Discordance between a deep learning model and clinical-grade variant pathogenicity classification in a rare disease cohort.

Genetic testing has become an essential component in the diagnosis and management of a wide range of clinical conditions, from cancer to developmental disorders, especially in rare Mendelian diseases. Efforts to identify rare phenotype-associated variants have predominantly focused on protein-truncating variants, while the interpretation of missense variants presents a considerable challenge. Deep learning algorithms excel in various applications across biomedical tasks1,2, yet accurately distinguishing between pathogenic and benign genetic variants remains an elusive goal3-5. Specifically, even the most sophisticated models encounter difficulties in accurately assessing the pathogenicity of missense variants of uncertain significance (VUS). Our investigation of AlphaMissense (AM)5, the latest iteration of deep learning methods for predicting the potential functional impact of missense variants and assessing gene essentiality, reveals important limitations in its ability to identify pathogenic missense variants within a rare disease cohort. Indeed, AM struggles to accurately assess the pathogenicity of variants in intrinsically disordered regions (IDRs), leading to unreliable gene-level essentiality scores for certain genes containing IDRs. This limitation highlights the challenges in applying AM faces in the context of clinical genetics6.

Prevalence of disordered eating and its relationship with rapid weight loss amongst male and female combat sport competitors: A prospective study.

OBJECTIVES: To compare prevalence and change scores of disordered eating (DE) in combat sport athletes by sex and explore the potential relationship between rapid weight loss (RWL) and DE scores. DESIGN: Prospective study based on 24 events (September 2022-2023). METHODS: A body mass (BM) questionnaire was completed at ~1 day post-competition providing pre-competition BM data for -7 days, -24 h, and weigh-in. The Athletic Disordered Eating (ADE) online questionnaire was completed at ~7 and ~28 days post-competition, providing overall DE and four subscale scores (food and energy control, bingeing, body control, and body discontent). RESULTS: There were 122, 132, and 89 respondents for the BM (77 % male), and ADE questionnaires at 7 (79 % male), and 28 days (74 % male). A large proportion of males' (83 %) and females' (89 %) DE scores were moderate to very high; minimal (17 % vs. 11 %), moderate (36 % vs. 32 %), high (37 % vs. 36 %), and very high (11 % vs. 21 %). Comparing DE change scores in males and females indicated deterioration (5 % vs. 0 %), improvement (3 % vs. 25 %, p = 0.013), and no difference (92 % vs. 75 %). Body discontent change score showed a significant sex difference (p = 0.014), with females improving (42 % vs. 17 %, p = 0.035) and males deteriorating (35 % vs. 4 %, p = 0.008). Correlation analyses were significant for RWL -7 days and males' food control score (R = 0.22, p = 0.031). CONCLUSIONS: Moderate to very high DE indications were identified in 4 of every 5 combat sport competitors. A sex-specific change in body discontent is evident, and most competitors struggle with their food-body relationship post-competition, irrespective of RWL magnitude.

How should we sample snail microbiomes?

Background: The microbiome is increasingly recognized to shape many aspects of its host biology and is a key determinant of health and disease. The microbiome may influence transmission of pathogens by their vectors, such as mosquitoes or aquatic snails. We previously sequenced the bacterial 16S V4 ribosomal DNA of the hemolymph (blood) of Biomphalaria spp. snails, one of the vectors of the human blood fluke schistosome. We showed that snail hemolymph harbored an abundant and diverse microbiome. This microbiome is distinct from the water environment and can discriminate snail species and populations. As hemolymph bathes snail organs, we then investigated the heterogeneity of the microbiome in these organs. Results: We dissected ten snails for each of two different species (B. alexandrina and B. glabrata) and collected their organs (ovotestis, hepatopancreas, gut, and stomach). We also ground in liquid nitrogen four whole snails of each species. We sampled the water in which the snails were living (environmental controls). Sequencing the 16S V4 rDNA revealed organ-specific microbiomes. These microbiomes harbored a lower diversity than the hemolymph microbiome, and the whole-snail microbiome. The organ microbiomes tend to cluster by physiological function. In addition, we showed that the whole-snail microbiome is more similar to hemolymph microbiome. Conclusions: These results are critical for future work on snail microbiomes and show the necessity of sampling individual organ microbiomes to provide a complete description of snail microbiomes.

