The experiences of familial mental illness stigma among individuals living with mental illnesses.

Persons with mental illnesses may experience stigma from their immediate family members in addition to other forms of stigma. Using semi-structured interviews, we investigated experiences of familial mental illness stigma among 15 people diagnosed with mental illnesses in a mid-sized city in Canada. We identified five themes that speak to participants' experiences of familial mental illness stigma and ways to reduce it. The themes include the following: diagnosis as a 'double-edged sword,' potential familial isolation, familial stigma as societal stigma localized, stories of acceptance, and confronting potential familial mental illness stigma. Participants' narratives indicate that familial mental illness stigma is rooted in the broader social or public stigma, which sees its way into familial relations as well. This stigma takes various forms, including relationship bias or unfair treatment, breakdown in romantic relationships, loss of status, verbal and emotional abuse, exclusion from decision-making, and alienation within their immediate and extended families. Familial mental illness stigma experiences negatively impact participant's psychological well-being and personal empowerment. However, participants also shared ways that family members create supportive environments or actively confront or prevent stigma. Overall, this study has contributed to knowledge on mental illness stigma, particularly familial mental illness stigma from the perspective of participants living with a mental illness in a high-income country. Suggestions for future research include a focus on strategies to prevent ongoing familial mental illness stigma and large-scale studies to explore familial mental illness stigma to understand why families might perpetrate stigma.

Managing high-risk behaviours and challenges to prevent housing loss in permanent supportive housing: a rapid review.

Permanent supportive housing is an effective intervention for stably housing most people experiencing homelessness and mental illness who have complex support needs. However, high-risk behaviours and challenges are prevalent among this population and have the potential to seriously harm health and threaten housing tenures. Yet, the research on the relationship between high-risk issues and housing stability in permanent supportive housing has not been previously synthesized. This rapid review aimed to identify the housing-related outcomes of high-risk behaviours and challenges in permanent supportive housing settings, as well as the approaches used by agencies and residents to address them. A range of high-risk behaviours and challenges were examined, including risks to self (overdose, suicide/suicide attempts, non-suicidal self-injury, falls/fall-related injuries), and risks to multiple parties and/or building (fire-setting/arson, hoarding, apartment takeovers, physical/sexual violence, property damage, drug selling, sex trafficking). The search strategy included four components to identify relevant academic and grey literature: (1) searches of MEDLINE, APA PsycINFO, and CINAHL Plus; (2) hand searches of three journals with aims specific to housing and homelessness; (3) website browsing/searching of seven homelessness, supportive housing, and mental health agencies and networks; and (4) Advanced Google searches. A total of 32 articles were eligible and included in the review. Six studies examined the impacts of high-risk behaviours and challenges on housing tenancies, with overdose being identified as a notable cause of death. Twenty-six studies examined approaches and barriers to managing high-risk behaviours and challenges in PSH programs. These were categorized into eight types of approaches: (1) clinical, (2) relational/educational, (3) surveillant, (4) restrictive, (5) strategic, (6) design-based, (7) legal, and (8) self-defence. Consistent across all approaches was a lack of rigorous examination of their effectiveness. Further, some approaches that are legal, restrictive, surveillant, or strategic in nature may be used to promote safety, but may conflict with other program objectives, including housing stability, or resident empowerment and choice. Research priorities were identified to address the key evidence gaps and move toward best practices for preventing and managing high-risk behaviours and challenges in permanent supportive housing.

Social Contact: Next Steps in an Effective Strategy to Mitigate the Stigma of Mental Illness.

