Violation of a Leggett-Garg Inequality Using Ideal Negative Measurements in Neutron Interferometry.

Leggett-Garg inequalities (LGIs) have been proposed in order to assess how far the predictions of quantum mechanics defy "macroscopic realism." With LGIs, correlations of measurements performed on a single system at different times are described. We report on an experiment that demonstrates the violation of an LGI with neutrons. The final measured value of the Leggett-Garg correlator K=1.120±0.007(stat)±0.019(sys), obtained in a neutron interferometric experiment, is clearly above the limit K=1 predicted by macrorealistic theories. The experimental results are analyzed within the framework of dynamical theory of neutron diffraction, evidently reproducing the obtained values.

Experimental congenital diaphragmatic hernia features an alteration of DNA sensing targets cGAS and STING.

BACKGROUND: The pathogenesis of congenital diaphragmatic hernia (CDH) depends on multiple factors. Activation of the DNA-sensing cyclic-GMP-AMP-synthase (cGAS) and Stimulator-of-Interferon-Genes (STING) pathway by double-stranded DNA (dsDNA) links environmental stimuli and inflammation. We hypothesized that nitrofen exposure alters cGAS and STING in human bronchial epithelial cells and fetal rat lungs. METHODS: We used the Quant-IT™-PicoGreen™ assay to assess dsDNA concentration in BEAS-2B cells after 24 h of nitrofen-exposure and performed immunofluorescence of cGAS/STING. We used nitrofen to induce CDH and harvested control and CDH lungs at embryonic day E15, E18 and E21 for cGAS/STING immunofluorescence, RT-qPCR and RNA-Scope™ in-situ-hybridization (E18, E21). RESULTS: We found a higher concentration of dsDNA following nitrofen treatment. Nitrofen-exposure to BEAS-2B cells increased cGAS and STING protein abundance. cGAS abundance was higher in nitrofen lungs at E15, E18 and E21. RNA-Scope in-situ-hybridization showed higher cGAS and STING expression in E18 and E21 lungs. RT-qPCR revealed higher mRNA expression levels of STING in E21 nitrofen-induced lungs. CONCLUSION: Our data suggest that nitrofen-exposure increases dsDNA content which leads to stimulation of the cGAS/STING pathway in human BEAS-2B cells and the nitrofen rat model of CDH. Consequently, DNA sensing and the cGAS-STING-pathway potentially contribute to abnormal lung development in CDH. IMPACT STATEMENT: We found an alteration of DNA sensing targets cGAS and STING in human BEAS-2B cells and experimental congenital diaphragmatic hernia with higher protein abundance and mRNA expression in cells and lung sections of nitrofen-treated rat pups. This is the first study to investigate DNA sensing, a potential link between environmental stimuli and inflammation, in experimental CDH. Our study extends the knowledge on the pathogenesis of experimental CDH.

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.

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.

Symptomatic perineural and intraneural invasion of the trigeminal nerve and subsequent abducens Nerve palsy by cutaneous squamous cell carcinoma.

A 74-year-old woman who presented initially with trigeminal neuralgia of the left forehead and scalp was later found to have a poorly differentiated squamous cell carcinoma (SCC) with large-nerve perineural and intraneural invasion of the left supraorbital nerve. Negative histopathologic margins were achieved in three stages of permanent fixed tissue en face processing and the final defect was repaired with a large rotation flap. Approximately one month after repair, the patient presented with new-onset diplopia and was found to have a complete left cranial nerve VI palsy suspicious for continued disease spread. MRI confirmed perineural spread along the ophthalmic branch of the trigeminal nerve through the superior orbital fissure into the cavernous sinus. She was subsequently treated with radiation therapy (66Gy in 33 fractions). The involvement of two distinct cranial nerves by perineural invasion is uncommon and has mostly been described involving branches of the trigeminal and facial nerves. This case highlights the rare presentation of perineural invasion involving both the trigeminal nerve and the abducens nerve. Anatomically, this clinical presentation can be explained by the retrograde perineural spread along the ophthalmic branch of the trigeminal nerve through the supraorbital fossa into the cavernous sinus where these two nerves are in close proximity.

