bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generalized Additive Mixed Modeling of Longitudinal Tumor Growth Reduces Bias and Improves Decision Making in Translational Oncology
Authors: Forrest William F. , Alicke Bruno , Mayba Oleg , Osinska Magdalena , Jakubczak Michal , Piatkowski Pawel , Choniawko Lech , Starr Alice , Gould Stephen E. 
Published: September 2020

Abstract

Scientists working in translational oncology regularly conduct multigroup studies of mice with serially measured tumors. Longitudinal data collected can feature mid-study dropouts and complex nonlinear temporal response patterns. Parametric statistical models such as ones assuming exponential growth are useful for summarizing tumor volume over ranges for which the growth model holds, with the advantage that the model's parameter estimates can be used to summarize between-group differences in tumor volume growth with statistical measures of uncertainty. However, these same assumed growth models are too rigid to recapitulate patterns observed in many experiments, which in turn diminishes the effectiveness of their parameter estimates as summary statistics. To address this problem, we generalized such models by adopting a nonparametric approach in which group-level response trends for logarithmically scaled tumor volume are estimated as regression splines in a generalized additive mixed model. We also describe a novel summary statistic for group level splines over user-defined, experimentally relevant time ranges. This statistic reduces to the log-linear growth rate for data well described by exponential growth and also has a sampling distribution across groups that is well approximated by a multivariate Gaussian, thus facilitating downstream analysis. Real-data examples show that this nonparametric approach not only enhances fidelity in describing nonlinear growth scenarios but also improves statistical power to detect interregimen differences when compared with the simple exponential model so that it generalizes the linear mixed effects paradigm for analysis of log-linear growth to nonlinear scenarios in a useful way.

Significance:
This work generalizes the statistical linear mixed modeling paradigm for summarizing longitudinally measured preclinical tumor volume studies to encompass studies with nonlinear and nonmonotonic group response patterns in a statistically rigorous manner.
Examining COVID-19 Preventive Behaviors among Cancer Survivors in the United States: An Analysis of the COVID-19 Impact Survey
Authors: Islam Jessica Y. , Camacho-Rivera Marlene , Vidot Denise C. 
Published: September 2020

Abstract

Background:
The COVID-19 pandemic has impacted adults with chronic diseases, and their health care delivery. Patterns of COVID-19–related preventive behaviors practiced by cancer survivors are unknown, including practices related to canceling doctor's appointments. We evaluated COVID-19–related preventive behaviors among cancer survivors in the United States.

Methods:
We used nationally representative data of 10,760 U.S. adults from the COVID-19 Impact Survey. We defined cancer survivors as those with a self-reported diagnosis of cancer (n = 854, 7.6%). We present frequencies and χ2 tests to evaluate COVID-19–related preventive behaviors among cancer survivors. We estimated determinants of canceling doctor's appointments among cancer survivors using Poisson regression models.

Results:
Cancer survivors were more likely to practice preventive behaviors, including social distancing (93%, χ2 P &lt; 0.001), wearing a face mask (93%, χ2 P &lt; 0.001), and avoiding crowded areas (84%, χ2 P &lt; 0.001) compared with adults without cancer. Cancer survivors were more likely to cancel doctor's appointments (41%, χ2 P &lt; 0.001), whereas they were less likely to cancel other social activities such as work (19%, χ2 P &lt; 0.001) and school-related (13%, χ2 P &lt; 0.001) activities. After adjustment for covariates, while non-Hispanic (NH)-Black cancer survivors were less likely to cancel a doctor's appointment compared with NH-White cancer survivors, cancer survivors aged 18 to 29, who were female, and who had least one comorbid condition were more likely.

Conclusions:
Cancer survivors are adhering to recommended preventive behaviors. Cancer survivor's continuity of care may be impacted by COVID-19, specifically young adults, females, and those with existing comorbid conditions.

