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Published solubility data for 4,5-dihydroxyanthraquinone-2-carboxylic acid dissolved in several organic solvents of varying polarity and hydrogen-bonding character are used to calculate the Abraham model solute descriptors. Calculated descriptor values suggest that 4,5-dihydroxyanthraquinone-2-carboxylic acid engages in intramolecular hydrogen formation between the two phenolic hydrogens and the proton acceptor sites (the lone electron pairs) on the neighboring quinone oxygen atom. Our study further shows that existing group contribution and machine learning methods provide rather poor estimates of the experimental-based solute descriptors of 4,5-dihydroxyanthraquinone-2-carboxylic acid, in part because the estimation methods to not account for the likely intramolecular hydrogen-bonds. The predictive aspect of the Abraham model is illustrated by predicting the solubility of 4,5-dihydroxyanthraquinone-2-carboxylic acid in 28 additional organic mono-solvents for which experimental data does not exist.

Abraham model L solute descriptors have been determined for 149 additional C11 to C42 monomethylated and polymethylated alkanes based on published Kovat’s retention indices based upon gas–liquid chromatographic measurements. The calculated solute descriptors, in combination with previously published Abraham model correlations, can be used to predict a number of very important chemical and thermodynamic properties including partition coefficients, molar solubility ratios, gas–liquid chromatographic and HPLC retention data, infinite dilution activity coefficients, molar enthalpies of solvation, standard molar vaporization and sublimation at 298 K, vapor pressures, and limiting diffusion coefficients. The predictive computations are illustrated by estimating both the standard molar enthalpies of sublimation and the enthalpies of solvation in benzene for the monomethylated and polymethylated alkanes considered in the current study.

Job burnout is related to both environmental and genetic factors. However, previous studies on job burnout in teachers have mainly focused on potential stressors in the environment, while ignoring genetic factors. Brain-derived neurotrophic factor (BNDF) may be a pathogenic factor involved in burnout symptoms. Therefore, this study further investigated the relationship between the BNDF gene polymorphism, job stress and job burnout in Chinese university teachers.Using a cross-sectional design, 361 faculty and staff members from a university in Beijing were enrolled. Job stress was measured with the Work Stress Scale. Job burnout was measured by the Chinese version of the Maslach Burnout Inventory which has three dimensions, namely emotional exhaustion (EE), cynicism (CY), and reduced personal accomplishment (PA). The BDNF gene rs16917237 polymorphism was genotyped in all participants.CY score was associated with education level (p 0.01), and PA score was associated with age (p 0.05). Job stress was positively correlated with EE (r = 0.776), CY (r = 0.457), and PA (r = 0.163) (all p 0.01). After controlling for gender, age and education level, the BDNF gene rs16917237 polymorphism did not affect job burnout, but it interacted with job stress to influence EE and CY (both p 0.05), indicating that individuals with TT genotype were more susceptible to higher levels of job stress, resulting in job burnout symptoms.Our results suggest that the BDNF gene rs16917237 TT genotype may be a risk factor for job burnout in Chinese university teachers.

Intratumoral heterogeneity (ITH) can promote cancer progression and treatment failure, but the complexity of the regulatory programs and contextual factors involved complicates its study. To understand the specific contribution of ITH to immune checkpoint blockade (ICB) response, we generated single cell-derived clonal sublines from an ICB-sensitive and genetically and phenotypically heterogeneous mouse melanoma model, M4. Genomic and single cell transcriptomic analyses uncovered the diversity of the sublines and evidenced their plasticity. Moreover, a wide range of tumor growth kinetics were observedin vivo, in part associated with mutational profiles and dependent on T cell-response. Further inquiry into melanoma differentiation states and tumor microenvironment (TME) subtypes of untreated tumors from the clonal sublines demonstrated correlations between highly inflamed and differentiated phenotypes with the response to anti-CTLA-4 treatment. Our results demonstrate that M4 sublines generate intratumoral heterogeneity at both levels of intrinsic differentiation status and extrinsic TME profiles, thereby impacting tumor evolution during therapeutic treatment. These clonal sublines proved to be a valuable resource to study the complex determinants of response to ICB, and specifically the role of melanoma plasticity in immune evasion mechanisms.

