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Chronic myeloid leukemia (CML) is initiated and maintained by BCR::ABL which is clinically targeted using tyrosine kinase inhibitors (TKIs). TKIs can induce long-term remission but are also not curative. Thus, CML is an ideal system to test our hypothesis that transcriptome-based state-transition models accurately predict cancer evolution and treatment response. We collected time-sequential blood samples from tetracycline-off (Tet-Off) BCR::ABL-inducible transgenic mice and wild-type controls. From the transcriptome, we constructed a CML state-space and a three-well leukemogenic potential landscape. The potential's stable critical points defined observable disease states. Early states were characterized by anti-CML genes opposing leukemia; late states were characterized by pro-CML genes. Genes with expression patterns shaped similarly to the potential landscape were identified as drivers of disease transition. Re-introduction of tetracycline to silence the BCR::ABL gene returned diseased mice transcriptomes to a near healthy state, without reaching it, suggesting parts of the transition are irreversible. TKI only reverted the transcriptome to an intermediate disease state, without approaching a state of health; disease relapse occurred soon after treatment. Using only the earliest time-point as initial conditions, our state-transition models accurately predicted both disease progression and treatment response, supporting this as a potentially valuable approach to time clinical intervention, before phenotypic changes become detectable., (© 2024. The Author(s).)

Chronic myeloid leukemia (CML) is initiated and maintained by BCR::ABL which is clinically targeted using tyrosine kinase inhibitors (TKIs). TKIs can induce long-term remission but are also not curative. Thus, CML is an ideal system to test our hypothesis that transcriptome-based state-transition models accurately predict cancer evolution and treatment response. We collected time-sequential blood samples from tetracycline-off (Tet-Off) BCR::ABL-inducible transgenic mice and wild-type controls. From the transcriptome, we constructed a CML state-space and a three-well leukemogenic potential landscape. The potential's stable critical points defined observable disease states. Early states were characterized by anti-CML genes opposing leukemia; late states were characterized by pro-CML genes. Genes with expression patterns shaped similarly to the potential landscape were identified as drivers of disease transition. Re-introduction of tetracycline to silence the BCR::ABL gene returned diseased mice transcriptomes to a near healthy state, without reaching it, suggesting parts of the transition are irreversible. TKI only reverted the transcriptome to an intermediate disease state, without approaching a state of health; disease relapse occurred soon after treatment. Using only the earliest time-point as initial conditions, our state-transition models accurately predicted both disease progression and treatment response, supporting this as a potentially valuable approach to time clinical intervention even before phenotypic changes become detectable.

In the public health portfolio of disaster tools, rapid needs assessments are essential intelligence data mining resources that can assess immediate needs in almost all hazard scenarios. Following prolonged and unusual seismic activity that caused significant structural damage, mainly in the southwest part of the island of Puerto Rico, thousands of area residents were forced to leave their homes and establish improvised camps. The austere environmental exposure and limited access to safety and hygiene services prompted public health authorities to request assistance with conducting a rapid needs assessment of those encampments. This report summarizes the design, organization, and execution of a rapid needs assessment of improvised camps following a strong sequence of earthquakes in Puerto Rico.

Objective: To evaluate the impact of Hurricanes Irma and Maria on 3 major chronic diseases in Puerto Rico., Methods: San Juan Overweight Adults Longitudinal study participants were re-evaluated after Hurricanes Irma and Maria (May 2019-July 2020) for the Preparedness to Reduce Exposures and Diseases Post-hurricanes and Augment Resilience study. This study compared the prevalence and incidence of asthma, depression, and hypertension within the same 364 individuals over time., Results: Asthma and depression prevalence and incidence did not change significantly after the hurricanes. The prevalence of hypertension increased significantly after the hurricanes (OR = 2.2, 95% CI: 1.2, 3.9). The incidence of hypertension after the hurricanes (IR = 9.0, 95% CI: 6.5, 12.4) increased significantly compared to before the hurricanes (IR = 6.1, 95% CI: 4.5, 8.0) (age-adjusted incidence rate ratio [aIRR] = 1.4, 95% CI: 4.5, 8.0) for similar time periods., Conclusion: Hurricanes Irma and Maria were associated with a significant increase in the prevalence and incidence of hypertension in this study population. Contrary to expectations, no significant increases were observed in depression and asthma prevalence after the hurricanes. Results from this study can inform better strategies to prevent and manage hypertension in the population affected by a hurricane.