Uses of Linguistic Context in Speech Listening: Does Acquired Hearing Loss Lead to Reduced Engagement of Prediction?

Research investigating the complex interplay of cognitive mechanisms involved in speech listening for people with hearing loss has been gaining prominence. In particular, linguistic context allows the use of several cognitive mechanisms that are not well distinguished in hearing science, namely those relating to "postdiction", "integration", and "prediction". We offer the perspective that an unacknowledged impact of hearing loss is the differential use of predictive mechanisms relative to age-matched individuals with normal hearing. As evidence, we first review how degraded auditory input leads to reduced prediction in people with normal hearing, then consider the literature exploring context use in people with acquired postlingual hearing loss. We argue that no research on hearing loss has directly assessed prediction. Because current interventions for hearing do not fully alleviate difficulty in conversation, and avoidance of spoken social interaction may be a mediator between hearing loss and cognitive decline, this perspective could lead to greater understanding of cognitive effects of hearing loss and provide insight regarding new targets for intervention.

Systemic absorption of triamcinolone acetonide is increased from intrasynovial versus extrasynovial sites and induces hyperglycemia, hyperinsulinemia, and suppression of the hypothalamic-pituitary-adrenal axis.

Steroid-associated laminitis remains a major concern with use of corticosteroids in horses. Individual case factors such as joint pathology, pre-existing endocrinopathies, or corticosteroid type, dose, and timing influencing steroid-induced laminitis risk have not been investigated. This study aimed to determine if systemic absorption of triamcinolone acetonide (TA) varies between intrasynovial (antebrachiocarpal) and extrasynovial (sacroiliac) injection sites, and to determine the effects of TA absorption on glucose, insulin, cortisol, and adrenocorticotropic hormone (ACTH). Twenty adult horses were randomized into antebrachiocarpal or sacroiliac joint injection groups, and each horse received bilateral injections with a total dose of 18 mg triamcinolone. Blood was collected prior to injection and at 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48, 60, and 72 h post-injection. Peak TA absorption occurred at 8 h in both groups, and was significantly higher in the intrasynovial group compared to the extrasynovial group (1.397 ng/mL, 0.672 ng/mL, p < 0.05). Plasma TA levels were significantly higher in the intrasynovial group from 8 to 36 h post-injection (p < 0.05). There was no difference in glucose, insulin, cortisol, or ACTH between groups at any time point. Insulin and glucose were significantly increased from baseline at all timepoints from 10-72 h and 1-72 h post-injection, respectively. Horses with elevated baseline insulin values (>20 µU/mL) from both groups experienced a more marked hyperinsulinemia, reaching a mean peak insulin of 197.5 µU/mL as compared to 90.06 µU/mL in those with normal baseline insulin. Cortisol and ACTH were significantly decreased from baseline at timepoints from 4-72 h post-injection in both groups. This study is the first to evaluate drug absorption from the sacroiliac site and demonstrates that drug absorption varies between intrasynovial and extrasynovial injection sites. TA absorption causes metabolic derangements, most notably a marked hyperinsulinemia that is more severe in horses with elevated baseline insulin values. The influence of baseline endocrinopathies on response to corticosteroid administration as well as the effect of corticosteroid-induced metabolic derangements warrant further investigation as risk factors for corticosteroid-associated laminitis.

What is the rate of definitive stoma after subtotal colectomy for inflammatory bowel disease? A nationwide study of 1860 patients.

