bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S15 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: September 2023

Percentage of each of three macrophage populations in individual FOVS from Patient 8
Data from Transcriptomic Signatures of MSI-High Metastatic Colorectal Cancer Predict Efficacy of Immune Checkpoint Inhibitors
Authors: Gallois Claire , Landi Matteo , Taieb Julien , Sroussi Marine , Saberzadeh-Ardestani Bahar , Cazelles Antoine , Lonardi Sara , Bergamo Francesca , Intini Rossana , Maddalena Giulia , Pietrantonio Filippo , Corti Francesca , Ambrosini Margherita , Martinetti Antonia , Germani Marco Maria , Boccaccio Chiara , Vetere Guglielmo , Mouillet-Richard Sophie , de Reynies Aurélien , Sinicrope Frank A. , Cremolini Chiara , Laurent-Puig Pierre
Published: September 2023

AbstractPurpose:
Microsatellite instability (MSI) is currently the only predictive biomarker of efficacy of immune checkpoint inhibitors (ICI) in metastatic colorectal cancers (mCRC). However, 10% to 40% of patients with MSI mCRC will experience a primary resistance to ICI.
Experimental Design:
In two cohorts of patients with MSI mCRC treated with ICI (exploratory, N = 103; validation, N = 35), 3′ RNA sequencing was performed from primary tumors. Previously described single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed.
Results:
In the exploratory cohort, the unsupervised clustering allowed the identification of three clusters of tumors with distinct transcriptional profiles: cluster A (“stromalHIGH-proliferationLOW”), cluster B (“stromalHIGH-proliferationMED”), and cluster C (“stromalLOW-proliferationHIGH”), with an enrichment of patients progressing at first disease assessment under ICI in cluster A (30% vs. 12% in cluster B and 8.1% in cluster C; P = 0.074). Progression-free survival (PFS) was also significantly shorter in patients belonging to cluster A, compared with clusters B or C (P < 0.001) with 2-year PFS rates of 33.5%, 80.5%, and 78.3%, respectively. In multivariate analysis, PFS was still significantly longer in patients belonging to cluster B [HR, 0.19; 95% confidence interval (CI), 0.08–0.45; P < 0.001] and cluster C (HR, 0.25; 95% CI, 0.10–0.59; P = 0.02), compared with patients belonging to cluster A. The association of this clustering with PFS under ICI was confirmed in the validation cohort. PFS related to non–ICI-based regimens was not significantly different according to cluster.
Conclusions:
This unsupervised transcriptomic classification identified three groups of MSI mCRCs with different compositions of TME cells and proliferative capacities of TME/tumor cells. The “stromalHIGH-proliferationLOW” cluster is associated with a poorer prognosis with ICI treatment.
Data from A Phase I/IIa Trial of Yttrium-90 Radioembolization in Combination with Durvalumab for Locally Advanced Unresectable Hepatocellular Carcinoma
Authors: Lee Yun Bin , Nam Joon Yeul , Cho Eun Ju , Lee Jeong-Hoon , Yu Su Jong , Kim Hyo-Cheol , Paeng Jin Chul , Yoon Jung-Hwan , Kim Yoon Jun
Published: September 2023

AbstractPurpose:
Synergistic effect of radiotherapy and immunotherapy for the treatment of hepatocellular carcinoma (HCC) has been reported. This phase I/IIa pilot trial evaluated preliminary efficacy and safety of combination of radioembolization with yttrium-90 microspheres (Y90-radioembolization) and durvalumab in patients with locally advanced unresectable HCC.
Patients and Methods:
Patients with Child-Pugh score ≤ 7 and locally advanced HCC, defined as Barcelona Clinic Liver Cancer (BCLC) stage B HCC or BCLC-C disease without extrahepatic metastases, received Y90-radioembolization followed by intravenous durvalumab 1,500 mg 7 to 14 days after Y90-radioembolization and every 4 weeks thereafter. Primary endpoint was time to progression (TTP) assessed by modified RECIST (mRECIST). Secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) determined by mRECIST, and safety.
Results:
All 24 patients enrolled received Y90-radioembolization and 23 received at least one dose of durvalumab. Median follow-up duration was 19.0 months (range, 2.2–24.2). Median TTP was 15.2 months [95% confidence interval (CI), 6.1–not estimated]. Median OS was not reached and 18-month OS rate was 58.3% (95% CI, 36.4–75.0). Median PFS was 6.9 months (95% CI, 5.4–15.2). Seven (29.2%) patients had a complete response and 13 (54.2%) had a partial response; ORR was 83.3% (95% CI, 62.6–95.3). Eleven (47.8%) patients experienced any-grade treatment-related adverse events. Two (8.7%) patients had grade 3 treatment-related adverse events (neutropenia and fever). None experienced any treatment-related serious adverse events.
Conclusions:
In patients with locally advanced unresectable HCC, the combination of Y90-radioembolization and durvalumab demonstrated promising efficacy and safety, warranting further evaluation in large-scale controlled trials.
Data from Evaluation of Somatic Mutations in Urine Samples as a Noninvasive Method for the Detection and Molecular Classification of Endometrial Cancer
Authors: Costas Laura , Onieva Irene , Pelegrina Beatriz , Marin Fátima , Carmona Álvaro , López-Querol Marta , Frias-Gomez Jon , Peremiquel-Trillas Paula , Martínez José Manuel , Dorca Eduard , Brunet Joan , Pineda Marta , Ponce Jordi , Matias-Guiu Xavier , de Sanjosé Silvia , Bosch Francesc Xavier , Alemany Laia , Paytubi Sonia
Published: September 2023