Across cancers, tumor cells can resemble embryonic cell states that may allow them to metastasize and evade therapies. Melanoma is a cancer of the melanocyte that exhibits a wide range of transcriptional states characterized by alterations in embryonic melanocyte gene expression patterns. How these states and their functions are related to the embryonic precursors of melanocytes, the melanoblasts, is unknown. Here, we present the first high-resolution single-cell RNA-seq profiles of embryonic melanocytic lineages in mice. We discover a diverse array of transcriptional cell states in this lineage and confirm, for the first time at the single-cell level, that melanocytes arise from Schwann-cell precursors (SCPs), a highly plastic cell population, via a newly described intermediate mesenchymal-like state. Via novel computational strategies to map these developmental cell states to metastatic melanoma, we find that SCP-resembling tumors are associated with exclusion of the immune cells and non-response to immune checkpoint blockade. In contrast, a higher mesenchymal profile underlies immune dysfunction and resistance to BRAF-inhibition therapy. We also carry out the first time-resolved single-cell RNA-seq study of early melanoma metastatic colonization, demonstrating that melanoma cells activate a SCP program transiently during early metastatic colonization. Finally, we discover a hybrid lineage state that resembles multiple melanocytic lineages simultaneously and is enriched in melanoma cells during metastatic seeding and in therapy resistance. Our work reveals that the lineage-specific mechanisms underlie melanoma progression/evolution, including early metastatic colonization and therapeutic resistance.

Food waste has become a significant issue in the foodservice industry. However, food waste management in buffet restaurants has rarely been investigated. Considering the popularity of buffet restaurants in Taiwan, this study serves as the first attempt to identify a corporate management approach to food waste reduction in Taiwanese buffet restaurants. The study case comprises two buffet restaurants of a large chain restaurant company in Taiwan. This study uses both individual in-depth interviews and a focus group, comprising 15 managers, chefs, and front-line employees. The results identify various strategies to mitigate food waste in buffet restaurants at different stages of operation: establishing a central kitchen, cooperating with qualified suppliers, accurate forecasting of food demand, aesthetic buffet table design, redesigning the service method, continually monitoring food waste, and proactive communication to customers. The 3R (Reduce–Reuse–Recycle) food waste hierarchy is also developed to encourage buffet restaurant practitioners to design appropriate food waste mitigation programs.

Experimental solubilities were determined for 31 solid nonelectrolyte organic compounds dissolved in tert-butyl acetate at 298.15 K. Results of the experimental measurements were combined with published mole fraction solubility data for two lipid-lowering medicinal compounds (lovastatin and simvastatin) in order to derive Abraham model expressions for solute transfer into the tert-butyl acetate mono-solvent. The derived correlations provided an accurate mathematical description of the observed experimental data. As part of the current study, previously published Abraham model solvent correlations for both ethyl acetate and butyl acetate were updated using much larger datasets that contained an additional 64 and 35 experimental data points, respectively. The mathematical correlations presented in the current study describe the observed solubility ratios of solutes dissolved in tert-butyl acetate, ethyl acetate, and butyl acetate to within an overall standard deviation of 0.15 log units or less.

