Historical and contemporary processes driving the origin and structure of an admixed population within a contact zone between subspecies of a north temperate diadromous fish.

Hybridization between divergent lineages can result in losses of distinct evolutionary taxa. Alternatively, hybridization can lead to increased genetic variability that may fuel local adaptation and the generation of novel traits and/or taxa. Here, we examined single-nucleotide polymorphisms generated using genotyping-by-sequencing in a population of Dolly Varden char (Pisces: Salmonidae) that is highly admixed within a contact zone between two subspecies (Salvelinus malma malma, Northern Dolly Varden [NDV] and S. m. lordi, Southern Dolly Varden [SDV]) in southwestern Alaska to assess the spatial distribution of hybrids and to test hypotheses on the origin of the admixed population. Ancestry analysis revealed that this admixed population is composed of advanced generation hybrids between NDV and SDV or advanced backcrosses to SDV; no F1 hybrids were detected. Coalescent-based demographic modelling supported the origin of this population about 55,000 years ago by secondary contact between NDV and SDV with low levels of contemporary gene flow. Ancestry in NDV and SDV varies within the watershed and ancestry in NDV was positively associated with distance upstream from the sea, contingent on habitat-type sampled, and negatively associated with the number of migrations that individual fish made to the sea. Our results suggest that divergence between subspecies over hundreds of thousands of years may not be associated with significant reproductive isolation, but that elevated diversity owing to hybridization may have contributed to adaptive divergence in habitat use and life history.

High grade adverse event reporting and enrolment in gynecologic oncology clinical trials.

OBJECTIVE: The primary objective is to assess factors associated with treatment related high grade (CTCAE grade ≥ 3) adverse event (AE) reporting among participants in gynecologic oncology clinical trials. METHODS: All AEs recorded in the Princess Margaret Clinical Trial adverse event database between 01/2016 and 12/2018 were evaluated. Gynecologic oncology clinical trials assessing systemic therapy were included. Inferential statistics on risk factors of related grade ≥ 3 adverse event reporting and GEE logistic models with Odds Ratios (OR) were performed. Multivariable analysis adjusting for age, clinical trial phase, sponsor, and therapy type. RESULTS: The gynecology cancer clinical trials accrued 317 unique patients (359 nested on trials) in 42 systemic therapy trials. In the period, 17,175 related AEs were reported in the gynecological cancer trials, 7.4% were grade ≥ 3. On multivariable analysis, no odds differences of grade ≥ 3 related AEs were detected according to study phase. Patients in immunotherapy clinical trials had lower odds of related grade ≥ 3 AEs than patients on targeted or other therapy (adjusted OR [aOR] 0.43; 95% CI 0.24-0.75). There was greater odds of related grade ≥ 3 AEs in clinical trials assessing combination vs single therapeutics (aOR 2.26, 95% CI 1.34-3.80). Patients aged ≥65 (aOR 1.77; 95% CI 1.08-2.89) had greater odds of related grade ≥ 3 AEs than patients aged 50 to 65 years. When compared to other disease sites, the odds of having a grade  ≥ 3 related AE reported in gynecology clinical trials was no different. CONCLUSIONS: In this cohort, factors influencing the odds of related grade ≥ 3 AE reporting in gynecologic trials included type of therapy and age. The study phase did not correlate with odds of high-grade AE reporting.

Impact of visit characteristics on intention to recommend HPV vaccine: An experiment with US health care professionals.

OBJECTIVE: Presumptive recommendations that assume parents want to vaccinate can increase human papillomavirus (HPV) vaccine uptake. We sought to examine how visit characteristics affect health care professionals' (HCPs) intention to use this evidence-based recommendation style. METHODS: In 2022, we conducted an online experiment with 2527 HCPs who had a role in adolescent vaccination in the United States. Participants read 1 of 8 randomly assigned vignettes about a well-child visit. Using a 2 × 2 × 2 between-subjects factorial design, the vignettes varied the following visit characteristics: patient age (9 vs. 12-year-old), prior parental vaccine refusal (yes vs. no), and time pressure on the HCP (low vs. high). HCPs reported on their intention to use a presumptive HPV vaccine recommendation, as well as on related attitudes, subjective norms, and self-efficacy. Analyses used 3-way analysis of variance and parallel mediation. RESULTS: Participants were pediatricians (26%), family/general medicine physicians (22%), advanced practitioners (24%), and nursing staff (28%). Overall, about two-thirds of HCPs (64%) intended to use a presumptive recommendation. Intentions were higher for older children (b = 0.23) and parents without prior vaccine refusal (b = 0.39, both p < 0.001). Time pressure had no main effect or interactions. HCPs' attitudes and self-efficacy partially mediated effects of patient age and prior vaccine refusal (range of b = 0.04-0.28, all p < 0.05). CONCLUSION: To better support visits with younger children and parents who have refused vaccines, HCPs may need more training for making presumptive recommendations for HPV vaccine. Reinforcing positive attitudes and self-efficacy can help HCPs adopt this evidence-based recommendation style.

