Miracle-dz/UniFAR-FTUs huggingface dataset:
Bedside Ultrasound in the Management of Cardiorenal Syndromes: An Updated Review

Background: Cardiorenal syndromes constitute a spectrum of disorders involving heart and kidney dysfunction modulated by a complex interplay of neurohormonal, inflammatory, and hemodynamic derangements. The management of such patients often poses a diagnostic and therapeutic challenge to physicians owing to gaps in understanding of pathophysiology, paucity of objective bedside diagnostic tools, and individual biases. Summary: In this narrative review, we discuss the role of clinician who performed bedside ultrasound in the management of patients with cardiorenal syndromes. Novel sonographic applications such as venous excess ultrasound score (VExUS) are reviewed in addition to the lung and focused cardiac ultrasound. Further, underrecognized causes of heart failure such as high-flow arteriovenous fistula are discussed. Key Message: Bedside ultrasound allows a comprehensive hemodynamic characterization of cardiorenal syndromes.
Klebsiella pneumoniae TolC contributes to antimicrobial resistance, exopolysaccharide production, and virulence

ABSTRACT Klebsiella pneumoniae is a Gram-negative bacterium that causes a variety of human diseases, ranging from pneumonia to urinary tract infections and invasive diseases. The emergence of K. pneumoniae strains that are resistant to multiple antibiotics has made treatment more complex and led to K. pneumoniae becoming a global health threat. Addressing this threat necessitates the development of new therapeutic strategies to combat this pathogen, including strategies to overcome antimicrobial resistance and therapeutics for novel targets such as antivirulence. Here, we investigated the function of TolC, an outer membrane protein essential for the function of tripartite transporters, in K. pneumoniae. Mutation of tolC rendered K. pneumoniae hypersensitive to multiple antibiotics. Moreover, the tolC mutation impaired capsule production and affected the expression of key capsule biosynthetic genes, indicating a regulatory role for TolC in capsule biosynthesis. Additionally, TolC was essential for growth under iron-limiting conditions, suggesting its involvement in iron acquisition. The tolC mutant exhibited increased adherence to human enterocytes and enhanced serum sensitivity. In the Galleria mellonella infection model, the tolC mutant displayed reduced virulence compared to the wild type. Our findings highlight the pleiotropic role of TolC in K. pneumoniae pathobiology, influencing antimicrobial resistance, capsule production, iron homeostasis, adherence to host cells, and virulence. Understanding the multifaceted role of TolC in K. pneumoniae may guide the development of new therapeutic strategies against this pathogen.
Evaluating the Efficacy and Safety of 4% 5-Fluorouracil Cream in Patients with Actinic Keratosis: An Expert Opinion

Actinic keratosis is a lesion that develops in sun-exposed areas of the skin and is considered to be a precancerous condition or an early in situ squamous cell carcinoma. Treatment of actinic keratosis is important for reducing skin cancer risk, with treatment choice based on patient-, lesion- and treatment-related considerations. Of the topical treatments used for field-directed therapy, those containing 5-fluorouracil are among the most effective and widely prescribed. The most recently developed topical 5-fluorouracil preparation (Tolak®; Pierre Fabre, France) contains 4% 5-fluorouracil in an aqueous cream. This narrative review discusses data on 4% 5-fluorouracil cream to treat actinic keratosis, and provides the authors’ expert opinion on issues associated with it use. The effect of the cream has been evaluated in phase 2 and 3 trials of adult patients with actinic keratosis on the face, ears or scalp. These trials included patients with severe baseline disease, defined by high lesion counts and large-size treatment fields, which possibly affected the proportion of patients who were able to achieve complete clearance. Other efficacy parameters (e.g. percentage change in lesion count, ≥ 75% clearance of lesions or clinically significant changes in validated severity scales) should also be assessed to fully evaluate 4% 5-fluorouracil treatment efficacy in these patients. Nevertheless, 4% 5-fluorouracil is associated with high efficacy, a low level of recurrence and a satisfactory safety profile. SIGNIFICANCE Actinic keratoses are lesions that appear on photodamaged skin (e.g. face, neck and upper limbs) preceding or accompanying invasive skin cancer and are typically treated with creams containing 5-fluorouracil. This article reviews clinical trial data on how a new cream containing 4% 5-fluorouracil performed in adults with actinic keratosis. Treatment with 4% 5-fluorouracil cream was highly efficacious, safe, and prevented disease recurrence in approximately 27% of patients who achieved complete clearance of lesions in phase 3 studies. However, all trials were performed in patients with severe disease and numerous actinic keratosis lesions, making it more difficult for more patients to achieve complete clearance. Thus, other endpoints, such as percentage change in lesion count, ≥75% clearance of lesions or clinically significant changes in validated severity scales,may better reflect the efficacy of 4% 5-fluorouracil.
Statistical analysis of the longitudinal fundamental movement skills data in the REACT project using the multilevel ordinal logistic model.