AbstractPurpose:
Current diagnostic methods for endometrial cancer lack specificity, leading to many women undergoing invasive procedures. The aim of this study was to evaluate somatic mutations in urine to accurately discriminate patients with endometrial cancer from controls.
Experimental Design:
Overall, 72 samples were analyzed using next-generation sequencing (NGS) with molecular identifiers targeting 47 genes. We evaluated urine supernatant samples from women with endometrial cancer (n = 19) and age-matched controls (n = 20). Cell pellets from urine and plasma samples from seven cases were sequenced; further, we also evaluated paired tumor samples from all cases. Finally, immunohistochemical markers for molecular profiling were evaluated in all tumor samples.
Results:
Overall, we were able to identify mutations in DNA from urine supernatant samples in 100% of endometrial cancers. In contrast, only one control (5%) showed variants at a variant allele frequency (VAF) ≥ 2% in the urine supernatant samples. The molecular classification obtained by using tumor samples and urine samples showed good agreement. Analyses in paired samples revealed a higher number of mutations and VAF in urine supernatants than in urine cell pellets and blood samples.
Conclusions:
Evaluation of somatic mutations using urine samples may offer a user-friendly and reliable tool for endometrial cancer detection and molecular classification. The diagnostic performance for endometrial cancer detection was very high, and cases could be molecularly classified using these noninvasive and self-collected samples. Additional multicenter evaluations using larger sample sizes are needed to validate the results and understand the potential of urine samples for the early detection and prognosis of endometrial cancer.
Precision Oncology Comes of Age: Designing Best-in-Class Small Molecules by Integrating Two Decades of Advances in Chemistry, Target Biology, and Data Science
Authors: Stuart Darrin D. , Guzman-Perez Angel , Brooijmans Natasja , Jackson Erica L. , Kryukov Gregory V. , Friedman Adam A. , Hoos Axel
Published: September 2023

Small-molecule drugs have enabled the practice of precision oncology for genetically defined patient populations since the first approval of imatinib in 2001. Scientific and technology advances over this 20-year period have driven the evolution of cancer biology, medicinal chemistry, and data science. Collectively, these advances provide tools to more consistently design best-in-class small-molecule drugs against known, previously undruggable, and novel cancer targets. The integration of these tools and their customization in the hands of skilled drug hunters will be necessary to enable the discovery of transformational therapies for patients across a wider spectrum of cancers.

Significance:

Target-centric small-molecule drug discovery necessitates the consideration of multiple approaches to identify chemical matter that can be optimized into drug candidates. To do this successfully and consistently, drug hunters require a comprehensive toolbox to avoid following the “law of instrument” or Maslow's hammer concept where only one tool is applied regardless of the requirements of the task. Combining our ever-increasing understanding of cancer and cancer targets with the technological advances in drug discovery described below will accelerate the next generation of small-molecule drugs in oncology.
Integrated Assessment of Computational Coronary Physiology From a Single Angiographic View in Patients Undergoing TAVI
Authors: Fezzi Simone , Ding Daixin , Scarsini Roberto , Huang Jiayue , Del Sole Paolo Alberto , Zhao Qiang , Pesarini Gabriele , Simpkin Andrew , Wijns William , Ribichini Flavio , Tu Shengxian
Published: September 2023

BACKGROUND:

Angiography-derived computational physiology is an appealing alternative to pressure-wire coronary physiology assessment. However, little is known about its reliability in the setting of severe aortic stenosis. This study sought to provide an integrated assessment of epicardial and microvascular coronary circulation by means of single-view angiography-derived physiology in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI).

METHODS:

Pre-TAVI angiographic projections of 198 stenotic coronary arteries (123 patients) were analyzed by means of Murray’s law-based quantitative flow ratio and angiography microvascular resistance. Wire-based reference measurements were available for comparison: fractional flow reserve (FFR) in all cases, instantaneous wave-free ratio in 148, and index of microvascular resistance in 42 arteries.

RESULTS:

No difference in terms of the number of ischemia-causing stenoses was detected between FFR ≤0.80 and Murray’s law-based quantitative flow ratio ≤0.80 (19.7% versus 19.2%;
P
=0.899), while this was significantly higher when instantaneous wave-free ratio ≤0.89 (44.6%;
P
=0.001) was used. The accuracy of Murray’s law-based quantitative flow ratio ≤0.80 in predicting pre-TAVI FFR ≤0.80 was significantly higher than the accuracy of instantaneous wave-free ratio ≤0.89 (93.4% versus 77.0%;
P
=0.001), driven by a higher positive predictive value (86.9% versus 50%). Similar findings were observed when considering post-TAVI FFR ≤0.80 as reference. In 82 cases with post-TAVI angiographic projections, Murray’s law-based quantitative flow ratio values remained stable, with a low rate of reclassification of stenosis significance (9.9%), similar to FFR and instantaneous wave-free ratio. Angiography microvascular resistance demonstrated a significant correlation (Rho=0.458;
P
=0.002) with index of microvascular resistance, showing an area under the curve of 0.887 (95% CI, 0.752–0.964) in predicting index of microvascular resistance ≥25.

