Of essential workers and working from home: Journalistic discourses and the precarities of a pandemic economy.

This article considers how reporting about work during the COVID-19 pandemic operated as a field of discourse that challenged the ideological workings of neoliberalism. By documenting the risks and stresses workers of all classes faced during the first year of the pandemic, the reporting began to question neoliberal capitalism as socially unsustainable. Drawing on a corpus of 151 long-form articles and commentary, we show how journalistic discourse structured relationships between different classes of workers and implicated institutions for failing to properly mitigate the risks associated with COVID-19, even though the discourse largely centered on professionals working from home. As the reporting substantiated the precarities revealed by the pandemic as social facts, it challenged presumptions that undergird neoliberal ideologies, though it remains to be seen whether journalism will discursively re-center neoliberal logics in the wake of the pandemic.

Oral Healthcare Implications of Dedicated Online Communities: A Computational Content Analysis of the r/Dentistry Subreddit.

The current study explores communication expressed by participants in a subreddit surrounding oral health care, moderated by dentists and dental hygienists. The corpus was analyzed through Leximancer, a computer-assisted program used for computational content analyses of large data sets. Users' personal disclosures about ongoing dental concerns, advice about others' self-care, and the role of interpersonal communication with and among health care providers emerged as dominant themes. The findings suggest that online communities may serve an important role that dentists are unable to fill in their limited interactions with individual patients. Such interaction spaces may therefore offer a fertile environment for future interventions to promote beneficial practices and achieve positive health-related outcomes.

Transcription factor Oct1 protects against hematopoietic stress and promotes acute myeloid leukemia.

A better understanding of the development and progression of acute myelogenous leukemia (AML) is necessary to improve patient outcome. Here we define roles for the transcription factor Oct1/Pou2f1 in AML and normal hematopoiesis. Inappropriate reactivation of the CDX2 gene is widely observed in leukemia patients and in leukemia mouse models. We show that Oct1 associates with the CDX2 promoter in both normal and AML primary patient samples, but recruits the histone demethylase Jmjd1a/Kdm3a to remove the repressive H3K9me2 mark only in malignant specimens. The CpG DNA immediately adjacent to the Oct1 binding site within the CDX2 promoter exhibits variable DNA methylation in healthy control blood and bone marrow samples, but complete demethylation in AML samples. In MLL-AF9-driven mouse models, partial loss of Oct1 protects from myeloid leukemia. Complete Oct1 loss completely suppresses leukemia but results in lethality from bone marrow failure. Loss of Oct1 in normal hematopoietic transplants results in superficially normal long-term reconstitution; however, animals become acutely sensitive to 5-fluorouracil, indicating that Oct1 is dispensable for normal hematopoiesis but protects blood progenitor cells against external chemotoxic stress. These findings elucidate a novel and important role for Oct1 in AML.

BRCA1 through Its E3 Ligase Activity Regulates the Transcription Factor Oct1 and Carbohydrate Metabolism.

The tumor suppressor BRCA1 regulates the DNA damage response (DDR) and other processes that remain incompletely defined. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal E3 ligase activity. Here, it is demonstrated that BRCA1 promotes oxidative metabolism by degrading Oct1 (POU2F1), a transcription factor with proglycolytic and tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells toward a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype. RNA sequencing (RNAseq) confirms deregulation of metabolic genes downstream of Oct1. BRCA1 mediates Oct1 ubiquitylation and degradation, and mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1-mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not perturb growth in standard culture, but inhibits growth in soft agar and xenograft assays. In primary breast cancer clinical specimens, Oct1 protein levels correlate positively with tumor aggressiveness and inversely with BRCA1. These results identify BRCA1 as an Oct1 ubiquitin ligase that catalyzes Oct1 degradation to promote oxidative metabolism and restrict tumorigenicity. Mol Cancer Res; 16(3); 439-52. ©2018 AACR.

Transcription factor Oct1 is a somatic and cancer stem cell determinant.

Defining master transcription factors governing somatic and cancer stem cell identity is an important goal. Here we show that the Oct4 paralog Oct1, a transcription factor implicated in stress responses, metabolic control, and poised transcription states, regulates normal and pathologic stem cell function. Oct1(HI) cells in the colon and small intestine co-express known stem cell markers. In primary malignant tissue, high Oct1 protein but not mRNA levels strongly correlate with the frequency of CD24(LO)CD44(HI) cancer-initiating cells. Reducing Oct1 expression via RNAi reduces the proportion of ALDH(HI) and dye efflux(HI) cells, and increasing Oct1 increases the proportion of ALDH(HI) cells. Normal ALDH(HI) cells harbor elevated Oct1 protein but not mRNA levels. Functionally, we show that Oct1 promotes tumor engraftment frequency and promotes hematopoietic stem cell engraftment potential in competitive and serial transplants. In addition to previously described Oct1 transcriptional targets, we identify four Oct1 targets associated with the stem cell phenotype. Cumulatively, the data indicate that Oct1 regulates normal and cancer stem cell function.

Update on immunohistochemical methods relevant to dermatopathology.

CONTEXT: Dermatopathology covers a large variety of entities, some having very similar histologic appearances. Immunohistochemistry is an incredibly helpful tool that is useful in diagnosis as well as prognosis of selected skin tumors. OBJECTIVE: To provide a comprehensive review of recent trends and immunohistochemical stains used by dermatopathologists. Emphasis is placed on new stains as well as novel uses of existing stains. DATA SOURCES: All data were gathered from published journal articles available through the National Center for Biotechnology Information PubMed database. CONCLUSIONS: New immunohistochemical targets are continually being found, contributing to more accurate diagnosis and classification of skin tumors. The presence of specific markers can be used to determine the aggressiveness of malignancies and design treatment strategies. In addition, application of existing stains can help determine intravascular spread of malignancy in primary cutaneous lesions. And use of rapid immunohistochemical staining techniques on frozen sections can assist in more complete excision of tumor margins. Immunohistochemistry is a highly versatile and growing tool of dermatopathologists.