OBJECTIVES The REACT project was designed around two main aims: (1) to assess children's growth and motor development after the COVID-19 pandemic and (2) to follow their fundamental movement skills' developmental trajectories over 18 months using a novel technological device (Meu Educativo®) in their physical education classes. In this article, our goal is to describe statistical analysis of the longitudinal ordinal motor development data that was obtained from these children using the multilevel ordinal logistic model. METHODS Longitudinal ordinal data are often collected in studies on motor development. For example, children or adolescents might be rated as having poor, good, or excellent performance levels in fundamental movement skills, and such ratings may be obtained yearly over time to assess changes in fundamental movement skills levels of performance. However, such longitudinal ordinal data are often analyzed using either methods for continuous outcomes, or by dichotomizing the ordinal outcome and using methods for binary data. These approaches are not optimal, and so we describe in detail the use of the multilevel ordinal logistic model for analysis of such data from the REACT project. Our intent is to provide an accessible description and application of this model for analysis of ordinal motor development data. DISCUSSION Our analyses show both the between-subjects and within-subjects effects of age on motor development outcomes across three timepoints. The between-subjects effect of age indicate that children that are older have higher motor development ratings, relative to thoese that are younger, whereas the within-subject effect of age indicates higher motor development ratings as a child ages. It is the latter effect that is particularly of interest in longitudinal studies of motor development, and an important advantage of using the multilevel ordinal logistic model relative to more traditional methods.
Engineered extracellular vesicles for delivering functional Cas9/gRNA to eliminate hepatitis B virus cccDNA and integration

ABSTRACT The persistence of HBV covalently closed circular DNA (cccDNA) and HBV integration into the host genome in infected hepatocytes pose significant challenges to the cure of chronic HBV infection. Although CRISPR/Cas9-mediated genome editing shows promise for targeted clearance of viral genomes, a safe and efficient delivery method is currently lacking. Here, we developed a novel approach by combining light-induced heterodimerization and protein acylation to enhance the loading efficiency of Cas9 protein into extracellular vesicles (EVs). Moreover, vesicular stomatitis virus-glycoprotein (VSV-G) was incorporated onto the EVs membrane, significantly facilitating the endosomal escape of Cas9 protein and increasing its gene editing activity in recipient cells. Our results demonstrated that engineered EVs containing Cas9/gRNA and VSV-G can effectively reduce viral antigens and cccDNA levels in the HBV-replicating and infected cell models. Notably, we also confirmed the antiviral activity and high safety of the engineered EVs in the HBV-replicating mouse model generated by hydrodynamic injection and the HBV transgenic mouse model. In conclusion, engineered EVs could successfully mediate functional CRISPR/Cas9 delivery both in vitro and in vivo, leading to the clearance of episomal cccDNA and integrated viral DNA fragments, and providing a novel therapeutic approach for curing chronic HBV infection.
Aggressive End-of-Life Care and Caregiver Satisfaction for Patients With Advanced Cancer

