Miracle-dz/UniFAR-FTUs huggingface dataset:
Polymyxin and lipopeptide antibiotics: membrane-targeting drugs of last resort

The polymyxin and lipopeptide classes of antibiotics are membrane-targeting drugs of last resort used to treat infections caused by multi-drug-resistant pathogens. Despite similar structures, these two antibiotic classes have distinct modes of action and clinical uses. The polymyxins target lipopolysaccharide in the membranes of most Gram-negative species and are often used to treat infections caused by carbapenem-resistant species such as Escherichia coli , Acinetobacter baumannii and Pseudomonas aeruginosa . By contrast, the lipopeptide daptomycin requires membrane phosphatidylglycerol for activity and is only used to treat infections caused by drug-resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. However, despite having distinct targets, both antibiotic classes cause membrane disruption, are potently bactericidal in vitro and share similarities in resistance mechanisms. Furthermore, there are concerns about the efficacy of these antibiotics, and there is increasing interest in using both polymyxins and daptomycin in combination therapies to improve patient outcomes. In this review article, we will explore what is known about these distinct but structurally similar classes of antibiotics, discuss recent advances in the field and highlight remaining gaps in our knowledge.
Phase transition of supercooled water confined in cooperative two-state domain

The question of ‘what is the structure of water? ’ has been regarded as one of the major scientific conundrums in condensed-matter physics due to the complex phase behavior and condensed structure of supercooled water. Great effort has been made so far using both theoretical analysis based on various mathematical models and computer simulations such as molecular dynamics and first-principle. However, these theoretical and simulation studies often do not have strong evidences of condensed-matter physics to support. In this study, a cooperative domain model is formulated to describe the dynamic phase transition of supercooled water between supercooled water and amorphous ice, both of which are composed of low- and high-density liquid water. Free volume theory is initially employed to identify the working principle of dynamic phase transition and its connection to glass transition in the supercooled water. Then a cooperative two-state model is developed to characterize the dynamic anomalies of supercooled water, including density, viscosity and self-diffusion coefficient. Finally, the proposed model is verified using the experimental results reported in literature.
Effects of HMGA2 gene silencing on cell cycle and apoptosis in the metastatic renal carcinoma cell line ACHN

Objective To explore the role of high mobility group AT-hook 2 (HMGA2) in the regulation of the cell cycle and apoptosis. Methods The renal carcinoma cell line ACHN was transiently transfected with small interfering RNA to knock down the expression of the HMGA2 gene. Cell cycle analysis was undertaken using flow cytometry. The mRNA and protein levels of HMGA2, E2F transcription factor 1 (E2F1), cyclin D1, cyclin dependent kinase 6 (CDK6), B-cell lymphoma-2 (Bcl-2), caspase-3 and caspase-9 were analysed using reverse transcription quantitative real-time polymerase chain reaction and Western blot analysis. Results The mRNA and protein levels of HMGA2 were significantly higher in renal carcinoma cell lines compared with the human renal proximal tubular epithelial cell line HKC. After HMGA2 gene-specific silencing, more cells entered the G0/G1 phase, while fewer cells entered the G2/M phase; and the cells exhibited early and late apoptosis. HMGA2 gene-specific silencing significantly reduced the mRNA and protein levels of E2F1, cyclin D1, CDK6 and Bcl-2; and increased the mRNA and protein levels of caspase-3 and caspase-9. Conclusion The HMGA2 gene may be involved in the tumorigenesis and development of renal cancer, thus inhibiting HMGA2 gene expression might provide a potential therapeutic target in the future.
Pre-frailty associated with traffic crashes in Japanese community-dwelling older drivers