Impact:
Insights into cancer survivors whose care may be most impacted by COVID-19 will be valuable toward surveillance and survivorship of U.S. cancer survivors.
An Epigenetic Mechanism Underlying Chromosome 17p Deletion–Driven Tumorigenesis
Authors: Chen Mei , Chen Xuelan , Li Shujun , Pan Xiangyu , Gong Yanqiu , Zheng Jianan , Xu Jing , Zhao Chengjian , Zhang Qi , Zhang Shan , Qi Lu , Wang Zhongwang , Shi Kaidou , Ding Bi-Sen , Xue Zhihong , Chen Lu , Yang Shengyong , Wang Yuan , Niu Ting , Dai Lunzhi , Lowe Scott W. , Chen Chong , Liu Yu 
Published: September 2020

Abstract

Chromosome copy-number variations are a hallmark of cancer. Among them, the prevalent chromosome 17p deletions are associated with poor prognosis and can promote tumorigenesis more than TP53 loss. Here, we use multiple functional genetic strategies and identify a new 17p tumor suppressor gene (TSG), plant homeodomain finger protein 23 (PHF23). Its deficiency impairs B-cell differentiation and promotes immature B-lymphoblastic malignancy. Mechanistically, we demonstrate that PHF23, an H3K4me3 reader, directly binds the SIN3–HDAC complex through its N-terminus and represses its deacetylation activity on H3K27ac. Thus, the PHF23–SIN3–HDAC (PSH) complex coordinates these two major active histone markers for the activation of downstream TSGs and differentiation-related genes. Furthermore, dysregulation of the PSH complex is essential for the development and maintenance of PHF23-deficient and 17p-deleted tumors. Hence, our study reveals a novel epigenetic regulatory mechanism that contributes to the pathology of 17p-deleted cancers and suggests a susceptibility in this disease.

Significance:
We identify PHF23, encoding an H3K4me3 reader, as a new TSG on chromosome 17p, which is frequently deleted in human cancers. Mechanistically, PHF23 forms a previously unreported histone-modifying complex, the PSH complex, which regulates gene activation through a synergistic link between H3K4me3 and H3K27ac.
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Carotid Intima‐Media Thickness and the Risk of Sudden Cardiac Death: The ARIC Study and the CHS
Authors: Suzuki Takeki , Wang Wanmei , Wilsdon Anthony , Butler Kenneth R. , Adabag Selcuk , Griswold Michael E. , Nambi Vijay , Rosamond Wayne , Sotoodehnia Nona , Mosley Thomas H. 
Published: September 2020

Background
Sudden cardiac death (SCD) is associated with severe coronary heart disease in the great majority of cases. Whether carotid intima‐media thickness (C‐IMT), a known surrogate marker of subclinical atherosclerosis, is associated with risk of SCD in a general population remains unknown. The objective of this study was to investigate the association between C‐IMT and risk of SCD.

Methods and Results
We examined a total of 20 862 participants: 15 307 participants of the ARIC (Atherosclerosis Risk in Communities) study and 5555 participants of the CHS (Cardiovascular Health Study). C‐IMT and common carotid artery intima‐media thickness was measured at baseline by ultrasound. Presence of plaque was judged by trained readers. Over a median of 23.5 years of follow‐up, 569 participants had SCD (1.81 cases per 1000 person‐years) in the ARIC study. Mean C‐IMT and common carotid artery intima‐media thickness were associated with risk of SCD after adjustment for traditional risk factors and time‐varying adjustors: hazard ratios (HRs) with 95% CIs for fourth versus first quartile were 1.64 (1.15–2.63) and 1.49 (1.05–2.11), respectively. In CHS, 302 participants developed SCD (4.64 cases per 1000 person‐years) over 13.1 years. Maximum C‐IMT was associated with risk of SCD after adjustment: HR (95% CI) for fourth versus first quartile was 1.75 (1.22–2.51). Presence of plaque was associated with 35% increased risk of SCD: HR (95% CI) of 1.37 (1.13–1.67) in the ARIC study and 1.32 (1.04–1.68) in CHS.

