Lymphovascular Invasion in Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Although there is a large body of literature regarding risk stratification and outcomes for perineural invasion (PNI) in cutaneous squamous cell carcinoma (cSCC), there is a relative paucity of studies exploring the role of lymphovascular invasion (LVI) in cSCC and a lack of clear evidence-based guidelines for how to manage patients with these tumors. OBJECTIVE: This article is intended to review the available literature regarding LVI in cSCC and formulate evidence-based recommendations for clinical management. METHODS AND MATERIALS: A literature review was conducted using PubMed to find relevant articles relating to outcomes and management of primary cSCC with LVI. RESULTS: The available literature suggests that LVI is a major risk factor for poor outcomes and increased morbidity and mortality in cSCC. CONCLUSION: Lymphovascular invasion is a very high-risk feature that should place these tumors in the highest-risk category, and management of these tumors should be similar to that of squamous cell carcinoma with PNI.

Nationwide Case-Control Analysis of Merkel Cell Carcinoma and Associated Skin Cancer Comorbidities: An Examination of the All of Us Database.

Introduction Merkel cell carcinoma is an aggressive neuroendocrine tumor that is related to immunosuppression and the Merkel cell polyomavirus. It is more common on the head and neck and has been associated with other skin malignancies such as basal cell carcinoma, squamous cell carcinoma, and melanoma. However, there has never been a nationwide investigation that quantifies Merkel cell carcinoma's connection with these subgroups. Methods Utilizing the National Institutes of Health's All of Us open-access database, a retrospective study was conducted by filtering for Merkel cell carcinoma through the International Classification of Diseases, 9th and 10th Clinical Modification codes 209.* and C4A.*, respectively. This led to the inclusion of 41 patients in the study, with each instance compared to four control patients without merkel cell carcinoma, matched by age, race, and gender. The data's demographics and skin cancer co-morbidities were collected and evaluated with odds ratios and 95% confidence intervals using Wald's method. Results In patients with merkel cell carcinoma, a statistically significant gradient of increasing risk for developing basal cell carcinoma (Odds Ratio, 11.63; 95% Confidence Interval, 4.30-31.45; P < 0.0001), squamous cell carcinoma (Odds Ratio, 15.09; 95% Confidence Interval, 3.87-58.84; P = 0.0001), and melanoma (Odds Ratio, 27.94; 95% Confidence Interval, 3.26-239.48; P = 0.0024) was observed. The race/ethnicity demographics showed that 85.4% of the patients were white, and they were at the highest risk of developing merkel cell carcinoma. However, the study has limitations, such as the inability to identify the stage of merkel cell carcinoma among patients and the lack of consideration for other confounding variables. Conclusion The study examines the link between merkel cell carcinoma and other skin malignancies, underscoring the need for more national research to better understand the underlying causes that contribute to this link. The findings also indicate the possibility of sample bias in the All of Us database, emphasizing the need to assess the patient population's representativeness in such investigations.

Impact of COVID-19-related experiences on health-related quality of life in cancer survivors in the United States.

OBJECTIVE: Little evidence exists on the impact of the COVID-19 pandemic on cancer survivors, limiting recommendations to improve health-related quality of life (HRQoL) in this population. We describe survivors' pandemic experiences and examine associations between COVID-19-related exposures, psychosocial experiences, and HRQoL. METHODS: Between May 2020-April 2021, survivors completed cross-sectional questionnaires capturing COVID-19-related exposures (e.g., exposure to virus, job loss); psychosocial experiences (i.e., COVID-19-related anxiety/depression, disruptions to health care and daily activities/social interactions, satisfaction with providers' response to COVID, financial hardship, perceived benefits of the pandemic, social support, and perceived stress management ability); and HRQoL. RESULTS: Data were collected from N = 11,325 survivors in the United States. Participants were mostly female (58%), White (89%) and non-Hispanic (88%), and age 63 on average. Breast cancer was the most common diagnosis (23%). Eight percent of participants reported being exposed to COVID-19; 1% tested positive. About 6% of participants lost their jobs, while 24% lost household income. Nearly 30% avoided attending in-person oncology appointments because of the pandemic. Poorer HRQoL was associated with demographic (younger age; female; non-Hispanic White), clinical (Medicare; stage IV disease; hematologic/digestive/respiratory system cancer), and psychosocial factors (low perceived benefits and stress management ability; more disruption to health care and daily activities/social interactions; financial hardship). CONCLUSIONS: COVID-19-related stressors were associated with various psychosocial experiences in cancer survivors, and these psychosocial experiences were associated with HRQoL above and beyond demographic and clinical factors.

