bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB357: CRISPR-Cas9 targeting of somatic mutations selectively kills cancer cells
Authors: Bowland Kirsten , Teh Selina Shiqing K. , Skaist Alyza , Hruban Ralph H. , Roberts Nicholas J. , Iacobuzio-Donahue Chrisine , Eshleman James R.
Published: April 2023

Pancreatic ductal adenocarcinoma (PDAC) accounts for 3% of all cancers but is the 3rd leading cause of cancer death in the United States. This staggering discrepancy is partly because most pancreatic cancers evade early detection and patients most commonly present with metastatic disease. As cancer initiates from a single transformed cell, passenger mutations that accumulate over the course of the patient’s lifetime in that cell are then clonally propagated to the growing tumor and metastases, providing a targetable molecular signature throughout the cancer. Here we propose a CRISPR-Cas9 gene therapy aimed at these tumor-specific somatic mutations. Using whole genome sequencing of rapid autopsy tumor and normal samples from five patient cases, we identified single base substitutions present in tumor tissues and absent in patient-matched normal tissue. A subset (6.6% on average) of these mutations lead to novel protospacer adjacent motif (PAM) sites. These tumor specific PAM sites are necessary for Cas9 binding and DNA scission and are therefore selectively targetable by CRISPR-Cas9 systems. Using a hybrid capture/NGS approach, we demonstrate in patients with multiple metastases that the majority of these novel PAM sites, ~70%, are maintained among the different metastases. Using multitarget sgRNA which cut at a known number of sites in the human genome, we determined a relationship between number of CRISPR-Cas9 cuts and growth inhibition in PDAC cells. We found that 8-10 cut sites in non-coding regions are sufficient to induce >95% cancer cell death. Finally, using cocultures of fluorescently labeled PDAC cells and a multiplexed sgRNA array targeting multiple tumor specific PAMs, we demonstrate selective cell killing of the targeted cell line. Importantly, deep sequencing of patient-matched normal lymphocytes lacking the tumor-specific PAMs treated with the same sgRNA array exhibited no editing at the targeted loci. This work establishes a bioinformatic platform for the discovery of tumor-specific CRISPR targets in the context of metastatic disease and demonstrates selective killing to cancer cells while sparing the patient’s normal cells. These data establish the proof of principle for a gene therapy approach targeting metastatic disease.

Citation Format: Kirsten Bowland, Selina Shiqing K. Teh, Alyza Skaist, Ralph H. Hruban, Nicholas J. Roberts, Chrisine Iacobuzio-Donahue, James R. Eshleman. CRISPR-Cas9 targeting of somatic mutations selectively kills cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB357.
Fetal High-Risk APOL1 Genotype Increases Risk for Small for Gestational Age in Term Infants Affected by Preeclampsia
Authors: Azhibekov Timur , Durodoye Razaq , Miller Anna K. , Simpson Claire L. , Davis Robert L. , Williams Scott M. , Bruggeman Leslie A.
Published: April 2023

Background: Hypertensive disorders of pregnancy cause fetal growth restriction and increased maternal morbidity and mortality, especially in women of African ancestry. Recently, preeclampsia risk was associated with polymorphisms in the apolipoprotein L1 (APOL1) gene in women of African ancestry. Objectives: We assessed APOL1 genotype effects on pregnancies with and without preeclampsia. Method: We conducted an unmatched case-control study of 1,358 mother-infant pairs from two independent cohorts of black women. Results: Term preeclampsia cases with high-risk APOL1 genotypes were more likely to be small for gestational age compared to APOL1 low-risk term cases (odds ratio [OR] 2.8) and APOL1 high-risk controls (OR 5.5). Among preterm pregnancies, fetal APOL1 genotype was associated with preeclampsia. Conclusions: Fetal APOL1 genotype was associated with preeclampsia in preterm infants and with altered fetal growth in term infants. This may indicate APOL1 genotype impacts a spectrum of pregnancy complications mediated by a common pathophysiological event of placental insufficiency.
Patients’ Perspectives on the Development of Prescription Opioid Use Disorder in Patients with Chronic Non-Cancer Pain
Authors: Davies Lisa E.M. , Koster Ellen S. , Damen Katinka F.M. , Beurmanjer Harmen , Schellekens Arnt F.A. , Bouvy Marcel L.
Published: April 2023

Introduction: In the past decade, prescription opioid use increased exponentially and concomitantly opioid use disorders (OUD) are becoming more common. Several risk factors for developing OUD have been identified, but little is known regarding the patients’ perspective on developing a prescription OUD. Methods: We recruited 25 adults undergoing treatment for prescription OUD. In-depth, semi-structured interviews focussed on experiences with long-term opioid use, knowledge and attitudes regarding opioids, and access to opioids. A directed content analysis was conducted on the transcribed interviews using NVivo. Results: Participants showed that the development of an OUD is affected by various factors which could be grouped into three themes: (1) experiences driving initiation, (2) experiences driving continuation, and (3) experiences with prescription OUD. Besides the need for pain management, the dynamics of patient-provider communication, care coordination, provider vigilance, and environmental support all contributed to the way patients used their opioids. Conclusion: Patients’ experiences illustrate that the first stage of the development of prescription OUD differs from the development of other substance addictions. Negative reinforcement might play a more prominent role in the early phase of prescription opioid use. Patients expressed a lack of guidance, both at the start of use and long-term use, easy access to new prescriptions and a lack of monitoring as main drivers of the development. Poorly controlled pain and subjective stress fuelled continuous opioid use.
Avoiding Prostate Biopsies in Patients at Low Risk for Prostate Cancer: A Prospective Evaluation of a PSA-Density-Based Safety Net
Authors: Bahlburg Henning , Tully Karl , Hoffmann Vincent , Hanske Julian , von Landenberg Nicolas , Roghmann Florian , Palisaar Rein-Jüri , Noldus Joachim , Berg Sebastian , Brock Marko
Published: April 2023