Background In recent years, the rates of suicide among young people have been increasing, and major depressive disorder (MDD) is regarded to be its main cause. Many factors such as thyroid dysfunction and metabolic abnormalities are thought to mediate this process, but the conclusions are inconsistent. This study investigated the rate of suicide attempts and associated risk factors among young, first-episode and drug-naïve Chinese Han patients with MDD. Methods A total of 917 patients with MDD (aged 18 ~ 35 years) were recruited. Demographic and clinical data were collected and thyroid function, fasting blood glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), positive symptom subscale of Positive and Negative Syndrome Scale (PANSS) and clinical global impression of severity scale (CGI-S) were adopted to assess depression, anxiety, psychotic symptoms and disease severity respectively. Results The rate of suicide attempts was 19.5% in young MDD patients. There were significant differences in age (p = 0.003), education level (p = 0.001), age of onset (p = 0.004) and disease duration (p = 0.001) between patients with and without suicide attempts. Compared with patients without suicide attempts, patients with suicide attempts had significantly higher scores on the HAMD-17, HAMA, PANSS positive symptom subscale and CGI-S (all p p p = 0.004), TPOAb (p p = 0.016), TC (p p p p p = 0.515), disease duration (OR = 1.100, 95%CI: 1.013–1.194, p = 0.024), HAMA score (OR = 1.313, 95%CI: 1.205–1.430, p p p = 0.025), TPOAb (OR = 1.004, 95%CI: 1.002–1.006, p p = 0.042) and LDL (OR = 0.736, 95%CI: 0.558–0.971, p = 0.030) were all independently associated with suicide attempts in young MDD patients. Conclusions In China, the rate of suicide attempts in young patients with MDD is quite high and thyroid dysfunction and metabolic abnormalities may be implicated in its pathogenesis.

BackgroundsSubclinical hypothyroidism (SCH) was reported to be associated with depression; however, its role in coexisting anxiety symptom in young patients with major depressive disorder (MDD) remains unclear. The objective of this study was to explore the relationship between SCH and anxiety symptom in young first-episode and drug-naïve (FEDN) MDD patients.MethodsA total of 520 outpatients diagnosed as FEDN MDD with SCH were recruited in this study. Their socio-demographic, clinical data and thyroid function parameters were collected. The Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD) were employed to measure the severity of anxiety symptom and depressive symptom, respectively. Based on the HAMA scores, patients who scored ≥ 25 were defined as anxious major depressive disorder (A-MDD) while others as non-anxious major depressive disorder (NA-MDD).ResultsThe prevalence rate of A-MDD was 15.8% in young FEDN MDD patients with comorbid SCH. Moreover, serum thyroid stimulating hormone (TSH) levels were significantly higher in patients with A-MDD compared with those with NA-MDD (p < 0.001). Multivariate binary logistic regression analysis indicated that A-MDD was associated with serum TSH levels with an odds ratio (OR) of 1.602. Serum TSH level of 6.17 mIU/L was the critical value to distinguish A-MDD and NA-MDD, with sensitivity of 0.805 and specificity of 0.539. There were no statistically significant differences between NA-MDD and A-MDD patients in terms of socio-demographic variables, serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidases antibody (TPOAb) and anti-thyroglobulin (TgAb) levels.ConclusionsA-MDD patients presented higher serum TSH level. It is suggested that serum TSH level may be a potential biomarker for predicting moderate and severe anxiety symptoms in young FEDN MDD patients with SCH.

The oxytocin receptors located in the corticotropin-releasing factor neurons of the paraventricular nucleus are stimulated by oxytocin. Oxytocin functions as the regulator of the corticotropin-releasing factor system and in turn promotes sleep quality. The objective of this study was to examine the main and genotype-genotype interactive effects of the oxytocin receptor gene (OXTR) polymorphisms on sleep quality. A total of 324 participants were randomly recruited from a university in Beijing, China. Sleep quality was measured with the Pittsburgh Sleep Quality Index. The OXTR single-nucleotide polymorphisms (rs2254298, rs2268498, rs13316193, rs2268490 and rs2268491) were genotyped. The results showed that gender and age were associated with various empathy traits (all p 0.001). The Pittsburgh Sleep Quality Index was positively correlated with the Personal Distress subscale of empathy (p 0.001). Both rs2254298 and rs2268491 interacted with rs13316193 to influence daytime dysfunction and Personal Distress (all p 0.05), indicating that in individuals with rs13316193 CC/CT genotype, those with rs2254298 AA/AG or rs2268491 TT/TC genotypes displayed higher daytime dysfunction and Personal Distress scores than those with rs2254298 GG or rs2268491 CC genotypes. Conversely, among the individuals with rs2254298 GG or rs2268491 CC genotypes, the rs13316193 C allele carriers had lower daytime dysfunction and Personal Distress scores than rs13316193 TT homozygotes. There was also a significant interaction between rs2268490 and rs2268498 on the sleep latency dimension of the Pittsburgh Sleep Quality Index. Our findings reveal for the first time the genotype-genotype interactions of the OXTR gene on sleep quality, which may open new research avenues for studying psychopathology involving sleep problems.