Effects of the Brief Simha Kriya Breathing Practice for Health Care Workers During the COVID-19 Pandemic.

Introduction: During the COVID-19 pandemic, health care workers (HCWs) experienced increased anxiety, depression, loneliness, and other mental health issues. HCWs need additional resources to cope with the mental health impact of their work. Yoga techniques could be helpful strategies to manage different stressors during times of uncertainty. Methods: This prospective, single-arm, trial examined the effects of a brief pranayama yoga practice on the wellbeing of HCWs during the height of COVID-19. HCWs were recruited through announcements and institutional websites at a large major cancer center in the southern United States. A short, prerecorded, 5-min breathwork video intervention called "Simha Kriya" was provided to participants, and they were encouraged to practice one to two times daily for 4 weeks. Participants completed self-report instruments at baseline and weeks 1 and 4, including: (1) Perceived Stress Scale (PSS); (2) Brief Resilient Coping Scale (BRCS); and (3) a questionnaire assessing the experience of COVID-19 among HCWs that had five subscales. HCWs also conducted a measure of breath holding time. Paired sample t-tests and mixed-effects analysis of variance models examined changes over time. Results: One hundred participants consented to the study, with 88 female, 60 white, 39 worked remotely, and 27 were clinical staff. Sixty-nine participants provided data at week 1 and 56 at week 4. Participants' adherence to the breathing exercises between weeks 1 and 4 was similar, with a mean of six times per week. At week 4, there were significant decreases in the COVID-19 Distress score (p < 0.0001) and COVID-19 Disruption (p = 0.013), yet no changes in the PSS. There were also significant increases in COVID-19 Stress Management (p = 0.0001) and BRCS scores (p = 0.012), but no changes in Perceived Benefits of COVID-19 and no changes in breath holding time. Discussion: Brief yoga-based breathing practices helped reduce pandemic-specific stress, improved resilience, and stress management skills in HCWs. Trial Registration Number: NCT04482647.

Revisiting the definition of dyslexia.

The International Dyslexia Association definition of dyslexia was updated 20 years ago and has been referenced frequently in research and practice. In this paper, researchers from the Florida Center for Reading Research consider the components of the definition and make recommendations for revisions. These include recognizing the persistence of word-reading, decoding, and spelling difficulties, acknowledging the multifactorial causal basis of dyslexia, clarifying exclusionary factors, and denoting comorbidity with other developmental disorders. It is also suggested that the academic and psychosocial consequences of dyslexia be highlighted to reinforce a preventive service delivery model. Lastly, the inclusion of dyslexia within a specific learning disability category is supported.

Integrative Oncology Approaches to Reduce Recurrence of Disease and Improve Survival.