People living with mental illnesses and their families may conceal their conditions to avoid prejudice and discrimination. Stigma often prevents people from receiving adequate health care and other social support services which could exacerbate social and health consequences such as unemployment, homelessness, substance use, and compulsory hospitalization. In this paper, we discuss social contact as a promising anti-stigma strategy for enhancing social interactions among people with mental illnesses, their families, and those without mental illnesses. In particularly, we consider next steps for an approach that works to reduce the stigma-related burden of mental illness. For social contact to be effective in reducing mental illness stigma, it requires broad social buy-in as well as implementation within care systems. Engagement with this approach can be driven through diverse contact-based education using collaborative efforts of society, academic institutions, policy-makers, health professionals, media, and governments. Ultimately, this work aims to consider the next steps in enacting social contact as an anti-stigma strategy through direct interventions and contact-based education. The success of this approach requires pragmatic public policies to support its implementation.

Policies and Interventions to Reduce Familial Mental Illness Stigma: A Scoping Review of Empirical Literature.

Although research to date has shown that there can be no health or sustainable development without good mental health, mental illness continues to significantly impact societies. A major challenge confronting people with mental illnesses and their families is the stigma that they endure. In this study, empirical literature was reviewed to assess policies and interventions that seek to reduce familial mental illness stigma across four countries. We used Arksey and O'Malley methodological framework, and a qualitative content analysis was employed to augment the descriptive data extracted. Seven studies published between 2000 and 2020 were analyzed. We propose herein three themes that align with interventions to reduce familial mental illness stigma: transformative education, sharing and disclosure, and social networking and support. The findings indicate that persuasive and purposeful education directed at the public to correct misconceptions surrounding mental illness, with attention to language, may help in reducing familial mental illness stigma. Disclosure of mental illness is encouraged among persons with mental illnesses and their families as a strategy to enhance mutual understanding. Social sharing also affords persons with mental illnesses opportunities to engage with their peers at different levels within the public sphere. Apart from these recommendations, we have noted a paucity of broad governmental-level policies and interventions to comprehensively address the negative attitudes of families toward their relatives. Future work must address this gap to identify effective interventions to create healthier and supportive environments that address familial mental illness stigma.

Studies into the determinants of skeletal muscle oxygen consumption: novel insight from near-infrared diffuse correlation spectroscopy.

KEY POINTS: Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion. Near-infrared spectroscopy (NIRS) is an established technique for characterizing the transport and utilization of oxygen through the microcirculation. Here we compared a combined NIRS-DCS system with conventional measures of oxygen delivery and utilization during handgrip exercise. The data show good concurrent validity between convective oxygen delivery and DCS-derived blood flow index, as well as between oxygen extraction at the conduit and microvascular level. We then manipulated forearm arterial perfusion pressure by adjusting the position of the exercising arm relative to the position of the heart. The data show that microvascular perfusion can be uncoupled from convective oxygen delivery, and that tissue saturation seemingly compensates to maintain skeletal muscle oxygen consumption. Taken together, these data support a novel role for NIRS-DCS in understanding the determinants of muscle oxygen consumption at the microvascular level. ABSTRACT: Diffuse correlation spectroscopy (DCS) is emerging as a powerful tool to assess skeletal muscle perfusion. Combining DCS with near-infrared spectroscopy (NIRS) introduces exciting possibilities for understanding the determinants of muscle oxygen consumption; however, no investigation has directly compared NIRS-DCS to conventional measures of oxygen delivery and utilization in an exercising limb. To address this knowledge gap, nine healthy males performed rhythmic handgrip exercise with simultaneous measurements by NIRS-DCS, Doppler blood flow and venous oxygen content. The two approaches showed good concurrent validity, with directionally similar responses between: (a) Doppler-derived forearm blood flow and DCS-derived blood flow index (BFI), and (b) venous oxygen saturation and NIRS-derived tissue saturation. To explore the utility of combined NIRS-DCS across the physiological spectrum, we manipulated forearm arterial perfusion pressure by altering the arm position above or below the level of the heart. As expected, Doppler-derived skeletal muscle blood flow increased with exercise in both arm positions, but with markedly different magnitudes (below: +424.3 ± 41.4 ml/min, above: +306 ± 12.0 ml/min, P = 0.002). In contrast, DCS-derived microvascular BFI increased to a similar extent with exercise, regardless of arm position (P = 0.65). Importantly, however, the time to reach BFI steady state was markedly slower with the arm above the heart, supporting the experimental design. Notably, we observed faster tissue desaturation at the onset of exercise with the arm above the heart, resulting in similar muscle oxygen consumption profiles throughout exercise. Taken together, these data support a novel role for NIRS-DCS in understanding the determinants of skeletal muscle oxygen utilization non-invasively and throughout exercise.