Background: Medical education has a long history of using structured oral examinations (SOE) to evaluate trainee aptitude for high-order processing. However, the SOE has received substantial criticism in recent years regarding limited reliability, possibility of bias and high cost. Methods: In this randomized control trial, 214 third year medical students rotating through the OB/GYN clerkship were divided into two groups, those who took the SOE (n=112) and those who did not (n=102). The mean scores of two required clerkship examinations, the Observed Standardized Clinical Examination (OSCE) and the National Board of Medical Examiners (NBME) subject exam, were compared between the SOE and the non-SOE groups.Results: We found no difference between group mean NMBE scores (SOE group: 75.6%, SD: 7.951 | non-SOE group: 73.9%, SD: 8.302 | p = 0.698) and actually found that those who did not participate in the SOE out-performed those who did in the OSCE (SOE group: 72.8%, SD: 4.978 | non-SOE group: 76.3%, SD: 5.331| p = 0.002). Discussion: Our results suggest that the implementation of the SOE in clerkship curriculum does not correlate with improved medical student performance or success.

The ability to behave in ways that benefit other individuals' well-being is among the most celebrated human characteristics crucial for social cohesiveness. Across mammalian species, animals display various forms of prosocial behaviors - comforting, helping, and resource sharing - to support others' emotions, goals, and/or material needs. In this review, we provide a cross-species view of the behavioral manifestations, proximate and ultimate drives, and neural mechanisms of prosocial behaviors. We summarize key findings from recent studies in humans and rodents that have shed light on the neural mechanisms underlying different processes essential for prosocial interactions, from perception and empathic sharing of others' states to prosocial decisions and actions.

The outbreak of the 2019 coronavirus disease (COVID-19) has significant effects on stress, emotion and sleep in the general public. The aim of this study was to explore the relationship between perceived stress and emotional symptoms during the first wave of the COVID-19 pandemic in China and to further determine whether insomnia could serve as a mediator in this relationship. A total of 1178 ordinary citizens living in mainland China conducted anonymous online surveys. The 10-item Perceived Stress Scale, the Insomnia Severity Index, the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder scale were used to estimate perceived stress, insomnia, depression and anxiety symptoms, respectively. Of the 1171 valid respondents from 132 cities in China, 46.6 % and 33.0 % showed symptoms of depression and anxiety, respectively. Perceived stress and insomnia independently predicted the prevalence of emotional symptoms and were positively correlated with the severity of these emotional symptoms. The mediation analyses further revealed a partial mediation effect of insomnia on the relationship between perceived stress and emotional symptoms during the first wave of the COVID-19 outbreak in China. Our findings can be used to formulate early psychological interventions to improve the mental health of vulnerable groups, specifically those with insomnia, during the COVID-19 pandemic.