AIM: Some patients with inflammatory bowel disease (IBD) require subtotal colectomy (STC) with ileostomy. The recent literature reports a significant number of patients who do not undergo subsequent surgery and are resigned to living with a definitive stoma. The aim of this work was to analyse the rate of definitive stoma and the cumulative incidence of secondary reconstructive surgery after STC for IBD in a large national cohort study. METHOD: A national retrospective study (2013-2021) was conducted on prospectively collected data from the French Medical Information System Database (PMSI). All patients undergoing STC in France were included. The association between definitive stoma and potential risk factors was studied using univariate and multivariate analyses. RESULTS: A total of 1860 patients were included (age 45 ± 9 years; median follow-up 30 months). Of these, 77% (n = 1442) presented with ulcerative colitis. Mortality and morbidity at 90 days after STC were 5% (n = 100) and 47% (n = 868), respectively. Reconstructive surgery was identified in 1255 patients (67%) at a mean interval of 7 months from STC. Seveny-four per cent (n = 932) underwent a completion proctectomy with ileal pouch anal anastomosis and 26% (n = 323) an ileorectal anastomosis. Six hundred and five (33%) patients with a definitive stoma had an abdominoperineal resection (n = 114; 19%) or did not have any further surgical procedure (n = 491; 81%). Independent risk factors for definitive stoma identified in multivariate analysis were older age, Crohn's disease, colorectal neoplasia, postoperative complication after STC, laparotomy and a low-volume hospital. CONCLUSION: We found that 33% of patients undergoing STC with ileostomy for IBD had definitive stoma. Modifiable risk factors for definitive stoma were laparotomy and a low-volume hospital.

Extended thoracic endovascular aortic repair is optimal therapy in acute complicated type B dissection.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) represents optimal therapy for complicated acute type B aortic dissection (aTBAD). Persistent knowledge gaps remain, including the optimal length of aortic coverage, impact on distal aortic remodeling, and fate of the dissected abdominal aorta. METHODS: Review of the Emory Aortic Database identified 92 patients who underwent TEVAR for complicated aTBAD from 2012 to 2018. Standard TEVAR covered aortic zones 3 and 4 (from the left subclavian to the mid-descending thoracic aorta). Extended TEVAR fully covered aortic zones 3 though 5 (from the left subclavian to the celiac artery). Long-term imaging, clinical follow-up, and overall and aortic-specific mortality were reviewed. RESULTS: Extended TEVAR (n = 52) required a greater length of coverage vs standard TEVAR (n = 40) (240 ± 32 mm vs 183 ± 23 mm; P < .01). In-hospital mortality occurred in 5.4% of patients (7.7% vs 2.5%; P = .27) owing to mesenteric malperfusion (n = 3) or rupture (n = 2). The overall incidences of postoperative stroke, transient paraparesis, paraplegia, and dialysis were 5.4% (3.9% vs 7.5%; P = .38), 3.2% (5.8% vs 0%; P = .18), 0%, and 0% respectively, equivalent between groups. Follow-up was 96.6% complete to a mean of 6.1 years (interquartile range, 3.5-8.6 years). There were significantly higher rates of complete thrombosis or obliteration of the entire thoracic false lumen after Extended TEVAR (82.2% vs 51.5%; P = .04). Distal aortic reinterventions were less frequent after extended TEVAR (5.8% vs 20%; P = .04). Late aorta-specific survival was 98.1% after extended TEVAR vs 92.3% for standard TEVAR (P = .32). CONCLUSIONS: Extended TEVAR for complicated aTBAD is safe, results in a high rate of total thoracic false lumen thrombosis/obliteration, and reduces distal reinterventions. Longer-term follow-up will be needed to demonstrate a survival benefit compared to limited aortic coverage.

Evaluation of a Conference on Cancer-Related Financial and Legal Issues: A Potential Resource to Counter Financial Toxicity.

This study describes the conception, development, and growth of the Triage Cancer Conference hosted by Triage Cancer, a national nonprofit organization providing free legal and financial education to the cancer community. We conducted a retrospective analysis of post-conference participant surveys. Descriptive statistics were calculated for participant demographics, and acceptability, feasibility, and appropriateness were evaluated. From 2016-2021, 1239 participants attended the conference and completed post-conference surveys. Participants included social workers (33%), nurses (30%), and cancer patients/survivors (21%), with representation from over 48 states. Among those who reported race, 16% were Black, and 7% were Hispanic. For acceptability, more than 90% of participants felt that the conference content, instructors, and format were suitable and useful. For feasibility, more than 90% of participants felt that the material was useful, with 93-96% reporting that they were likely to share the information and 98% reporting that they would attend another triage cancer event. Appropriateness was also high, with >80-90% reporting that the sessions met the pre-defined objectives. Triage Cancer fills an important gap in mitigating financial toxicity, and formal evaluation of these programs allows us to build evidence of the role and impact of these existing resources. Future research should focus on adding validated patient-reported outcomes, longer-term follow-up, and ensuring inclusion and evaluation of outcome metrics among vulnerable populations.