Conclusions
C‐IMT was associated with risk of SCD in 2 biracial community‐based cohorts. C‐IMT may be used as a marker of SCD risk and potentially to initiate early therapeutic interventions to mitigate the risk.
Connecting Land–Atmosphere Interactions to Surface Heterogeneity in CHEESEHEAD19
Authors: Butterworth Brian J. , Desai Ankur R. , Townsend Philip A. , Petty Grant W. , Andresen Christian G. , Bertram Timothy H. , Kruger Eric L. , Mineau James K. , Olson Erik R. , Paleri Sreenath , Pertzborn Rosalyn A. , Pettersen Claire , Stoy Paul C. , Thom Jonathan E. , Vermeuel Michael P. , Wagner Timothy J. , Wright Daniel B. , Zheng Ting , Metzger Stefan , Schwartz Mark D. , Iglinski Trevor J. , Mauder Matthias , Speidel Johannes , Vogelmann Hannes , Wanner Luise , Augustine Travis J. , Brown William O. J. , Oncley Steven P. , Buban Michael , Lee Temple R. , Cleary Patricia , Durden David J. , Florian Christopher R. , Lantz Kathleen , Riihimaki Laura D. , Sedlar Joseph , Meyers Tilden P. , Plummer David M. , Guzman Eliceo Ruiz , Smith Elizabeth N. , Sühring Matthias , Turner David D. , Wang Zhien , White Loren D. , Wilczak James M. 
Published: September 2020

AbstractThe Chequamegon Heterogeneous Ecosystem Energy-Balance Study Enabled by a High-Density Extensive Array of Detectors 2019 (CHEESEHEAD19) is an ongoing National Science Foundation project based on an intensive field campaign that occurred from June to October 2019. The purpose of the study is to examine how the atmospheric boundary layer (ABL) responds to spatial heterogeneity in surface energy fluxes. One of the main objectives is to test whether lack of energy balance closure measured by eddy covariance (EC) towers is related to mesoscale atmospheric processes. Finally, the project evaluates data-driven methods for scaling surface energy fluxes, with the aim to improve model–data comparison and integration. To address these questions, an extensive suite of ground, tower, profiling, and airborne instrumentation was deployed over a 10 km × 10 km domain of a heterogeneous forest ecosystem in the Chequamegon–Nicolet National Forest in northern Wisconsin, United States, centered on an existing 447-m tower that anchors an AmeriFlux/NOAA supersite (US-PFa/WLEF). The project deployed one of the world’s highest-density networks of above-canopy EC measurements of surface energy fluxes. This tower EC network was coupled with spatial measurements of EC fluxes from aircraft; maps of leaf and canopy properties derived from airborne spectroscopy, ground-based measurements of plant productivity, phenology, and physiology; and atmospheric profiles of wind, water vapor, and temperature using radar, sodar, lidar, microwave radiometers, infrared interferometers, and radiosondes. These observations are being used with large-eddy simulation and scaling experiments to better understand submesoscale processes and improve formulations of subgrid-scale processes in numerical weather and climate models.
Antecedents for the Shapiro–Keyser Cyclone Model in the Bergen School Literature
Authors: Schultz David M. , Keyser Daniel 
Published: September 2020

AbstractTwo widely accepted conceptual models of extratropical cyclone structure and evolution exist: the Norwegian and Shapiro–Keyser cyclone models. The Norwegian cyclone model was developed around 1920 by the Bergen School meteorologists. This model has come to feature an acute angle between the cold and warm fronts, with the reduction in the area of the warm sector during the evolution of the cyclone corresponding to the formation of an occluded front. The Shapiro–Keyser cyclone model was developed around 1990 and was motivated by the recognition of alternative frontal structures depicted in model simulations and observations of rapidly developing extratropical cyclones. This model features a right angle between the cold and warm fronts (T-bone), a weakening of the poleward portion of the cold front (frontal fracture), an extension of the warm or occluded front to the rear of and around the cyclone (bent-back front), and the wrapping around of the bent-back front to form a warm-core seclusion of post-cold-frontal air. Although the Norwegian cyclone model preceded the Shapiro–Keyser cyclone model by 70 years, antecedents of features of the Shapiro–Keyser cyclone model were apparent in observations, analyses, and conceptual models presented by the Bergen School meteorologists, their adherents, and their progeny. These “lost” antecedents are collected here for the first time to show that the Bergen School meteorologists were aware of them, although not all of the antecedents survived until their reintroduction into the Shapiro–Keyser cyclone model in 1990. Thus, the Shapiro–Keyser cyclone model can be viewed as a synthesis of various elements of cyclone structure and evolution recognized by the Bergen School meteorologists.
Family Caregiver Perspectives on Benefits and Challenges of Caring for Older Adults With Paid Caregivers
Authors: Shaw Amy L. , Riffin Catherine A. , Shalev Ariel , Kaur Harveen , Sterling Madeline R. 
Published: September 2020