Abstract Objectives: Frailty might be useful to identify older drivers who are at risk for traffic crashes. We aim to examine the association between pre-frailty/frailty defined by the Kihon Checklist (KCL) and the involvement of traffic crashes and clarify whether some domains of the KCL are associated with traffic crashes. Methods: This cross-sectional study analyzed data from 2,208 Japanese community-dwelling older drivers aged ≥ 65 years in Kasama City, who participated in our postal survey in November 2019. A self-reported history of traffic crashes was used to divide participants into non-crash-involved and crash-involved groups. Results: A total of 192 (8.7%) participants had been involved in traffic crashes in the past year. The crash-involved group was found to have gained more body mass index, driven more frequently, and scored higher on the total KCL score than the non-crash-involved group (all P < .05). Binary logistic regression analyses showed that after adjusting for age, sex, education, driving frequency, and driving distance, pre-frailty (OR = 1.52, 95% CI: 1.10–2.10) was more significantly associated with traffic crashes as compared to robustness. Those who had impairment in the oral domain (OR = 1.57, 95% CI: 1.09–2.27) and memory domain (OR = 1.38, 95% CI: 1.01–1.90) were also more likely to be involved in traffic crashes. Conclusion: The results suggest that identifying pre-frailty may play an important pole in crash prevention. Additionally, more attention should be given to older drivers with oral dysfunction and cognitive impairment.
Oxidative and glycolytic skeletal muscles deploy protective mechanisms to avoid atrophy under pathophysiological iron overload

Iron excess has been proposed as an essential factor in skeletal muscle wasting. Studies have reported correlations between muscle iron accumulation and atrophy, either through ageing or by using experimental models of secondary iron overload. However, iron treatments performed in most of these studies induced an extra‐pathophysiological iron overload, more representative of intoxication or poisoning. The main objective of this study was to determine the impact of iron excess closer to pathophysiological conditions on structural and metabolic adaptations (i) in differentiated myotubes and (ii) in skeletal muscle exhibiting oxidative (i.e. the soleus) or glycolytic (i.e. the gastrocnemius) metabolic phenotypes.
Effect of long‐term soccer training on changes in cardiac function during exercise in elite youth soccer players

It is unclear what the effect of long‐term, high‐volume soccer training has on left ventricular (LV) function during exercise in youth soccer players. This study evaluated changes in LV function during submaximal exercise in a group of highly trained male soccer players (SP) as they transitioned over a three‐year period from pre‐adolescent to adolescent athletes. Data were compared to age‐ and sex‐matched recreationally active controls (CON) over the same time period. Twenty‐two SP from two professional English Premier League youth soccer academies (age: 12.0 ± 0.3 years at start of the study) and 15 CON (age: 11.7 ± 0.3 years) were recruited. Two‐dimensional echocardiography was used to quantify LV function during exercise at the same submaximal metabolic load (approx. 45%VO2peak) across the 3 years. After controlling for growth and maturation, there were training‐induced changes and superiority (p < 0.001) in cardiac index (QIndex) from year 1 in the SP compared to CON. SP (year 1: 6.13 ± 0.76; year 2: 6.94 ± 1.31; and year 3: 7.20 ± 1.81 L/min/m2) compared to CON (year 1: 5.15 ± 1.12; year 2: 4.67 ± 1.04; and year 3: 5.49 ± 1.06 L/min/m2). Similar training‐induced increases were noted for mitral inflow velocity (E): SP (year 1: 129 ± 12; year 2: 143 ± 16; and year 3: 135 ± 18 cm/s) compared to CON (year 1: 113 ± 10; year 2: 111 ± 12; and year 3: 121 ± 9 cm/s). This study indicated that there was evidence of yearly, training‐induced increases in left ventricular function during submaximal exercise independent from the influence of growth and maturation in elite youth SP.
Lean termelés és üzleti teljesítmény – nemzetközi empirikus eredmények (Lean production and business performance – international empirical results)