Introduction and Objectives: Decision-making to perform prostate biopsy should include individual risk assessment. Patients classified as low risk by the Rotterdam Prostate Cancer Risk Calculator are advised to forego biopsy (PBx). There is concern about missing clinically significant prostate cancer (csPCa). A clear pathway for follow-up is needed. Material and Methods: Data for 111 consecutive patients were collected. Patients were encouraged to adhere to a PSA-density-based safety net after PBx was omitted. Cut off values indicating a re-evaluation were PSA density >0.15 ng/mL/ccm in PBx-naïve patients and >0.2 ng/mL/ccm in men with past-PBx. Primary endpoint was whether men had their PSA taken regularly. Secondary endpoint was whether a new multiparametric MRI was performed when PSA-density increased. Tertiary endpoint was whether biopsy was performed when risk stratification revealed an increased risk. Results: Median follow-up was 12 months (IQR 9–15 months). The primary endpoint was reached by 97.2% (n = 106). The secondary endpoint was reached by 30% (n = 3). The tertiary endpoint was reached by 50% (n = 2). Histopathologic analyses revealed csPCa in none of these cases. Risk stratification did not change (p = 0.187) with the majority of patients (89.2%, n = 99). Conclusion: The concern of missing csPCa when omitting PBx in the risk-stratified pathway may be negated. Changes in risk stratification during follow-up should lead to subsequent PBx. We suggest implementing a safety net based on PSA density and digital rectal examination (DRE).
Peripher ulzerative Keratitis – eine interdisziplinäre Herausforderung
Authors: Linke Stephan J.
Published: April 2023

Purpose: of review: To discuss peripheral ulcerative keratitis, with a focus on the evaluation and management of associated systemic diseases. Recent findings: Peripheral ulcerative keratitis (PUK) is a sight-threatening condition that is often defined by the presence of a crescent-shaped area of peripheral corneal thinning, an epithelial defect, and an inflammatory corneal infiltrate. It is highly associated with rheumatoid arthritis, systemic necrotizing vasculitides like granulomatosis with polyangiitis, and collagen vascular diseases like systemic lupus erythematosus. Undertreated PUK carries a risk of vision loss and premature death. Summary: Multidisciplinary collaboration between the ophthalmologist, rheumatologist, and other consultants is required. Early and aggressive steroid-sparing therapy should be considered in cases due to noninfectious systemic disease.
Identification and Validation of Cyclin A2 and Cyclin E2 as Potential Biomarkers in Small Cell Lung Cancer
Authors: Zhang Xiangxin , Yang Liu , Huang Bing , Yin Jiangwen , Wei Yutao
Published: April 2023

Introduction: Small cell lung cancer (SCLC) is a special type of lung cancer sensitive to radiotherapy and chemotherapy but is prone to drug resistance and recurrence and has a very poor prognosis. This study aimed to explore the potential biomarkers and therapeutic targets for SCLC. Methods: After batch normalization of GSE40275, GSE1037, and GSE44447 datasets, R was used to screen SCLC’s differentially expressed genes (DEGs) and hub genes. We used immunohistochemistry (IHC) to assess the tissue’s expression level of the hub gene. The clinical value of the hub gene was further evaluated based on the collected clinical-pathological data. Results: In this study, a total of 230 DEGs (133 upregulated and 97 downregulated) were screened by the R package. The IHC showed that the expression of CCNA2 and CCNE2 in SCLC tissues was significantly higher than that in normal tissues (p < 0.01). Overexpression of CCNA2 was closely associated with the extensive period of NCCN (p = 0.004), tumor position (p = 0.046), and clinical stage (p = 0.002). The high expression levels of CCNE2 were related to high survival in chemotherapy patients (p = 0.019). Conclusion: CCNA2 and CCNE2 may serve as potential biomarkers of diagnosis and treatment for SCLC.
Two levels of basic nursing education in Croatia
Authors: Abou Aldan Damjan , Franković Sanda
Published: April 2023

