Assembly of Pyrenes through a Quadruple Photochemical Cascade: Blocking Groups Allow Diversion from the Double Mallory Path to Photocyclization at the Bay Region.

We present a six-step cascade that converts 1,3-distyrylbenzenes (-stilbenes) into nonsymmetric pyrenes in 40-60% yields. This sequence merges photochemical steps, ,-alkene isomerization, a 6π photochemical electrocyclization (Mallory photocyclization); the new bay region cyclization, with two radical iodine-mediated aromatization steps; and an optional aryl migration. This work illustrates how the inherent challenges of engineering excited state reactivity can be addressed by logical design.

TET2 promotes tumor antigen presentation and T cell IFN-γ, which is enhanced by vitamin C.

Immune evasion by tumors is promoted by low T cell infiltration, ineffective T cell activity directed against the tumor, and reduced tumor antigen presentation. The TET2 DNA dioxygenase gene is frequently mutated in hematopoietic malignancies and loss of TET enzymatic activity is found in a variety of solid tumors. We showed previously that vitamin C (VC), a cofactor of TET2, enhances tumor-associated T cell recruitment and checkpoint inhibitor therapy responses in a TET2-dependent manner.

Endosteal stem cells at the bone-blood interface: A double-edged sword for rapid bone formation: Bone marrow endosteal stem cells provide a robust source of bone-making osteoblasts both in normal and abnormal bone formation.

Endosteal stem cells are a subclass of bone marrow skeletal stem cell populations that are particularly important for rapid bone formation occurring in growth and regeneration. These stem cells are strategically located near the bone surface in a specialized microenvironment of the endosteal niche. These stem cells are abundant in young stages but eventually depleted and replaced by other stem cell types residing in a non-endosteal perisinusoidal niche.

Prevalence and impact of human papillomavirus (HPV) in adults with cystic fibrosis: A self-reported cross-sectional Canadian survey.

Background: In persons with cystic fibrosis (pwCF), little is known about the prevalence or impact of HPV on quality of life and attitudes towards vaccination.

Methods: We conducted a national online survey of adult pwCF. We sought to determine the prevalence of self-reported HPV infection, disease-associated complications and effects on quality of life.

Delivery and evaluation of simulations to promote authentic and meaningful engagement in childhood disability research.

Background: In 2019, our interdisciplinary team of researchers, family members, and youth co-designed four simulation training videos and accompanying facilitation resources to prepare youth, family members, trainees, and researchers to build the knowledge and skills to engage in patient-oriented research (POR) authentically and meaningfully. Videos covered challenges in aspects of the research process including (1) forming a project team; (2) identifying project objectives and priorities; (3) agreeing on results; and (4) carrying out knowledge translation.

Methods: The purpose of the study was to deliver four simulation training videos across 2 two-hour facilitated workshops with researchers, trainees, and family partners.

Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis.

The bone marrow contains various populations of skeletal stem cells (SSCs) in the stromal compartment, which are important regulators of bone formation. It is well-described that leptin receptor (LepR) perivascular stromal cells provide a major source of bone-forming osteoblasts in adult and aged bone marrow. However, the identity of SSCs in young bone marrow and how they coordinate active bone formation remains unclear.

The fate of early perichondrial cells in developing bones.

In endochondral bone development, bone-forming osteoblasts and bone marrow stromal cells have dual origins in the fetal cartilage and its surrounding perichondrium. However, how early perichondrial cells distinctively contribute to developing bones remain unidentified. Here we show using in vivo cell-lineage analyses that Dlx5 fetal perichondrial cells marked by Dlx5-creER do not generate cartilage but sustainably contribute to cortical bone and marrow stromal compartments in a manner complementary to fetal chondrocyte derivatives under the regulation of Hedgehog signaling.

Left ventricular remodeling following aortic root and ascending aneurysm repair.