CONCLUSIONS:

Angiography-derived physiology provides a valid, reliable, and systematic assessment of the coronary circulation in a complex scenario, such as severe aortic stenosis.
Elimination of CaMKIIδ Autophosphorylation by CRISPR-Cas9 Base Editing Improves Survival and Cardiac Function in Heart Failure in Mice
Authors: Lebek Simon , Caravia Xurde M. , Chemello Francesco , Tan Wei , McAnally John R. , Chen Kenian , Xu Lin , Liu Ning , Bassel-Duby Rhonda , Olson Eric N.
Published: September 2023

BACKGROUND:

Cardiovascular diseases are the main cause of worldwide morbidity and mortality, highlighting the need for new therapeutic strategies. Autophosphorylation and subsequent overactivation of the cardiac stress-responsive enzyme CaMKIIδ (Ca
2+
/calmodulin-dependent protein kinase IIδ) serves as a central driver of multiple cardiac disorders.

METHODS:

To develop a comprehensive therapy for heart failure, we used CRISPR-Cas9 adenine base editing to ablate the autophosphorylation site of CaMKIIδ. We generated mice harboring a phospho-resistant CaMKIIδ mutation in the germline and subjected these mice to severe transverse aortic constriction, a model for heart failure. Cardiac function, transcriptional changes, apoptosis, and fibrosis were assessed by echocardiography, RNA sequencing, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and standard histology, respectively. Specificity toward
CaMKIIδ
gene editing was assessed using deep amplicon sequencing. Cellular Ca
2+
homeostasis was analyzed using epifluorescence microscopy in Fura-2–loaded cardiomyocytes.

RESULTS:

Within 2 weeks after severe transverse aortic constriction surgery, 65% of all wild-type mice died, and the surviving mice showed dramatically impaired cardiac function. In contrast to wild-type mice, CaMKIIδ phospho-resistant gene-edited mice showed a mortality rate of only 11% and exhibited substantially improved cardiac function after severe transverse aortic constriction. Moreover, CaMKIIδ phospho-resistant mice were protected from heart failure–related aberrant changes in cardiac gene expression, myocardial apoptosis, and subsequent fibrosis, which were observed in wild-type mice after severe transverse aortic constriction. On the basis of identical mouse and human genome sequences encoding the autophosphorylation site of
CaMKIIδ
, we deployed the same editing strategy to modify this pathogenic site in human induced pluripotent stem cells. It is notable that we detected a >2000-fold increased specificity for editing of
CaMKIIδ
compared with other
CaMKII
isoforms, which is an important safety feature. While wild-type cardiomyocytes showed impaired Ca
2+
transients and an increased frequency of arrhythmias after chronic β-adrenergic stress,
CaMKIIδ
-edited cardiomyocytes were protected from these adverse responses.

CONCLUSIONS:

Ablation of CaMKIIδ autophosphorylation by adenine base editing may offer a potential broad-based therapeutic concept for human cardiac disease.
Modeling the cell-type-specific mesoscale murine connectome with anterograde tracing experiments
Authors: Koelle Samson , Mastrovito Dana , Whitesell Jennifer D. , Hirokawa Karla E. , Zeng Hongkui , Meila Marina , Harris Julie A. , Mihalas Stefan
Published: September 2023

The Allen Mouse Brain Connectivity Atlas consists of anterograde tracing experiments targeting diverse structures and classes of projecting neurons. Beyond regional anterograde tracing done in C57BL/6 wild-type mice, a large fraction of experiments are performed using transgenic Cre-lines. This allows access to cell-class-specific whole-brain connectivity information, with class defined by the transgenic lines. However, even though the number of experiments is large, it does not come close to covering all existing cell classes in every area where they exist. Here, we study how much we can fill in these gaps and estimate the cell-class-specific connectivity function given the simplifying assumptions that nearby voxels have smoothly varying projections, but that these projection tensors can change sharply depending on the region and class of the projecting cells. This paper describes the conversion of Cre-line tracer experiments into class-specific connectivity matrices representing the connection strengths between source and target structures. We introduce and validate a novel statistical model for creation of connectivity matrices. We extend the Nadaraya-Watson kernel learning method that we previously used to fill in spatial gaps to also fill in gaps in cell-class connectivity information. To do this, we construct a “cell-class space” based on class-specific averaged regionalized projections and combine smoothing in 3D space as well as in this abstract space to share information between similar neuron classes. Using this method, we construct a set of connectivity matrices using multiple levels of resolution at which discontinuities in connectivity are assumed. We show that the connectivities obtained from this model display expected cell-type- and structure-specific connectivities. We also show that the wild-type connectivity matrix can be factored using a sparse set of factors, and analyze the informativeness of this latent variable model.
Inequality Below the Poverty Line since 1967: The Role of the U.S. Welfare State
Authors: Parolin Zachary , Desmond Matthew , Wimer Christopher
Published: September 2023

