KorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid.

Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB-KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.

Hypoalbuminemia and Nutritional Status in Children With Cancer.

Background: In children with cancer, poor nutritional status adversely affects outcomes. Hypoalbuminemia is common in pediatric oncology patients, and in some groups is associated with inferior survival rates. We sought to determine if serum albumin associates with body mass index (BMI) percentile and if combining serum albumin and BMI is associated with survival.

Designing Patient-Reported Measures of Fertility: Cognitive Interview Findings from Adolescents and Young Adults with Cancer.

Fertility concerns (FC) are central to the well-being of many adolescent and young adult (AYA) cancer survivors. Clinical conversations about FC and fertility preservation are suboptimal, increasing patient distress. The goal of this project was to establish content validity and comprehensibility of self-report questions on FCs for AYAs with cancer.

LazyAF, a pipeline for accessible medium-scale prediction of protein-protein interactions.

Artificial intelligence has revolutionized the field of protein structure prediction. However, with more powerful and complex software being developed, it is accessibility and ease of use rather than capability that is quickly becoming a limiting factor to end users. LazyAF is a Google Colaboratory-based pipeline which integrates the existing ColabFold BATCH software to streamline the process of medium-scale protein-protein interaction prediction.

Modelling the Effectiveness of Tepotinib in Comparison to Standard-of-Care Treatments in Patients with Advanced Non-small Cell Lung Cancer (NSCLC) Harbouring METex14 Skipping in the UK.

Background: Patients with non-small cell lung cancer harbouring mesenchymal-epithelial transition exon 14 (METex14) skipping typically demonstrate poorer prognosis than overall non-small cell lung cancer. Until recently, no targeted treatments were available for patients with non-small cell lung cancer harbouring METex14 skipping in the UK, with limited treatments available.

Objective: This study estimates the long-term survival and quality-adjusted life-year benefit of MET inhibitor tepotinib versus current standard of care from a UK perspective.

Evolution of a Plasmid Regulatory Circuit Ameliorates Plasmid Fitness Cost.

Plasmids play a major role in rapid adaptation of bacteria by facilitating horizontal transfer of diverse genes, most notably those conferring antibiotic resistance. While most plasmids that replicate in a broad range of bacteria also persist well in diverse hosts, there are exceptions that are poorly understood. We investigated why a broad-host range plasmid, pBP136, originally found in clinical isolates, quickly became extinct in laboratory populations.

Discovery of lirafugratinib (RLY-4008), a highly selective irreversible small-molecule inhibitor of FGFR2.

Fibroblast growth factor receptor (FGFR) kinase inhibitors have been shown to be effective in the treatment of intrahepatic cholangiocarcinoma and other advanced solid tumors harboring alterations, but the toxicity of these drugs frequently leads to dose reduction or interruption of treatment such that maximum efficacy cannot be achieved. The most common adverse effects are hyperphosphatemia caused by FGFR1 inhibition and diarrhea due to FGFR4 inhibition, as current therapies are not selective among the FGFRs. Designing selective inhibitors has proved difficult with conventional approaches because the orthosteric sites of FGFR family members are observed to be highly similar in X-ray structures.

Practice Variations in Managing Infantile Hemangiomas.

Infantile hemangioma (IH) is the most common benign tumor of infancy. For children with IH who require treatment, propranolol and other beta blockers have been shown to be safe and effective. Although consensus guidelines for managing IH have been published, anecdotal experience suggests that there remain variations in management.

Evidence of a role for CutRS and actinorhodin in the secretion stress response in M145.

CutRS was the first two-component system to be identified in species and is highly conserved in this genus. It was reported >25 years ago that deletion of increases the production of the antibiotic actinorhodin in . However, despite this early work, the function of CutRS has remained enigmatic until now.

Barriers to Genetic Testing in Vascular Malformations.

Importance: Vascular malformations (VMs) are rare disorders of vasculogenesis associated with substantial morbidity. Improved understanding of their genetic basis is increasingly guiding management, but logistical barriers to obtaining genetic testing in patients with VM may constrain treatment options.

Objectives: To examine the institutional mechanisms for and obstacles to obtaining genetic testing for VM.

Fertility Preservation Decisional Turning Points for Adolescents and Young Adults With Cancer: Exploring Alignment and Divergence by Race and Ethnicity.

Purpose: For adolescents and young adults (AYAs) with cancer, fertility preservation (FP) decision making is complex and distressing. Racial/ethnic minority (REM) AYAs experience disparities in FP awareness, uptake, and outcomes. A turning point (TP) is a point of reflection, change, or decisive moment(s) resulting in changes in perspectives or trajectories.

CTP switches in ParABS-mediated bacterial chromosome segregation and beyond.

Segregation of genetic material is a fundamental process in biology. In many bacterial species, segregation of chromosomes and low-copy plasmids is facilitated by the tripartite ParA-ParB-parS system. This system consists of a centromeric parS DNA site and interacting proteins ParA and ParB that are capable of hydrolyzing adenosine triphosphate and cytidine triphosphate (CTP), respectively.

