Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes.

Background: Natural killer (NK) cells are important contributors to antitumor immunity in clear-cell renal cell carcinoma (ccRCC). However, their phenotype, function, and association with clinical outcomes in ccRCC remain poorly understood.

Materials And Methods: We analyzed single-cell RNA sequencing data from 13 primary tumors, 1 localized tumor extension, and 1 metastasis from ccRCC patients at different clinical stages.

Nf1 mutation disrupts activity-dependent oligodendroglial plasticity and motor learning in mice.

Neurogenetic disorders, such as neurofibromatosis type 1 (NF1), can cause cognitive and motor impairments, traditionally attributed to intrinsic neuronal defects such as disruption of synaptic function. Activity-regulated oligodendroglial plasticity also contributes to cognitive and motor functions by tuning neural circuit dynamics. However, the relevance of oligodendroglial plasticity to neurological dysfunction in NF1 is unclear.

Tumor microenvironmental determinants of high-risk DCIS progression.

Ductal carcinoma (DCIS) constitutes an array of morphologically recognized intraductal neoplasms in the mammary ductal tree defined by an increased risk for subsequent invasive carcinomas at or near the site of biopsy detection. However, only 15-45% of untreated DCIS cases progress to invasive cancer, so understanding mechanisms that prevent progression is key to avoid overtreatment and provides a basis for alternative therapies and prevention. This study was designed to characterize the tumor microenvironment and molecular profile of high-risk DCIS that grew to a large size but remained as DCIS.

St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.

St. John's wort (SJW) extract, a herbal medicine with antidepressant effects, is a potent inducer of intestinal and/or hepatic cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), which can cause clinically relevant drug interactions. It is currently not known whether SJW can also induce P-gp activity at the human blood-brain barrier (BBB), which may potentially lead to decreased brain exposure and efficacy of certain central nervous system (CNS)-targeted P-gp substrate drugs.

Antigenic targets in clear cell renal cell carcinoma.

Immune checkpoint inhibitors (ICIs) have transformed the management of advanced renal cell carcinoma (RCC), but most patients still do not receive a long-term benefit from these therapies, and many experience off-target, immune-related adverse effects. RCC is also different from many other ICI-responsive tumors, as it has only a modest mutation burden, and total neoantigen load does not correlate with ICI response. In order to improve the efficacy and safety of immunotherapies for RCC, it is therefore critical to identify the antigens that are targeted in effective anti-tumor immunity.

Temporal variation of mycorrhization rates in a tree diversity experiment.

While mycorrhization rates have been studied in different contexts, not much is known about their temporal patterns across seasons. Here, we asked how mycorrhization rates of 10 deciduous trees assessed by microscopy changed from winter to spring to early summer. We made use of a tree diversity experiment on nutrient-rich soil (former farmland) in Central Germany.

Examining medical student volunteering during the COVID-19 pandemic as a prosocial behaviour during an emergency.

Purpose: Understanding the factors that influence prosocial behaviour during the COVID-19 pandemic is essential due to the disruption to healthcare provision.

Methods: We conducted an in-depth, mixed-methods cross-sectional survey, from 2 May 2020 to 15 June 2020, of medical students at medical schools in the United Kingdom. Data analysis was informed by Latané and Darley's theory of prosocial behaviour during an emergency.

Clinical support during COVID-19: An opportunity for service and learning? A cross-sectional survey of UK medical students.

Purpose: Medical students providing support to clinical teams during Covid-19 may have been an opportunity for service and learning. We aimed to understand why the reported educational impact has been mixed to inform future placements.

Methods: We conducted a cross-sectional survey of medical students at UK medical schools during the first Covid-19 'lockdown' period in the UK (March-July 2020).

Genetic requirements for repair of lesions caused by single genomic ribonucleotides in S phase.

Single ribonucleoside monophosphates (rNMPs) are transiently present in eukaryotic genomes. The RNase H2-dependent ribonucleotide excision repair (RER) pathway ensures error-free rNMP removal. In some pathological conditions, rNMP removal is impaired.

Gender differences in motor and non-motor symptoms in individuals with mild-moderate Parkinson's disease.

Background: Parkinson's disease (PD) affects both men and women with documented gender differences across functional domains, with findings varying among reports. Knowledge regarding gender differences in PD for different geographic locations is important for further understanding of the disease and for developing personalized gender-specific PD assessment tools and therapies.

Objective: This study aimed to examine gender differences in PD-related motor, motor-cognitive, cognitive, and psychosocial function in people with PD from the southern United States (US).

Remote and in-person research education for people with Parkinson's disease and their care partners.

Objective: TeleDREAMS, a distance learning version of the Developing a Research Participation Enhancement and Advocacy Training Program for Diverse Seniors (DREAMS) program, provides remote clinical research process and advocacy education to older adults with Parkinson's disease (PD) and their care partners.

Method: Participants engaged in remote learning, reading eight weekly clinical research process and advocacy education modules. They also had weekly half hour phone discussions with staff about each module.

Relationship between parental history of dementia, motor-cognitive and executive function performance in African American women.

People with parental history (PH) of Alzheimer's Disease (AD) and Alzheimer's Disease and related dementias (ADRD) are themselves at risk of developing dementia. ADRD are more prevalent in African Americans and women. A decline in executive function and motor-cognitive integration can cause an impaired performance of functional skills.