Since the War on Poverty in the 1960s, the U.S. social safety net has shifted away from direct cash assistance for the lowest-income households and toward tax-based transfers targeted at working families with children. Previous research has assessed this shift by evaluating its effect on the national poverty rate. Doing so, however, overlooks how it may also have led to increased inequality among low-income households. We apply a decomposition framework to measure how changes in taxes/transfers and composition have affected trends in inequality below the poverty line from 1967 to 2019. Income inequality among the poorest households has been volatile since the 1960s, and changes to the American welfare state played a decisive role in expanding or reducing inequality below the poverty line. Unlike in previous decades, after the mid-1990s, the policies that most reduced poverty were also those that most increased inequality among the poor. These findings challenge standard theories regarding the effectiveness of income transfers in reducing poverty by revealing that recent state-led antipoverty efforts have placed the near poor and the deeply poor on divergent paths.
Temperature Measurement of Trapped, Thermally Sensitive Single Particles in an Optical Trap Using Raman Spectroscopy
Authors: Ai Yukai , Pan Yong-Le , Videen Gorden , Wang Chuji
Published: September 2023

Single particles trapped in an optical trap may experience temperature elevation, yet direct measurement of temperature and its distribution inside the optical trap of several to hundreds of microns in size remains a big challenge. We introduce a method that can measure the temperature inside a universal optical trap (UOT) using Raman spectroscopy of single trapped particles of high thermal conductivity. We measured temperature and temperature distributions inside the UOT using Raman shifts of single-walled carbon nanotubes (SWCNTs) and micron-sized diamonds (MSDs), which are heated by trapping laser beams directly or indirectly, depending on the location of the particle in the trap. We show that the temperature at the center of the UOT is much lower than the temperature along the hollow beams that form a hollow, cage-shaped UOT. In the range of the trapping laser power of 200–2950 mW, the surface temperature of particles trapped at the center of a UOT changes from 322 K to 830 K, correspondingly. This result gives a heating rate as a high thermal-absorbing particle trapped in the center of the UOT with 18.3 ± 0.4 °C/100 mW. In addition, the temperature gradient outside the UOT was also characterized by trapping SWCNT particles outside the UOT. Results show that when a light-absorbing particle is trapped for the study of material property, phase transitions, surface equilibrium process, chemical reactions, etc., this method can be used to measure temperature distribution and its variations in the trap and its surroundings.
Decreasing Variation to Enhance Accurate Identification of Hypothermic Infants in Pediatric Primary Care
Authors: Burkhardt Mary Carol , Schlottmann Haley , Reyner Allison , Mescher Anne
Published: September 2023

Hypothermia can be the first and only sign of sepsis in young infants, yet there is a paucity of standard recommendations for pediatric primary-care office management of those infants identified. The SMART aim of this study was to standardize the identification and care of infants age 0 to 49 days at risk of hypothermia in pediatric primary care by decreasing the percent of infants with temperatures ≤36.5°C from 24% to 10% within 2 years. Over the course of this project, variation in documented temperatures ≤36.5°C decreased from 24% to 7% of encounters. Temperatures ≤36.5°C were documented for 951 infants or 13.4% (1078 of 8020 encounters). Of the 951 infants with temperatures ≤36.5°C, 96.1% were rewarmed in the office. Thirty-one patients ultimately required hospitalization. Application of quality improvement in a primary-care office decreased low temperatures by standardizing care, empowering staff, and triaging at-risk infants to the most appropriate level of care.
Assessing the effectiveness of a school educational video on cancer and radiotherapy
Authors: Minamitani Masanari , Katano Atsuto , Nakagawa Keiichi
Published: September 2023

Background:

Japan has recently begun introducing educational programmes on cancer as part of health and physical education (HPE) classes in schools. In support of this work, the Japanese Society for Radiation Oncology has developed an educational video to enhance children’s understanding of cancer and radiotherapy.

Objectives:

This study examined the perceived effectiveness of this video among teachers and clarified whether their specialisation played a role in their responses.

Methods:

An online survey was administered to junior and senior high school teachers without a history of cancer. Respondents’ demographic characteristics, healthy lifestyle habits, anxiety about cancer treatment and knowledge about cancer and radiotherapy were surveyed pre- and post-video. We compared the data from science teachers, HPE teachers and teachers of other specialties. Subsequently, we performed a multiple logistic regression analysis to estimate significant factors that predicted post-watch correct-answer rates.

Results:

Science teachers were less anxious about radiotherapy and surgery than the other-specialty teachers. They were also the most knowledgeable about cancer and radiotherapy. Post-viewing correct-answer rates improved, except for questions about the work of medical physicists and damage to normal cells. The multiple regression analysis identified age (β = .07), sex (β = .08), anxiety about radiotherapy (β = −.09) and pre-video correct-answer rates (β = .46) as significant factors predicting post-watch correct-answer rates.