Inter- and intra-tumor heterogeneity of SMAD4 loss in head and neck squamous cell carcinomas.

Reports regarding the frequency of SMAD4 loss in human head and neck squamous cell carcinoma (HNSCC) vary significantly. We have shown that SMAD4 deletion contributes to HNSCC initiation and progression. Therefore, accurately detecting genetic SMAD4 loss is critical to determine prognosis and therapeutic interventions in personalized medicine. We developed a SMAD4 fluorescence in situ hybridization (FISH) assay to identify chromosomal SMAD4 loss at the single cell level of primary HNSCC specimens and patient derived xenograft (PDX) tumors derived from HNSCCs. SMAD4 heterozygous loss was detected in 35% of primary HNSCCs and 41.3% of PDX tumors. Additionally, 4.3% of PDX tumors had SMAD4 homozygous loss. These frequencies of SMAD4 loss were similar to those in The Cancer Genome Atlas (TCGA). However, we identified significant heterogeneities of SMAD4 loss (partial or complete) among cells within each tumor. We also found that aneuploidy (monosomy and polysomy) contributed greatly to how to define chromosomal SMAD4 deletion. Furthermore, in cultured PDX tumors, SMAD4 mutant cells outcompeted SMAD4 wildtype cells, resulting in establishing homogenous SMAD4 mutant HNSCC cell lines with partial or complete genomic SMAD4 loss, suggesting a survival advantage of SMAD4 mutant cells. Taken together, our study reveals inter- and intra-tumor heterogeneities of SMAD4 chromosomal loss in HNSCCs. Further, SMAD4 FISH assay provides a platform for future clinical diagnosis of SMAD4 chromosomal loss that potentially serves as a molecular marker for prognosis and therapeutic intervention in cancer patients.

Interventions to address burden among family caregivers of persons aging with TBI: A scoping review.

PURPOSE: To capture the scope of literature exploring interventions for caregivers of aging persons with TBI. METHODS: A scoping review of peer reviewed literature was conducted in two phases. Phase I: Searching seven databases, two independent raters screened articles using a set of predetermined criteria. Included articles were reviewed, and categorized according to common themes. Phase II: Five stakeholders were engaged in a consultation. A content analysis was performed by extracting statements from each interview using an inductive strategy, and organizing each into themes. FINDINGS: A total of 11 articles were included in the final analysis. Inter-rater reliability was assessed at both the title and abstract search [98.8% agreement; k = 0.3425 (95% CI, .246 to .439), p < .05]; and the full-text review [83% agreement; k = 0.542 (95% CI, 0.340 to 0.745), p < .05] phases. Seven articles identified potential interventions, and four identified and evaluated an intervention. Interventions targeted subjective burden (n = 4) and objective burden (n = 4), with caregiver knowledge and skill development (n = 3) classified as a sub-category of objective burden. Stakeholders overwhelmingly emphasized the need for interventions to reduce objective burden. IMPLICATIONS: Included articles were primarily composed of levels six and seven evidence, suggesting that this literature is in an early stage of development. Future research should emphasize the development and evaluation of interventions to reduce objective burden.

Suboptimal Agreement Among Cytopathologists in Diagnosis of Malignancy Based on Endoscopic Ultrasound Needle Aspirates of Solid Pancreatic Lesions: A Validation Study.