Aggressive end-of-life care in patients with advanced cancer is associated with poor experiences and outcomes. The purpose of the study was to examine the impact of aggressive end-of-life care on caregiver satisfaction for caregivers of bereaved advanced cancer patients. Data of 101 caregivers were gathered using a longitudinal, descriptive correlational design study. Postdeath interviews were conducted 2 months after the patient’s death. The most common end-of-life care indicators were patient not enrolled in hospice or enrolled within 3 days of death, >1 hospitalization, and intensive care unit admission. More than one-third of patients received at least one of the aggressive end-of-life care indicators in the last 30 days of life. From the multiple linear regression analyses, patient intensive care unit admission and having more than one hospitalization significantly affected caregiver satisfaction with care. Understanding caregiver satisfaction with care may improve the clinical practice of nurses who have crucial role in patients’ end-of-life care.
Ichthayofaunal Diversity & Anthropogenic Stress on Deepor Beel: the only Ramsar site in Assam

North East India is the conjunction of Himalaya and In-Burma biodiversity hotspots. Deepor Beel, in Assam, has been designated a wetland of international importance under the Ramsar Convention on Wetlands, at the eighth meeting of the Conference of Contracting Parties (COP8) held recently at Valencia in Spain. Again, considering the varieties of bird species found in the Beel, Birdlife International has also declared Deepor Beel as an Important Bird Sanctuary. Deepor Beel which is the lone Ramsar site of Assam is facing danger from various angles. In this study, attempt has been made to identify the current conservation threats to biodiversity in and around the Beel periphery. Thus the study provides immense scope in conservation of the water birds and its habitat.
Kinematic models of large‐scale flow in the Earth's mantle

It is likely that the motions of the lithospheric plates strongly influence the accompanying large-scale flow in the earth's mantle. In order to isolate and understand the effects of the plate motions on the large scale flow, we calculate simple kinematic models in which the observed plate motions and geometries are imposed as boundary conditions; thermal buoyancy forces are ignored and the flow is determined by the mass flux imposed by the moving plates. With the assumption of a layered, radially symmetric, Newtonian rheology, the flow accompanying the observed plate motions is calculated analytically. The flow is in general complicated, but for models in which whole-mantle flow occurs, the dips of subduction zones are predicted remarkably well by the flow modesl. Circulation does not from simple closed cells and flow under slowly moving plates is not closely related to the direction of plate motion. There is little return flow under the Pacific unless the lithosphere is essentially decoupled from the mantle by an extremely weak low viscosity layer. Only viscosity contrasts between the upper and lower mantle of three to four orders of magnitude are sufficient to confine flow to the upper mantle. For a wide range of mantle viscosity structures, significant mixing between the upper and lower mantle is expected over geologic time. On the basis of these models, the source rock for oceanic ridge basalt probably lies below the asthenosphere. A comparison of the magnitude of the deviatoric stress with theoretical flow mechanism calculations and with models of postglacial rebound indicate that the assumption of Newtonian viscosity is plausible. The drag on the lithosphere is compared to that calculated assuming simple shear. On a regional basis, the stresses can differ by up to 90°, e.g., in eastern North America. Small plates have higher apparent drag coefficients than larger ones. The normal stress at the base of the lithosphere is excessive in models in which the flow is confined to the upper 700 km of the mantle unless the lithosphere is decoupled from the mantle by an extremely low viscosity layer.
Targeting cyclin-dependent kinases in rheumatoid arthritis and psoriasis – a review of current evidence