Cutaneous drug eruptions induced by sorafenib: a case series.

Sorafenib, an epidermal growth factor receptor inhibitor, is a novel treatment used for malignancies resistant to traditional chemotherapy. Epidermal growth factor receptors (EGFR) are a family of 4 transmembrane tyrosine kinase receptors that, via signal transduction pathways, mediate cell growth, differentiation, and survival. Sorafenib is a targeted drug specifically engineered to inhibit Raf serine/threonine kinases, which are part of the reticular activating system (RAS) oncogene pathway. In addition, in vitro studies have shown sorafenib to be a potent multikinase inhibitor, targeting receptor tyrosine kinases associated with tumor angiogenesis (VEGFR-2, VEGFR-3, and PDGFR-beta) and progression. Initially, approved for use in advanced renal cell carcinoma, sorafenib is being studied for the treatment of other solid tumors at our institution. During the clinical trial, 4 patients were referred to the dermatology clinic for evaluation and treatment of diffuse erythematous eruptions all occurring 8 to 10 days after initiating sorafenib at a dose of 400 mg twice daily. These eruptions occurred in demographically similar patients and displayed similar clinical characteristics and histopathological findings. Clinically, 3 of 4 patients had facial erythema, 3 of 4 had generalized macular erythema, 3 of 4 had widespread follicular-based papular eruption, and 4 of 4 had palmoplantar erythrodysesthesia. Half of the patients had cutaneous eruptions without systemic effects, while the other half had hypersensitivity reactions requiring withdrawal from clinical trial. This is the first case series illustrating drug eruptions induced by sorafenib.

Risk of nonmelanoma skin cancer with azathioprine use.

While often life-saving for many complex diseases, iatrogenic immunosuppression has been associated with life-threatening infections and malignancies. Among these malignancies is skin cancer. Skin cancer is the most common form of cancer in the United States; the nonmelanoma skin cancers have an annual incidence of greater than 1,000,000 people in the US. It is well documented that the risk of nonmelanoma skin cancer (NMSC) is increased in those who are immunosuppressed. While many articles have been published on skin cancer risk in organ transplant recipients, little has been written regarding the incidence of nonmelanoma skin cancer in inflammatory bowel disease. A review of the literature of patients who are immunosuppressed for autoimmune disorders, and specifically, inflammatory bowel diseases, is discussed, as well as clinical presentations and treatment options.

Control of mitotic exit by PP2A regulation of Cdc25C and Cdk1.

Inactivation of maturation-promoting factor [(MPF) Cdk1/Cyclin B] is a key event in the exit from mitosis. Although degradation of Cyclin B is important for MPF inactivation, recent studies indicate that Cdk1 phosphorylation and inactivation occur before Cyclin B degradation and, therefore, also may be important steps in the exit from mitosis. Cdk1 activity is controlled by the Cdc25C phosphatase, which is turned on at the G(2)/M transition to catalyze Cdk1 activation. PP2A:B56delta is a negative regulator of Cdc25C during interphase. We show here that PP2A:B56delta also regulates Cdc25C at mitosis. Failure of PP2A:B56delta to dephosphorylate Cdc25C at mitosis results in prolonged hyperphosphorylation and activation of Cdc25C, causing persistent dephosphorylation and, hence, activation of Cdk1. This constitutive activation of Cdc25C and Cdk1 leads to a delayed exit from mitosis. Consistent with Cdk1 as a major biological target of B56delta, stable knockdown and germ-line mouse KO of B56delta leads to compensatory transcriptional up-regulation of Wee1 kinase to oppose the Cdc25C activity and permit cell survival. These observations place PP2A:B56delta as a key upstream regulator of Cdk1 activity upon exit from mitosis.

Cutaneous Rosai-Dorfman disease: comprehensive review of cases reported in the medical literature since 1990 and presentation of an illustrative case.

BACKGROUND: The latest comprehensive review of primary cutaneous Rosai-Dorfman disease was published as part of an exhaustive survey of sinus histiocytosis with massive lymphadenopathy in 1990. Since then, much progress has been made in the understanding of malignant lymphoma and benign disorders of lymphoid and histiocytic origin. OBJECTIVE: We reviewed cases of primary cutaneous Rosai-Dorfman disease published since 1990 and discuss their clinical and pathologic features, comparing them with cases of systemic Rosai-Dorfman disease. METHODS: We conducted a search of the National Library of Medicine PubMed database for cases of cutaneous Rosai-Dorfman disease reported in the English-language medical literature since February 1990. RESULTS: We identified 72 patients with cutaneous Rosai-Dorfman (female to male ratio 1:0.5). The gross appearance and number or distribution of lesions were highly variable. Abnormal laboratory data included peripheral blood cytopenias (10 patients) and increased gammaglobulin fraction (10 patients). The response to treatment was variable. CONCLUSION: Purely cutaneous disease without the characteristic lymphadenopathy is rare but has been increasingly reported in the literature. Compared with patients with systemic Rosai-Dorfman disease, patients with primary cutaneous Rosai-Dorfman disease are older, women are more commonly affected, and whites are more likely than blacks to be afflicted.