Transcriptome and cytogenetic profiling analysis of matched in situ/invasive cutaneous squamous cell carcinomas from immunocompetent patients.

Although most cutaneous squamous cell carcinomas (cSCCs) develop from actinic keratoses (AKs), the key events in this evolution remain unclear. We have combined the results of different genomic and expression array platforms on matched concomitant samples of sun-exposed skin (SES), AK, and cSCC from 10 immunocompetent patients. Gene expression analysis and copy number alterations were assessed using GeneChip Human Gene 2.0 ST Array (Affymetrix, Santa Clara, CA) and CytoScan HD Cytogenetics Solution (Affymetrix) platforms, respectively. Integration of transcriptome and genome results was evaluated using the DR-Integrator tool. Additional studies (qPCR, immunohistochemistry, and Western blot) were performed for selected genes. FOSL1 and BNC1 encode transcription factors whose expression was increased in cSCC in the expression array and the qPCR. By immunohistochemistry, FOSL1 showed an intense staining at the invasive front of cSCC samples and BNC1 expression varied from a nuclear (SES) to a cytoplasmic location (cSCC). Western blot analyses confirmed the enhancement of FOSL1 and BNC1. In addition, the smallest overlapping regions (SORIs) of genomic imbalance involving at least three of the samples were selected. One of the SORIs was a deletion in the p24.1 band of chromosome 3, shared by seven of the cSCCs. A strong correlation in the integration analysis was found for NEK10, a gene contained in the previously mentioned SORI. Loss of NEK10 expression in cSCC was confirmed by immunohistochemistry and Western blot analyses. In addition, functional studies in NEK10 depleted cells were performed. In conclusion, we identified FOSL1 and BNC1, which could act as tumor drivers, and NEK10, which could function as a tumor suppressor, to be differentially expressed during cSCC development.

A Myxoid Fibrotic Reaction Pattern is Associated with Metastatic Risk in Cutaneous Squamous Cell Carcinoma.

Although desmoplasia has been associated with poor prognoses in cutaneous squamous cell carcinoma, little attention has been paid to the patterns of fibrosis. This study aimed to examine the different stromal fibrotic patterns as markers of metastatic risk. We performed a multicenter retrospective study that included 102 cutaneous squamous cell carcinomas (52 non-metastatic and 50 metastatic carcinomas). Clinical and histopathological data were registered. The fibrotic reaction pattern was classified as mature, intermediate or immature depending on the presence of keloid-like collagen and myxoid stroma. The immature pattern (areas characterized by myxoid changes with no inflammation) was observed in 18 samples and its presence was significantly associated with immunosuppression, budding, desmoplasia, perineural invasion, anatomic level, tumoural depth and metastatic risk in the multivariate analysis. Our findings suggest that the presence of an immature myxoid fibrotic pattern, which can be easily identified by routine hematoxylin-eosin staining, is strongly associated with metastatic risk.

The Polycomb proteins RING1B and EZH2 repress the tumoral pro-inflammatory function in metastasizing primary cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epigenetic regulation of gene expression may allow tumoral cells to acquire new functions in order to escape from the primary tumor. The aim of this study was to investigate the expression and function of proteins of the Polycomb family of epigenetic regulators in the metastatic process of cSCC. A higher expression of RING1B and EZH2 was detected by immunohistochemistry in a series of primary cSCC tumors that metastasized (MSCCs) when compared with non-metastasizing cSCCs (non-MSCCs). Stable downregulation of RING1B and EZH2 in cSCC cells results in enhanced expression of inflammatory cytokines and activation of the NF-κB signaling pathway. Accordingly, non-MSCCs display higher levels of membranous pS176-inhibitor of NF-kB kinase, and their stroma is enriched in neutrophils and eosinophils when compared with MSCCs. In vitro, hematopoietic cells exhibit a substantial migratory response to supernatants from Polycomb-depleted cSCC cells. Altogether, these data indicate that RING1B and EZH2 repress the innate inflammatory cSCC function and impair tumor immunosurveillance and suggest that patients with high-risk cSCCs could benefit from clinical therapies addressed to harness the immune response.

PD-L1 Expression is Increased in Metastasizing Squamous Cell Carcinomas and Their Metastases.