Introduction: There is a worldwide debate on the level at which the basic education of nurses should be organized. If it is at the baccalaureate level, as one view claims, it is doubtful who will perform the basic nursing care. This doubt also directed the reform of nursing education in the Republic of Croatia. The process itself was accompanied by a desire to preserve the existing rights of all nurses, and to ensure that all nursing interventions are carried out by licensed nurses. This paper aims to describe the process of adapting nursing education before Croatia acceded to the European Union. Also, the aim is to determine the differences between vocational and baccalaureate curriculum. Methods: The literature on nursing education was reviewed. Articles and documents about Union accession were studied. Nursing curricula were analysed. Results: In the Republic of Croatia, there are two levels of basic education. Both programs are in line with the European Union Directive. The Nursing Act separates these two levels with different competencies. The education reform respected the rights of nurses who were employed at the moment of joining. The education reform has ensured the implementation of nursing care by licensed nurses in all segments of the nursing process. Conclusion: Two levels of education ensured the development of nursing and the possibility of further education for nurses. The monopoly over all basic nursing skills is preserved.
Deset godina djelovanja Društva za kvalitetu Hrvatske udruge medicinskih sestara od 2012. do 2022. godine
Authors: Kolundžić Smiljana , Bišćan Josipa
Published: April 2023

Uvod: Profesionalno udruživanje medicinskih sestara prema zajedničkom području stručnog interesa tradicija je Hrvatske udruge medicinskih sestara (HUMS). Društvo za kvalitetu (DZK) HUMS-a osnovano je 2012. godine prateći trend zapošljavanja medicinskih sestara u Jedinicama za kvalitetu (JZK) i njihove specifične potrebe za stručnim usavršavanjem. Cilj je ovog rada prikazati 10 godina djelovanja DZK-a od njegova osnivanja 2012. godine. Metode: Podaci prikazani u radu prikupljeni su iz zapisnika skupština, izvještaja o radu DZK-a, kratkih priopćenja i pisama uredniku Sestrinskog glasnika te tekstova koje su na internetu objavile sestrinske organizacije, a koji su značajni za djelatnost Društva. Rezultati: DZK HUMS-a osnovan je 28. 6. 2012. godine sa svrhom zajedničkog okupljanja medicinskih sestara / tehničara koji rade na radnim mjestima u JZK-u te glavnih sestara odjela i ustanova. Društvo djeluje s ciljem jačanja specifičnih kompetencija medicinskih sestara koje rade u JZK-u kako bi se kontinuirano unapređivala kvaliteta sestrinske skrbi. Društvo je organiziralo: 9 konferencija, 11 simpozija, 2 tečaja druge kategorije i 1 tečaj prve kategorije, 8 stručnih skupova kojima je obilježen Svjetski dan prevencije dekubitusa od kojih su 2 održana kao simpoziji, a ostali su bili samostalni stručni skupovi, 5 radionica, 10 online stručnih sastanaka i objavljivalo je razne publikacije. Djelatnost Društva ostvarivana je i u suradnji s drugim stručnim društvima medicinskih sestara i liječnika, raznim zdravstvenim ustanovama i organizatorima stručnih skupova sa zajedničkim područjem interesa u unapređenju kvalitete zdravstvene zaštite. Zaključak: U 10 godina kontinuiranog djelovanja Društvo za kvalitetu sukladno ciljevima osnivanja omogućava medicinskim sestrama stručno usavršavanje te stjecanje znanja i vještina temeljenih na specifičnim kompetencijama u području osiguranja i unapređenja kvalitete zdravstvene zaštite i sigurnosti pacijenata.
Upravljanje medicinskim uređajima u Objedinjenom hitnom bolničkom prijemu
Authors: Žderić Milana , Režić Slađana
Published: April 2023

Objedinjeni hitni bolnički prijem ustrojstvena je jedinica za prijem hitnih bolesnika u kojoj se provode trijaža, dijagnostički i terapijski postupci. Kako bi se postigao učinkovit odgovor u hitnim situacijama, neophodni su odgovarajući i ispravni medicinski uređaji. Medicinski uređaji koji su prema Pravilniku o minimalnim uvjetima za obavljanje djelatnosti hitne medicine potrebni za rad u hitnoj službi sljedeći su: aspirator, defibrilator, EKG uređaj, glukometar, infuzomat, perfuzor, kapnometar i transportni respirator. Medicinski uređaji doprinose učinkovitosti i poboljšanju kvalitete zdravstvene skrbi. Uređaj je klinički učinkovit ako se njime pravilno rukuje prema uputama proizvođača. Održavanje medicinskih uređaja važno je u svrhu smanjenja troškova bolesnika, smanjenja nezadovoljstva bolesnika, pravodobnog liječenja bolesnika i smanjenja smrtnosti tijekom skrbi. Sigurnost bolesnika i zdravstvenog osoblja ne smije biti ugrožena. Rizici povezani s korištenjem medicinskih uređaja moraju se minimizirati. Medicinske sestre trebaju uspostaviti proces upravljanja medicinskim uređajima i osigurati da je uređaj prikladan, da se koristi u skladu s tvorničkim uputama te da se održava u sigurnom stanju. Čest su uzrok pogrešaka nedostaci medicinske opreme u dizajnu, pogrešno rukovanje i kvar uređaja. Medicinske sestre u Objedinjenom hitnom prijemu glavni su korisnici medicinskih uređaja. Moraju biti upoznate s načinom korištenja medicinskih uređaja kako bi se smanjila mogućnost pogrešaka tijekom njihove primjene i kako bi se prevenirale moguće komplikacije koje utječu na sigurnost bolesnika.
Observed Turbulent Dissipation Rate in a Landfalling Tropical Cyclone Boundary Layer
Authors: Fang Qingguo , Chu Kekuan , Zhou Bowen , Chen Xunlai , Peng Zhen , Zhang Chunsheng , Luo Ming , Zhao Chunyang
Published: April 2023