ActinoBase: tools and protocols for researchers working on and other filamentous actinobacteria.

Actinobacteria is an ancient phylum of Gram-positive bacteria with a characteristic high GC content to their DNA. The ActinoBase Wiki is focused on the filamentous actinobacteria, such as species, and the techniques and growth conditions used to study them. These organisms are studied because of their complex developmental life cycles and diverse specialised metabolism which produces many of the antibiotics currently used in the clinic.

Molecular Pathogenesis of Sporadic Desmoid Tumours and Its Implications for Novel Therapies: A Systematised Narrative Review.

Sporadic desmoid-type fibromatosis is a rare, fibroblastic soft-tissue neoplasm with local aggressiveness but no metastatic potential. Aberrant Wnt/β-catenin signalling has been extensively linked to desmoid pathogenesis, although little is known about other molecular drivers and no established treatment approach exists. We aimed to summarise the current literature regarding the molecular pathogenesis of sporadic desmoid-type fibromatosis and to discuss the effects of both current and emerging novel therapies targeting these mechanisms.

Safety of propranolol for infantile hemangioma in infants less than five weeks corrected age.

Background/objectives: Propranolol is used to treat problematic infantile hemangiomas (IHs), but its safety in infants <5 weeks corrected age has not been established. The objective of this study was to assess the safety and efficacy of propranolol for treatment of IH in infants <5 weeks corrected age, or 45 weeks corrected gestational age (CGA).

Methods: We performed a single institution, retrospective review of patients treated with propranolol prior to the age of 6 months between 2017 and 2021.

Influence of design and material characteristics on 3D printed flow-cells for heat transfer-based analytical devices.

Redesigning 3D-printed flow cells is reported used for heat transfer based detection of biomolecules from a flow-through system to an addition-type measurement cell. The aim of this study is to assess the performance of this new measurement design and critically analyse the influence of material properties and 3D printing approach on thermal analysis. Particular attention is paid to reduce the time to stabilisation, the sample volume in order to make the technique suitable for clinical applications, and improving the sensitivity of the platform by decreasing the noise and interference of air bubbles.

Computed Tomography Scans in Children With Hemophilia After Minor Head Trauma.

Objectives: Children with hemophilia have the usual childhood risk of falls and head trauma. Head computed tomographies (HCTs) are fast, detailed, and readily available, but increased radiation exposure in the pediatric population is now recognized as causing increased brain malignancy. By examining the incidence of intracranial cerebral hemorrhage in this population, we will be able to weigh risks and benefits of HCT use more accurately.

Infantile Hemangioma: A Current Review.

Infantile hemangiomas (IHs) are common vascular lesions which are benign but can cause significant functional and cosmetic morbidity. Since the fortuitous discovery of propranolol being effective to treat IH over a decade ago, the therapy and prognosis for children with IH have improved dramatically. Oral propranolol (as well as other oral beta-blockers and topical timolol) are safe and effective treatments, and have now supplanted other therapies.

COVID-19-Related Reduction in Emergency Health Care Utilization Among Febrile Pediatric Oncology Patients.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic has disrupted normal health care utilization patterns worldwide, including decreasing emergency department (ED) visits for various medical emergencies. We examined whether this pattern was present in febrile pediatric oncology patients. In this single-center cohort study, we conducted a retrospective chart review of ED visits of febrile pediatric oncology patients during the first 4 months of the global SARS-CoV-2 pandemic and compared those data to the same time periods in the previous 2 years.

Eutectic Mixture of Lidocaine and Prilocaine Decreases Movement and Propofol Requirements for Pediatric Lumbar Puncture During Deep Sedation: A Randomized, Placebo-Controlled, Double Blind Trial.

Deep sedation/general anesthesia is commonly used in pediatric oncology patients undergoing lumbar puncture (LP). Propofol is often used for sedation, with or without a narcotic. We hypothesized that eutectic mixture of lidocaine and prilocaine (EMLA) would allow for lower cumulative doses of propofol and less movement.

A conceptual model of fertility concerns among adolescents and young adults with cancer.

Objective: For adolescents and young adults (AYAs), cancer-related fertility concerns (FC) are salient, disruptive, and complex. Clinical communication about FC and fertility preservation options are suboptimal, increasing patient distress. The purpose of this study is to construct a conceptual model of FC among AYAs with cancer to inform future measurement development.

Nontranfusional Management of Severe Anemia in an Adolescent Jehovah's Witness Patient.

Severe anemia in Jehovah's Witness patients has long been a complex and sometimes divisive issue, especially in children and adolescents. In adolescent patients old enough to express their wishes, the decision to transfuse becomes more complicated. We present the case of a 12-year-old Jehovah's Witness female with severe anemia (hemoglobin of 2.