PURPOSE OF REVIEW: After a cancer diagnosis, patients ask what they can do in addition to the recommended treatments to increase their survival. Many turn to integrative medicine modalities and lifestyle changes to improve their chances of survival. Numerous studies have demonstrated that lifestyle changes can significantly improve survival rates for cancer patients. Less support exists for the use of natural products or supplements to improve cancer survival. In this manuscript, we review key findings and evidence in the areas of healthy eating habits, physical activity, stress management and social support, and sleep quality, as well as natural products and supplements as they relate to the cancer recurrence and survival. RECENT FINDINGS: While more research is needed to fully understand the mechanisms underlying the associations between lifestyle changes and cancer survival, findings suggest that lifestyle modifications in the areas of diet, physical activity, stress management and social support, and sleep quality improve clinical cancer outcomes. This is especially true for programs that modify more than one lifestyle habit. To date, outside of supplementing with vitamin D to maintain adequate levels, conflicting conclusion within the research remain regarding the efficacy of using natural products or supplement to improve cancer recurrence of disease or cancer survival. A call for further research is warranted. Lifestyle screening and counseling should be incorporated into cancer treatment plans to help improve patient outcomes. While the scientific community strives for the pursuit of high-quality research on natural products to enhance cancer survival, transparency, dialogue, and psychological safety between patients and clinicians must continue to be emphasized. Proactive inquiry by clinicians regarding patients' supplement use will allow for an informed discussion of the benefits and risks of natural products and supplements, as well as a re-emphasis of the evidence supporting diet and other lifestyle habits to increase survival.

Words matter: The use of generic "you" in expressive writing in an oncology setting.

The use of generic "you" (GY) in writing samples fosters psychological distancing and functions as a linguistic mechanism to facilitate emotion regulation. This method of creating psychological distance from the traumatic experience of cancer may be used by patients processing emotions. We used behavioral coding to analyze expressive writing samples collected from 138 cancer patients to examine the association between the use of "you" and cancer-related symptoms and psychological outcomes. Occurrences of GY were low, but our qualitative results showed how the use of GY could create a universal experience of cancer. The use of GY was not associated with cancer-related symptoms and depressive symptoms, but longitudinal analyses revealed that those using GY had fewer intrusive thoughts and avoidance behaviors across the follow-up period of 1, 4, and 10 months after the intervention. The development of psychological self-distancing prompts to use in writing interventions or as a clinical tool for cancer patients should be explored.

Use of facial hair in classic movie heroes / Uso del vello facial en héroes del cine clásico

The film industry uses dermatological findings to help viewers differentiate between heroes and villains. This study sought to determine whether there is a significant association between the presence of facial hair and character type.Top 10 male heroes and villains were analyzed from the American Film Institute’s 100 Greatest Heroes and Villains list for the presence of facial hair. A total of 20 characters were analyzed from 19 films. Facial hair was defined as hair present on the face that could easily and clearly be identified as a beard, goatee, or mustache.All 10 villains analyzed in this study had no facial hair compared to 5 heroes with this feature (100 % vs. 50 % respectively). The type of facial hair noted on heroes was a combination of beard and mustache. Fisher’s Exact test revealed a significant association between the presence of facial hair and character type (p=0.0325).Based on this analysis, there appears to be a tendency to help viewers distinguish heroes from villains by using mutable features. The use of facial hair to identify heroes is notable because while not a dermatological disorder, previous research has revealed higher use of dermatological findings in antagonists compared to protagonists. (AU)

La industria cinematográfica utiliza hallazgos dermatológicos para ayudar a los espectadores a diferenciar entre héroes y villanos. Este estudio buscó determinar si existe una asociación significativa entre la presencia de vello facial y el tipo de carácter. Se analizaron los 10 mejores héroes y villanos masculinos de la lista de los 100 mejores héroes y villanos del American Film Institute para detectar la presencia de vello facial. Se analizaron un total de 20 personajes de 19 películas. El vello facial se definió como el cabello presente en la cara que podía identificarse fácil y claramente como barba, perilla o bigote. Los 10 villanos analizados en este estudio no tenían vello facial en comparación con 5 héroes con esta característica (100 % frente a 50 % respectivamente). El tipo de vello facial observado en los héroes era una combinación de barba y bigote. La prueba Exacta de Fisher reveló una asociación significativa entre la presencia de vello facial y el tipo de carácter (p=0,0325).Según este análisis, parece haber una tendencia a ayudar a los espectadores a distinguir héroes de villanos mediante el uso de características mutables. El uso del vello facial para identificar héroes es notable porque, si bien no es un trastorno dermatológico, investigaciones anteriores han revelado un mayor uso de hallazgos dermatológicos en los antagonistas en comparación con los protagonistas. (AU)

PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects.