Identifying and characterizing the factors that affect presence in virtual environments has been acknowledged as a critical step to improving Virtual Reality (VR) applications in the built environment domain. In the search to identify those factors, the research objective was to test whether three-dimensional perception affects presence in virtual environments. A controlled within-group experiment utilizing perception and presence questionnaires was conducted, followed by data analysis, to test the hypothesized unidirectional association between three-dimensional perception and presence in two different virtual environments (non-immersive and immersive). Results indicate no association in either of the systems studied, contrary to the assumption of many scholars in the field but in line with recent studies on the topic. Consequently, VR applications in architectural design may not necessarily need to incorporate advanced stereoscopic visualization techniques to deliver highly immersive experiences, which may be achieved by addressing factors other than depth realism. As findings suggest that the levels of presence experienced by users are not subject to the display mode of a 3D model (whether immersive or non-immersive display), it may still be possible for professionals involved in the review of 3D models (e.g., designers, contractors, clients) to experience high levels of presence through non-stereoscopic VR systems provided that other presence-promoting factors are included., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Head and neck squamous cell cancer (HNSCC) occurs at higher rates among persons with HIV (PWH). This study compares the impact of sociodemographic and clinicopathologic characteristics on outcomes among PWH-HNSCC compared with HNSCC patients without HIV., Methods: Patient data from HNSCC individuals were collected at a single academic hospital center between 2002 and 2018. Forty-eight patients with HIV (HIV-HNSCC) and 2894 HNSCC patients without HIV were included. Multivariate analysis determined predictors of survival using Cox proportional hazards regression model. HIV-positive and -negative tumors were analyzed by quantitative immunofluorescence for expression of CD4, CD8, CD20 and PD-L1., Results: HIV-HNSCC patients had a lower median overall survival than HNSCC patients without HIV (34 [18-84] vs 94 [86-103] months; P < .001). In multivariate analysis that included age, sex, race/ethnicity, stage, site, tobacco use, time to treatment initiation, and insurance status, HIV was an independent predictor of poorer survival, with a hazard ratio of 1.98 (95% CI: 1.32-2.97; P < .001). PWH with human papillomavirus (HPV)-positive oropharyngeal tumors also had worse prognosis than HPV-positive oropharyngeal tumors in the population without HIV (P < .001). The tumor microenvironment among HIV-HNSCC patients revealed lower intratumoral CD8 infiltration among HIV+ HPV+ tumors compared with HIV- HPV+ tumors (P = .04)., Conclusions: HIV-HNSCC patients had worse prognosis than the non-HIV population, with HIV being an independent predictor of poor clinical outcomes when accounting for important sociodemographic and clinicopathologic factors. Our findings highlight differences in tumor biology that require further detailed characterization in large cohorts and increased inclusion of PWH in immunotherapy trials., Competing Interests: Potential conflicts of interest. B. E. reports consulting fees from Theratechnologies and Genentech/Roche unrelated to this work; participation on an Advisory Board for Theratechnologies unrelated to this work; and stock or stock options with Bausch Health Companies and Bristol Myers Squibb. G. G. reports support unrelated to this work from the Yale Transplant Group (author works as a statistician working at the Yale Center for Analytical Sciences; part of the author's effort is covered by Yale Transplant for providing statistical support for their research studies). K. A. S. reports grants or contracts unrelated to this work from Navigate Biopharma, Tesaro/GSK, Moderna, Inc, Takeda, Surface Oncology, Pierre-Fabre Research Institute, Merck, Bristol-Myers Squibb, AstraZeneca, Ribon Therapeutics, Eli Lilly, Boehringer-Ingelheim, and Akoya Biosciences (all contracted to Yale University); consulting fees paid to the author from Clinica Alemana Santiago, Shattuck Labs, Genmab, AstraZeneca, EMD Serono, Takeda, Torque/Repertoire Therapeutics, Takeda, Agenus, Genmab, OnCusp, Parthenon Therapeutics, Bristol-Myers Squibb, Roche, CDR Life, Sensei Therapeutics, Molecular Templates, and Merck; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from PeerView, Forefront Collaborative, Merck; payment for expert testimony from AstraZeneca; and support for attending meetings and/or travel from Fluidigm. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: This study aimed to compare demographics, disease characteristics, and outcomes of patients with HIV-infection with non-small-cell lung cancer (NSCLC) with the general NSCLC population., Patients and Methods: A retrospective cohort study was used to compare the HIV-infected and -uninfected groups. Medical records of all patients who were HIV-positive diagnosed with NSCLC between 2000 and 2016 at Yale New Haven Hospital (New Haven, CT) were reviewed and compared with the general Yale NSCLC population regarding demographics, NSCLC characteristics, treatment, and survival. Log-rank tests and Kaplan-Meier curves were used to analyze survival differences. Unadjusted and adjusted Cox proportional hazard models were used to assess predictors of survival., Results: Thirty-five patients with HIV-NSCLC and 5187 general patients with NSCLC were identified. The median age at cancer diagnosis was 54 years (interquartile range [IQR], 49-59 years) for patients with HIV-NSCLC versus 68 years (IQR, 61-76 years) for patients with NSCLC (P < .001). Both groups had high rates of tobacco use. At the time of NSCLC diagnosis, 80% of patients with HIV-NSCLC were on antiretroviral therapy, 60% had an HIV-1 RNA < 400 copies/mL, and their median CD4 was 407 cells/μL (IQR, 218-592 cells/μL). Histology, cancer stage, and first-line cancer treatment regimens were not significantly different between groups. The overall median survival was 12.4 months (95% confidence interval [CI], 7.2-20.4 months) for patients with HIV-NSCLC versus 22.8 months (95% CI, 21.2-24.1 months) for general patients with NSCLC. Patients with HIV-NSCLC had decreased survival at 2 years (P = .028) and 3 years (P = .014) compared with general patients with NSCLC. HIV status was an independent risk factor for poorer outcomes when controlling for other factors (hazard ratio, 1.8; 95% CI, 1.24-2.62)., Conclusion: Despite similar histology, stage, and treatment between groups, patients with HIV had worse outcomes for NSCLC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Morphogen concentration changes in space as well as over time during development. However, how these dynamics are interpreted by cells to specify fate is not well understood. Here, we focus on two morphogens: the maternal transcription factors Bicoid and Dorsal, which directly regulate target genes to pattern Drosophila embryos. The actions of these factors at enhancers has been thoroughly dissected and provides a rich platform for understanding direct input by morphogens and their changing roles over time. Importantly, Bicoid and Dorsal do not work alone; we also discuss additional inputs that work with morphogens to control spatiotemporal gene expression in embryos., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)