Probing ligand conformation and net dimensionality in a series of tetraphenylethene-based metal-organic frameworks.

Tetraphenylethene-based ligands with lowered symmetry are promising building blocks for the construction of novel luminescent metal-organic frameworks (MOFs). However, few examples have been reported, and predicting the ligand conformation and the dimensionality of the resulting MOF remains challenging. In order to uncover how synthetic conditions and accessible ligand conformations may affect the resulting MOF structure, four new MOF structures were synthesized under solvothermal conditions using the meta-coordinated tetraphenylethene-based ligand m-ETTC and paddlewheel SBUs composed of Co(II), Cu(II), and Zn(II). WSU-10 (WSU = Washington State University) is formed with either Zn or Cu comprising stacked psuedo-2D layers. The dimensionality of WSU-10 can be intentionally increased through the addition of pyrazine as a pillar ligand into the synthesis, forming the 3D structure WSU-11. The third structure, WSU-20, is formed by the combination of Zn or Co with m-ETTC and is intrinsically 3D without the use of a pillar ligand; interestingly, this is the result of a distortion in the paddlewheel SBU. Finally, Cu was also found to form a new structure (WSU-12), which displays an m-ETTC conformation unique from that found in the other isolated MOFs. Structural features are compared across the series and a mechanistic relationship between WSU-10 and -20 is proposed, providing insight into the factors that can encourage the generation of frameworks with increased dimensionality.

Microbial community structure of plant-based meat alternatives.

A reduction in animal-based diets has driven market demand for alternative meat products, currently raising a new generation of plant-based meat alternatives (PBMAs). It remains unclear whether these substitutes are a short-lived trend or become established in the long term. Over the last few years, the trend of increasing sales and diversifying product range has continued, but publication activities in this field are currently limited mainly to market research and food technology topics. As their popularity increases, questions emerge about the safety and nutritional risks of these novel products. Even though all the examined products must be heated before consumption, consumers lack experience with this type of product and thus further research into product safety, is desirable. To consider these issues, we examined 32 PBMAs from Austrian supermarkets. Based on 16S rRNA gene amplicon sequencing, the majority of the products were dominated by lactic acid bacteria (either Leuconostoc or Latilactobacillus), and generally had low alpha diversity. Pseudomonadota (like Pseudomonas and Shewanella) dominated the other part of the products. In addition to LABs, a high diversity of different Bacillus, but also some Enterobacteriaceae and potentially pathogenic species were isolated with the culturing approach. We assume that especially the dominance of heterofermentative LABs has high relevance for the product stability and quality with the potential to increase shelf life of the products. The number of isolated Enterobacteriaceae and potential pathogens were low, but they still demonstrated that these products are suitable for their presence.

Hydroxychloroquine inhibits hemolysis-induced arterial thrombosis ex vivo and improves lung perfusion in hemin-treated mice.

