Optical Coherence Tomography Used as a Modality to Delineate Basal Cell Carcinoma prior to Mohs Micrographic Surgery

Optical coherence tomography (OCT) has potential as a modality for in vivo imaging of non-melanoma skin cancer (NMSC). By allowing identification of sub-surface margins of NMSC lesions, the use of OCT could improve the rate of complete excision and reduce the average number of stages during Mohs micrographic surgery (MMS). The objective of this study was to use OCT to delineate the apparent sub-surface margins of NMSC lesions prior to their excision by MMS. Lesions were scanned with reference to a physical marker on the skin, and the apparent margins were then identified from the OCT images and marked on the skin. Photographs of these margins and the Mohs defect were correlated and compared. OCT appears capable of visualizing the transition from lesional to normal tissue. In this case study, margins marked by use of the OCT system before surgery exhibit excellent correlation with the MMS defect. OCT offers the promise of better outcomes by enabling accurate margin mapping of NMSC in advance of MMS. Priorities now are to demonstrate this capability in a larger study, and to understand clearly indications and contraindications for use

CAUSEL: an epigenome- and genome-editing pipeline for establishing function of noncoding GWAS variants

The vast majority of disease-associated single nucleotide polymorphisms (SNPs) mapped by genome-wide association studies (GWAS) are located in the non-protein coding genome, but establishing the functional and mechanistic roles of these sequence variants has proven challenging. Here, we describe a general pipeline in which candidate functional SNPs are first evaluated by fine-mapping, epigenomic profiling, and epigenome editing and then interrogated for causal function by using genome editing to create isogenic cell lines. To validate this approach, we analyzed the 6q22.1 prostate cancer risk locus and identified rs339331 as the top scoring SNP. Epigenome editing confirmed that rs339331 possessed regulatory potential. Using transcription activator-like effector nuclease (TALEN)-mediated genome-editing, we created a panel of isogenic 22Rv1 prostate cancer cell lines representing all three genotypes (TT, TC, CC) at rs339331. Introduction of the “T” risk allele increased transcription of the RFX6 gene, increased HOXB13 binding at the rs339331 region, and increased deposition of the enhancer-associated H3K4me2 histone mark at the rs339331 region. The cell lines also differed in cellular morphology and adhesion, and pathway analysis of differentially expressed genes suggested an influence of androgens. In summary, we have developed and validated a widely accessible approach to establish functional causality for non-coding sequence variants identified by GWAS

Memory in Interaction: An Analysis of Repeat Calls to a Home Birth Helpline

Drawing on a corpus of 80 calls to a Home Birth helpline, we use conversation analysis to analyze how callers and call takers display to one another that they are talking for a second or subsequent time. We focus in particular on the role of memory in these interactions. We show how caller and call taker are oriented to remembering at the beginning of calls as displayed in what we call the recognition-solicit pre-sequence, how participants are oriented to issues of forgetting and remembering during the course of repeat calls, and how remembering and forgetting are made manifest in interaction. Our analysis shows how the human capacity to remember and propensity to forget have reverberating implications in calling for help

Actions in Practice: On details in collections

Several of the contributions to the Lynch et al. Special issue make the claim that conversation- analytic research into epistemics is ‘routinely crafted at the expense of actual, produced and constitutive detail, and what that detail may show us’. Here, we seek to address the inappositeness of this critique by tracing precisely how it is that recognizable actions emerge from distinct practices of interaction. We begin by reviewing some of the foundational tenets of conversation-analytic theory and method – including the relationship between position and composition, and the making of collections – as these appear to be primary sources of confusion for many of the contributors to the Lynch et al. Special Issue. We then target some of the specific arguments presented in the Special Issue, including the alleged ‘over-hearer’s’ writing of metrics, the provision of so- called ‘alternative’ analyses and the supposed ‘crafting’ of generalizations in epistemics research. In addition, in light of Lynch’s more general assertion that conversation analysis (CA) has recently been experiencing a ‘rapprochement’ with what he disparagingly refers to as the ‘juggernaut’ of linguistics, we discuss the specific expertise that linguists have to offer in analyzing particular sorts of interactional detail. The article as a whole thus illustrates that, rather than being produced ‘at the expense of actual, produced and constitutive detail’, conversation-analytic findings – including its work in epistemics – are unambiguously anchored in such detail. We conclude by offering our comments as to the link between CA and linguistics more generally, arguing that this relationship has long proven to be – and indeed continues to be – a mutually beneficial one