Programmed cell death ligand 1 (PD-L1) expression by tumor cells plays an important role in the inhibition of T cell-mediated immune response in cancer. PD-L1 expression by tumor cells has been linked to poor prognosis in a wide variety of cancers. However, PD-L1 expression in cutaneous squamous cell carcinoma (cSCC) has been scarcely studied, and its role as a prognosis biomarker remains controversial. The association of PD-L1 expression and the metastatic risk in a series of cSCC was assessed. PD-L1 and CD8 immunostainings of full excision sections of 99 primary tumors and 24 lymphatic metastases were semiquantitatively evaluated. Primary cSCCs were grouped according to the development of lymphatic metastatic spread [metastasizing squamous cell carcinoma (MSCC)] (n = 48) or the absence of progression [nonmetastasizing squamous cell carcinoma (NMSCC)] (n = 51). PD-L1-positive expression (cut off ≥1%) was found in 26% NMSCCs and in 50% MSCCs (P = 0.02). PD-L1 association with an increased metastatic risk was confirmed in the multivariate analysis (P < 0.05), along with the following features: recurrence, poor differentiation, and perineural invasion. Ninety percent of the metastases of PD-L1-positive tumors were also positive for PD-L1, displaying a trend toward a higher PD-L1 expression when compared with their primary tumors (P = 0.058). No significant differences in the peritumoral inflammatory infiltrate or in the expression of CD8 were found between metastasizing and nonmetastasizing primary tumors. Our results suggest that PD-L1 may play a relevant role in metastatic spread and may be a candidate prognostic biomarker in cSCC.

Pancreatic panniculitis: A case series from a tertiary university hospital in Spain.

Pancreatic panniculitis is a rare type that only occurs in 2-3% of all patients with pancreatic diseases. It is usually described in association with benign pancreatic disease and less commonly in association with pancreatic carcinoma. We describe a case of pancreatic panniculitis as the first manifestation of underlying ampullary adenocarcinoma and a new case of pancreatitis, panniculitis and polyarthritis (PPP-Syndrome). Pancreatic panniculitis may be the cutaneous manifestation of pancreatic allograft rejection after simultaneous pancreas-kidney transplantation.

MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and frequently progresses from an actinic keratosis (AK), a sun-induced keratinocyte intraepithelial neoplasia (KIN). Epigenetic mechanisms involved in the phenomenon of progression from AK to cSCC remain to be elicited. METHODS: Expression of microRNAs in sun-exposed skin, AK and cSCC was analysed by Agilent microarrays. DNA methylation of miR-204 promoter was determined by bisulphite treatment and pyrosequencing. Identification of miR-204 targets and pathways was accomplished in HaCat cells. Immunofluorescence and immunohistochemistry were used to analyze STAT3 activation and PTPN11 expression in human biopsies. RESULTS: cSCCs display a marked downregulation of miR-204 expression when compared to AK. DNA methylation of miR-204 promoter was identified as one of the repressive mechanisms that accounts for miR-204 silencing in cSCC. In HaCaT cells miR-204 inhibits STAT3 and favours the MAPK signaling pathway, likely acting through PTPN11, a nuclear tyrosine phosphatase that is a direct miR-204 target. In non-peritumoral AK lesions, activated STAT3, as detected by pY705-STAT3 immunofluorescence, is retained in the membrane and cytoplasm compartments, whereas AK lesions adjacent to cSCCs display activated STAT3 in the nuclei. CONCLUSIONS: Our data suggest that miR-204 may act as a "rheostat" that controls the signalling towards the MAPK pathway or the STAT3 pathway in the progression from AK to cSCC.

Music to decrease anxiety in college students during the COVID-19 pandemic.

The COVID-19 pandemic impacted the world in a multiplicity of ways. For college students, considered emerging adults in a time of transition between adolescence and adulthood, the stressors were multiplied by severe disruptions in education, social activities, family distress, and job losses. Significant impact on mental health in college students has been reported during this period. We investigated the effect of a previously researched music experience on the anxiety levels of 36 performing arts college students. Results showed a high level of anxiety pre-intervention, but a significant decrease and normative levels at posttest. Although a small sample size warrants caution in generalization, these results show the feasibility of theoretically sound, brief music experiences to address significant distress in vulnerable populations.

"Music Therapy Was Never on the Table": Perspectives of Parents of Young Autistic Children.

Parent coaching of music interventions is emerging as a viable model for families with young autistic children, yet recruitment difficulties have been apparent in previous studies. Understanding parent perspectives of early intervention services is critical to ensure that interventions are acceptable, feasible, and effective for all family members. In order to understand possible parental resistance to this type of parent education, we explored perspectives regarding music therapy, research, and parent coaching in parents of young autistic children. Fourteen parents attended virtual focus groups to discuss their experiences. We used a descriptive phenomenological approach to uncover the essence of their experience. Our findings indicate that, contrary to our preconceptions, participants did not show negative dispositions towards music therapy, research, or parent coaching. Instead, most participants had very little or no knowledge of music therapy services. They had limited experience with research in general, and only two participants had experienced music therapy directly. Several participants had varying amounts of experience with parent participation or parent coaching outside of music therapy and shared positive experiences with it. Parents seemed willing and eager to learn music strategies to support their children and saw value in the use of music for their child's development. First-contact providers (i.e., early interventionists and diagnosticians) and social media seem influential in parents' decision-making as they navigate early intervention services soon after diagnosis. Music therapy organizations are encouraged to design targeted efforts to make information on music therapy available through these sources.