A lean termeles javit a vallalatok operativ teljesitmenyen. Korabbi kutatasokkal osszhangban ezt nemzetkozi kerdőives felmeresből szarmazo eredmenyek is alatamasztjak. Nem mutathato ki azonban egyertelmű kapcsolat a lean termeles es az uzleti teljesitmeny kozott. A szerzők kutatasukban – kifejezetten a tobb lean eszkozt elmelyulten hasznalo es jo operativ eredmenyekkel rendelkező un. halado lean termelők uzleti eredmenyeire fokuszalva – azonositottak az uzleti teljesitmenyt befolyasolo tenyezőket. Bar szamos tenyező kivul esik a termelesmenedzsment hataskoren (pl. piaci dinamika, uj piacra lepők szama, szemelyre szabas), de a termek/szolgaltatas aranyanak befolyasolasan, a beszallitok es a kapacitastartalekok menedzsmentjen keresztul a termelesnek is van lehetősege az uzleti teljesitmeny javitasara. Vegul, bar kozvetlen kapcsolat nem mutathato ki a lean termeles es az uzleti teljesitmeny kozott, de a szerzők varakozasai szerint a folyamatosan javulo operativ teljesitmeny kiegyensulyozott es stabil uzleti teljesitmeny alapja lehet. A halado lean vallalatok pedig nagyobb esellyel kerulhetnek (maradhatnak? ) a jo uzleti teljesitmennyel buszkelkedő vallalatok korebe(n). ____________ The lean production has improved the operational performance of companies. However a clear link between lean production and business performance can not be detected. In their research the authors have identified the factors affecting business performance focusing on business results of the advanced lean producers. Although a direct connection is not detected between lean production and business performance, but according to the author expects the continuously improving operational performance shall be a base for the balanced and stable business performance.
Intracranial response in helmet oblique impacts

The purpose of this work was to investigate the influence of the presence of the body in helmet oblique impacts on the tissue level response of the human head. The kinematic field of the head obtained from full-body and detached-head oblique impacts were used to drive a validated Finite Element model of the human head and evaluate predictors of the diffuse axonal injury (Von Mises stress in the brain) and subdural haematoma (internal energy of the Cerebro-Spinal Fluid (CSF)). It was found that the presence of the body considerably influences the intracranial response. To take into account this effect in detached-head impacts, inertial properties of the head were modified. When the head mass was increased, the Von Mises stress in the brain and the internal energy of the CSF decreased for impacts with relatively high tangential velocities. Modifying the head inertia matrix lowered the Von Mises stress in the brain and the internal energy of the CSF. The best correlation between the modified detached-head and full-body impact results was found when both the head mass and its inertia matrix were modified.
Increased ERCP volume improves cholangiogram interpretation: a new performance measure for ERCP training?

Background/Aims Cholangiogram interpretation is not used as a key performance indicator (KPI) of endoscopic retrograde cholangiopancreatography (ERCP) training, and national societies recommend different minimum numbers per annum to maintain competence. This study aimed to determine the relationship between correct ERCP cholangiogram interpretation and experience. Methods One hundred fifty ERCPists were surveyed to appropriately interpret ERCP cholangiographic findings. There were three groups of 50 participants each: “Trainees,” “Consultants group 1” (performed >75 ERCPs per year), and “Consultants group 2” (performed >100 ERCPs per year). Results Trainees was inferior to Consultants groups 1 and 2 in identifying all findings except choledocholithiasis outside the intrahepatic duct on the initial or completion/occlusion cholangiogram. Consultants group 1 was inferior to Consultants group 2 in identifying Strasberg type A bile leaks (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.77–0.96), Strasberg type B (OR, 0.84; 95% CI, 0.74–0.95), and Bismuth type 2 hilar strictures (OR, 0.81; 95% CI, 0.69–0.95). Conclusions This investigation supports the notion that cholangiogram interpretation improves with increased annual ERCP case volumes. Thus, a higher annual volume of procedures performed may improve the ability to correctly interpret particularly difficult findings. Cholangiogram interpretation, in addition to bile duct cannulation, could be considered as another KPI of ERCP training.
Clinicians' opinions on the clinical relevance of anatomy education at Stellenbosch University