Large scale clinical trials: lessons from the COVID-19 pandemic.

Background: The COVID-19 pandemic has presented substantial new challenges to clinical and research teams. Our objective was to analyse the experience of investigators and research delivery staff regarding the research response to COVID-19 in order to identify these challenges as well as solutions for future pandemic planning.

Methods: We conducted a survey of diverse research staff involved in delivery of COVID-19 clinical trials across the UK.

Mre11-Rad50 oligomerization promotes DNA double-strand break repair.

The conserved Mre11-Rad50 complex is crucial for the detection, signaling, end tethering and processing of DNA double-strand breaks. While it is known that Mre11-Rad50 foci formation at DNA lesions accompanies repair, the underlying molecular assembly mechanisms and functional implications remained unclear. Combining pathway reconstitution in electron microscopy, biochemical assays and genetic studies, we show that S.

Vascular Surgery Curriculum for Medical Students: A National Targeted Needs Assessment.

Background: At present, neither the American College of Surgeons (ACS) nor the Society for Vascular Surgery (SVS) provides curriculum recommendations for medical students rotating on a vascular surgery service. We sent a targeted needs assessment to vascular surgeons across the country in order to investigate the need for a structured curriculum for medical students participating in a vascular surgery rotation during their clinical clerkships.

Methods: The survey was developed with input from medical students, vascular surgeons, and medical educators.

NF1 mutation drives neuronal activity-dependent initiation of optic glioma.

Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours. Although the role of neurons in tumour progression has previously been demonstrated, the importance of neuronal activity to tumour initiation is less clear-particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood, raising  the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation.

Mixing tree species associated with arbuscular or ectotrophic mycorrhizae reveals dual mycorrhization and interactive effects on the fungal partners.

Recent studies found that the majority of shrub and tree species are associated with both arbuscular mycorrhizal (AM) and ectomycorrhizal (EM) fungi. However, our knowledge on how different mycorrhizal types interact with each other is still limited. We asked whether the combination of hosts with a preferred association with either AM or EM fungi increases the host tree roots' mycorrhization rate and affects AM and EM fungal richness and community composition.

COVIDReady2 study protocol: cross-sectional survey of medical student volunteering and education during the COVID-19 pandemic in the United Kingdom.

Background: The coronavirus disease 2019 pandemic has led to global disruption of healthcare. Many students volunteered to provide clinical support. Volunteering to work in a clinical capacity was a unique medical education opportunity; however, it is unknown whether this was a positive learning experience or which volunteering roles were of most benefit to students.

Progressive immune dysfunction with advancing disease stage in renal cell carcinoma.

The tumor immune microenvironment plays a critical role in cancer progression and response to immunotherapy in clear cell renal cell carcinoma (ccRCC), yet the composition and phenotypic states of immune cells in this tumor are incompletely characterized. We performed single-cell RNA and T cell receptor sequencing on 164,722 individual cells from tumor and adjacent non-tumor tissue in patients with ccRCC across disease stages: early, locally advanced, and advanced/metastatic. Terminally exhausted CD8 T cells were enriched in metastatic disease and were restricted in T cell receptor diversity.

Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein.

Heart development relies on PTMs that control cardiomyocyte proliferation, differentiation and cardiac morphogenesis. We generated a map of phosphorylation sites during the early stages of cardiac postnatal development in mice; we quantified over 10,000 phosphorylation sites and 5000 proteins that were assigned to different pathways. Analysis of mitochondrial proteins led to the identification of PGC-1- and ERR-induced regulator in muscle 1 (PERM1), which is specifically expressed in skeletal muscle and heart tissue and associates with the outer mitochondrial membrane.

Non-coding RNAs at the Eukaryotic rDNA Locus: RNA-DNA Hybrids and Beyond.

The human ribosomal DNA (rDNA) locus encodes a variety of long non-coding RNAs (lncRNAs). Among them, the canonical ribosomal RNAs that are the catalytic components of the ribosomes, as well as regulatory lncRNAs including promoter-associated RNAs (pRNA), stress-induced promoter and pre-rRNA antisense RNAs (PAPAS), and different intergenic spacer derived lncRNA species (IGSRNA). In addition, externally encoded lncRNAs are imported into the nucleolus, which orchestrate the complex regulation of the nucleolar state in normal and stress conditions via a plethora of molecular mechanisms.

Resident Perspectives on Teaching During Awake Surgical Procedures.

Introduction: Residents learn technical and communication skills during training and practice both concurrently during awake surgical procedures. Patients have expressed mixed views on resident involvement in their surgical care, making this context challenging for residents to navigate. We sought to qualitatively explore resident perspectives on teaching during awake surgical procedures.

Bridging the Gap: Interdepartmental Quality Improvement and Patient Safety Curriculum Created by Hospital Leaders, Faculty, and Trainees.

Background: The Accreditation Council for Graduate Medical Education Clinical Learning Environment Review recommends that quality improvement/patient safety (QI/PS) experts, program faculty, and trainees collectively develop QI/PS education.

Objective: Faculty, hospital leaders, and resident and fellow champions at the University of Chicago designed an interdepartmental curriculum to train postgraduate year 1 (PGY-1) residents on core QI/PS principles, measuring outcomes of knowledge, attitudes, and event reporting.

Methods: The curriculum consisted of 3 sessions: PS, quality assessment, and QI.