Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection.

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers.

rDNA array length is a major determinant of replicative lifespan in budding yeast.

The complex processes and interactions that regulate aging and determine lifespan are not fully defined for any organism. Here, taking advantage of recent technological advances in studying aging in budding yeast, we discovered a previously unappreciated relationship between the number of copies of the ribosomal RNA gene present in its chromosomal array and replicative lifespan (RLS). Specifically, the chromosomal ribosomal DNA (rDNA) copy number (rDNA CN) positively correlated with RLS and this interaction explained over 70% of variability in RLS among a series of wild-type strains.

Tumor mutational burden and somatic mutation status to predict disease recurrence in advanced melanoma.

Tumor mutational burden (TMB) has recently been identified as a biomarker of response to immune checkpoint inhibitors in many cancers, including melanoma. Co-assessment of TMB with inflammatory markers and genetic mutations may better predict disease outcomes. The goal of this study was to evaluate the potential for TMB and somatic mutations in combination to predict the recurrence of disease in advanced melanoma.

International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

Objective: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma.

Summary Background Data: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization.

Experiences of New Mothers During the Coronavirus Disease 2019 (COVID-19) Pandemic.

Objective: To describe postpartum experiences of women who gave birth during the coronavirus disease 2019 (COVID-19) pandemic, to identify short-term and long-term opportunities to address maternal-child health during this pandemic.

Methods: This qualitative photo-elicitation study asked 30 women between 3 and 10 weeks postpartum to take photographs that encompassed their experience as a new mother during the pandemic. Two trained interviewers elicited elements of this experience using the photos as an anchor during virtual, hour-long interviews.

A Retrospective, Observational Analysis of Tumor Infiltrating Lymphocytes and Tumor Regression in Melanoma.

Background: Tumor infiltrating lymphocytes (TILs) and regression are thought to be distinct markers of the immune response to melanoma.

Objective: This study sought to analyze the relationship of TIL grade and presence of regression to each other and to other prognostic histopathologic and clinical values in melanoma.

Materials And Methods: A retrospective analysis was conducted using patients diagnosed with melanoma between 2013 and 2019 whose complete histopathologic reports were available.

A genome-scale yeast library with inducible expression of individual genes.

The ability to switch a gene from off to on and monitor dynamic changes provides a powerful approach for probing gene function and elucidating causal regulatory relationships. Here, we developed and characterized YETI (Yeast Estradiol strains with Titratable Induction), a collection in which > 5,600 yeast genes are engineered for transcriptional inducibility with single-gene precision at their native loci and without plasmids. Each strain contains SGA screening markers and a unique barcode, enabling high-throughput genetics.

RAGE interacts with the necroptotic protein RIPK3 and mediates transfusion-induced danger signal release.

RBC transfusion is associated with increased morbidity and mortality in critically ill patients. Endothelial cell necroptosis and subsequent damage-associated molecular pattern (DAMP) release has been identified as a mechanism of injury following RBC transfusion. Mounting evidence implicates the pro-inflammatory pattern recognition receptor, Receptor for Advanced Glycation End Products (RAGE), in initiating cell death programmes such as necroptosis.

Patients with Lemierre syndrome have a high risk of new thromboembolic complications, clinical sequelae and death: an analysis of 712 cases.

Background: Lemierre syndrome is characterized by head/neck vein thrombosis and septic embolism usually complicating an acute oropharyngeal bacterial infection in adolescents and young adults. We described the course of Lemierre syndrome in the contemporary era.

Methods: In our individual-level analysis of 712 patients (2000-2017), we included cases described as Lemierre syndrome if these criteria were met: (i) primary site of bacterial infection in the head/neck; (ii) objectively confirmed local thrombotic complications or septic embolism.

Plasma receptor interacting protein kinase-3 levels are associated with acute respiratory distress syndrome in sepsis and trauma: a cohort study.

Background: Necroptosis, a form of programmed cell death mediated by receptor interacting serine/threonine-protein kinase-3 (RIPK3), is implicated in murine models of acute respiratory distress syndrome (ARDS). We hypothesized that plasma RIPK3 concentrations in sepsis and trauma would be associated with ARDS development and that plasma RIPK3 would reflect changes in lung tissue RIPK3 in a murine model of systemic inflammation.

Methods: We utilized prospective cohort studies of critically ill sepsis (n = 120) and trauma (n = 180) patients and measured plasma RIPK3 at presentation and 48 h.

Human papilloma virus-associated squamous cell carcinoma of the larynx in an 18-year-old woman.

Background: Human papilloma virus (HPV)-associated malignancies are considered to be sexually transmitted diseases.

Methods: We report a HPV-positive larynx cancer in an 18-year-old female clarinet player, despite vaccination with the quadrivalent HPV-6-11-16-18-vaccine Gardasil (Merck Sharp & Dohme Corp., West Point, Pennsylvania).

Progress in ultrahigh energy resolution EELS.