Anatomical science is a fundamental element of undergraduate medical education; thus, it is imperative that the course serves future medical professionals when entering clinical practice. However, anatomical education has faced challenges in recent years including decreased allocated time, increased class sizes and over‐stretched staff. Technological advancements in anatomical education may provide relief to these issues. Therefore, exploring clinicians' perspective on the clinical relevance and efficacy of anatomical education, within an African context, can inform its future. This study used a qualitative research approach within an interpretive paradigm. Eight semi‐structured one‐on‐one interviews were conducted with clinicians associated with Stellenbosch University and Tygerberg Hospital. Thematic analysis was employed to analyze the data, creating themes and codes. Trust worthiness of the data was ensured through peer debriefing and member checking. Results reveal that clinicians find clinically relevant anatomy valuable to students. However, some feel that this is not delivered effectively at present. Clinicians see potential for the incorporation of clinical technologies into anatomical pedagogy. Although clinicians are hopeful for new technological developments in anatomical education, concerns were reported about its autonomous nature. This study concludes that although clinically relevant anatomical education is beneficial to students, the time and the resources via which it is delivered should be considered. There is optimism for the future of anatomical education with the advancements of technologically based educational resources, however, new resources should be incorporated with planning and supervision.
A prospective multicentre screening study on multidrug-resistant organisms in intensive care units in the Dutch–German cross-border region, 2017 to 2018: the importance of healthcare structures

Background Antimicrobial resistance poses a risk for healthcare, both in the community and hospitals. The spread of multidrug-resistant organisms (MDROs) occurs mostly on a local and regional level, following movement of patients, but also occurs across national borders. Aim The aim of this observational study was to determine the prevalence of MDROs in a European cross-border region to understand differences and improve infection prevention based on real-time routine data and workflows. Methods Between September 2017 and June 2018, 23 hospitals in the Dutch (NL)–German (DE) cross-border region (BR) participated in the study. During 8 consecutive weeks, patients were screened upon admission to intensive care units (ICUs) for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) and rectal carriage of vancomycin-resistant Enterococcus faecium/E. faecalis (VRE), third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) and carbapenem-resistant Enterobacteriaceae (CRE). All samples were processed in the associated laboratories. Results A total of 3,365 patients were screened (median age: 68 years (IQR: 57–77); male/female ratio: 59.7/40.3; NL-BR: n = 1,202; DE-BR: n = 2,163). Median screening compliance was 60.4% (NL-BR: 56.9%; DE-BR: 62.9%). MDRO prevalence was higher in DE-BR than in NL-BR, namely 1.7% vs 0.6% for MRSA (p = 0.006), 2.7% vs 0.1% for VRE (p < 0.001) and 6.6% vs 3.6% for 3GCRE (p < 0.001), whereas CRE prevalence was comparable (0.2% in DE-BR vs 0.0% in NL-BR ICUs). Conclusions This first prospective multicentre screening study in a European cross-border region shows high heterogenicity in MDRO carriage prevalence in NL-BR and DE-BR ICUs. This indicates that the prevalence is probably influenced by the different healthcare structures.
Leptomeningeal anastomoses: Mechanisms of pial collateral remodeling in ischemic stroke

Abstract Arterial collateralization, as determined by leptomeningeal anastomoses or pial collateral vessels, is a well‐established vital player in cerebral blood flow restoration and neurological recovery from ischemic stroke. A secondary network of cerebral collateral circulation apart from the Circle of Willis, exist as remnants of arteriole development that connect the distal arteries in the pia mater. Recent interest lies in understanding the cellular and molecular adaptations that control the growth and remodeling, or arteriogenesis, of these pre‐existing collateral vessels. New findings from both animal models and human studies of ischemic stroke suggest a multi‐factorial and complex, temporospatial interplay of endothelium, immune and vessel‐associated cell interactions may work in concert to facilitate or thwart arteriogenesis. These valuable reports may provide critical insight into potential predictors of the pial collateral response in patients with large vessel occlusion and may aid in therapeutics to enhance collateral function and improve recovery from stroke. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology
Acute paraparesis syndrome after ruptured anterior communicating artery aneurysm