BACKGROUND & AIMS: Despite the widespread use of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to sample pancreatic lesions and the standardization of pancreaticobiliary cytopathologic nomenclature, there are few data on inter-observer agreement among cytopathologists evaluating pancreatic cytologic specimens obtained by EUS-FNA. We developed a scoring system to assess agreement among cytopathologists in overall diagnosis and quantitative and qualitative parameters, and evaluated factors associated with agreement. METHODS: We performed a prospective study to validate results from our pilot study that demonstrated moderate to substantial inter-observer agreement among cytopathologists for the final cytologic diagnosis. In the first phase, 3 cytopathologists refined criteria for assessment of quantity and quality measures. During phase 2, EUS-FNA specimens of solid pancreatic lesions from 46 patients were evaluated by 11 cytopathologists at 5 tertiary care centers using a standardized scoring tool. Individual quantitative and qualitative measures were scored and an overall cytologic diagnosis was determined. Clinical and EUS parameters were assessed as predictors of unanimous agreement. Inter-observer agreement (IOA) was calculated using multi-rater kappa (κ) statistics and a logistic regression model was created to identify factors associated with unanimous agreement. RESULTS: The IOA for final diagnoses, based on cytologic analysis, was moderate (κ = 0.56; 95% CI, 0.43-0.70). Kappa values did not increase when categories of suspicious for malignancy, malignant, and neoplasm were combined. IOA was slight to moderate for individual quantitative (κ = 0.007; 95% CI, -0.03 to -0.04) and qualitative parameters (κ = 0.5; 95% CI, 0.47-0.53). Jaundice was the only factor associated with agreement among all cytopathologists on multivariate analysis (odds ratio for unanimous agreement, 5.3; 95% CI, 1.1-26.89). CONCLUSIONS: There is a suboptimal level of agreement among cytopathologists in the diagnosis of malignancy based on analysis of EUS-FNA specimens obtained from solid pancreatic masses. Strategies are needed to refine the cytologic criteria for diagnosis of malignancy and enhance tissue acquisition techniques to improve diagnostic reproducibility among cytopathologists.

Outcomes of Bethesda categories III and IV thyroid nodules over 5 years and performance of the Afirma gene expression classifier: A single-institution study.

OBJECTIVE: The second edition Bethesda System for Reporting Thyroid Cytology estimates 6%-18% malignancy rate of category III (B3) and 10%-40% for category IV (B4) nodules; however, reported malignancy rates have considerable variability among institutions. Use of molecular classifiers (including Afirma Gene Expression Classifier, GEC) can be utilized in management of thyroid nodules. Our objective was to analyse malignancy rates of B3 and B4 nodules and determine clinical outcomes of GEC Benign nodules. METHODS: A retrospective analysis of 2019 thyroid FNAs was performed at the University of Colorado from 2011 to 2015, including molecular, surgical and clinical follow-up. RESULTS: Of 2019 FNAs analysed, 231 (11.4%) were diagnosed as B3 and 80 (4.0%) as B4. GEC was obtained in 54.1% of B3 cases, with nearly half (48.8%) having a Benign result. Surgery was performed in 40.7% B3 cases with a 24.5% malignancy rate, ranging 8%-38% by year. In the B4 group, 52.5% underwent molecular testing with 28.6% as GEC Benign. About 68.8% of B4 cases underwent surgery with a 20% malignancy rate, ranging 0%-42% by year. Seventy-three GEC Benign cases were reviewed: 5 (6.8%) underwent surgery, with none demonstrating malignancy in the target nodule. Size remained stable for most GEC Benign nodules: 75.9% (B3) and 71.4% (B4) with no malignancy on repeat FNA. CONCLUSIONS: Our 5-year review demonstrated that malignancy rates of B3 and B4 nodules showed year-to-year variability. We suggest that clinicians use a multi-year average of their institution's malignancy rates to optimally manage patients. Follow-up for GEC Benign cases thus far supports their indolent nature.