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical phenotypes. The missense variants in individuals with CDH are located within the actin-binding domains of the protein but are not predicted to affect protein structure, whereas the variants in individuals with osteoporosis are predicted to result in loss of function. A mouse knockin model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Both the mouse model and one adult human male with a CDH-associated PLS3 variant were observed to have increased rather than decreased bone mineral density. Together, these clinical and functional data in humans and mice reveal that specific missense variants affecting the actin-binding domains of PLS3 might have a gain-of-function effect and cause a Mendelian congenital disorder.

Validation of a Simulation-Based Resuscitation Curriculum for Maternal Cardiac Arrest.

OBJECTIVE: To assess the knowledge, skills, and self-efficacy of health care participants completing a simulation-based blended learning training curriculum on managing maternal medical emergencies and maternal cardiac arrest (Obstetric Life Support). METHODS: A formative assessment of the Obstetric Life Support curriculum was performed with a prehospital cohort comprising emergency medical services professionals and a hospital-based cohort comprising health care professionals who work primarily in hospital or urgent care settings and respond to maternal medical emergencies. The training consisted of self-guided precourse work and an instructor-led simulation course using a customized low-fidelity simulator. Baseline and postcourse assessments included multiple-choice cognitive test, self-efficacy questionnaire, and graded Megacode assessment of the team leader. Megacode scores and pass rates were analyzed descriptively. Pre- and post-self-confidence assessments were compared with an exact binomial test, and cognitive scores were compared with generalized linear mixed models. RESULTS: The training was offered to 88 participants between December 2019 and November 2021. Eighty-five participants consented to participation; 77 participants completed the training over eight sessions. At baseline, fewer than half of participants were able to achieve a passing score on the cognitive assessment as determined by the expert panel. After the course, mean cognitive assessment scores improved by 13 points, from 69.4% at baseline to 82.4% after the course (95% CI 10.9-15.1, P <.001). Megacode scores averaged 90.7±6.4%. The Megacode pass rate was 96.1%. There were significant improvements in participant self-efficacy, and the majority of participants (92.6%) agreed or strongly agreed that the course met its educational objectives. CONCLUSION: After completing a simulation-based blended learning program focused on managing maternal cardiac arrest using a customized low-fidelity simulator, most participants achieved a defensible passing Megacode score and significantly improved their knowledge, skills, and self-efficacy.

Overactivated Epithelial NF-κB Disrupts Lung Development in Congenital Diaphragmatic Hernia.

Abnormal lung development is the main cause of morbidity and mortality in neonates with congenital diaphragmatic hernia (CDH), a common birth defect (1:2,500) of largely unknown pathobiology. Recent studies discovered that inflammatory processes, and specifically NF-κB-associated pathways, are enriched in human and experimental CDH. However, the molecular signaling of NF-κB in abnormal CDH lung development and its potential as a therapeutic target require further investigation. Using sections and hypoplastic lung explant cultures from the nitrofen rat model of CDH and human fetal CDH lungs, we demonstrate that NF-κB and its downstream transcriptional targets are hyperactive during abnormal lung formation in CDH. NF-κB activity was especially elevated in the airway epithelium of nitrofen and human CDH lungs at different developmental stages. Fetal rat lung explants had impaired pseudoglandular airway branching after exposure to nitrofen, together with increased phosphorylation and transcriptional activity of NF-κB. Dexamethasone, the broad and clinically applicable antiinflammatory NF-κB antagonist, rescued lung branching and normalized NF-κB signaling in hypoplastic lung explants. Moreover, specific NF-κB inhibition with curcumenol similarly rescued ex vivo lung hypoplasia and restored NF-κB signaling. Last, we showed that prenatal intraperitoneal dexamethasone administration to pregnant rat dams carrying fetuses with hypoplastic lungs significantly improves lung branching and normalizes NF-κB in vivo. Our results indicate that NF-κB is aberrantly activated in human and nitrofen CDH lungs. Antiinflammatory treatment with dexamethasone and/or specific NF-κB inhibition should be investigated further as a therapeutic avenue to target lung hypoplasia in CDH.

