Phase 4 Multinational Multicenter Retrospective and Prospective Real-World Study of Nivolumab in Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck.

This study examined the real-world use of nivolumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). This was a multinational retrospective study (VOLUME) assessing treatment effectiveness and safety outcomes and a prospective study (VOLUME-PRO) assessing HRQoL and patient-reported symptoms. There were 447 and 51 patients in VOLUME and VOLUME-PRO, respectively.

Self-Esteem Mediates the Effects of Loneliness on Problematic Alcohol Use.

Loneliness has been associated with problematic alcohol use, but it is not known whether self-perceptions mediate this relationship. In this study, the general population in China (N = 1123) and Germany (N = 1018) was surveyed to assess whether self-esteem and self-efficacy mediate the effect of loneliness on problematic alcohol use in two culturally distinct environments. Multiple regression analysis demonstrated that higher AUDIT scores were negatively associated with self-esteem ( = -0.

Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes.

Background: Amongst risk alleles associated with late-onset Alzheimer's disease (AD), those that converged on the regulation of microglia activity have emerged as central to disease progression. Yet, how canonical amyloid-β (Aβ) and tau pathologies regulate microglia subtypes during the progression of AD remains poorly understood.

Methods: We use single-cell RNA-sequencing to profile microglia subtypes from mice exhibiting both Aβ and tau pathologies across disease progression.

How to Effectively Leverage Twitter as a Medical Student.

Twitter provides students with a centralized platform to learn about numerous opportunities within radiology. The platform can be immensely beneficial to students by providing opportunities to learn, network, connect with mentors, and find events while also preparing applicants for The Match. Having a prominent Twitter presence can pay dividends in the long term throughout one's training.

Evaluating the Public Climate School-A School-Based Programme to Promote Climate Awareness and Action in Students: Protocol of a Cluster-Controlled Pilot Study.

School-based programmes may promote knowledge and skills required to address climate change and better health and well-being in adolescents, yet evidence of their effectiveness is limited. In preparation for evaluating the Public Climate School, a school-based intervention to promote climate awareness and action in adolescents, we conduct a pilot study intended to assess procedures for participant recruitment, retention, and data collection, data quality issues and to provide preliminary parameter estimates to guide sample size calculations. This unblinded, cluster-controlled pilot study targets students in twelve classes from grades seven to thirteen in German public schools.

Cancer risk among firefighters and police in the Ontario workforce.

Objective: Firefighters and police often work in high-stress, complex environments with known and suspected carcinogenic exposures. We aimed to characterise cancer incidence among firefighters and police.

Methods: The Occupational Disease Surveillance System (ODSS) was used to identify workers employed as firefighters or police in Ontario.

Poor health disparities among racialized students in a Canadian university.

Objective: The short report aims to examine differences in self-rated general health across racialized post-secondary students at a university in Ontario, Canada.

Methods: Binary logistic regression analysis was used to examine poor health as an outcome among racialized students as whole, as well as across Asian, South Asian, Afro-Caribbean and Middle Eastern student groups in comparison to white Caucasian post-secondary students.

Results: After adjusting for several covariates, racialized students as a whole had 2.

Expansion of myeloid-derived suppressor cells contributes to metabolic osteoarthritis through subchondral bone remodeling.

Background: Osteoarthritis (OA) subsequent to acute joint injury accounts for a significant proportion of all arthropathies. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells classically known for potent immune-suppressive activity; however, MDSCs can also differentiate into osteoclasts. In addition, this population is known to be expanded during metabolic disease.

Systemic Therapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma- A Systematic Review and Meta-Analysis.

Background: The most effective regimen is unclear for patients with recurrent or metastatic head and neck squamous cell carcinomas (R/M HNSCC). We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating only systemic therapy for R/M HNSCC.

Methods: This systematic review followed PRISMA and the Cochrane Collaboration Handbook for Systematic Reviews of Interventions.

The Epigenomics of Pituitary Adenoma.

The vast majority of pituitary tumors are benign and behave accordingly; however, a fraction are invasive and are more aggressive, with a very small fraction being frankly malignant. The cellular pathways that drive transformation in pituitary neoplasms are poorly characterized, and current classification methods are not reliable correlates of clinical behavior. Novel techniques in epigenetics, the study of alterations in gene expression without changes to the genetic code, provide a new dimension to characterize tumors, and may hold implications for prognostication and management.

Equally Interchangeable? How Sex and Gender Affect Transplantation.

Organ transplantation as an option to overcome end-stage diseases is common in countries with advanced healthcare systems and is increasingly provided in emerging and developing countries. A review of the literature points to sex- and gender-based inequity in the field with differences reported at each step of the transplant process, including access to a transplantation waiting list, access to transplantation once waitlisted, as well as outcome after transplantation. In this review, we summarize the data regarding sex- and gender-based disparity in adult and pediatric kidney, liver, lung, heart, and hematopoietic stem cell transplantation and argue that there are not only biological but also psychological and socioeconomic issues that contribute to disparity in the outcome, as well as an inequitable access to transplantation for women and girls.