BACKGROUND: Free labile hemin acts as a damage-associated molecular pattern during acute and chronic hemolysis and muscle injury, supporting platelet activation and thrombosis. OBJECTIVES: To investigate the anti-thrombotic potential of hydroxychloroquine on hemolysis-induced platelet activation and arterial thrombosis. METHODS: The effect of hydroxychloroquine on hemin-induced platelet activation and hemolysis-induced platelet recruitment and aggregation was measured in washed platelets and hemolyzed blood, respectively. Its effect on ferric-chloride (FeCl3)-induced arterial thrombosis and lung perfusion following hemin injection was assessed in wild-type mice. RESULTS: Erythrocyte lysis and endothelial cell activation cooperatively supported platelet aggregation and thrombosis at arterial shear stress. This thrombotic effect was reversed by hydroxychloroquine. In a purified system, hydroxychloroquine inhibited platelet build-up on immobilized von Willebrand factor in hemolyzed blood without altering initial platelet recruitment. Hydroxychloroquine inhibited hemin-induced platelet activation and phosphatidylserine exposure independently of reactive oxygen species generation. In the presence of hemin, hydroxychloroquine did not alter glycoprotein VI shedding but reduced C-type-lectin-like-2 expression on platelets. In vivo, hydroxychloroquine reversed pulmonary perfusion decline induced by exogenous administration of hemin. In arterial thrombosis models, hydroxychloroquine inhibited ferric-chloride-induced thrombosis in the carotid artery and reduced von Willebrand factor accumulation in the thrombi. CONCLUSION: Hydroxychloroquine inhibited hemolysis-induced arterial thrombosis ex vivo and improved pulmonary perfusion in hemin-treated mice, supporting a potential benefit of its use as an adjuvant therapy in hemolytic diseases to limit arterial thrombosis and to improve organ perfusion.

Ultrasoft platelet-like particles stop bleeding in rodent and porcine models of trauma.

Uncontrolled bleeding after trauma represents a substantial clinical problem. The current standard of care to treat bleeding after trauma is transfusion of blood products including platelets; however, donated platelets have a short shelf life, are in limited supply, and carry immunogenicity and contamination risks. Consequently, there is a critical need to develop hemostatic platelet alternatives. To this end, we developed synthetic platelet-like particles (PLPs), formulated by functionalizing highly deformable microgel particles composed of ultralow cross-linked poly (N-isopropylacrylamide) with fibrin-binding ligands. The fibrin-binding ligand was designed to target to wound sites, and the cross-linking of fibrin polymers was designed to enhance clot formation. The ultralow cross-linking of the microgels allows the particles to undergo large shape changes that mimic platelet shape change after activation; when coupled to fibrin-binding ligands, this shape change facilitates clot retraction, which in turn can enhance clot stability and contribute to healing. Given these features, we hypothesized that synthetic PLPs could enhance clotting in trauma models and promote healing after clotting. We first assessed PLP activity in vitro and found that PLPs selectively bound fibrin and enhanced clot formation. In murine and porcine models of traumatic injury, PLPs reduced bleeding and facilitated healing of injured tissue in both prophylactic and immediate treatment settings. We determined through biodistribution experiments that PLPs were renally cleared, possibly enabled by ultrasoft particle properties. The performance of synthetic PLPs in the preclinical studies shown here supports future translational investigation of these hemostatic therapeutics in a trauma setting.

Ranavirus and helminth parasite co-infection in invasive American bullfrogs in the Atlantic forest, Brazil.

Emerging infectious diseases threaten amphibian species across the globe. In Brazil, the American bullfrog (Aquarana catesbeiana) is a highly invasive species that can potentially transmit parasites and pathogens to native amphibians. This is the first assessment of co-infection of Ranavirus and helminth macroparasites in invasive populations of bullfrogs in South America. We collected, measured, and euthanized 65 specimens of A. catesbeiana sampled from 9 sites across three states of Brazil in the Atlantic Forest biome. We collected and identified helminth macroparasites and sampled host liver tissue to test for the presence and load of Ranavirus with quantitative PCR. We documented patterns of prevalence, parasite load, and co-infection with generalized linear mixed models, generalized logistic regressions, and randomization tests. Most individual bullfrogs did not exhibit clinical signs of infection, but the overall Ranavirus prevalence was 27% (95% confidence interval, [CI 17-38]). Bullfrogs were infected with helminth macroparasites from 5 taxa. Co-infection of helminth macroparasites and Ranavirus was also common (21% CI [12-31]). Bullfrog size was positively correlated with total macroparasite abundance and richness, and the best-fitting model included a significant interaction between bullfrog size and Ranavirus infection status. We observed a negative correlation between Ranavirus viral load and nematode abundance (slope = -0.22, P = 0.03). Invasive bullfrogs (A. catesbeiana) in Brazil were frequently infected with both Ranavirus and helminth macroparasites, so adult bullfrogs could serve as reservoir hosts for both pathogens and parasites. However, many macroparasites collected were encysted and not developing. Coinfection patterns suggest a potential interaction between Ranavirus and macroparasites because helminth abundance increased with bullfrog size but was lower in Ranavirus infected individuals. Future studies of bullfrogs in the Atlantic Forest should investigate their potential role in pathogen and parasite transmission to native anurans.