Machine learning in the evaluation of voice and swallowing in the head and neck cancer patient.

PURPOSE OF REVIEW: The purpose of this review is to present recent advances and limitations in machine learning applied to the evaluation of speech, voice, and swallowing in head and neck cancer. RECENT FINDINGS: Novel machine learning models incorporating diverse data modalities with improved discriminatory capabilities have been developed for predicting toxicities following head and neck cancer therapy, including dysphagia, dysphonia, xerostomia, and weight loss as well as guiding treatment planning. Machine learning has been applied to the care of posttreatment voice and swallowing dysfunction by offering objective and standardized assessments and aiding innovative technologies for functional restoration. Voice and speech are also being utilized in machine learning algorithms to screen laryngeal cancer. SUMMARY: Machine learning has the potential to help optimize, assess, predict, and rehabilitate voice and swallowing function in head and neck cancer patients as well as aid in cancer screening. However, existing studies are limited by the lack of sufficient external validation and generalizability, insufficient transparency and reproducibility, and no clear superior predictive modeling strategies. Algorithms and applications will need to be trained on large multiinstitutional data sets, incorporate sociodemographic data to reduce bias, and achieve validation through clinical trials for optimal performance and utility.

Cell wall melanin impedes growth of the Cryptococcus neoformans polysaccharide capsule by sequestering calcium.

Cryptococcus neoformans has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of C. neoformans within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their non-melanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response. Significance Statement: Cryptococcus neoformans is an opportunistic fungal pathogen that presents a significant health risk for immunocompromised individuals. We report an interaction between the two major cryptococcal virulence factors, the polysaccharide capsule and melanin. Melanin impacted the growth and maintenance of the polysaccharide capsule, resulting in loss of capsular material during melanization. Our results suggest that melanin can act as a sink for calcium, thereby limiting its availability to form ionic bridges between polysaccharide chains on the growing surface of the outer capsule. As polysaccharide is continuously exported to support capsule growth, failure of melanized cells to incorporate this material results in a higher concentration of shed polysaccharide in the extracellular milieu, which is expected to interfere with host immunity.

A Systematic Review of the Psychosocial Impact of Endometriosis before and after Treatment.

While endometriosis is a common gynecologic disease associated with infertility, the psychosocial impact of endometriosis has not been evaluated against various quality of life (QoL) instruments and compared with other chronic illnesses. We rigorously analyzed the psychosocial burden of endometriosis in adult women and compared standardized and validated QoL scores of women with and without endometriosis, before and following treatment, and against other chronic illnesses. We searched PubMed, PsychINFO Embase, and Cochrane Reviews and ClinicalTrials.gov from January 1990 to December 2022 for publications using a detailed list of search terms related to QoL, endometriosis, and questionnaires. Only English-language publications that evaluated the association between Endometriosis and QoL using standardized and validated questionnaires measured at baseline and following treatment were considered. Four reviewers first performed a title and abstract screening followed by full text-review to finalize included articles. QoL scores of women with endometriosis were measured at baseline and analyzed against women without endometriosis and women with endometriosis who had undergone treatment. Additionally, baseline endometriosis scores were assessed against the published QoL scores of populations with other chronic conditions. Assessment of risk of bias was performed in accordance with Cochrane and Newcastle-Ottawa Scale guidelines. A total of 30 articles were included in this review: 4 randomized trials and 26 observational studies. The diagnosis and experience of women with symptomatic endometriosis had an equal or worse QoL score than that of other chronic conditions including heart disease, diabetes, and breast cancer when compared using the 36-Item Short Form Survey and World Health Organization Quality of Life questionnaires. Evidence showed association between low QoL and infertility, sexual dysfunction, mental health struggles, physical pain, poor sleep and fatigue. QoL scores were lower at baseline compared to following treatment in the majority of these domains. Endometriosis is associated with significant psychosocial burden and impaired QoL scores across baseline measurements in comparison to controls and other chronic illnesses. Medical and surgical interventions significantly decreased experienced burdens and improved QoL of women with endometriosis.