Background: Many older adults receive help from both family caregivers and home care workers. We aimed to understand family caregivers’ perspectives on home care workers. Methods: This qualitative study took place at an academic medical center in New York, N.Y. We interviewed family caregivers of community-dwelling older adults about their experiences with home care workers. We analyzed transcripts thematically. Results: We interviewed 17 family caregivers and identified four major themes: (a) home care workers provide functional and emotional support; (b) home care is logistically challenging; (c) finding the right fit between home care workers, older adults, and families is essential; and (d) home care workers and family caregivers coordinate care well beyond the initiation of home care. Conclusion: Despite its logistical challenges, home care benefits patients and family caregivers. Given the growing prevalence of caregiving, clinicians and family caregivers might benefit from training and support about working with home care workers.
Secondary hemophagocytic lymphohistiocytosis versus cytokine release syndrome in severe COVID-19 patients
Authors: Hakim Nausheen N , Chi Jeffrey , Olazagasti Coral , Liu Johnson M 
Published: September 2020

COVID-19 or SARS-CoV-2 infection can lead to severe acute respiratory distress syndrome/pneumonia with features of cytokine storm reminiscent of secondary hemophagocytic lymphohistiocytosis (HLH), which can be diagnosed by the calculated HScore. Recent reports have suggested favorable responses to the interleukin-1 receptor antagonist, anakinra in patients with COVID-19 associated secondary HLH. In our single institution study, we compared 14 COVID-19 cytokine storm patients with 10 secondary HLH patients seen immediately prior to the pandemic (non-COVID-19), to determine whether diagnostic features of secondary HLH were typically seen in COVID-19 patients presenting with cytokine storm. Although most of our COVID-19 patients did not fulfill diagnostic criteria for HLH, we hypothesize that identification of HLH may relate to the severity or timing of cytokine release. Based on our observations, we would suggest distinguishing between cytokine release syndrome and secondary HLH, reserving the latter term for cases fulfilling diagnostic criteria. Impact statement Severe COVID-19 associated pneumonia and acute respiratory distress syndrome has recently been described with life-threatening features of cytokine storm and loosely referred to as hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS). Although a recent report indicated favorable responses to the interleukin-1 receptor antagonist, anakinra in eight patients with COVID-19 secondary HLH diagnosed using the HScore calculation, others have suggested that the diagnosis of secondary HLH is uncommon and that the use of the HScore has limited value in guiding immunomodulatory therapy for COVID-19. Here, we provide additional perspective on this important controversy based upon comparisons between 14 COVID-19 cytokine storm patients and 10 secondary HLH patients seen immediately prior to the pandemic. We hypothesize that identification of HLH may relate to the severity or timing of cytokine release and suggest distinguishing between cytokine release syndrome and secondary HLH, reserving the latter term for cases fulfilling diagnostic criteria.
Management of severe asthma: summary of the European Respiratory Society/American Thoracic Society task force report
Authors: Khurana Sandhya , Bush Andrew , Holguin Fernando 
Published: September 2020