Carbohydrate Ingestion Increases Interstitial Glucose and Mitigates Neuromuscular Fatigue During Single-Leg Knee Extensions.

INTRODUCTION: We aimed to investigate the neuromuscular contributions to enhanced fatigue resistance with carbohydrate ingestion, and to identify whether fatigue is associated with changes in interstitial glucose levels assessed using a continuous glucose monitor (CGM). METHODS: Twelve healthy participants (6 males, 6 females) performed isokinetic single-leg knee extensions (90°/s) at 20% of the maximal voluntary contraction (MVC) torque until MVC torque reached 60% of its initial value (i.e, task failure). Central and peripheral fatigue were evaluated every 15 min during the fatigue task using the interpolated twitch technique (ITT), and electrically evoked torque. Using a single-blinded cross-over design, participants ingested carbohydrates (CHO) (85 g sucrose/h), or a placebo (PLA), at regular intervals during the fatigue task. Minute-by-minute interstitial glucose levels measured via CGM, and whole blood glucose readings were obtained intermittently during the fatiguing task. RESULTS: CHO ingestion increased time to task failure over PLA (113 ± 69 vs. 81 ± 49 min; mean ± SD; p < 0.001) and was associated with higher glycemia as measured by CGM (106 ± 18 vs 88 ± 10 mg/dL, p < 0.001) and whole blood glucose sampling (104 ± 17 vs 89 ± 10 mg/dL, p < 0.001). When assessing the values in the CHO condition at a similar timepoint to those at task failure in the PLA condition (i.e., ~81 min), MVC torque, % voluntary activation, and 10 Hz torque were all better preserved in the CHO vs. PLA condition (p < 0.05). CONCLUSIONS: Exogenous CHO intake mitigates neuromuscular fatigue at both the central and peripheral levels by raising glucose concentrations rather than by preventing hypoglycemia.

Used to Be a Dime, Now It's a Dollar: Revised Speech Perception in Noise Key Word Predictability Revisited 40 Years On.

PURPOSE: Almost 40 years after its development, in this article, we reexamine the relevance and validity of the ubiquitously used Revised Speech Perception in Noise (R-SPiN) sentence corpus. The R-SPiN corpus includes "high-context" and "low-context" sentences and has been widely used in the field of hearing research to examine the benefit derived from semantic context across English-speaking listeners, but research investigating age differences has yielded somewhat inconsistent findings. We assess the appropriateness of the corpus for use today in different English-language cultures (i.e., British and American) as well as for older and younger adults. METHOD: Two hundred forty participants, including older (60-80 years) and younger (19-31 years) adult groups in the the United Kingdom and United States, completed a cloze task consisting of R-SPiN sentences with the final word removed. Cloze, as a measure of predictability, and entropy, as a measure of response uncertainty, were compared between culture and age groups. RESULTS: Most critically, of the 200 "high-context" stimuli, only around half were assessed as highly predictable for older adults (United Kingdom: 109; United States: 107); and fewer still, for younger adults (United Kingdom: 75; United States: 81). We also found dominant responses to these "high-context" stimuli varied between cultures, with U.S. responses being more likely to match the original R-SPiN target. CONCLUSIONS: Our findings highlight the issue of incomplete transferability of corpus items across English-language cultures as well as diminished equivalency for older and younger adults. By identifying relevant items for each population, this work could facilitate the interpretation of inconsistent findings in the literature, particularly relating to age effects.

Identifying Psychosis Episodes in Psychiatric Admission Notes via Rule-based Methods, Machine Learning, and Pre-Trained Language Models.

