Alkene Thianthrenation Unlocks Diverse Cation Synthons: Recent Progress and New Opportunities.

Oxidative alkene functionalization reactions are a fundamental class of complexity-building organic transformations. However, the majority of established approaches rely on electrophilic reagents that limit the diversity of groups that can be installed. Recent advances have established a new approach that instead relies on the transformation of alkenes into thianthrene-derived cationic electrophiles.

PRMT1 Inhibition Selectively Targets BNC1-Dependent Proliferation, but not Migration in Squamous Cell Carcinoma.

Squamous Cell Carcinoma (SCC) develops in stratified epithelial tissues and demonstrates frequent alterations in transcriptional regulators. We sought to discover SCC-specific transcriptional programs and identified the transcription factor Basonuclin 1 (BNC1) as highly expressed in SCC compared to other tumor types. RNA-seq and ChIP-seq analysis identified pro-proliferative genes activated by BNC1 in SCC cells and keratinocytes.

Diastereoselective Synthesis of Cyclopropanes from Carbon Pronucleophiles and Alkenes.

Cyclopropanes are desirable structural motifs with valuable applications in drug discovery and beyond. Established alkene cyclopropanation methods give rise to cyclopropanes with a limited array of substituents, are difficult to scale, or both. Herein, we disclose a new cyclopropane synthesis through the formal coupling of abundant carbon pronucleophiles and unactivated alkenes.

Increasing coordination and responsivity of emotion-related brain regions with a heart rate variability biofeedback randomized trial.

Heart rate variability is a robust biomarker of emotional well-being, consistent with the shared brain networks regulating emotion regulation and heart rate. While high heart rate oscillatory activity clearly indicates healthy regulatory brain systems, can increasing this oscillatory activity also enhance brain function? To test this possibility, we randomly assigned 106 young adult participants to one of two 5-week interventions involving daily biofeedback that either increased heart rate oscillations (Osc+ condition) or had little effect on heart rate oscillations (Osc- condition) and examined effects on brain activity during rest and during regulating emotion. While there were no significant changes in the right amygdala-medial prefrontal cortex (MPFC) functional connectivity (our primary outcome), the Osc+ intervention increased left amygdala-MPFC functional connectivity and functional connectivity in emotion-related resting-state networks during rest.

Associations between locus coeruleus MRI contrast and physiological responses to acute stress in younger and older adults.

Acute stress activates the brain's locus coeruleus (LC)-noradrenaline system. Recent studies indicate that a magnetic resonance imaging (MRI)-based measure of LC structure is associated with better cognitive outcomes in later life. Yet despite the LC's documented role in promoting physiological arousal during acute stress, no studies have examined whether MRI-assessed LC structure is related to arousal responses to acute stress.

Momentary social interactions and affect in later life varied across the early stages of the COVID-19 pandemic.

The COVID-19 pandemic has impacted many different facets of life. The infectious nature of the disease has led to significant changes in social interactions in everyday life. The present study examined how older adults' patterns of everyday momentary social interactions (i.

Evaluating the Efficacy of Two Regional Pain Management Modalities in Autologous Breast Reconstruction.

Unlabelled: At our institution, multimodal opiate-sparing pain management is the cornerstone of our enhanced recovery program for autologous breast reconstruction. The purpose of this study was to compare postoperative outcomes and pain control metrics following implementation of an enhanced recovery program with two different regional analgesia approaches.

Methods: This retrospective cohort study identified 145 women who underwent autologous breast reconstruction from 2015 to 2017.

Stress Measurement in Primary Care: Conceptual Issues, Barriers, Resources, and Recommendations for Study.

Objective: Exposure to stressors in daily life and dysregulated stress responses are associated with increased risk for a variety of chronic mental and physical health problems, including anxiety disorders, depression, asthma, heart disease, certain cancers, and autoimmune and neurodegenerative disorders. Despite this fact, stress exposure and responses are rarely assessed in the primary care setting and infrequently targeted for disease prevention or treatment.