3D models for mohs micrographic surgery: a review on its use in patient education.

The use of a 3D model for patient education has shown encouraging results in surgical specialties like plastic surgery and neurosurgery, amongst many others; however, there is limited research on the clinical application of 3D models for Mohs Micrographic Surgery. This study delves into the utilization of 3D models for patient education in Mohs Surgery by juxtaposing different 3D modalities, highlighting their differences, and exploring potential avenues for future integration of 3D models into clinical practice. A literature search in the scientific database MEDLINE through PubMed and OVID and on the ProQuest Health & Medical Collection database was performed on the use of a 3D model for patient education. We limited the search to articles available in English and considered those mentioning the educational use of 3D models, especially for patient education, after excluding duplicate titles. We did not exclude articles based on publication year due to limited availability of literature. Utilizing 3D models for patient education within the framework of Mohs Micrographic surgery, including a 3D multicolored clay model and a 3D model accompanied by an educational video intervention, presents substantial advantages. 3D models offer a visual and tactile means to improve patients' comprehension of the Mohs procedure, the affected area, and possible outcomes. They hold the potential to reduce patient anxiety and improve decision-making. Currently, literature on the use of 3D models for patient education in Mohs Micrographic Surgery is limited, warranting further research in this area.

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.

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.

Transobturator-cable-fixation in pelvic ring injuries with symphyseal disruption - a last resort?

PURPOSE: The role of transobturator-cable-fixation (TOCF) in traumatic symphyseal rupture of the pelvic ring remains unclear. This case series aims to evaluate TOCF in complex and revision cases in pelvic surgery. METHODS: A retrospective analysis of a chronological case series was conducted, studying pelvic fractures stabilized using TOCF between January 2006 and December 2022. The variables considered included age, gender, fracture classification, Injury Severity Score (ISS), Body Mass Index (BMI), trauma mechanism, time to surgery, fixation technique, hospital duration, complications, status on discharge (Glasgow Outcome Scale; GOS), follow-up time and indication for the use of TOCF. RESULTS: All patients (N = 7) were male with a mean age of 64 years and a mean BMI of 29. The mean ISS was 45, with the lowest ISS of 25, indicating that only polytraumatized patients were included. Two anterior-posterior-compression-, four lateral-compression-, and one vertical-shear-pelvic-injury were identified. TOCF was added in six cases to support symphyseal plating and in one case to external fixation. The mean hospital stay was 49 days and the mean follow-up duration was 8.5 months. No complications associated with TOCF were observed during the surgical procedure or follow-up. CONCLUSION: TOCF showed no procedure-associated complications and effectively supported symphyseal healing in all cases. The main indications were obesity, poor bone quality in elderly patients, and revision cases. TOCF could be considered as a last treatment option in open-book pelvic injuries where plating or external fixation is at risk to fail.

Evidence-based and Patient-centered Indication for Knee Arthroplasty - Update of the Guideline. / Evidenzbasierte und patientenorientierte Indikationsstellung zur Knieendoprothese ­ Update der Leitlinie.