Early Identification of Children with Dyslexia: Variables Differentially Predict Poor Reading Versus Unexpected Poor Reading.

Definitions of dyslexia typically make reference to unexpected poor reading, although how best to operationalize unexpected remains an issue. When operationally defined as reading below expectations based on level of oral language, cases of unexpected poor reading make up fewer than half of cases of poor reading, and cases of unexpected poor reading occur throughout the range of reading proficiency. An implication is that what optimally predicts poor reading may not optimally predict unexpected poor reading. The goal of the three presented studies was to test this implication empirically. In Study 1, a model-based meta-analysis, phonological awareness accounted for 40% of the variance in decoding but only 1% of the variance in decoding that was unexpected based on level of vocabulary. Conversely, unexpected phonological awareness accounted for 34% of the variance in unexpected decoding but only 1% of the variance in decoding. An analogous pattern of results occurred for reading comprehension. In Study 2, a study of 766 children in kindergarten, first grade, and second grade, latent variables were used to represent oral vocabulary, phonological awareness, and decoding. As was seen in Study 1, unexpected decoding was better predicted by unexpected phonological awareness than by phonological awareness. In Study 3, a longitudinal study of 1,025 children followed from preschool through grade 2, the pattern of results mirrored those of Studies 1 and 2. An important implication of these studies is that typical assessments may be better at identifying poor reading than they are at identifying unexpected poor reading or dyslexia.

Development and initial psychometric evaluation of a COVID-related psychosocial experiences questionnaire for cancer survivors.

BACKGROUND: Cancer survivors are at elevated risk of psychological problems related to COVID-19, yet no published measure adequately assesses their psychosocial experiences during the pandemic. PURPOSE: Describe the development and factor structure of a comprehensive, self-report measure (COVID-19 Practical and Psychosocial Experiences questionnaire [COVID-PPE]) assessing the pandemic's impact on US cancer survivors. METHODS: The sample (n = 10,584) was divided into three groups to assess COVID-PPE factor structure by conducting: (1) initial calibration/exploratory analysis of the factor structure of 37 items (n = 5070), (2) confirmatory factor analysis of the best-fitting model (36 items after item removal; n = 5140), and (3) post-hoc confirmatory analysis with an additional six items not collected in the first two groups (42 items; n = 374). RESULTS: The final COVID-PPE was divided into two sets of subscales, conceptualized as Risk Factors and Protective Factors. The five Risk Factors subscales were labeled Anxiety Symptoms, Depression Symptoms, Health Care Disruptions, Disruptions to Daily Activities and Social Interactions, and Financial Hardship. The four Protective Factors subscales were labeled Perceived Benefits, Provider Satisfaction, Perceived Stress Management Skills, and Social Support. Internal consistency was acceptable for seven subscales (αs = 0.726-0.895; ωs = 0.802-0.895) but poor or questionable for the remaining two subscales (αs = 0.599-0.681; ωs = 0.586-0.692). CONCLUSIONS: To our knowledge, this is the first published self-report measure comprehensively capturing psychosocial impact-both positive and negative-of the pandemic on cancer survivors. Future work should evaluate predictive utility of COVID-PPE subscales, particularly as the pandemic evolves, which may inform recommendations for cancer survivors and facilitate identification of survivors most in need of intervention.

Trib1 Deficiency Promotes Hyperlipidemia, Inflammation, and Atherosclerosis in LDL Receptor Knockout Mice.

