Evidence of DNA methylation heterogeneity and epipolymorphism in kidney cancer tissue samples.

Clear cell renal cell carcinoma (ccRCC) is characterised by significant genetic heterogeneity, which has diagnostic and prognostic implications. Very limited evidence is available regarding DNA methylation heterogeneity. We therefore generate sequence level DNA methylation data on 136 multi-region tumour and normal kidney tissue from 18 ccRCC patients, along with matched whole exome sequencing (85 samples) and gene expression (47 samples) data on a subset of samples.

Proximity and Prior Medical Engagement Influence Follow-Up After Ruptured Abdominal Aortic Aneurysm.

Objective: Post-repair surveillance of ruptured abdominal aortic aneurysm (rAAA) is critical for detecting potential complications. Substantial loss to follow-up has been reported in populations undergoing elective endovascular aortic repair (EVAR); however, there is limited data on follow-up rate among patients presenting with rupture. Thus, we investigated follow-up trends and factors influencing retention at a major academic referral center with a wide service area.

How Do Gepotidacin and Zoliflodacin Stabilize DNA-Cleavage Complexes with Bacterial Type IIA Topoisomerases? 2. A Single Moving Metal Mechanism.

DNA gyrase is a bacterial type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology and an archetypical target of antibiotics. The widely used quinolone class of drugs use a water-metal ion bridge in interacting with the GyrA subunit of DNA gyrase. Zoliflodacin sits in the same pocket as quinolones but interacts with the GyrB subunit and also stabilizes lethal double-stranded DNA breaks.

Development and validation of a high-throughput qPCR platform for the detection of soil-transmitted helminth infections.

Background: Historically, soil-transmitted helminth (STH) control and prevention strategies have relied on mass drug administration efforts targeting preschool and school-aged children. While these efforts have succeeded in reducing morbidity associated with STH infection, recent modeling efforts have suggested that expanding intervention to treatment of the entire community could achieve transmission interruption in some settings. Testing the feasibility of such an approach requires large-scale clinical trials, such as the DeWorm3 cluster randomized trial.

Neuromodulation Strategies in Lennox-Gastaut Syndrome: Practical Clinical Guidance from the Pediatric Epilepsy Research Consortium.

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, cognitive impairment, and distinctive electroencephalographic patterns. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS), have emerged as important treatment options for patients with LGS who do not respond adequately to antiseizure medications. This review, developed with input from the Pediatric Epilepsy Research Consortium (PERC) LGS Special Interest Group, provides practical guidance for clinicians on the use of these neuromodulation approaches in patients with LGS.

Racial Disparities in Clinical Trial Enrollment Among Patients Diagnosed With Prostate Cancer: A Population-Based Cohort of Oncology Practices.

Although clinical trials should be accessible to all patients, persistent racial and ethnic disparities in clinical trial enrollment exist. Herein, we examine racial disparities in clinical trial enrollment among prostate cancer patients from a large population-based cohort of oncology practices in the United States. Using CancerLinQ Discovery, we identified men with regional (N1+) and/or metastatic (M1) prostate cancer diagnosed from 2011 to 2023.

Kinomic profiling to predict sunitinib response of patients with metastasized clear cell Renal Cell Carcinoma.

Introduction: Treatment with Sunitinib, a potent multitargeted receptor tyrosine kinase inhibitor (TKI) has increased the progression-free survival (PFS) and overall-survival (OS) of patients with metastasized renal cell carcinoma (mRCC). With modest OS improvement and variable response and toxicity predictive and/or prognostic biomarkers are needed to personalize patient management: Prediction of individual TKI therapy response and resistance will increase successful treatment outcome while reducing unnecessary drug use and expense. The aim of this study was to investigate whether kinase activity analysis can predict sunitinib response and/or toxicity using tissue samples obtained from primary clear cell RCC (ccRCC) from a cohort of clinically annotated patients with mRCC receiving sunitinib as first-line treatment.

Understanding Cognitive Aging Through White Matter: A Fixel-Based Analysis.

Diffusion-weighted imaging (DWI) has been frequently used to examine age-related deterioration of white matter microstructure and its relationship to cognitive decline. However, typical tensor-based analytical approaches are often difficult to interpret due to the challenge of decomposing and (mis)interpreting the impact of crossing fibers within a voxel. We hypothesized that a novel analytical approach capable of resolving fiber-specific changes within each voxel (i.

Delivering the news of an intraoperative death; literature-based guidance from the American Association for Thoracic Surgery Wellness Committee.

Objectives: Fortunately, operating room deaths and unexpected deaths are infrequent occurrences. However, when they occur, the surgeon is called upon to deliver this news to family and loved ones. There is a paucity of literature on this topic and little guidance preparing cardiothoracic surgeons for this important but difficult situation.

Making the most of an abundance of data.

The Guest Editors introduce the special issue based on talks at the CCP4 Study Weekend 2023. The virtual issue is available at https://journals.iucr.

Feline Diabetes Is Associated with Deficits in Markers of Insulin Signaling in Peripheral Tissues.

Like humans, cats have a strong relationship between decreasing insulin sensitivity and the development of diabetes with obesity. However, the underlying molecular mechanisms of impaired insulin secretion and signaling in cats remain largely unknown. A total of 54 client-owned nondiabetic lean ( = 15), overweight ( = 15), and diabetic ( = 24) cats were included in the study.

Spatiotemporal distribution patterns and assembly mechanisms of eukaryotic plankton communities in Liujiaxia Reservoir at the northeastern edge of the Tibetan Plateau.