Cell cycle arrest in replicative senescence is not an immediate consequence of telomere dysfunction.

In replicative senescence, cells with critically-short telomeres activate a DNA-damage response leading to cell-cycle arrest, while those without telomere dysfunction would be expected to cycle normally. However, population growth declines more gradually than such a simple binary switch between cycling and non-cycling states would predict. We show here that late-passage cultures of human fibroblasts are not a simple mixture of cycling and non-cycling cells.

Mixing old and young: enhancing rejuvenation and accelerating aging.

Donor age and recipient age are factors that influence transplantation outcomes. Aside from age-associated differences in intrinsic graft function and alloimmune responses, the ability of young and old cells to exert either rejuvenating or aging effects extrinsically may also apply to the transplantation of hematopoietic stem cells or solid organ transplants. While the potential for rejuvenation mediated by the transfer of youthful cells is currently being explored for therapeutic applications, aspects that relate to accelerating aging are no less clinically significant.

The Impact of Sex on Alloimmunity.

Transplantation outcomes are known to be affected by multiple factors, including donor and recipient sex. Aside from the physiological characteristics of male and female donor allografts, accumulating evidence suggests that additional features underlie sex-specific immune responses that affect graft survival. We discuss here aspects of innate and adaptive alloimmunity that are specific to males and females in the context of underlying genetic and hormonal factors.

Induction chemotherapy for squamous cell carcinomas of the oral cavity: A cumulative meta-analysis.

Unlabelled: Induction chemotherapy (ICT) is a controversial treatment for head and neck squamous cell carcinomas (HNSCC). Despite numerous randomized controlled trials (RCTs), a majority do not have enough statistical power alone to conclude ICT's treatment value among oral squamous carcinoma patients (OSCC) since many addressed HNSCC as one entity instead of by specific subtypes. By performing a systematic review and cumulative meta-analysis, we aim to determine the benefits of ICT in OSCC therapy.

The neuritic plaque facilitates pathological conversion of tau in an Alzheimer's disease mouse model.

A central question in Alzheimer's Disease (AD) is whether the neuritic plaque is necessary and sufficient for the development of tau pathology. Hyperphosphorylation of tau is found within dystrophic neurites surrounding β-amyloid deposits in AD mouse models but the pathological conversion of tau is absent. Likewise, expression of a human tau repeat domain in mice is insufficient to drive the pathological conversion of tau.

Mutations in TRNT1 cause congenital sideroblastic anemia with immunodeficiency, fevers, and developmental delay (SIFD).

Mutations in genes encoding proteins that are involved in mitochondrial heme synthesis, iron-sulfur cluster biogenesis, and mitochondrial protein synthesis have previously been implicated in the pathogenesis of the congenital sideroblastic anemias (CSAs). We recently described a syndromic form of CSA associated with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD). Here we demonstrate that SIFD is caused by biallelic mutations in TRNT1, the gene encoding the CCA-adding enzyme essential for maturation of both nuclear and mitochondrial transfer RNAs.

Super-enhancers in the control of cell identity and disease.

Super-enhancers are large clusters of transcriptional enhancers that drive expression of genes that define cell identity. Improved understanding of the roles that super-enhancers play in biology would be afforded by knowing the constellation of factors that constitute these domains and by identifying super-enhancers across the spectrum of human cell types. We describe here the population of transcription factors, cofactors, chromatin regulators, and transcription apparatus occupying super-enhancers in embryonic stem cells and evidence that super-enhancers are highly transcribed.

Selective inhibition of tumor oncogenes by disruption of super-enhancers.

Chromatin regulators have become attractive targets for cancer therapy, but it is unclear why inhibition of these ubiquitous regulators should have gene-specific effects in tumor cells. Here, we investigate how inhibition of the widely expressed transcriptional coactivator BRD4 leads to selective inhibition of the MYC oncogene in multiple myeloma (MM). BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes.

Ribosomal DNA integrating rAAV-rDNA vectors allow for stable transgene expression.

Although recombinant adeno-associated virus (rAAV) vectors are proving to be efficacious in clinical trials, the episomal character of the delivered transgene restricts their effectiveness to use in quiescent tissues, and may not provide lifelong expression. In contrast, integrating vectors enhance the risk of insertional mutagenesis. In an attempt to overcome both of these limitations, we created new rAAV-rDNA vectors, with an expression cassette flanked by ribosomal DNA (rDNA) sequences capable of homologous recombination into genomic rDNA.

Human tRNA-derived small RNAs in the global regulation of RNA silencing.

Competition between mammalian RNAi-related gene silencing pathways is well documented. It is therefore important to identify all classes of small RNAs to determine their relationship with RNAi and how they affect each other functionally. Here, we identify two types of 5'-phosphate, 3'-hydroxylated human tRNA-derived small RNAs (tsRNAs).