Conclusion:

The video was beneficial in enhancing teachers’ understanding of cancer and radiotherapy. Compared with HPE and other-specialty teachers, science teachers were superior in terms of cancer and radiotherapy comprehension. There may be value in exploring possibilities for cross-disciplinary instruction involving not only HPE but also science teachers in cancer education, especially radiotherapy education.
Has South Korea’s policy of relocating public institutions been successful? A case study of 12 agglomeration areas under the Innovation City Policy
Authors: Kang Song Hee , Lee Jae Seung , Kim Saehoon
Published: September 2023

South Korea’s Innovation City policy aims to balance the geography of economic activity across the country by relocating public institutions to local cities. The economic impact of relocating public institutions to local cities has been assessed by examining job creation, public spending, the quality of public services or demands for housing and employment in donor cities. However, as economies have become increasingly knowledge-based, the attractiveness of urban areas to young workers has become a metric to measure an area’s economic development potential. There is a paucity of research on the economic impact of relocating public institutions that analyses the attractiveness of the destination cities for young people. Thus, this paper examines the migration of young people to evaluate the economic impact of relocating public institutions on the balanced geography of economic activity across the country. The examination was conducted by analysing the effects of (1) agglomeration area location type and (2) general place quality on young people’s migration. Quasi-experimental research and panel regression (2010–2019) were conducted on 12 agglomeration areas. The findings revealed that relocating public institutions was more likely to attract young migrants than the control group, whereas outskirt agglomeration areas attracted and retained young people more than inner city agglomeration areas. Relocating public institutions is a strategic means of attracting young people to local cities to balance the geography of economic activity. Here, the effect of relocating public institutions on young people’s migration varies depending on the location of agglomeration areas and the place quality of destination cities.
Executive Orders: Mandating Inclusion in the Federal Workplace: Insights from Federal Executive Departments’ Strategic Plans
Authors: Sweeting Karen D.
Published: September 2023

Inclusion remains a very real and legitimate concern in contemporary workplaces. This research examines how executive orders from the Obama, Trump, and Biden administrations influenced Biden era Federal Executive Departments’ strategic plans. This study analyzed the interpretation and understanding of departments’ prioritization and articulation of inclusion across seven core functional areas: (a) leadership; (b) policies, practices, and procedures; (c) human resource management; (d) culture, climate, and norms; (e) emotion, engagement, and perceptions; (f) training and professional development; and (g) accountability and sustainability. The findings reveal that inclusion cannot be mandated or rubberstamped. Inclusion is a subjective endeavor that can result in multiple realities as different employees can experience/observe the same event differently, sometimes infinitely so. The seven core functional areas offer a pathway to embedding inclusive practices and initiatives in the workplace. They create a common approach the federal government can undertake, prioritizing broader knowledge and fundamental awareness of the intertwined nature of experiences, perceptions, emotions, and reasons to foster a sense of belonging.
Model-free adaptive backstepping control for a class of uncertain nonlinear systems
Authors: Segheri Mohamed , Boudjemaa Fares , Nemra Abdelkrim , Bibi Youssouf
Published: September 2023

Most nonlinear dynamic systems are characterized by uncertainties in models and parameters. Deterministic models cannot account for these uncertainties; therefore, model-based control using such models cannot provide the required performance. It is crucial to establish a practical concept of model-free control as a powerful alternative to model-based control. This paper develops a model-free adaptive backstepping control (MFABC) based on type 2 fuzzy Petri nets for a class of uncertain nonlinear systems. To provide valuable robustness to the MFABC structure, we have exploited the universal approximation property of type 2 fuzzy Petri nets to approximate the different nonlinear functions of the uncertain nonlinear system. The parameter adaptive laws are designed by the Lyapunov function; the stability and error convergence can be guaranteed. The simulation tests show that the proposed MFABC can provide good performance and high accuracy compared with the backstepping control. Moreover, the stability of this control scheme is affirmed.
Lookism Climate in Organizations: Construct Development and Validation of a Scale
Authors: Dossinger Karyn , Wanberg Connie R. , Song Youjeong , Basbug Gokce
Published: September 2023

Research suggests that physically attractive employees receive myriad workplace and career advantages compared to less attractive employees. Despite calls for more attention to the role of organizational context in understanding this phenomenon, a theoretically grounded conceptualization of an employer's value for physically attractive employees and a method of measuring this aspect of the work environment is currently absent from the literature. In this study, we introduce the construct lookism climate, which reflects perceptions that a given work environment implicitly or explicitly values employee physical attractiveness. We develop and validate a measure of lookism climate using eight samples comprising 1,857 full-time employed adults in the United States and South Korea. We establish the psychometric properties and nomological network of the Lookism Climate Scale (LCS), including its factor structure, convergent, discriminant, and criterion validity, and measurement equivalence. We provide evidence that the LCS can be used as an assessment of an individual's perceptions of workplace climate as well as employees’ shared conceptualization of climate. We also offer narrative examples of employee experiences with lookism climate. The introduction of the construct lookism climate and the LCS provides a pathway for future researchers to develop a deeper understanding of how organizational context contributes to the “beauty premium” in the workplace.
White Parent and Caregiver Perceptions of, and Resistance to, Equity and Anti-Racism Work in an Independent School
Authors: Clonan-Roy Katherine “Katie” , Maton Rhiannon , Jacobs Charlotte E. , Matthews Casey , Kokozos Michael , Kitzmiller Erika
Published: September 2023

Background:

Between early 2020 and today, our society has experienced a distressing global pandemic, horrifying brutalities committed against BIPOC individuals and communities, uprisings for racial justice, and a violent attack on our nation’s capital. While these events and phenomena have been challenging and traumatic, they have also inspired calls for equity-focused action within and beyond schools.