BACKGROUND: Genetic variants at the TRIB1 gene locus are strongly associated with plasma lipid traits and the risk of coronary artery disease in humans. Here, we analyzed the consequences of Trib1 deficiency on lipid metabolism and atherosclerotic lesion formation in atherosclerosis-susceptible Ldlr-/- mice. METHODS: Trib1-/- mice were crossed onto the Ldlr-/- background to generate double-knockout mice (Trib1-/-Ldlr-/-) and fed a semisynthetic, modified AIN76 diet (0.02% cholesterol and 4.3% fat) until 20 weeks of age. RESULTS: Trib1-/-Ldlr-/- mice had profoundly larger (5.8-fold) and more advanced atherosclerotic lesions at the aortic root as compared with Trib1+/+Ldlr-/- controls. Further, we observed significantly elevated plasma total cholesterol and triglyceride levels in Trib1-/-Ldlr-/- mice, resulting from higher VLDL (very-low-density lipoprotein) secretion. Lipidomics analysis revealed that loss of Trib1 altered hepatic lipid composition, including the accumulation of cholesterol and proinflammatory ceramide species, which was accompanied by signs of hepatic inflammation and injury. Concomitantly, we detected higher plasma levels of IL (interleukin)-6 and LCN2 (lipocalin 2), suggesting increased systemic inflammation in Trib1-/-Ldlr-/- mice. Hepatic transcriptome analysis demonstrated significant upregulation of key genes controlling lipid metabolism and inflammation in Trib1-/-Ldlr-/- mice. Further experiments suggested that these effects may be mediated through pathways involving a C/EPB (CCAAT/enhancer binding protein)-PPARγ (peroxisome proliferator-activated receptor γ) axis and JNK (c-Jun N-terminal kinase) signaling. CONCLUSIONS: We provide experimental evidence that Trib1 deficiency promotes atherosclerotic lesion formation in a complex manner that includes the modulation of lipid metabolism and inflammation.

Quantum causality emerging in a delayed-choice quantum Cheshire Cat experiment with neutrons.

We report an experiment with neutrons in a silicon perfect crystal interferometer, that realizes a quantum Cheshire Cat in a delayed choice setting. In our setup the quantum Cheshire Cat is established by spatially separating the particle and its property (i.e. the neutron and its spin) into the two different paths of the interferometer. The condition for a delayed choice setting is achieved by postponing the choice of path assignment for the quantum Cheshire Cat, i.e. which path is taken by the particle and which by its property, until the point in time when the neutron wave function has already split and entered the interferometer. The results of the experiment suggest not only the fact that the neutrons and its spin are separated and take different paths in the interferometer, but also quantum-mechanical causality is implied, insomuch that the behavior of a quantum system is affected by the choice of the selection at a later point in time.

A Tracheal Aspirate-derived Airway Basal Cell Model Reveals a Proinflammatory Epithelial Defect in Congenital Diaphragmatic Hernia.

Rationale: Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm and lung hypoplasia. The pathophysiology of lung defects in CDH is poorly understood. Objectives: To establish a translational model of human airway epithelium in CDH for pathogenic investigation and therapeutic testing. Methods: We developed a robust methodology of epithelial progenitor derivation from tracheal aspirates of newborns. Basal stem cells (BSCs) from patients with CDH and preterm and term non-CDH control subjects were derived and analyzed by bulk RNA sequencing, assay for transposase accessible chromatin with sequencing, and air-liquid interface differentiation. Lung sections from fetal human CDH samples and the nitrofen rat model of CDH were subjected to histological assessment of epithelial defects. Therapeutics to restore epithelial differentiation were evaluated in human epithelial cell culture and the nitrofen rat model of CDH. Measurements and Main Results: Transcriptomic and epigenetic profiling of CDH and control BSCs reveals a proinflammatory signature that is manifested by hyperactive nuclear factor kappa B and independent of severity and hernia size. In addition, CDH BSCs exhibit defective epithelial differentiation in vitro that recapitulates epithelial phenotypes found in fetal human CDH lung samples and fetal tracheas of the nitrofen rat model of CDH. Furthermore, blockade of nuclear factor kappa B hyperactivity normalizes epithelial differentiation phenotypes of human CDH BSCs in vitro and in nitrofen rat tracheas in vivo. Conclusions: Our findings have identified an underlying proinflammatory signature and BSC differentiation defects as a potential therapeutic target for airway epithelial defects in CDH.