Neglect, online invasive exploitation, and childhood sexual abuse in Hong Kong: Breaking the links.

BACKGROUND: Childhood sexual abuse (CSA) is a form of maltreatment that involves a child in sexual activity that she or he cannot fully comprehend or is unable to give informed consent to. The empirical link between child neglect and contact child sexual abuse is well established but little research examines mediators that explain this link. OBJECTIVE: This study tests online risk behaviors and unwanted sexual experiences online as sequential mediators of the neglect - CSA relationship. PARTICIPANT AND SETTING: The study uses a representative cross-sectional sample of 1097 Hong Kong adolescents. METHODS: Preacher and Hayes' (2008) non-parametric bootstrap approach was used to test three mediation hypotheses. RESULTS: Baseline logistic regression models showed neglected children had 11.2 times higher odds of reporting contact CSA (p < .001). Similarly, neglect was associated with 3.5 times higher odds of more online risk behavior (p < .001), which in turn was associated with 2.7 times higher odds of more online invasive exploitation (p < .001). Online invasive exploitation was associated with 2.7 times higher odds of reporting offline contact CSA (p < .001). The study found online risk behaviors to be a significant mediator of the relationship between neglect and online invasive exploitation (unwanted online sexual experiences). Online invasive exploitation, in turn, mediated the relationship between online risk behaviors and offline contact CSA. CONCLUSION: The findings highlight the importance of intervening against neglect as it appears to play a vital role in the etiology of contact CSA in Hong Kong.

Coding with the machines: machine-assisted coding of rare event data.

While machine coding of data has dramatically advanced in recent years, the literature raises significant concerns about validation of LLM classification showing, for example, that reliability varies greatly by prompt and temperature tuning, across subject areas and tasks-especially in "zero-shot" applications. This paper contributes to the discussion of validation in several different ways. To test the relative performance of supervised and semi-supervised algorithms when coding political data, we compare three models' performances to each other over multiple iterations for each model and to trained expert coding of data. We also examine changes in performance resulting from prompt engineering and pre-processing of source data. To ameliorate concerns regarding LLM's pre-training on test data, we assess performance by updating an existing dataset beyond what is publicly available. Overall, we find that only GPT-4 approaches trained expert coders when coding contexts familiar to human coders and codes more consistently across contexts. We conclude by discussing some benefits and drawbacks of machine coding moving forward.

Identifying Healthcare Professionals With Lower Human Papillomavirus (HPV) Vaccine Recommendation Quality: A Systematic Review.

PURPOSE: Strengthening healthcare professionals' (HCPs) communication is an evidence-based approach to increasing human papillomavirus (HPV) vaccine uptake among adolescents. To better target future interventions, we sought to synthesize evidence on HCP subgroups who most need to improve their HPV vaccine recommendation quality. METHODS: We searched five databases for quantitative studies published from 2012 to 2022 on HPV vaccine recommendation quality, including recommendation consistency and strength, for United States adolescents. Two coders independently abstracted data from each eligible study, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We summarized variation in recommendation quality by clinical and HCP characteristics. RESULTS: The 28 eligible studies indicated that relatively low proportions of HCPs used higher-quality recommendation practices (median: 61% across 30 measures) and that recommendation quality varied across HCP subgroups. The most consistent findings were that more pediatric HCPs used higher-quality recommendations than family medicine HCPs (8 of 11 studies, 2-60 percentage point difference) and that HPV-related knowledge was associated with higher recommendation quality (four of seven studies). Most studies observed no differences in recommendation quality by clinical role (e.g., provider vs. nurse) or HCP demographics (e.g., gender, age, race/ethnicity). DISCUSSION: Studies suggest a substantial need to improve HCPs' recommendation quality, with opportunities for targeting future interventions.

Solution Synthesis of NdTe3 Magnetic Nanosheets.