Purpose:

Many schools have intensified their diversity, equity, inclusion, justice, and anti-racism (DEIJA) work by revising their curricula, providing equity-focused professional development for educators, offering extracurricular programs like affinity and accountability spaces for BIPOC and white students, and many other initiatives. However, this work has occurred against a contentious backdrop, including parent and caregiver resistance to DEIJA work and attacks on schools for allegedly teaching critical race theory.

Research Design:

Between the summer of 2020 and the spring of 2022, we conducted research with one independent school, called the Waterford School, in a metropolitan area as it engaged in intensified DEIJA work. During this time, we surveyed and ran focus groups with caregivers, students, faculty, staff, and administrators to capture their experiences with and perspectives on school DEIJA work. White caregivers were the most vocal and resistant constituent group, and in this article, we examine the perspectives that they brought to these conversations on Waterford’s DEIJA initiatives.

Conclusions:

This analysis shows how, in both their support of and dissent to the DEIJA work, white caregivers’ perspectives often reflected and reinforced characteristics associated with white supremacy culture (WSC). We also show how caregivers’ perspectives on the DEIJA work and pressure on Waterford often posed racial equity detours, which created an illusion of progress toward racial equity while obscuring ongoing racial inequity.
Discovering research data management trends from job advertisements using a text-mining approach
Authors: Sheriff Naseema , Sevukan R
Published: September 2023

In today’s data-driven culture, research data management (RDM) is essential for the research community. The demand for reusing research datasets is a challenging and diverse process for the scientific community. Despite this, it is essential in RDM to discover trends and themes using text mining, which is scarce. The purpose of this study is to employ text mining to discover insights from job advertisements associated with RDM profiles, which collected 810 advertisements. We found RDM-related patterns using latent Dirichlet allocation (LDA) and identified three key contexts. The first is ‘research services in libraries’, with the topics of research services, research information, research universities, collection processes and library services. The second context is ‘research data’, which includes RDM, business data, university data, research data, health research, science research, social science research, data centres, data services, statistical software, digital scholarship and digital preservation. The third context is ‘workplace environment’, and the topics are leadership, work development and scientific position. Job title normalisation reveals names such as ‘data librarian’, ‘librarian’, ‘director’, ‘data curator’, ‘data manager’, ‘research data librarian’, ‘data specialist’ and ‘data officer’ are frequently employed. Focusing on titles with a single or double occurrence is new and interesting for developing nations. Reputable institutions such as Harvard, Stanford and the Massachusetts Institute of Technology, as well as countries such as the United States, the United Kingdom, Canada and Germany, are the major participants in RDM practises and services. This discovery will assist higher education institutions, RDM stakeholders, which aid in the formulation of curriculum, and job seekers to familiarise themselves with the themes.
Gender and enterprise: The use of entrepreneurship support organisations by men and women
Authors: Gilfillan Colin , Jones Andrew
Published: September 2023

This In Perspective paper reflects on the use by men and women of entrepreneurship support organisations (ESOs). It arose through an inquiry conducted in partnership by London South Bank University and Shared Enterprise, the latter being an ESO based in London. As part of the inquiry, a small number of other ESOs in London were interviewed, who revealed that the majority of their participants were women, although the gender imbalance is not as extreme as is the case with Shared Enterprise. On the other hand, far more enterprises in Britain are led by men than are led by women. According to the Longitudinal Small Business Survey (LSBS), only 20% of very small businesses (no employees) were led by women, and 60% were led solely by a man. A similar proportion – 19% – of small- and medium-sized enterprises (SMEs) with employees was defined as led by women. A combination of interviews with Shared Enterprise participants and a desk review leads to a (tentative) solution to this seemingly puzzling paradox: women who aspire to entrepreneurship use ESOs more than men because they need them more.
Effectiveness and safety of opioids on breathlessness and exercise endurance in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis of randomised controlled trials
Authors: Liu Meilu , Xiao Wei , Du Longyi , Yu Yan , Chen Xugui , Mao Bing , Fu Juanjuan
Published: September 2023

Background:

Opioids are recommended to treat advanced refractory dyspnoea despite optimal therapy by the American Thoracic Society clinical practice guidelines, while newly published randomised controlled trials of opioids in chronic obstructive pulmonary disease yield conflicting results.

Aim:

This study aimed to evaluate the effectiveness and safety of opioids for patients with chronic obstructive pulmonary disease.

Design:

Systematic review and meta-analysis (PROSPERO CRD42021272556).

Data sources:

Databases of PubMed, EMBASE and CENTRAL were searched from inception to 2022 for eligible randomised controlled trials.