Based on turbulence measurements from sonic anemometers instrumented at multiple levels on a 356-m-tall meteorological tower located on the south coast of China, an observation study of the turbulent dissipation rate (ε) in a landfalling tropical cyclone boundary layer (TCBL) is conducted. Three indirect methods (i.e., the power spectra, the second- and the third-order structure functions) are compared for the calculation of ε. The third-order structure function computes the smallest ε among the three methods, but shows the largest uncertainty. The second-order structure function gives similar ε estimates as the power spectra, and is adopted for its reduced uncertainty. The measured ε in the landfalling TCBL is O(10−1) m2 s−3, much greater than typical atmospheric boundary layer values as well as oceanic TCBL values. The value of ε is found to scale with the local friction velocity rather than the surface friction velocity, implying a highly localized nature of turbulence. Conventional parameterizations of ε are evaluated against observations. Process-based ε models assuming a local balance between shear production and dissipation prove inadequate, as shear production merely accounts for half of the dissipation away from the surface. In comparison, scaling-based ε models used by planetary boundary layer (PBL) schemes are more advantageous. With both tuning of the model coefficients and adjustment of the dissipation length scale, the performance of an ε model in a widely used PBL scheme is shown to produce similar values to the observations.

Significance Statement

Dissipation in a turbulent flow refers to the conversion of kinetic energy to heat through molecular viscosity, and is of key dynamic and thermal–dynamic importance in the tropical cyclone boundary layer (TCBL). Past observations of ε in the TCBL have been rare. Few existing ones are based on surface and flight measurements that are either constrained in height or limited in time. This study utilizes turbulence measurements taken from a 356-m meteorological tower to study dissipation of a landfalling TC. The tall tower platform offers a valuable turbulence dataset that extends beyond the surface layer of the TCBL. The observations are used to improve the physical understanding of dissipation, and to evaluate diagnostic ε models for numerical weather prediction.
Predictable and Unpredictable Components of Cape Town Winter Rainfall
Authors: Cash Benjamin A. , Burls Natalie J. , Howar Laila V.
Published: April 2023

In early 2018, due in part to a severe and extended meteorological drought, Cape Town was at risk of being one of the first major metropolitan areas in the world to run out of water. The magnitude of the crisis was exacerbated by the fact that such a prolonged and severe drought was both unanticipated and unpredicted. In this work, we analyze data from both observations and seasonal forecasts made as part of the North American Multimodel Ensemble (NMME) to better understand the predictability of rainfall in the Cape Town (CT) region. We find that there are statistically significant correlations between observed CT rainfall and sea surface temperatures in the tropical Atlantic (∼0.45) as well as a pattern of 200-mb geopotential height (z200) anomalies resembling the Southern Annular Mode (SAM; ∼0.4). Examination of hindcasts from the NMME demonstrates that the models accurately reproduce the observed correlation between CT rainfall and z200 anomalies. However, they fail to reproduce correlations between CT rainfall and the tropical South Atlantic. Decomposition of the correlations into contributions from predictable and unpredictable components indicates that CT rainfall in the models is dominated by unpredicted atmospheric variability (correlation ∼ 0.84) relative to predicted (correlation ∼ 0.14), which may be related to the failure to simulate the connection with the tropical Atlantic.

Significance Statement

Water crises are occurring with increasing severity and frequency around the globe. The ability to accurately forecast wet season rainfall would be invaluable to water managers and other decision-makers. Here, we explore the reasons behind the failure of a suite of operational seasonal forecast models to accurately predict rainfall in the Cape Town region of South Africa.
Incidence and Reflection of Offshore Subinertial and Barotropic Pressure Signals in Wide Shelf Seas
Authors: Wu Hui
Published: April 2023

The response of a wide shelf to subinertial and barotropic offshore pressure signals from the shelf edge was investigated. By relaxing the semigeostrophic approximation, an elliptical wave structure equation was formulated and solved with the integral transform method. It was found that when the imposed offshore signal has an along-shelf length scale similar to the shelf width, it can efficiently break the potential vorticity barrier and propagate toward the coast, producing a significant coastal sea level setup. Thereafter, the pressure signal reflects from the coast or the sloping topography, producing a transient eddy and propagates to the downshelf. The intensities of the coastal setup and the eddy increase as the along-shelf scale of the subinertial signal decreases or when its time scale is close to the inertial period. For a signal with longer time scale, the eddy is insignificant. The nature of the shelf response is controlled by the shelf conductivity κ ≡ r/(fsB), in which r is the Rayleigh friction coefficient, f is the Coriolis parameter, s is the shelf slope, and B is the shelf width, respectively. For a given offshore signal, coastal setup increases with κ. For large κ, the eddy energy is concentrated at low modes, producing a large eddy, whereas a small κ produces a small eddy. The proposed theory can explain coastal sea level fluctuations under eddy impingement in the Mid-Atlantic Bight or other similar areas.