Vaccinia Virus Protein C6 Is a Virulence Factor that Binds TBK-1 Adaptor Proteins and Inhibits Activation of IRF3 and IRF7

Recognition of viruses by pattern recognition receptors (PRRs) causes interferon-β (IFN-β) induction, a key event in the anti-viral innate immune response, and also a target of viral immune evasion. Here the vaccinia virus (VACV) protein C6 is identified as an inhibitor of PRR-induced IFN-β expression by a functional screen of select VACV open reading frames expressed individually in mammalian cells. C6 is a member of a family of Bcl-2-like poxvirus proteins, many of which have been shown to inhibit innate immune signalling pathways. PRRs activate both NF-κB and IFN regulatory factors (IRFs) to activate the IFN-β promoter induction. Data presented here show that C6 inhibits IRF3 activation and translocation into the nucleus, but does not inhibit NF-κB activation. C6 inhibits IRF3 and IRF7 activation downstream of the kinases TANK binding kinase 1 (TBK1) and IκB kinase-ε (IKKε), which phosphorylate and activate these IRFs. However, C6 does not inhibit TBK1- and IKKε-independent IRF7 activation or the induction of promoters by constitutively active forms of IRF3 or IRF7, indicating that C6 acts at the level of the TBK1/IKKε complex. Consistent with this notion, C6 immunoprecipitated with the TBK1 complex scaffold proteins TANK, SINTBAD and NAP1. C6 is expressed early during infection and is present in both nucleus and cytoplasm. Mutant viruses in which the C6L gene is deleted, or mutated so that the C6 protein is not expressed, replicated normally in cell culture but were attenuated in two in vivo models of infection compared to wild type and revertant controls. Thus C6 contributes to VACV virulence and might do so via the inhibition of PRR-induced activation of IRF3 and IRF7

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Primary clear cell carcinoma of the vulva: A case report.

Clear cell carcinoma (CCC) of the vulva is extremely rare. We report a case of a 54-year-old woman who presented with a 5&nbsp;cm mass of the mons pubis. She underwent needle biopsy demonstrating CCC. She then underwent radical vulvectomy with bilateral inguinofemoral lymph node dissection. Surgical pathology revealed CCC of the vulva with lymphovascular space invasion (LVSI) and metastatic carcinoma in 1/7 inguinal lymph nodes. The patient has a history of endometriosis, raising suspicion that her CCC could have arisen from endometriosis in the mons. She completed adjuvant treatment with cisplatin and concurrent external beam radiation therapy with radiographic evidence of complete response. However, short-interval imaging demonstrated multi-focal recurrence, which was confirmed with supraclavicular lymph node biopsy. She then completed 8 cycles carboplatin, paclitaxel, and biosimilar bevacizumab-bvzr with favorable response on imaging. She was continued on bevacizumab maintenance. She was later started on pembroluzimab for disease progression based on new mediastinal adenopathy and worsening retroperitoneal lymphadenopathy. She received eight cycles of pembrolizumab with ongoing disease progression before enrolling in hospice and discontinuing cancer-directed treatment. As described in the related literature which we summarize here, the majority of reported cases of vulvar CCC arise from endometriosis implants at the site of prior episiotomy or from the Bartholins gland. This patient had clinical history of endometriosis; prior tissue sampling was not performed to support the diagnosis. Given the absence of data regarding this rare type of primary vulvar cancer, treatment of this patients disease was based on existing data specific to squamous cell carcinoma of the vulva and extrapolated from treatment guidelines for CCC of the ovary and endometrium. Continued research is needed on this rare form of vulvar carcinoma to determine the risk factors, prognostic factors, and treatment recommendations specific to this disease

Bienestar subjetivo, espiritualidad, aculturación y rasgos de personalidad: hacia una comprensión de los inmigrantes argentinos en Israel