Educational aimsThis article is mainly intended for trainees and specialists who are interested in the management of severe asthma.It aims to inform readers about the updated ERS/ATS recommendations for management of severe asthma, specifically on the topics of biologics, macrolides and long-acting muscarinic antagonists.It also provides guidance on utilisation of available biomarkers in selecting advanced therapies in severe asthma.
Appropriateness of intensive care treatments near the end of life during the COVID-19 pandemic
Authors: Cardona Magnolia , Anstey Matthew , Lewis Ebony T. , Shanmugam Shantiban , Hillman Ken , Psirides Alex 
Published: September 2020

The patient and family perspective on the appropriateness of intensive care unit (ICU) treatments involves preferences, values and social constructs beyond medical criteria. The clinician's perception of inappropriateness is more reliant on clinical judgment. Earlier consultation with families before ICU admission and patient education on the outcomes of life-sustaining therapies may help reconcile these provider–patient disagreements. However, global emergencies like COVID-19 change the usual paradigm of end-of-life care, as it is a new disease with only scarce predictive information about it. Pandemics can also bring about the burdensome predicament of doctors having to make unwanted choices of rationing access to the ICU when demand for otherwise life-saving resources exceeds supply. Evidence-based prognostic checklists may guide treatment triage but the principles of shared decision-making are unchanged. Yet, they need to be altered with respect to COVID-19, defining likely outcomes and likelihood of benefit for the patient, and clarifying their willingness to take on the risks inherent to being in an ICU for 2 weeks for those eligible. For patients who are admitted during the prodrome of COVID-19 disease, or those who deteriorate in the second week, clinicians have some lead time in hospital to have appropriate discussions about ceilings of treatments offered based on severity.Key pointsThe patient and family perspective on inappropriateness of intensive care at the end of life often differs from the clinician's opinion due to the nonmedical frame of mind.To improve satisfaction with communication on treatment goals, consultation on patient values and inclusion of social constructs in addition to clinical prediction is a good start to reconcile differences between physician and health service users’ viewpoints.During pandemics, where health systems may collapse, different admission criteria driven by the need to ration services may be warranted.Educational aimsTo explore the extent to which older patients and their families are involved in decisions about appropriateness of intensive care admission or treatmentsTo understand how patients or their families define inappropriate intensive care admission or treatmentsTo reflect on the implications of decision to admit or not to admit to the intensive care unit in the face of acute resource shortages during a pandemic
Restoring pars intermedia dopamine concentrations and tyrosine hydroxylase expression levels with pergolide: evidence from horses with pituitary pars intermedia dysfunction
Authors: Fortin Jessica S. , Benskey Matthew J. , Lookingland Keith J. , Patterson Jon S. , Howey Erin B. , Goudreau John L. , Schott Harold C. 
Published: September 2020

AbstractBackgroundPituitary pars intermedia dysfunction (PPID) develops slowly in aged horses as degeneration of hypothalamic dopaminergic neurons leads to proliferation of pars intermedia (PI) melanotropes through hyperplasia and adenoma formation. Dopamine (DA) concentrations and tyrosine hydroxylase (TH) immunoreactivity are markedly reduced in PI tissue of PPID-affected equids and treatment with the DA receptor agonist pergolide results in notable clinical improvement. Thus, we hypothesized that pergolide treatment of PPID-affected horses would result in greater DA and TH levels in PI tissue collected from PPID-affected horses versus untreated PPID-affected horses.To test this hypothesis, pituitary glands were removed from 18 horses: four untreated PPID-affected horses, four aged and four young horses without signs of PPID, and six PPID-affected horses that had been treated with pergolide at 2 µg/kg orally once daily for 6 months. DA concentrations and TH expression levels in PI tissues were determined by high performance liquid chromatography with electrochemical detection and Western blot analyses, respectively.ResultsDA and TH levels were lowest in PI collected from untreated PPID-affected horses while levels in the pergolide treated horses were similar to those of aged horses without signs of PPID.ConclusionsThese findings provide evidence of restoration of DA and TH levels following treatment with pergolide. Equine PPID is a potential animal model of dopaminergic neurodegeneration, which could provide insight into human neurodegenerative diseases.