ABSTRACT Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with synovial proliferation and bone erosion, which leads to the structural and functional impairment of the joints. Immune cells, together with synoviocytes, induce a pro-inflammatory environment and novel treatment agents target inflammatory cytokines. Psoriasis is a chronic immune-mediated skin disease, and several cytokines are considered as typical mediators in the progression of the disease, including IL-23, IL-22, and IL-17, among others. Area covered In this review, we try to evaluate whether cyclin-dependent kinases (CDK), enzymes that regulate cell cycle and transcription of various genes, could become novel therapeutic targets in RA and psoriasis. We present the main results of in vitro and in vivo studies, as well as scarce clinical reports. Expert opinion CDK inhibitors seem promising for treating RA and psoriasis because of their multidirectional effects. CDK inhibitors may affect not only the process of osteoclastogenesis, thereby reducing joint destruction in RA, but also the process of apoptosis of neutrophils and macrophages responsible for the development of inflammation in both RA and psoriasis. However, assessing the efficacy of these drugs in clinical practice requires multi-center, long-term clinical trials evaluating the effectiveness and safety of CDK-blocking therapy in RA and psoriasis.
Preschool teachers’ knowledge, beliefs, and self-efficacy concerning autism: A parallel mixed-methods study of an intervention to improve autism identification

Preschool teachers can play a critical role in early detection of autism. Equipping preschool teachers with prerequisite knowledge and skills would allow them to identify children with probable autism and referral to diagnostic services. This study aimed to investigate the impact of an educational module (EMiASD) that prepared preschool teachers to identify autism symptoms. The sample included 144 preschool teachers, of which 120 were stratified and randomly assigned to an intervention arm receiving training in EMiASD (n = 60) or a comparison arm receiving standard training (n = 60) using a parallel mixed-methods design. Responses to open-ended questions about video case studies revealed improvement in the identification of autism symptoms in preschool teachers in the intervention arm, in contrast to preschool teachers in the comparison arm. Moreover, significant changes in knowledge, belief, and self-efficacy about autism favoured EMiASD. Overall, these results demonstrate the influence of EMiASD in the Yemeni cultural context. Lay Abstract Preschool teachers can play a critical role in early detection of autism. Equipping preschool teachers with prerequisite knowledge and skills would allow them to identify children with probable autism and referral to diagnostic services. This study aimed to investigate the impact of an educational module (EMiASD) that prepared preschool teachers to identify autism symptoms. The sample included 144 preschool teachers, of which 120 were stratified and randomly assigned to an intervention arm receiving training in EMiASD (n = 60) or a comparison arm receiving standard training (n = 60) using a parallel mixed-methods design. Responses to open-ended questions about video case studies revealed improvement in the identification of autism symptoms in preschool teachers in the intervention arm, in contrast to preschool teachers in the comparison arm. Moreover, significant changes in knowledge, belief, and self-efficacy about autism favoured EMiASD. Overall, these results demonstrate the influence of EMiASD in the Yemeni cultural context.
Modelling the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity in a cohort of Australian adults

Dietary guidelines are increasingly promoting mostly plant-based diets, limits on red meat consumption, and plant-based sources of protein for health and environmental reasons. It is unclear how the resulting food substitutions associate with insulin resistance, a risk factor for type 2 diabetes. We modelled the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity. We included 783 participants (55% female) from the Childhood Determinants of Adult Health study, a population-based cohort of Australians. In adulthood, diet was assessed at three time points using food frequency questionnaires: 2004-2006, 2009-2011, and 2017-2019. We calculated the average daily intake of each food group in standard serves. Insulin sensitivity was estimated from fasting glucose and insulin concentrations in 2017-2019 (aged 39-49 years) using homeostasis model assessment. Replacing red meat with a combination of plant-based alternatives was associated with higher insulin sensitivity (β = 10·5 percentage points, 95% confidence interval: 4·1-17·4). Adjustment for waist circumference attenuated this association by 61·7%. Replacing red meat with either legumes, nuts/seeds, or whole grains was likewise associated with higher insulin sensitivity. Point estimates were similar but less precise when replacing processed meat with plant-based alternatives. Our modelling suggests that regularly replacing red meat, and possibly processed meat, with plant-based alternatives may associate with higher insulin sensitivity. Further, abdominal adiposity may be an important mediator in this relationship. Our findings support advice to prioritise plant-based sources of protein at the expense of red meat consumption.
Southern South America