Significance Statement

Coastal sea level and shelf circulation are greatly affected by offshore pressure signals, e.g., mesoscale eddy impingements or boundary current fluctuations. It is often assumed that the along-shelf length scale of the forcing is much larger than the shelf width, i.e., the semigeostrophic approximation. Here in this study, we found this approximation significantly underestimates the shelf–ocean interaction. A general shelf wave equation was developed that relaxed the semigeostrophic approximation and was solved analytically with a novel mathematical method. The solution can characterize the shelf response to subinertial offshore forcing at arbitrary spatiotemporal scales. It was found that for a subinertial signal with scale close to or smaller than the shelf width, significant coastal sea level setup and transient eddy can be formed, which was consistent with realistic phenomena. The new theory could promote the understanding of coastal sea level variations and along-/cross-shelf transports at synoptic and intermediate scales.
Characteristics of Diagnostics for Identifying Elevated Convection over the British Isles in a Convection-Allowing Model
Authors: Flack David L. A. , Lehnert Matthew , Lean Humphrey W. , Willington Steve
Published: April 2023

Identifying modes of convection can be useful in both forecasting and research. For example, it allows for potentially different impacts to be determined in forecasting contexts and stratification of model behavior in research contexts. One area where identification could be particularly beneficial is elevated convection. Elevated convection is not routinely examined (outside of an operational environment) within a physical-process perspective in operational numerical weather prediction model evaluation or verification. Using convection-allowing model (CAM) output the characteristics of four elevated convection diagnostics [based on boundary layer, convective available potential energy (CAPE) ratios, downdraft, and inflow layer properties] are examined in operational forecasts during the U.K. Testbed Summer 2021 run at the Met Office. A survey of the practical use of these diagnostics in a simulated operational environment revealed that diagnostics based on CAPE ratios and inflow layer properties were preferred. These diagnostics were the smoothest varying in both space and time. Treating the CAPE ratio and downdraft properties diagnostics as proxies for updrafts and downdrafts, respectively, showed that updrafts were slightly more likely to be resolved than downdrafts. However, a substantial proportion of both are unresolved in current CAMs. Filtering the CAPE ratios by the inflow layer properties led to improved spatial and temporal characteristics, and thus indicates a potentially useful diagnostic for both research and forecasting.

Significance Statement

Understanding diagnostics is important to be able to analyze model data. Four diagnostics to identify elevated convection are characterized from kilometer-scale operational forecasts. Diagnosing elevated convection from model data is important as these events are often associated with impactful forecast busts. Therefore, being able to identify how the model is representing these events could lead to model improvements. Two diagnostics were deemed to be of practical use based on current kilometer-scale forecasts: convective available potential energy ratios and inflow layer properties. These diagnostics varied smoothly in space and time. The two diagnostics were combined to produce a filtered diagnostic that could be useful in both research and operations.
Toward a Meta-Psychological Methodology: Reflections on Maslow and the Role of Experiencing and Perspective in Scientific Methods
Authors: Levitt Heidi M.
Published: April 2023

In this brief article, I consider two concepts that Maslow advances in Toward a Humanistic Biology that relate to the role of scientific observation in psychological research and were forward-thinking at his writing. These are the importance of the humanistic concept of experiencing as a way of developing understanding, and the recognition of the impact of the perceptive capacities of observers. I consider these concepts in light of advances in critical and qualitative psychology, integrating concepts such as epistemic privilege and the use of experiencing as a method toward critical science—offering a contemporary foundation for a meta-psychological methodology.
Influence of Economic Scarcity on Race Perception
Authors: Antunes Rosana de Almeida , Gonçalves Edimilson dos Santos , Bernardino Leonardo Gomes , Casalecchi João Guilherme Siqueira , Grebot Ivan Bouchardet da Fonseca , de Moraes Rui
Published: April 2023

Racial socioeconomic gaps are widened in periods of economic recession. Besides social and institutional factors, black people also struggle with many psychological factors. The literature reports racial-biased complex behaviors and high-level processes that are influenced by economic scarcity. A previous study found a bias at the perceptual level: an experimental manipulation of scarcity (a subliminal priming paradigm) lowered the black-white race categorization threshold. Here we present a conceptual replication in a higher ecological setup. In our main analysis we compared the categorization threshold of participants that received the Brazilian government’s emergency economic aid in the context of the COVID-19 pandemic ( n = 136) and participants that did not receive the economic aid ( n = 135) in an online psychophysical task that presented faces in a black-white race continuum . Additionally, we analyzed the economic impact of COVID-19 on household income, and in cases of family unemployment. Our results do not support the claim that perception of race is influenced by economic scarcity. Interestingly, we found that when people differ greatly in terms of racial prejudice, they encode visual information related to race differently. People with higher scores on a prejudice scale needed more phenotypic traits of the black race to categorize a face as black. We discuss the results in terms of differences in method and sample.
Secondary Data Analysis of ENETS Survey: Different Age Workers have Different Priorities When Evaluating Life Satisfaction
Authors: Gray-Gariazzo Nora , Martínez-Zelaya Gonzalo , Bilbaoz M Angeles
Published: April 2023