There is a great migratory flow from Argentina to Israel, because there is one of the largest Jewish communities in the world today. Many judeo-argentines choose Israel as an alternative for settlement due to the political and economic instability that has rocked Argentina in recent decades. During the 2001 Argentine economic crisis, Israel saw the largest number of these Olim (Hebrew for “immigrants”) arrive in the country (Babis, 2016). A survey was recently administered among 220 Argentinians living in Israel, assessing many variables for a wide range of research inquiries. The present study is interested in the subjective well-being of immigrants related to their spirituality and the Big Five personality traits at the time of their migration, and its correlation with the acculturation trends of this sample population.Es posible apreciar un gran flujo migratorio de Argentina a Israel, porque hoy en día existe allí una de las comunidades judías más grandes del mundo. Muchos judeo-argentinos eligen Israel como alternativa de asentamiento debido a la inestabilidad política y económica que ha sacudido a Argentina en las últimas décadas. Durante la crisis económica argentina de 2001, Israel vio llegar al país el mayor número de estos "olim" (en hebreo para “inmigrantes”) (Babis, 2016). Para el presente estudio se administró una encuesta entre 220 argentinos que viven en Israel, evaluando distintas variables para una amplia gama de temas. El trabajo está interesado en explorar el bienestar subjetivo de los inmigrantes relacionado con su espiritualidad, los rasgos de personalidad de los Cinco Grandes en el momento de su migración, y su asociación con las tendencias de aculturación en dicha población

Perspectives of gynecologic oncology fellowship training and preparedness for practice.

We aimed to examine the preparedness of recent gynecologic oncology fellowship graduates for independent practice.We conducted a web-based survey study using REDCap targeting Society of Gynecologic Oncology (SGO) members who graduated gynecologic oncology fellowship within the last six years. The survey included 52 items assessing fellowship training experiences, level of comfort in performing core gynecologic oncology surgical procedures and administering cancer-directed therapies. Questions also addressed factors driving participants selection of fellowship programs, educational experience, research and preparedness for independent practice. A total of 296 participants were invited to complete the survey. Response rate was 42% with n&nbsp;=&nbsp;124 completed surveys included for analysis. The highest ranked factor for fellowship selection was fit with program 36% (n&nbsp;=&nbsp;45). Upon completing fellowship, most were uncomfortable performing ureteral conduit formation 84% (n&nbsp;=&nbsp;103), ureteroneocystostomy 77% (n&nbsp;=&nbsp;94), exenteration 68% (n&nbsp;=&nbsp;83), splenectomy 67% (n&nbsp;=&nbsp;83) and lower anterior resection 41% (n&nbsp;=&nbsp;51). Most were comfortable managing intraoperative complications 85% (n&nbsp;=&nbsp;104) and standard cancer staging procedures (range: 61%-99%). Majority were comfortable providing cancer directed therapies with chemotherapy 99% (n&nbsp;=&nbsp;123), immunotherapy 84% (n&nbsp;=&nbsp;104), and poly ADP-ribose polymerase (PARP) inhibitors 97% (n&nbsp;=&nbsp;120). Upon completing fellowship, 77% (n&nbsp;=&nbsp;95) report having mentorship that met their expectations during fellowship and 94% (n&nbsp;=&nbsp;116) felt they were ready for independent practice. Majority of fellowship graduates were prepared for independent practice and felt comfortable performing routine surgical procedures and cancer directed treatment. However, most are not comfortable with ultra-radical gynecologic oncology procedures. Maximizing surgical opportunities during fellowship training and acquiring early career mentorship may help

Post-transcriptional modifications in the small subunit ribosomal RNA from Thermotoga maritima, including presence of a novel modified cytidine

Post-transcriptional modifications of RNA are nearly ubiquitous in the principal RNAs involved in translation. However, in the case of rRNA the functional roles of modification are far less established than for tRNA, and are subject to less knowledge in terms of specific nucleoside identities and their sequence locations. Post-transcriptional modifications have been studied in the SSU rRNA from Thermotoga maritima (optimal growth 80°C), one of the most deeply branched organisms in the Eubacterial phylogenetic tree. A total of 10 different modified nucleosides were found, the greatest number reported for bacterial SSU rRNA, occupying a net of ∼14 sequence sites, compared with a similar number of sites recently reported for Thermus thermophilus and 11 for Escherichia coli. The relatively large number of modifications in Thermotoga offers modest support for the notion that thermophile rRNAs are more extensively modified than those from mesophiles. Seven of the Thermotoga modified sites are identical (location and identity) to those in E. coli. An unusual derivative of cytidine was found, designated N-330 (M (r) 330.117), and was sequenced to position 1404 in the decoding region of the rRNA. It was unexpectedly found to be identical to an earlier reported nucleoside of unknown structure at the same location in the SSU RNA of the archaeal mesophile Haloferax volcanii