Method: In this narrative review, we describe the primary reasons for this striking disjoint between the centrality of stress for promoting disease and how rarely it is assessed by summarizing the main conceptual, measurement, practical, and reimbursement issues that have made stress difficult to routinely measure in primary care.

Electrochemical Synthesis of Allylic Amines from Terminal Alkenes and Secondary Amines.

Allylic amines are valuable synthetic targets en route to diverse biologically active amine products. Current allylic C-H amination strategies remain limited with respect to the viable -substituents. Herein, we disclose a new electrochemical process to prepare aliphatic allylic amines by coupling two abundant starting materials: secondary amines and unactivated alkenes.

Regulation of 5-Hydroxymethylcytosine by TET2 Contributes to Squamous Cell Carcinoma Tumorigenesis.

DNA methylation is a key regulatory event controlling a variety of physiological processes and can have dramatic effects on gene transcription. Methylated cytosine (5-methylcytosine) can be oxidized by the TET family of enzymes to 5-hydroxymethylcytosine (5-hmC), a key intermediate in the demethylation cycle, and 5-hmC levels are reduced in malignancies such as acute myeloid leukemia and melanoma. We constructed a tissue microarray of human cutaneous squamous cell carcinoma tumors and found a global reduction in 5-hmC levels compared with that in the adjacent skin.

Aziridine synthesis by coupling amines and alkenes via an electrogenerated dication.

Aziridines-three-membered nitrogen-containing cyclic molecules-are important synthetic targets. Their substantial ring strain and resultant proclivity towards ring-opening reactions makes them versatile precursors of diverse amine products, and, in some cases, the aziridine functional group itself imbues important biological (for example, anti-tumour) activity. Transformation of ubiquitous alkenes into aziridines is an attractive synthetic strategy, but is typically accomplished using electrophilic nitrogen sources rather than widely available amine nucleophiles.

Oral myeloid sarcoma as an uncommon manifestation of acute myeloid leukemia: A case series and review of the literature.

Background And Overview: Oral myeloid sarcoma (MS) is an extramedullary tumor that can occur in the setting of acute myeloid leukemia, either as the first sign of an underlying disease or later in the course of disease. The authors' aim was to present the clinical features of oral MS and review the literature.

Case Description: Case 1 was an 82-year-old woman with an asymptomatic erythematous swelling on the maxillary gingiva and no history of hematologic malignancy.

Histopathologic Spectrum of Intraoral Irritant and Contact Hypersensitivity Reactions: A Series of 12 cases.

Background: Irritant contact stomatitis (ICS) and contact hypersensitivity stomatitis (CHS) are often caused by alcohol, flavoring agents and additives in dentifrices and foods, and contactants with high or low pH. A well-recognized contactant for ICS is Listerine™ mouthwash, while that for CHS is cinnamic aldehyde. However, many other flavoring agents and even smokeless tobacco are contactants that cause mucosal lesions that are entirely reversible.

ATF-3 expression inhibits melanoma growth by downregulating ERK and AKT pathways.

Activating transcription factor 3 (ATF-3), a cyclic AMP-dependent transcription factor, has been shown to play a regulatory role in melanoma, although its function during tumor progression remains unclear. Here, we demonstrate that ATF-3 exhibits tumor suppressive function in melanoma. Specifically, ATF-3 nuclear expression was significantly diminished with melanoma progression from nevi to primary to metastatic patient melanomas, correlating low expression with poor prognosis.

Age patterns in subjective well-being are partially accounted for by psychological and social factors associated with aging.

Subjective well-being has captured the interest of scientists and policy-makers as a way of knowing how individuals and groups evaluate and experience their lives: that is, their sense of meaning, their satisfaction with life, and their everyday moods. One of the more striking findings in this literature is a strong association between age and subjective well-being: in Western countries it has a U-shaped association over the lifespan. Despite many efforts, the reason for the curve is largely unexplained, for example, by traditional demographic variables.