Eukaryotic plankton are important parts of the aquatic ecosystem and their community composition and spatiotemporal distribution patterns are affected by environmental factors. The Liujiaxia Reservoir is located at the northeastern edge of the Tibetan Plateau and is a vital resource for communities and agriculture in the region. Revealing the plankton diversity and their correlation with environmental factors is essential for understanding the ecological processes and mechanisms by which plankton contribute to, and maintain the ecosystem function of, the Liujiaxia Reservoir and beyond.

Comparative efficacy and safety of mid-neck vs. supraclavicular vagus nerve stimulation in pediatric drug-resistant epilepsy.

Objectives: A supraclavicular insertion approach for vagus nerve stimulation (VNS) may permit a wider range of VNS settings compared to traditional insertion techniques due to increased anatomic distance between VNS leads and the recurrent laryngeal nerve. Beyond potential technical advantages, this approach could offer greater cosmetic satisfaction for patients. However, the safety and efficacy of the supraclavicular approach is uncertain.

Mycobacterium leprae in Nine-Banded Armadillos (Dasypus novemcinctus), Ecuador.

We found Mycobacterium leprae, the most common etiologic agent of Hansen disease or leprosy, in tissues from 9 (18.75%) of 48 nine-banded armadillos (Dasypus novemcinctus) collected across continental Ecuador. Finding evidence of a wildlife reservoir is the first step to recognizing leprosy zoonotic transmission pathway in Ecuador or elsewhere.

Increased ambient temperature and hyponatraemia presentations: A ten-year retrospective study at an Australian hospital.

Objectives: To determine the relationship between ambient air temperature and the incidence of hyponatraemia in a heat-prone region.

Design And Setting: We conducted a retrospective study that correlated serum sodium concentrations documented at The Austin Hospital in Melbourne over ten years from January 2014 to December 2023, with publicly available temperature data from the Australian Bureau of Meteorology.

Main Outcome Measures: Serum sodium concentrations and incidence of hyponatraemia admissions when correlated to temperature, and following heatwave events, defined as temperature above 30°C over five consecutive days.

Open Revascularization for Acute Mesenteric Ischemia is Associated with Increased Morbidity and Mortality when Compared to Endovascular Intervention.

Objectives: Historically, open approaches have been considered the primary treatment for acute mesenteric ischemia (AMI) due to the potential for bowel resection. However, the use of endovascular therapy is increasing. Given the paucity of current data, this study aims to compare outcomes between open and endovascular interventions for AMI.

Women have higher morbidity and mortality after repair of complex aortic aneurysms due to symptomatic presentation and more extensive aneurysms.

Objective: Prior studies have found disparities in outcomes by sex after repair of abdominal aortic aneurysms. However, little is known about the disparities in outcomes after endovascular repair of complex abdominal aortic aneurysms. This study aims to assess differences in presentation and outcomes by sex after endovascular repair of complex abdominal aortic aneurysms.

Niche-specific metabolic phenotypes can be used to identify antimicrobial targets in pathogens.

Bacterial pathogens pose a major risk to human health, leading to tens of millions of deaths annually and significant global economic losses. While bacterial infections are typically treated with antibiotic regimens, there has been a rapid emergence of antimicrobial resistant (AMR) bacterial strains due to antibiotic overuse. Because of this, treatment of infections with traditional antimicrobials has become increasingly difficult, necessitating the development of innovative approaches for deeply understanding pathogen function.

Small-rotative fixed-target serial synchrotron crystallography (SR-FT-SSX) for molecular crystals.

The increasing availability of ultrabright Light Sources is facilitating the study of smaller crystals at faster timescales but with an increased risk of severe X-ray damage, leading to developments in multi-crystal methods such as serial crystallography (SX). SX studies on crystals with small unit cells are challenging as very few reflections are recorded in a single data image, making it difficult to determine the orientation matrix for each crystal and thus preventing the combination of the data from all crystals for structure solution. We herein present a Small-Rotative Fixed-Target Serial Synchrotron Crystallography (SR-FT-SSX) methodology, in which rotation of the serial target through a small diffraction angle at each crystal delivers high-quality data, facilitating ab initio unit cell determination and atomic-scale structure solution.

The effects of deep brain stimulation on sleep: a systematic review and meta-analysis.

Background: Deep brain stimulation (DBS) is a standard treatment for movement disorders, epilepsy, and others, yet its influence on postprocedural sleep quality remains an under-researched topic.

Study Objectives: We performed a systematic review and meta-analysis of all DBS effects on sleep.

Methods: The use of preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) was utilized.

How Do Gepotidacin and Zoliflodacin Stabilize DNA Cleavage Complexes with Bacterial Type IIA Topoisomerases? 1. Experimental Definition of Metal Binding Sites.

One of the challenges for experimental structural biology in the 21st century is to see chemical reactions happen. () DNA gyrase is a type IIA topoisomerase that can create temporary double-stranded DNA breaks to regulate DNA topology. Drugs, such as gepotidacin, zoliflodacin and the quinolone moxifloxacin, can stabilize these normally transient DNA strand breaks and kill bacteria.

New insights and investigation: Morphomolecular notes on the infraciliature, taxonomy, and systematics of pleurostomatid ciliates (Protozoa, Ciliophora), with establishment of a new suborder, two new genera, and three new species.

Pleurostomatid ciliates, as a highly diverse and widely distributed unicellular eukaryote group, play a crucial role in the cycling of nutrients and energy in microbial food webs. However, research on pleurostomatids remains insufficient, resulting in a paucity of molecular information and substantial gaps in knowledge of their phylogenetic relationships. In recent years, we investigated pleurostomatid diversity in various Chinese habitats, including their systematic relationships and taxonomic circumscriptions, which were comprehensively analyzed using an integrative morphomolecular approach.