Results:

Twenty-four studies including 975 patients, were included. In cross-over studies, opioids improved breathlessness (standardised mean difference, −0.43; 95% CI, −0.55 to −0.30; I2 = 18%) and exercise endurance (standardised mean difference, 0.22; 95% CI, 0.02–0.41; I2 = 70%). However, opioids failed to improve dyspnoea (standardised mean difference, −0.02; 95% CI, −0.22 to 0.19; I2 = 39%) and exercise endurance (standardised mean difference, 0.00; 95% CI, −0.27 to 0.27; I2 = 0%) in parallel control studies that administered sustained-release opioids for more than 1 week. The opioids used in most crossover studies were short-acting and rarely associated with serious adverse effects. Only minor side effects such as dizziness, nausea, constipation and vomiting were identified for short-acting opioids.

Conclusions:

Sustained-release opioids did not improve dyspnoea and exercise endurance. Short-acting opioids appeared to be safe, have potential to lessen dyspnoea and improve exercise endurance, supporting benefit in managing episodes of breathlessness and providing prophylactic treatment for exertional dyspnoea.
Preliminary pharmacokinetics and patient experience of jet-injected dexmedetomidine in healthy adults
Authors: Whittle Nicola M , Sleigh Jamie W , McKeage James W , Termaat Jonathan , Voss Logan J , Anderson Brian J
Published: September 2023

Jet injection is a drug delivery system without a needle. A compressed liquid drug formulation pierces the skin, depositing the drug into the subcutaneous or intramuscular tissues. We investigated the pharmacokinetics and patient experience of dexmedetomidine administered using jet injection in six healthy adult study participants. This needleless jet injection device was used to administer dexmedetomidine 0.5 μg/kg to the subcutaneous tissues overlying the deltoid muscle. Serum concentrations of dexmedetomidine were assayed at approximately 5 minutes, 15 minutes, 30 minutes, 1 hour and 4 hours after administration. Pharmacokinetic interrogation of concentration time profiles estimated an absorption half time for jet-injected dexmedetomidine of 21 minutes (coefficient of variation 69.4%) with a relative bioavailability assumed unity. In our samples the measured median peak (range) concentration was 0.164 μg/l (0.011–0.325 μg/l), observed in the sample taken at a median (range) of 13.5 minutes (11–30 minutes). The Richmond agitation sedation scale was used to assess the sedative effect, and scored 0 (alert and calm) or –1 (drowsy) in all participants. Five of the six participants stated they would prefer jet injection to needle injection in the future and one had no preference. The findings suggest that the use of a larger dose (>2 μg/kg) would be required to achieve the clinically relevant target concentration of 1 μg/l necessary to achieve deeper sedation (Richmond agitation sedation scale ≤3).
Evaluation of the therapeutic effect of chitosan scaffolds loaded with the different concentrations of Hesperidin in bone regeneration in rat model
Authors: Gharibblouk Mohadese , Haji Ghasem Kashani Maryam , Nasiri Meysam , Ehterami Arian , Tabatabai Tayebeh Sadat , Salehi Majid
Published: September 2023

Bone grafts are widely used to improve bone healing but this method is costly and make some serious problems like infection in long-term use. To solve these problems, tissue engineering by using scaffolds made of different materials can be used as a supportive structure to enhance bone healing. In the current study, 3-D chitosan (CS) bone scaffold was developed by freeze-drying techniques for bone tissue engineering. The efficiency of the CS scaffold was improved by loading different concentrations of Hesperidin (Hes). Scaffolds were characterized by different mechanical and biological tests to evaluate their properties. In addition, the effect of scaffolds on bone healing was evaluated by a rat femur defect model. Results showed that the porosity of scaffolds was about 45–257 µm and Hes has a negative effect on the mechanical strength of scaffolds. Also, due to the hydrophilic properties of Hes, the degradation rate increased. Histological and CT-Scan evaluation showed that the treated groups which scaffold loaded with 1% and 10% of Hes were fully replaced by new bone and collagenous matrix compared to control and Hesperidin (0%, 0.01%, 0.1%) treated groups. The Runx2 gene expression was significantly increased by 1% and 10% compared to other groups. These results showed the positive effect of the fabricated scaffold on osteogenesis and bone healing and the possibility of using it in clinical trials.
Associations Between Patient-Reported Experiences with Opioid Use Disorder Treatment and Unmet Treatment Needs and Discontinuation Among Virginia Medicaid Members
Authors: Marks Sarah J. , Pham Huyen , McCray Neil , Palazzolo Jennifer , Harrell Ashley , Lowe Jason , Bachireddy Chethan , Guerra Lauren , Cunningham Peter J. , Barnes Andrew J.
Published: September 2023

Background:

Many payers, including Medicaid, the largest payer of opioid use disorder (OUD) treatment, are pursuing treatment-related quality improvement initiatives. Yet, how patient-reported experiences with OUD treatment relate to patient-centered outcomes remains poorly understood.

Aim:

To examine associations between Medicaid members’ OUD treatment experiences, outpatient treatment settings, demographic and social factors, and members’ self-report of unmet needs during treatment and treatment discontinuation.

Methods:

A sample of Virginia Medicaid members aged 21 years or older with OUD diagnoses who received outpatient OUD treatment completed a mail survey between January 2020 and August 2021 (n = 1042, weighted n = 9244). A treatment experience index was constructed from responses to four items from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) relating to feelings of involvement, safety, and respect and having treatment explained in an understandable way; two additional CAHPS items: “given options for treatment” and “able to refuse treatment” were also assessed. Weighted imputed logistic regressions tested adjusted associations between members’ treatment experiences, demographic and social factors, and two outcomes capturing unmet needs during treatment and treatment discontinuation.