Neodymium tritelluride is a layered van der Waals material, with correlated electronic properties including high electronic mobility, charge density waves, and antiferromagnetism. We developed a solution synthesis method to form free-standing nanosheets of NdTe3, with nanosheet lateral dimensions of 200-400 nm. The morphology of the nanosheet was influenced by the neodymium precursor. When Nd[(N(SiMe3)2]3 was used as the metal source the nanosheet thickness average was 12 ± 2.5 nm, alternatively the combination of NdCl3 and Li(N(SiMe3)2) led to thicker nanosheets, approximately 19 ± 2.4 nm. We believe that the difference in thickness and changes in surface chemistry point to the role of chloride in accelerating nanocrystal growth for the synthesis with NdCl3 (and Li(N(SiMe3)2). Both types of nanosheets exhibit charge density wave (CDW) distortions as measured using electron diffraction and investigated using variable temperature Raman scattering. Interestingly, the magnetic studies suggest a distinct change in properties between 12 and 19 nm thickness in antiferromagnetic NdTe3.

From struggle to strength in African and Middle Eastern newcomers' integration stories to Canada: A participatory health equity research study.

BACKGROUND AND OBJECTIVES: Newcomers (immigrants, refugees, and international students) face many personal, gender, cultural, environmental and health system barriers when integrating into a new society. These struggles can affect their health and social care, reducing access to mental health care. This study explores the lived experiences of African and Middle Eastern newcomers to Ontario, Canada. An understanding of newcomer integration challenges, successes and social justice issues is needed to improve health equity and social services. METHODS: In this qualitative study, we used a participatory research approach to collect stories reflecting participants' integration perspectives and experiences. Beginning with our immigrant community network, we used snowball sampling to recruit newcomers, ages 18 to 30, originating from Africa or the Middle East. We used qualitative narrative analysis to interpret stories, identifying context themes, integrating related barriers and facilitators, and resolutions and learnings. We shared our findings and sought final feedback from our participants. FINDINGS: A total of 18 newcomers, 78% female and approximately half post-secondary students, participated in the study. Participants described an unknown and intimidating migration context, with periods of loneliness and isolation aggravated by cold winter conditions and unfamiliar language and culture. Amidst the struggles, the support of friends and family, along with engaging in schoolwork, exploring new learning opportunities, and participating in community services, all facilitated integration and forged new resilience. CONCLUSIONS: Community building, friendships, and local services emerged as key elements for future immigrant service research. Utilizing a participatory health research approach allowed us to respond to the call for social justice-oriented research that helps to generate scientific knowledge for promoting culturally adaptive health care and access for marginalized populations.

Gastro-Esophageal Cancer: Can Radiomic Parameters from Baseline 18F-FDG-PET/CT Predict the Development of Distant Metastatic Disease?

We aimed to determine if clinical parameters and radiomics combined with sarcopenia status derived from baseline 18F-FDG-PET/CT could predict developing metastatic disease and overall survival (OS) in gastroesophageal cancer (GEC). Patients referred for primary staging who underwent 18F-FDG-PET/CT from 2008 to 2019 were evaluated retrospectively. Overall, 243 GEC patients (mean age = 64) were enrolled. Clinical, histopathology, and sarcopenia data were obtained, and primary tumor radiomics features were extracted. For classification (early-stage vs. advanced disease), the association of the studied parameters was evaluated. Various clinical and radiomics models were developed and assessed. Accuracy and area under the curve (AUC) were calculated. For OS prediction, univariable and multivariable Cox analyses were performed. The best model included PET/CT radiomics features, clinical data, and sarcopenia score (accuracy = 80%; AUC = 88%). For OS prediction, various clinical, CT, and PET features entered the multivariable analysis. Three clinical factors (advanced disease, age ≥ 70 and ECOG ≥ 2), along with one CT-derived and one PET-derived radiomics feature, retained their significance. Overall, 18F-FDG PET/CT radiomics seems to have a potential added value in identifying GEC patients with advanced disease and may enhance the performance of baseline clinical parameters. These features may also have a prognostic value for OS, improving the decision-making for GEC patients.

Late Cardiac Toxic Effects Associated With Treatment Protocols for Hodgkin Lymphoma in Children.