Objective: Adverse left ventricular remodeling due to a mismatch between stiffness of native aortic tissue and current polyester grafts may be under-recognized. This study was conducted to evaluate the impact of proximal aortic replacement on adverse remodeling of the left ventricle.

Materials And Methods: All aortic root and ascending aortic aneurysm patients were identified ( = 2,001, 2006-2019).

Codesigning simulations and analyzing the process to ascertain principles of authentic and meaningful research engagement in childhood disability research.

Background: Including youth with disabilities and their families as partners in childhood disability research is imperative but can be challenging to do in an authentic and meaningful way. Simulation allows individuals to learn in a controlled environment and provides an opportunity to try new approaches. The objectives of the research study were to (1) codesign a suite of simulations and facilitation resources and understand how stakeholders engaged in the codesign process; and (2) describe the principles of authentic and meaningful research engagement as identified by stakeholders.

Postoperative complications after gastrointestinal pediatric surgical procedures: outcomes and socio-demographic risk factors.

Background: Several socio-demographic characteristics are associated with complications following certain pediatric surgical procedures. In this comprehensive study, we sought to determine socio-demographic risk factors and resource utilization of children with complications after common pediatric surgical procedures.

Methods: We performed a population-based cohort study utilizing the 2016 Healthcare Cost and Use Project Kids' Inpatient Database (KID) to identify and characterize pediatric patients (age 0-21 years) in the United States with common inpatient pediatric gastrointestinal surgical procedures: appendectomy, cholecystectomy, colonic resection, pyloromyotomy and small bowel resection.

Outcomes of infectious syphilis in pregnant patients and maternal factors associated with congenital syphilis diagnosis, Alberta, 2017-2020.

Background: Congenital syphilis (CS) is a significant public health challenge, requiring early diagnosis and treatment to improve infant outcomes. The aim of this study is to describe public health outcomes of infectious syphilis cases among pregnant patients and factors associated with a CS diagnosis for their infant.

Methods: We conducted a retrospective review of demographic and clinical characteristics of infectious syphilis cases diagnosed during pregnancy and resulting infant outcomes in Alberta from 2017 to 2020 from the provincial communicable disease database.

Human papillomavirus (HPV) and cervical dysplasia in adult female cystic fibrosis (CF) lung transplant recipients.

Human papillomavirus (HPV) is the principal risk factor for cervical cancer. Transplant recipients are at a disproportionate risk of HPV complications. We conducted a single-centre, retrospective study of adult female cystic fibrosis (CF) lung transplant recipients between 2008 and 2021.

Single-Cell Transcriptomic Analysis Reveals Developmental Relationships and Specific Markers of Mouse Periodontium Cellular Subsets.

The periodontium is essential for supporting the functionality of the tooth, composed of diversity of mineralized and non-mineralized tissues such as the cementum, the periodontal ligament (PDL) and the alveolar bone. The periodontium is developmentally derived from the dental follicle (DF), a fibrous tissue surrounding the developing tooth bud. We previously showed through lineage-tracing experiments that DF contains mesenchymal progenitor cells expressing parathyroid hormone-related protein (PTHrP), which give rise to cells forming the periodontal attachment apparatus in a manner regulated by autocrine signaling through the PTH/PTHrP receptor.

Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that renders it largely refractory to immunotherapy. We implemented a multimodal analysis approach to elucidate the immune landscape in PDA. Using a combination of CyTOF, single-cell RNA sequencing, and multiplex immunohistochemistry on patient tumors, matched blood, and non-malignant samples, we uncovered a complex network of immune-suppressive cellular interactions.

Comparative Analysis of Molecular and Serologic Testing for Primary Syphilis: A Population-Based Cohort Study.

Rising rates of syphilis () requires rapid diagnosis and treatment to manage the growing epidemic. Syphilis serology is imperfect and requires interpretation of multiple tests while molecular diagnostics allows for potential yes-no identification of highly infective, primary anogenital lesions. Accuracy of this testing modality has thus far been limited to small, highly selective studies.

Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow.