Do factors impacting life satisfaction remain stable, or do they change, during the life course of workers? This study analyses the relationships between life satisfaction and age. This study is a secondary analysis of data from ENETS a health and working conditions survey. Workers were grouped into 5 age ranges. A scale of life satisfaction was analyzed, investigating aspects such as income, level of debt, physical and mental health, among others. The confirmatory factor analysis (CFA) showed that 4 of the 5 age ranges have a unifactorial structure, but for those under 30 years of age, 2 factors associated with “psychophysical well-being” and “material well-being” were identified. Thus, at different stages of productive life different priorities affect life satisfaction, this should be considered to optimize the human resources management.
Does Universal Health Insurance in Korea provide a Lesson for U.S. Health Care Financing?
Authors: Phan Phillip
Published: April 2023

This note provides a commentary on Lee, C. “Is Universal Health Insurance Superior in Terms of Healthcare Payment? Estimating the Financial Burden of Healthcare in Korea: 2009 to 2019.” INQUIRY, 2022, 59:1-8. Lee, using a unique data set, shows that the Korean single payer system is regressive, despite previous attempts to increase public expenditures. The policy recommendation, to improve access by making public payments even more progressive to household income, is examined. This note concludes that making health expenditures progressive to household income does not solve the root cause of the demand for health care, a key factor in health care access, nor can the policy implications generalize to the multi-payer U.S. system.
A Systematic Review and Narrative Synthesis of Interventions to Address Substance Use Disorders and Other Mental Health Disorders in Prison Settings With a Focus on Low- and Middle-Income Countries
Authors: Jordan Ashly E. , Kashino Wataru , Suhartono Sanita , Campello Giovanna , Busse Anja
Published: April 2023

Interventions to treat substance use disorders (SUDs) and other mental health disorders (MHDs) in prison settings vary in both availability and effectiveness across contexts. Furthermore, incomplete characterization of intervention efficacy and/or effectiveness impacts the ability to know whether an intervention with demonstrated effectiveness in one setting will be effective in another setting. We systematically reviewed the literature for studies of interventions for SUDs and other MHDs conducted in prison settings, and synthesized the identified interventions and identified evidence gaps. Search strategies yielded 9,599 articles published between January 1, 2010, and December 31, 2020. A total of 82 articles were identified as eligible with interventions presented for SUDs ( n = 52), for MHDs ( n = 23), and for SUDs/MHDs ( n = 7). Findings point to a narrow range of interventions of demonstrated effectiveness and to important gaps in the evidence-base for which high-quality research, particularly in low- and middle-income settings, is needed.
A Comparison Controlled Study Examining Outcome for Children With Autism Receiving Intensive Behavioral Intervention (IBI)
Authors: Wójcik Marta , Eikeseth Svein , Eikeseth Fillip Ferreira , Budzinska Ewa , Budzinska Anna
Published: April 2023

This study evaluated the effects of a center-based Intensive Behavioral Intervention (IBI) model for preschool aged children with autism. Outcomes of 25 children receiving IBI was compared to the outcomes of 14 children receiving autism specific, eclectic, special education. Both provisions were described as appropriate treatment options by the professional agency who diagnosed the children, and the decision of where to enroll the child was made by the parents after consultations with the specialists. After 14 months of treatment, children from the IBI group improved significantly on standard scores in intellectual functioning and adaptive behavior and had a significant reduction in autism severity compared to the children in the autism specific, eclectic, special education group. Results suggest that preschool aged children with autism may make large gains in intellectual and adaptive functioning and improvement in autism severity with IBI, and that effects of IBI may be similar to that of EIBI. These findings must be interpreted with caution due to the limitations inherent in the present comparison-controlled design.
Ultrasound Patterns and Disease Progression in Medullary Sponge Kidney in Adults
Authors: Gliga Mirela Liana , Chirila Cristian , Chirila Paula Maria
Published: April 2023

Our paper presents the ultrasound (US) patterns of a rare kidney disease—medullary sponge kidney (MSK)—that have not been described before in comparison with other causes of medullary hyperechogenicity and correlates them with the severity of the disease and prognosis. This is a clinical observational study of all US examinations in the Nephrology Department over a period of 6 years. The abdominal US focused on the kidneys was recorded. US characteristics of the medulla and cortex were analyzed. We found 10 patients with characteristic daisy flower (DF) kidneys. Positive diagnosis in association with other renal risk factors, prognosis, and evolution were evaluated. Two patterns of medullary hyperechogenicity were found and were correlated with disease severity and kidney function. The first pattern is a homogenous echogenicity of the medulla described as a “daisy-like” appearance. The second pattern: calcifications associated with medullar echogenicity, stone production, nephrocalcinosis, and impaired kidney function: “atypical daisy-like.” Medullary hyperechogenicity can have more US patterns. In MSK, if the medullary echogenicity is homogenous the evolution is benign, whereas the second, inhomogeneous pattern, has a variable clinical presentation with nephrocalcinosis and the outcome is more severe, leading to chronic kidney disease and impairing the quality of life.
Transforming Visions into Actions: Strategic change as a future-making process
Authors: Pettit Krista L. , Balogun Julia , Bennett Mandy
Published: April 2023