Increasing Number of Passes Beyond 4 Does Not Increase Sensitivity of Detection of Pancreatic Malignancy by Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

BACKGROUND & AIMS: It is not clear exactly how many passes are required to determine whether pancreatic masses are malignant using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). We aimed to define the per-pass diagnostic yield of EUS-FNA for establishing the malignancy of a pancreatic mass, and identify factors associated with detection of malignancies. METHODS: In a prospective study, 239 patients with solid pancreatic masses were randomly assigned to groups that underwent EUS-FNA, with the number of passes determined by an on-site cytopathology evaluation or set at 7 passes, at 3 tertiary referral centers. A final diagnosis of pancreatic malignancy was made based on findings from cytology, surgery, or a follow-up evaluation at least 1 year after EUS-FNA. The cumulative sensitivity of detection of malignancy by EUS-FNA was calculated after each pass; in the primary analysis, lesions categorized as malignant or suspicious were considered as positive findings. RESULTS: Pancreatic malignancies were found in 202 patients (84.5% of the study population). EUS-FNA detected malignancies with 96% sensitivity (95% confidence interval [CI], 92%-98%); 4 passes of EUS-FNA detected malignancies with 92% sensitivity (95% CI, 87%-95%). Tumor size greater than 2 cm was the only variable associated with positive results from cytology analysis (odds ratio, 7.8; 95% CI, 1.9-31.6). In masses larger than 2 cm, 4 passes of EUS-FNA detected malignancies with 93% sensitivity (95% CI, 89%-96%) and in masses ≤2 cm, 6 passes was associated with 82% sensitivity (95% CI, 61%-93%). Sensitivity of detection did not increase with increasing number of passes. CONCLUSIONS: In a prospective study, we found 4 passes of EUS-FNA to be sufficient to detect malignant pancreatic masses; increasing the number of passes did not increase the sensitivity of detection. Tumor size greater than 2 cm was associated with malignancy, and a greater number of passes may be required to evaluate masses 2 cm or less. ClinicalTrials.gov number, NCT01386931.

The clinical impact of immediate on-site cytopathology evaluation during endoscopic ultrasound-guided fine needle aspiration of pancreatic masses: a prospective multicenter randomized controlled trial.

OBJECTIVES: Observational data on the impact of on-site cytopathology evaluation (OCE) during endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) of pancreatic masses have reported conflicting results. We aimed to compare the diagnostic yield of malignancy and proportion of inadequate specimens between patients undergoing EUS-FNA of pancreatic masses with and without OCE. METHODS: In this multicenter randomized controlled trial, consecutive patients with solid pancreatic mass underwent randomization for EUS-FNA with or without OCE. The number of FNA passes in the OCE+ arm was dictated by the on-site cytopathologist, whereas seven passes were performed in OCE- arm. EUS-FNA protocol was standardized, and slides were reviewed by cytopathologists using standardized criteria for cytologic characteristics and diagnosis. RESULTS: A total of 241 patients (121 OCE+, 120 OCE-) were included. There was no difference between the two groups in diagnostic yield of malignancy (OCE+ 75.2% vs. OCE- 71.6%, P=0.45) and proportion of inadequate specimens (9.8 vs. 13.3%, P=0.31). Procedures in OCE+ group required fewer EUS-FNA passes (median, OCE+ 4 vs. OCE- 7, P<0.0001). There was no significant difference between the two groups with regard to overall procedure time, adverse events, number of repeat procedures, costs (based on baseline cost-minimization analysis), and accuracy (using predefined criteria for final diagnosis of malignancy). There was no difference between the two groups with respect to cytologic characteristics of cellularity, bloodiness, number of cells/slide, and contamination. CONCLUSIONS: Results of this study demonstrated no significant difference in the diagnostic yield of malignancy, proportion of inadequate specimens, and accuracy in patients with pancreatic mass undergoing EUS-FNA with or without OCE.