Knee arthroplasty is one of the most frequently performed operations in Germany, with approximately 170000 procedures per year. It is therefore essential that physicians should adhere to an appropriate, and patient-centered indication process. The updated guideline indication criteria for knee arthroplasty (EKIT-Knee) contain recommendations, which are based on current evidence and agreed upon by a broad consensus panel. For practical use, the checklist has also been updated.For this guideline update, a systematic literature research was conducted in order to analyse (inter-)national guidelines and systematic reviews focusing on osteoarthritis of the knee and knee arthroplasty, to answer clinically relevant questions on diagnostic, predictors of outcome, risk factors and contraindications.Knee arthroplasty should solely be performed in patients with radiologically proven moderate or severe osteoarthritis of the knee (Kellgren-Lawrence grade 3 or 4), after previous non-surgical treatment for at least three months, in patients with high subjective burden with regard to knee-related complaints and after exclusion of possible contraindications (infection, comorbidities, BMI ≥ 40 kg/m2). Modifiable risk factors (such as smoking, diabetes mellitus, anaemia) should be addressed and optimised in advance. After meeting current guideline indications, a shared decision-making process between patients and surgeons is recommended, in order to maintain high quality surgical management of patients with osteoarthritis of the knee.The update of the S2k-guideline was expanded to include unicondylar knee arthroplasty, the preoperative optimisation of modifiable risk factors was added and the main indication criteria were specified.

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.

Fetal hypoplastic lungs have multilineage inflammation that is reversed by amniotic fluid stem cell extracellular vesicle treatment.

Antenatal administration of extracellular vesicles from amniotic fluid stem cells (AFSC-EVs) reverses features of pulmonary hypoplasia in models of congenital diaphragmatic hernia (CDH). However, it remains unknown which lung cellular compartments and biological pathways are affected by AFSC-EV therapy. Herein, we conducted single-nucleus RNA sequencing (snRNA-seq) on rat fetal CDH lungs treated with vehicle or AFSC-EVs. We identified that intra-amniotically injected AFSC-EVs reach the fetal lung in rats with CDH, where they promote lung branching morphogenesis and epithelial cell differentiation. Moreover, snRNA-seq revealed that rat fetal CDH lungs have a multilineage inflammatory signature with macrophage enrichment, which is reversed by AFSC-EV treatment. Macrophage enrichment in CDH fetal rat lungs was confirmed by immunofluorescence, flow cytometry, and inhibition studies with GW2580. Moreover, we validated macrophage enrichment in human fetal CDH lung autopsy samples. Together, this study advances knowledge on the pathogenesis of pulmonary hypoplasia and further evidence on the value of an EV-based therapy for CDH fetuses.

Effects of combined exercise training on the inflammatory profile of older cancer patients treated with systemic therapy.

Cancer-related fatigue (CRF) is a major issue in older cancer patients as it is associated with functional decline and a lower quality of life, and an increased inflammatory activity during cancer therapy is suspected to play a key role in CRF etiology. Combined aerobic and resistance exercise training is known to reduce CRF, and this could be mediated by a protective effect against this increased inflammatory activity. Hence, the main objective was to measure the effect of a 12-week combined exercise training on the inflammatory profile of older cancer patients undergoing systemic therapy. A secondary objective was to verify if there was an association between inflammatory profile and CRF. Methods: Twenty older non-metastatic cancer patients initiating chemotherapy and/or hormone therapy were randomly assigned to 12 weeks of supervised, combined exercise or a control group (static stretching). Primary outcomes were the inflammatory profile, Indoleamine 2,3-deoxygenase activity (KYN/TRP ratio), and CRF (FACIT-F questionnaire). Control outcomes were the fasting nutritional and hormonal blood profiles, body composition (iDXA), physical activity habits (PASE questionnaire), nutritional habits (3-day log), and treatment-related variables. Results: No worsening of the inflammatory profile was observed in both arms of the study after the intervention. No significant change in CRF was observed, although there was a trend for a reduction in the experimental group (p â€‹= â€‹0.10). Significant correlations were found at both timepoints between the KYN/TRP ratio and the delay with the previous treatment received (p â€‹≤ â€‹0.03). Conclusion: These results suggest that exercise might have elicited a positive effect on CRF, which was not mediated by the modulation of the pro-inflammatory cytokine profile. However, the decrease in IL-6/IL-10 ratio in the exercise group might reflect a possible anti-inflammatory effect of exercise. Moreover, exploratory analyses suggest that an acute effect of chemotherapy treatments influenced the inflammatory profile measurements, which could explain the absence of change in the fasting inflammatory profile.