This paper draws on a longitudinal, qualitative study to develop an empirically grounded model of strategic change as a future-making process. We provide an alternative to linear models of strategic change and illustrate how, through iterative future-making cycles, an abstract vision for the future transforms into action. Our study exposes how shifts in the locus of situated actions and movement of people and ideas between organizational spaces widen participation and transform an imagined future into the everyday ways of working across an organization. We highlight the inclusionary affordances of bounded spaces as sites for interactions where movement of ideas and participants designing a desired future ‘give form’ and ‘make’ the future in the present.
Legitimizing political power from below. A reinterpretation of the founding myths of Thebes, Athens, and Rome as a critique against private and public violence
Authors: Calloni Marina
Published: April 2023

What do we mean when affirming ‘the powerful return of the state’? Do we have in mind the jus ad bellum employed by aggressive states, or are we thinking of the duties that a state has towards its citizens? Starting from these questions, this article aims to reconceptualize the issue of the political legitimacy of a state by reconsidering the relationship between power and violence. Among other forms of emergencies and violence, then, a legitimate state needs to be capable of responding to gender-based (sexual and domestic) violence.

To reinforce my suggestion, I will reinterpret some Greek and Roman myths related to the founding of cities (Thebes, Athens and Rome). Through these myths, we will be able to illustrate, in particular, the necessity for a state to be capable of combating both public and private violence, reframing the notion of nemesis (as a fate that can be changed by descendants) and fear (as a status that can be stopped in the present).
Toxicologic Pathology Forum Opinion: Interpretation of Gliosis in the Brain and Spinal Cord Observed During Nonclinical Safety Studies
Authors: Bolon Brad
Published: April 2023

Gliosis, defined as a nonneoplastic reaction (hypertrophy and/or proliferation) of astrocytes and/or microglial cells, is a frequent finding in the central nervous system (CNS [brain and/or spinal cord]) in nonclinical safety studies. Gliosis in rodents and nonrodents occurs at low incidence as a spontaneous finding and is induced by various test articles (e.g., biomolecules, cell and gene therapies, small molecules) delivered centrally (i.e., by injection or infusion into cerebrospinal fluid or neural tissue) or systemically. Several CNS gliosis patterns occur in nonclinical species. First, gliosis may accompany degeneration and/or necrosis of cells (mainly neurons) or neural parenchyma (neuron processes and myelin). Second, gliosis often follows inflammation (i.e., leukocyte accumulation causing parenchymal damage) or neoplasm formation. Third, gliosis may appear as variably sized, randomly scattered foci of reactive glial cells in the absence of visible parenchymal damage or inflammation. In interpreting test article–related CNS gliosis, adversity is indicated by parenchymal injury (e.g., degeneration, necrosis, or inflammation) and not the mere existence of a glial reaction. In the absence of clear structural damage to the parenchyma, gliosis as a standalone CNS finding should be interpreted as a nonadverse reaction to regional alterations in microenvironmental conditions rather than as evidence of a glial reaction associated with neurotoxicity.
Constructing Relative Effect Priors for Research Prioritization and Trial Design: A Meta-epidemiological Analysis
Authors: Glynn David , Nikolaidis Georgios , Jankovic Dina , Welton Nicky J.
Published: April 2023

Background

Bayesian methods have potential for efficient design of randomized clinical trials (RCTs) by incorporating existing evidence. Furthermore, value of information (VOI) methods estimate the value of reducing decision uncertainty, aiding transparent research prioritization. These methods require a prior distribution describing current uncertainty in key parameters, such as relative treatment effect (RTE). However, at the time of designing and commissioning research, there may be no data to base the prior on. The aim of this article is to present methods to construct priors for RTEs based on a collection of previous RCTs.

Methods

We developed 2 Bayesian hierarchical models that captured variability in RTE between studies within disease area accounting for study characteristics. We illustrate the methods using a data set of 743 published RCTs across 9 disease areas to obtain predictive distributions for RTEs for a range of disease areas. We illustrate how the priors from such an analysis can be used in a VOI analysis for an RCT in bladder cancer and compare the results with those using an uninformative prior.

Results

For most disease areas, the predicted RTE favored new interventions over comparators. The predicted effects and uncertainty differed across the 9 disease areas. VOI analysis showed that the expected value of research is much lower with our empirically derived prior compared with an uninformative prior.

Conclusions

This study demonstrates a novel approach to generating informative priors that can be used to aid research prioritization and trial design. The methods can also be used to combine RCT evidence with expert opinion. Further work is needed to create a rich database of RCT evidence that can be used to form off-the-shelf priors.

Highlights

Bayesian methods have potential to aid the efficient design of randomized clinical trials (RCTs) by incorporating existing evidence. Value-of-information (VOI) methods can be used to aid research prioritization by calculating the value of current decision uncertainty. These methods require a distribution describing current uncertainty in key parameters, that is, “prior distributions.” This article demonstrates a methodology to estimate prior distributions for relative treatment effects (odds and hazard ratios) estimated from a collection of previous RCTs. These results may be combined with expert elicitation to facilitate 1) value-of-information methods to prioritize research or 2) Bayesian methods for research design.
Analysis Framework to Assess Crash Severity for Large Trucks on Rural Interstate Roads Utilizing the Latent Class and Random Parameter Model
Authors: Gaweesh Sherif M. , Ahmed Irfan , Ahmed Mohamed M.
Published: April 2023