Results:

More positive scores on the treatment experiences index were associated with lower adjusted odds of reporting unmet needs during treatment (aOR: 0.52, 95% CI: 0.41-0.66) and discontinuation (aOR: 0.63, 95% CI: 0.47-0.79). Respondents with serious psychological distress had higher odds of reporting unmet needs during treatment (aOR: 1.69 95% CI: 1.14-2.51) and discontinuation (aOR: 1.84, 95% CI: 1.21-2.82), as did individuals with housing insecurity (unmet needs: (aOR: 1.65, 95% CI: 1.11-2.44); treatment discontinuation: (aOR: 1.56, 95% CI: 1.04-2.36)).

Conclusion:

Using a first-of-its-kind survey of Medicaid members with OUD, we found that members who had more positive treatment experiences were less likely to report unmet treatment needs and discontinue treatment. Care approaches focused on improving patient experience are critical to delivering effective, high-quality OUD treatment.
Breastfeeding Behavior Within the Covid-19 Related Obstetric and Neonatal Outcome Study (CRONOS)
Authors: Zöllkau Janine , Heimann Yvonne , Hagenbeck Carsten , Pecks Ulrich , Abou-Dakn Michael , Schlösser Rolf , Schohe Anna , Dressler-Steinbach Iris , Manz Maike , Banz-Jansen Constanze , Reuschel Edith , Iannaccone Antonella , Bohlmann Michael K. , Kraft Katrina , Fill Malfertheiner Sara , Wimberger Pauline , Kolben Thomas , Bartmann Catharina , Longardt Ann-Carolin
Published: September 2023

Background:

The SARS-CoV-2 pandemic and its influence on peripartum processes worldwide led to issues in breastfeeding support.

Research Aim:

The aim of this study was to describe breastfeeding behavior and peripartum in-hospital management during the pandemic in Germany and Austria.

Methods:

This study was a descriptive study using a combination of secondary longitudinal data and a cross-sectional online survey. Registry data from the prospective multicenter COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS) cohort study (longitudinal, medical records of 1,815 parent-neonate pairs with confirmed SARS-CoV-2 infection during pregnancy) and a cross-sectional online survey of CRONOS hospitals’ physicians ( N = 67) were used for a descriptive comparison of feeding outcomes and postpartum management.

Results:

In 93.7% (n = 1700) of the cases in which information on the neonate's diet was provided, feeding was with the mother’s own milk. Among neonates not receiving their mother’s own milk, 24.3% ( n = 26) reported SARS-CoV-2 infection as the reason. Peripartum maternal SARS-CoV-2 infection, severe maternal COVID-19 including the need for intensive care unit (ICU) treatment or invasive ventilation, preterm birth, mandatory delivery due to COVID-19, and neonatal ICU admission were associated with lower rates of breastfeeding. Rooming-in positively influenced breastfeeding without affecting neonatal SARS-CoV-2 frequency (4.2% vs. 5.6%). CRONOS hospitals reported that feeding an infant their mother’s own milk continued to be supported during the pandemic. In cases of severe COVID-19, four of five hospitals encouraged breastfeeding.

Conclusion:

Maintaining rooming-in and breastfeeding support services in the CRONOS hospitals during the pandemic resulted in high breastfeeding rates.
Aerothermodynamic analysis and rear wake assessment of shock wave interference over blunt leading edge at Mach 6.5
Authors: Singh Gaurav Shivpratap , Sharma Chirag , Padhy Siddhant Swaroop , Dinesan Deepu , John Bibin
Published: September 2023

A detailed numerical study of shock-wave interference on a cylindrical blunt leading edge in hypersonic flow is carried out to reveal the effect of shock-shock interaction on peak heating and blunt body aerodynamics. This study is unique in that it examines the effect of interactions on rear wake formation and aerodynamic forces acting on the blunt body. Six different shock wave interference patterns described by Edney are studied for a freestream Mach number of 6.5. Compressible Reynolds-averaged Navier–Stokes equations are solved using finite volume method to obtain accurate prediction of the flowfield and aerodynamic loads. Hugoniot jump conditions are imposed in the inlet boundary to realize oblique shock of desired strength to interact with the detached shock at specific location. Numerical predictions are in good agreement with reported experimental measurements. The results obtained in this study reveals that the type of shock-shock interaction pattern can significantly alter the characteristics of the rear wake. Comparisons to undisturbed flow conditions reveal that Type II to VI interactions lead to an increase in wake size, whereas Type I interaction shows a marginal reduction. These changes in wake size are attributed to modifications in the forebody boundary layer induced by the shock-shock interactions. In the case of Type I interaction, however, the transmitted wave interacting with the rear wake is found to be responsible for the marginal reduction in wake size. This study also shows that changes to the rear wake structure caused by the change in interaction type can affect aerodynamic loads. Type VI interaction recorded a maximum drag coefficient of 2.96, whereas Type IV interaction yielded a maximum lift coefficient of 0.992. These findings demonstrate the potential for dynamically adjusting the control forces of a flying body by manipulating shock interference.