Occupation and the process of transition from homelessness.

BACKGROUND: The incorporation of meaningful activity or occupation in supporting those transitioning from homelessness to being housed has been promoted by researchers; however, there is little evidence to support the promotion of initiatives encouraging its use in support models. PURPOSE: This manuscript aims to advocate for further research into the role of occupation in supporting persons transitioning from homelessness to permanent housing. KEY ISSUES: The transition from homelessness to becoming housed can be facilitated through use of occupation as a way of promoting the security of meaningful roles and a "housed identity" among persons experiencing homelessness. IMPLICATIONS: By promoting an emphasis on occupation, persons experiencing homelessness may undergo a positive change in identity. This change may improve housing tenure and the likelihood of a more permanent transition away from homelessness. More research is required to identify the relationship between occupation and the transition from homelessness.

Adamantinoma of the Ulnar Shaft Reconstructed With a Vascularized Free Fibula.

We describe a 36-year-old man with a long-standing diagnosis of ulnar fibrous dysplasia with associated fracture of the ulna. He presented with a growing and increasingly tender forearm mass and was diagnosed with adamantinoma of the ulna, for which he underwent wide resection of the ulnar diaphysis followed by reconstruction with a vascularized fibula autograft. This case serves to emphasize the importance of performing a stepwise workup for the diagnosis of osseous neoplasms even in cases with long-standing diagnoses. [Orthopedics. 2024;47(2):e102-e105.].

Effectiveness of Interventions for Meaningful Activity Participation in Homelessness: A Systematic Review.

Background. Meaningful activity participation has been identified as a key outcome of services designed to support individuals during and following homelessness. Little is known about the effectiveness of interventions for promoting this outcome. Purpose. To identify the range and effectiveness of interventions on promoting meaningful activity participation among persons with experiences of homelessness. Method. We conducted a systematic review using the Joanna Briggs Institute methodology following PRISMA guidelines including a critical appraisal and narrative synthesis. Findings. Of 12,343 titles and abstracts screened, we included 12 studies. The authors of the included studies primarily used standardized measures of meaningful activity engagement. Critical appraisal scores ranged from 50.0 to 77.8. The most common interventions evaluated in the included studies were psychosocial interventions (n = 6; 50.0%), followed by case management and housing support interventions (n = 4; 33.3%) and Housing First (n = 2; 16.7%). While several interventions demonstrated effectiveness in promoting meaningful activity participation including psychosocial and case management interventions, Housing First, Critical Time Intervention, and a peer support intervention were found to be ineffective for promoting engagement in meaningful activity. Conclusion. Few intervention studies have been conducted that demonstrate effectiveness for promoting participation in meaningful activity for individuals during and following homelessness. Occupational therapy researchers and practitioners can build on existing evidence by developing and evaluating novel approaches by co-designing interventions in collaboration with persons with experiences of homelessness and service providers.

Participatory Research with Persons who Experience Mental Illness in Occupational Therapy: A Scoping Review.

Background. Persons who experience mental illness also face stigma and discrimination that frequently lead to a loss of ability to exercise autonomy and agency in their lives. Purpose. The range and breadth of literature exploring participatory research with persons living with mental illness are unknown in occupational therapy and occupation science. We initiated this study to fill this gap in the existing occupational therapy and occupational science literature. Method. Using the method of Arksey and O'Malley, we have conducted a scoping review to identify the range and breadth of literature. A qualitative content analysis was performed. Findings. A total of 34 articles were included in the narrative synthesis. The content analysis led to three related themes from the included studies: (1) coming together; (2) unique potential of participatory research; and (3) challenges in conducting participatory research. Conclusions. This review highlights that participatory research is well suited to research conducted with persons living with mental illness to support meaningful engagement and minimize stigma throughout the research process. This review can guide future participatory research and practice in occupational therapy and occupational science with persons living with mental illness.