Early and accurate diagnosis is crucial for effective treatment and improved outcomes, yet identifying psychotic episodes presents significant challenges due to its complex nature and the varied presentation of symptoms among individuals. One of the primary difficulties lies in the underreporting and underdiagnosis of psychosis, compounded by the stigma surrounding mental health and the individuals' often diminished insight into their condition. Existing efforts leveraging Electronic Health Records (EHRs) to retrospectively identify psychosis typically rely on structured data, such as medical codes and patient demographics, which frequently lack essential information. Addressing these challenges, our study leverages Natural Language Processing (NLP) algorithms to analyze psychiatric admission notes for the diagnosis of psychosis, providing a detailed evaluation of rule-based algorithms, machine learning models, and pre-trained language models. Additionally, the study investigates the effectiveness of employing keywords to streamline extensive note data before training and evaluating the models. Analyzing 4,617 initial psychiatric admission notes (1,196 cases of psychosis versus 3,433 controls) from 2005 to 2019, we discovered that the XGBoost classifier employing Term Frequency-Inverse Document Frequency (TF-IDF) features derived from notes pre-selected by expert-curated keywords, attained the highest performance with an F1 score of 0.8881 (AUROC [95% CI]: 0.9725 [0.9717, 0.9733]). BlueBERT demonstrated comparable efficacy an F1 score of 0.8841 (AUROC [95% CI]: 0.97 [0.9580, 0.9820]) on the same set of notes. Both models markedly outperformed traditional International Classification of Diseases (ICD) code-based detection methods from discharge summaries, which had an F1 score of 0.7608, thus improving the margin by 0.12. Furthermore, our findings indicate that keyword pre-selection markedly enhances the performance of both machine learning and pre-trained language models. This study illustrates the potential of NLP techniques to improve psychosis detection within admission notes and aims to serve as a foundational reference for future research on applying NLP for psychosis identification in EHR notes.

A Needs Assessment Approach for Adolescent and Young Adult Sexual and Gender Diverse Cancer Survivors.

Sexual and gender diverse (SGD) adolescent and young adult (AYA) cancer survivors are an increasing and vulnerable group with unique needs that often remain unmet in the healthcare system. This paper describes the conceptualization and development of a community-based organization dedicated to serving SGD AYAs, in addition to reporting on the results of a community-led needs assessment. A total of 56 SGD AYA community members completed the online survey. Most participants were between the ages of 26 to 33, identified as white, cisgender, bisexual women, and had hematologic malignancies. Identified unmet needs of SGD AYAs included the following: sexual health and family planning; gender affirmation; financial stability; and emotional support. Areas within the community organization were identified as gaps, areas of expansion, and assets. Results highlight the role of community and academic partnerships in improving cancer care delivery for SGD AYA cancer survivors.

Prognostic and functional importance of both overt and subclinical left ventricular systolic dysfunction in systemic sclerosis.