Psychological and Neural Differences of Music Processing in Autistic Individuals: A Scoping Review.

Despite abundant research and clinical evidence of the effectiveness of music interventions for people in the autism spectrum, understanding of music processing in this community is limited. We explored whether research evidence of differences in music processing within the autistic community is available. We developed a scoping review to search for literature with the terms "music", "processing," and "autism" (and variants). We searched PubMed, CINAHL, Scopus, Web of Science, PsycInfo, Academic Search Complete, ERIC, and Music Index databases for a total of 10,857 articles, with 5,236 duplicates. The remaining 5,621 titles and abstracts were screened for eligibility by a team of four undergraduate and graduate students and the PI. Seventy-five studies were included for data extraction. Data were analyzed with descriptive statistics regarding author, study, stimulus, and participant information, and a thematic analysis of outcome and findings. Our findings are preliminary given the emerging nature of the literature, the use of mostly non-musical auditory stimuli, passive listening experiences, and underreported demographics. However, the literature shows some evidence of differences in music processing for autistic individuals, including reduced habituation to non-musical and musical stimuli; truncated, delayed, or divergent developmental trajectories; and possible compensatory higher-order mechanisms that yield similar behavioral responses even in the presence of divergent neural correlates. Music therapists are encouraged to adopt a developmental perspective, not only of general skills, but specifically of music skill development in this community, and to extrapolate these findings with caution, given the current limitations in the evidence.

Music Stimuli for Mindfulness Practice: A Replication Study.

Mindfulness is a natural human capacity to be aware of the present moment, without judgment, rejection, or attachment to it. Cultivating a mindful state has been related to improvements in mood and stress management. Mindfulness practices may be enhanced with music. The purpose of this study was to replicate a previous study regarding the effectiveness, preference, and usefulness of different auditory stimuli for mindfulness practice. Undergraduate nonmusicians (N = 53) listened to 4 different auditory stimuli of increasing complexity, guiding them in a mindfulness experience. Participants rated their mindfulness experience, provided data on their absorption in music, and ranked auditory stimuli according to preference and usefulness for mindfulness practice. A within-subjects design was used to compare the four conditions, counterbalanced, and randomized across participants. Similar to the original study, Friedman analysis of variances (ANOVAs) and post hoc analyses indicated that participants ranked the Melody and Harmony conditions as most preferred and useful. Different from the original results, the repeated-measures ANOVA of the Mindful Attention Awareness Scale scores did not reveal significant differences among auditory stimuli for mindfulness experience. These results provide support for the use of music in mindfulness experiences with a mildly complex stimulus (script, beat, harmony, and melody). However, partially replicated results indicate the need to investigate the discrepancy between participants' effectiveness ratings and preference/usefulness rankings.

Improving a Parent Coaching Model of Music Interventions for Young Autistic Children.

Parenting a child on the autism spectrum can be rewarding and enriching, but it may also increase risk of parental fatigue, stress, anxiety, and depression. Parent-mediated interventions contribute to increase family satisfaction and child social communication while helping to decrease parental stress and fatigue. Parent coaching, the education of parents in evidence-based strategies, has become common in the autism field. However, parent coaching in music therapy has only recently emerged and has limited research with families with an autistic member. In this study, we attempted to improve a previously published model of parent coaching, adapting only one aspect of the Early Start Denver Model (ESDM), the sensory social routine (SSR) to create a music intervention. Four parents participated in this 6-session parent coaching study. We compared the SSR-based intervention with and without music, in an alternating treatment design. Measures included parental responsiveness, child receptive and initiation joint attention, parent-child similar affect and synchronized gaze, and the Parent Coaching-ESDM (PC-ESDM) parent fidelity rating system. Results from these observational measures were mixed, with better parental responses in the no-music condition, but improved child responses and parent-child synchrony in the music condition for 3 out of the 4 participants. Parent learning increased for all participants, and 3 out of the 4 reached fidelity (a score of at least 80%), according to the PC-ESDM. Although mixed results were observed across participants, implications for practice are possible. Better outcome measures of this complex intervention are needed.

Outcomes of a Course-based Undergraduate Research Experience (CURE) for Music Therapy and Music Education Students.