Brain metastases (BrM) remain an intractable, deadly complication for advanced melanoma patients and efficient therapeutic strategies are desperately needed. The tumor microenvironment (TME) plays an important role in response to therapy. However, studies addressing the contribution of the TME to therapy efficacy for BrM are lacking, mostly due to limited access to human samples and scarcity of appropriate preclinical models. Here, we describe two novel isogenic immunocompetent BrM models generated by intracardiac injection of UV-induced mouse melanoma cell lines, representative of mutant-RAS human melanoma subtypes. We used these models to test immune checkpoint blockade (ICB) therapy and to interrogate the role of the TME in therapeutic efficacy. To evaluate response, we developed and applied a new machine-learning method to quantify metastatic burden. We investigated the TME by high-parametric flow cytometry and single-cell RNA sequencing (scRNA-seq). We showed that the models have distinct metastatic behaviors, with BR1 being mostly brain tropic and BR3 displaying widespread metastases. Notably, BR1 BrM were sensitive to ICB with a better response to anti-PD-L1/anti-CTLA-4 combination therapy as compared to monotherapies. In contrast, BR3 BrM were resistant to both mono- and combination therapies. Interestingly, we found that ICB efficacy on extracranial BR3 metastases is organ-dependent. Characterization of the BrM immune microenvironment before and after treatment revealed dramatic differences between the models. Untreated BR1 BrM showed significant recruitment of T cells, dendritic cells, and natural killer cells, while neutrophils were enriched in untreated ICB-resistant BR3 BrM. Moreover, we uncovered phenotypically distinct microglia populations exclusively present in ICB-sensitive BR1 BrM that positively correlated with T cell infiltration. Consistent with this finding, scRNA-seq showed upregulation of genes encoding for T cell-attracting chemokines and antigen presentation uniquely in the BR1-associated microglia. Post-treatment analysis of the brain TME highlighted beneficial changes induced by ICB in the responsive BR1 model, including increased recruitment of CD8 T cells with an activated phenotype, while a mild recruitment of exhausted T cells was observed in the resistant BR3 model. Altogether, our data emphasize the importance of interrogating the BrM TME to understand therapeutic response. Our unique BrM models, mirroring the diversity of ICB response observed in patients, provide a robust platform for the much-needed mechanistic studies to optimize BrM therapy. Deciphering the contribution of the newly identified BR1 BrM-associated microglia to ICB efficacy will be crucial to the identification of novel therapeutic targets. Citation Format: Amélie Lopès, Jessica Rappaport, Eva Pérez Guijarro, Quanyi Chen, Emily Wu, Isabella Church, April Huang, Jessica Bridge, Sung Chin, Cari Smith, Charli Gruen, Khiem C. Lam, Romina E. Araya, Antonella Sassano, Chi-Ping Day, Glenn Merlino, Romina S. Goldszmid. Interrogating the role of the immune microenvironment in the response of brain metastases to immunotherapy using new preclinical melanoma models. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5188.

Treatment-resistant schizophrenia (TRS) is a prevalent clinical problem with heterogeneous presentations. However, the clinical trial designs for new treatments are still lacking. This study aimed to assess the efficacy of ziprasidone plus sertraline in TRS patients as compared to ziprasidone monotherapy. We conducted a 24 weeks, randomized, controlled, double-blinded clinical research trial. 62 treatment-resistant patients with acute exacerbation SZ were randomly allocated to receive a usual dose of ziprasidone (120–160 mg/d) monotherapy (Control group) and 53 TRS inpatients were to receive a low dose of ziprasidone (60–80 mg/d) in combination with sertraline (ZS group). Treatment outcomes were measured by the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Rating Scale (HAMD), CGI-Severity (CGI-S) and Personal and Social Performance Scale (PSP) at baseline, week 4, 8, 12, and 24. Relative to control group, the patients in ZS group showed greater reductions in the following: PANSS positive symptom, negative symptom, total score, and HAMD total score. Additionally, the patients in ZS group had a greater increase in PSP total score. Notably, the reduction in HAMD was positively correlated with the reduction in PANSS total score. The reduction in CGI-S was a predictor for the improvement of psychosocial functioning in patients. Furthermore, the ZS group had a lower rate of side effects compared to the control group. Our findings suggest that a low dose of ziprasidone in combination with sertraline is an effective therapy for the clinical symptoms as compared to a usual dose of ziprasidone in the treatment-resistant patients with acute exacerbation SZ.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT04076371.