"It's like your days are empty and yet there's life all around": A mixed methods, multi-site study exploring boredom during and following homelessness.

PURPOSE: To identify experiences of boredom and associations with psychosocial well-being during and following homelessness. METHODS: Using a convergent, mixed-methods explanatory design, we conducted quantitative interviews with 164 participants) (n = 102 unhoused; n = 62 housed following homelessness) using a 92-item protocol involving demographic components and seven standardized measures of psychosocial well-being. A sub-sample (n = 32) was approached to participate in qualitative interviews. Data were analyzed by group (unhoused; housed). Quantitative data were analyzed using descriptive statistics designed to generate insights into boredom, meaningful activity engagement, and their associations with psychosocial well-being during and following homelessness. Qualitative data were analyzed using thematic analysis. Quantitative and qualitative findings were integrated at the stage of discussion. RESULTS: Quantitative analyses revealed small to moderate correlations between boredom and increased hopelessness (rs = .376, p < .01), increased drug use (rs = .194, p < .05), and lowered mental well-being (rs = -.366, p < .01). There were no statistically significant differences between unhoused and housed participants on any standardized measures. Hierarchical regression analyses revealed that housing status was not a significant predictor of boredom or meaningful activity engagement (p>.05). Qualitative interviews revealed profound boredom during and following homelessness imposing negative influences on mental well-being and driving substance use. CONCLUSIONS: Boredom and meaningful activity are important outcomes that require focused attention in services designed to support individuals during and following homelessness. Attention to this construct in future research, practice, and policy has the potential to support the well-being of individuals who experience homelessness, and to contribute to efforts aimed at homelessness prevention.

Pre-operative thyroglobulin measurement for thyroid cancer risk of recurrence and response to therapy.

BACKGROUND: Thyroid cancer has an overall favorable prognosis, but no pre-operative biochemical marker has been shown to distinguish between low and high-risk disease or predict response to therapy. METHODS: We retrospectively reviewed 162 patients that underwent thyroid surgery for thyroid cancer between 2006 and 2022 in whom a pre-operative thyroglobulin level (Tg) was measured. We subdivided patients into low, intermediate and high-risk thyroid cancer and based on their response to therapy per ATA guidelines. RESULTS: We showed that as pre-operative Tg level increased, patients were more likely to have high-risk disease (p â€‹< â€‹0.01). We found a linear association between the primary tumor size and high-risk histology with pre-operative Tg (p â€‹< â€‹0.01). Pre-operative Tg level was significantly associated with response to therapy following initial surgical management. Specifically, as pre-operative Tg increases, patients were less likely to achieve an excellent response (p â€‹< â€‹0.01). CONCLUSIONS: Our retrospective analysis demonstrated that pre-operative Tg is significantly associated with ATA structural risk of recurrence and response to therapy and may have the potential to guide initial therapy and follow-up management.

Thyroid Cancer Polygenic Risk Score Improves Classification of Thyroid Nodules as Benign or Malignant.

CONTEXT: Thyroid nodule ultrasound-based risk stratification schemas rely on the presence of high-risk sonographic features. However, some malignant thyroid nodules have benign appearance on thyroid ultrasound. New methods for thyroid nodule risk assessment are needed. OBJECTIVE: We investigated polygenic risk score (PRS) accounting for inherited thyroid cancer risk combined with ultrasound-based analysis for improved thyroid nodule risk assessment. METHODS: The convolutional neural network classifier was trained on thyroid ultrasound still images and cine clips from 621 thyroid nodules. Phenome-wide association study (PheWAS) and PRS PheWAS were used to optimize PRS for distinguishing benign and malignant nodules. PRS was evaluated in 73 346 participants in the Colorado Center for Personalized Medicine Biobank. RESULTS: When the deep learning model output was combined with thyroid cancer PRS and genetic ancestry estimates, the area under the receiver operating characteristic curve (AUROC) of the benign vs malignant thyroid nodule classifier increased from 0.83 to 0.89 (DeLong, P value = .007). The combined deep learning and genetic classifier achieved a clinically relevant sensitivity of 0.95, 95% CI [0.88-0.99], specificity of 0.63 [0.55-0.70], and positive and negative predictive values of 0.47 [0.41-0.58] and 0.97 [0.92-0.99], respectively. AUROC improvement was consistent in European ancestry-stratified analysis (0.83 and 0.87 for deep learning and deep learning combined with PRS classifiers, respectively). Elevated PRS was associated with a greater risk of thyroid cancer structural disease recurrence (ordinal logistic regression, P value = .002). CONCLUSION: Augmenting ultrasound-based risk assessment with PRS improves diagnostic accuracy.

