total, 1004 patients were included (865 females), with a total of 1660 echocardiographic examinations. The most frequent findings were mitral, tricuspid, and aortic valve regurgitation (found in 36.7%, 25.4%, and 17.7% of all patients), aortic valve sclerosis (20.1%), left ventricular dysfunction (21.5%), and left atrial dilatation (19.2%). Only pericardial effusions were more frequent in cases with treatment escalation (10.9% of cases with escalated therapy vs 6.9% of cases without, p = 0.007). In 314 patients who received follow-up examinations, echocardiographic findings were found to change between examinations. Only 73 of all 1660 examinations were discussed in depth considering the treatment strategy in the hospital discharge letter. Conclusion Patients with CTDs exhibited a wide, dynamically changing spectrum of echocardiographic abnormalities. Most findings neither reflected disease activity nor appeared to influence the therapeutic regimen.
RecT Recombinase Expression Enables Efficient Gene Editing in Enterococcus spp.

Enterococcus faecium is widely recognized as an emerging public health threat with the rise of drug resistance and nosocomial infections. Nevertheless, commensal Enterococcus strains possess beneficial health functions in mammals to upregulate host immunity and prevent microbial infections. ABSTRACT Enterococcus faecium is a ubiquitous Gram-positive bacterium that has been recovered from the environment, food, and microbiota of mammals. Commensal strains of E. faecium can confer beneficial effects on host physiology and immunity, but antibiotic usage has afforded antibiotic-resistant and pathogenic isolates from livestock and humans. However, the dissection of E. faecium functions and mechanisms has been restricted by inefficient gene-editing methods. To address these limitations, here, we report that the expression of E. faecium RecT recombinase significantly improves the efficiency of recombineering technologies in both commensal and antibiotic-resistant strains of E. faecium and other Enterococcus species such as E. durans and E. hirae. Notably, the expression of RecT in combination with clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 and guide RNAs (gRNAs) enabled highly efficient scarless single-stranded DNA recombineering to generate specific gene-editing mutants in E. faecium. Moreover, we demonstrate that E. faecium RecT expression facilitated chromosomal insertions of double-stranded DNA templates encoding antibiotic-selectable markers to generate gene deletion mutants. As a further proof of principle, we use CRISPR-Cas9-mediated recombineering to knock out both sortase A genes in E. faecium for downstream functional characterization. The general RecT-mediated recombineering methods described here should significantly enhance genetic studies of E. faecium and other closely related species for functional and mechanistic studies. IMPORTANCE Enterococcus faecium is widely recognized as an emerging public health threat with the rise of drug resistance and nosocomial infections. Nevertheless, commensal Enterococcus strains possess beneficial health functions in mammals to upregulate host immunity and prevent microbial infections. This functional dichotomy of Enterococcus species and strains highlights the need for in-depth studies to discover and characterize the genetic components underlying its diverse activities. However, current genetic engineering methods in E. faecium still require passive homologous recombination from plasmid DNA. This involves the successful cloning of multiple homologous fragments into a plasmid, introducing the plasmid into E. faecium, and screening for double-crossover events that can collectively take up to multiple weeks to perform. To alleviate these challenges, we show that RecT recombinase enables the rapid and efficient integration of mutagenic DNA templates to generate substitutions, deletions, and insertions in the genomic DNA of E. faecium. These improved recombineering methods should facilitate functional and mechanistic studies of Enterococcus.
Supine hypotensive syndrome of pregnancy

Since the first description of supine hypotensive syndrome in the 1950s, its potentially detrimental effects on otherwise healthy women during late pregnancy have become a persistent challenge in obstetric practice. Establishing a 15° left lateral tilt during labour and caesarean section is a fundamental principle of obstetric care, universally adopted and upheld by current guidelines and recommendations. Reassessment of the original landmark studies in the light of current physiological and anatomical knowledge questions adherence to this standard in clinical practice. The modern practice of providing vasopressor support during caesarean delivery under neuraxial anaesthesia appears to negate any potential negative effects of a maternal full supine position. Recent MRI studies provide evidence as to the cause of supine hypotension and the physiological effects of different maternal positions at term. This review highlights current data on the acute supine hypotensive syndrome in contrast to traditional knowledge and established practice.
Simulation for teaching cardiorespiratory resuscitation by teams: setting and performance assessment*

Abstract Objective: to evaluate the acquisition of cognitive knowledge in cardiorespiratory resuscitation through training mediated by health simulation and to verify satisfaction with the teaching methodology design. Method: a study of quasi-experimental intervention, of the before and after type, with only one group. Population composed of medical students in the internship phase, nurses and resident physicians, nursing technicians and nurses of the institution’s effective staff. Convenience sampling consisting of 91 participants. Data collected through the Sociodemographic and Educational Questionnaire, Knowledge Test and Simulation Design Scale. Data was organized in tables and analyzed based on absolute frequencies, measures of central tendency and dispersion, Cronbach’s alpha reliability test, Wilcoxon’s test. Results: the increase in cognitive learning was 81.9%, being that for nursing technicians it was 117.8 %. Wilcoxon’s test showed a significant increase (p<0.0001) in knowledge. The Simulation Design Scale, displayed 4.55 of global mean. Cronbach’s alpha pointed good internal consistency (0.898). Conclusion: the health simulation was effective as a learning-teaching method in cardiorespiratory resuscitation, being effective in increasing knowledge in cardiorespiratory arrest, with a great level of design satisfaction.
A rare case of RGR/CDHR1 haplotype identified in Bulgarian patient with cone-rod dystrophy

ABSTRACT Aim To present a rare clinical case of CDHR1-related retinopathy with cone and rod involvementconfirmed clinically, electrophysiologically and genetically as a cone-rod dystrophy. Material and methods A 26-year-old woman underwent detailed ophthalmic examinationincluding fundus photography, full-field and multifocal electroretinography, visual field testing, optical coherence tomography and fluorescein angiography, which established the clinical diagnosis. Next-generation sequencing of a custom panel including 140 of the most common genes for inherited retinal degenerations was used for mutation screening. Results The symptoms onset was two years ago included gradual loss of vision and photophobia. The clinical findings were reduced visual acuity, central and peripheral scotomas, sporadic pigmentary cells localized mainly in the peripheral retina, a thinner retina in the macula and peripherally, moderate retinal vessels attenuation and reduced cone and rod ERG responses. The genetic analysisfound that the patient was homozygous for two already reported mutations: RGR-c.196A>C (p.Ser66Arg) variant and a co-segregating frame-shift deletion in CDHR1-c. 2522_2528delTCTCTGA (p.Ile841Serfs119*). Segregation analysis showed that the two mutations were transmitted by the asymptomatic heterozygous parents. Conclusion The rare haplotype of RGR mutation co-segregating incis- with CDHR1 mutation in our patient has been previously described in Albanian patients with recessive retinal dystrophy. Our findings add further support to the hypothesis of a common ancestral haplotype spread in the Balkan population. The comprehensive clinical, electrophysiological and genetic testing of patients with rare hereditary retinal dystrophies is essential for the correct diagnosis and the choice of potential novel therapies.