Objectives With the COVID-19 pandemic, psychiatry residencies (academic, community, and hybrid) have adopted different learning modalities to preserve a high quality of educational training. There is minimal data on specific program adaptations, related change perspectives, and program type stratification. This study aims to analyze trends in curriculum changes in accredited psychiatry residency programs in the United States. Methods Program directors of accredited general psychiatry programs in the United States were surveyed to assess both general program details and changes in educational content, delivery, and perspectives of their respective program curricula. Data was analyzed with SPSS with 0.05 significance level. Results A total of 63 program directors of 264 eligible programs were included (23.9%). We observed a dramatic shift to integrate virtual learning post-pandemic (98.5%) compared to pre-pandemic (3%). However, there was no association between these modality changes and program type [ P = 0.1343]. Furthermore, changes were noted in respect to didactic content (60%), decreased rotation sites (38%), and increased telemedicine exposure (84%) with no change of wellness days (67%) or protected time (97%) and above changes had no association with program type. Interestingly, we found the use of virtual educational platforms was described as positive (59.7%) with 9 programs noting a future transition to a hybrid learning model for didactics and grand rounds. Conclusions The findings suggest that pandemic-related curriculum adaptations infiltrated all different types of psychiatry residencies and suggest a national trend to continue virtual platform integration into psychiatry didactics. However, future investigation of virtual learning outcomes are warranted.

Background Population-based studies to examine cervical cancer screening and prevention among sexual and gender diverse (SGD) individuals have been limited. We conducted a state-wide survey in New Mexico (NM) to examine differences in cervical cancer screening and HPV vaccination uptake based on gender and sexual orientation. Methods The survey was advertised using mailed flyers, social media, and targeted internet ads across the state. We received a total of 2534 responses, of which 797 respondents were cervical cancer screening eligible (i.e., between 21-65 years old, had a cervix, and did not have a prior cervical cancer diagnosis) and provided information about cervical cancer screening and were included in this analysis. Descriptive statistics were conducted using SAS 9.4. Results Of the 797 respondents, 83% were 21 - 40 years old, 44% were white, 34% reported an annual household income below $50,000, 83% were employed, 81% had health insurance, and 73% reported having a primary care provider. Fourteen percent were transgender men or nonbinary, 86% were cisgender women, 34% were bisexual, 48% were lesbian, and 18% were queer. While there were no statistical differences in self-reported cervical cancer screening based on gender identity, 31% of cisgender women and 25% of transgender men and nonbinary individuals reported never receiving a Pap test. The top reason for never receiving a Pap test among cisgender women was that their healthcare provider told them they did not need it (17%) and for transgender men and nonbinary individuals the top reasons were that they had an HPV vaccine (21%) or that it was too painful, unpleasant, or embarrassing (21%). There were significant statistical differences based on sexual orientation for receiving a Pap test (p Citation Format: Prajakta Adsul, Deborah Kanda, Emily Wu, Molly McClain, Vernon Shane Pankratz, Shiraz Mishra, Bernard Tawfik, Uma Nair, Tamara Stimatze, Purnima Madhivanan, Miria Kano. Examining differences based on gender and sexual orientation for cervical cancer screening and prevention behaviors [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A097.