Replacing 30 Gy in 10 fractions with stereotactic body radiation therapy for bone metastases: A large multi-site single institution experience 2016-2018.

Background: Bone metastases cause significant morbidity in patients with cancer, and radiation therapy (RT) is an effective treatment approach. Indications for more complex ablative techniques are emerging. We sought to evaluate RT trends at a large multi-site tertiary cancer center.

Resting-State Connectivity of Auditory and Reward Systems in Alzheimer's Disease and Mild Cognitive Impairment.

Music-based interventions (MBI) have become increasingly widely adopted for dementia and related disorders. Previous research shows that music engages reward-related regions through functional connectivity with the auditory system, but evidence for the effectiveness of MBI is mixed in older adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD). This underscores the need for a unified mechanistic understanding to motivate MBIs.

Dermatologic adverse events related to the PI3Kα inhibitor alpelisib (BYL719) in patients with breast cancer.

Purpose: Rash develops in approximately 50% of patients receiving alpelisib for breast cancer, often requiring dose modifications. Here, we describe the clinicopathologic, laboratory, and management characteristics of alpelisib-related dermatologic adverse events (dAEs).

Methods: A single center-retrospective analysis was conducted.

Heightened Stress in Employed Individuals Is Linked to Altered Variability and Inertia in Emotions.

Stress has been widely recognized as a key factor contributing to health outcomes and psychological well-being. While some growing evidence points to stress as having an effect on emotion dynamics characteristics, there has yet to be a test of how global perceptions of stress are associated with not only average levels of emotions but also the variability in the intensity of the emotions, as well as how emotions linger (inertia), and whether these characteristics differ by age. In an effort to better understand how stress influences the emotional experiences of individuals, we examined associations between perceived stress levels and emotion dynamics indices in a sample of 859 working individuals over 24 h.

Childhood Physical Neglect Is Associated With Exaggerated Systemic and Intracellular Inflammatory Responses to Repeated Psychosocial Stress in Adulthood.

Experiences of child maltreatment are associated with a host of adverse mental and physical health outcomes in adulthood. Altered reactivity to psychosocial stress exposure may partially explain known associations between early experiences of maltreatment and later life health. The present study focuses on examining whether experiences of child maltreatment are associated with physiological reactions to initial and repeated psychosocial stress in adulthood.

Targeting the PI5P4K Lipid Kinase Family in Cancer Using Covalent Inhibitors.

The PI5P4Ks have been demonstrated to be important for cancer cell proliferation and other diseases. However, the therapeutic potential of targeting these kinases is understudied due to a lack of potent, specific small molecules available. Here, we present the discovery and characterization of a pan-PI5P4K inhibitor, THZ-P1-2, that covalently targets cysteines on a disordered loop in PI5P4Kα/β/γ.

Successful use of fondaparinux in the setting of heparin-induced thrombocytopenia with thrombosis confirmed by serotonin-release assay and Factor V Leiden.

What Is Known And Objective: The off-label use of fondaparinux in patients with heparin-induced thrombocytopenia with thrombosis (HITT) has historically been controversial. We present a case of successful fondaparinux use to treat HITT confirmed by the serotonin-release assay in the setting of other significant clotting and bleeding risk factors.

Case Summary: We report a 19-year-old male with a history of Factor V Leiden and recent neurosurgery treated with fondaparinux after developing HITT confirmed by the serotonin-release assay (SRA).

The Coin in Hand-Extended Version: Development and Validation of a Multicultural Performance Validity Test.

The number of computerized and reliable performance validity tests are scarce. This study aims to address this issue by validating a free and computerized performance validity test: the Coin in Hand-Extended Version (CIH-EV). The CIH-EV test was administered in four countries (Colombia, Spain, Portugal, and the United States) and performance was compared with other commonly used validated tests.