Service restrictions from emergency shelters among people experiencing homelessness: Uncovering pathways into unsheltered homelessness and institutional circuitry.

Service restrictions refer to temporary or permanent bans of individuals from a program or an organization's services, and are widely used in emergency shelter systems. Limited research exists on how service restrictions unfold and their impacts on people experiencing homelessness. This qualitative study used in-depth interviews with timeline mapping to examine the antecedents and consequences of service restrictions from emergency shelters among people experiencing homelessness in two cities in Ontario, Canada. A total of 49 people experiencing homelessness who had been restricted from an emergency shelter program in the past year were recruited and included in the study analysis. A pragmatic and integrative approach was used for data analysis that involved the development of meta-matrices to identify prominent and divergent perspectives and experiences with regard to service restriction antecedents and consequences. Study findings underscored that service restrictions were often the result of violence and aggression, primarily between service users. There were regional differences in other service restriction reasons, including substance use and possession. Service restrictions affected the shelter status of almost all participants, with many subsequently experiencing unsheltered homelessness, and cycling through institutional health, social, and criminal justice services (i.e., institutional circuitry). Other health and social consequences included substance use relapses and hospitalizations; cold-related injuries due to post-restriction unsheltered homelessness; suicidality; food insecurity; diminished contact with support network and connections; and intense feelings of anger, fear, and hopelessness. Overall, the study findings advance our understanding of the role of homeless services in pathways into unsheltered homelessness and institutional circuitry, which raise critical questions about how to mitigate the harms associated with service restrictions, while concurrently facilitating safety and upholding the rights of people experiencing homelessness and emergency shelter staff.

Facile chemical functionalization of proteins through intein-linked yeast display.

Intein-mediated expressed protein ligation (EPL) permits the site-specific chemical customization of proteins. While traditional techniques have used purified, soluble proteins, we have extended these methods to release and modify intein fusion proteins expressed on the yeast surface, thereby eliminating the need for soluble protein expression and purification. To this end, we sought to simultaneously release yeast surface-displayed proteins and selectively conjugate with chemical functionalities compatible with EPL and click chemistry. Single-chain antibodies (scFv) and green fluorescent protein (GFP) were displayed on the yeast surface as fusions to the N-terminus of the Mxe GyrA intein. ScFv and GFP were released from the yeast surface with either a sulfur nucleophile (MESNA) or a nitrogen nucleophile (hydrazine) linked to an azido group. The hydrazine azide permitted the simultaneous release and azido functionalization of displayed proteins, but nonspecific reactions with other yeast proteins were detected, and cleavage efficiency was limited. In contrast, MESNA released significantly more protein from the yeast surface while also generating a unique thioester at the carboxy-terminus of the released protein. These protein thioesters were subsequently reacted with a cysteine alkyne in an EPL reaction and then employed in an azide-alkyne cycloaddition to immobilize the scFv and GFP on an azide-decorated surface with >90% site-specificity. Importantly, the immobilized proteins retained their activity. Since yeast surface display is also a protein engineering platform, these approaches provide a particularly powerful tool for the rapid assessment of engineered proteins.