Abstract Here, we describe a series of 7 patients who presented with acute paraparesis due to anterior communicating artery aneurysm rupture. This study aimed to assess the clinical and radiological factors associated with acute paraparesis syndrome caused by subarachnoid hemorrhage (SAH). Between June 2005 and December 2012, our institution consecutively treated 210 patients with anterior communicating aneurysm rupture within 24 hours after ictus. We divided the patients into 2 groups based on the presence (n = 7) and absence (n = 203) of acute paraparesis after anterior communicating aneurysm rupture. Diffusion-weighted magnetic resonance imaging revealed high intensity in the medial aspects of the bilateral frontal lobes in 3 patients. The mean third ventricular distance at the time of admission was 9.2 mm (range, 8–12.5 mm), and the mean bicaudate distance was 33.9 mm (range, 24–39 mm). There was a significant difference in the bicaudate distance (P = .001) and third ventricle distance (P = .001) between the 2 groups. Acute hydrocephalus and global cerebral edema (GCE) were confirmed radiologically in all patients in the acute paraparesis group. The presence of acute hydrocephalus (P = .001) and GCE (P = .003) were significantly different between the groups. Acute paraparesis syndrome after SAH is transient and gradually improves if the patient does not develop severe vasospasm. The present study demonstrates that acute paraparesis after SAH is associated with acute hydrocephalus and GCE.
Association between Psoriasis Disease and IFN-λ Gene Polymorphisms

ABSTRACT Psoriasis is one of the most common chronic immune-mediated skin diseases, having a strong genetic predisposition. Psoriasis is a T-cell-mediated disease with a mixed Th1/Th17 cytokines environment. IL-23/IL-17 axis hyperactivation is the primary pathogenesis. Psoriasis lesions have been known to exhibit high IFN-λ1 and IFN-stimulated genes (ISGs) expression, which appears to be driven by Th17 cells. However, the role and mechanism of IFN-λs in psoriasis disease remains unknown. The study aimed to investigate the relationship between IL-28B and IL-29 gene polymorphisms with psoriasis disease and clinical severity. We performed single-nucleotide polymorphisms (SNPs) of IL-28B rs12979860 (IL-28 C/T), rs8099917 (IL-28 T/G), and IL-29 rs30461 (IL-29 T/C) in 140 patients with psoriasis disease and 159 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequency distributions of the rs12979860 (IL-28 C/T) and rs30461 (IL-29 T/C) polymorphisms were similar in the patient and control groups and were not statistically significant. The TG genotype of rs8099917 was statistically significantly different in patients from both groups. The TG genotype increased the risk of disease1.9-fold. The G allele may be associated with the pathogenesis of psoriasis.
Afora : ad hoc routing in the face of misbehaving nodes

This thesis describes Afora, a multi-hop wireless ad hoc routing algorithm that finds working routes despite misbehaving participants. If one or more routes from a source to a destination exist that are entirely out of radio range of any attacker, Afora will eventually find and use one of them; this is the best that a routing protocol can do. This property holds even if misbehaving nodes generate or forge routing information, and even if they lie on the shortest path between source and destination. Afora does not directly use or require any public key or certificate infrastructure. Instead, it assumes that applications (or higher-level protocols such as IPSec) verify whether they are talking to the desired peer, and that they notify Afora when this is (or is not) the case. Afora uses these notifications to decide whether to keep trying alternate routes until it finds one that works. Afora’s key contribution is its ability to find alternate routes in the face of misbehaving nodes that actively generate false routing information. Thesis Supervisor: Robert Morris Title: Assistant Professor