OBJECTIVES: To quantify the frequency and clinical implications of systemic sclerosis (SSc)-associated left ventricular function (LV) impairment. METHODS: Australian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 echocardiographic LVEF measurement were included. Overt LV dysfunction was indicated by reduced LV ejection fraction (LVEF) and subclinical LV dysfunction was measured using impaired LV global longitudinal strain (LV-GLS>-16 %). Those with secondary causes of LV dysfunction (myocardial ischaemia, valvulopathy and pulmonary arterial hypertension) were excluded. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Generalised estimating equations(GEE) were used to model longitudinal data. Kaplan-Meier and Cox proportional hazard models were used for survival analyses. RESULTS: Of 1141 participants with no co-morbid cardiac disease, 2.4 % ever recorded a LVEF<50 %, while only 0.6 % ever recorded a LVEF≤40 %. LV-GLS data were available for 90 % of participants at one centre (n = 218). Impaired LV-GLS was detected in 21 % despite LVEF≥50 %. Those with a LVEF<50 % were more frequently male (p = 0.01) with dcSSc (p < 0.01), higher inflammatory markers (p < 0.02) and skeletal muscle disease (p < 0.05). In multivariable analyses, recording a LVEF<50 % was associated with increased mortality (HR2.3, 95 %CI1.0-4.8, p = 0.04). Impaired LV-GLS was also associated with poorer survival in univariable analyses (HR3.4, 95 %CI1.0-11.8, p = 0.05). Those with a LVEF<50 % more frequently recorded WHO Class III/IV dyspnoea (OR3.5, 95 %CI1.6-7.7, p < 0.01), with shorter six-minute walk distance (p = 0.01), higher Health Assessment Questionnaire-Disability Index scores (p < 0.01) and lower Short Form-36 Physical Component Summary scores (p = 0.02). Increased dyspnoea (WHO Class III/IV dyspnoea; OR3.6, 95 %CI1.4-9.2, p < 0.01) was also seen in those with impaired LV-GLS. CONCLUSIONS: Both overt and subclinical SSc-associated LV dysfunction are associated with worse survival and impaired physical function. The frequency of abnormal LV-GLS in those with consistently normal LVEF suggests an under-appreciated burden of subtle LV systolic dysfunction in SSc that has a significant impact on patient symptomatology.

Evaluation of the HEAL™ing Mental Health program: A prospective cohort study of short-term changes from a physical activity and lifestyle education program for people with mental health disorders living in rural Australia.

This study aimed to evaluate short-term outcomes of the HEAL™ing Mental Health program, an 8-week intervention for change in functional, behavioural and physiological health and wellbeing designed for people living with mental health conditions in rural or regional areas of Australia. A prospective cohort study was completed, reporting on 19 items (pre-program) and 15 (post-participation change), organised across seven domains. Participants took part in an Accredited Exercise Physiologist/Nurse led supervised group exercise (60 minutes) and healthy lifestyle education program (60 minutes). Separate linear mixed models with restricted maximum likelihood were used to examine the primary research question considering the effect of the program on: walking (min/week); planned, incidental and total physical activity (min/week); sitting time; active days; fruit and vegetable intake; body mass index; waist circumference; blood pressure; 6 minute walk distance; 30 second sit-to-stand; psychological distress symptoms; and stage of behaviour change. There were 99 participants (31 males, 68 females) out of 117 participants completed more than 50% of program sessions. Twelve of 15 measures achieved their desired target change and a statistically significant change toward the desired outcome was reported for 14 of 15 measures. Positive results were obtained for participants completing more than 50% of sessions, suggesting that HEAL™ ing Mental Health program is effective to increase physical activity and healthy lifestyle choices in individuals who self-report a mental health disorder.

Conditioned preferences: Gated by experience, context, and endocrine systems.

Central to the navigation of an ever-changing environment is the ability to form positive associations with places and conspecifics. The functions of location and social conditioned preferences are often studied independently, limiting our understanding of their interplay. Furthermore, a de-emphasis on natural functions of conditioned preferences has led to neurobiological interpretations separated from ecological context. By adopting a naturalistic and ethological perspective, we uncover complexities underlying the expression of conditioned preferences. Development of conditioned preferences is a combination of motivation, reward, associative learning, and context, including for social and spatial environments. Both social- and location-dependent reward-responsive behaviors and their conditioning rely on internal state-gating mechanisms that include neuroendocrine and hormone systems such as opioids, dopamine, testosterone, estradiol, and oxytocin. Such reinforced behavior emerges from mechanisms integrating past experience and current social and environmental conditions. Moreover, social context, environmental stimuli, and internal state gate and modulate motivation and learning via associative reward, shaping the conditioning process. We highlight research incorporating these concepts, focusing on the integration of social neuroendocrine mechanisms and behavioral conditioning. We explore three paradigms: 1) conditioned place preference, 2) conditioned social preference, and 3) social conditioned place preference. We highlight nonclassical species to emphasize the naturalistic applications of these conditioned preferences. To fully appreciate the complex integration of spatial and social information, future research must identify neural networks where endocrine systems exert influence on such behaviors. Such research promises to provide valuable insights into conditioned preferences within a broader naturalistic context.