Importance: Contemporary North American trials for children with Hodgkin lymphoma (HL) have decreased radiation therapy (RT) use and increased pharmacologic cardioprotection but also increased the cumulative doxorubicin dose, making overall treatment consequences for late cardiac toxic effects uncertain. Objective: To estimate the risk of cardiac toxic effects associated with treatments used in modern pediatric HL clinical trials. Design, Setting, and Participants: For this cohort study, Fine and Gray models were fitted using survivors in the Childhood Cancer Survivor Study who were diagnosed with HL between January 1, 1970, and December 31, 1999, and were followed for a median of 23.5 (range, 5.0-46.3) years. These models were applied to the exposures in the study population to estimate the 30-year cumulative incidence of cardiac disease. The study population comprised patients with intermediate-risk or high-risk HL treated in 4 consecutive Children's Oncology Group clinical trials from September 2002 to October 2022: AHOD0031, AHOD0831, AHOD1331, and S1826. Data analysis was performed from April 2020 to February 2023. Exposures: All patients received chemotherapy including doxorubicin, and some patients received mediastinal RT, dexrazoxane, or mediastinal RT and dexrazoxane. Main Outcomes and Measures: Estimated 30-year cumulative incidence of grade 3 to 5 cardiac disease. Results: The study cohort comprised 2563 patients, with a median age at diagnosis of 15 (range, 1-22) years. More than half of the patients were male (1357 [52.9%]). All 2563 patients received doxorubicin, 1362 patients (53.1%) received mediastinal RT, and 307 patients (12.0%) received dexrazoxane. Radiation therapy use and the median mean heart dose among patients receiving RT decreased, whereas the planned cumulative dose of doxorubicin and use of dexrazoxane cardioprotection increased. For patients treated at age 15 years, the estimated 30-year cumulative incidence of severe or fatal cardiac disease was 9.6% (95% CI, 4.2%-16.4%) in the AHOD0031 standard treatment group (enrolled 2002-2009), 8.6% (95% CI, 3.8%-14.9%) in the AHOD0831 trial (enrolled 2009-2012), 8.2% (95% CI, 3.6%-14.3%) in the AHOD1331 trial (enrolled 2015-2019), and 6.2% (95% CI, 2.7%-10.9%) in the S1826 trial (enrolled 2019-2022), whereas the expected rate in an untreated population was 5.0% (95% CI, 2.1%-9.3%). Despite the estimated reduction in late cardiac morbidity, the frequency of recommended echocardiographic screening among survivors will increase based on current guidelines. Conclusions and Relevance: In this cohort study of sequential HL trials, reductions in the proportion of children receiving mediastinal RT and increases in dexrazoxane use were estimated to offset the increased doxorubicin dose and produce a net reduction in late cardiac disease. Further studies on dexrazoxane are warranted to confirm whether its role in reducing cardiac toxic effects is maintained long term. These findings suggest that survivorship follow-up guidelines should be refined to align with the risks associated with treatment.

Negative symptoms in treatment-resistant schizophrenia and its relationship with functioning.

BACKGROUND: Recent operational criteria for treatment-resistant schizophrenia (TRS) recognized positive and negative symptoms. TRS patients may have heterogeneity in negative symptoms, but empirical data were lacking. We aimed to characterize TRS patients based on negative symptoms using cluster analysis, and to examine between-cluster differences in social functioning. METHODS: We administered the Clinical Assessment Interview of Negative symptoms (CAINS), Brief Negative Symptom Scale (BNSS), the Positive and Negative Syndrome Scale (PANSS) and the Social and Occupational Functional Assessment (SOFAS to 126 TRS outpatients. All patients also completed the Temporal Experience of Pleasure Scale (TEPS), the Emotion Expressivity Scale (EES), and the Social Functional Scale (SFS). A two-stage hierarchical cluster analysis was performed with the CAINS, TEPS and EES as clustering variables. We validated the clusters using ANOVAs to compare group differences in the BNSS, PANSS, SOFAS and SFS. RESULTS: Clustering indices supported a 3-cluster solution. Clusters 1 (n = 46) and 3 (n = 16) exhibited higher CAINS scores than Cluster 2 (n = 64), and were negative-symptom TRS subtypes. Cluster 1 reported lower TEPS than Cluster 3; but Cluster 3 reported lower EES than Cluster 1. Upon validation, Clusters 1 and 3 exhibited higher BNSS scores than Cluster 2, but only Cluster 1 exhibited lower SOFAS and higher PANSS general symptoms than Cluster 2. Both Clusters 1 and 3 had higher self-report functioning than Cluster 2. CONCLUSION: We provided evidence for heterogeneity of negative symptoms in TRS. Negative symptoms can characterize TRS patients and predict functional outcome.