Electron energy loss spectroscopy (EELS) in the electron microscope has progressed remarkably in the last five years. Advances in monochromator and spectrometer design have improved the energy resolution attainable in a scanning transmission electron microscope (STEM) to 4.2 meV, and new applications of ultrahigh energy resolution EELS have not lagged behind.

Lemierre Syndrome: Clinical Update and Protocol for a Systematic Review and Individual Patient Data Meta-analysis.

Lemierre syndrome usually affects otherwise healthy adolescents or young adults and occurs at an overall rate of 1 to 10 cases per million person-years with an estimated fatality rate of 4 to 9%. Diagnostic criteria remain debated and include acute neck/head bacterial infection (often tonsillitis caused by anaerobes at high potential for sepsis and vascular invasion, notably ) complicated by local vein thrombosis, usually involving the internal jugular vein, and systemic septic embolism. Medical treatment is based on antibiotic therapy with anaerobic coverage, anticoagulant drugs and supportive care in case of sepsis.

Pumilio-dependent localization of mRNAs at the cell front coordinates multiple pathways required for chemotaxis.

Chemotaxis is a specialized form of directed cell migration important for normal development, wound healing, and cancer metastasis. In the social amoeba Dictyostelium discoideum, four signaling pathways act synergistically to maintain directional cell migration. However, it is unknown how these pathways are coordinated in space and time to achieve persistent chemotaxis.

Red Blood Cells Homeostatically Bind Mitochondrial DNA through TLR9 to Maintain Quiescence and to Prevent Lung Injury.

Rationale: Potentially hazardous CpG-containing cell-free mitochondrial DNA (cf-mtDNA) is routinely released into the circulation and is associated with morbidity and mortality in critically ill patients. How the body avoids inappropriate innate immune activation by cf-mtDNA remains unknown. Because red blood cells (RBCs) modulate innate immune responses by scavenging chemokines, we hypothesized that RBCs may attenuate CpG-induced lung inflammation through direct scavenging of CpG-containing DNA.

Budding yeast Wee1 distinguishes spindle pole bodies to guide their pattern of age-dependent segregation.

Many asymmetrically dividing cells unequally partition cellular structures according to age. Yet, it is unclear how cells differentiate pre-existing from newly synthesized material. Yeast cells segregate the spindle pole body (SPB, centrosome equivalent) inherited from the previous mitosis to the bud, while keeping the new one in the mother cell.

S. aureus blocks efferocytosis of neutrophils by macrophages through the activity of its virulence factor alpha toxin.

Bacterial pneumonia, such as those caused by Staphylococcus aureus, is associated with an influx of inflammatory neutrophils into the lung tissue and airways. Regulation and clearance of recruited neutrophils is essential for preventing tissue damage by "friendly fire", a responsibility of macrophages in a process called efferocytosis. We hypothesized that S.

Plasma Levels of Receptor Interacting Protein Kinase-3 (RIP3), an Essential Mediator of Necroptosis, are Associated with Acute Kidney Injury in Critically Ill Trauma Patients.

Background: Receptor interacting protein kinase-3 (RIP3) is a key mediator of necroptosis, a form of regulated cell death recently implicated in murine models of renal ischemia-reperfusion injury and transfusion-associated endothelial injury. The importance of necroptosis in human AKI is unknown. We hypothesized that plasma RIP3 concentrations would be associated with acute kidney injury (AKI) after severe trauma.

Asymmetry of the budding yeast Tem1 GTPase at spindle poles is required for spindle positioning but not for mitotic exit.

The asymmetrically dividing yeast S. cerevisiae assembles a bipolar spindle well after establishing the future site of cell division (i.e.

Septic thrombosis of the internal jugular vein: Lemierre's syndrome revisited.

Objectives/hypothesis: Study of the clinical evolution of a primary ear, nose, and throat infection complicated by septic thrombophlebitis of the internal jugular vein.

Study Design: Retrospective case-control study.

Patients And Methods: From 1998 to 2010, 23 patients at our institution were diagnosed with a septic thrombosis of the internal jugular vein.

The Mitotic Exit Network: new turns on old pathways.

In budding yeast, the Mitotic Exit Network (MEN) is a signaling pathway known to drive cells out of mitosis and promote the faithful division of cells. The MEN triggers inactivation of cyclin-dependent kinase (Cdk1), the master regulator of mitosis, and the onset of cytokinesis after segregation of the daughter nuclei. The current model of the MEN suggests that MEN activity is restricted to late anaphase and coordinated with proper alignment of the spindle pole bodies (SPBs) with the division axis.

Extended frequency range hearing thresholds and otoacoustic emissions in acute acoustic trauma.

Objective: We sought to evaluate the relative value of pure tone audiometry (PTA), extended high-frequency audiometry (EFA) and transiently evoked otoacoustic emissions (OAE) and distortion products when monitoring acute acoustic trauma (AAT).

Study Design: Controlled prospective clinical study.

Setting: Tertiary referral center.