Truck freight has high importance to the national economy as it handles more cargo than other types of freight transportation. To improve the safety of commercial vehicles, several studies have focused on determining factors leading to crashes. Parametric models have been extensively employed to explain crash causal factors for heavy trucks. Unlike studies in the past, a comprehensive framework was proposed in this study to compare crash underlying factors utilizing several statistical approaches. The structural equation modeling approach was used to assess latent factors affecting the crash severity of large trucks. In addition, ordinary (binary) logistic and random parameter models were employed to assess the direct effect of the observed data, and the heterogeneity in parameter means was also estimated. Three crash categories were investigated: single-truck crashes, multi-vehicle truck crashes, and total truck crashes. A total of five years of crash data from 2015 to 2019 were analyzed. The results showed that multiple observed variables were factored to measure crash severity. Direct and indirect effects were identified, in which challenging roadway conditions had an indirect effect on crash severity for single-truck crashes. Random parameter logit models indicated that roadway geometry and adverse weather conditions were among the significant contributing factors increasing crash severity for trucks. This study recommends that improving the situational awareness of truck drivers, providing more frequent rest stops, updating variable speed limit algorithms, and integrating roadway geometry information into connected vehicle applications in Wyoming could be considered to assist stakeholders in promoting safety on rural interstate corridors.
Risk Factors for Upper Airway Diseases
Authors: Duse M. , Leonardi L. , Zicari A.M. , De Castro G. , Indinnimeo L.
Published: April 2023

Upper respiratory infection is the most common reason for seeking medical care for children. Recurrent viral respiratory infections and subsequent complications are a burden for children, their families and society. It has been estimated that at least 6% of children younger than 6 yr of age presents recurrent respiratory infections, as consequence of an increased exposure to infectious agents during the first years of life, when immune functions are still immature. Pediatricians must identify risk factors predisposing to upper respiratory tract infections and plan specific preventive strategies, ie avoidance of precocious day-care attendance and secondary smoke. Vaccination against influenza and pneumococcal diseases should always be recommended.
The Clinical Spectrum of Rhinosinusitis in Children
Authors: Leo G. , Incorvaia C.
Published: April 2023

Rhinosinusitis is an extremely common disease that is often underreported, especially in children. Its clinical spectrum includes acute rhinosinusitis (ARS) — which may present in the forms of ARS with persistent symptoms and ARS with severe symptoms — and chronic rhinosinusitis (CRS), characterized by a duration longer than 12 weeks and prevalence of symptoms such as nasal congestion and cough. Moreover, rhinosinusitis may present with associated disorders, that are nasal polyposis and aspirin sensitivity, asthma, otitis media with effusion, and gastroesophageal reflux. A particular form is fungal rhinosinusitis, presenting in an invasive and noninvasive form, the latter including allergic fungal sinusitis, which is the most common form of fungal rhinosinusitis and should be suspected in children with nasal polyposis and atopy.
Rhinosinusitis and Asthma
Authors: Marseglia G.L. , Caimmi S. , Marseglia A. , Poddighe D. , Leone M. , Caimmi D. , Ciprandi G. , Castellazzi A.M.
Published: April 2023

Chronic rhinosinusitis and asthma are not simply localized disease processes but part of a systemic inflammatory disease affecting the respiratory tract. There is a correlation between severity of asthma and the clinical and imaging features of rhinosinusitis. It is very important to understand that in patients with chronic sinus disease, both upper and lower airways need to be evaluated and treated and that in patients with moderate or severe asthma, the sinus area should always be investigated, regardless from the presence or not of nasal symptoms. Nasal endoscopy may be considered a feasible and correct approach in asthmatic children to investigate rhinosinusal or adenoid infections, even if they do not present with any clinical sign. Thus, it becomes more and more important to perform a simple easy and safe nasal endoscopy, in order to have a better chance to treat asthmatic children correctly by identifying a subclinical or an occult rhinosinusal infection.
Upper Respiratory Tract Infections and Atopy
Authors: Pollini F. , Capristo C. , Boner A.L.
Published: April 2023

Upper respiratory tract infections and allergic diseases are particularly common in children. It seems that atopy may predispose to more severe symptoms during infections and may facilitate together with other genetic factors and with adverse environmental conditions the occurrence of chronic rhinosinusitis (CRS) and chronic otitis media with effusion (OME). The initial event in CRS is the obstruction of the osteomeatal complex, while obstruction and dysfunction of the Eustachian tube may be the preliminary event for the development of OME.
Diagnostic Imaging of the Pediatric Nasal Cavity and Paranasal Sinuses
Authors: Triulzi F.
Published: April 2023

The vast majority of nasal and paranasal sinuses (PNS) diseases in childhood are of inflammatory origin, in particular during the early rapid development of PNS rhinosinusitis are exceedingly frequent in both acute and chronic forms. However other diseases such as primarily congenital malformation, but also neoplasms can affect the nasal cavity (NC) and PNS during pediatric age. Modern radiological techniques such as multidetector computerized tomography (MDCT) or magnetic resonance imaging (MRI) are becoming of greater importance in the diagnosis of chronic or complicated inflammatory processes of NC and PNS and in the differential diagnosis with the other less frequent diseases. The characteristic features of MDCT and MRI and their diagnostic role in the more frequent pediatric inflammatory, neoplastic and congenital diseases of NC and PNS are reviewed.