The five-year survival rate of pancreatic ductal adenocarcinoma (PDAC) is currently 11% [CP1] and by 2030 PDAC is expected to become the second leading cause of cancer related death. Understanding PDAC initiation and maintenance is important for the advancement of treatment. Mouse models allow us to study the mechanisms of PDAC initiation and progression. The most common genetically engineered mouse model (GEMM) of PDAC utilizes a knock-in of Cre recombinase [FB2] into the pancreatic transcription factor 1a (Ptf1a)locus to drive pancreas specific oncogenic KRAS expression. Alternative GEMMs express Cre recombinase from the Mist1/Bhlha15 locus (Mist1-CreER) or from elastase enzyme promoter-driven constructs (Ela-CreER). How these models differ in their ability to promote neoplasia is unknown. We hypothesized that differences in GEMMs may provide insight into mechanisms of PDAC initiation and progression. Here, we compare the tamoxifen-inducible Ptf1a-CreER, [FB3] Mist1-CreER and Ela-CreER models in their response to oncogenic KRAS expression. KRASG12D was induced with tamoxifen gavage 6-8 weeks postpartum and caerulein was used to induce pancreatitis. Histological analyses (H&E and IHC for amylase, cytokeratin 19, Fos and Jun) were performed on fixed tissue to assess associated phenotypic changes. Tissues from Ptf1a-CreER, Mist1-CreER and Ela-CreER mice were harvested 3 weeks after tamoxifen administration and processed for RNA sequencing. Phenotypically, in the presence of oncogenic KRAS and after pancreatitis induction, Ptf1a-CreER pancreata exhibited extensive tissue remodeling - acinar to ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN) - with a dense fibroinflammatory response in contrast to both Mist1-CreER and Ela-CreER pancreata. Mist1-CreER and Ela-CreER pancreata had much more variable penetrance with tissues often showing little to no ADM and PanINs despite oncogenic KRAS expression and prior pancreatitis. At the gene expression level, Mist1-CreER pancreata showed fewer differentially expressed genes when compared to wild type tissue than Ptf1a-CreER under the same conditions. In total, less than 70 differentially expressed genes were common between the two models. Members of the AP-1 transcriptional complex (fos and c-jun) previously implicated in neoplastic progression were specifically increased only in Ptf1a-CreER mice.[FB4] Taken together, our histological, and transcriptional data indicates mice lacking one copy of Ptf1a (Ptf1a-CreER) undergo more dramatic histological changes after pancreatitis injury and oncogenic KRAS induction when compared to the GEMMs with both copies of Ptf1a intact. Additionally, mice in the Ptf1a-CreER group show a more marked molecular response to oncogenic KRAS induction, suggesting the absence of a single copy of the acinar fate transcription factor Ptf1a disrupted pancreatic homeostasis and poised it for transformation. Further comparison of PDAC GEMMs will yield clearer insight into mechanisms of PDAC initiation and progression. Citation Format: Joyce K. Thompson, Fatemeh Mousavi, Justine Lau, Emily Wu, Christopher Pin, Filip Bednar. Comparison of pancreatic cancer mouse models identifies potential drivers of tumor initiation and progression [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A070.

5533 Background: Population-based studies to examine cervical cancer screening (CCS) and prevention among sexual and gender diverse (SGD) individuals have been limited. We conducted a state-wide survey in New Mexico to examine differences in CCS and HPV vaccination uptake based on gender and sexual orientation. Methods: The survey was advertised using mailed flyers, social media, and targeted internet ads across the state. We received a total of 2534 responses, of which 797 respondents were CCS eligible (i.e., between 21-65 years old, had a cervix, and did not have a prior cervical cancer diagnosis) and provided information about CCS and were included in this analysis. Descriptive statistics were conducted using SAS 9.4. Results: Of the 797 respondents, 83% were 21 - 40 years old, 44% were white, 34% reported an annual household income below $50,000, 83% were employed, 81% had health insurance, and 73% reported having a primary care provider. Fourteen percent were transgender men or nonbinary, 86% were cisgender women, 34% were bisexual, 48% were lesbian, and 18% were queer. While there were no statistical differences in self-reported CCS based on gender identity, 31% of cisgender women and 25% of transgender men and nonbinary individuals reported never receiving a Pap test. The top reason for never receiving a Pap test among cisgender women was that their healthcare provider told them they did not need it (17%) and for transgender men and nonbinary individuals the top reasons were that they had an HPV vaccine (21%) or that it was too painful, unpleasant, or embarrassing (21%). There were significant statistical differences based on sexual orientation for receiving a Pap test (p < 0.001) and for being up to date on screening (Pap test in the past 3 years, a co-test, or primary HPV test in the past 5 years) (p = 0.03). Among lesbians, 39% reported never having a Pap test, compared with 17% of bisexuals and 30% of queer individuals. For lesbians, the top reason for not receiving a Pap test was not knowing that Pap tests existed (19%), while the top reason for both bisexual and queer individuals was that their healthcare provider told them they did not need it (17% and 19%, respectively). No significant differences were noted in HPV vaccination uptake among respondents. Conclusions: In order to address sexual orientation differences noted in our study, future research is needed to explore mechanisms through which these differences operate using community-based approaches. Additionally, educational interventions inclusive of different gender identities and sexual orientations are needed to improve motivations for screening uptake among SGD individuals. Finally, specific considerations for SGD individuals should be incorporated into screening recommendations and guidelines and clearly communicated to providers, further enabling them to make recommendations for these populations.