The region was host to some 9,200 refugees and asylumseekers, of whom half received support from UNHCR. All countries in the region have signed the Mexico Plan of Action and progress was made with its implementation. New refugee legislation was passed in Argentina, Bolivia and Uruguay. Protection networks were strengthened to increase border monitoring, and the region expanded its emerging resettlement programme. There are now consolidated resettlement programmes in Brazil and Chile and a new programme in Argentina. UNHCR also entered into discussions with Uruguay on beginning resettlement in 2006.
The distribution, impacts and identifi cation of exotic stipoid grasses in Australia

Exotic stipoid grasses are one of the most signifi cant issues affecting grazing industries and threatening nationally important remnant grasslands in Australia. This paper documents their distribution, impacts and identifi cation. It also discusses how these grasses are coming into Australia and makes recommendations on how this could be addressed.
The European Commission's Policy Towards the Southern Gas Corridor: Between National Interests and Economic Fundamentals

The European Union launched the ambitious Southern Gas Corridor initiative with the goal of enhancing the security of its energy supply. The corridor - a virtual transit route running from the gas-rich Caspian basin to the EU while bypassing Russian soil - is meant to increase diversification of the EU’s supplier and transit countries. While various projects have been proposed to give life to the corridor, the European Commission has given particular support to the realisation of Nabucco, a 3,893km pipeline running from Turkey to the European gas hub of Baumgarten in Austria, via Bulgaria, Romania, and Hungary. The Commission’s choice is, however, flawed in several respects, as it fails to take account of key factors, such as the diverging, and sometimes conflicting, interests of individual EU member states, the geopolitical challenges of the Caspian basin, and the commercial constraints on Nabucco. This short-sighted approach has hindered the efficient development of the Southern Gas Corridor and weakened the EU’s energy policy.
Effect of a moderate alcohol dose on physiological responses during rest and prolonged cycling

Abstract Aim: We examined the acute effects of a moderate alcohol dose (48 g) ingested before prolonged cycling on acute physiological responses in eight healthy males (mean ± SD; 23 ± 2 years; 1.77 ± 0.04 m; 75.8 ± 4.1 kg). Methods: In a randomized order, euhydrated participants completed two experimental sessions with the sequence of 150-min seated at rest, 90-min of cycling at 50% of the maximal rate of oxygen consumption (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} $\dot{\textrm V}\textrm O$\end{document}2max), 120-min seated at rest. Participants drank 250 mL of flavored squash with or without alcohol (vodka; ~16 g) at 10, 40, and 70 min of the initial resting phase, giving a cumulative fluid intake of 750 mL with 48 g of alcohol. Heart rate, blood glucose, breath alcohol concentration, and respiratory gasses were recorded throughout the entire trial with cumulative urine volume recorded during both rest phases. Results: Total carbohydrate (control = 115 ± 19 g: alcohol = 119 ± 21 g; P = 0.303) and lipid (control = 17 ± 4 g: alcohol = 20 ± 7 g; P = 0.169) oxidation was similar between conditions. Average heart rate was 7% higher in the alcohol condition (control = 111 ± 12 bpm; alcohol = 119 ± 11 bpm; P = 0.003). Blood glucose concentrations were similar between conditions during (P = 0.782) and after exercise (P = 0.247). Urine output was initially increased between conditions following alcohol ingestion before diminishing (P < 0.001) with no difference in total cumulative urine output (P = 0.331). Conclusion: Consuming an alcoholic drink containing 48 g of alcohol in the hour before moderate intensity sub-maximal aerobic exercise led to detectable increases in heart rate and rate of urine production with no effect on substrate use.