Bone marrow houses a multifunctional stromal cell population expressing C-X-C motif chemokine ligand 12 (CXCL12), termed CXCL12-abundant reticular (CAR) cells, that regulates osteogenesis and adipogenesis. The quiescent pre-adipocyte-like subset of CXCL12 stromal cells ("Adipo-CAR" cells) is localized to sinusoidal surfaces and particularly enriched for hematopoiesis-supporting cytokines. However, detailed characteristics of these CXCL12 pre-adipocyte-like stromal cells and how they contribute to marrow adipogenesis remain largely unknown.

Clinical characteristics and outcomes for paediatric patients admitted with congenital or acquired syphilis: a population-based cohort study.

Objectives: Paediatric congenital and acquired syphilis cases have been increasing since 2012 in the USA. Potential differences in associated hospitalisation trends and healthcare utilisation between the two syphilis entities have not yet been assessed. We sought to compare these entities and describe their clinical characteristics, distribution and impact in the USA.

Epidemiology of cardiac implantable electronic device infections in the United States: A population-based cohort study.

Background: Trends in cardiac implantable electronic device (CIED) infections have been studied previously. However, coding for administrative data is more granular in contemporary data sets and indications for CIED implantation have expanded.

Objective: The purpose of this study was to provide an update on the rates of CIED infection and the influence of different variables including sex, length of stay (LOS), and costs in the United States.

Molecular Diagnosis of Vaginitis: Comparing Quantitative PCR and Microbiome Profiling Approaches to Current Microscopy Scoring.

Vaginitis is often diagnosed by microscopy and limited to testing for bacterial vaginosis (BV), vulvovaginal candidiasis, and trichomoniasis. Approximately 10% of vaginal swabs are negative but designated "altered flora" by BV Nugent score, leaving clinicians unsure how to treat patients. Accurate and comprehensive vaginitis diagnostics are needed to direct treatment and reduce risks of recurrent or more severe infections.

Effort-based decision-making impairment in patients with clinically-stabilized first-episode psychosis and its relationship with amotivation and psychosocial functioning.

Effort-based decision-making has recently been proposed as a potential mechanism contributing to motivational deficits (amotivation) in psychotic disorder. Previous research has identified altered effort allocation in chronic schizophrenia, but produced mixed results regarding its relationship with amotivation. No study has investigated effort allocation in first-episode psychosis (FEP).

Comparison of cognitive functions between first-episode schizophrenia patients, their unaffected siblings and individuals at clinical high-risk for psychosis.

Background: Cognitive impairment is a core feature of schizophrenia and has been observed in both familial (FHR) and clinical high-risk (CHR) samples. Nonetheless, there is a paucity of research directly contrasting cognitive profiles in these two high-risk states and first-episode schizophrenia. This study aimed to compare cognitive functions in patients with first-episode schizophrenia-spectrum disorder (FES), their unaffected siblings (FHR), CHR individuals and healthy controls.

Diagnostic challenges in pyogenic spinal infection: an expanded role for FDG-PET/CT.

In a preliminary investigation of FDG-PET/CT for assessment of therapy response of pyogenic spine infection, it was concluded that activity confined to the margins of a destroyed or degenerated joint with bone-on-bone contact represents nonseptic inflammation, regardless of the intensity of uptake. Only activity in bone, soft tissue, or within the epidural space represents active infection. The purpose of this investigation was to assess the performance of these pattern-based interpretation criteria in a series of problem cases of proven or suspected spine infection.

Patterns and predictors of trajectories for social and occupational functioning in patients presenting with first-episode non-affective psychosis: A three-year follow-up study.

Background: Functional impairment is prevalent in patients with first-episode psychosis (FEP). Longitudinal course of functioning in the early stage of psychotic illness is under-studied. In this report, we aimed to investigate the patterns and baseline predictors of social-occupational functional trajectories over 3 years, utilizing growth mixture modeling (GMM) analysis, in a large representative Chinese young FEP cohort in Hong Kong.