Course-based undergraduate research experiences (CUREs) involve entire classes of students researching a question or problem that is of interest to the scholarly community with an unknown outcome to both students and instructor. The purpose of this pre-experimental one-group posttest design study was to explore outcomes of a CURE for music therapy and music education students enrolled in a music psychology course. Specifically, we examined differences in scientific thinking, personal gains, research skills, and attitudes and behaviors of students resulting from their participation in a CURE experience, as well as students' perceived benefits of a CURE experience. Student participants (N = 30) completed the Undergraduate Research Student Self-Assessment. Likert-type items from the self-assessment were analyzed using descriptive statistics, and open-ended questions analyzed for common themes using content analysis. Students reported moderate gains across three areas (i.e., thinking and working like a scientist, personal gains, and research skills), with greatest gains reported for thinking and working like a scientist. Students reported limited change for changes in attitudes and behaviors as a researcher. The authors discuss implications and recommendations for future CUREs.

Reporting quality of music intervention research in healthcare: A systematic review.

INTRODUCTION: Concomitant with the growth of music intervention research, are concerns about inadequate intervention reporting and inconsistent terminology, which limits validity, replicability, and clinical application of findings. OBJECTIVE: Examine reporting quality of music intervention research, in chronic and acute medical settings, using the Checklist for Reporting Music-based Interventions. In addition, describe patient populations and primary outcomes, intervention content and corresponding interventionist qualifications, and terminology. METHODS: Searching MEDLINE, PubMed, CINAHL, HealthSTAR, and PsycINFO we identified articles meeting inclusion/exclusion criteria for a five-year period (2010-2015) and extracted relevant data. Coded material included reporting quality across seven areas (theory, content, delivery schedule, interventionist qualifications, treatment fidelity, setting, unit of delivery), author/journal information, patient population/outcomes, and terminology. RESULTS: Of 860 articles, 187 met review criteria (128 experimental; 59 quasi-experimental), with 121 publishing journals, and authors from 31 countries. Overall reporting quality was poor with <50% providing information for four of the seven checklist components (theory, interventionist qualifications, treatment fidelity, setting). Intervention content reporting was also poor with <50% providing information about the music used, decibel levels/volume controls, or materials. Credentialed music therapists and registered nurses delivered most interventions, with clear differences in content and delivery. Terminology was varied and inconsistent. CONCLUSIONS: Problems with reporting quality impedes meaningful interpretation and cross-study comparisons. Inconsistent and misapplied terminology also create barriers to interprofessional communication and translation of findings to patient care. Improved reporting quality and creation of shared language will advance scientific rigor and clinical relevance of music intervention research.

An Emerging Theoretical Model of Music Therapy Student Development.

BACKGROUND: Music therapy students negotiate a complex relationship with music and its use in clinical work throughout their education and training. This distinct, pervasive, and evolving relationship suggests a developmental process unique to music therapy. OBJECTIVE: The purpose of this grounded theory study was to create a theoretical model of music therapy students' developmental process, beginning with a study within one large Midwestern university. METHODS: Participants (N = 15) were music therapy students who completed one 60-minute intensive interview, followed by a 20-minute member check meeting. Recorded interviews were transcribed, analyzed, and coded using open and axial coding. RESULTS: The theoretical model that emerged was a six-step sequential developmental progression that included the following themes: (a) Personal Connection, (b) Turning Point, (c) Adjusting Relationship with Music, (d) Growth and Development, (e) Evolution, and (f) Empowerment. The first three steps are linear; development continues in a cyclical process among the last three steps. As the cycle continues, music therapy students continue to grow and develop their skills, leading to increased empowerment, and more specifically, increased self-efficacy and competence. CONCLUSIONS: Further exploration of the model is needed to inform educators' and other key stakeholders' understanding of student needs and concerns as they progress through music therapy degree programs.

Effect of music therapy on the anxiety levels and sleep patterns of abused women in shelters.

The purpose of this study was to explore the effect of a music therapy procedure (music listening paired with progressive muscle relaxation) on the reduction of anxiety and improvement of sleep patterns in abused women in shelters. Twenty-eight women residing in 2 domestic violence shelters in a Midwestern city met with the researcher on 5 consecutive days for half-hour sessions. A pretest-posttest design with control and experimental groups was used. The dependent variables included: stait anxiety measured by the STAI (Spielberger et al., 1983) before and after each music stimulus, sleep quality as measured by the PSQI (Buysse et al., 1989) on the first and last sessions, and levels of fatigue as measured by the Fatigue Scale (Lee, 1992) at waking time. The independent variable was a 20-minute recording of participant-selected music with a Progressive Muscle Relaxation script. Results indicated that music therapy constituted an effective method for reducing anxiety levels. Results also indicated a significant effect on sleep quality for the experimental group, but not for the control group. No significant relationships were found between anxiety levels and sleep quality, nor fatigue levels and sleep quality. These results seem promising in the light of domestic violence research, which has found that a greater amount of personal resources is a crucial aspect of abused women's recovery process. Reduction of anxiety and improvement of sleep quality can be considered as increased personal resources, and seem feasible through the use of music therapy.